Cognitive testing of the Children's Palliative Outcome Scale (C-POS) with children, young people and their parents/carers.

BACKGROUND: The Children's Palliative Outcome Scale (C-POS) is being developed using best methodological guidance on outcome measure development, This recommends cognitive testing, an established method of item improvement, prior to psychometric testing. AIM: To cognitively test C-POS within the target population to establish comprehensibility, comprehensiveness, relevance and acceptability. DESIGN: Cross-sectional cognitive interview study following COnsensus-based Standards for the selection of health Measurement INstruments (COSMIN) methodology and Rothrock guidance on outcome measure development. Cognitive interviews were conducted using 'think aloud' and verbal probing techniques. SETTING/PARTICIPANTS: Children 5-⩽17 years old with life-limiting conditions and parents/carers of children with life-limiting conditions were recruited from 14 UK sites. RESULTS: Forty-eight individuals participated (36 parents; 12 children) in cognitively testing the five versions of C-POS over two to seven rounds. Content and length were acceptable, and all questions were considered important. Refinements were made to parent/carer versions to be inclusive of non-verbal children such as changing 'share' to 'express' feelings; and 'being able to ask questions' to 'having the appropriate information'. Changes to improve comprehensibility of items such as 'living life to the fullest' were also made. Parents reported that completing an outcome measure can be distressing but this is anticipated and that being asked is important. CONCLUSION: Cognitive interviewing has facilitated refinement of the C-POS, especially for non-verbal children who represent a large proportion of those with a life-limiting condition. This study has enhanced the face and content validity of the measure and provided preliminary evidence for acceptability for use in routine practice.

Sex differences in response to cognitive behavioural therapy for insomnia: A chart review of 455 patients with chronic insomnia.

BACKGROUND: Insomnia is more prevalent in females, however studies examining sex differences in response to insomnia treatment are scarce. This study assessed sex-specific differences in cognitive behavioural therapy for insomnia (CBT-I)-related changes in insomnia symptoms in a large clinical cohort. METHODS: A chart review was conducted of a clinical cohort (females n = 305, males n = 150) referred to a sleep clinic. Participants had a registered psychologist confirm diagnosis of chronic insomnia according to DSM-IV/V criteria and a Level 1 or 2 sleep study. Daily sleep diaries and questionnaires including the Insomnia Severity Index (ISI), Flinders Fatigue Scale (FFS), the Daytime Feelings and Functioning Scale (DFFS), and the Depression, Anxiety and Stress Scale-21 items (DASS), were administered at baseline, post-treatment, and three-month follow-up. Linear mixed models determined interactions between sex and timepoint on symptoms. RESULTS: Mean (SD) age was 51.7 yrs (15.7, range = 18-90 yrs), and mean BMI was 26.3 kg/m2 (4.9), neither of which differed by sex. At pre-treatment, females demonstrated higher objective total sleep time (min) [343.5 (97.6) vs 323.8 min (92.1), p = 0.044], ISI [19.7 (4.2) vs 18.6 (4.4), p = 0.033], and FFS scores [19.2 (6.0) vs 16.9 (7.2), p = 0.003]. Compared to males, females experienced a greater reduction in FFS and DFFS scores and DASS depressive symptoms (p for interaction: 0.017, 0.043, 0.016 respectively) from baseline to follow-up. The greater reduction in depressive symptoms did not persist after controlling for age, BMI, and sleep apnea severity. Subjective total sleep time similarly increased across treatment for both males [baseline: 335.7 (15.1), post: 357.9 (15.5)] and females [baseline: 318.3 (10.4), post: 354.4 (10.7)], p for interaction: 0.22. CONCLUSION: Females and males experience similar, substantial benefits from CBT-I after accounting for comorbidities, suggesting the same treatment can resolve insomnia in both sexes.

'My life is a mess but I cope': An analysis of the language children and young people use to describe their own life-limiting or life-threatening condition.

