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Child safeguarding services intervene when a child is at risk of serious emotional or physical harm. Oxfordshire County Council is implementing a new approach to child safeguarding (Family Solutions Plus [FSP]) with a greater focus on whole family support and reducing the need for foster care. We sampled two cohorts of children closed within 1 year and examined the time spent in services. The sample included 474 children entering services before the new model's implementation and 561 children after. A greater proportion of children receiving FSP required a single care plan before their case was closed (85.9%; 69.4%, p < 0.001) and only experienced the lowest level plan (74.5%; 61.8%, p < 0.001). On average, this group spent less time in services for the period being observed (MD = 17.58, 95% confidence interval = 6.19, 28.96). At this early stage, no significant reduction in the number of children requiring foster care was seen (5.5%; 3.9%, p = 0.23). These initial findings suggest a potential association of FSP with a reduced number and level of care plans as well as length of time. Local authorities in England may investigate further whether FSP is a potentially useful model in improving safeguarding services. [ABSTRACT FROM AUTHOR]

Background: Endometriosis is a common condition causing chronic pain, fatigue and gut symptoms. Research suggests that dietary changes may improve symptoms; however, evidence is lacking. The present study aimed to investigate the nutritional practices and needs of individuals with endometriosis (IWE) and the management of endometriosis by dietitians in the UK, focusing on gut symptoms. Methods: Two online questionnaires were distributed via social media: a survey of dietitians working with IWE and functional gut symptoms and a survey of IWE. Results: All respondents to the dietitian survey (n = 21) used the low fermentable oligosaccharides disaccharides monosaccharides and polyols (FODMAP) diet in IWE, with the majority 69.3% (n = 14), reporting positive adherence and patient benefit. Dietitians recommended more training (85.7%, n = 18) and resources (81%, n = 17) for IWE. Of those who completed the IWE questionnaire (n = 1385), 38.5% (n = 533) had coexisting irritable bowel syndrome. Only 24.1% (n = 330) had satisfactory relief of gut symptoms. The most common symptoms were tiredness, bloating and abdominal pain, experienced by 85.5% (n = 1163), 75.3% (n = 1025) and 67.3% (n = 917), respectively. Some 52.2% (n = 723) had tried dietary modifications to relieve their gut symptoms; 36.7% (n = 500) ate a restricted diet at present; 13.5% (n = 184) experienced recent unintentional weight loss and 29.8% (n = 407) a decreased appetite Some 13.2% (n = 183) had seen a dietitian regarding their gut symptoms. Of those who had not seen a dietitian, 57.7% (n = 693) would find it useful to. Conclusions: Gut symptoms and dietary restriction are very common in IWE; however, dietetic input is not. More research on the role of nutrition and dietetics in the management of endometriosis is recommended. Key Points: Endometriosis is a common condition causing chronic pain, fatigue and gut symptoms.Research suggests that dietary changes may improve symptoms; however, the evidence is weak.This survey study of dietitians and people with endometriosis found that gut symptoms and dietary restriction are very common in endometriosis; however, dietetic input is not. [ABSTRACT FROM AUTHOR]

Background: During the Covid‐19 pandemic, there has been a worldwide increase in the use of digital technology. Many people with learning disabilities have learned new digital skills, taken part in online activities, and kept in touch with family and friends using video calls. However, the experiences of digital participation or nonparticipation for the people with profound and multiple learning disabilities (PMLD) is less understood. Method: Between December 2020 and August 2021, family carers or paid support workers of adults with PMLD completed an online survey around the experiences of the person they care for during the Covid‐19 pandemic, including questions on Internet use. We draw on the findings of this UK‐wide study to explore the digital participation of the people with PMLD during the pandemic. Findings: Around half of the people with PMLD had Internet access at home. Around half of the participants interacted with others on video calls like Facetime or Zoom and most commonly used the Internet for being with family and friends online and streaming TV and films. In the event of another lockdown, 27.5% of the people supporting someone with PMLD said they would like support with technology to make seeing friends and family easier. For some the people, digital participation during the pandemic was not beneficial enough to want to continue when restrictions eased. For others, the new online experiences had the potential to be developed in their postpandemic lives. Conclusion: Around half of the people surveyed participated in digital activities during Covid‐19. Future attention is needed to afford more people opportunities, and respond to access barriers experienced for the people with PMLD and those that support them. Accessible summary: During the Covid‐19 pandemic, a lot of people with learning disabilities used the Internet more than they had done before. Before this research, we did not know very much about how people with profound and multiple learning disabilities might be able to use the Internet.Family carers or paid support workers of people with profound and multiple learning disabilities filled in an online survey about their experiences during the Covid‐19 pandemic. This included how people with profound and multiple learning disabilities used the Internet.The researchers found that around half of people with profound and multiple learning disabilities in the study had Internet access at home. People with profound and multiple learning disabilities mostly used the Internet for being with friends and family online and for streaming TV and films. Around half of people with profound and multiple learning disabilities used video calls (like FaceTime or Zoom).If there is another pandemic, and people cannot go out, more help with technology is needed so that people with profound and multiple learning disabilities can see their family and friends online. This is very important for people who do not live with family.Some people thought digital participation was useful during the pandemic, but they preferred to see people in‐person. For others, being online was a new way of being with other people that they wanted to carry on using or make better. [ABSTRACT FROM AUTHOR]

Introduction: Preliminary data suggest that high power short duration (HPSD) ablation for pulmonary vein isolation (PVI) are safe. Limited data are available on its effectiveness. Aim was to evaluate HPSD ablation in atrial fibrillation ablation using a novel Qdot Micro catheter. Methods and Results: Prospective multicenter study evaluating safety and efficacy of PVI with HPSD ablation. First pass isolation (FPI) and sustained PVI was assessed. If FPI was not achieved additional ablation index (AI)‐guided ablation with 45 W was performed and metrics predictive of this were determined. Sixty‐five patients and 260 veins were treated. Procedural and LA dwell time was 93.9 ± 30.4 and 60.5 ± 23.1 min, respectively. FPI was achieved in 47 (72.3%) patients and 231 veins (88.8%) with an ablation duration of 4.6 ± 1.0 min. Twenty‐nine veins required additional AI‐guided ablation to achieve initial PVI with 24 anatomical sites ablated with the right posterior carina being the most common site (37.5%). A contact force of ≥8 g (area under the curve [AUC]: 0.81; p < 0.001) and catheter position variation of ≤1.2 mm (AUC: 0.79; p < 0.001) with HPSD were strongly predictive of not requiring additional AI‐guided ablation. Out of the 260 veins, only 5 (1.9%) veins showed acute reconnection. HPSD ablation was associated with shorter procedure times (93.9 vs. 159.4 min; p < 0.001), ablation times (6.1 vs. 27.7 min; p < 0.001), and lower rates of PV reconnection (9.2% vs. 30.8%; p = 0.004) compared to moderate power cohort. Conclusions: HPSD ablation is an effective ablation modality which results in effective PVI whilst maintaining a safety profile. Its superiority needs to be evaluated in randomized controlled trials. [ABSTRACT FROM AUTHOR]

