Interventions to control children's screen use and their effect on sleep: A systematic review and meta-analysis.

Prolonged viewing of screen-based media is associated with poor sleep in children. Previous systematic reviews have analysed the effectiveness of interventions that aim to limit children's screen use; however, none have evaluated its effect on sleep. The aim of this systematic review was to evaluate the effect of interventions that incorporate strategies to control children's screen use on screen use and sleep. The databases Pubmed, Embase, Eric, Scopus and PsycInfo were searched during October 2017 and updated in February 2019 for experimental studies with a control that assessed interventions to control screen use in children aged 2-14 years and reported both screen use and sleep outcomes. From 3,872 initial records, 11 studies (six randomized control [RCT], four cluster RCT and one cluster, quasi-experimental) were eligible for inclusion. A total of 4,656 children aged 2-13 years were included in the studies. The mean reduction in screen time was 0.56 hr (33 min)/day (95% confidence interval [CI], 0.92, 0.20) and the mean sleep duration increased by 0.19 hr (11 min)/day (95% CI, 0.05, 0.33). Bedtime was advanced by 0.16 hr (10 min) on weekdays and by 1.0 hr at the weekend. Subgroup analyses indicated stronger intervention effects for interventions of shorter duration (<3 months), which specifically targeted screen use or sleep, and those with direct participant contact. In conclusion, small improvements in screen time and sleep duration can be achieved in children. It is not possible to determine if a reduction in screen time directly improves sleep, due to the limited number of studies, the presence of co-interventions, issues with studies' methodological quality and heterogeneity.

Development of a core outcome set for interventions to prevent stillbirth.

AIMS: To develop a core outcome set for trials investigating interventions to prevent stillbirth. MATERIALS & METHODS: Outcomes identified from a systematic literature review and semi-structured interviews with parents in Australia and the UK were entered into a two-round online Delphi survey and focus group/consensus meetings. RESULTS: A core outcome set containing 11 outcomes in two categories. Five outcomes were related to the mother; fetal loss, onset of and mode of delivery, maternal mortality or near miss, psychological and social impact on the women, women's knowledge. Six outcomes were related to the baby; timing of stillbirth, neonatal mortality, gestational age at delivery, birthweight, congenital anomaly, NICU/SCBU or other higher-level neonatal care length of stay. CONCLUSIONS: Implementation and dissemination of this core outcome set in future trials will contribute towards coordinated outcome reporting and advancing usefulness of research to guide clinical practice.

Interval training versus continuous exercise in patients with coronary artery disease: a meta-analysis.

BACKGROUND: High aerobic capacity is inversely related to cardiovascular disease morbidity and mortality. Recent studies suggest greater improvements in aerobic capacity with high-intensity interval training (interval) compared to moderate-intensity continuous aerobic exercise (continuous). Therefore we perform a meta-analysis of randomised controlled trials comparing the effectiveness of INTERVAL versus CONTINUOUS in aerobic capacity, amongst patients with stable coronary artery disease (CAD) and preserved ejection fraction METHODS: We searched PubMed, EMBASE, CINAHL, the Australia and New Zealand Clinical Trials Register, clinicaltrials.gov and TROVE for randomised controlled trials comparing INTERVAL with CONTINUOUS in patients with CAD. Studies published in the English language up to December 2013 were eligible for inclusion. Aerobic capacity, quantified by peak oxygen consumption (VO2peak) post exercise training was extracted and compared post-intervention between INTERVAL and CONTINUOUS by way of a fixed model meta-analysis. Secondary outcomes including anaerobic threshold, blood pressure and high-density lipoproteins (HDL) were also analysed. RESULTS: Six independent studies with 229 patients (n=99 randomised to INTERVAL) were included in the meta-analysis. There was a significantly higher increase in VO2peak following INTERVAL compared to CONTINUOUS (Weighted Mean Difference=1.53 ml•kg(-1)min(-1), 95% CI 0.84 to 2.23) with homogeneity displayed between studies (Chi Squared=2.69; P=0.7). Significant effects of INTERVAL compared to CONTINUOUS were also found for anaerobic threshold but not systolic blood pressure. CONCLUSION: In patients with CAD, INTERVAL appears more effective than CONTINUOUS for the improvement of aerobic capacity in patients with CAD. However, long-term studies assessing morbidity and mortality following INTERVAL are required before this approach can be more widely adopted.

Developing a core outcome set in interventions to prevent stillbirth: A systematic review on variations of outcome reporting.

