Intestinal dysbiosis and inflammation in children with repaired esophageal atresia.

OBJECTIVES: This study aims to compare the intestinal microbiota and intestinal inflammation of children with esophageal atresia (EA) to matched healthy controls, and to investigate the relationship between these factors and clinical outcomes. METHODS: A cross-sectional study of 35 children with EA and 35 matched healthy controls (HC) from a single tertiary pediatric hospital in Australia was conducted. Demographic and dietary data were collected using surveys. Stool samples were analyzed using 16S rRNA sequencing, and fecal calprotectin measurements were used to measure intestinal inflammation. Comparisons were made between the groups, and correlations between the microbiota and clinical factors were investigated in the EA cohort. RESULTS: Compared to HC, children with EA had similar alpha diversity, but beta diversity analysis revealed clustering of EA and HC cohorts. Children with EA had a significantly higher relative abundance of the order Lactobacillales, and a lower abundance of the genus uncultured Bacteroidales S24-7. Fecal calprotectin was significantly higher in children with EA compared to HC. In the EA cohort, children taking proton pump inhibitors (PPI's) had lower alpha diversity and higher calprotectin levels compared to those not taking PPI's. There was a negative correlation between calprotectin and length/height-for-age z scores, and children with higher calprotectin levels had a greater burden of gastrointestinal symptoms. CONCLUSIONS: Children with EA have an altered intestinal microbiota compared to HC, which is likely related to PPI use, and may be impacting on growth and quality of life. It is important to rationalize PPI use in this cohort.

Are serious games seriously good at preparing students for clinical practice?: A randomized controlled trial.

PURPOSE: Serious games (SGs) have great potential for pediatric medical education. This study evaluated the efficacy of a SG in improving learner satisfaction, knowledge, and behavior. MATERIALS AND METHODS: This was an investigator-blinded randomized controlled trial (RCT) comparing a SG against two controls: (i) adaptive tutorial (AT), and (ii) low-stimulus control (LSC). SG is a highly immersive role-playing game in a virtual hospital. AT delivers interactive web-based lessons. LSC is paper-based clinical practice guidelines. Metropolitan senior medical students at UNSW were eligible. A total of 154 enrolled and were block randomized to one intervention. Participants had access to one intervention for 8 weeks which taught pediatric acute asthma and seizure assessment and management. Satisfaction was assessed with Likert-scale responses to 5 statements and 2 free-text comments. Knowledge was assessed with 10 multiple-choice questions (MCQs). Clinical behavior was assessed during a 30-point simulated clinical management scenario (CMS). Primary analysis was performed on a modified intention-to-treat basis and compared: (1) SG vs. AT; and (2) SG vs. LSC. RESULTS: A total of 118 participants were included in the primary analysis (modified intention-to-treat model). No significant differences in MCQ results between the SG and control groups. SG group outperformed the LSC group in the CMS, with a moderate effect (score out of 30: 20.8 (3.2) vs. 18.7 (3.2), respectively, d = 0.65 (0.2-1.1), p = 0.005). No statistically significant difference between SG and AT groups in the CMS (score: 20.8 (3.2) vs. 19.8 (3.1), respectively, d = 0.31 (-0.1 to 0.8), p = 0.18). A sensitivity analysis (per-protocol model) was performed with similar outcomes. CONCLUSIONS: This is the first investigator-blinded RCT assessing the efficacy of a highly immersive SG on learner attitudes, knowledge acquisition, and performance in simulated pediatric clinical scenarios. The SG demonstrated improved translation of knowledge to a simulated clinical environment, particularly compared to LSC. SGs show promise in pediatric medical education.

A validated artificial intelligence-based pipeline for population-wide primary immunodeficiency screening.