Burns are common causes of paediatric emergency care attendance; approximately ten per cent result from maltreatment. Following emergency department (ED) attendance with a burn by 232 under five‐year‐olds, 11 risk factors for maltreatment were collected via health visitor (HV) telephone surveys. Three of these risk factors (domestic violence, social care involvement and developmental impairment) were also available in ED records, and information collected was compared between the two. Non‐parametric Fisher's exact tests were applied. Fifty‐nine per cent of children lived in families with risk factors for maltreatment. Prominent risk factors known by HVs included: prior injuries (n = 55, 23.7%), carer/parent mental health problems (n = 48, 20.7%), domestic violence (n = 47, 20.3%) and social care involvement (n = 45, 19.4%). A total of 158 cases had complete data for all 11 risk factors: 49 (31.0%) lived in households with one factor, 22 (13.9%) with two factors and 27 (17.1%) with three or more risk factors. In cases where HVs recorded the following risk factors as present, EDs recorded five of 47 (10.6%) for domestic violence, ten of 45 (22.2%) with social care involvement and four of 23 (17.4%) with developmental impairment. Many risk factors that were known to HVs were not identified by EDs staff despite being part of a standardised proforma. Maltreatment risk assessment could be improved if EDs staff had access to HV information. Key Practitioner Messages: Fifty‐nine per cent of pre‐school children who attended an ED with a burn live in a family with one or more maltreatment risk factors, as identified by HV records.ED staff should be able to access a child's HV record electronically at the time of presentation, to identify known maltreatment risk factors.The lack of integration of community and acute setting health records is a barrier to comprehensive assessment and treatment decisions for children in EDs, especially in relation to safeguarding risks. [ABSTRACT FROM AUTHOR]

Background While discussion continues over the future implementation of lung cancer screening, low participation from higher risk groups could limit the effectiveness of any national screening programme. Objectives To compare smokers' beliefs about lung cancer screening with those of former and never smokers within a low socioeconomic status ( SES) sample, to explore the views of lower SES smokers and ex-smokers in-depth, and to provide insights into effective engagement strategies. Design, setting and participants Using proactive, community-based recruitment methods, we surveyed 175 individuals from socioeconomically deprived communities with high smoking prevalence and subsequently interviewed 21 smokers and ex-smokers. Participants were approached in community settings or responded to a mail-out from their housing association. Results Interviewees were supportive of screening in principle, but many were doubtful about its ability to deliver long-term survival benefit for their generation of 'heavy smokers.' Lung cancer was perceived as an uncontrollable disease, and the survey data showed that fatalism, worry and perceived risk of lung cancer were particularly high among smokers compared with non-smokers. Perceived blame and stigma around lung cancer as a self-inflicted smokers' disease were implicated by interviewees as important social deterrents of screening participation. The belief that lungs are not a treatable organ appeared to be a common lay explanation for poor survival and undermined the potential value of screening. Conclusions Attitudes towards screening among this high-risk group are complex. Invitation strategies need to be carefully devised to achieve equitable participation in screening. [ABSTRACT FROM AUTHOR]

Background In the UK, the closure of 'long-stay' hospitals was accompanied by the development of community teams (CTs) to support people with intellectual disabilities (IDs) to live in community settings. The self-reported experiences of staff working in such teams have been neglected. Methods Focusing on a single county-wide service, comprising five multi-disciplinary and inter-agency CTs, we measured perceptions among the health care and care management Team members of (1) their personal well-being; (2) the functioning of their team; and (3) the organisation's commitment to quality, and culture. Results Almost three-quarters of the questionnaires were returned (73/101; 72%). The scores of health care practitioners and care managers were very similar: (1) the MBI scores of more than half the respondents were 'of concern'; (2) similarly, almost four in ten respondents' scores on the Vision scale of the TCI were 'of concern'; (3) the perceived commitment to quality (QIIS-II Part 2) was uncertain; and (4) the organisational culture (QIIS-II, Part 1) was viewed as primarily hierarchical. Discussion The perceived absence of a vision for the service, combined with a dominant culture viewed by its members as strongly focussed on bureaucracy and process, potentially compromises the ability of these CTs to respond proactively to the needs of people with IDs. Given the changes in legislation, policy and practice that have taken place since CTs were established, it would be timely to revisit their role and purpose. [ABSTRACT FROM AUTHOR]

Objective Juvenile dermatomyositis (DM) is a rare and severe autoimmune condition characterized by rash and proximal muscle weakness. While some patients respond to standard treatment, others do not. This study was carried out to investigate whether histopathologic findings and myositis-specific autoantibodies (MSAs) have prognostic significance in juvenile DM. Methods Muscle biopsy samples (n = 101) from patients in the UK Juvenile Dermatomyositis Cohort and Biomarker Study were stained, analyzed, and scored for severity of histopathologic features. In addition, autoantibodies were measured in the serum or plasma of patients (n = 90) and longitudinal clinical data were collected (median duration of follow-up 4.9 years). Long-term treatment status (on or off medication over time) was modeled using generalized estimating equations. Results Muscle biopsy scores differed according to MSA subgroup. When the effects of MSA subgroup were accounted for, increased severity of muscle histopathologic features was predictive of an increased risk of remaining on treatment over time: for the global pathology score (histopathologist's visual analog scale [hVAS] score), 1.48-fold higher odds (95% confidence interval [95% CI] 1.12-1.96; P = 0.0058), and for the total biopsy score (determined with the standardized score tool), 1.10-fold higher odds (95% CI 1.01-1.21; P = 0.038). A protective effect was identified in patients with anti-Mi-2 autoantibodies, in whom the odds of remaining on treatment were 7.06-fold lower (95% CI 1.41-35.36; P = 0.018) despite muscle biopsy scores indicating more severe disease. In patients with anti-nuclear matrix protein 2 autoantibodies, anti-transcription intermediary factor 1γ autoantibodies, or no detectable autoantibody, increased histopathologic severity alone, without adjustment for the effect of MSA subtype, was predictive of the risk of remaining on treatment: for the hVAS global pathology score, 1.61-fold higher odds (95% CI 1.16-2.22; P = 0.004), and for the total biopsy score, 1.13-fold higher odds (95% CI 1.03-1.24; P = 0.013). Conclusion Histopathologic severity, in combination with MSA subtype, is predictive of the risk of remaining on treatment in patients with juvenile DM and may be useful for discussing probable treatment length with parents and patients. Understanding these associations may identify patients at greater risk of severe disease. [ABSTRACT FROM AUTHOR]

