Lay-led and peer support interventions for adolescents with asthma.

BACKGROUND: Adolescents with asthma are at high risk of poor adherence with treatment. This may be compounded by activities that worsen asthma, in particular smoking. Additional support above and beyond routine care has the potential to encourage good self-management. We wanted to find out whether sessions led by their peers or by lay leaders help to reduce these risks and improve asthma outcomes among adolescents. OBJECTIVES: To assess the safety and efficacy of lay-led and peer support interventions for adolescents with asthma. SEARCH METHODS: We identified trials from the Cochrane Airways Trials Register, which contains reports of randomised trials obtained from multiple electronic and handsearched sources, and we searched trial registries and reference lists of primary studies. We conducted the most recent searches on 25 November 2016. SELECTION CRITERIA: Eligible studies randomised adolescents with asthma to an intervention led by lay people or peers or to a control. We included parallel randomised controlled trials with individual or cluster designs. We included studies reported as full text, those published as abstract only and unpublished data. DATA COLLECTION AND ANALYSIS: Two review authors screened the searches, extracted numerical data and study characteristics and assessed each included study for risk of bias. Primary outcomes were asthma-related quality of life and exacerbations requiring at least a course of oral steroids. We graded the analyses and presented evidence in a 'Summary of findings' table.We analysed dichotomous data as odds ratios, and continuous data as mean differences (MD) or standardised mean differences, all with a random-effects model. We assessed clinical, methodological and statistical heterogeneity when performing meta-analyses, and we described skewed data narratively. MAIN RESULTS: Five studies including a total of 1146 participants met the inclusion criteria for this review. As ever with systematic reviews of complex interventions, studies varied by design (cluster and individually randomised), duration (2.5 to 9 months), setting (school, day camp, primary care) and intervention content. Most risk of bias concerns were related to blinding and incomplete reporting, which limited the meta-analyses that could be performed. Studies generally controlled well for selection and attrition biases.All participants were between 11 and 17 years of age. Asthma diagnosis and severity varied, as did smoking prevalence. Three studies used the Triple A programme; one of these studies tested the addition of a smoke-free pledge; another delivered peer support group sessions and mp3 messaging to encourage adherence; and the third compared a peer-led asthma day camp with an equivalent camp led by healthcare practitioners.We had low confidence in all findings owing to risk of bias, inconsistency and imprecision. Results from an analysis of asthma-related quality of life based on the prespecified random-effects model were imprecise and showed no differences (MD 0.40, 95% confidence interval (CI) -0.02 to 0.81); a sensitivity analysis based on a fixed-effect model and a responder analysis suggested small benefit may be derived for this outcome. Most other results were summarised narratively and did not show an important benefit of the intervention; studies provided no analysable data on asthma exacerbations or unscheduled visits (data were skewed), and one study measuring adherence reported a drop in both groups. Effects on asthma control favoured the intervention but findings were not statistically significant. Results from two studies with high levels of baseline smoking showed some promise for self-efficacy to stop smoking, but overall nicotine dependence and smoking-related knowledge were not significantly better in the intervention group. Investigators did not report adverse events. AUTHORS' CONCLUSIONS: Although weak evidence suggests that lay-led and peer support interventions could lead to a small improvement in asthma-related quality of life for adolescents, benefits for asthma control, exacerbations and medication adherence remain unproven. Current evidence is insufficient to reveal whether routine use of lay-led or peer support programmes is beneficial for adolescents receiving asthma care.Ongoing and future research may help to identify target populations for lay-led and peer support interventions, along with attributes that constitute a successful programme

Changes to healthcare utilisation and symptoms for common mental health problems over the first 21 months of the COVID-19 pandemic: parallel analyses of electronic health records and survey data in England

BACKGROUND: Few studies have investigated the effect of the COVID-19 pandemic on mental health beyond 2020. This study quantifies changes to healthcare utilisation and symptoms for common mental health problems over the pandemic’s first 21 months. METHODS: Parallel cohort studies using primary care database and survey data for adults (≥16 years) in England from January 2015 to December 2021: 16,551,842 from the Clinical Practice Research Datalink (CPRD) and 40,699 from the UK Household Longitudinal Survey (UKHLS). Interrupted time-series models estimated changes in monthly prevalence of presentations and prescribed medications for anxiety and depression (CPRD); and self-reported psychological distress (UKHLS). The pandemic period was divided into five phases: 1st Wave (April–May 2020); post-1st Wave (June–September 2020); 2nd Wave (October 2020–February 2021); post 2nd Wave (March–May 2021); 3rd Wave (June–December 2021). FINDINGS: Primary care presentations for depression or anxiety dropped during the first wave (4.6 fewer monthly appointments per 1000 patients, 4.4–4.8) and remained lower than expected throughout follow-up. Self-reported psychological distress exceeded expected levels during the first (Prevalence Ratio = 1.378, 95% CI 1.289–1.459) and second waves (PR = 1.285, 1.189–1.377), returning towards expected levels during the third wave (PR = 1.038, 0.929–1.154). Increases in psychological distress and declines in presentations were greater for women. The decrease in primary care presentations for depression and anxiety exceeded that for physical health conditions (rheumatoid arthritis, diabetes, urinary tract infections). Anxiety and depression prescriptions returned to pre-pandemic levels during the second wave due to increased repeat prescriptions. INTERPRETATION: Despite periods of distress during the pandemic, we did not find an enduring effect on common mental health problems. The fall in primary care presentations for anxiety or depression suggests changing healthcare utilisation for mental distress and a potential treatment gap. FUNDING: National Institute for Health and Care Research (NIHR)

