Adeno-Associated Virus 2 and Human Adenovirus F41 in Wastewater during Outbreak of Severe Acute Hepatitis in Children, Ireland.

During April-July 2022, outbreaks of severe acute hepatitis of unknown etiology (SAHUE) were reported in 35 countries. Five percent of cases required liver transplantation, and 22 patients died. Viral metagenomic studies of clinical samples from SAHUE cases showed a correlation with human adenovirus F type 41 (HAdV-F41) and adeno-associated virus type 2 (AAV2). To explore the association between those DNA viruses and SAHUE in children in Ireland, we quantified HAdV-F41 and AAV2 in samples collected from a wastewater treatment plant serving 40% of Ireland's population. We noted a high correlation between HAdV-F41 and AAV2 circulation in the community and SAHUE clinical cases. Next-generation sequencing of the adenovirus hexon in wastewater demonstrated HAdV-F41 was the predominant HAdV type circulating. Our environmental analysis showed increased HAdV-F41 and AAV2 prevalence in the community during the SAHUE outbreak. Our findings highlight how wastewater sampling could aid in surveillance for respiratory adenovirus species.

Embedding key word sign prompts in a shared book reading activity: The impact on communication between children with Down syndrome and their parents.

BACKGROUND: Children with Down syndrome have speech and language difficulties that are disproportionate to their overall intellectual ability and relative strengths in the use of gesture. Shared book reading between parents and their children provides an effective context in which language development can be facilitated. However, children with Down syndrome often take a passive role in shared book reading and the use of key word signing (KWS) as a shared book reading technique has never been investigated. AIMS: This study aimed to compare children with Down syndrome's participation and use of KWS across two methods of shared book reading - one in which a book had key-word sign prompts embedded (signed condition) and the other in which a book was read as normal (unsigned condition). Measures of child and parent communicative behaviour were taken in each condition to establish if differences emerged. METHODS & PROCEDURES: A total of 36 children with Down syndrome (aged between 18 and 61 months) and their mothers took part in the study. Parent-child dyads were videoed at home reading two books, one in a signed and one in an unsigned condition. Child measures included total number of signs produced in each condition and levels of attention and initiation as measured by the Pivotal Behaviour Rating Scale. Parent measures included total number of utterances, mean length of utterance (MLU) in morphemes and vocabulary diversity (VOCD). Parental measures were transcribed using the Codes for Human Analysis Transcripts (CHAT) software and analysed by the Computerised Language Analysis software (CLAN). Contrasts in outcomes between the signed and unsigned conditions were estimated using Poisson and linear mixed-effects models, determined by the type of data. OUTCOMES & RESULTS: Results showed that children attempted to sign significantly more in the signed than unsigned condition, as well as showing significant increases in their levels of attention and initiation. There was also a significant increase in the total number of utterances used by parents in the signed versus unsigned condition and a decrease in MLU. VOCD was similar in both conditions. CONCLUSIONS & IMPLICATIONS: This study shows that the simple act of embedding key word signs into commercially available books, during shared book reading between parents and young children with Down syndrome, positively affects children's participation (initiation and attention) and use of KWS. The use of KWS as a core shared book reading technique may therefore be a fruitful avenue to facilitate growth in the language abilities of young children with Down syndrome. WHAT THIS PAPER ADDS: What is already known on this subject Most children with Down syndrome have significant speech and language difficulties, with relative strengths in the use of gesture. Shared book reading is an activity reported to positively affect language. However, children with Down syndrome are reported to take a passive role in shared book reading and are therefore more dependent on their parents to use techniques that facilitate their levels of participation, in order to maximise potential benefits. To the best of our knowledge, the communicative effects of embedding key word signing (KWS) in shared book reading have never been examined with children with Down syndrome. What this paper adds to existing knowledge This is the first study to investigate the communicative impact of parents embedding KWS in a shared book reading activity with their young children with Down syndrome. Our findings show that this relatively simple manipulation resulted in Increase in children's sign attempts. Increase in children's overall participation in shared book reading (indicated by levels of attention and initiation). Increase in the number of utterances produced by parents (primarily as a result of repetitions). Decrease in parental mean length of utterance. These findings suggest that embedding KWS in shared book reading is likely to facilitate increased language abilities in this cohort. What are the potential or actual clinical implications of this work? Shared book reading is part of the daily routine for many parents and their children with Down syndrome. Integrating KWS is a relatively simple adaptation to this activity which is likely to enhance children's language skills. Therapists can encourage parents to do this at home to support work carried out at school and in a clinical setting.