Objectives To assess the effect of continuous positive airway pressure ( CPAP) on napping behavior in adults aged 60 and older with obstructive sleep apnea-hypopnea syndrome ( OSAHS). Design Retrospective cohort study using questionnaires. Setting Sleep center. Participants Individuals starting CPAP treatment between April 2010 and March 2012 (mean age 65.2 ± 4.7; M:F = 3.9:1; N = 107). Measurements All subjects underwent sleep studies, clinical reviews, and CPAP adherence checks and completed a questionnaire regarding CPAP adherence, current employment status, sleep patterns before and after CPAP, and factors affecting their current sleep patterns. Results CPAP treatment duration was 82.7 ± 30.0 weeks, and objective adherence was 5.4 ± 2.0 hours per night overall. Daytime nap frequency before CPAP treatment was higher in those with a history of stroke or cardiovascular disease. Both sexes had a significant reduction in daytime napping (men, P < .001; women, P = .008), evening napping (men, P < .001; women, P = .02), and daily nap duration (men, P < .001; women, P = .02). Logistic regression analysis showed that the reduction in self-reported daily nap duration was associated with younger age (odds ratio ( OR) = 0.86, P = .04), a decrease in ESS score ( OR = 1.20, P = .03), and longer self-reported daily nap duration at baseline ( OR = 31.52, P < .001). Conclusion Long-term CPAP treatment in older adults with OSAHS can play a significant role in reducing nap frequency and daily nap duration. Aging or shorter baseline daily nap duration may attenuate this effect. [ABSTRACT FROM AUTHOR]

Objective To identify long noncoding RNAs (lncRNAs), including long intergenic noncoding RNAs (lincRNAs), antisense RNAs, and pseudogenes, associated with the inflammatory response in human primary osteoarthritis (OA) chondrocytes and to explore their expression and function in OA. Methods OA cartilage was obtained from patients with hip or knee OA following joint replacement surgery. Non-OA cartilage was obtained from postmortem donors and patients with fracture of the neck of the femur. Primary OA chondrocytes were isolated by collagenase digestion. LncRNA expression analysis was performed by RNA sequencing (RNAseq) and quantitative reverse transcriptase-polymerase chain reaction. Modulation of lncRNA chondrocyte expression was achieved using LNA longRNA GapmeRs (Exiqon). Cytokine production was measured with Luminex. Results RNAseq identified 983 lncRNAs in primary human hip OA chondrocytes, 183 of which had not previously been identified. Following interleukin-1β (IL-1β) stimulation, we identified 125 lincRNAs that were differentially expressed. The lincRNA p50-associated cyclooxygenase 2-extragenic RNA (PACER) and 2 novel chondrocyte inflammation-associated lincRNAs (CILinc01 and CILinc02) were differentially expressed in both knee and hip OA cartilage compared to non-OA cartilage. In primary OA chondrocytes, these lincRNAs were rapidly and transiently induced in response to multiple proinflammatory cytokines. Knockdown of CILinc01 and CILinc02 expression in human chondrocytes significantly enhanced the IL-1-stimulated secretion of proinflammatory cytokines. Conclusion The inflammatory response in human OA chondrocytes is associated with widespread changes in the profile of lncRNAs, including PACER, CILinc01, and CILinc02. Differential expression of CILinc01 and CIinc02 in hip and knee OA cartilage, and their role in modulating cytokine production during the chondrocyte inflammatory response, suggest that they may play an important role in mediating inflammation-driven cartilage degeneration in OA. [ABSTRACT FROM AUTHOR]

Focal But Not Diffuse Fibrosis Burden Predicts CRT Remodeling Response Introduction Many heart failure patients with dyssynchrony do not reverse remodel (RR) in response to cardiac resynchronization therapy (CRT). The presence of focal and diffuse interstitial myocardial fibrosis may explain this high nonresponse rate. T1 mapping is a new cardiac magnetic resonance imaging (CMR) technique that overcomes the limitations of conventional contrast CMR and provides reliable quantitative assessment of diffuse myocardial fibrosis. The study tested the hypothesis that focal and diffuse fibrosis quantification would correlate with a lack of left ventricular (LV) RR to CRT. Methods and Results In a prospective study of 48 consecutive patients (27 ischemic cardiomyopathy, 21 dilated cardiomyopathy) LV scar burdens were quantified (scar core and gray zone using late gadolinium enhancement LGE CMR; interstitial fibrosis using T1 mapping) before CRT implant. LV RR was defined by a ≥ 15% reduction in LV end-systolic volume 6 months postimplant. Twenty-seven (56%) patients were responders with RR. Association between scar quantification and LV RR was assessed using the Poisson regression model. Univariate analysis showed that QRS duration/morphology, scar core, and gray zone volumes expressed as % of LV mass and extracellular volume index (ECV) (a measure of interstitial fibrosis from T1 mapping) to be significant predictors of LV RR. Multivariable-adjusted analyses demonstrated scar core quantification (≥13.7% LV mass) to be the only independent predictor of LV RR (prevalence ratio 0.40, P = 0.038). Conclusions Focal scar burden detected by LGE CMR is associated with a poor response to CRT. Diffuse interstitial fibrosis assessment by T1 mapping, however, is not independently predictive of CRT response. [ABSTRACT FROM AUTHOR]

Objective. To examine the potential of chronic severe bacterial infection to generate rheumatoid factor (RF) and anti-citrullinated protein antibodies (ACPAs), by studying patients with bronchiectasis (BR) alone and BR patients with rheumatoid arthritis (BR/RA). Methods. We studied 122 patients with BR alone, 50 patients with BR/RA, and 50 RA patients without lung disease, as well as 87 patients with asthma and 79 healthy subjects as controls. RF levels were measured using an automated analyzer, and cyclic citrullinated peptide 2 (CCP-2) was used to detect ACPAs. The fine specificities of citrullinated a-enolase peptide 1 (CEP-1), Citvimentin, and Cit-fibrinogen to their arginine-containing control peptides (arginine-containing a-enolase peptide 1 [REP-1], vimentin, and fibrinogen) were measured by enzyme-linked immunosorbent assay. Results. Among the BR patients and control subjects, 39% and 42%, respectively, were ever-smokers. The frequency of RF positivity in serum was increased in BR patients compared with controls (25% versus 10%), as were the frequencies of antibodies to CCP-2 (5% versus 0%), CEP-1 (7% versus 4%), Cit-vimentin (7% versus 4%), and Cit-fibrinogen (12% versus 4%), although only the differences for RF and Cit-fibrinogen were significant (P < 0.05). We observed a corresponding increase in the frequency of antibodies to the arginine-containing control peptides in BR patients compared with controls (for REP-1, 19% versus 4% [P < 0.01]; for vimentin, 16% versus 4% [P < 0.05]), demonstrating that the ACPA response in patients with BR is not citrulline specific. The lack of citrulline specificity was further confirmed by absorption studies. In BR/RA patients, all ACPA responses were highly citrulline specific. Conclusion. Bronchiectasis is an unusual but potent model for the induction of autoimmunity in RA by bacterial infection in the lung. Our study suggests that the ACPA response is not citrulline specific during the early stages of tolerance breakdown but becomes more specific in patients with BR in whom BR/RA develops. [ABSTRACT FROM AUTHOR]