BACKGROUND: Children and young people with life-limiting and life-threatening conditions have multidimensional needs and heterogenous cognitive and communicative abilities. There is limited evidence to support clinicians to tailor their communication to each individual child. AIM: To explore the language children and young people use to describe their own condition, to inform strategies for discussing needs and priorities. DESIGN: Positioned within a social constructivist paradigm, a secondary discourse analysis of semi-structured interview data was conducted incorporating the discourse dynamics approach for figurative language. SETTING/PARTICIPANTS: A total of 26 children and young people aged 5-17 years with life-limiting or life-threatening conditions (6 cancer; 20 non-cancer) were recruited from nine clinical services (six hospitals and three hospices) across two UK nations. RESULTS: The language children and young people use positions them as 'experts in their condition'. They combine medical terminology with their preferred terms for their body to describe symptoms and treatments, and use comparatives and superlatives to communicate their health status. Their language depicts their condition as a 'series of (functional and social) losses', which single them out from their peers as 'the sick one'. Older children and young people also incorporate figurative language to expand their descriptions. CONCLUSION/DISCUSSION: Children and young people can provide rich descriptions of their condition. Paying attention to their lexical choices, and converging one's language towards theirs, may enable more child-centred discussions. Expanding discussions about 'what matters most' with consideration of the losses and differences they have experienced may facilitate a fuller assessment of their concerns, preferences and priorities.

What are the anticipated benefits, risks, barriers and facilitators to implementing person-centred outcome measures into routine care for children and young people with life-limiting and life-threatening conditions? A qualitative interview study with key stakeholders.

BACKGROUND: There is a growing evidence-base underpinning implementation of person-centred outcome measures into adult palliative care. However evidence on how best to achieve this with children facing life-threatening and life-limiting conditions is limited. AIM: To identify the anticipated benefits, risks, barriers and facilitators to implementing person-centred outcome measures for children with life-limiting and life-threatening conditions. DESIGN: Cross-sectional qualitative semi-structured interview study with key stakeholders analysed using Framework analysis informed by the adapted-Consolidated Framework for Implementation Research. SETTING/PARTICIPANTS: A total of n = 26 children with life-limiting or life-threatening conditions, n = 40 parents/carers, n = 13 siblings and n = 15 health and social care professionals recruited from six hospitals and three children's hospices and n = 12 Commissioners of health services. RESULTS: All participants were supportive of future implementation of person-centred outcome measures into care. Anticipated benefits included: better understanding of patient and family priorities, improved communication and collaborative working between professionals and families and standardisation in data collection and reporting. Anticipated risks included increased workload for staff and measures not being used as intended. Implementation barriers included: acceptability and usability of outcome measures by children; burden and capacity of parents/carers regarding completion; privacy concerns; and language barriers. Implementation facilitators included designing measures using language that is meaningful to children and families, ensuring potential benefits of person-centred outcome measures are communicated to encourage 'buy-in' and administering measures with known and trusted professional. CONCLUSIONS: Implementation of person-centred outcome measures offer potential benefits for children with life-limiting and life-threatening conditions. Eight recommendations are made to maximise benefits and minimise risks in implementation.

Tripolar concentric ring electrodes for capturing localised electroencephalography signals during sleep.

By design, tripolar concentric ring electrodes (TCRE) provide more focal brain activity signals than conventional electroencephalography (EEG) electrodes placed further apart. This study compared spectral characteristics and rates of data loss to noisy epochs with TCRE versus conventional EEG signals recorded during sleep. A total of 20 healthy sleepers (12 females; mean [standard deviation] age 27.8 [9.6] years) underwent a 9-h sleep study. Participants were set up for polysomnography recording with TCRE to assess brain activity from 18 sites and conventional electrodes for EEG, eyes, and muscle movement. A fast Fourier transform using multitaper-based estimation was applied in 5-s epochs to scored sleep. Odds ratios with Bonferroni-adjusted 95% confidence intervals were calculated to determine the proportional differences in the number of noisy epochs between electrode types. Relative power was compared in frequency bands throughout sleep. Linear mixed models showed significant main effects of signal type (p < 0.001) and sleep stage (p < 0.001) on relative spectral power in each power band, with lower relative spectral power across all stages in TCRE versus EEG in alpha, beta, sigma, and theta activity, and greater delta power in all stages. Scalp topography plots showed distinct beta activation in the right parietal lobe with TCRE versus EEG. EEG showed higher rates of noisy epochs compared to TCRE (1.3% versus 0.8%, p < 0.001). TCRE signals showed marked differences in brain activity compared to EEG, consistent with more focal measurements and region-specific differences during sleep. TCRE may be useful for evaluating regional differences in brain activity with reduced muscle artefact compared to conventional EEG.