How reliable is assessment of children's sentence comprehension using a self-directed app? A comparison of supported versus independent use.

This study reports on the feasibility of using the Test of Complex Syntax- Electronic (TECS-E), as a self-directed app, to measure sentence comprehension in children aged 4 to 5 ½ years old; how testing apps might be adapted for effective independent use; and agreement levels between face-to-face supported computerized and independent computerized testing with this cohort. A pilot phase was completed with 4 to 4;06-year-old children, to determine the appropriate functional app features required to facilitate independent test completion. Following the integration of identified features, children completed the app independently or with adult support (4-4;05 (n = 22) 4;06-4;11 months (n = 55) and 5 to 5;05 (n = 113)) and test re-test reliability was examined. Independent test completion posed problems for children under 5 years but for those over 5, TECS-E is a reliable method to assess children's understanding of complex sentences, when used independently.

Happy Talk: A pilot effectiveness study of a targeted-selective speech-language and communication intervention for children from areas of social disadvantage.

BACKGROUND: Despite the public health implications of language difficulties associated with social disadvantage, there is a dearth of effectiveness studies investigating the effects of targeted speech and language programmes in this area. AIMS: To determine the effects of a targeted selective community-based child language intervention programme (Happy Talk), which simultaneously engaged with parents and early childhood educators, in the Republic of Ireland. METHODS & PROCEDURES: A mixed methods methodology was applied with quantitative outcome and qualitative process data collected. Effectiveness was examined using a quasi-experimental single blind study design comparing Happy Talk with 'usual care' across four preschools. Qualitative process data were also gathered to examine the acceptability and feasibility of the Happy Talk approach in practice, and to identify factors to improve the probability of successful wider implementation. Child language (PLS-5) and quality-of-life measures were administered pre- and immediately post- the 11-week intervention. Responsiveness was assessed as the parental outcome, and the oral language environment of preschools was measured using the Communication Supporting Classroom Observation Tool (CSCOT). Retrospective acceptability was analysed with reference to the theoretical framework of acceptability (v 2). OUTCOMES & RESULTS: Pre-/post-expressive and composite language scores were collected for 58 children, and receptive scores for 54 children. Multiple linear regression revealed significant intervention effects for comprehension and total language with large and moderate effect sizes, respectively (0.60 and 0.46 SD). No significant effect was shown for parental responsiveness. No effects were found for the preschool environment or children's quality of life. Preschool staff deemed the programme to be an acceptable method of enhancing children's speech and language skills and rated the intervention positively. CONCLUSIONS & IMPLICATIONS: The Happy Talk pilot effectiveness trial shows that comprehension can be improved (with a large effect) in preschool children from areas of social disadvantage, following an 11-week intervention, in which parents and preschool staff are simultaneously engaged. The ecological validity of the programme, as well as feasibility and acceptability to staff, make it a suitable programme to be delivered at scale. WHAT THIS PAPER ADDS: What is already known on the subject Up to 50% of children from socially disadvantaged areas enter preschool with speech and language difficulties. The majority of intervention studies are (1) researcher led; (2) efficacy trials carried out in ideal conditions; and (3) focus on working with parents or early childhood educators rather than engaging with both groups simultaneously. Many studies omit child language outcomes, and those that include them tend to show relatively modest effects for expressive language and negligible effects for receptive language. What this paper adds to existing knowledge This pilot study shows that the Happy Talk programme, which is embedded in the community and which simultaneously engages with parents and early childhood educators, is highly effective in improving children's receptive language skills. These findings are particularly important in the context of (1) the study taking place in real world conditions; and (2) the programme being designed and refined by speech and language therapy services, rather than one which is researcher led. What are the potential or actual clinical implications of this work? Implementing an 11-week targeted selective community-based language intervention can result in a large positive effect on receptive language for children from areas of social disadvantage. The study findings highlight the importance of embedding intervention programmes in the community and of simultaneously engaging with parents and preschool staff.