Background Communication difficulties are common in cerebral palsy (CP) and are frequently associated with motor, intellectual and sensory impairments. Speech and language therapy research comprises single-case experimental design and small group studies, limiting evidence-based intervention and possibly exacerbating variation in practice. Aims To describe the assessment and intervention practices of speech-language therapist (SLTs) in the UK in their management of communication difficulties associated with CP in childhood. Methods & Procedures An online survey of the assessments and interventions employed by UK SLTs working with children and young people with CP was conducted. The survey was publicized via NHS trusts, the Royal College of Speech and Language Therapists (RCSLT) and private practice associations using a variety of social media. The survey was open from 5 December 2011 to 30 January 2012. Outcomes & Results Two hundred and sixty-five UK SLTs who worked with children and young people with CP in England ( n = 199), Wales ( n = 13), Scotland ( n = 36) and Northern Ireland ( n = 17) completed the survey. SLTs reported using a wide variety of published, standardized tests, but most commonly reported assessing oromotor function, speech, receptive and expressive language, and communication skills by observation or using assessment schedules they had developed themselves. The most highly prioritized areas for intervention were: dysphagia, alternative and augmentative (AAC)/interaction and receptive language. SLTs reported using a wide variety of techniques to address difficulties in speech, language and communication. Some interventions used have no supporting evidence. Many SLTs felt unable to estimate the hours of therapy per year children and young people with CP and communication disorders received from their service. Conclusions & Implications The assessment and management of communication difficulties associated with CP in childhood varies widely in the UK. Lack of standard assessment practices prevents comparisons across time or services. The adoption of a standard set of agreed clinical measures would enable benchmarking of service provision, permit the development of large-scale research studies using routine clinical data and facilitate the identification of potential participants for research studies in the UK. Some interventions provided lack evidence. Recent systematic reviews could guide intervention, but robust evidence is needed in most areas addressed in clinical practice. [ABSTRACT FROM AUTHOR]

Background Emotional neglect can be characterized as cold or critical parenting and denotes a parent intentionally or unintentionally overlooking the signs that a child needs comfort or attention and ignoring its emotional needs. Parental emotional neglect is widely posited as an antecedent of anxiety disorder, with attachment researchers arguing for anxious-ambivalent attachment style as a mediating factor. Method Childhood experience of neglect and abuse, including antipathy (cold, critical parenting), attachment styles, and anxiety disorders were assessed in a high-risk sample of 160 adolescents and young adults by means of interview measures. Results Antipathy was associated with 12-month prevalence of anxiety disorders in the sample. Anxious-ambivalent attachment scores statistically mediated the relationship between antipathy and anxiety disorders. Conclusions Clinicians treating anxiety disorders in youths need to consider that emotional neglect in childhood in the form of antipathy could lead to anxious-ambivalent internal working models operating around fear of rejection and fear of separation. [ABSTRACT FROM AUTHOR]

Background Catheter-based contact force sensing (CFS) technology gives detailed information regarding contact between the catheter tip and myocardium. This may result in more effective ablation procedures. The primary objective of this study was comparison of remote robotic navigation (RRN) and Manual CFS ablation. The secondary objective was to compare CFS with non-CFS ablation for both navigation modes. Methods Prospective registries of consecutive cases undergoing their first ablation for persistent atrial fibrillation (AF) from six hospitals in the United Kingdom and South Africa were analyzed: 50 Manual/CFS and 50 RRN/CFS cases were included. Historical control non-CFS ablation patients were matched by propensity score, giving a total 200 patient cohort. Results RRN/CFS was associated with improved single procedure 1-year success rates (64% vs 36%, P = 0.01) and shorter fluoroscopy times (41% reduction, P < 0.0005) than Manual/CFS ablation, without any difference in procedure times (P = 0.8). The mean contact force was higher in RRN/CFS than Manual/CFS cases (16 [15-18 g] vs 13 [12-15 g], respectively, P = 0.003). Compared with non-CFS historical controls, CFS cases had higher 1-year success rates for RRN (64% vs 36%, P = 0.01), but not Manual ablation (36% vs 38%, P = 1). Procedure times were reduced for CFS cases (20%, P < 0.005 both navigation modes), as were fluoroscopy times (Manual: 43%, RRN 83%, P < 0.005 for both). There were no differences in rates of major or minor complications for either comparison (P > 0.5). Conclusions A combination of RRN and CFS is associated with improved success rates at 1 year and fluoroscopy times for persistent AF ablation, compared with Manual ablation and non-CFS RRN ablation. [ABSTRACT FROM AUTHOR]

Objective Functionally impaired Treg cells expressing abnormally low levels of CTLA-4 have been well documented in rheumatoid arthritis (RA). However, the molecular defect underlying this reduced expression is unknown. The aims of this study were to assess the role of DNA methylation in regulating CTLA-4 expression in Treg cells isolated from RA patients and to elucidate the mechanism of their reduced suppressor function. Methods CTLA-4 expression in Treg cells from RA patients and healthy controls was measured by quantitative polymerase chain reaction (PCR) and flow cytometry. Methylation of the CTLA-4 gene promoter was analyzed by bisulfite-specific PCR, followed by sequencing. Methylation-dependent transcriptional activity of the CTLA-4 gene promoter was measured by luciferase assay, and NF-AT binding to the CTLA-4 gene promoter was determined by chromatin immunoprecipitation. The role of CTLA-4 expression in controlling Teff cells was analyzed using an autologous mixed lymphocyte reaction. Results Down-regulation of CTLA-4 expression in Treg cells from RA patients was caused by methylation of a previously unidentified NF-AT binding site within the CTLA-4 gene promoter. As a consequence, Treg cells were unable to induce expression and activation of the tryptophan-degrading enzyme indoleamine 2,3-dioxygenase (IDO), which in turn resulted in a failure to activate the immunomodulatory kynurenine pathway. Conclusion We show for the first time that epigenetic modifications contribute to defective Treg cell function in RA through an inability to activate the IDO pathway. Therefore, this study sets a precedent for investigating potential therapeutic strategies aimed at reinforcing the IDO pathway in RA patients. [ABSTRACT FROM AUTHOR]

Objective To examine whether the B cell tropic γ-herpesvirus Epstein-Barr virus (EBV) is aberrantly expressed in its latent and lytic forms within ectopic lymphoid structures (ELS) in the salivary glands of patients with Sjögren's syndrome (SS), and to investigate the relationship between EBV dysregulation, B cell activation, in situ differentiation of autoreactive plasma cells, disease-specific autoantibody production, and cytotoxicity. Methods Latent and lytic EBV infection in the salivary glands of 28 patients with SS and 38 patients with nonspecific chronic sialadenitis (NSCS), characterized for the presence or absence of ELS, was investigated by reverse transcription-polymerase chain reaction, in situ hybridization, and immunohistochemical/immunofluorescence staining. Glandular versus synovial production of anti−Ro 52, anti-citrullinated protein antibodies (ACPAs), and anti-EBV peptide antibodies was analyzed in situ or in vivo in human SS/SCID and human rheumatoid arthritis/SCID mouse chimeras. Results EBV dysregulation within inflammatory infiltrates was observed exclusively in ELS+ SS salivary gland tissue, as revealed by latent EBV infection and lytic EBV infection in B cells and plasma cells, respectively. Conversely, epithelial latent membrane protein 2A expression was observed in both patients with SS and patients with NSCS. Importantly, perifollicular plasma cells displaying Ro 52 immunoreactivity were frequently infected by EBV. Furthermore, ELS-containing SS salivary gland tissue that was transplanted into SCID mice supported the production of anti-Ro 52/anti-La 48 and anti-EBV antibodies but not ACPAs. Analysis of CD4+ and CD8+ T cell localization and granzyme B expression demonstrated that the persistence of EBV in ELS-containing SS salivary glands was associated with follicular exclusion of CD8+ T cells and impaired CD8-mediated cytotoxicity. Conclusion Active EBV infection is selectively associated with ELS in the salivary glands of patients with SS and appears to contribute to local growth and differentiation of disease-specific autoreactive B cells. [ABSTRACT FROM AUTHOR]