Regular snoring is associated with uncontrolled hypertension.

Snoring may be a risk factor for cardiovascular disease independent of other co-morbidities. However, most prior studies have relied on subjective, self-report, snoring evaluation. This study assessed snoring prevalence objectively over multiple months using in-home monitoring technology, and its association with hypertension prevalence. In this study, 12,287 participants were monitored nightly for approximately six months using under-the-mattress sensor technology to estimate the average percentage of sleep time spent snoring per night and the estimated apnea-hypopnea index (eAHI). Blood pressure cuff measurements from multiple daytime assessments were averaged to define uncontrolled hypertension based on mean systolic blood pressure≥140 mmHg and/or a mean diastolic blood pressure ≥90 mmHg. Associations between snoring and uncontrolled hypertension were examined using logistic regressions controlled for age, body mass index, sex, and eAHI. Participants were middle-aged (mean ± SD; 50 ± 12 y) and most were male (88%). There were 2467 cases (20%) with uncontrolled hypertension. Approximately 29, 14 and 7% of the study population snored for an average of >10, 20, and 30% per night, respectively. A higher proportion of time spent snoring (75th vs. 5th; 12% vs. 0.04%) was associated with a ~1.9-fold increase (OR [95%CI]; 1.87 [1.63, 2.15]) in uncontrolled hypertension independent of sleep apnea. Multi-night objective snoring assessments and repeat daytime blood pressure recordings in a large global consumer sample, indicate that snoring is common and positively associated with hypertension. These findings highlight the potential clinical utility of simple, objective, and noninvasive methods to detect snoring and its potential adverse health consequences.

Estimating vigilance from the pre-work shift sleep using an under-mattress sleep sensor.

Predicting vigilance impairment in high-risk shift work occupations is critical to help to reduce workplace errors and accidents. Current methods rely on multi-night, often manually entered, sleep data. This study developed a machine learning model for predicting vigilance errors based on a single prior sleep period, derived from an under-mattress sensor. Twenty-four healthy volunteers (mean [SD] age = 27.6 [9.5] years, 12 male) attended the laboratory on two separate occasions, 1 month apart, to compare wake performance and sleep under two different lighting conditions. Each condition occurred over an 8 day protocol comprising a baseline sleep opportunity from 10 p.m. to 7 a.m., a 27 h wake period, then daytime sleep opportunities from 10 a.m. to 7 p.m. on days 3-7. From 12 a.m. to 8 a.m. on each of days 4-7, participants completed simulated night shifts that included six 10 min psychomotor vigilance task (PVT) trials per shift. Sleep was assessed using an under-mattress sensor. Using extra-trees machine learning models, PVT performance (reaction times <500 ms, reaction, and lapses) during each night shift was predicted based on the preceding daytime sleep. The final extra-trees model demonstrated moderate accuracy for predicting PVT performance, with standard errors (RMSE) of 19.9 ms (reaction time, 359 [41.6]ms), 0.42 reactions/s (reaction speed, 2.5 [0.6] reactions/s), and 7.2 (lapses, 10.5 [12.3]). The model also correctly classified 84% of trials containing ≥5 lapses (Matthews correlation coefficient = 0.59, F1 = 0.83). Model performance is comparable to current fatigue prediction models that rely upon self-report or manually entered data. This efficient approach may help to manage fatigue and safety in non-standard work schedules.

