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Opinions about the importance of various measures of disease activity in rheumatoid arthritis gathered from a survey of 20% of British rheumatologists showed a wide diversity for all clinical variables. 'Paper patients' have been developed as a method of investigating actual clinical decisions rather than expressed opinions. Assessments based on 'paper patients' correlate highly (r = +0.901) with those made on the equivalent real patients when seen in person. [ABSTRACT FROM PUBLISHER]

Objective: To explore feasibility of using child/young person patient-reported outcome measures (PROMs) routinely in practice, using vision-specific instruments and paediatric ophthalmology as the exemplar.Methods: Participants comprised patients aged 8-17 years, with visual impairment or low vision (visual acuity of the logarithm of the minimum angle of resolution (logMAR) worse than 0.3 in the better eye), attending the Department of Ophthalmology at Great Ormond Street Hospital, London, UK. All participants completed age-appropriate PROMs before attending their outpatient appointment. Half were randomly assigned to completion at home, with the choice of paper-and-pencil or electronic format. The other half were invited to complete PROMs during their hospital appointment, and randomly assigned to completion format. All participants completed a face-to-face survey exploring their attitudes and preferences. Analysis comprised survival analysis, and direct comparisons of proportions, with complementary qualitative data analysis.Results: 93 patients participated. 48 (98%) completing PROMs at home chose the paper-and-pencil format. Completion at home took longer than at hospital (median=20, vs 14 min, p<0.001). Visual acuity was associated with completion time (p=0.007) and missing data (p=0.03). Overall, 52 (60%) reported a preference for completion at home but there was no clear preference for format (37 (43%) preferred either format).Conclusion: PROM completion at home ahead of hospital appointments may be preferable for collecting complete, high-quality datasets. Despite equipoise on preference for format, the majority of those completing at home chose the traditional paper-and-pencil format, despite impaired sight. These findings should inform implementation of child/young person PROMs into routine practice. [ABSTRACT FROM AUTHOR]

Background: Current evidence suggests that chlamydia screening programmes can be cost-effective, conditional on assumptions within mathematical models. We explored differences in cost estimates used in published economic evaluations of chlamydia screening from seven countries (four papers each from UK and the Netherlands, two each from Sweden and Australia, and one each from Ireland, Canada and Denmark).Methods: From these studies, we extracted management cost estimates for seven major chlamydia sequelae. In order to compare the influence of different sequelae considered in each paper and their corresponding management costs on the total cost per case of untreated chlamydia, we applied reported unit sequelae management costs considered in each paper to a set of untreated infection to sequela progression probabilities. All costs were adjusted to 2013/2014 Great British Pound (GBP) values.Results: Sequelae management costs ranged from £171 to £3635 (pelvic inflammatory disease); £953 to £3615 (ectopic pregnancy); £546 to £6752 (tubal factor infertility); £159 to £3341 (chronic pelvic pain); £22 to £1008 (epididymitis); £11 to £1459 (neonatal conjunctivitis) and £433 to £3992 (neonatal pneumonia). Total cost of sequelae per case of untreated chlamydia ranged from £37 to £412.Conclusions: There was substantial variation in cost per case of chlamydia sequelae used in published chlamydia screening economic evaluations, which likely arose from different assumptions about disease management pathways and the country perspectives taken. In light of this, when interpreting these studies, the reader should be satisfied that the cost estimates used sufficiently reflect the perspective taken and current disease management for their respective context. [ABSTRACT FROM AUTHOR]

In a companion paper, we showed how local hospital leaders could assess systems and identify key safety concerns and targets for system improvement. In the present paper, we consider how these leaders might implement practical, low-cost interventions to improve safety. Our focus is on making immediate safety improvements both to directly improve patient care and as a foundation for advancing care in the longer-term. We describe a 'portfolio' approach to safety improvement in four broad categories: prioritising critical processes, such as checking drug doses; strengthening the overall system of care, for example, by introducing multiprofessional handovers; control of known risks, such as only using continuous positive airway pressure when appropriate conditions are met; and enhancing detection and response to hazardous situations, such as introducing brief team meetings to identify and respond to immediate threats and challenges. Local clinical leaders and managers face numerous challenges in delivering safe care but, if given sufficient support, they are nevertheless in a position to bring about major improvements. Skills in improving safety and quality should be recognised as equivalent to any other form of (sub)specialty training and as an essential element of any senior clinical or management role. National professional organisations need to promote appropriate education and provide coaching, mentorship and support to local leaders. [ABSTRACT FROM AUTHOR]

Introduction: The South African National Department of Health sought to improve syndromic management of sexually transmitted infections (STIs). Continuing medical education on STIs was delivered at primary healthcare (PHC) clinics using one of three training methods: (1) lecture, (2) computer and (3) paper-based. Clinics with training were compared with control clinics.Methods: Ten PHC clinics were randomly assigned to control and 10 to each training method arm. Clinicians participated in on-site training on six modules; two per week for three weeks. Each clinic was visited by three or four unannounced standardised patient (SP) actors pre-training and post-training. Male SPs reported symptoms of male urethritis syndrome and female SPs reported symptoms of vaginal discharge syndrome. Quality of healthcare was measured by whether or not clinicians completed five tasks: HIV test, genital exam, correct medications, condoms and partner notification.Results: An average of 31% of clinicians from each PHC attended each module. Quality of STI care was low. Pre-training (n=128) clinicians completed an average of 1.63 tasks. Post-training (n=114) they completed 1.73. There was no change in the number of STI tasks completed in the control arm and an 11% increase overall in the training arms relative to the control (ratio of relative risk (RRR)=1.11, 95% CI 0.67 to 1.84). Across training arms, there was a 26% increase (RRR=1.26, 95% CI 0.77 to 2.06) associated with lecture, 17% increase (RRR=1.17, 95% CI 0.59 to 2.28) with paper-based and 13% decrease (RRR=0.87, 95% CI 0.40 to 1.90) with computer arm relative to the control.Conclusions: Future interventions should address increasing training attendance and computer-based training effectiveness.Trial Registration Number: AEARCTR-0000668. [ABSTRACT FROM AUTHOR]