BACKGROUND: Identification of patients with underlying inborn errors of immunity and inherent susceptibility to infection remains challenging. The ensuing protracted diagnostic odyssey for such patients often results in greater morbidity and suboptimal outcomes, underscoring a need to develop systematic methods for improving diagnostic rates. OBJECTIVE: The principal aim of this study is to build and validate a generalizable analytical pipeline for population-wide detection of infection susceptibility and risk of primary immunodeficiency. METHODS: This prospective, longitudinal cohort study coupled weighted rules with a machine learning classifier for risk stratification. Claims data were analyzed from a diverse population (n = 427,110) iteratively over 30 months. Cohort outcomes were enumerated for new diagnoses, hospitalizations, and acute care visits. This study followed TRIPOD (Transparent Reporting of a multivariable prediction model for Individual Prognosis Or Diagnosis) standards. RESULTS: Cohort members initially identified as high risk were proportionally more likely to receive a diagnosis of primary immunodeficiency compared to those at low-medium risk or those without claims of interest respectively (9% vs 1.5% vs 0.2%; P < .001, chi-square test). Subsequent machine learning stratification enabled an annualized individual snapshot of complexity for triaging referrals. This study's top-performing machine learning model for visit-level prediction used a single dense layer neural network architecture (area under the receiver-operator characteristic curve = 0.98; F1 score = 0.98). CONCLUSIONS: A 2-step analytical pipeline can facilitate identification of individuals with primary immunodeficiency and accurately quantify clinical risk.

Striking the Right Balance and Supporting Social Aspirations: How Agency and Choice Play out in a Recovery-Oriented Mental Health Service.

INTRODUCTION: There has been an increasing drive for a transformation of the mental health system towards recovery orientation, with research identifying a series of key recovery principles. It has been argued that these principles remain rhetoric rather than routine practice, and it remains unclear how these are operationalised and promoted within inpatient settings. AIM: To address the knowledge gap of how staff and service-users enact recovery principles during the daily workings of an inpatient mental health service. METHOD: Twenty-one interviews were conducted with staff and service-users at a recovery-oriented inpatient service in the United Kingdom. Data was analysed using framework analysis. FINDINGS: Analysis of research interview data identified three subcategories grouped under the category of choice. These categories were: a delicate balancing act, acceptability of choices, and social issues impacting choice. DISCUSSION: Staff were uncertain of their role in promoting choice, resulting in service-users feeling unsupported in their recovery. Staff had to adopt a titrated approach to social inclusion, to protect service-users from discrimination and rejection. IMPLICATIONS: Mental health professionals need to take a more proactive role in enabling service-users to realise their social aspirations, as well as managing any adverse impacts of stigma and discrimination.

Children With Cystic Fibrosis Have Elevated Levels of Fecal Chitinase-3-like-1.

Although chitinase-3-like-1 (CHI3L1), predominately produced by epithelial cells and macrophages, is relevant to pulmonary disease in cystic fibrosis (CF), fecal levels have not yet been assessed in children with CF. Fecal CHI3L1 was measured with a commercial immunoassay using fecal samples provided by children with CF and healthy control (HC) children. Higher median (interquartile range) fecal CHI3L1 levels were seen in the 52 children with CF than in the 35 controls: 15.97 (3.34-50.53) ng/g versus 2.93 (2.13-9.27) ng/g ( P = 0.001). Fecal CHI3LI did not differ according to sex. In the children with CF, fecal CHI3L1 levels did not correlate with growth parameters nor were the levels affected by pancreatic insufficiency. Children with CF had higher fecal CHI3L1 levels, suggesting underlying gut inflammation. Further work is required to confirm the current findings and to ascertain the longer-term significance of elevated CHI3L1.

Evaluating the Dietary Intake of Children With Esophageal Atresia: A Prospective, Controlled, Observational Study.