Mealtime and patient factors associated with meal completion in hospitalised older patients: An exploratory observation study.

AIMS AND OBJECTIVES: To examine mealtime and patient factors associated with meal completion among hospitalised older patients. We also considered contextual factors such as staffing levels and ward communication. BACKGROUND: Sub-optimum nutrition is a modifiable risk factor for hospital associated decline (HAD) in older patients. Yet, the quality of mealtime experiences can be overlooked within ward routinised practice. DESIGN: Cross sectional, descriptive observation study. METHODS: We undertook structured observation of mealtimes examining patient positioning, mealtime set-up and feeding assistance. The outcome was meal completion categorised as 0, 25%, 50%, 75% or 100%. Data were collected on patient characteristics and ward context. We used mixed-effects ordinal regression models to examine patient and mealtime factors associated with higher meal completion producing odds ratios (OR) and 95% confidence intervals (CI). The study was reported as per STROBE guidelines. RESULTS: We included 60 patients with a median age of 82 years (IQR 76-87) and clinical frailty score of 5 IQR (4-6). Of the 279 meals, 51% were eaten completely, 6% three quarters, 15% half, 18% a quarter and 10% were not eaten at all. Mealtime predictors with a weak association with less-meal completion were requiring assistance, special diets, lying in bed, and red tray (indicator of nutrition risk), but were not statistically significant. Significant patient-level factors were higher values for frailty (OR 0.34 [0.11-1.04]) and Malnutrition Universal Screening Tool (OR 0.22 [0.08-0.62]). The average nurse-to-patient ratio was 1:5.5. CONCLUSION: Patient factors were the strongest predictors for meal completion, but mealtime factors had a subtle influence. The nursing teams' capacity to prioritise mealtimes above competing demands is important as part of a comprehensive nutrition strategy. RELEVANCE TO CLINICAL PRACTISE: Nurses are central to optimising nutrition for frail older patients. It requires ward leadership to instil a culture of prioritising assisted mealtimes, improved communication, greater autonomy to tailor nutrition strategies and safe staffing levels.

Treatment estimands in clinical trials of patients hospitalised for COVID-19: ensuring trials ask the right questions.

When designing a clinical trial, explicitly defining the treatment estimands of interest (that which is to be estimated) can help to clarify trial objectives and ensure the questions being addressed by the trial are clinically meaningful. There are several challenges when defining estimands. Here, we discuss a number of these in the context of trials of treatments for patients hospitalised with COVID-19 and make suggestions for how estimands should be defined for key outcomes. We suggest that treatment effects should usually be measured as differences in proportions (or risk or odds ratios) for outcomes such as death and requirement for ventilation, and differences in means for outcomes such as the number of days ventilated. We further recommend that truncation due to death should be handled differently depending on whether a patient- or resource-focused perspective is taken; for the former, a composite approach should be used, while for the latter, a while-alive approach is preferred. Finally, we suggest that discontinuation of randomised treatment should be handled from a treatment policy perspective, where non-adherence is ignored in the analysis (i.e. intention to treat).

Prevention of adverse drug reactions in hospitalized older patients with multi-morbidity and polypharmacy: the SENATOR* randomized controlled clinical trial.