OBJECTIVE: To determine which outcomes have been previously reported in previous stillbirth prevention studies. RESEARCH DESIGN: Systematic review of reviews: We searched the Cochrane Database of Systematic Reviews, EMBASE and Pubmed for systematic reviews and meta- analyses investigating interventions to prevent stillbirth and its major risk factors. DATA COLLECTION AND ANALYSIS: Two reviewers identified and extracted outcomes independently. Outcomes were categorised under relevant domains for analysis. Frequency of each outcome was also determined. MAIN RESULTS: From 51 eligible reviews, 16 reviews addressed stillbirth prevention specifically while 35 reviews evaluated the efficacies of prevention or management of the eight major risk factors of stillbirth. Two hundred and thirty-seven outcomes were extracted, including 150 maternal outcomes and 87 offspring outcomes. Stillbirth (35/51), perinatal mortality (34/51) and neonatal mortality (33/51) were the most commonly reported outcomes followed by birthweight (29/51), caesarean section (28/51) and preeclampsia/eclampsia (23/51). Self-reported mother/family focused outcomes on their experiences and views were reported in 10/51 reviews. CONCLUSION: In studies evaluating prevention of stillbirth there is a large variety in outcomes, with discrepancies in nomenclature and measurements. Woman/family-centred outcomes are often missing from studies. There is a need for a core outcome sets agreed by all stakeholders containing the recommended minimum data to be reported in future studies investigating prevention of stillbirth.

Mitochondrial uncoupler FCCP activates proton conductance but does not block store-operated Ca(2+) current in liver cells.

Uncouplers of mitochondrial oxidative phosphorylation, including carbonilcyanide p-triflouromethoxyphenylhydrazone (FCCP) and carbonilcyanide m-cholorophenylhydrazone (CCCP), are widely used in experimental research to investigate the role of mitochondria in cellular function. Unfortunately, it is very difficult to interpret the results obtained in intact cells using FCCP and CCCP, as these agents not only inhibit mitochondrial potential, but may also affect membrane potential and cell volume. Here we show by whole-cell patch clamping that in primary rat hepatocytes and H4IIE liver cells, FCCP induced large proton currents across the plasma membrane, but did not activate any other observable conductance. In intact hepatocytes FCCP inhibits thapsigargin-activated store-operated Ca(2+) entry, but in patch clamping under the conditions of strong Ca(2+) buffering it has no effect on store-operated Ca(2+) current (I(SOC)). These results indicate that there is no direct connection between mitochondria and activation of I(SOC) in liver cells and support the notion of indirect regulation of I(SOC) by mitochondrial Ca(2+) buffering.

A small component of the endoplasmic reticulum is required for store-operated Ca2+ channel activation in liver cells: evidence from studies using TRPV1 and taurodeoxycholic acid.

The question of whether the activation of SOCs (store-operated Ca(2+) channels) requires the whole or part of the ER (endoplasmic reticulum) has not been fully resolved. The role of a putative sub-compartment of the ER in SOC activation in liver cells was investigated using ectopically expressed TRPV1 (transient receptor potential vanilloid 1), a non-selective cation channel, and TDCA (taurodeoxycholic acid), an activator of SOCs, to release Ca(2+) from different regions of the ER. TRPV1 was expressed in the ER and in the plasma membrane. The amount of Ca(2+) released from the ER by a TRPV1 agonist, measured using fura-2, was the same as that released by a SERCA (sarcoplasmic/endoplasmic reticulum Ca(2+)-ATPase) inhibitor, indicating that TRPV1 agonist-sensitive stores substantially overlap with SERCA inhibitor-sensitive stores. In contrast with SERCA inhibitors, TRPV1 agonists did not activate store-operated Ca(2+) entry. These findings were confirmed by patch-clamp recording. Using FFP-18, it was shown that SERCA inhibitors release Ca(2+) from the ER located closer to the plasma membrane than the region from which TRPV1 agonists release Ca(2+). In contrast with SERCA inhibitors, TRPV1 agonists did not induce a redistribution of STIM1 (stromal interaction molecule 1). TDCA caused the release of Ca(2+) from the ER, which was detected by FFP-18 but not by fura-2, and a redistribution of STIM1 to puncta similar to that caused by SERCA inhibitors. It is concluded that in liver cells, Ca(2+) release from a small component of the ER located near the plasma membrane is required to induce STIM1 redistribution and SOC activation.

Store-operated Ca(2+) channels and Stromal Interaction Molecule 1 (STIM1) are targets for the actions of bile acids on liver cells.

