Novel antiinflammatory biologics shaped by parasite-host coevolution.

Parasitic helminth infections, while a major cause of neglected tropical disease burden, negatively correlate with the incidence of immune-mediated inflammatory diseases such as inflammatory bowel diseases (IBD). To evade expulsion, helminths have developed sophisticated mechanisms to regulate their host's immune responses. Controlled experimental human helminth infections have been assessed clinically for treating inflammatory conditions; however, such a radical therapeutic modality has challenges. An alternative approach is to harness the immunomodulatory properties within the worm's excretory-secretory (ES) complement, its secretome. Here, we report a biologics discovery and validation pipeline to generate and screen in vivo a recombinant cell-free secretome library of helminth-derived immunomodulatory proteins. We successfully expressed 78 recombinant ES proteins from gastrointestinal hookworms and screened the crude in vitro translation reactions for anti-IBD properties in a mouse model of acute colitis. After statistical filtering and ranking, 20 proteins conferred significant protection against various parameters of colitis. Lead candidates from distinct protein families, including annexins, transthyretins, nematode-specific retinol-binding proteins, and SCP/TAPS were identified. Representative proteins were produced in mammalian cells and further validated, including ex vivo suppression of inflammatory cytokine secretion by T cells from IBD patient colon biopsies. Proteins identified herein offer promise as novel, safe, and mechanistically differentiated biologics for treating the globally increasing burden of inflammatory diseases.

Early mobilisation in critically ill children: Does routine patient screening reduce time to commencing mobilisation?

OBJECTIVE: The objective of this study was to investigate the impact of daily screening for medical readiness to participate in early mobilisation in the paediatric intensive care unit (PICU), on reducing time to mobilisation and to explore the safety-, feasibility-, and patient-level barriers to the practice. METHODS: An interventional study with a historical control group was conducted in a PICU in a tertiary teaching hospital in Australia. The Early Mobilisation Screening Checklist was applied at 24-48 h of PICU stay with the aim to reduce time to commencing mobilisation. All patients aged term to 18 years admitted to the PICU for >48 h were included in this study. Data on time to mobilisation and patient characteristics were collected by an unblinded case note audit of children admitted to the PICU over 5 months in 2018 for the baseline group and over a corresponding period in 2019 for the intervention group. MEASUREMENTS AND MAIN RESULTS: A total of 71 children were enrolled. Survival analysis was used to compare time to mobilisation between groups, and a cox regression model found that children in the intervention group were 1.26 times more likely to participate in mobility, but this was not statistically significant (P = 0.391, log rank test for equality of survival functions). Early mobilisation was safe, with no adverse events reported in 177 participant mobilisation days. Feasibility was demonstrated by 62% of participants mobilising within 72 h of admission. Mechanical ventilation during stay (P = 0.043) and days receiving sedation infusion (% of days) (P = 0.042) were associated with a decreased likelihood of participating in mobility. CONCLUSIONS: Implementation of routine screening alone does not significantly reduce time to commencing mobility in the PICU. Early mobilisation in the PICU is safe and feasible and resulted in no adverse events during mobilisation. Patient characteristics influencing participation in mobility warrant further exploration.

Interventions for smoking cessation in Indigenous populations.

This review has been withdrawn because it does it does not include recent evidence and does not reflect up-to-date Cochrane methodological standards.

Interventions for tobacco use prevention in Indigenous youth.

This review has been withdrawn because it does it does not include recent evidence and does not reflect up-to-date Cochrane methodological standards.

Evaluating the Reliability of the Needs in Recovery Assessment (NiRA) with Simulated Patients.

INTRODUCTION: The Needs in Recovery Assessment (NiRA) is a tool designed to support recovery-oriented and person-centred approaches in mental health services through facilitating the identification and prioritisation of needs. The aim of this study was to evaluate the interrater reliability of the NiRA. Method: Ten mental health clinicians from various professional backgrounds used the NiRA to facilitate assessment interviews with Simulated Patients. Completed and semi-completed NiRA forms, questionnaires, and audio-visual recordings of assessment interviews were collected for analysis. The interrater reliability of the NiRA was calculated using percent agreement and Gwet's Agreement Coefficient (AC)1. Results: Percent agreement across all items of the finalised tool was 0.84 (item range: 0.55 to 1.0). Overall interrater reliability (Gwet's AC1) was 0.70 (95% CI 0.64-0.76) with items ranging from -0.08 to 1.0. Conclusion: The NiRA is a reliable tool and is ready to be trialled in a feasibility study in clinical settings. It is anticipated that the NiRA will facilitate a deeper understanding of service users' needs and a more targeted approach to meeting unmet needs.