Objective To assess survival and incidence of organ-based complications in a large single-center cohort of unselected systemic sclerosis (SSc) patients, and to explore predictors of survival and clinically significant pulmonary fibrosis (PF) and pulmonary hypertension (PH). Methods The study cohort consisted of 398 consecutive SSc patients, followed up for up to 15 years. Cox proportional hazards analysis with demographic, clinical, and laboratory characteristics as predictor variables was used to develop prediction models for pulmonary complications and survival. Results The overall survival estimate at the end of followup was 57% among patients with limited cutaneous SSc (lcSSc) and 50% among patients with diffuse cutaneous SSc (dcSSc) ( P = 0.017). We found that greater age at disease onset, dcSSc, lower diffusing capacity for carbon monoxide (DL co), lower hemoglobin levels, higher serum creatinine levels, and the presence of PH or cardiac involvement were independent predictors of worse survival. Over the entire followup period, 42% of dcSSc patients and 22% of lcSSc patients developed clinically significant PF ( P < 0.001). The variables that predicted clinically significant PF development were dcSSc, greater age at onset, lower forced vital capacity and DL co, and the presence of anti-topoisomerase I antibody, while the presence of anticentromere antibody was protective. There was no difference in cumulative incidence of PH between the 2 subsets-24% in lcSSc and 18% in dcSSc ( P = 0.558). Incidence rates were 1-2% per year. The PH prediction model demonstrated that greater age at onset, increase in serum creatinine levels, lower DL co, and the presence of anti-RNA polymerase III or anti-U3 RNP antibodies were associated with increased risk of PH, while anti-topoisomerase I antibody positivity reduced the hazard. Conclusion Our study provides data on long-term outcome of SSc and the timing and frequency of major organ complications. The predictive models we present could be used as clinical tools for patient risk stratification and could facilitate cohort enrichment for event-driven studies. [ABSTRACT FROM AUTHOR]

Background Peer relations is a vulnerable area of functioning in children with specific language impairment ( SLI), but little is known about the developmental trajectories of individuals. Methods Peer problems were investigated over a 9-year period (from 7 to 16 years of age) in 171 children with a history of SLI. Discrete factor growth modelling was used to chart developmental trajectories. Multinomial logistic regression analysis was conducted to investigate factors associated with group membership. Results Four distinct developmental trajectories were identified: low-level/no problems in peer relations (22.2% of participants), childhood-limited problems (12.3%), childhood-onset persistent problems (39.2%) and adolescent-onset problems (26.3%). Risk of poor trajectories of peer relations was greater for those children with pragmatic language difficulties. Prosocial behaviour was the factor most strongly associated with trajectory group membership. Overall, the more prosocial children with better pragmatic language skills and lower levels of emotional problems had less difficulty in developing peer relations. Conclusions Analysis of developmental trajectories enriches our understanding of social development. A sizeable minority in the present sample sustained positive relations through childhood and adolescence, and others overcame early difficulties to achieve low levels of problems by their early teens; the majority, however, showed childhood-onset persistent or adolescent-onset problems. [ABSTRACT FROM AUTHOR]

Objectives Occult (surface antigen-negative/ DNA-positive) hepatitis B virus ( HBV) infection is common in areas of the world where HBV is endemic. The main objectives of this study were to determine the prevalence of occult HBV infection in HIV-infected African migrants to the UK and to determine factors associated with occult coinfection. Methods This anonymized point-prevalence study identified Africans attending three HIV clinics, focussing on patients naïve to antiretroviral therapy ( ART). Stored blood samples were tested for HBV DNA. Prevalence was calculated in the entire cohort, as well as in subpopulations. Risk factors for occult HBV coinfection were identified using logistic regression analysis. Results Among 335 HIV-positive African migrants, the prevalence of occult HBV coinfection was 4.5% [95% confidence interval ( CI) 2.8-7.4%] overall, and 6.5% (95% CI 3.9-10.6%) and 0.8% (95% CI 0.2-4.6%) in ART-naïve and ART-experienced patients, respectively. Among ART-naïve anti- HBV core (anti- HBc)-positive patients, the prevalence was 16.4% (95% CI 8.3-25.6%). The strongest predictor of occult coinfection was anti- HBc positivity [odds ratio ( OR) 7.4; 95% CI 2.0-27.6]. Median HBV DNA and ALT levels were 54 IU/mL [interquartile range ( IQR) 33-513 IU/mL] and 22 U/L ( IQR 13-27 U/L), respectively. Conclusions Occult HBV coinfection remains under-diagnosed in African HIV-infected patients in the UK. Given the range of HBV DNA levels observed, further studies are warranted to determine its clinical significance and to guide screening strategies and ART selection in these patients. [ABSTRACT FROM AUTHOR]

Rationale and aim To compare clinical features and management of paediatric community-acquired pneumonia ( PCAP) following the publication of UK pneumonia guidelines in 2002 with data from a similar survey at the same hospitals in 2001-2002 (pre-guidelines). Methods A prospective survey of 11 hospitals in Northern England was undertaken during 2008-2009. Clinical and laboratory data were recorded on children aged ≤16 years who presented with clinical and radiological features of pneumonia. Results 542 children were included. There was a reduction in all investigations performed ( P < 0.001) except C-reactive protein ( P = 0.448) between surveys. These included full blood count (76% to 61%); blood culture (70% to 53%) and testing of respiratory secretions for viruses (24% to 12%) and bacteria (18% to 8%). Compared to pre-guidelines, there was a reduction in the use of intravenous antibiotics as a proportion of the total prescribed from 47% to 36% ( P < 0.001) and a change in the route of antibiotic administration with increasing preference for oral alone (16% pre-compared to 50% post-guidelines, P < 0.001). Conclusion Apart from the acute phase reactants that should not be measured routinely, these changes are in line with the guideline recommendations. Improvements in antibiotic use are possible and have implications for future antimicrobial stewardship programmes. Further work using cost-effectiveness analysis may also demonstrate a financial benefit to health services from adoption of guidelines. [ABSTRACT FROM AUTHOR]