Cholestasis is a significant contributor to liver pathology and can lead to primary sclerosis and liver failure. Cholestatic bile acids induce apoptosis and necrosis in hepatocytes but these effects can be partially alleviated by the pharmacological application of choleretic bile acids. These actions of bile acids on hepatocytes require changes in the release of Ca(2+) from intracellular stores and in Ca(2+) entry. However, the nature of the Ca(2+) entry pathway affected is not known. We show here using whole cell patch clamp experiments with H4-IIE liver cells that taurodeoxycholic acid (TDCA) and other choleretic bile acids reversibly activate an inwardly-rectifying current with characteristics similar to those of store-operated Ca(2+) channels (SOCs), while lithocholic acid (LCA) and other cholestatic bile acids inhibit SOCs. The activation of Ca(2+) entry was observed upon direct addition of the bile acid to the incubation medium, whereas the inhibition of SOCs required a 12 h pre-incubation. In cells loaded with fura-2, choleretic bile acids activated a Gd(3+)-inhibitable Ca(2+) entry, while cholestatic bile acids inhibited the release of Ca(2+) from intracellular stores and Ca(2+) entry induced by 2,5-di-(tert-butyl)-1,4-benzohydro-quinone (DBHQ). TDCA and LCA each caused a reversible redistribution of stromal interaction molecule 1 (STIM1, the endoplasmic reticulum Ca(2+) sensor required for the activation of Ca(2+) release-activated Ca(2+) channels and some other SOCs) to puncta, similar to that induced by thapsigargin. Knockdown of Stim1 using siRNA caused substantial inhibition of Ca(2+)-entry activated by choleretic bile acids. It is concluded that choleretic and cholestatic bile acids activate and inhibit, respectively, the previously well-characterised Ca(2+)-selective hepatocyte SOCs through mechanisms which involve the bile acid-induced redistribution of STIM1.

The impact of integrated care for people with chronic conditions on hospital and emergency department utilization: a rapid review.

AIM: Integrated care commonly involves provision of comprehensive community-based care for people with chronic conditions. It is anticipated that implementation of integrated care, with a proactive approach to management of chronic conditions, will reduce reliance on hospital and emergency department (ED) services. The aim of this rapid review was to summarize the best available evidence on the impact of integrated care for patients with chronic conditions on hospital and ED utilization and investigate trends in outcomes over time. METHODS: Given the large body of literature available on this topic, this rapid review considered existing systematic reviews and meta-analyses that included adults with chronic conditions. Any model of integrated care that involved management of patients across the continuum of care, with the aim to provide more care in community settings, was considered for inclusion. A search of PubMed, CINAHL, Google Advanced, and websites of international healthcare provider organizations was conducted to locate relevant published and gray literature. RESULTS: A total of 13 systematic reviews were included. Overall, evidence suggests that integrated care may reduce the risk of hospitalization, with reviews including patients with diverse chronic conditions showing a 19% reduction. Integrated care appears effective in reducing readmissions for patients with heart failure, with an absolute risk reduction of 8% for first and 19% for subsequent rehospitalization. For ED presentations, evidence indicates that integrated care has no effect overall but may reduce ED visits for patients aged 65 years or more. For patients with chronic obstructive pulmonary disease, integrated care was associated with reductions in length of stay ranging from 2.5 to 4 days. Studies with shorter follow-up, from 3 to 12 months, in general appeared to show a greater impact of integrated care than studies with longer follow-up of 18 months or more. CONCLUSION: The evidence identified suggests integrated care generally reduces utilization of hospital services. In some instances, there were no differences observed between integrated care and usual care, but no included reviews reported increased utilization of these services. The impact of integrated care may be greater in the short-term, given the ultimate deterioration associated with advanced chronic disease which may negate any long-term benefits.

Phospholipase C-gamma1 is required for the activation of store-operated Ca2+ channels in liver cells.

Repetitive hormone-induced changes in concentration of free cytoplasmic Ca2+ in hepatocytes require Ca2+ entry through receptor-activated Ca2+ channels and SOCs (store-operated Ca2+ channels). SOCs are activated by a decrease in Ca2+ concentration in the intracellular Ca2+ stores, but the molecular components and mechanisms are not well understood. Some studies with other cell types suggest that PLC-gamma (phospholipase C-gamma) is involved in the activation of receptor-activated Ca2+ channels and/or SOCs, independently of PLC-gamma-mediated generation of IP3 (inositol 1,4,5-trisphosphate). The nature of the Ca2+ channels regulated by PLC-gamma has not been defined clearly. The aim of the present study was to determine if PLC-gamma is required for the activation of SOCs in liver cells. Transfection of H4IIE cells derived from rat hepatocytes with siRNA (short interfering RNA) targeted to PLC-gamma1 caused a reduction (by approx. 70%) in the PLC-gamma1 protein expression, with maximal effect at 72-96 h. This was associated with a decrease (by approx. 60%) in the amplitude of the I(SOC) (store-operated Ca2+ current) developed in response to intracellular perfusion with either IP(3) or thapsigargin. Knockdown of STIM1 (stromal interaction molecule type 1) by siRNA also resulted in a significant reduction (approx. 80% at 72 h post-transfection) of the I(SOC) amplitude. Immunoprecipitation of PLC-gamma1 and STIM1, however, suggested that under the experimental conditions these proteins do not interact with each other. It is concluded that the PLC-gamma1 protein, independently of IP3 generation and STIM1, is required to couple endoplasmic reticulum Ca2+ release to the activation of SOCs in the plasma membrane of H4IIE liver cells.

