Psychosocial Interventions and Wellbeing in Individuals with Diabetes Mellitus: A Systematic Review and Meta-Analysis

Purpose: A number of studies, including systematic reviews, show beneficial effects of psychosocial interventions for people with diabetes mellitus; however, they have not been assessed using meta-analysis. The purpose of this meta-analysis of randomized controlled trials is to investigate the effects of psychosocial interventions on depressive and anxiety symptoms, quality of life and self-efficacy in individuals with diabetes mellitus. Methods: The databases Pubmed, MEDLINE, CINAHL, PsycINFO, Scopus, Web of Science and SocINDEX were searched with no year restriction. Eligible studies were randomized controlled trials published in English that included individuals diagnosed with diabetes mellitus, aged 18 years or above, who engaged in a psychosocial intervention, with outcome measures addressing depressive or anxiety symptomology, quality of life or self-efficacy. Eligible studies needed to compare the intervention to usual care. Study selection was completed using Covidence and meta-analysis was undertaken using Comprehensive Meta-Analysis software. Results: Seven studies were included in the meta-analysis. Five studies investigated the effects of psychosocial interventions and showed a medium to large benefit for depressive symptoms (SMD: -0.70; CI: -1.27, -0.13) which persisted at follow up (SMD: -1.54, CI: -2.97, -0.12). Similar results were not seen immediately post-intervention in the three studies that assessed anxiety symptoms (SMD: -0.30; CI: -0.69, 0.10); however, a medium beneficial effect was seen at follow up (SMD = -0.61, CI = -0.92 to -0.31). Small benefits were seen in the three studies assessing quality of life outcomes (SMD: 0.30, CI: 0.06, 0.55). No benefit was seen in the two studies assessing self-efficacy (SMD: 0.23, CI: -0.11, 0.57). Conclusions: The results of the current study provide preliminary evidence that psychosocial interventions, compared to usual care, reduce depressive symptoms, and may improve quality of life in individuals with diabetes. However, only a few studies were included and the clinical significance of these findings is unknown

Land-use change to bioenergy: grassland to short rotation coppice willow has an improved carbon balance

The effect of a transition from grassland to second-generation (2G) bioenergy on soil carbon and greenhouse gas (GHG) balance is uncertain, with limited empirical data on which to validate landscape-scale models, sustainability criteria and energy policies. Here, we quantified soil carbon, soil GHG emissions and whole ecosystem carbon balance for short rotation coppice (SRC) bioenergy willow and a paired grassland site, both planted at commercial scale. We quantified the carbon balance for a 2-year period and captured the effects of a commercial harvest in the SRC willow at the end of the first cycle. Soil fluxes of nitrous oxide (N2O) and methane (CH4) did not contribute significantly to the GHG balance of these land uses. Soil respiration was lower in SRC willow (912 ± 42 g C m?2 yr?1) than in grassland (1522 ± 39 g C m?2 yr?1). Net ecosystem exchange (NEE) reflected this with the grassland a net source of carbon with mean NEE of 119 ± 10 g C m?2 yr?1 and SRC willow a net sink, ?620 ± 18 g C m?2 yr?1. When carbon removed from the ecosystem in harvested products was considered (Net Biome Productivity), SRC willow remained a net sink (221 ± 66 g C m?2 yr?1). Despite the SRC willow site being a net sink for carbon, soil carbon stocks (0–30 cm) were higher under the grassland. There was a larger NEE and increase in ecosystem respiration in the SRC willow after harvest; however, the site still remained a carbon sink. Our results indicate that once established, significant carbon savings are likely in SRC willow compared with the minimally managed grassland at this site. Although these observed impacts may be site and management dependent, they provide evidence that land-use transition to 2G bioenergy has potential to provide a significant improvement on the ecosystem service of climate regulation relative to grassland systems

Low leisure-based sitting time and being physically active were associated with reduced odds of death and diabetes in people with chronic obstructive pulmonary disease: a cohort study