Psychological therapies for the treatment of depression in chronic obstructive pulmonary disease.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) has been recognised as a global health concern, and one of the leading causes of morbidity and mortality worldwide. Projections of the World Health Organization (WHO) indicate that prevalence rates of COPD continue to increase, and by 2030, it will become the world's third leading cause of death. Depression is a major comorbidity amongst patients with COPD, with an estimate prevalence of up to 80% in severe stages of COPD. Prevalence studies show that patients who have COPD are four times as likely to develop depression compared to those without COPD. Regrettably, they rarely receive appropriate treatment for COPD-related depression. Available findings from trials indicate that untreated depression is associated with worse compliance with medical treatment, poor quality of life, increased mortality rates, increased hospital admissions and readmissions, prolonged length of hospital stay, and subsequently, increased costs to the healthcare system. Given the burden and high prevalence of untreated depression, it is important to evaluate and update existing experimental evidence using rigorous methodology, and to identify effective psychological therapies for patients with COPD-related depression. OBJECTIVES: To assess the effectiveness of psychological therapies for the treatment of depression in patients with chronic obstructive pulmonary disease. SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (2018, Issue 11), and Ovid MEDLINE, Embase and PsycINFO from June 2016 to 26 November 2018. Previously these databases were searched via the Cochrane Airways and Common Mental Disorders Groups' Specialised Trials Registers (all years to June 2016). We searched ClinicalTrials.gov, the ISRCTN registry, and the World Health Organization International Clinical Trials Registry Platform (ICTRP) to 26 November 2018 to identify unpublished or ongoing trials. Additionally, the grey literature databases and the reference lists of studies initially identified for full-text screening were also searched. SELECTION CRITERIA: Eligible for inclusion were randomised controlled trials that compared the use of psychological therapies with either no intervention, education, or combined with a co-intervention and compared with the same co-intervention in a population of patients with COPD whose depressive symptoms were measured before or at baseline assessment. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed the titles and abstracts identified by the search to determine which studies satisfied the inclusion criteria. We assessed two primary outcomes: depressive symptoms and adverse events; and the following secondary outcomes: quality of life, dyspnoea, forced expiratory volume in one second (FEV1), exercise tolerance, hospital length of stay or readmission rate, and cost-effectiveness. Potentially eligible full-text articles were also independently assessed by two review authors. A PRISMA flow diagram was prepared to demonstrate the decision process in detail. We used the Cochrane 'Risk of bias' evaluation tool to examine the risk of bias, and assessed the quality of evidence using the GRADE framework. All outcomes were continuous, therefore, we calculated the pooled standardised mean difference (SMD) or mean difference (MD) with a corresponding 95% confidence interval (CI). We used a random-effects model to calculate treatment effects. MAIN RESULTS: The findings are based on 13 randomised controlled trials (RCTs), with a total of 1500 participants. In some of the included studies, the investigators did not recruit participants with clinically confirmed depression but applied screening criteria after randomisation. Hence, across the studies, baseline scores for depressive symptoms varied from no symptoms to severe depression. The severity of COPD across the studies was moderate to severe.Primary outcomesThere was a small effect showing the effectiveness of psychological therapies in improving depressive symptoms when compared to no intervention (SMD 0.19, 95% CI 0.05 to 0.33; P = 0.009; 6 studies, 764 participants), or to education (SMD 0.23, 95% CI 0.06 to 0.41; P = 0.010; 3 studies, 507 participants).Two studies compared psychological therapies plus a co-intervention versus the co-intervention alone (i.e. pulmonary rehabilitation (PR)). The results suggest that a psychological therapy combined with a PR programme can reduce depressive symptoms more than a PR programme alone (SMD 0.37, 95% CI -0.00 to 0.74; P = 0.05; 2 studies, 112 participants).We rated the quality of evidence as very low. Owing to the nature of psychological therapies, blinding of participants, personnel, and outcome assessment was a concern.None of the included studies measured adverse events.Secondary outcomesQuality of life was measured in four studies in the comparison with no intervention, and in three studies in the comparison with education. We found inconclusive results for improving quality of life. However, when we pooled data from two studies using the same measure, the result suggested that psychological therapy improved quality of life better than no intervention. One study measured hospital admission rates and cost-effectiveness and showed significant reductions in the intervention group compared to the education group. We rated the quality of evidence as very low for the secondary outcomes. AUTHORS' CONCLUSIONS: The findings from this review indicate that psychological therapies (using a CBT-based approach) may be effective for treating COPD-related depression, but the evidence is limited. Depressive symptoms improved more in the intervention groups compared to: 1) no intervention (attention placebo or standard care), 2) educational interventions, and 3) a co-intervention (pulmonary rehabilitation). However, the effect sizes were small and quality of the evidence very low due to clinical heterogeneity and risk of bias. This means that more experimental studies with larger numbers of participants are needed, to confirm the potential beneficial effects of therapies with a CBT approach for COPD-related depression.New trials should also address the gap in knowledge related to limited data on adverse effects, and the secondary outcomes of quality of life, dyspnoea, forced expiratory volume in one second (FEV1), exercise tolerance, hospital length of stay and frequency of readmissions, and cost-effectiveness. Also, new research studies need to adhere to robust methodology to produce higher quality evidence.