OBJECTIVES: Children with esophageal atresia (EA) often have feeding difficulties and dysphagia, which may compromise their nutritional status. This study aimed to compare dietary intake between children with EA and matched healthy controls (HC) and to investigate the relationship between dietary factors, growth, dysphagia, and feeding difficulties in the EA cohort. METHODS: This cross-sectional cohort study recruited children with EA and HC aged 2-17 years from a tertiary pediatric hospital in Australia. Growth parameters were measured. Dietary intake was assessed using the validated Australian Child and Adolescent Eating Survey. Dysphagia and feeding difficulties were assessed using objective questionnaires. RESULTS: Twenty-one children with EA were matched for age and sex with 21 HC. Compared to HC, children with EA had lower mean z scores for height-for-age, but mean weight-for-age and body mass index-for-age z scores were similar. Energy intake was similar between the groups. The diet of children with EA consisted of a higher proportion of fats and lower proportion of carbohydrates compared to matched HC. Dysphagia severity in children with EA positively correlated with proportion of energy from fats and saturated fats. CONCLUSIONS: Children with EA have similar energy intake and growth parameters to HC, but their diet consists of a higher proportion of fats and lower proportion of carbohydrates compared to HC. Targeted dietary interventions and parental education are necessary.

Systematic Review of Authentication and Authorization Advancements for the Internet of Things.

Technologies for the Internet of Things (IoT) are maturing, yet no common standards dictate their direction, leaving space for a plethora of research directions and opportunities. Among the most important IoT topics is security. When we design a robust system, it is important to know the available options for facing common tasks related to access control, authentication, and authorization. In this review, we systematically analyze 1622 peer-reviewed publications from October 2017 to December 2020 to find the taxonomy of security solutions. In addition, we assess and categorize current practices related to IoT security solutions, commonly involved technologies, and standards applied in recent research. This manuscript provides a practical road map to recent research, guiding the reader and providing an overview of recent research efforts.

Protein kinase A negatively regulates Ca2+ signalling in Toxoplasma gondii.

The phylum Apicomplexa comprises a group of obligate intracellular parasites that alternate between intracellular replicating stages and actively motile extracellular forms that move through tissue. Parasite cytosolic Ca2+ signalling activates motility, but how this is switched off after invasion is complete to allow for replication to begin is not understood. Here, we show that the cyclic adenosine monophosphate (cAMP)-dependent protein kinase A catalytic subunit 1 (PKAc1) of Toxoplasma is responsible for suppression of Ca2+ signalling upon host cell invasion. We demonstrate that PKAc1 is sequestered to the parasite periphery by dual acylation of PKA regulatory subunit 1 (PKAr1). Upon genetic depletion of PKAc1 we show that newly invaded parasites exit host cells shortly thereafter, in a perforin-like protein 1 (PLP-1)-dependent fashion. Furthermore, we demonstrate that loss of PKAc1 prevents rapid down-regulation of cytosolic [Ca2+] levels shortly after invasion. We also provide evidence that loss of PKAc1 sensitises parasites to cyclic GMP (cGMP)-induced Ca2+ signalling, thus demonstrating a functional link between cAMP and these other signalling modalities. Together, this work provides a new paradigm in understanding how Toxoplasma and related apicomplexan parasites regulate infectivity.

End of life care for people with severe mental illness: Mixed methods systematic review and thematic synthesis (the MENLOC study).

BACKGROUND: Parity of esteem means that end-of-life care for people with severe mental illness should be of equal quality to that experienced by all. AIM: To synthesise international, English language, research and UK policy and guidance relating to the organisation, provision, and receipt of end-of-life care for people with severe mental illness. DESIGN: A mixed methods systematic review was conducted following the Evidence for Policy and Practice Information and Co-ordinating Centre approach and informed by a stakeholder group. We employed thematic synthesis to bring together data from both qualitative and quantitative studies, and from non-research material. We assessed the strength of synthesised findings using the Confidence in the Evidence from Reviews of Qualitative Research (CERQual) and Grading of Recommendations, Assessment, Development and Evaluation (GRADE) approaches. DATA SOURCES: Ten electronic databases were searched from inception to December 2019, along with 62 organisational websites. Quality appraisal was conducted using Critical Appraisal Skills Programme checklists or other study design-specific alternatives as necessary. RESULTS: Of the 11,904 citations retrieved, 34 research publications were included plus 28 non-research items. The majority of research was of high or acceptable quality. An overarching synthesis including 52 summary statements, with assessments of confidence in the underpinning evidence, was produced using four themes: Structure of the system; Professional issues; Contexts of care; and Living with severe mental illness. CONCLUSIONS: Implications for services and practice reflect evidence in which there is a high degree of confidence. Partnership should be developed across the mental health and end-of-life systems, and ways found to support people to die where they choose. Staff caring for people with severe mental illness at the end-of-life need education, support and supervision. End-of-life care for people with severe mental illness requires a team approach, including advocacy. Proactive physical health care for people with severe mental illness is needed to tackle problems of delayed diagnosis.