Questions In people with chronic obstructive pulmonary disease (COPD), are activity phenotypes (based on physical activity and recreational screen time) associated with mortality and cardiometabolic risk factors? Design Cohort study. Participants People with COPD aged ≥ 40 years and who were current or ex-smokers were identified from the 2003 Scottish Health Survey. Outcome measures Data were collected regarding demographics, anthropometric measurements, medical history, physical activity, sedentary behaviour, health outcomes, and mortality. Analysis Participants were categorised into one of the following activity phenotypes: ‘couch potatoes’ were those who were insufficiently active with high leisure-based sitting time and/or no domestic physical activity; ‘light movers’ were insufficiently active with some domestic physical activity; ‘sedentary exercisers’ were sufficiently active with high leisure-based sitting time; and ‘busy bees’ were sufficiently active with low leisure-based sitting time. ‘Sufficiently active’ was defined as adhering to physical activity (PA) recommendations of ≥ 7.5 metabolic equivalent (MET) hours/week. ‘Low leisure-based sitting time’ was defined as ≤ 200 minutes of recreational screen time/day. Results The 584 participants had a mean age of 64 years (SD 12) and 52% were male. Over 5.5 years (SD 1.3) of follow-up, there were 81 all-cause deaths from 433 COPD participants with available data. Compared to the ‘couch potatoes’, there was a reduced risk of all-cause mortality in the ‘busy bees’ (Hazard Ratio 0.26, 95% CI 0.11 to 0.65) with a trend towards a reduction in mortality risk in the other phenotypes. The odds of diabetes were lower in the ‘busy bees’ compared to the ‘couch potatoes’ (OR 0.14, 95% CI 0.03 to 0.67). Conclusions Adhering to physical activity guidelines and keeping leisure-based sitting time low had a mortality benefit and lowered the odds of diabetes in people with COPD

Inhaled Corticosteroids Alone and in Combination With Long-Acting beta(2) Receptor Agonists to Treat Reduced Lung Function in Preterm-Born Children A Randomized Clinical Trial:A Randomized Clinical Trial

IMPORTANCE: Decreases in future lung function are a hallmark of preterm birth, but studies for management of decreased lung function are limited. OBJECTIVE: To determine whether 12 weeks of treatment with inhaled corticosteroids (ICS) alone or in combination with long-acting β(2) agonists (LABA) improves spirometry and exercise capacity in school-aged preterm-born children who had percent predicted forced expiratory volume in 1 second (%FEV(1)) less than or equal to 85% compared with inhaled placebo treatment. DESIGN, SETTING, AND PARTICIPANTS: A double-blind, randomized, placebo-controlled trial was conducted to evaluate ICS and ICS/LABA against placebo. Preterm-born children (age, 7-12 years; gestation ≤34 weeks at birth) who did not have clinically significant congenital, cardiopulmonary, or neurodevelopmental abnormalities underwent spirometry, exercise testing, and measurement of fractional exhaled nitric oxide before and after treatment. A total of 144 preterm-born children at the Children’s Hospital for Wales in Cardiff, UK, were identified and enrolled between July 1, 2017, and August 31, 2019. INTERVENTIONS: Each child was randomized to 1 of 3 cohorts: fluticasone propionate, 50 μg, with placebo; fluticasone propionate, 50 μg, with salmeterol, 25 μg; or placebo inhalers, all given as 2 puffs twice daily for 12 weeks. Children receiving preexisting ICS treatment underwent washout prior to randomization to ICS or ICS/LABA. MAIN OUTCOMES AND MEASURES: The primary outcome was between-group differences assessed by adjusted pretreatment and posttreatment differences of %FEV(1) using analysis of covariance. Intention-to-treat analysis was conducted. RESULTS: Of 144 preterm-born children who were identified with %FEV(1) less than or equal to 85%, 53 were randomized. Treatment allocation was 20 children receiving ICS (including 5 with prerandomization ICS), 19 children receiving ICS/LABA (including 4 with prerandomization ICS), and 14 children receiving placebo. The mean (SD) age of children was 10.8 (1.2) years, and 29 of the randomized children (55%) were female. The posttreatment %FEV(1) was adjusted for sex, gestation, bronchopulmonary dysplasia, intrauterine growth restriction, pretreatment corticosteroid status, treatment group, and pretreatment values. Posttreatment adjusted means for %FEV(1), using analysis of covariance, were 7.7% (95% CI, −0.27% to 15.72%; P = .16) higher in the ICS group and 14.1% (95% CI, 7.3% to 21.0%; P = .002) higher in the ICS/LABA group compared with the placebo group. Active treatment decreased the fractional exhaled nitric oxide and improved postexercise bronchodilator response but did not improve exercise capacity. One child developed cough when starting inhaler treatment; no other adverse events reported during the trial could be attributed to the inhaler treatment. CONCLUSIONS AND RELEVANCE: The results of this randomized clinical trial suggest that combined ICS/LABA treatment is beneficial for prematurity-associated lung disease in children. TRIAL REGISTRATION: EudraCT number: 2015-003712-2