Brivaracetam is a high-affinity synaptic vesicle protein 2A ligand, in Phase III clinical development for epilepsy. This study assessed the effect of brivaracetam 400 mg/day on the pharmacokinetics and pharmacodynamics of a combination oral contraceptive (OC) containing 30 µg ethinylestradiol and 150 µg levonorgestrel, in healthy pre-menopausal women. This open-label, single-center, randomized, two-way crossover, multiple oral dose study (N01080) included two consecutive 28-day cycles without (control) or with brivaracetam (test), and a 28-day follow-up. OC was taken on Days 1-21 of every cycle and brivaracetam 200 mg twice daily was administered on Days 1-20 of the test cycle. Ethinylestradiol and levonorgestrel pharmacokinetics were determined on Day 20 and endogenous hormones were measured frequently during both control and test cycles. Overall, 23/24 participants (age: 19-39 years) completed the study. AUC ratio (90% confidence interval) for brivaracetam versus control was 0.73 (0.69, 0.78) for ethinylestradiol and 0.78 (0.72, 0.83) for levonorgestrel, outside pre-defined bioequivalence limits (0.80-1.25). Levels of endogenous hormones were similar and normal during brivaracetam and control cycles. Brivaracetam in combination with OC was well tolerated. Brivaracetam 400 mg/day co-administered with a combination OC in healthy women reduced ethinylestradiol and levonorgestrel plasma levels but did not result in ovulation. [ABSTRACT FROM AUTHOR]

Background While studies of ex-orphanage care show adverse effects on development, the longer-term impact on mid-life psychosocial functioning and physical health has not been established. Methods Orphanage records provided baseline data on a sample of 100 Hong Kong Chinese girls who were subsequently adopted into the UK. A mid-life follow-up using standardised questionnaires and face-to-face interviews assessed current circumstances, life satisfaction and mental and physical health outcomes. Comparisons were made with age-matched UK-born adopted and nonadopted women. Results Half the group spent between 1 and 2 years in orphanages, average age at adoptive placement was 23 months and 72% participated in the follow-up. Despite this poor early start, mid-life outcomes were commensurate with the comparison groups in terms of mental and physical health measures. Serious psychiatric and social difficulties were largely absent. Although the timing and extent of exposure to orphanage care did not influence outcome, participants' reports of poorer quality adoptive family experience and a negative view of their adoption were significantly associated with poorer mental health outcomes (difference in means = 0.76, 95% CI 1.33-0.19, p = .01; difference in means = 1.2, 95% CI 0.68-1.73, p = .01, respectively). Conclusions Moderately depriving orphanage care did not predict enduring adverse consequences in mid-life but subsequent poor adoption experience was associated with outcome. [ABSTRACT FROM AUTHOR]

Objectives We evaluated the emergence of drug resistance in patients failing first-line regimens containing one nonnucleoside reverse transcriptase inhibitor ( NNRTI) administered with zidovudine ( ZDV) + lamivudine (the ZDV group) or non-thymidine analogues (non- TAs) (tenofovir or abacavir, + lamivudine or emtricitabine; the non- TA group). Methods Three hundred HIV-1-infected patients failing a first-line NNRTI-containing regimen (nevirapine, n = 148; efavirenz, n = 152) were included in the analysis. Virological failure was defined as viraemia ≥ 400 HIV-1 RNA copies/mL for the first time at least 6 months after starting the NNRTI-based regimen. For each patient, a genotypic resistance test at failure was available. The presence of drug-resistance mutations in HIV-1 reverse transcriptase was evaluated by comparing patients treated with NNRTI + zidovudine + lamivudine vs. those treated with NNRTI + non- TA. Results A total of 208 patients were failing with NNRTI + zidovudine + lamivudine and 92 with NNRTI + non- TA. No significant differences were observed between the non- TA group and the ZDV group regarding the time of virological failure [median (interquartile range): 12 (8-25) vs. 13 (9-32) months, respectively; P = 0.119] and viraemia [median (interquartile range): 4.0 (3.2-4.9) vs. 4.0 (3.3-4.7) log10 copies/mL, respectively; P = 0.894]. Resistance to reverse transcriptase inhibitors ( RTIs) occurred at a significant lower frequency in the non- TA group than in the ZDV group (54.3 vs. 75.5%, respectively; P = 0.001). This difference was mainly attributable to a significantly lower prevalence of NNRTI resistance (54.3 vs. 74.0%, respectively; P = 0.002) and of the nucleoside reverse transcriptase inhibitor ( NRTI) mutation M184V (23.9 vs. 63.5%, respectively; P < 0.001) in the non- TA group compared with the ZDV group. As expected, the mutation K65R was found only in the non- TA group (18.5%; P < 0.001). Conclusions At first-line regimen failure, a lower prevalence of RTI resistance was found in patients treated with NNRTI + non- TA compared with those treated with NNRTI + zidovudine + lamivudine. These results confirm that the choice of backbone may influence the prevalence of drug resistance at virological failure. [ABSTRACT FROM AUTHOR]

Background To examine whether the nutritional status of aged undernourished residents in care could be improved through dietary modification to increase energy intake but not portion size. Methods A 12-week cluster randomised controlled trial was carried out in 21 residential care homes. Participants comprised undernourished residents with a body mass index (BMI) <18.5 kg m-2. All menus were analysed to evaluate nutrient provision. Energy and macronutrient intakes of undernourished residents were estimated using 3-day weighed food intake diaries. Those resident in homes randomised to intervention had their usual meals enriched with energy-dense foods to a maximum of +1673 kJ day−1. Results Of 445 residents screened, 41 (9%) had a BMI <18.5 kg m-2 and entered the study. Despite adequate food provision, energy and macronutrient intakes were below UK dietary reference values. Mean (SEM) energy intake increased [+556 (372) kJ, P = 0.154] in residents allocated to intervention but fell in those residents in 'control homes' receiving usual care [−151 (351) kJ, P = 0.676]. Weight change [+1.3 (0.53) kg, P = 0.03] was seen in intervention residents but not in controls [−0.2 (1.5) kg, P = 0.536]. Between-group differences for changes in weight and energy intake were not significant ( P = 0.08 and 0.20, respectively). Six residents allocated to the intervention increased their BMI >18.5 kg m-2 ( P = 0.018). Conclusions Achieving weight gain in frail older people is difficult. These results suggest that enriching food could help address undernutrition and slow chronic weight loss. Interventions of a longer duration are needed to confirm or exclude the value of food enrichment. [ABSTRACT FROM AUTHOR]

Objective Inflammatory arthritis is associated with systemic manifestations including alterations in metabolism. We used nuclear magnetic resonance (NMR) spectroscopy-based metabolomics to assess metabolic fingerprints in serum from patients with established rheumatoid arthritis (RA) and those with early arthritis. Methods Serum samples were collected from newly presenting patients with established RA who were naive for disease-modifying antirheumatic drugs, matched healthy controls, and 2 groups of patients with synovitis of ≤3 months' duration whose outcomes were determined at clinical followup. Serum metabolomic profiles were assessed using 1-dimensional 1H-NMR spectroscopy. Discriminating metabolites were identified, and the relationships between metabolomic profiles and clinical variables including outcomes were examined. Results The serum metabolic fingerprint in established RA was clearly distinct from that of healthy controls. In early arthritis, we were able to stratify the patients according to the level of current inflammation, with C-reactive protein correlating with metabolic differences in 2 separate groups ( P < 0.001). Lactate and lipids were important discriminators of inflammatory burden in both early arthritis patient groups. The sensitivities and specificities of models to predict the development of either RA or persistent arthritis in patients with early arthritis were low. Conclusion The metabolic fingerprint reflects inflammatory disease activity in patients with synovitis, demonstrating that underlying inflammatory processes drive significant changes in metabolism that can be measured in the peripheral blood. The identification of metabolic alterations may provide insights into disease mechanisms operating in patients with inflammatory arthritis. [ABSTRACT FROM AUTHOR]