Resuscitating Cardiopulmonary Resuscitation Training in a Virtual Reality: Prospective Interventional Study.

BACKGROUND: Simulation-based technologies are emerging to enhance medical education in the digital era. However, there is limited data for the use of virtual reality simulation in pediatric medical education. We developed Virtual Doc as a highly immersive virtual reality simulation to teach pediatric cardiopulmonary resuscitation skills to medical students. OBJECTIVE: The primary objectives of this study were to evaluate participant satisfaction and perceived educational efficacy of Virtual Doc. The secondary aim of this study was to assess the game play features of Virtual Doc. METHODS: We conducted a prospective closed beta-testing study at the University of New South Wales (Sydney, Australia) in 2018. All medical students from the 6-year undergraduate program were eligible to participate and were recruited through voluntary convenience sampling. Participants attended a 1-hour testing session and attempted at least one full resuscitation case using the virtual reality simulator. Following this, participants were asked to complete an anonymous postsession questionnaire. Responses were analyzed using descriptive statistics. RESULTS: A total of 26 participants were recruited, consented to participate in this study, and attended a 1-hour in-person closed beta-testing session, and 88% (23/26) of participants completed the anonymous questionnaire and were included in this study. Regarding participant satisfaction, Virtual Doc was enjoyed by 91% (21/23) of participants, with 74% (17/23) intending to recommend the simulation to a colleague and 66% (15/23) intending to recommend the simulation to a friend. In assessment of the perceived educational value of Virtual Doc, 70% (16/23) of participants agreed they had an improved understanding of cardiopulmonary resuscitation, and 78% (18/23) agreed that Virtual Doc will help prepare for and deal with real-life clinical scenarios. Furthermore, 91% (21/23) of participants agreed with the development of additional Virtual Doc cases as beneficial for learning. An evaluation of the game play features as our secondary objective revealed that 70% (16/23) of participants agreed with ease in understanding how to use Virtual Doc, and 74% (17/23) found the game play elements useful in understanding cardiopulmonary resuscitation. One-third (7/23, 30%) found it easy to work with the interactive elements. In addition, 74% (17/23) were interested in interacting with other students within the simulation. CONCLUSIONS: Our study demonstrates a positive response regarding trainee satisfaction and perceived educational efficacy of Virtual Doc. The simulation was widely accepted by the majority of users and may have the potential to improve educational learning objectives.

Protein O-fucosyltransferase 2-mediated O-glycosylation of the adhesin MIC2 is dispensable for Toxoplasma gondii tachyzoite infection.

Toxoplasma gondii is a ubiquitous, obligate intracellular eukaryotic parasite that causes congenital birth defects, disease in immunocompromised individuals, and blindness. Protein glycosylation plays an important role in the infectivity and evasion of immune responses of many eukaryotic parasites and is also of great relevance to vaccine design. Here we demonstrate that micronemal protein 2 (MIC2), a motility-associated adhesin of T. gondii, has highly glycosylated thrombospondin repeat (TSR) domains. Using affinity-purified MIC2 and MS/MS analysis along with enzymatic digestion assays, we observed that at least seven C-linked and three O-linked glycosylation sites exist within MIC2, with >95% occupancy at these O-glycosylation sites. We found that addition of O-glycans to MIC2 is mediated by a protein O-fucosyltransferase 2 homolog (TgPOFUT2) encoded by the TGGT1_273550 gene. Even though POFUT2 homologs are important for stabilizing motility-associated adhesins and for host infection in other apicomplexan parasites, loss of TgPOFUT2 in T. gondii had only a modest impact on MIC2 levels and the wider parasite proteome. Consistent with this, both plaque formation and tachyzoite invasion were broadly similar in the presence or absence of TgPOFUT2. These findings indicate that TgPOFUT2 O-glycosylates MIC2 and that this glycan, in contrast to previous findings in another study, is dispensable in T. gondii tachyzoites and for T. gondii infectivity.

