Detecting sleep apnea in adults with Down syndrome using WatchPAT: A feasibility study

BACKGROUND: In daily practice, sleep apnea is underdiagnosed in people with Down syndrome. The WatchPAT can detect sleep apnea in a less invasive way. AIM: This study aimed to evaluate the feasibility of the WatchPAT to detect sleep apnea in individuals with Down syndrome. METHODS AND PROCEDURES: Thirty-one participants with Down syndrome (aged 18+) were included. Sleep apnea was detected with the WatchPAT and compared to results of the STOP-Bang Questionnaire (current practice). Experiences of participants, caregivers and clinicians were studied using a combination of quantitative and qualitative methods. OUTCOMES AND RESULTS: Among the 68% of participants who accepted the WatchPAT, sleep apnea was detected in 95% of participants. Younger participants and participants with mild/moderate intellectual disabilities were more likely to accept the device. STOP-Bang did not detect most cases of sleep apnea. For the degree of sleep apnea, interrater reliability was substantial (k = 0.71) to almost perfect (k = 0.91). Considering experiences, caregivers and clinicians were predominantly positive about the WatchPAT. CONCLUSIONS: Our study showed that the WatchPAT is a promising device to detect sleep apnea in people with Down syndrome. Compared to polysomnography, detection with this device is less invasive and less burdensome for people with Down syndrome. Furthermore, the WatchPAT is a relatively accessible solution to implement in care institutions

Validity of instruments to measure physical activity may be questionable due to a lack of conceptual frameworks: a systematic review

BACKGROUND: Regulators' guidance documents for the development and validation of patient reported outcomes (PROs) advise the use of conceptual frameworks, which outline the structure of the concept that a PRO aims to measure. It is unknown if currently available PROs are based on conceptual frameworks. This study, limited to a specific case, aimed (i) to identify conceptual frameworks of physical activity in chronic respiratory patients or similar populations (chronic heart disease patients or the elderly), and (ii) to assess if the development and validation of PROs to measure physical activity in these populations were based on a conceptual framework of physical activity. METHODS: Two systematic reviews were conducted through search in Medline, Embase, Psychinfo, and Cinahl databases up to January 2010. RESULTS: In the first review only 2 references, identified from 581 references about physical activity in the defined populations, provided a conceptual framework of physical activity in COPD patients. In the second review, out of 103 studies developing PROs to measure physical activity or related constructs, none of them was based on a conceptual framework of physical activity. CONCLUSIONS: These findings raise concerns about how the large body of evidence from studies that use physical activity PRO instruments should be evaluated by health care providers, guideline developers, and regulatory bodies

Validity and responsiveness of the Daily- and Clinical visit-PROactive Physical Activity in COPD (D-PPAC and C-PPAC) instruments

BACKGROUND The Daily-PROactive and Clinical visit-PROactive Physical Activity (D-PPAC and C-PPAC) instruments in chronic obstructive pulmonary disease (COPD) combines questionnaire with activity monitor data to measure patients' experience of physical activity. Their amount, difficulty and total scores range from 0 (worst) to 100 (best) but require further psychometric evaluation. OBJECTIVE To test reliability, validity and responsiveness, and to define minimal important difference (MID), of the D-PPAC and C-PPAC instruments, in a large population of patients with stable COPD from diverse severities, settings and countries. METHODS We used data from seven randomised controlled trials to evaluate D-PPAC and C-PPAC internal consistency and construct validity by sex, age groups, COPD severity, country and language as well as responsiveness to interventions, ability to detect change and MID. RESULTS We included 1324 patients (mean (SD) age 66 (8) years, forced expiratory volume in 1 s 55 (17)% predicted). Scores covered almost the full range from 0 to 100, showed strong internal consistency after stratification and correlated as a priori hypothesised with dyspnoea, health-related quality of life and exercise capacity. Difficulty scores improved after pharmacological treatment and pulmonary rehabilitation, while amount scores improved after behavioural physical activity interventions. All scores were responsive to changes in self-reported physical activity experience (both worsening and improvement) and to the occurrence of COPD exacerbations during follow-up. The MID was estimated to 6 for amount and difficulty scores and 4 for total score. CONCLUSIONS The D-PPAC and C-PPAC instruments are reliable and valid across diverse COPD populations and responsive to pharmacological and non-pharmacological interventions and changes in clinically relevant variables

The Drosophila Melanogaster RAD54 Homolog, DmRAD54, Is Involved in the Repair of Radiation Damage and Recombination

The RAD54 gene of Saccharomyces cerevisiae plays a crucial role in recombinational repair of double-strand breaks in DNA. Here the isolation and functional characterization of the RAD54 homolog of the fruit fly Drosophila melanogaster, DmRAD54, are described. The putative Dmrad54 protein displays 46 to 57% identity to its homologs from yeast and mammals. DmRAD54 RNA was detected at all stages of fly development, but an increased level was observed in early embryos and ovarian tissue. To determine the function of DmRAD54, a null mutant was isolated by random mutagenesis. DmRAD54-deficient flies develop normally, but the females are sterile. Early development appears normal, but the eggs do not hatch, indicating an essential role for DmRAD54 in development. The larvae of mutant flies are highly sensitive to X rays and methyl methanesulfonate. Moreover, this mutant is defective in X- ray-induced mitotic recombination as measured by a somatic mutation and recombination test. These phenotypes are consistent with a defect in the repair of double-strand breaks and imply that the RAD54 gene is crucial in repair and recombination in a multicellular organism. The results also indicate that the recombinational repair pathway is functionally conserved in evolution