Sleep-wake state discrepancy does not impair the efficacy of cognitive behavioural therapy for insomnia: Findings from a large clinic sample.

The current study determined the extent to which sleep-wake state discrepancy impairs the efficacy of cognitive behavioural therapy for insomnia in a real-world clinical sample. Sleep-wake state discrepancy occurs when there is an inconsistency between a person's subjective and objective sleep, and is a common phenomenon amongst patients with insomnia. Limited information is available on the effectiveness of cognitive behavioural therapy for insomnia in treating patients who experience significant sleep-wake state discrepancy in "real-world" samples. In the present study, all patients with insomnia received cognitive behavioural therapy for insomnia through an outpatient insomnia program (N = 386; mean age = 51.96 years, SD = 15.62; 65.97% [N = 254] female). Prior to treatment, participants completed a polysomnography sleep study and sleep diary, which was used to calculate sleep-wake state discrepancy. At pre-treatment, post-treatment and 3-month follow-up, participants completed the Insomnia Severity Index and other questionnaires, and 1 week of sleep diaries from which sleep-onset latency, wake after sleep onset and other sleep variables were calculated. There were no differences in self-reported sleep-onset latency, wake after sleep onset or Insomnia Severity Index scores at post-treatment or 3-month follow-up between quintiles of sleep-wake state discrepancy. These results indicate that sleep-wake state discrepancy at pre-treatment does not predict treatment response to cognitive behavioural therapy for insomnia. Future research could examine multi-night assessments of sleep-wake state discrepancy to determine whether variations in discrepancy may relate to pre-treatment insomnia severity and cognitive behavioural therapy for insomnia outcomes.

Boabom: A Feasible and Acceptable Approach to Helping College Students Manage Stress.

Objective: College students in the United States report high rates of psychological health concerns. Psychological and physical complementary health approaches have been found to be protective for college students. The aims of this study were to assess the feasibility and acceptability of Boabom, a martial art, with college students and to explore any changes in psychosocial outcomes. Participants: Twenty-six college students (25 females; mean age 21.73 years) participated in an 8-week Boabom intervention. Methods: Feasibility measures were attendance and retention of participants; acceptability was based on participants' cognitive and emotional responses to Boabom and was determined through analysis of focus group data. Psychosocial outcomes were assessed through analyses of pre- and postintervention measures of mindfulness, perceived stress, anxiety, depression, resilience, perceived health, and life satisfaction. Results: The Boabom intervention was feasible as 23 of 26 participants attended at least six of eight classes, and 22 participants attended the last class. Students found the intervention acceptable, with three themes emerging from the focus group data to describe the participants' experience with Boabom: (1) disengaging from constant, daily stress and breathing and moving as a group leads to sense of calm, (2) empowerment through incremental mastery of skills, and (3) recognition of the value of health benefits to be gained. Participants reported positive changes in mindfulness, perceived stress, anxiety, depression, resilience, perceived health, and life satisfaction from pre- to postintervention. Conclusions: Boabom may be a feasible and acceptable offering for college students; still, further piloting with other college student populations is recommended.

Are we getting enough sleep? Frequent irregular sleep found in an analysis of over 11 million nights of objective in-home sleep data.

OBJECTIVES: Evidence-based guidelines recommend that adults should sleep 7-9 h/night for optimal health and function. This study used noninvasive, multinight, objective sleep monitoring to determine average sleep duration and sleep duration variability in a large global community sample, and how often participants met the recommended sleep duration range. METHODS: Data were analyzed from registered users of the Withings under-mattress Sleep Analyzer (predominantly located in Europe and North America) who had ≥28 nights of sleep recordings, averaging ≥4 per week. Sleep durations (the average and standard deviation) were assessed across a ∼9-month period. Associations between age groups, sex, and sleep duration were assessed using linear and logistic regressions, and proportions of participants within (7-9 hours) or outside (<7 hours or >9 hours) the recommended sleep duration range were calculated. RESULTS: The sample consisted of 67,254 adults (52,523 males, 14,731 females; aged mean ± SD 50 ± 12 years). About 30% of adults demonstrated an average sleep duration outside the recommended 7-9 h/night. Even in participants with an average sleep duration within 7-9 hours, about 40% of nights were outside this range. Only 15% of participants slept between 7 and 9 hours for at least 5 nights per week. Female participants had significantly longer sleep durations than male participants, and middle-aged participants had shorter sleep durations than younger or older participants. CONCLUSIONS: These findings indicate that a considerable proportion of adults are not regularly sleeping the recommended 7-9 h/night. Even among those who do, irregular sleep is prevalent. These novel data raise several important questions regarding sleep requirements and the need for improved sleep health policy and advocacy.