An apically located hybrid guanylate cyclase-ATPase is critical for the initiation of Ca2+ signaling and motility in Toxoplasma gondii.

Protozoan parasites of the phylum Apicomplexa actively move through tissue to initiate and perpetuate infection. The regulation of parasite motility relies on cyclic nucleotide-dependent kinases, but how these kinases are activated remains unknown. Here, using an array of biochemical and cell biology approaches, we show that the apicomplexan parasite Toxoplasma gondii expresses a large guanylate cyclase (TgGC) protein, which contains several upstream ATPase transporter-like domains. We show that TgGC has a dynamic localization, being concentrated at the apical tip in extracellular parasites, which then relocates to a more cytosolic distribution during intracellular replication. Conditional TgGC knockdown revealed that this protein is essential for acute-stage tachyzoite growth, as TgGC-deficient parasites were defective in motility, host cell attachment, invasion, and subsequent host cell egress. We show that TgGC is critical for a rapid rise in cytosolic [Ca2+] and for secretion of microneme organelles upon stimulation with a cGMP agonist, but these deficiencies can be bypassed by direct activation of signaling by a Ca2+ ionophore. Furthermore, we found that TgGC is required for transducing changes in extracellular pH and [K+] to activate cytosolic [Ca2+] flux. Together, the results of our work implicate TgGC as a putative signal transducer that activates Ca2+ signaling and motility in Toxoplasma.

Cystic Fibrosis-related Liver Disease is Associated With Increased Disease Burden and Endocrine Comorbidities.

BACKGROUND: Cystic fibrosis-related liver disease (CFLD) is the leading nonpulmonary cause of mortality in cystic fibrosis (CF). We evaluated and compared the burden of disease and nonrespiratory comorbidities of those with severe CFLD and those without (noCFLD). METHODS: A retrospective nationwide (Australia) longitudinal review (from 1998 to 2016) of severe CFLD patients compared with noCFLD controls (matched 1 : 1 for age, genotype, pancreatic insufficiency, and center). RESULTS: One hundred sixty-six patients with severe CFLD and 166 with noCFLD were identified. Forced expiratory volume in 1 second percentage of predicted (FEV1%) was significantly lower in CFLD than noCFLD across all ages (estimate [SE] -6.05% [2.12]; P = 0.004). Median (IQR) hospitalizations per patient per year were higher in CFLD than noCFLD for: respiratory indications (0.6 [0.2-1.3] vs 0.4 [0.1-0.9]; P = 0.002); gastrointestinal indications (0.09 [0-0.2] vs 0 [0-0.05]; P < 0.001); and other indications (0.05 [0-0.2] vs 0 [0-0.1]; P = 0.03). In the CFLD cohort, there was increased use of nasogastric (12.6% vs 5.4%; OR 2.51 [95% CI 1.06-6.46]; P = 0.03) and gastrostomy nutritional supplementation (22.9% vs 13.2%; OR 1.93 [95% CI 1.05-3.63]; P = 0.03). Additionally, the CFLD cohort had a higher frequency of bone diseases, osteopenia (26.5% vs 16.8%; OR 1.77 [95%CI 1.01-3.15]; P = 0.04) and osteoporosis (16.2% vs 8.4%; OR 2.1 [95% CI 1.01-4.52]; P = 0.04), as well as CF-related diabetes (38.5% vs 19.2%; OR 2.61 [95% CI 1.55-4.47]; P = 0.001). CONCLUSIONS: Patients with severe CFLD have greater disease burden, with higher number of hospitalizations (both respiratory and nonrespiratory indications), nutritional interventions, and are at higher risk of CF-related bone disease and diabetes.

Evaluating the Dietary Intakes of Energy, Macronutrients, Sugar, Fiber, and Micronutrients in Children With Celiac Disease.