Adjuvant therapy with antidepressants for the management of inflammatory bowel disease.

BACKGROUND: Symptoms of anxiety and depression are common in inflammatory bowel disease (IBD). Antidepressants are taken by approximately 30% of people with IBD. However, there are no current guidelines on treating co-morbid anxiety and depression in people with IBD with antidepressants, nor are there clear data on the role of antidepressants in managing physical symptoms of IBD. OBJECTIVES: The objectives were to assess the efficacy and safety of antidepressants for treating anxiety and depression in IBD, and to assess the effects of antidepressants on quality of life (QoL) and managing disease activity in IBD. SEARCH METHODS: We searched MEDLINE; Embase, CINAHL, PsycINFO, CENTRAL, and the Cochrane IBD Group Specialized Register from inception to 23 August 2018. Reference lists, trials registers, conference proceedings and grey literature were also searched. SELECTION CRITERIA: Randomised controlled trials (RCTs) and observational studies comparing any type of antidepressant to placebo, no treatment or an active therapy for IBD were included. DATA COLLECTION AND ANALYSIS: Two authors independently screened search results, extracted data and assessed bias using the Cochrane risk of bias tool. We used the Newcastle-Ottawa Scale to assess quality of observational studies. GRADE was used to evaluate the certainty of the evidence supporting the outcomes. Primary outcomes included anxiety and depression. Anxiety was assessed using the Hospital Anxiety and Depression Scale (HADS) or the Hamilton Anxiety Rating Scale (HARS). Depression was assessed using HADS or the Beck Depression Inventory. Secondary outcomes included adverse events (AEs), serious AEs, withdrawal due to AEs, quality of life (QoL), clinical remission, relapse, pain, hospital admissions, surgery, and need for steroid treatment. QoL was assessed using the WHO-QOL-BREF questionnaire. We calculated the risk ratio (RR) and corresponding 95% confidence intervals (CI) for dichotomous outcomes. For continuous outcomes, we calculated the mean difference (MD) with 95% CI. A fixed-effect model was used for analysis. MAIN RESULTS: We included four studies (188 participants). Two studies were double-blind RCTs, one was a non-randomised controlled trial, and one was an observational retrospective case-matched study. The age of participants ranged from 27 to 37.8 years. In three studies participants had quiescent IBD and in one study participants had active or quiescent IBD. Participants in one study had co-morbid anxiety or depression. One study used duloxetine (60 mg daily), one study used fluoxetine (20 mg daily), one study used tianeptine (36 mg daily), and one study used various antidepressants in clinical ranges. Three studies had placebo controls and one study had a no treatment control group. One RCT was rated as low risk of bias and the other was rated as high risk of bias (incomplete outcome data). The non-randomised controlled trial was rated as high risk of bias (random sequence generation, allocation concealment, blinding). The observational study was rated as high methodological quality, but is still considered to be at high risk of bias given its observational design.The effect of antidepressants on anxiety and depression is uncertain. At 12 weeks, the mean anxiety score in antidepressant participants was 6.11 + 3 compared to 8.5 + 3.45 in placebo participants (MD -2.39, 95% -4.30 to -0.48, 44 participants, low certainty evidence). At 12 months, the mean anxiety score in antidepressant participants was 3.8 + 2.5 compared to 4.2 + 4.9 in placebo participants (MD -0.40, 95% -3.47 to 2.67, 26 participants; low certainty evidence). At 12 weeks, the mean depression score in antidepressant participants was 7.47 + 2.42 compared to 10.5 + 3.57 in placebo participants (MD -3.03, 95% CI -4.83 to -1.23, 44 participants; low certainty evidence). At 12 months, the mean depression score in antidepressant participants was 2.9 + 2.8 compared to 3.1 + 3.4 in placebo participants (MD -0.20, 95% -2.62 to 2.22, 26 participants; low certainty evidence).The effect of antidepressants on AEs is uncertain. Fifty-seven per cent (8/14) of antidepressant participants group reported AEs versus 25% (3/12) of placebo participants (RR 2.29, 95% CI 0.78 to 6.73, low certainty evidence). Commonly reported AEs include nausea, headache, dizziness, drowsiness, sexual problems, insomnia, fatigue, low mood/anxiety, dry mouth, muscle spasms and hot flushes. None of the included studies reported any serious AEs. None of the included studies reported on pain.One study (44 participants) reported on QoL at 12 weeks and another study (26 participants) reported on QoL at 12 months. Physical, Psychological, Social and Environmental QoL were improved at 12 weeks compared to placebo (all low certainty evidence). There were no group differences in QoL at 12 months (all low certainty evidence). The effect of antidepressants on maintenance of clinical remission and endoscopic relapse is uncertain. At 12 months, 64% (9/14) of participants in the antidepressant group maintained clinical remission compared to 67% (8/12) of placebo participants (RR 0.96, 95% CI 0.55 to 1.69; low certainty evidence). At 12 months, none (0/30) of participants in the antidepressant group had endoscopic relapse compared to 10% (3/30) of placebo participants (RR 0.14, 95% CI 0.01 to 2.65; very low certainty evidence). AUTHORS' CONCLUSIONS: The results for the outcomes assessed in this review are uncertain and no firm conclusions regarding the efficacy and safety of antidepressants in IBD can be drawn. Future studies should employ RCT designs, with a longer follow-up and develop solutions to address attrition. Inclusion of objective markers of disease activity is strongly recommended as is testing antidepressants from different classes, as at present it is unclear if any antidepressant (or class thereof) has differential efficacy.