BACKGROUND: Multi-morbidity and polypharmacy increase the risk of non-trivial adverse drug reactions (ADRs) in older people during hospitalization. Despite this, there are no established interventions for hospital-acquired ADR prevention. METHODS: We undertook a pragmatic, multi-national, parallel arm prospective randomized open-label, blinded endpoint (PROBE) controlled trial enrolling patients at six European medical centres. We randomized 1,537 older medical and surgical patients with multi-morbidity and polypharmacy on admission in a 1:1 ratio to SENATOR software-guided medication optimization plus standard care (intervention, n = 772, mean number of daily medications = 9.34) or standard care alone (control, n = 765, mean number of daily medications = 9.23) using block randomization stratified by site and admission type. Attending clinicians in the intervention arm received SENATOR-generated advice at a single time point with recommendations they could choose to adopt or not. The primary endpoint was occurrence of probable or certain ADRs within 14 days of randomization. Secondary endpoints were primary endpoint derivatives; tertiary endpoints included all-cause mortality, re-hospitalization, composite healthcare utilization and health-related quality of life. RESULTS: For the primary endpoint, there was no difference between the intervention and control groups (24.5 vs. 24.8%; OR 0.98; 95% CI 0.77-1.24; P = 0.88). Similarly, with secondary and tertiary endpoints, there were no significant differences. Among attending clinicians in the intervention group, implementation of SENATOR software-generated medication advice points was poor (~15%). CONCLUSIONS: In this trial, uptake of software-generated medication advice to minimize ADRs was poor and did not reduce ADR incidence during index hospitalization.

Augmented exercise in hospital improves physical performance and reduces negative post hospitalization events: a randomized controlled trial.

BACKGROUND: To measure the effects of an augmented prescribed exercise programme versus usual care, on physical performance, quality of life and healthcare utilisation for frail older medical patients in the acute setting. METHODS: This was a parallel single-blinded randomised controlled trial. Within 2 days of admission, older medical inpatients with an anticipated length of stay ≥3 days, needing assistance/aid to walk, were blindly randomly allocated to the intervention or control group. Until discharge, both groups received twice daily, Monday-to-Friday half-hour assisted exercises, assisted by a staff physiotherapist. The intervention group completed tailored strengthening and balance exercises; the control group performed stretching and relaxation exercises. Length of stay was the primary outcome measure. Blindly assessed secondary measures included readmissions within 3 months, and physical performance (Short Physical Performance Battery) and quality of life (EuroQOL-5D-5 L) at discharge and at 3 months. Time-to-event analysis was used to measure differences in length of stay, and regression models were used to measure differences in physical performance, quality of life, adverse events (falls, deaths) and negative events (prolonged hospitalisation, institutionalisation). RESULTS: Of the 199 patients allocated, 190 patients' (aged 80 ± 7.5 years) data were analysed. Groups were comparable at baseline. In intention-to-treat analysis, length of stay did not differ between groups (HR 1.09 (95% CI, 0.77-1.56) p = 0.6). Physical performance was better in the intervention group at discharge (difference 0.88 (95% CI, 0.20-1.57) p = 0.01), but lost at follow-up (difference 0.45 (95% CI, - 0.43 - 1.33) p = 0.3). An improvement in quality of life was detected at follow-up in the intervention group (difference 0.28 (95% CI, 0.9-0.47) p = 0.004). Overall, fewer negative events occurred in the intervention group (OR 0.46 (95% CI 0.23-0.92) p = 0.03). CONCLUSION: Improvements in physical performance, quality of life and fewer negative events suggest that this intervention is of value to frail medical inpatients. Its effect on length of stay remains unclear. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02463864, registered prospectively 26.05.2015.

Impact of BCG vaccination on incidence of tuberculosis disease in southern Ireland.

