mHealth intervention delivered in general practice to increase physical activity and reduce sedentary behaviour of patients with prediabetes and type 2 diabetes (ENERGISED): rationale and study protocol for a pragmatic randomised controlled trial

Background The growing number of patients with type 2 diabetes and prediabetes is a major public health concern. Physical activity is a cornerstone of diabetes management and may prevent its onset in prediabetes patients. Despite this, many patients with (pre)diabetes remain physically inactive. Primary care physicians are well-situated to deliver interventions to increase their patients' physical activity levels. However, effective and sustainable physical activity interventions for (pre)diabetes patients that can be translated into routine primary care are lacking. Methods We describe the rationale and protocol for a 12-month pragmatic, multicentre, randomised, controlled trial assessing the effectiveness of an mHealth intervention delivered in general practice to increase physical activity and reduce sedentary behaviour of patients with prediabetes and type 2 diabetes (ENERGISED). Twenty-one general practices will recruit 340 patients with (pre)diabetes during routine health check-ups. Patients allocated to the active control arm will receive a Fitbit activity tracker to self-monitor their daily steps and try to achieve the recommended step goal. Patients allocated to the intervention arm will additionally receive the mHealth intervention, including the delivery of several text messages per week, with some of them delivered just in time, based on data continuously collected by the Fitbit tracker. The trial consists of two phases, each lasting six months: the lead-in phase, when the mHealth intervention will be supported with human phone counselling, and the maintenance phase, when the intervention will be fully automated. The primary outcome, average ambulatory activity (steps/day) measured by a wrist-worn accelerometer, will be assessed at the end of the maintenance phase at 12 months. Discussion The trial has several strengths, such as the choice of active control to isolate the net effect of the intervention beyond simple self-monitoring with an activity tracker, broad eligibility criteria allowing for the inclusion of patients without a smartphone, procedures to minimise selection bias, and involvement of a relatively large number of general practices. These design choices contribute to the trial’s pragmatic character and ensure that the intervention, if effective, can be translated into routine primary care practice, allowing important public health benefits

A pedometer-based walking intervention with and without email counseling in general practice: a pilot randomized controlled trial

Abstract Background General practitioners play a fundamental role in combatting the current epidemic of physical inactivity, and pedometer-based walking interventions are able to increase physical activity levels of their patients. Supplementing these interventions with email counseling driven by feedback from the pedometer has the potential to further improve their effectiveness but it has to be yet confirmed in clinical trials. Therefore, the aim of our pilot randomized controlled trial is to evaluate the feasibility and potential efficacy of future trials designed to assess the additional benefit of email counseling added to a pedometer-based intervention in a primary care setting. Methods Physically inactive patients were opportunistically recruited from four general practices and randomized to a 12-week pedometer-based intervention with or without email counseling. To explore the feasibility of future trials, we assessed the speed and efficiency of recruitment, adherence to wearing the pedometer, and engagement with email counseling. To evaluate the potential efficacy, daily step-count was the primary outcome and blood pressure, waist and hip circumference, and body mass were the secondary outcomes. Additionally, we conducted a qualitative analysis of structured interviews with the participating general practitioners. Results The opportunistic recruitment has been shown to be feasible and acceptable, but relatively slow and inefficient; moreover, general practitioners selectively recruited overweight and obese patients. Patients manifested high adherence, wearing the pedometer on 83% (± 20) of days. All patients from the counseling group actively participated in email communication and responded to 46% (± 22) of the emails they received. Both groups significantly increased their daily step-count (pedometer-plus-email, + 2119, p = 0.002; pedometer-alone, + 1336, p = 0.03), but the difference between groups was not significant (p = 0.18). When analyzing both groups combined, there was a significant decrease in body mass (− 0.68 kg, p = 0.04), waist circumference (− 1.73 cm, p = 0.03), and systolic blood pressure (− 3.48 mmHg, p = 0.045). Conclusions This study demonstrates that adding email counseling to a pedometer-based intervention in a primary care setting is feasible and might have the potential to increase the efficacy of such an intervention in increasing physical activity levels. Trial registration The trial was retrospectively registered at ClinicalTrials.gov (ID: NCT03135561, date: April 26, 2017)

Mental health and quality of life benefits of a pedometer-based walking intervention delivered in a primary care setting