Needs of Individuals Recovering from a First-Episode of Mental Illness: A Qualitative Descriptive Analysis of Focus Group Discussions.

A broad array of needs often arise for individuals when significant physical or mental illness occurs. The aim of this study was to investigate the needs experienced by individuals recovering from a first-episode of mental illness, to explore how these needs have been assessed and to gauge the acceptability of participating in formal, systematic needs assessments in the future. Fifteen individuals who had presented to a tertiary mental health service within the previous 3 years, and who were considered to be recovering from a first-episode of mental illness discussed their current and previous needs in small focus groups. A qualitative descriptive methodology was adopted to analyse data. Three themes incorporating the broad range of inter-related and often complex needs were identified as being: the need for safety, stability and security; the need to be understood and to understand and; the need for support networks and services. Participants reported a lack of involvement in discussions with mental health clinicians regarding their needs, and were in favour of participating in formal, systematic needs assessments in the future.

Psychological therapies for the treatment of anxiety disorders in chronic obstructive pulmonary disease.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) (commonly referred to as chronic bronchitis and emphysema) is a chronic lung condition characterised by the inflammation of airways and irreversible destruction of pulmonary tissue leading to progressively worsening dyspnoea. It is a leading international cause of disability and death in adults. Evidence suggests that there is an increased prevalence of anxiety disorders in people with COPD. The severity of anxiety has been shown to correlate with the severity of COPD, however anxiety can occur with all stages of COPD severity. Coexisting anxiety and COPD contribute to poor health outcomes in terms of exercise tolerance, quality of life and COPD exacerbations. The evidence for treatment of anxiety disorders in this population is limited, with a paucity of evidence to support the efficacy of medication-only treatments. It is therefore important to evaluate psychological therapies for the alleviation of these symptoms in people with COPD. OBJECTIVES: To assess the effects of psychological therapies for the treatment of anxiety disorders in people with chronic obstructive pulmonary disease. SEARCH METHODS: We searched the specialised registers of two Cochrane Review Groups: Cochrane Common Mental Disorders (CCMD) and Cochrane Airways (CAG) (to 14 August 2015). The specialised registers include reports of relevant randomised controlled trials from The Cochrane Library, MEDLINE, Embase, and PsycINFO. We carried out complementary searches on PsycINFO and CENTRAL to ensure no studies had been missed. We applied no date or language restrictions. SELECTION CRITERIA: We considered all randomised controlled trials (RCTs), cluster-randomised trials and cross-over trials of psychological therapies for people (aged over 40 years) with COPD and coexisting anxiety disorders (as confirmed by recognised diagnostic criteria or a validated measurement scale), where this was compared with either no intervention or education only. We included studies in which the psychological therapy was delivered in combination with another intervention (co-intervention) only if there was a comparison group that received the co-intervention alone. DATA COLLECTION AND ANALYSIS: Two review authors independently screened citations to identify studies for inclusion and extracted data into a pilot-tested standardised template. We resolved any conflicts that arose through discussion. We contacted authors of included studies to obtain missing or raw data. We performed meta-analyses using the fixed-effect model and, if we found substantial heterogeneity, we reanalysed the data using the random-effects model. MAIN RESULTS: We identified three prospective RCTs for inclusion in this review (319 participants available to assess the primary outcome of anxiety). The studies included people from the outpatient setting, with the majority of participants being male. All three studies assessed psychological therapy (cognitive behavioural therapy) plus co-intervention versus co-intervention alone. We assessed the quality of evidence contributing to all outcomes as low due to small sample sizes and substantial heterogeneity in the analyses. Two of the three studies had prespecified protocols available for comparison between prespecified methodology and outcomes reported within the final publications.We observed some evidence of improvement in anxiety over 3 to 12 months, as measured by the Beck Anxiety Inventory (range from 0 to 63 points), with psychological therapies performing better than the co-intervention comparator arm (mean difference (MD) -4.41 points, 95% confidence interval (CI) -8.28 to -0.53; P = 0.03). There was however, substantial heterogeneity between the studies (I2 = 62%), which limited the ability to draw reliable conclusions. No adverse events were reported. AUTHORS' CONCLUSIONS: We found only low-quality evidence for the efficacy of psychological therapies among people with COPD with anxiety. Based on the small number of included studies identified and the low quality of the evidence, it is difficult to draw any meaningful and reliable conclusions. No adverse events or harms of psychotherapy intervention were reported.A limitation of this review is that all three included studies recruited participants with both anxiety and depression, not just anxiety, which may confound the results. We downgraded the quality of evidence in the 'Summary of findings' table primarily due to the small sample size of included trials. Larger RCTs evaluating psychological interventions with a minimum 12-month follow-up period are needed to assess long-term efficacy.