BACKGROUND: Tuberculosis (TB) is the ninth leading cause of death worldwide and the leading cause from a single infectious agent. Bacillus Calmette-Guerin (BCG) is the only licensed vaccine for TB, yet its efficacy remains debated with variations in vaccine sub-strains, policies, and practices observed across the world. Three BCG vaccination policies were implemented across adjoining regions in the South West of Ireland from 1972; neonatal vaccination (vaccinated Region-A), vaccination of children aged 10-12 years (vaccinated Region-B) and no vaccination (unvaccinated Region-C). The aim of this study is to examine the impact of different BCG vaccination policies on incidence of TB disease in the South of Ireland over a 13-year period. METHODS: Cases of active TB disease from 2003 to 2016 were identified through surveillance data. Residential addresses for each case were geocoded using the Google Maps API. Addresses were linked to 2011 census population data and to Local Health Offices BCG coverage data for study regions A-C. A steady-state population was assumed to calculate the 13-year incidence of TB disease. Using SatScan (v9.4.4), spatial clusters were identified at a small area level with the spatial scan statistic based on the discrete Poisson probability distribution. RESULTS: Of 621 TB disease cases identified, 510 could be linked to the study area based on the reported addresses. The median age was 42 years (range 4 months - 94 years), 65% male and 66% Irish born. The incidence of TB disease was higher in the unvaccinated population, region-C 132/100,000 (95% CI 116-150) versus vaccinated region-A 56/100,000 (95%CI 45-69) and region-B 44/100,000 (95%CI 29-63). A spatial cluster analysis identified a single high-risk cluster in region -C where the relative risk (vs. the areas outside of the cluster) was 4.94 (95% CI 4.03 to 5.96). CONCLUSION: Our study demonstrates significant regional variation in the incidence of TB in demographically similar populations based on BCG vaccination policy. This observation is particularly noteworthy in a country with low TB disease incidence such as Ireland. These findings strengthen existing data demonstrating efficacy of BCG vaccination for primary prevention of TB disease.

The effect of SENATOR (Software ENgine for the Assessment and optimisation of drug and non-drug Therapy in Older peRsons) on incident adverse drug reactions (ADRs) in an older hospital cohort - Trial Protocol.

BACKGROUND: The aim of this trial is to evaluate the effect of SENATOR software on incident, adverse drug reactions (ADRs) in older, multimorbid, hospitalized patients. The SENATOR software produces a report designed to optimize older patients' current prescriptions by applying the published STOPP and START criteria, highlighting drug-drug and drug-disease interactions and providing non-pharmacological recommendations aimed at reducing the risk of incident delirium. METHODS: We will conduct a multinational, pragmatic, parallel arm Prospective Randomized Open-label, Blinded Endpoint (PROBE) controlled trial. Patients with acute illnesses are screened for recruitment within 48 h of arrival to hospital and enrolled if they meet the relevant entry criteria. Participants' medical history, current prescriptions, select laboratory tests, electrocardiogram, cognitive status and functional status are collected and entered into a dedicated trial database. Patients are individually randomized with equal allocation ratio. Randomization is stratified by site and medical versus surgical admission, and uses random block sizes. Patients randomized to either arm receive standard routine pharmaceutical clinical care as it exists in each site. Additionally, in the intervention arm an individualized SENATOR-generated medication advice report based on the participant's clinical and medication data is placed in their medical record and a senior medical staff member is requested to review it and adopt any of its recommendations that they judge appropriate. The trial's primary outcome is the proportion of patients experiencing at least one adjudicated probable or certain, non-trivial ADR, during the index hospitalization, assessed at 14 days post-randomization or at index hospital discharge if it occurs earlier. Potential ADRs are identified retrospectively by the site researchers who complete a Potential Endpoint Form (one per type of event) that is adjudicated by a blinded, expert committee. All occurrences of 12 pre-specified events, which represent the majority of ADRs, are reported to the committee along with other suspected ADRs. Participants are followed up 12 (+/- 4) weeks post-index hospital discharge to assess medication quality and healthcare utilization. This is the first clinical trial to examine the effectiveness of a software intervention on incident ADRs and associated healthcare costs during hospitalization in older people with multi-morbidity and polypharmacy. TRIAL REGISTRATION NUMBER: Clinicaltrials.gov NCT02097654 , 27 March 2014.