Effect of Anti-TNF Biologic Exposure During Pregnancy on Villitis of Unknown Etiology Diagnoses in Patients with Autoimmune Disease.

Tumor necrosis factor-α (TNF-α) antagonists are highly effective in controlling autoimmune diseases. This has led to speculation that they might also be useful in treating inflammatory placental conditions, such as chronic villitis of unknown etiology (VUE). VUE affects 10-15% of term placentas and is associated with recurrent fetal growth restriction (FGR) and pregnancy loss. We aimed to evaluate outcomes in patients with autoimmune diseases with and without anti-TNF-α biologic exposure during gestation. This retrospective cohort study compared pregnant women with autoimmune disease taking anti-TNF-α biologics (n = 89) to pregnant women with autoimmune disease but not taking a biologic (n = 53). We extracted data on all patients meeting our inclusion criteria over a 20-year period. Our primary outcome was the diagnosis of VUE by histology. Our secondary outcomes were maternal and neonatal complications such as preeclampsia, FGR, and neonatal intensive care admission. Kruskal-Wallis and chi-squared tests were performed as appropriate for statistical analysis. Maternal characteristics were comparable between groups, and there was no increase in adverse pregnancy outcomes based on anti-TNF-α treatment. Exposure to anti-TNF-α therapy had no significant effect on the incidence of VUE or other obstetric complications. Within the cohort exposed to anti-TNF-α biologics during pregnancy, the rate of VUE was 9.3%, which is comparable to the reported general population risk. Our data support the safety profile of biologic use in pregnancy.

Safety and immunogenicity of ChAdOx1 85A prime followed by MVA85A boost compared with BCG revaccination among Ugandan adolescents who received BCG at birth: a randomised, open-label trial.

BACKGROUND: BCG confers reduced, variable protection against pulmonary tuberculosis. A more effective vaccine is needed. We evaluated the safety and immunogenicity of candidate regimen ChAdOx1 85A-MVA85A compared with BCG revaccination among Ugandan adolescents. METHODS: After ChAdOx1 85A dose escalation and age de-escalation, we did a randomised open-label phase 2a trial among healthy adolescents aged 12-17 years, who were BCG vaccinated at birth, without evident tuberculosis exposure, in Entebbe, Uganda. Participants were randomly assigned (1:1) using a block size of 6, to ChAdOx1 85A followed by MVA85A (on day 56) or BCG (Moscow strain). Laboratory staff were masked to group assignment. Primary outcomes were solicited and unsolicited adverse events (AEs) up to day 28 and serious adverse events (SAEs) throughout the trial; and IFN-γ ELISpot response to antigen 85A (day 63 [geometric mean] and days 0-224 [area under the curve; AUC). FINDINGS: Six adults (group 1, n=3; group 2, n=3) and six adolescents (group 3, n=3; group 4, n=3) were enrolled in the ChAdOx1 85A-only dose-escalation and age de-escalation studies (July to August, 2019). In the phase 2a trial, 60 adolescents were randomly assigned to ChAdOx1 85A-MVA85A (group 5, n=30) or BCG (group 6, n=30; December, 2019, to October, 2020). All 60 participants from groups 5 and 6 were included in the safety analysis, with 28 of 30 from group 5 (ChAdOx1 85A-MVA85A) and 29 of 30 from group 6 (BCG revaccination) analysed for immunogenicity outcomes. In the randomised trial, 60 AEs were reported among 23 (77%) of 30 participants following ChAdOx1 85A-MVA85A, 31 were systemic, with one severe event that occurred after the MVA85A boost that was rapidly self-limiting. All 30 participants in the BCG revaccination group reported at least one mild to moderate solicited AE; most were local reactions. There were no SAEs in either group. Ag85A-specific IFN-γ ELISpot responses peaked on day 63 in the ChAdOx1 85A-MVA85A group and were higher in the ChAdOx1 85A-MVA85A group compared with the BCG revaccination group (geometric mean ratio 30·59 [95% CI 17·46-53·59], p<0·0001, day 63; AUC mean difference 57 091 [95% CI 40 524-73 658], p<0·0001, days 0-224). INTERPRETATION: The ChAdOx1 85A-MVA85A regimen was safe and induced stronger Ag85A-specific responses than BCG revaccination. Our findings support further development of booster tuberculosis vaccines. FUNDING: UK Research and Innovations and Medical Research Council. TRANSLATIONS: For the Swahili and Luganda translations of the abstract see Supplementary Materials section.