Assessing healthcare professionals' experiences of integrated care: do surveys tell the full story?

BACKGROUND: Integrated care is the combination of different healthcare services with the goal to provide comprehensive, seamless, effective and efficient patient care. Assessing the experiences of healthcare professionals (HCPs) is an important aspect when evaluating integrated care strategies. AIMS: The aim of this rapid review was to investigate if quantitative surveys used to assess HCPs' experiences with integrated care capture all the aspects highlighted as being important in qualitative research, with a view to informing future survey development. METHODS: The review considered all types of health professionals in primary care, and hospital and specialist services, with a specific focus on the provision of integrated care aimed at improving the patient journey. PubMed, CINAHL and grey literature sources were searched for relevant surveys/program evaluations and qualitative research studies. Full text articles deemed to be of relevance to the review were appraised for methodological quality using abridged critical appraisal instruments from the Joanna Briggs Institute. Data were extracted from included studies using standardized data extraction templates. Findings from included studies were grouped into domains based on similarity of meaning. Similarities and differences in the domains covered in quantitative surveys and those identified as being important in qualitative research were explored. RESULTS: A total of 37 studies (19 quantitative surveys, 14 qualitative studies and four mixed-method studies) were included in the review. A range of healthcare professions participated in the included studies, the majority being primary care providers. Common domains identified from quantitative surveys and qualitative studies included Communication, Agreement on Clear Roles and Responsibilities, Facilities, Information Systems, and Coordination of Care and Access. Qualitative research highlighted domains identified by HCPs as being relevant to their experiences with integrated care that have not routinely being surveyed, including Workload, Clear Leadership/Decision-Making, Management, Flexibility of Integrated Care Model, Engagement, Usefulness of Integrated Care and Collaboration, and Positive Impact/Clinical Benefits/Practice Level Benefits. CONCLUSION: There were several domains identified from qualitative research that are not routinely included in quantitative surveys to assess health professionals' experiences of integrated care. In addition, the qualitative findings suggest that the experiences of HCPs are often impacted by deeper aspects than those measured by existing surveys. Incorporation of targeted items within these domains in the design of surveys should enhance the capture of data that are relevant to the experiences of HCPs with integrated care, which may assist in more comprehensive evaluation and subsequent improvement of integrated care programs.

ClC-1 chloride channel: Matching its properties to a role in skeletal muscle.

1. ClC-1 is a Cl- channel in mammalian skeletal muscle that plays an important role in membrane repolarization following muscular contraction. Reduction of ClC-1 conductance results in myotonia, a state characterized by muscle hyperexcitability. 2. As is the case for other members of the ClC family, ClC-1 exists as a dimer that forms a double-barrelled channel. Each barrel, or pore, of ClC-1 is gated by its own gate ('fast' or 'single pore' gate), whereas both pores are gated simultaneously by another mechanism ('slow' or 'common' gate). 3. Comparison of the biophysical and pharmacological properties of heterologously expressed ClC-1 with the properties of the Cl- conductance measured in skeletal muscle strongly suggests that ClC-1 is the major Cl- channel responsible for muscle repolarization. However, not all results obtained in experiments on whole muscle or muscle fibres support this notion. 4. In the present review we attempt to bring together the current knowledge of ClC-1 with the physiology of skeletal muscle.

Glucagon activates Ca2+ and Cl- channels in rat hepatocytes.

Glucagon is one of the major hormonal regulators of glucose metabolism, counteracting the hepatic effects of insulin when the concentration of glucose in the bloodstream falls below a certain level. Glucagon also regulates bile flow, hepatocellular volume and membrane potential of hepatocytes. It is clear that changes in cell volume and membrane potential cannot occur without significant ion fluxes across the plasma membrane. The effects of glucagon on membrane currents in hepatocytes, however, are not well understood. Here we show, by patch-clamping of rat hepatocytes, that glucagon activates two types of currents: a small inwardly rectifying Ca2+ current with characteristics similar to those of the store-operated Ca2+ current and a larger outwardly rectifying Cl- current similar to that activated by cell swelling. We show that the mechanism of glucagon action on membrane conductance involves phospholipase C and adenylyl cyclase. Contribution of the adenylyl cyclase-dependent pathway to activation of the currents depended on Epac (exchange protein directly activated by cAMP), but not on protein kinase A. The activation of Ca2+ and Cl- channels is likely to play a key role in the mechanisms by which glucagon regulates hepatocyte metabolism and volume.