Randomized placebo controlled trial evaluating the safety and efficacy of single low-dose intracoronary insulin-like growth factor following percutaneous coronary intervention in acute myocardial infarction (RESUS-AMI).

BACKGROUND: Residual and significant postinfarction left ventricular (LV) dysfunction, despite technically successful percutaneous coronary intervention (PCI) for ST-elevation myocardial infarction (STEMI), remains an important clinical issue. In preclinical models, low-dose insulin-like growth factor 1 (IGF1) has potent cytoprotective and positive cardiac remodeling effects. We studied the safety and efficacy of immediate post-PCI low-dose intracoronary IGF1 infusion in STEMI patients. METHODS: Using a double-blind, placebo-controlled, multidose study design, we randomized 47 STEMI patients with significantly reduced (≤40%) LV ejection fraction (LVEF) after successful PCI to single intracoronary infusion of placebo (n = 15), 1.5 ng IGF1 (n = 16), or 15 ng IGF1 (n = 16). All received optimal medical therapy. Safety end points were freedom from hypoglycemia, hypotension, or significant arrhythmias within 1 hour of therapy. The primary efficacy end point was LVEF, and secondary end points were LV volumes, mass, stroke volume, and infarct size at 2-month follow-up, all assessed by magnetic resonance imaging. Treatment effects were estimated by analysis of covariance adjusted for baseline (24 hours) outcome. RESULTS: No significant differences in safety end points occurred between treatment groups out to 30 days (χ2 test, P value = .77). There were no statistically significant differences in baseline (24 hours post STEMI) clinical characteristics or LVEF among groups. LVEF at 2 months, compared to baseline, increased in all groups, with no statistically significant differences related to treatment assignment. However, compared with placebo or 1.5 ng IGF1, treatment with 15 ng IGF1 was associated with a significant improvement in indexed LV end-diastolic volume (P = .018), LV mass (P = .004), and stroke volume (P = .016). Late gadolinium enhancement (±SD) at 2 months was lower in 15 ng IGF1 (34.5 ± 29.6 g) compared to placebo (49.1 ± 19.3 g) or 1.5 ng IGF1 (47.4 ± 22.4 g) treated patients, although the result was not statistically significant (P = .095). CONCLUSIONS: In this pilot trial, low-dose IGF1, given after optimal mechanical reperfusion in STEMI, is safe but does not improve LVEF. However, there is a signal for a dose-dependent benefit on post-MI remodeling that may warrant further study.

Comparative Models of Biological and Social Pathways to Predict Child Growth through Age 2 Years from Birth Cohorts in Brazil, India, the Philippines, and South Africa.

Background: Early growth faltering accounts for one-third of child deaths, and adversely impacts the health and human capital of surviving children. Social as well as biological factors contribute to growth faltering, but their relative strength and interrelations in different contexts have not been fully described. Objective: The aim of this study was to use structural equation modelling to explore social and biological multidetermination of child height at age 2 y in longitudinal data from 4 birth cohort studies in low- and middle-income countries. Methods: We analyzed data from 13,824 participants in birth cohort studies in Brazil, India, the Philippines, and South Africa. We used exploratory structural equation models, with height-for-age at 24 mo as the outcome to derive factors, and path analysis to estimate relations among a wide set of social and biological variables common to the 4 sites. Results: The prevalence of stunting at 24 mo ranged from 14.0% in Brazil to 67.7% in the Philippines. Maternal height and birthweight were strongly predictive of height-for-age at 24 mo in all 4 sites (all P values <0.001). Three social-environmental factors, which we characterized as "child circumstances," "family socioeconomic status," and "community facilities," were identified in all sites. Each social-environmental factor was also strongly predictive of height-for-age at 24 mo (all P values <0.001), with some relations partly mediated through birthweight. The biological pathways accounted for 59% of the total explained variance and the social-environmental pathways accounted for 41%. The resulting path coefficients were broadly similar across the 4 sites. Conclusions: Early child growth faltering is determined by both biological and social factors. Maternal height, itself a marker of intergenerational deprivation, strongly influences child height at 2 y, including indirect effects through birthweight and social factors. However, concurrent social factors, many of which are modifiable, directly and indirectly contribute to child growth. This study highlights opportunities for interventions that address both biological and social determinants over the long and short term.