OBJECTIVES: Children with celiac disease (CD) follow a lifelong gluten-free diet. This restrictive diet may be associated with nutritional compromise. Our objectives were, therefore, to evaluate the dietary composition (energy, macronutrients and micronutrients, and fiber) in children with CD compared with healthy controls (HC) and relationship between dietary composition and socioeconomic status. METHODS: This cross-sectional, case-control study recruited children with CD ages 2 to 18 years and HC matched for age, sex, and socioeconomic status. Clinical, sociodemographic, and dietary information were collected. A false discovery rate correction was applied to the P-value for multiple comparisons (q-value). RESULTS: Sixty-five CD children were matched with 65 HC (mean [SD] age: 10.2 [3.6] vs 10.1 [3.7] years, P = 0.96). Compared with HC, CD children had higher intakes of energy (2413.2 [489.9] vs 2190.8 (593.5) kcal/day, P = 0.02), total fat (818.1 ±â€Š180.9 vs 714.3 ±â€Š212.2 kcal/day, q = 0.018), and subtypes of fat (saturated, polyunsaturated, and monounsaturated). There were no differences in other macronutrients, sugar, micronutrients, or fiber between CD and HC, and no difference in dietary intake among CD between socioeconomic disadvantage versus advantage. Children with CD had lower weight z-scores (-0.06 [1.05] vs 0.47 [0.96], P = 0.003) and body mass index (BMI) z-scores (-0.02 [0.88] vs 0.41 [1.09], P = 0.02) than HC. CONCLUSIONS: Children with CD had higher calorie and fat intake compared with HC. Despite this, CD children had lower weight and BMI z-scores compared with HC.

Probiotics for people with cystic fibrosis.