Mass media interventions for preventing smoking in young people.

BACKGROUND: Mass media interventions can be used as a way of delivering preventive health messages. They have the potential to reach and modify the knowledge, attitudes and behaviour of a large proportion of the community. OBJECTIVES: To assess the effects of mass media interventions on preventing smoking in young people, and whether it can reduce smoking uptake among youth (under 25 years), improve smoking attitudes, intentions and knowledge, improve self-efficacy/self-esteem, and improve perceptions about smoking, including the choice to follow positive role models. SEARCH METHODS: We searched the Cochrane Tobacco Addiction Group Specialized Register, with additional searches of MEDLINE and Embase in June 2016. This is an update of a review first published in 1998. SELECTION CRITERIA: Randomized trials, controlled trials without randomization and interrupted time-series studies that assessed the effect of mass media campaigns (defined as channels of communication such as television, radio, newspapers, social media, billboards, posters, leaflets or booklets intended to reach large numbers of people and which are not dependent on person-to-person contact) in influencing the smoking behaviour (either objective or self-reported) of young people under the age of 25 years. We define smoking behaviour as the presence or absence of tobacco smoking or other tobacco use, or both, and the frequency of tobacco use. Eligible comparators included education or no intervention. DATA COLLECTION AND ANALYSIS: Two review authors independently extracted information relating to the characteristics and the content of media interventions, participants, outcomes, methods of the study and risks of bias. We combined studies using qualitative narrative synthesis. We assessed the risks of bias for each study using the Cochrane 'Risk of bias' tool, alongside additional domains to account for the nature of the intervention. We assessed the quality of evidence contributing to outcomes using GRADE. MAIN RESULTS: We identified eight eligible studies reporting information about mass media smoking campaigns, one of which is new for this update. Seven of the studies used a controlled trial design and one an interrupted time-series analysis. Risks of bias were high across all included studies and there was considerable heterogeneity in study design, intervention and population being assessed.Three studies (n = 17,385), one of which compared a mass media intervention to no intervention and two of which evaluated mass media interventions as adjuncts to school-based interventions, found that the mass media interventions reduced the smoking behaviour of young people. The remaining five studies (n = 72,740) did not detect a significant effect on smoking behaviour. These included three studies comparing a mass media intervention to no intervention, one study evaluating a mass media intervention as an adjunct to a school-based intervention, and one interrupted time-series study of a social media intervention. The three campaigns which found a significant effect described their theoretical basis, used formative research in designing the campaign messages, and used message broadcast of reasonable intensity over extensive periods of time. However, some of the campaigns which did not detect an effect also exhibited these characteristics. Effective campaigns tended to last longer (minimum 3 years) and were more intense (more contact time) for both school-based lessons (minimum eight lessons per grade) and media spots (minimum four weeks' duration across multiple media channels with between 167 and 350 TV and radio spots). Implementation of combined school-based components (e.g. school posters) and the use of repetitive media messages delivered by multiple channels (e.g. newspapers, radio, television) appeared to contribute to successful campaigns. AUTHORS' CONCLUSIONS: Certainty about the effects of mass media campaigns on smoking behaviour in youth is very low, due to inconsistency between studies in both design and results, and due to methodological issues amongst the included studies. It would therefore be unwise to offer firm conclusions based on the evidence in this review. Methodologically rigorous studies investigating the effect of social media and novel forms of technology as part of tobacco prevention campaigns for youth are needed.

Are general practice characteristics predictors of good glycaemic control in patients with diabetes? A cross-sectional study.

OBJECTIVES: To determine whether certain characteristics of general practices are associated with good glycaemic control in patients with diabetes and with completing an annual cycle of care (ACC). RESEARCH DESIGN AND METHODS: Our cross-sectional analysis used baseline data from the Australian Diabetes Care Project conducted between 2011 and 2014. Practice characteristics were self-reported. Characteristics of the patients that were assessed included glycaemic control (HbA1c level ≤ 53 mmol/mol), age, sex, duration of diabetes, socio-economic disadvantage (SEIFA) score, the complexity of the patient's condition, and whether the patient had completed an ACC for diabetes in the past 18 months. Clustered logistic regression was used to establish predictors of glycaemic control and a completed ACC. RESULTS: Data were available from 147 general practices and 5455 patients with established type 1 or type 2 diabetes in three Australian states. After adjustment for other patient characteristics, only the patient completing an ACC was statistically significant as a predictor of glycaemic control (P = 0.011). In a multivariate model, the practice having a chronic disease-focused practice nurse (P = 0.036) and running educational events for patients with diabetes (P = 0.004) were statistically significant predictors of the patient having complete an ACC. CONCLUSIONS: Patient characteristics are moderately good predictors of whether the patient is in glycaemic control, whereas practice characteristics appear to predict only the likelihood of patients completing an ACC. The ACC is an established indicator of good diabetes management. This is the first study to report a positive association between having completed an ACC and the patient being in glycaemic control.