Objective Quantitative sensory testing (QST) and questionnaire-based assessments have been used to demonstrate features of neuropathic pain in subjects with musculoskeletal pain. However, their direct relationship has not been investigated in the community. The purpose of this study was to conduct an observational study to describe the characteristics of joint pain and to examine the relationship between QST measures and the PainDETECT Questionnaire (PD-Q). Methods Warm detection, heat pain, and mechanical pain thresholds as well as mechanical pain sensitivity over the sternum were determined and the PD-Q scores were calculated in a cross-sectional study of 462 participants in the Chingford Study. Comparisons were made between subjects with and those without joint pain. Logistic regression modeling was used to describe the association between neuropathic pain features, as determined by the PD-Q score, and each of the QST measures individually, adjusting for age, body mass index, and use of pain-modifying medications. Results A total of 66.2% of the subjects reported recent joint pain, with a median average pain severity of 5 of 10. There was increased sensitivity to painful stimuli in the group with pain as compared to the pain-free group, and this persisted after stratification by pain-modifying medication use. While only 6.7% of subjects had possible neuropathic pain features and 1.9% likely neuropathic pain features according to the standard PD-Q thresholds, features of neuropathic pain were common and were present in >50% of those reporting pain of at least moderate severity. Heat pain thresholds and mechanical pain sensitivity were significantly associated with features of neuropathic pain identified using the PD-Q, with an odds ratio (OR) of 0.88 (95% confidence interval [95% CI] 0.79-0.97; P = 0.011) and an OR of 1.24 (95% CI 1.04-1.48; P = 0.018), respectively. Conclusion QST measures and the PD-Q identified features of neuropathic pain in subjects in this community-based study, with significant overlap between the findings of the two techniques. [ABSTRACT FROM AUTHOR]

Background School lunches potentially provide an important source of nutrients for children, although studies have shown that their food choices are not always associated with health benefits. The present study aimed to evaluate the effects of a kitchen-based intervention on intake from school lunches undertaken in 2005. Methods The three-phase study comprised a pre-intervention observation, the intervention itself and a post-intervention observation. Children aged 12-16 years attending a large, inner-city, secondary school in London were invited to participate. The intervention consisted of small, practical changes to the school menu with the purpose of reducing total and saturated fat and increasing fruit and vegetable consumption. Intake was evaluated using a weighed technique. Results One hundred and eighty and 198 children participated in the pre- and post-intervention phases, respectively. After the intervention, a significant reduction was observed in mean (SD) intake of total fat [44% (8%) versus 40% (9%) total energy, P < 0.01] and of saturated fat [13% (6%) versus 10% (6%), P < 0.01]. The children also ate significantly more fruit and vegetables [12.0 (10.4) g versus 30.0 (30.5) g total weight, P < 0.001]. However, after the intervention, the mean intakes of total and saturated fat, fruit and vegetables were still significantly below the Caroline Walker Trust guidelines for school lunches. Conclusions The present study shows that total and saturated fat and fruit and vegetable intake from school lunches can be significantly improved by a short, kitchen-based intervention. Although the benefits were limited, the results support further work in this area. [ABSTRACT FROM AUTHOR]

Aims Although smoking prevalence among people with severe mental illness is high, it remains largely unaddressed. This pragmatic pilot project aimed to develop and implement a tailored tobacco dependence service in mental health settings and to assess its impact, as well as barriers and facilitators to implementation. Design An integrative service model, spanning acute, rehabilitation and community services, including the design of tailored instruments and referral pathways, delivered by two mental health professionals. Setting and participants Four adult acute and two rehabilitation wards (129 beds), and the community recovery team (2038 cases) of the United Kingdom's largest Mental Health Trust. Measurements Audit of smoking information in patient notes; service uptake; quit attempts; smoking cessation and reduction; qualitative data on implementation barriers/facilitators. Findings A total of 110 patients attended at least one support session: 53 inpatients (23% of inpatient smokers) and 57 community (of unknown number of community smokers, as recording of smoking status is not mandatory). Thirty-four of these (31%) made a quit attempt; 17 (15%) stopped smoking and 29 (26%) reduced cigarette consumption by up to 50% at the final contact. Barriers to service implementation related to: (i) trust policy, systems and procedures, (ii) staff knowledge and attitudes and (iii) illness-related factors. Conclusions Despite the strong anti-smoking climate in the United Kingdom, including a law requiring smoke-free policies in mental health settings, establishing a smoking cessation treatment service for people with mental illness proved difficult, due to complex systemic barriers. However, there is clearly a demand, by patients, for such a service. [ABSTRACT FROM AUTHOR]

Background and Purpose Despite the finding that 40% to 60% of stroke patients suffer from knee joint hyperextension during gait, there is a lack of agreement of the possible causes of this problem. The aim of this study was to determine whether there is a relationship between lower limb muscle weakness and knee joint hyperextension in hemiparetic stroke patients. Methods This is a cross-sectional observational comparison study. Twenty patients (mean age 66 years) who had suffered a single hemiparetic stroke and were ambulant with no major lower limb joint pathology participated. Muscle strength of the hip extensors, hip flexors, hip abductors, knee extensors, knee flexors, ankle plantarflexors and ankle dorsiflexors of both limbs was measured using a hand-held dynamometer. Computerized and visual gait analysis identified subjects with and without knee hyperextension in loading response and midstance. Subjects were categorized as having weakness of a particular muscle group if the difference in strength between the paretic and non-paretic muscle was greater than 50%. The Pearson's chi-squared test was used to evaluate the association between weakness and knee hyperextension. Results A strong relationship was found between ankle plantarflexor weakness and knee hyperextension during midstance ( p = 0.044). No relationship was found between lower limb muscle weakness and knee hyperextension during loading response ( p > 0.05). No relationship was found between any other lower limb muscle groups and knee hyperextension in midstance ( p > 0.05). Conclusions Weak ankle plantarflexors, in particular gastrocnemius, may have an important role in the presence of knee hyperextension. The results of this study did not support a role for weak hamstrings or quadriceps in knee hyperextension during gait. Further research is needed to clarify the role of gastrocnemius during the stance phase and to determine if strengthening weak gastrocnemius reduces knee hyperextension. Copyright © 2011 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Rationale Peer review has been widely used within the National Health Service to facilitate health quality improvement but evaluation has been limited particularly over the longer-term. Change within the National Health Service (NHS) can take a prolonged period - 1-2 years - to occur. We report here a 3-year evaluation of the largest randomized trial of peer review ever conducted in the UK. Aim To evaluate whether targeted mutual peer review of respiratory units brings about improvements in services for chronic obstructive pulmonary disease (COPD) over 3 years. Methods The peer review intervention was a reciprocal supportive exercise that included clinicians, hospital management, commissioners and patients, which focused on the quality of the provision of four specific evidence-based aspects of COPD care. Results Follow-up at 36 months demonstrated limited significant quantitative differences in the quality of services offered in the two groups but a strong trend in favour of intervention sites. Qualitative data suggested many benefits of peer review in most but not all intervention units and some control teams. The data identify factors that promote and obstruct change. Conclusion The findings demonstrate significant change in service provision over 3 years in both control and intervention sites with great variability in both groups. The combined quantitative and qualitative findings indicate that targeted mutual peer review is associated with improved quality of care, improvements in service delivery and with changes within departments that promote and are precursors to quality improvement. The generic findings of this study have potential implications for the application of peer review throughout the NHS. [ABSTRACT FROM AUTHOR]