Delayed melatonin circadian timing, lower melatonin output, and sleep disruptions in myopic, or short-sighted, children.

STUDY OBJECTIVES: This study investigated the differences in melatonin circadian timing and output, sleep characteristics, and cognitive function in myopic and non-myopic (or emmetropic) children, aged 8-15 years. METHODS: Twenty-six myopes (refractive error [mean ±â€…standard error mean] -2.06 ±â€…0.23 diopters) and 19 emmetropes (-0.06 ±â€…0.04 diopters), aged 11.74 ±â€…2.31 years were recruited. Circadian timing was assessed using salivary dim-light melatonin onset (DLMO), collected half-hourly for 7 hours, beginning 5 hours before and finishing 2 hours after individual average sleep onset in a sleep laboratory. Nocturnal melatonin output was assessed via aMT6s levels from urine voids collected from 05:30 pm to 8:00 am the following morning. Actigraphy-derived objective sleep timing were acquired for a week prior to the sleep laboratory visit. Cognitive assessments of sustained attention (using psychomotor vigilance task [PVT]) and working memory (using digit spans) were performed on the night of sleep laboratory. RESULTS: Myopic children (9:07 pm ±â€…14 minutes) exhibited a DLMO phase-delay of 1 hour 8 minutes compared to emmetropes (7:59 pm ±â€…13 minutes), p = 0.002. aMT6s melatonin levels were significantly lower among myopes (18.70 ±â€…2.38) than emmetropes (32.35 ±â€…6.93, p = 0.001). Myopes also exhibited significantly delayed sleep onset, delayed wake-up time, poor and reduced sleep, and more evening-type diurnal preference than emmetropes (all p < 0.05). Finally, myopes showed a slower reaction time in the PVT (p < 0.05), but not digit span tasks at night. CONCLUSIONS: These findings suggest a potential association between circadian rhythm dysfunction and myopia in children.

A realist interview study of a participatory public mental health project "#KindnessByPost".

BACKGROUND: #KindnessByPost (KbP) is a participatory public health initiative in which people anonymously send and receive cards containing messages of goodwill with others also taking part in the programme. Quantitative evaluations of KbP consistently find evidence of improvements to people's mental wellbeing and feelings of loneliness after participation and three months later. Our aim in the present study is to develop a programme theory of KbP, which describes for whom the KbP intervention improves mental wellbeing, other reported impacts, in which contexts it has these effects, and the mechanisms by which it works. METHODS: We use a realist interviewing methodology to develop the programme theory. We conducted a focus group with the KbP executive team, and 20 one-to-one interviews with KbP participants. During analysis, a co-production working group iteratively developed a Theory of Change model comprising context-mechanism-outcome statements [CMOs] to map out the mechanisms present in KbP. RESULTS: We developed 145 CMO statements, which we condensed and categorized into 32 overarching CMOs across nine thematic topics: access to scheme; pathways to involvement; resources; culture; giving post; receiving post; content of received post; community; long term impact. These CMOs set out pathways through which KbP benefited participants, including from doing something kind for someone else, of receiving post and appreciating the effort that went into it, and from the creative process of creating post and writing the messages inside them. Effects were sustained in part through people keeping the cards and through the social media communities that emerged around KbP. DISCUSSION: Both giving and receiving post and the sense of community benefited participants and improved their mood and feelings of connectedness with others. Connection with a stranger, rather than friends or family, was also an important feature of the initiative for participants. Our wide range of CMO pathways by which KbP produced positive outcomes may mean that the intervention is applicable or adaptable across many communities and settings. Taken together with evidence from the quantitative evaluations, KbP is potentially an effective, low-cost, and highly scalable public health intervention for reducing loneliness and improving wellbeing.