The supportive care needs of parents with a child with a rare disease: results of an online survey.

BACKGROUND: Parents caring for a child affected by a rare disease have unmet needs, the origins of which are complex and varied. Our aim was to determine the supportive care needs of parents caring for a child with a rare disease. METHODS: An online survey was developed consisting of 45 questions (108 items) and separated into six domains. The survey included questions about perceived level of satisfaction with receiving care, experiences and needs of providing daily care, the impacts of disease on relationships, the emotional and psychological burdens of disease, and parents overall satisfaction with the support received. RESULTS: Three-hundred and one parents from Australia and New Zealand completed the survey; 91 % (n = 275/301) were mothers, with 132 distinct rare diseases being reported. Fifty-four percent (n = 140/259) of parents were dissatisfied with health professionals' level of knowledge and awareness of disease; 71 % (n = 130/183) of parents felt they received less support compared to other parents. Information regarding present (60 %, n = 146/240) and future services (72 %, n = 174/240) available for their child were considered important. Almost half of parents (45 %, n = 106/236) struggled financially, 38 % (n = 99/236) reduced their working hours and 34 % (n = 79/236) ceased paid employment. Forty-two percent (n = 99/223) of parents had no access to a disease specific support group, and 58 % (n = 134/230) stated that their number of friends had reduced since the birth of their child; 75 % (n = 173/230) had no contact with other parents with a child with a similar disease, and 46 % (n = 106/230) reported feeling socially isolated and desperately lonely. Most frequent emotions expressed by parents in the week prior to completing the survey were anxiety and fear (53 %, n = 119/223), anger and frustration (46 %, n = 103/223) and uncertainty (39 %, n = 88/223). CONCLUSION: This study is the first to develop an online survey specifically for use with parents to investigate their supportive care needs across a large and diverse group of rare diseases. The findings highlight that parents with a child with a rare disease have common unmet needs regardless of what disease their child has. Such information may allow health providers to improve child outcomes through improving parental supportive care.

The Supportive Care Needs of Parents With a Child With a Rare Disease: A Qualitative Descriptive Study.

There are few studies that exist which focus specifically on parents with a child with a rare disease. The purpose of this study was to better understand the lived experiences and supportive care needs (SCN) of parents caring for a child across a spectrum of rare diseases. A qualitative descriptive approach was used to guide the research, and four semi-structured focus group interviews were conducted with 23 parents (17 mothers and 6 fathers). Participants described 'feeling boxed-in outside the box' due to a number of limitations unique to their child's disease, daily practical challenges in providing care and the various relational impacts of caring for a child with a rare disease were discussed. The results from this study help to give clearer direction for health professionals on where to focus future efforts in better meeting the supportive care needs of parents and their child with a rare disease.

Preoperative factors predicting clinical outcome following laparoscopic fundoplication.

BACKGROUND: Antireflux surgery is effective for the treatment of gastroesophageal reflux, but not all patients benefit equally from it. The challenge is to identify the patients who will ultimately benefit from antireflux surgery. The aim of this study was to identify preoperative factors that predict clinical outcome after antireflux surgery, with special interest in the influence of socioeconomic factors. METHODS: Preoperative clinical and socioeconomic data from 1,650 patients who were to undergo laparoscopic fundoplication were collected prospectively. Clinical outcome measures (persistent heartburn, dysphagia, satisfaction) were assessed at short-term (1 year) and longer-term (≥ 3 years) follow-up. RESULTS: At early follow-up, male gender (relative risk [RR] 1.091, p < 0.001) and the presence of a hiatus hernia (RR 1.065, p = 0.002) were independently associated with less heartburn. Male gender was also associated with higher overall satisfaction (RR 1.046, p = 0.034). An association was found between postoperative dysphagia and age (RR 0.988, p = 0.007) and the absence of a hiatus hernia (RR 0.767, p = 0.001). At longer-term follow-up, only male gender (RR 1.125, p < 0.001) was an independent prognostic factor for heartburn control. Male gender (RR 0.761, p = 0.001), the presence of a hiatus hernia (RR 0.823, p = 0.014), and cerebrovascular comorbidities (RR 1.306, p = 0.019) were independent prognosticators for dysphagia at longer-term follow-up. A hiatus hernia was the only factor associated with better overall satisfaction. Socioeconomic factors did not influence any clinical outcomes at short- and longer-term follow-up. CONCLUSION: Male gender and hiatus hernia are associated with a better clinical outcome following laparoscopic fundoplication, whereas socioeconomic status does not influence outcome.