Single-cell phenotypes of peripheral blood immune cells in early and late stages of non-alcoholic fatty liver disease

Background/Aims Immune and inflammatory cells respond to multiple pathological hits in the development of nonalcoholic steatohepatitis (NASH) and fibrosis. Relatively little is known about how their type and function change through the non-alcoholic fatty liver disease (NAFLD) spectrum. Here we used multi-dimensional mass cytometry and a tailored bioinformatic approach to study circulating immune cells sampled from healthy individuals and people with NAFLD. Methods Cytometry by time of flight using 36 metal-conjugated antibodies was applied to peripheral blood mononuclear cells (PBMCs) from biopsy-proven NASH fibrosis (late disease), steatosis (early disease), and healthy patients. Supervised and unsupervised analyses were used, findings confirmed, and mechanisms assessed using independent healthy and disease PBMC samples. Results Of 36 PBMC clusters, 21 changed between controls and disease samples. Significant differences were observed between diseases stages with changes in T cells and myeloid cells throughout disease and B cell changes in late stages. Semi-supervised gating and re-clustering showed that disease stages were associated with fewer monocytes with active signalling and more inactive NK cells; B and T cells bearing activation markers were reduced in late stages, while B cells bearing co-stimulatory molecules were increased. Functionally, disease states were associated with fewer activated mucosal-associated invariant T cells and reduced toll-like receptor-mediated cytokine production in late disease. Conclusions A range of innate and adaptive immune changes begin early in NAFLD, and disease stages are associated with a functionally less active phenotype compared to controls. Further study of the immune response in NAFLD spectrum may give insight into mechanisms of disease with potential clinical application

Effectiveness of a peer-refugee delivered psychological intervention to reduce psychological distress among adult Syrian refugees in the Netherlands: study protocol

Background: Syrian refugees face multiple hardships and adversities which put them at risk for the development of mental health problems. However, access to adequate mental health care in host countries is limited. The WHO has developed Problem Management Plus (PM+), a brief, scalable psychological intervention, delivered by non-specialist helpers, that addresses common mental disorders in people affected by adversity. This study is part of the STRENGTHS project, that aims to evaluate peer-refugee delivered psychological interventions for Syrian refugees in Europe and the Middle East. Objective: To evaluate the effectiveness and cost-effectiveness of the peer-refugee delivered PM+ intervention among Syrian refugees with elevated levels of psychological distress in the Netherlands. Methods: PM+ will be tested in a randomized controlled trial (RCT) among Arabic-speaking Syrian refugees in the Netherlands aged 18 years and above with self-reported psychological distress (Kessler Psychological Distress Scale; K10 >15) and impaired daily functioning (WHO Disability Assessment Schedule; WHODAS 2.0 >16). Participants (N = 380) will be randomized into care as usual with PM+ (CAU/PM+, n = 190) or CAU only (CAU, n = 190). Baseline, 1-week post-intervention, and 3-month and 12-month follow-up assessments will be conducted. Primary outcomes are symptoms of depression and anxiety. Secondary outcomes are functional impairment, posttraumatic stress disorder symptoms, self-identified problems, anger, health and productivity costs, and hair cortisol concentrations. A process evaluation will be carried out to evaluate treatment dose, protocol fidelity and stakeholder views on barriers and facilitators to implementing PM+. Results and Conclusions: PM+ has proved effectiveness in other populations and settings. After positive evaluation, the adapted manual and training materials for individual PM+ will be made available through the WHO to encourage further replication and scaling up. Trial registration: Trial registration Dutch Trial Registry, NL7552, registered prospectively on March 1, 2019. Medical Ethics Review Committee VU Medical Center Protocol ID 2017.320, 7 September 2017

Validity and responsiveness of the Daily- and Clinical visit-PROactive Physical Activity in COPD (D-PPAC and C-PPAC) instruments

Background: The Daily-PROactive and Clinical visit-PROactive Physical Activity (D-PPAC and C-PPAC) instruments in chronic obstructive pulmonary disease (COPD) combines questionnaire with activity monitor data to measure patients' experience of physical activity. Their amount, difficulty and total scores range from 0 (worst) to 100 (best) but require further psychometric evaluation. Objective: To test reliability, validity and responsiveness, and to define minimal important difference (MID), of the D-PPAC and C-PPAC instruments, in a large population of patients with stable COPD from diverse severities, settings and countries. Methods: We used data from seven randomised controlled trials to evaluate D-PPAC and C-PPAC internal consistency and construct validity by sex, age groups, COPD severity, country and language as well as responsiveness to interventions, ability to detect change and MID. Results: We included 1324 patients (mean (SD) age 66 (8) years, forced expiratory volume in 1 s 55 (17)% predicted). Scores covered almost the full range from 0 to 100, showed strong internal consistency after stratification and correlated as a priori hypothesised with dyspnoea, health-related quality of life and exercise capacity. Difficulty scores improved after pharmacological treatment and pulmonary rehabilitation, while amount scores improved after behavioural physical activity interventions. All scores were responsive to changes in self-reported physical activity experience (both worsening and improvement) and to the occurrence of COPD exacerbations during follow-up. The MID was estimated to 6 for amount and difficulty scores and 4 for total score. Conclusions: The D-PPAC and C-PPAC instruments are reliable and valid across diverse COPD populations and responsive to pharmacological and non-pharmacological interventions and changes in clinically relevant variables