USP16 is an ISG15 cross-reactive deubiquitinase that targets pro-ISG15 and ISGylated proteins involved in metabolism.

Interferon-induced ubiquitin (Ub)-like modifier ISG15 covalently modifies host and viral proteins to restrict viral infections. Its function is counteracted by the canonical deISGylase USP18 or Ub-specific protease 18. Notwithstanding indications for the existence of other ISG15 cross-reactive proteases, these remain to be identified. Here, we identify deubiquitinase USP16 as an ISG15 cross-reactive protease by means of ISG15 activity-based profiling. Recombinant USP16 cleaved pro-ISG15 and ISG15 isopeptide-linked model substrates in vitro, as well as ISGylated substrates from cell lysates. Moreover, interferon-induced stimulation of ISGylation was increased by depletion of USP16. The USP16-dependent ISG15 interactome indicated that the deISGylating function of USP16 may regulate metabolic pathways. Targeted enzymes include malate dehydrogenase, cytoplasmic superoxide dismutase 1, fructose-bisphosphate aldolase A, and cytoplasmic glutamic-oxaloacetic transaminase 1. USP16 may thus contribute to the regulation of a subset of metabolism-related proteins during type-I interferon responses.

Age, 12-Step Group Involvement, and Relapse Affect Use of Sobriety Date as Recovery Start Date: A Mixed Methods Analysis.

The purpose of this paper is to explore the use of sobriety date as recovery start date, from the perspective of those in recovery, using a mixed methods approach. We report findings from 389 individuals who identify as being in recovery from a substance and/or alcohol use disorder concerning how they define their recovery start date. We report findings from logistic regression examining how the use of a sobriety date as a recovery start date differs across age, 12-step group engagement, and previous relapse occurrence. We complement these findings with qualitative data from focus groups discussions of how 44 individuals who identify as in recovery define what "recovery" means, how and why people choose their recovery start date, and the significance of sobriety in recovery start date definitions. About 50% (n = 182) of the quantitative sample defined their recovery start date as their date of last substance use or their first day of sobriety. Individuals who were younger, engaged in 12-step groups, and did not report a relapse had significantly greater odds of using a sobriety date as their recovery start date. Focus groups revealed nuances around sobriety date and, what for some was, a broader concept of recovery. The current findings prioritize the views of those in recovery to understand and define their own recovery start date. How those in recovery think about and define their recovery start date may have particular meaning. Research and clinical work would benefit from inquiring about recovery and sobriety dates separately.

Targeted Mass Spectrometry Reveals Interferon-Dependent Eicosanoid and Fatty Acid Alterations in Chronic Myeloid Leukaemia.