Background: Physical activity level is positively associated with mental health and health-related quality of life. Primary care providers are ideally situated to offer physical activity interventions, and pedometers are commonly used as motivational tools to increase walking. However, several recent trials of pedometer-based interventions in primary care settings neither improved patients' quality of life nor reduced anxiety or depression, but these interventions only had relatively modest effects on physical activity levels. Objective: Our aim was to assess whether a pedometer-based walking intervention delivered in a primary care setting affects anxiety, depression, and health-related quality of life. Methods: A quasi-experimental, pre-post, single group study was conducted in 23 physically inactive patients from four general practices who participated in a pedometer-based intervention. The patients were administered the Hospital Anxiety and Depression Scale (HADS) and MOS 36-Item Short-Form Health Survey (SF-36) questionnaires before and after the 3-month intervention. Results: Following the intervention, the patients increased their walking volume by 1,676 steps per day (p < .001). Both the anxiety (-1.4, p = .011) and depression (-2.4, p = .001) subscales of HADS decreased, while the physical functioning (+6, p = .023), social functioning (+9, p = .035), mental health (+12, p = .001), vitality (+12, p = .003), and general health (+7, p = .013) subscales of SF-36 increased. Conclusions: Providing physically inactive patients with a pedometer and encouraging them to walk more in a primary care setting was associated with lower anxiety and depression scores, and improved health-related quality of life

Validity of six consumer-level activity monitors for measuring steps in patients with chronic heart failure.

IntroductionAlthough numerous activity trackers have been validated in healthy populations, validation is lacking in chronic heart failure patients who normally walk at a slower pace, making it difficult for researchers and clinicians to implement activity monitors during physical activity interventions.MethodsSix consumer-level activity monitors were validated in a 3-day field study in patients with chronic heart failure and healthy individuals under free living conditions. Furthermore, the same devices were evaluated in a lab-based study during treadmill walking at speeds of 2.4, 3.0, 3.6, and 4.2 km·h-1. Concordance correlation coefficients (CCC) were used to evaluate the agreement between the activity monitors and the criterion, and mean absolute percentage errors (MAPE) were calculated to assess differences between each device and the criterion (MAPE ResultsIn the field study of healthy individuals, all but one of the activity monitors showed a substantial correlation (CCC ≥0.95) with the criterion device and MAPE ConclusionsEven though none of the tested activity monitors fall within arbitrary thresholds for validity, most of them perform reasonably well enough to be useful tools that clinicians can use to simply motivate chronic heart failure patients to walk more

Utility of chemokines CCL2, CXCL8, 10 and 13 and interleukin 6 in the pediatric cohort for the recognition of neuroinflammation and in the context of traditional cerebrospinal fluid neuroinflammatory biomarkers.

BackgroundThe recognition of active inflammation in the central nervous system (CNS) in the absence of infectious agents is challenging. The present study aimed to determine the diagnostic relevance of five selected chemo/cytokines in the recognition of CNS inflammation and in the context of traditional cerebrospinal fluid (CSF) biomarkers (white blood cell [WBC] counts, oligoclonal bands, protein levels, CSF/serum albumin ratios) and clinical diagnoses.MethodsC-C and C-X-C motif ligands (CCL2, CXCL8, 10 and 13) and interleukin (IL) 6 levels in the CSF and serum from 37 control and 87 symptomatic children with ten different (mostly noninfectious) inflammatory CNS disorders (16 of which had follow-up samples after recovery) were determined using Luminex multiple bead technology and software. Nonparametric tests were used; p ResultsCompared with the control CSF samples, levels of all investigated chemo/cytokines were increased in symptomatic CSF samples, and only IL-6 remained elevated in recovery samples (p ≤ 0.001). CSF CXCL-13 levels (> 10.9 pg/mL) were the best individual discriminatory criterion to differentiate neuroinflammation (specificity/sensitivity: 97/72% and 97/61% for samples without pleocytosis), followed by CSF WBC counts (specificity/sensitivity: 97/62%). The clinical utility of the remaining CSF chemo/cytokine levels was determined in descending order of sensitivities corresponding to thresholds that ensured 97% specificity for neuroinflammation in samples without pleocytosis (pg/mL; sensitivity %): IL-6 (3.8; 34), CXCL8 (32; 26), CXCL10 (317; 24) and CCL2 (387; 10). Different diagnosis-related patterns of CSF chemo/cytokines were observed.ConclusionsThe increased CSF level of CXCL13 was the marker with the greatest predictive utility for the general recognition of neuroinflammation among all of the individually investigated biomarkers. The potential clinical utility of chemo/cytokines in the differential diagnosis of neuroinflammatory diseases was identified

What matters in chronic <i>Burkholderia cenocepacia</i> infection in cystic fibrosis: Insights from comparative genomics