Background Antepartum haemorrhage of unknown origin ( APHUO) is associated with preterm birth and perinatal mortality. Aim To determine whether smoking beyond the first trimester of pregnancy was an independent risk factor for APHUO. Methods Rates of APHUO were compared between non-smokers and smokers, and non-smokers and ceased smokers. Participants were healthy nulliparous women recruited to the Screening for Pregnancy Endpoints ( SCOPE) prospective cohort study in New Zealand, Australia, Ireland and United Kingdom. Logistic regression was used to compare adjusted odds ratio, 95% confidence intervals ( OR, 95% CI) of APHUO between continued smokers and non-smokers, adjusting for possible confounders. Results Of the 3513 participants, 77.9% ( n = 2737) were non-smokers, 10.6% ( n = 371) ceased in the first trimester and 11.5% ( n = 405) continued smoking beyond the first trimester. APHUO rates were higher in smokers than non-smokers (7.4%, n = 30 vs 4.5%, n = 122; P = 0.01), but there was no difference between ceased smokers and non-smokers (4.3%, n = 16 vs 4.5%, n = 122; P = 0.90). Smoking was no longer significantly associated with APHUO after adjustment for confounders (adjusted OR = 1.28, 95% CI 0.76-2.14), but vaginal bleeding in early pregnancy (adjusted OR = 2.98, 95% CI 2.12-4.18) and overweight/obesity (adjusted OR = 1.43, 95% CI 1.02-1.99) were independent risk factors. First trimester folic acid use was associated with a reduced risk (adjusted OR = 0.44, 95% CI 0.25-0.77). Conclusion Smoking is not an independent risk factor for APHUO after adjustment for confounders, but other risk and protective factors have been identified. [ABSTRACT FROM AUTHOR]

Background For many adults with an intellectual disability (ID), mealtimes carry significant health risks. While research and allied clinical guidance has focused mainly on dysphagia, adults with a range of physical and behavioural difficulties require mealtime support to ensure safety and adequate nutrition. The extent of need for and nature of such support within the wider ID population has yet to be reported. Methods In this study, we have estimated the prevalence of need for mealtime support among people with ID in the UK, using a population of 2230 adults known to specialist ID services (in Cambridgeshire, UK, total population 586 900). In a sample ( n = 69, aged 19 to 79 years, with mild to profound ID), we characterised the support provided, using a structured proforma to consult support workers and carers providing mealtime support, and health and social care records. Results Mealtime support was found to be required by a significant minority of people with ID for complex and varied reasons. Prevalence of need for such support was estimated at 15% of adults known to specialist ID services or 56 per 100 000 total population. Within a sample, support required was found to vary widely in nature (from texture modification or environmental adaptation to enteral feeding) and in overall level (from minimal to full support, dependent on functional skills). Needs had increased over time in almost half ( n = 34, 49.3%). Reasons for support included difficulties getting food into the body ( n = 56, 82.2%), risky eating and drinking behaviours ( n = 31, 44.9%) and slow eating or food refusal ( n = 30, 43.5%). These proportions translate into crude estimates of the prevalence of these difficulties within the known ID population of 11.9%, 6.6% and 6.4% respectively. Within the sample of those requiring mealtime support, need for support was reported to be contributed to by the presence of additional disability or illness (e.g. visual impairment, poor dentition and dementia; n = 45, 65.2%) and by psychological or behavioural issues (e.g. challenging behaviour, emotional disturbance; n = 36, 52.2%). Conclusions These findings not only highlight the need for a multidisciplinary approach to mealtime interventions (paying particular attention to psychological and environmental as well as physical issues), but also signal the daily difficulties faced by carers and paid support workers providing such support and illustrate their potentially crucial role in managing the serious health risks associated with eating and drinking difficulties in this population. [ABSTRACT FROM AUTHOR]

Background: Functional constipation is common in childhood; diets in affluent industrialised countries may be a significant contributory factor as a result of inadequate fibre content. Only a few intervention studies have been reported where childhood constipation has been treated by increasing dietary fibre. The present study aimed to demonstrate that dietary fibre intakes of children with constipation can be increased using a specifically-designed behaviour modification technique with a self-monitoring and reward system. Methods: Forty-three children, aged 2-14 years, with functional constipation (defined as less than three bowel movements per week with hard stools and difficulty or delay in defecation) were randomised to one of two treatment groups: Control ( n = 20), receiving general advice on increasing dietary fibre intake, or Intervention ( n = 23), using the intervention tool. Fibre intake, laxative use and stool frequency were assessed at baseline, and at 3, 6 and 12 months, using parent-filled diaries. Results: A behavioural intervention method significantly increases the fibre intakes of children with constipation at 3 months compared to standard dietary treatment ( P = 0.005), remaining so after adjusting for baseline fibre intake ( P = 0.007). Follow-up at 6 and 12 months showed no further increase. No significant benefit in terms of a reduction in laxative use or increased stool frequency associated with additional fibre intake was demonstrated. Conclusions: The findings confirm the difficulties encountered in beginning and maintaining high-fibre diets in children. [ABSTRACT FROM AUTHOR]

Introduction Significant event analysis (SEA) is now well established in UK primary care. Previously, considerable variation has been reported in the knowledge, skills and attitudes of general practitioners undertaking SEA. Little is known about the wider team's understanding, participation or perceptions. We therefore aimed to determine the awareness, degree of analysis and perceived risk of recurrence of a recent significant event, types of discussion forums, staff groups' participation and perceived barriers. Comparisons were made with a 2003 survey and significant changes described. Method A postal questionnaire survey was undertaken of a random selection of general practice team members in National Health Service Greater Glasgow in 2008/9. Results In total, 375/711 respondents (53%) from 111 practices participated. The vast majority was aware of a recent significant event, 29% reported not implementing a change and 23% perceived the risk of recurrence as moderate to high. Administrative and community-based staff were infrequently involved in meetings. Dedicated significant event meetings remain uncommon ( P = 0.06). Perceptions improved since 2003, but lack of time remained a concern. Discussion This survey was the first known attempt to include all members of the primary care team while studying SEA. Awareness and analysis levels were high, but only lead to sustainable improvement of care quality and clinical safety if teams implement change. Greater use should be made of dedicated SEA meetings and participation of all staff groups increased to gain full benefits. Lack of time can be managed pragmatically by prioritizing events based on their perceived severity, potential for change and potential team involvement. [ABSTRACT FROM AUTHOR]