Transitioning from manual to stirred-tank bioreactor manufacturing of IDCT, An allogeneiccell therapy to treat lumbar degenerative disc disease

DiscGenics is a clinical stage regenerative medicine company focused on developing cell therapies that alleviate pain and restore function in patients with degenerative disc disease (DDD), a major cause of low back pain which is a driver of disability worldwide. The Company’s lead product candidate, IDCT, is a homologous, allogeneic, off-the-shelf, injectable cell therapy under investigational use in the US (ClinicalTrials.gov Identifier: NCT03347708). The manufacturing process for IDCT involves isolating cells from donated intervertebral disc tissue and expanding them into proprietary progenitor cells known as discogenic cells. For preclinical and early clinical testing, cell production was a manual process which relied on pooling individual flasks to achieve the desired lot size. For successful scale-up and commercial production, DiscGenics seeks to modify the IDCT manufacturing process to utilize one large, single vessel per lot, while also applying bioprocess controls and more robust analytical methods to ensure consistent and optimal production of drug product. Once these changes are implemented, the product critical quality attributes (CQAs) must be maintained. DiscGenics has engaged GE Healthcare (GEHC) and the Centre for Commercialization of Regenerative Medicine (CCRM) for assay, media, and process development at the Centre for Advanced Therapeutic Cell Technologies (CATCT) in Toronto, ON., Canada. In partnership with the Federal Economic Development Agency for Southern Ontario (FedDev Ontario), CATCT accelerates the development, industrialization, and adoption of cell manufacturing technologies to improve patient access to cell and gene therapies. In this collaborative project, discogenic cells were generated in traditional static culture using CellStacks (Corning), in PBS-MINI bioreactor systems (PBS Biotech), and in stirred-tank reactors (STRs) (Eppendorf), which was led by the GEHC/CCRM team. Parameters such as cell viability, fold growth, and identity via flow cytometry were compared across modalities. For the STRs, multiple control parameters were evaluated to improve cell growth and assess successful maintenance of a consistent environment for cell quality. In this study, we found that we are able to maintain CQAs between the production modalities, with cell growth being significantly improved in the STR platform. In the STRs, in-process measurements of metabolites aligned with cell growth found using a custom sampling method. Increased cell expansion was facilitated by modified agitation, inoculation, and perfusion feeding strategies. Additionally, the process-controlled STRs provide non-invasive, continuous process data monitoring which allow for development of specified control ranges of manufacturing parameters. The quality by design (QbD) approach taken for the STR process development and improvement has allowed an increase in the lot size, process knowledge, and data-driven process definition. This presentation describes the approach and benefits of transitioning from a manual process to a suspension-based, process-controlled, stirred-tank reactor to produce allogeneic cell therapies