Tissue and Bronchoalveolar Lavage Biomarkers in Idiopathic Pulmonary Fibrosis Patients on Pirfenidone.

BACKGROUND: Pirfenidone is a novel anti-fibrotic agent in idiopathic pulmonary fibrosis with proven clinical benefit. Better human tissue models to demonstrate the immunomodulatory and anti-fibrotic effect of pirfenidone are required. OBJECTIVES: The purpose of the study was to use transbronchial lung cryobiopsy (TBLC), a novel technique which provides substantial tissue samples, and a large panel of biomarkers to temporally assess disease activity and response to pirfenidone therapy. METHODS: Thirteen patients with confirmed idiopathic pulmonary fibrosis (IPF) underwent full physiological and radiological assessment at diagnosis and after 6-month pirfenidone therapy. They underwent assessment for a wide range of potential serum and bronchoalveolar lavage biomarkers of disease activity. Finally, they underwent TBLC before and after treatment. Tissue samples were assessed for numbers of fibroblast foci, for Ki-67, a marker of tissue proliferation and caspase-3, a marker of tissue apoptosis. RESULTS: All patients completed treatment and investigations without significant incident. There was no significant fall in number of fibroblast foci per unit tissue volume after treatment (pre-treatment: 0.14/mm2 vs. post-treatment 0.08/mm2, p = 0.1). Likewise, there was no significant change in other markers of tissue proliferation, Ki-67 or Caspase-3 with pirfenidone treatment. We found an increase in three bronchoalveolar lavage angiogenesis cytokines, Placental Growth Factor, Vascular Endothelial Growth Factor-A, and basic Fibroblast Growth Factor, two anti-inflammatory cytokines Interleukin-10 and Interleukin-4 and Surfactant Protein-D. CONCLUSIONS: TBLC offers a unique opportunity to potentially assess the course of disease activity and response to novel anti-fibrotic activity in IPF.

A protocol to measure the impact of intentional changes to nurse staffing and skill-mix in medical and surgical wards.

AIM: The aim of this research is to measure the impact that planned changes to nurse staffing and skill-mix have on patient, nurse, and organizational outcomes. BACKGROUND: It has been highlighted that there are several design limitations in studies that explore the relationship between nurse staffing and patient, nurse and organizational outcomes; not least that the vast majority of research in this area emanates from studies that are predominantly observational in design. There are limited studies that measure nurse, patient, organizational, and economic outcomes using a longitudinal design following a planned change in nurse staffing. DESIGN: The research will employ a longitudinal, multimethod approach to evaluate the impact that planned changes in nurse staffing and skill-mix have on wards in three pilot hospitals. METHODS: Administrative data collection will take place on a shift-by-shift basis prospectively over a three-year period including the measurement of nursing sensitive outcomes: cross-sectional patient experience data and nurse outcomes (nursing work, job satisfaction, burnout, missed care) will be collected at intervals prior to, during and after the implementation of planned changes in nurse staffing and skill-mix. Data will be analysed using interrupted time-series models, adjusted for key hospital, ward and patient-level factors. An economic costing of the changes will further investigate the resources required for the intervention that can then be aggregated to a national level for future roll-out plans. DISCUSSION: The study aims to provide evidence on the impact of planned changes to nurse staffing and skill-mix based on a systematic approach using a longitudinal design and to determine the extent to which the approach can be implemented at a national level.

A person-centred analysis of the time-use, daily activities and health-related quality of life of Irish school-going late adolescents.