Health outcomes of a subsidised fruit and vegetable program for Aboriginal children in northern New South Wales.

OBJECTIVE: To evaluate the impact of a fruit and vegetable subsidy program on short-term health outcomes of disadvantaged Aboriginal children. DESIGN, SETTING AND PARTICIPANTS: A before-and-after study involving clinical assessments, health record audits and blood testing of all children aged 0-17 2013s (n = 167) from 55 participating families at baseline and after 12 months at three Aboriginal community-controlled health services in New South Wales. All assessments were completed between December 2008 and September 2010. INTERVENTION: A weekly box of subsidised fruit and vegetables linked to preventive health services and nutrition promotion at an Aboriginal Medical Service. MAIN OUTCOME MEASURES: Change in episodes of illness, health service and emergency department attendances, antibiotic prescriptions and anthropometry. RESULTS: There was a significant decrease in oral antibiotics prescribed (- 0.5 prescriptions/2013; 95% CI, - 0.8 to - 0.2) during 12 months of participation in the program compared with the 12 months before the program. The proportion of children classified as overweight or obese at baseline was 28.3% (38/134) and the proportion in each weight category did not change (P = 0.721) after 12 months. A small but significant increase in mean haemoglobin level (3.1 g/L; 95% CI, 1.4-4.8 g/L) was shown, although the proportion with iron deficiency (baseline, 41%; follow-up, 37%; P = 0.440) and anaemia (baseline, 8%; follow-up, 5%; P = 0.453) did not change significantly. CONCLUSION: it and vegetable subsidy program was associated with improvements in some indicators of short-term health status among disadvantaged Aboriginal children. A controlled trial is warranted to investigate the sustainability and feasibility of healthy food subsidy programs in Australia.

Physical training for asthma.

BACKGROUND: People with asthma may show less tolerance to exercise due to worsening asthma symptoms during exercise or other reasons such as deconditioning as a consequence of inactivity. Some may restrict activities as per medical advice or family influence and this might result in reduced physical fitness. Physical training programs aim to improve physical fitness, neuromuscular coordination and self confidence. Subjectively, many people with asthma report that they are symptomatically better when fit, but results from trials have varied and have been difficult to compare because of different designs and training protocols. Also, as exercise can induce asthma, the safety of exercise programmes needs to be considered. OBJECTIVES: To gain a better understanding of the effect of physical training on the respiratory and general health of people with asthma, from randomised trials. SEARCH METHODS: We searched the Cochrane Airways Group Specialised Register of trials up to January 2013. SELECTION CRITERIA: We included randomised trials of people over eight years of age with asthma who were randomised to undertake physical training or not. Physical training had to be undertaken for at least 20 minutes, two times a week, over a minimum period of four weeks. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed eligibility for inclusion and undertook risk of bias assessment for the included studies. MAIN RESULTS: Twenty-one studies (772 participants) were included in this review with two additional 2012 studies identified as 'awaiting classification'. Physical training was well tolerated with no adverse effects reported. None of the studies mentioned worsening of asthma symptoms following physical training. Physical training showed marked improvement in cardiopulmonary fitness as measured by a statistically and clinically significant increase in maximum oxygen uptake (mean difference (MD) 4.92 mL/kg/min; 95% confidence interval (CI) 3.98 to 5.87; P < 0.00001; 8 studies on 267 participants); however, no statistically significant effects were observed for forced expiratory volume in 1 second (FEV1), forced vital capacity (FVC), minute ventilation at maximal exercise (VEmax) or peak expiratory flow rate (PEFR). Meta-analysis of four studies detected a statistically significant increase in maximum heart rate, and following a sensitivity analysis and removal of two studies significance was maintained (MD 3.67 bpm; 95% CI 0.90 to 3.44; P = 0.01). Although there were insufficient data to pool results due to diverse reporting tools, there was some evidence to suggest that physical training may have positive effects on health-related quality of life, with four of five studies producing a statistically and clinically significant benefit. AUTHORS' CONCLUSIONS: This review demonstrated that physical training showed significant improvement in maximum oxygen uptake, though no effects were observed in other measures of pulmonary function. Physical training was well tolerated among people with asthma in the included studies and, as such, people with stable asthma should be encouraged to participate in regular exercise training, without fear of symptom exacerbation. More research is needed to understand the mechanisms by which physical activity impacts asthma management.

Standardizing the approach to evidence-based upper limb rehabilitation after stroke.