Bioactive lipids are involved in cellular signalling events with links to human disease. Many of these are involved in inflammation under normal and pathological conditions. Despite being attractive molecules from a pharmacological point of view, the detection and quantification of lipids has been a major challenge. Here, we have optimised a liquid chromatography-dynamic multiple reaction monitoring-targeted mass spectrometry (LC-dMRM-MS) approach to profile eicosanoids and fatty acids in biological samples. In particular, by applying this analytic workflow to study a cellular model of chronic myeloid leukaemia (CML), we found that the levels of intra- and extracellular 2-Arachidonoylglycerol (2-AG), intracellular Arachidonic Acid (AA), extracellular Prostaglandin F2α (PGF2α), extracellular 5-Hydroxyeicosatetraenoic acid (5-HETE), extracellular Palmitic acid (PA, C16:0) and extracellular Stearic acid (SA, C18:0), were altered in response to immunomodulation by type I interferon (IFN-I), a currently approved treatment for CML. Our observations indicate changes in eicosanoid and fatty acid metabolism, with potential relevance in the context of cancer inflammation and CML.

Comparative short-term safety and efficacy of hypnotics: A quantitative risk-benefit analysis.

Several professional societies have provided recommendations for prescribing medications for insomnia. None has provided an integrative analysis that concurrently quantifies safety and efficacy (e.g., risk-benefit ratios). This represents an important gap for informing clinician decision-making. Accordingly, the aim of the present review is to provide such an analysis for five classes of sleep-promoting medications. Adverse event data values were extracted from the most recent FDA-approved package inserts and converted to an integer before being placebo-adjusted and standardized as a rate per 1000 (AEr). Efficacy data, pre-to-post self-reported data for active and placebo conditions were acquired from pivotal trials identified in "white papers" and systematic reviews/meta-analyses. Weighted effect sizes were calculated for subjective sleep latency, wake time after sleep onset and total sleep time, and then were averaged by medication class for each sleep continuity variable. Overall efficacy was represented by a single variable, SWT (sleep latency + wake time after sleep onset + total sleep time). Risk-benefit was represented using a simple ratio value. For safety, it was found that melatonin receptor agonists had the lowest adverse event rate (AEr = 43.1), and non-benzodiazepine benzodiazepine receptor agonists had the highest rate (AEr = 255.0). For efficacy, it was found that the pre-to-post placebo adjusted effect sizes were largest for benzodiazepines (effect size = 1.94) and smallest for melatonin receptor agonists (effect size = 0.109). For risk-benefit, histamine antagonist had the most favourable profile (risk-benefit = 69.5), while melatonin receptor agonist had the least favourable profile (risk-benefit = 395.7). Overall, the combined metric for risk-benefit suggests that treatment with a histamine antagonist is optimal and potentially represents the best first-line therapy for the medical management of insomnia.

Achieving consensus on priority items for paediatric palliative care outcome measurement: Results from a modified Delphi survey, engagement with a children's research involvement group and expert item generation.

BACKGROUND: There is no validated outcome measure for use in children's palliative care outside sub-Saharan Africa. Stakeholders must be involved in the development of such measures to ensure face and content validity. AIM: To gain expert stakeholder consensus on items for inclusion in a paediatric palliative care outcome measure to establish face and content validity. DESIGN: This study was conducted in two phases following Rothrock and COSMIN guidance on patient-reported outcome measure development. Phase 1: Three-round modified Delphi survey to establish consensus on priority items. Phase 2: Item generation meeting with key stakeholders to develop initial measure versions. A young person's advisory group was also consulted on priority outcomes. SETTING AND PARTICIPANTS: Delphi survey: Parents and professionals with experience of caring for a child with a life-limiting condition. Young person's advisory group: young people age 10-20 years. Item generation meeting: bereaved parents, academics and clinicians. RESULTS: Phase 1: Delphi survey (n = 82). Agreement increased from Kendall's W = 0.17 to W = 0.61, indicating movement towards consensus. Agreement between professional and parent ranking was poor (Cohen's kappa 0.13). Professionals prioritised physical symptoms, whereas parents prioritised psychosocial and practical concerns. Advisory group: Children (n = 22) prioritised items related to living a 'normal life' in addition to items prioritised by adult participants. Phase 2: Five age/developmental stage appropriate child and proxy-reported versions of C-POS, containing 13 items, were drafted. CONCLUSIONS: This study highlights the importance and feasibility of involving key stakeholders in PROM item generation, as important differences were found in the priority outcomes identified by children, parents and professionals.