Direct Compression Behavior of Low- and High-Methoxylated Pectins

The objective of this study was to evaluate possible usefulness of pectins for direct compression of tablets. The deformation behavior of pectin grades of different degree of methoxylation (DM), namely, 5%, 10%, 25%, 35%, 40%, 50%, and 60% were, examined in terms of yield pressures (YP) derived from Heckel profiles for both compression and decompression and measurements of elastic recovery after ejection. All pectin grades showed a high degree of elastic recovery. DM 60% exhibited most plastic deformation (YP 70.4 MPa) whereas DM 5% (104.6 MPa) and DM 10% (114.7 MPa) least. However, DM 60% gave no coherent tablets, whereas tablet tensile strengths for DM 5% and DM 10% were comparable to Starch 1500®. Also, Heckel profiles were similar to Starch 1500®. For sieved fractions (180–250 and 90–125 μm) of DM 25% and DM 40% originating from the very same batch, YPs were alike, indicating minor effects of particle size. These facts indicate that DM is important for the compaction behavior, and batch-to-batch variability should also be considered. Therefore, pectins of low degree of methoxylation may have a potential as direct compression excipients

The Sec1/Munc18 protein Vps45 regulates cellular levels of its SNARE binding partners Tlg2 and Snc2 in Saccharomyces cerevisiae

Intracellular membrane trafficking pathways must be tightly regulated to ensure proper functioning of all eukaryotic cells. Central to membrane trafficking is the formation of specific SNARE (soluble N-ethylmeleimide-sensitive factor attachment protein receptor) complexes between proteins on opposing lipid bilayers. The Sec1/Munc18 (SM) family of proteins play an essential role in SNARE-mediated membrane fusion, and like the SNAREs are conserved through evolution from yeast to humans. The SM protein Vps45 is required for the formation of yeast endosomal SNARE complexes and is thus essential for traffic through the endosomal system. Here we report that, in addition to its role in regulating SNARE complex assembly, Vps45 regulates cellular levels of its SNARE binding partners: the syntaxin Tlg2 and the v-SNARE Snc2: Cells lacking Vps45 have reduced cellular levels of Tlg2 and Snc2; and elevation of Vps45 levels results in concomitant increases in the levels of both Tlg2 and Snc2. As well as regulating traffic through the endosomal system, the Snc v-SNAREs are also required for exocytosis. Unlike most vps mutants, cells lacking Vps45 display multiple growth phenotypes. Here we report that these can be reversed by selectively restoring Snc2 levels in vps45 mutant cells. Our data indicate that as well as functioning as part of the machinery that controls SNARE complex assembly, Vps45 also plays a key role in determining the levels of its cognate SNARE proteins; another key factor in regulation of membrane traffic

Boosting Long-term Memory via Wakeful Rest: Intentional Rehearsal is not Necessary, Automatic Consolidation is Sufficient.

<div><p>People perform better on tests of delayed free recall if learning is followed immediately by a short wakeful rest than by a short period of sensory stimulation. Animal and human work suggests that wakeful resting provides optimal conditions for the consolidation of recently acquired memories. However, an alternative account cannot be ruled out, namely that wakeful resting provides optimal conditions for intentional rehearsal of recently acquired memories, thus driving superior memory. Here we utilised non-recallable words to examine whether wakeful rest boosts long-term memory, even when new memories could not be rehearsed intentionally during the wakeful rest delay. The probing of non-recallable words requires a recognition paradigm. Therefore, we first established, via Experiment 1, that the rest-induced boost in memory observed via free recall can be replicated in a recognition paradigm, using concrete nouns. In Experiment 2, participants heard 30 non-recallable non-words, presented as ‘foreign names in a bridge club abroad’ and then either rested wakefully or played a visual spot-the-difference game for 10 minutes. Retention was probed via recognition at two time points, 15 minutes and 7 days after presentation. As in Experiment 1, wakeful rest boosted recognition significantly, and this boost was maintained for at least 7 days. Our results indicate that the enhancement of memory via wakeful rest is <i>not</i> dependent upon intentional rehearsal of learned material during the rest period. We thus conclude that consolidation is <i>sufficient</i> for this rest-induced memory boost to emerge. We propose that wakeful resting allows for superior memory consolidation, resulting in stronger and/or more veridical representations of experienced events which can be detected via tests of free recall and recognition.</p></div