BACKGROUND: Cystic fibrosis (CF) is a multisystem disease and the importance of growth and nutrition has been well established, given its implications for lung function and overall survival. It has been established that intestinal dysbiosis (i.e. microbial imbalance) and inflammation is present in people with CF. Probiotics are commercially available (over-the-counter) and may improve both intestinal and overall health. OBJECTIVES: To assess the efficacy and safety of probiotics for improving health outcomes in children and adults with CF. SEARCH METHODS: We searched the Cochrane Cystic Fibrosis Trials Register, compiled from electronic database searches and handsearching of journals and conference abstract books. Date of last register search: 20 January 2020. We also searched ongoing trials registries and the reference lists of relevant articles and reviews. Date of last search: 29 January 2019. SELECTION CRITERIA: Randomised or quasi-randomised controlled trials (RCTs) assessing efficacies and safety of probiotics in children and adults with CF. Cross-over RCTs with a washout phase were included and for those without a washout period, only the first phase of each trial was analysed. DATA COLLECTION AND ANALYSIS: We independently extracted data and assessed the risk of bias of the included trials; we used GRADE to assess the certainty of the evidence. We contacted trial authors for additional data. Meta-analyses were undertaken on outcomes at several time points. MAIN RESULTS: We identified 17 trials and included 12 RCTs (11 completed and one trial protocol - this trial was terminated early) (464 participants). Eight trials included only children, whilst four trials included both children and adults. Trial duration ranged from one to 12 months. Nine trials compared a probiotic (seven single strain and three multistrain preparations) with a placebo preparation, two trials compared a synbiotic (multistrain) with a placebo preparation and one trial compared two probiotic preparations. Overall we judged the risk of bias in the 12 trials to be low. Three trials had a high risk of performance bias, two trials a high risk of attrition bias and six trials a high risk of reporting bias. Only two trials were judged to have low or unclear risk of bias for all domains. Four trials were sponsored by grants only, two trials by industry only, two trials by both grants and industry and three trials had an unknown funding source. Combined data from four trials (225 participants) suggested probiotics may reduce the number of pulmonary exacerbations during a four to 12 month time-frame, mean difference (MD) -0.32 episodes per participant (95% confidence interval (CI) -0.68 to 0.03; P = 0.07) (low-certainty evidence); however, the 95% CI includes the possibility of both an increased and a reduced number of exacerbations. Additionally, two trials (127 participants) found no evidence of an effect on the duration of antibiotic therapy during the same time period. Combined data from four trials (177 participants) demonstrated probiotics may reduce faecal calprotectin, MD -47.4 µg/g (95% CI -93.28 to -1.54; P = 0.04) (low-certainty evidence), but the results for other biomarkers mainly did not show any difference between probiotics and placebo. Two trials (91 participants) found no evidence of effect on height, weight or body mass index (low-certainty evidence). Combined data from five trials (284 participants) suggested there was no difference in lung function (forced expiratory volume at one second (FEV1) % predicted) during a three- to 12-month time frame, MD 1.36% (95% CI -1.20 to 3.91; P = 0.30) (low-certainty evidence). Combined data from two trials (115 participants) suggested there was no difference in hospitalisation rates during a three- to 12-month time frame, MD -0.44 admissions per participant (95% CI -1.41 to 0.54; P = 0.38) (low-certainty evidence). One trial (37 participants) reported health-related quality of life and while the parent report favoured probiotics, SMD 0.87 (95% CI 0.19 to 1.55) the child self-report did not identify any effect, SMD 0.59 (95% CI -0.07 to 1.26) (low-certainty evidence). There were limited results for gastrointestinal symptoms and intestinal microbial profile which were not analysable. Only four trials and one trial protocol (298 participants) reported adverse events as a priori hypotheses. No trials reported any deaths. One terminated trial (12 participants and available as a protocol only) reported a severe allergic reaction (severe urticaria) for one participant in the probiotic group. Two trials reported a single adverse event each (vomiting in one child and diarrhoea in one child). The estimated number needed to harm for any adverse reaction (serious or not) is 52 people (low-certainty evidence). AUTHORS' CONCLUSIONS: Probiotics significantly reduce faecal calprotectin (a marker of intestinal inflammation) in children and adults with CF, however the clinical implications of this require further investigation. Probiotics may make little or no difference to pulmonary exacerbation rates, however, further evidence is required before firm conclusions can be made. Probiotics are associated with a small number of adverse events including vomiting, diarrhoea and allergic reactions. In children and adults with CF, probiotics may be considered by patients and their healthcare providers. Given the variability of probiotic composition and dosage, further adequately-powered multicentre RCTs of at least 12 months duration are required to best assess the efficacy and safety of probiotics for children and adults with CF.

Paediatric pancreatic diseases.

Paediatric pancreatic diseases are often under-recognised and may be associated with severe diseases and significant clinical consequences. In recent years, advances have been made in key areas, particularly with the contributions from international societies and study groups focused on paediatric pancreatic disease research. This review focuses on the two key manifestations of pancreatic disorders in childhood, pancreatitis and exocrine pancreatic dysfunction.

Recovery-focused mental health care planning and co-ordination in acute inpatient mental health settings: a cross national comparative mixed methods study.

BACKGROUND: Involving mental health service users in planning and reviewing their care can help personalised care focused on recovery, with the aim of developing goals specific to the individual and designed to maximise achievements and social integration. We aimed to ascertain the views of service users, carers and staff in acute inpatient wards on factors that facilitated or acted as barriers to collaborative, recovery-focused care. METHODS: A cross-national comparative mixed-methods study involving 19 mental health wards in six service provider sites in England and Wales. This included a survey using established standardised measures of service users (n = 301) and staff (n = 290) and embedded case studies involving interviews with staff, service users and carers (n = 76). Quantitative and qualitative data were analysed within and across sites using descriptive and inferential statistics, and framework method. RESULTS: For service users, when recovery-oriented focus was high, the quality of care was rated highly, as was the quality of therapeutic relationships. For staff, there was a moderate correlation between recovery orientation and quality of therapeutic relationships, with considerable variability. Staff members rated the quality of therapeutic relationships higher than service users did. Staff accounts of routine collaboration contrasted with a more mixed picture in service user accounts. Definitions and understandings of recovery varied, as did views of hospital care in promoting recovery. Managing risk was a central issue for staff, and service users were aware of measures taken to keep them safe, although their involvement in discussions was less apparent. CONCLUSIONS: There is positive practice within acute inpatient wards, with evidence of commitment to safe, respectful, compassionate care. Recovery ideas were evident but there remained ambivalence on their relevance to inpatient care. Service users were aware of efforts taken to keep them safe, but despite measures described by staff, they did not feel routinely involved in care planning or risk management decisions. Research on increasing therapeutic contact time, shared decision making in risk assessment and using recovery focused tools could further promote personalised and recovery-focused care planning. This paper arises from a larger study published by National Institute for Health Research (Simpson A, et al, Health Serv Deliv Res 5(26), 2017).