Ground-based walking training improves quality of life and exercise capacity in COPD

This study was designed to determine the effect of ground-based walking training on health-related quality of life and exercise capacity in people with chronic obstructive pulmonary disease (COPD). People with COPD were randomised to either a walking group that received supervised, ground-based walking training two to three times a week for 8–10 weeks, or a control group that received usual medical care and did not participate in exercise training. 130 out of 143 participants (mean±SD age 69±8 years, forced expiratory volume in 1 s 43±15% predicted) completed the study. Compared to the control group, the walking group demonstrated greater improvements in the St George’s Respiratory Questionnaire total score (mean difference -6 points (95% CI -10– -2), p<0.003), Chronic Respiratory Disease Questionnaire total score (mean difference 7 points (95% CI 2–11), p<0.01) and endurance shuttle walk test time (mean difference 208 s (95% CI 104–313), p<0.001). This study shows that ground-based walking training is an effective training modality that improves quality of life and endurance exercise capacity in people with COPD

Acquisition of a large virulence plasmid (pINV) promoted temperature-dependent virulence and global dispersal of O96:H19 enteroinvasive Escherichia coli

Enteroinvasive Escherichia coli (EIEC) and Shigella are closely related agents of bacillary dysentery. It is widely viewed that EIEC and Shigella species evolved from E. coli via independent acquisitions of a large virulence plasmid (pINV) encoding a type 3 secretion system (T3SS). Sequence Type (ST)99 O96:H19 E. coli is a novel clone of EIEC responsible for recent outbreaks in Europe and South America. Here, we use 92 whole genome sequences to reconstruct a dated phylogeny of ST99 E. coli, revealing distinct phylogenomic clusters of pINV-positive and -negative isolates. To study the impact of pINV acquisition on the virulence of this clone, we developed an EIEC-zebrafish infection model showing that virulence of ST99 EIEC is thermoregulated. Strikingly, zebrafish infection using a T3SS-deficient ST99 EIEC strain and the oldest available pINV-negative isolate reveals a separate, temperature-independent mechanism of virulence, indicating that ST99 non-EIEC strains were virulent before pINV acquisition. Taken together, these results suggest that an already pathogenic E. coli acquired pINV and that virulence of ST99 isolates became thermoregulated once pINV was acquired

Shuttle walk tests in people with COPD who demonstrate exercise-induced oxygen desaturation: An analysis of test repeatability and cardiorespiratory responses

© 2017, © The Author(s) 2017. Exercise-induced oxygen desaturation (EID) is prevalent in people with chronic obstructive pulmonary disease (COPD). This article reports a sub-analysis from a randomized controlled trial (RCT) in people with COPD and EID (COPD/EID). The primary aim, in people with COPD/ EID, was to determine the repeatability of the distance and time walked in the incremental shuttle walk test (ISWT) and endurance shuttle walk test (ESWT), respectively. A secondary aim was to determine whether any participant characteristics predicted those who did not demonstrate improvements on a repeat ISWT or ESWT. Participants with nadir oxygen saturation (SpO2) &lt; 90% on the 6-minute walk test were recruited to the RCT. Two ISWTs and two ESWTs were then performed as part of the baseline assessments, and participants were included in this sub-analysis if their nadir SpO2was &lt;90% during the better of two ISWTs. Repeatability of the tests was analysed using Bland–Altman plots and paired t-tests. Participant characteristics of age, lung function, level of nadir SpO2and end-test dyspnoea were used to predict those who were not likely to demonstrate improvements on a repeat test using receiver operating curves. Eighty-seven participants (mean age (standard deviation, SD) 70 (7) years; forced expiratory volume in one second (FEV1) 47 (17)% predicted) were included. The mean differences (coefficient of repeatability) for the ISWTs and ESWTs were 9 m (55 m) and 19 seconds (142 seconds) respectively (p &lt; 0.05). No participant characteristic predicted the absence of improvement on the second ISWT (area under the curve (AUC) ranged from 0.49 to 0.58, all p &gt; 0.2) or the second ESWT (AUC ranged from 0.43 to 0.52, all p &gt; 0.3). Although repeating the tests showed only small improvements in distance (ISWT) and time (ESWT) walked in people with COPD/EID, the variability was large making definite conclusions about test repeatability in these individuals difficult