PURPOSE: The health, well-being and quality of life of the world's 1.2 billion adolescents are global priorities. A focus on their patterns or profiles of time-use and how these relate to health-related quality of life (HRQoL) may help to enhance their well-being and address the increasing burden of non-communicable diseases in adulthood. This study sought to establish whether distinct profiles of adolescent 24-h time-use exist and to examine the relationship of any identified profiles to self-reported HRQoL. METHOD: This cross-sectional study gathered data from a random sample of 731 adolescents (response rate 52%) from 28 schools (response rate 76%) across Cork city and county. A person-centred approach, latent profile analysis, was used to examine adolescent 24-h time-use and relate the identified profiles to HRQoL. RESULTS: Three male profiles emerged, namely productive, high leisure and all-rounder. Two female profiles, higher study/lower leisure and moderate study/higher leisure, were identified. The quantitative and qualitative differences in male and female profiles support the gendered nature of adolescent time-use. No unifying trends emerged in the analysis of probable responses in the HRQoL domains across profiles. Females in the moderate study/higher leisure group were twice as likely to have above-average global HRQoL. CONCLUSION: Distinct time-use profiles can be identified amongst adolescents, but their relationship with HRQoL is complex. Rich mixed-method research is required to illuminate our understanding of how quantities and qualities of time-use shape lifestyle patterns and how these can enhance the HRQoL of adolescents in the twenty-first century.

Associations of linear growth and relative weight gain during early life with adult health and human capital in countries of low and middle income: findings from five birth cohort studies.

BACKGROUND: Fast weight gain and linear growth in children in low-income and middle-income countries are associated with enhanced survival and improved cognitive development, but might increase risk of obesity and related adult cardiometabolic diseases. We investigated how linear growth and relative weight gain during infancy and childhood are related to health and human capital outcomes in young adults. METHODS: We used data from five prospective birth cohort studies from Brazil, Guatemala, India, the Philippines, and South Africa. We investigated body-mass index, systolic and diastolic blood pressure, plasma glucose concentration, height, years of attained schooling, and related categorical indicators of adverse outcomes in young adults. With linear and logistic regression models, we assessed how these outcomes relate to birthweight and to statistically independent measures representing linear growth and weight gain independent of linear growth (relative weight gain) in three age periods: 0-2 years, 2 years to mid-childhood, and mid-childhood to adulthood. FINDINGS: We obtained data for 8362 participants who had at least one adult outcome of interest. A higher birthweight was consistently associated with an adult body-mass index of greater than 25 kg/m(2) (odds ratio 1·28, 95% CI 1·21-1·35) and a reduced likelihood of short adult stature (0·49, 0·44-0·54) and of not completing secondary school (0·82, 0·78-0·87). Faster linear growth was strongly associated with a reduced risk of short adult stature (age 2 years: 0·23, 0·20-0·52; mid-childhood: 0·39, 0·36-0·43) and of not completing secondary school (age 2 years: 0·74, 0·67-0·78; mid-childhood: 0·87, 0·83-0·92), but did raise the likelihood of overweight (age 2 years: 1·24, 1·17-1·31; mid-childhood: 1·12, 1·06-1·18) and elevated blood pressure (age 2 years: 1·12, 1·06-1·19; mid-childhood: 1·07, 1·01-1·13). Faster relative weight gain was associated with an increased risk of adult overweight (age 2 years: 1·51, 1·43-1·60; mid-childhood: 1·76, 1·69-1·91) and elevated blood pressure (age 2 years: 1·07, 1·01-1·13; mid-childhood: 1·22, 1·15-1·30). Linear growth and relative weight gain were not associated with dysglycaemia, but a higher birthweight was associated with decreased risk of the disorder (0·89, 0·81-0·98). INTERPRETATION: Interventions in countries of low and middle income to increase birthweight and linear growth during the first 2 years of life are likely to result in substantial gains in height and schooling and give some protection from adult chronic disease risk factors, with few adverse trade-offs. FUNDING: Wellcome Trust and Bill & Melinda Gates Foundation.