BACKGROUND AND PURPOSE: To describe the development of a clinical algorithm to enable standardized intervention prescription and progression for upper limb rehabilitation post stroke. METHODS: We developed a standardized clinical algorithm that involved assessment of 18 critical impairments of upper limb function and application of task-specific exercises appropriate to the level of impairment. These tasks were consistent with recent evidence-based guidelines. We tested the feasibility of the algorithm with 20 participants recently discharged from inpatient rehabilitation following stroke who received outpatient therapy according to the clinical algorithm. Participants' abilities were regularly re-evaluated and task difficulty progressed. Outcomes were assessed at the level of impairment (Action Research Arm Test, Fugl-Meyer Assessment) and activity (Motor Activity Log). RESULTS: All participants attended the 9 sessions of training over the 3-week intervention period (100% compliance). No adverse events were reported. There were significant improvements in all outcome measures (P < .01). CONCLUSIONS: This evidence-based upper limb clinical algorithm provides a framework for standardizing task-specific training following stroke based on the assessment of functioning of the individual following stroke in day-to-day life. This approach is appropriate for patients with different functional levels and may be used to standardize individual or group self-directed practice sessions or to standardize the intervention and progressions in experimental studies.

Impaired sexual function and prostate cancer: a mixed method investigation into the experiences of men and their partners.

AIMS AND OBJECTIVES: To explore issues related to sexual function and relationships, for men and their wives or partners, following diagnosis and treatment for prostate cancer. BACKGROUND: A diagnosis of prostate cancer and subsequent treatment result in a significant number of men experiencing some impairment to their sexual function. There is scant research into the impact of changed sexual function on these men's masculinity, sexuality, intimate relationships and their needs regarding counselling and supportive care. DESIGN: Internet-based survey. METHODS: Focus groups and couple interviews were used to improve validity for questionnaire items designed to provide insight into men's experiences of prostate cancer in areas such as sexual function and relationships. The questionnaire included both closed and open-ended questions and had the option for the wife or partner to complete a section. RESULTS: Qualitative research revealed 17 specific categories within three key themes: sexual dysfunction, loss of libido and masculinity. The questionnaire found, unexpectedly, the majority of men said that they had sufficient emotional and psychological support. Wives/partners confirmed cancer had impacted on their partner's feelings of masculinity (71%), compared to 42% of men who felt that this was the case. Predictors of loss of libido, erectile dysfunction and 'feeling less of a man' were developed. Univariate predictors included hormone therapy, regrets about treatment choice, cancer having impacted on masculinity and distress during the last week. CONCLUSIONS: Men are not able to clearly identify the challenges prostate cancer brings especially changes to their masculinity. RELEVANCE TO CLINICAL PRACTICE: The findings strongly suggest that for men with prostate cancer, nursing assessments of men's sexual health be augmented by information gained from their partners; further, these assessments should be augmented with a careful exploration of these men's psyche guided by the knowledge that masculinity influences perceptions of self (being a man) and help seeking.

Aberrant protein expression of Appl1, Sortilin and Syndecan-1 during the biological progression of prostate cancer.

Diagnosis and assessment of patients with prostate cancer is dependent on accurate interpretation and grading of histopathology. However, morphology does not necessarily reflect the complex biological changes occurring in prostate cancer disease progression, and current biomarkers have demonstrated limited clinical utility in patient assessment. This study aimed to develop biomarkers that accurately define prostate cancer biology by distinguishing specific pathological features that enable reliable interpretation of pathology for accurate Gleason grading of patients. Online gene expression databases were interrogated and a pathogenic pathway for prostate cancer was identified. The protein expression of key genes in the pathway, including adaptor protein containing a pleckstrin homology (PH) domain, phosphotyrosine-binding (PTB) domain, and leucine zipper motif 1 (Appl1), Sortilin and Syndecan-1, was examined by immunohistochemistry (IHC) in a pilot study of 29 patients with prostate cancer, using monoclonal antibodies designed against unique epitopes. Appl1, Sortilin, and Syndecan-1 expression was first assessed in a tissue microarray cohort of 112 patient samples, demonstrating that the monoclonal antibodies clearly illustrate gland morphologies. To determine the impact of a novel IHC-assisted interpretation (the utility of Appl1, Sortilin, and Syndecan-1 labelling as a panel) of Gleason grading, versus standard haematoxylin and eosin (H&E) Gleason grade assignment, a radical prostatectomy sample cohort comprising 114 patients was assessed. In comparison to H&E, the utility of the biomarker panel reduced subjectivity in interpretation of prostate cancer tissue morphology and improved the reliability of pathology assessment, resulting in Gleason grade redistribution for 41% of patient samples. Importantly, for equivocal IHC-assisted labelling and H&E staining results, the cancer morphology interpretation could be more accurately applied upon re-review of the H&E tissue sections. This study addresses a key issue in the field of prostate cancer pathology by presenting a novel combination of three biomarkers and has the potential to transform clinical pathology practice by standardising the interpretation of the tissue morphology.