Do You See What I See?:Quantifying Inter-Observer Variability in an Intertidal Marine Citizen Science Experiment

Citizen science represents an effective means of collecting ecological data; however, the quality/reliability of these data is often questioned. Quality assurance procedures are therefore important to determine the validity of citizen science data and to promote confidence in conclusions. Here, data generated by a marine citizen science project conducted at 12 sites across the United Kingdom was used to investigate whether the use of a simple, low-taxonomic-resolution field-monitoring protocol allowed trained citizen scientists to generate data comparable to those of professional scientists. To do this, differences between field estimates of algal percentage cover generated by different observer units (i.e., trained citizen scientists, professional scientists, and combined units), and digitally derived baseline estimates were examined. The results show that in the field, citizen scientists generated data similar to those of professional scientists, demonstrating that training, coupled with the use of a simple, low-taxonomic-resolution protocol can allow citizen scientists to generate robust datasets in which variability likely represents ecological variation/change as opposed to observer variation. The results also show, irrespective of observer unit, that differences between field and digital baseline estimates of algal percentage cover were greatest in plots with medium levels of algal cover, highlighting that additional/enhanced training for all participants could be beneficial in this area. The approach presented can serve as a guide for existing and future projects with similar protocols to assess their data quality, to strengthen participant training/protocols, and ultimately to promote the incorporation of robust citizen science datasets into environmental research and management

Lessons learnt from a discontinued randomised controlled trial:Adalimumab injection compared with placebo for patients receiving physiotherapy treatment for sciatica (Subcutaneous Injection of Adalimumab Trial compared with Control: SCIATiC)

Background Adalimumab, a biological treatment targeting tumour necrosis factor α, might be useful in sciatica. This paper describes the challenges faced when developing a new treatment pathway for a randomised controlled trial of adalimumab for people with sciatica, as well as the reasons why the trial discussed was stopped early. Methods A pragmatic, parallel group, randomised controlled trial with blinded (masked) participants, clinicians, outcome assessment and statistical analysis was conducted in six UK sites. Participants were identified and recruited from general practices, musculoskeletal services and outpatient physiotherapy clinics. They were adults with persistent symptoms of sciatica of 1 to 6 months’ duration with moderate to high level of disability. Eligibility was assessed by research physiotherapists according to clinical criteria, and participants were randomised to receive two doses of adalimumab (80 mg then 40 mg 2 weeks later) or saline placebo subcutaneous injections in the posterior lateral thigh. Both groups were referred for a course of physiotherapy. Outcomes were measured at baseline, 6-week, 6-month and 12-month follow-up. The main outcome measure was disability measured using the Oswestry Disability Index. The planned sample size was 332, with the first 50 in an internal pilot phase. Results The internal pilot phase was discontinued after 10 months from opening owing to low recruitment (two of the six sites active, eight participants recruited). There were several challenges: contractual delays; one site did not complete contract negotiations, and two sites signed contracts shortly before trial closure; site withdrawal owing to patient safety concerns; difficulties obtaining excess treatment costs; and in the two sites that did recruit, recruitment was slower than planned because of operational issues and low uptake by potential participants. Conclusions Improved patient care requires robust clinical research within contexts in which treatments can realistically be provided. Step changes in treatment, such as the introduction of biologic treatments for severe sciatica, raise complex issues that can delay trial initiation and retard recruitment. Additional preparatory work might be required before testing novel treatments. A randomised controlled trial of tumour necrosis factor-α blockade is still needed to determine its cost-effectiveness in severe sciatica