Quality of life, recovery and decision-making: a mixed methods study of mental health recovery in social care.

PURPOSE: Mental health care is a complex system that includes social care organisations providing support for people with continuing needs. The relationship over time between decisional conflict, social support, quality of life and recovery outcomes across two time periods for people experiencing mental health problems in receipt of social care was investigated. METHODS: This is a mixed methods study comprised of a quantitative survey at two time points using measures of decisional conflict, social support, recovery and quality of life in a random sample (n = 122) using social care services in Wales, UK. In addition, 16 qualitative case studies were developed from data collected from individuals, a supportive other and a care worker (n = 41) to investigate trajectories of care. Survey responses were statistically analysed using SPSS and case study data were thematically analysed. RESULTS: Participants reported increasing decisional conflict and decreasing social support, recovery and quality of life over the two time points. Linear regression indicated that higher recovery scores predict better quality of life ratings and as ratings for social support decline this is associated with lower quality of life. Correlational analysis indicated that lower decisional conflict is associated with higher quality of life. Thematic analysis indicated that 'connectedness and recovery' is a product of 'navigating the system of care' and the experience of 'choice and involvement' achieved by individuals seeking help. CONCLUSIONS: These results indicate that quality of life for people experiencing mental health difficulties is positively associated with social support and recovery and negatively associated with decisional delay.

Too Busy to Talk: Examining Service User Involvement in Nursing Work.

Traditional ideas of mental health nursing are challenged in contemporary healthcare settings by developments focussed on more partnership and collaboration with people using mental health services. Yet service users have reported limited involvement in planning their own care. The purpose of this research was to explore accounts from multiple perspectives about service user involvement in mental health nursing processes. Qualitative research interviews and focus groups with mental health nursing students (n = 18), qualified nurses (n = 17) and service users (n = 13) were conducted, audio-recorded and transcribed verbatim. Participants' transcribed talk was thematically analysed to examine understandings about service user involvement and mental health nursing. Nursing work was often described as task-focussed, with limited collaboration with service users in areas like care planning. Service user involvement was seldom mentioned by nurses themselves, indicating it did not form an important part of mental health nursing processes. Mental health nurses appear to be complicit in care processes that do not include involvement of service users and may discourage novice practitioners from attempts at engagement.

Populations of Phytophthora rubi Show Little Differentiation and High Rates of Migration Among States in the Western United States.

Population genetics is a powerful tool to understand patterns and evolutionary processes that are involved in plant-pathogen emergence and adaptation to agricultural ecosystems. We are interested in studying the population dynamics of Phytophthora rubi, the causal agent of Phytophthora root rot in raspberry. P. rubi is found in the western United States, where most of the fresh and processed raspberries are produced. We used genotyping-by-sequencing to characterize genetic diversity in populations of P. rubi sampled in the United States and other countries. Our results confirm that P. rubi is a monophyletic species with complete lineage sorting from its sister taxon P. fragariae. Overall, populations of P. rubi show low genetic diversity across the western United States. Demographic analyses suggest that populations of P. rubi from the western United States are the source of pathogen migration to Europe. We found no evidence for population differentiation at a global or regional (western United States) level. Finally, our results provide evidence of migration from California and Oregon into Washington. This report provides new insights into the evolution and structure of global and western United States populations of the raspberry pathogen P. rubi, indicating that human activity might be involved in moving the pathogen among regions and fields.