<div><p><i>Burkholderia cenocepacia</i> causes severe pulmonary infections in cystic fibrosis (CF) patients. Since the bacterium is virtually untreatable by antibiotics, chronic infections persist for years and might develop into fatal septic pneumonia (cepacia syndrome, CS). To devise new strategies to combat chronic <i>B</i>. <i>cenocepacia</i> infections, it is essential to obtain comprehensive knowledge about their pathogenesis. We conducted a comparative genomic analysis of 32 Czech isolates of epidemic clone <i>B</i>. <i>cenocepacia</i> ST32 isolated from various stages of chronic infection in 8 CF patients. High numbers of large-scale deletions were found to occur during chronic infection, affecting preferentially genomic islands and nonessential replicons. Recombination between insertion sequences (IS) was inferred as the mechanism behind deletion formation; the most numerous IS group was specific for the ST32 clone and has undergone transposition burst since its divergence. Genes functionally related to transition metal metabolism were identified as hotspots for deletions and IS insertions. This functional category was also represented among genes where nonsynonymous point mutations and indels occurred parallelly among patients. Another category exhibiting parallel mutations was oxidative stress protection; mutations in catalase KatG resulted in impaired detoxification of hydrogen peroxide. Deep sequencing revealed substantial polymorphism in genes of both categories within the sputum <i>B</i>. <i>cenocepacia</i> ST32 populations, indicating extensive adaptive evolution. Neither oxidative stress response nor transition metal metabolism genes were previously reported to undergo parallel evolution during chronic CF infection. Mutations in <i>katG</i> and copper metabolism genes were overrepresented in patients where chronic infection developed into CS. Among professional phagocytes, macrophages use both hydrogen peroxide and copper for their bactericidal activity; our results thus tentatively point to macrophages as suspects in pathogenesis towards the fatal CS.</p></div

Parallel mutations in <i>B</i>. <i>cenocepacia</i> ST32 sputum populations from 12 chronically infected, non-CS patients.

<p>Parallel mutations in <i>B</i>. <i>cenocepacia</i> ST32 sputum populations from 12 chronically infected, non-CS patients.</p

Overview of sequenced <i>B</i>. <i>cenocepacia</i> ST32 isolates.

<p>(A) Sample collection chart. Bacteria were isolated at indicated time points and named by patient IDs (1 to 8) and chronology of isolation A to D (i.e., isolates 1A to 1D, 2A to 2D etc.). Isolates 2C and 2D, 5C and 5D, 7C and 7D, and 8C and 8D overlapped due to their concurrent isolation at the time of CS (see <a href="http://www.plospathogens.org/article/info:doi/10.1371/journal.ppat.1006762#ppat.1006762.s004" target="_blank">S1 Table</a> for details). (B) Whole-genome phylogeny. Consensus genomic sequences obtained by mapping sequencing reads onto the complete reference genome were used for tree inference. The Maximum-Likelihood tree was constructed from 2,754 variant nucleotide positions using the CSIPhylogeny pipeline [<a href="http://www.plospathogens.org/article/info:doi/10.1371/journal.ppat.1006762#ppat.1006762.ref074" target="_blank">74</a>]. (C) SNP accumulation during chronic infection. SNPs informative of within-patient evolution (see <a href="http://www.plospathogens.org/article/info:doi/10.1371/journal.ppat.1006762#sec012" target="_blank">Materials and Methods</a>) were plotted against time elapsed from the first Bcc culture positivity to the point of bacterial isolation.</p

Localization of mutations in proteins under parallel evolution during chronic infection.

<p>Protein chains under parallel evolution are denoted in light blue, their functional domains are denoted in dark blue (DHp in CusS, βi4 in RpoB). Cofactors are denoted as forest green spheres, catalytic and active site amino acids are denoted as lime green spheres. Amino acids homologous to residues affected by mutations during chronic Bcc infection (<a href="http://www.plospathogens.org/article/info:doi/10.1371/journal.ppat.1006762#ppat.1006762.s013" target="_blank">S10 Table</a>) are denoted as spheres and colored as explained in the legend (for ST32 WGS data, see <a href="http://www.plospathogens.org/article/info:doi/10.1371/journal.ppat.1006762#ppat.1006762.g003" target="_blank">Fig 3</a>; for ST32 DPS data, see <a href="http://www.plospathogens.org/article/info:doi/10.1371/journal.ppat.1006762#ppat.1006762.t001" target="_blank">Table 1</a>; for IIIA WGS data, see <a href="http://www.plospathogens.org/article/info:doi/10.1371/journal.ppat.1006762#ppat.1006762.s012" target="_blank">S9 Table</a>). Visualizations were carried out in Chimera [<a href="http://www.plospathogens.org/article/info:doi/10.1371/journal.ppat.1006762#ppat.1006762.ref083" target="_blank">83</a>].</p