Syntaxin 16 is a master recruitment factor for cytokinesis

Recently it was shown that both recycling endosome and endosomal sorting complex required for transport (ESCRT) components are required for cytokinesis, in which they are believed to act in a sequential manner to bring about secondary ingression and abscission, respectively. However, it is not clear how either of these complexes is targeted to the midbody and whether their delivery is coordinated. The trafficking of membrane vesicles between different intracellular organelles involves the formation of soluble N-ethylmalei­mide–sensitive factor attachment protein receptor (SNARE) complexes. Although membrane traffic is known to play an important role in cytokinesis, the contribution and identity of intracellular SNAREs to cytokinesis remain unclear. Here we demonstrate that syntaxin 16 is a key regulator of cytokinesis, as it is required for recruitment of both recycling endosome–associated Exocyst and ESCRT machinery during late telophase, and therefore that these two distinct facets of cytokinesis are inextricably linked

Smc5/6: a link between DNA repair and unidirectional replication?

Of the three structural maintenance of chromosome (SMC) complexes, two directly regulate chromosome dynamics. The third, Smc5/6, functions mainly in homologous recombination and in completing DNA replication. The literature suggests that Smc5/6 coordinates DNA repair, in part through post-translational modification of uncharacterized target proteins that can dictate their subcellular localization, and that Smc5/6 also functions to establish DNA-damage-dependent cohesion. A nucleolar-specific Smc5/6 function has been proposed because Smc5/6 yeast mutants display penetrant phenotypes of ribosomal DNA (rDNA) instability. rDNA repeats are replicated unidirectionally. Here, we propose that unidirectional replication, combined with global Smc5/6 functions, can explain the apparent rDNA specificity

Effects of the COVID-19 pandemic on primary care-recorded mental illness and self-harm episodes in the UK: a population-based cohort study

BACKGROUND: The COVID-19 pandemic has adversely affected population mental health. We aimed to assess temporal trends in primary care-recorded common mental illness, episodes of self-harm, psychotropic medication prescribing, and general practitioner (GP) referrals to mental health services during the COVID-19 emergency in the UK. METHODS: We did a population-based cohort study using primary care electronic health records from general practices registered on the UK Clinical Practice Research Datalink (CPRD). We included patient records from Jan 1, 2010, to Sept 10, 2020, to establish long-term trends and patterns of seasonality, but focused primarily on the period January, 2019-September, 2020. We extracted data on clinical codes entered into patient records to estimate the incidence of depression and anxiety disorders, self-harm, prescriptions for antidepressants and benzodiazepines, and GP referrals to mental health services, and assessed event rates of all psychotropic prescriptions and self-harm. We used mean-dispersion negative binomial regression models to predict expected monthly incidence and overall event rates, which were then compared with observed rates to assess the percentage reduction in incidence and event rates after March, 2020. We also stratified analyses by sex, age group, and practice-level Index of Multiple Deprivation quintiles. FINDINGS: We identified 14 210 507 patients from 1697 UK general practices registered in the CPRD databases. In April, 2020, compared with expected rates, the incidence of primary care-recorded depression had reduced by 43·0% (95% CI 38·3-47·4), anxiety disorders by 47·8% (44·3-51·2), and first antidepressant prescribing by 36·4% (33·9-38·8) in English general practices. Reductions in first diagnoses of depression and anxiety disorders were largest for adults of working age (18-44 and 45-64 years) and for patients registered at practices in more deprived areas. The incidence of self-harm was 37·6% (34·8-40·3%) lower than expected in April, 2020, and the reduction was greatest for women and individuals aged younger than 45 years. By September, 2020, rates of incident depression, anxiety disorder, and self-harm were similar to expected levels. In Northern Ireland, Scotland, and Wales, rates of incident depression and anxiety disorder remained around a third lower than expected to September, 2020. In April, 2020, the rate of referral to mental health services was less than a quarter of the expected rate for the time of year (75·3% reduction [74·0-76·4]). INTERPRETATION: Consequences of the considerable reductions in primary care-recorded mental illness and self-harm could include more patients subsequently presenting with greater severity of mental illness and increasing incidence of non-fatal self-harm and suicide. Addressing the effects of future lockdowns and longer-term impacts of economic instability on mental health should be prioritised. FUNDING: National Institute for Health Research and Medical Research Council