Background Patient decision aids (PDAs) are evidence-based tools designed to help patients make specific and deliberated choices among healthcare options. The International Patient Decision Aid Standards (IPDAS) Collaboration review papers and Cochrane systematic review of PDAs have found significant gaps in the reporting of evaluations of PDAs, including poor or limited reporting of PDA content, development methods and delivery. This study sought to develop and reach consensus on reporting guidelines to improve the quality of publications evaluating PDAs. Methods An international workgroup, consisting of members from IPDAS Collaboration, followed established methods to develop reporting guidelines for PDA evaluation studies. This paper describes the results from three completed phases: (1) planning, (2) drafting and (3) consensus, which included a modified, two-stage, online international Delphi process. The work was conducted over 2 years with bimonthly conference calls and three inperson meetings. The workgroup used input from these phases to produce a final set of recommended items in the form of a checklist. Results The SUNDAE Checklist (Standards for UNiversal reporting of patient Decision Aid Evaluations) includes 26 items recommended for studies reporting evaluations of PDAs. In the two-stage Delphi process, 117/143 (82%) experts from 14 countries completed round 1 and 96/1 17 (82%) completed round 2. Respondents reached a high level of consensus on the importance of the items and indicated strong willingness to use the items when reporting PDA studies. Conclusion The SUNDAE Checklist will help ensure that reports of PDA evaluation studies are understandable, transparent and of high quality. A separate Explanation and Elaboration publication provides additional details to support use of the checklist. [ABSTRACT FROM AUTHOR]

Background: No data on healthcare utilisation and associated costs for the many rare entities of children's interstitial lung diseases (chILD) exist. This paper portrays healthcare utilisation structures among individuals with chILD, provides a pan-European estimate of a 3-month interval per-capita costs and delineates crucial cost drivers.Methods: Based on longitudinal healthcare resource utilisation pattern of 445 children included in the Kids Lung Register diagnosed with chILD across 10 European countries, we delineated direct medical and non-medical costs of care per 3-month interval. Country-specific utilisation patterns were assessed with a children-tailored modification of the validated FIMA questionnaire and valued by German unit costs. Costs of care and their drivers were subsequently identified via gamma-distributed generalised linear regression models.Results: During the 3 months prior to inclusion into the registry (baseline), the rate of hospital admissions and inpatient days was high. Unadjusted direct medical per capita costs (€19 818) exceeded indirect (€1 907) and direct non-medical costs (€1 125) by far. Country-specific total costs ranged from €8 713 in Italy to €28 788 in Poland. Highest expenses were caused by the disease categories 'diffuse parenchymal lung disease (DPLD)-diffuse developmental disorders' (€45 536) and 'DPLD-unclear in the non-neonate' (€47 011). During a follow-up time of up to 5 years, direct medical costs dropped, whereas indirect costs and non-medical costs remained stable.Conclusions: This is the first prospective, longitudinal study analysing healthcare resource utilisation and costs for chILD across different European countries. Our results indicate that chILD is associated with high utilisation of healthcare services, placing a substantial economic burden on health systems. [ABSTRACT FROM AUTHOR]

Objective: Closed-loop systems have been used to optimise insulin delivery in children with diabetes, but they have not been tested in neonatal intensive care. Extremely preterm infants are prone to hyperglycaemia and hypoglycaemia; both of which have been associated with adverse outcomes. Insulin sensitivity is notoriously variable in these babies and glucose control is time-consuming, with management requiring frequent changes of dextrose-containing fluids and careful monitoring of insulin treatment. We aimed to evaluate the feasibility of closed-loop management of glucose control in these infants.Design and Setting: Single-centre feasibility study with a randomised parallel design in a neonatal intensive care unit. Eligibility criteria included birth weight <1200 g and <48 hours of age. All infants had subcutaneous continuous glucose monitoring for the first week of life, with those in the intervention group receiving closed-loop insulin delivery in a prespecified window, between 48 and 72 hours of age during which time the primary outcome was percentage of time in target (sensor glucose 4-8 mmol/L).Results: The mean (SD) gestational age and birth weight of intervention and control study arms were 27.0 (2.4) weeks, 962 (164) g and 27.5 (2.8) weeks, 823 (282) g, respectively, and were not significantly different. The time in target was dramatically increased from median (IQR) 26% (6-64) with paper guidance to 91% (78-99) during closed loop (p<0.001). There were no serious adverse events and no difference in total insulin infused.Conclusions: Closed-loop glucose control based on subcutaneous glucose measurements appears feasible as a potential method of optimising glucose control in extremely preterm infants. [ABSTRACT FROM AUTHOR]

Objectives: Many countries are now using primary human papillomavirus (HPV) testing for cervical screening, testing for high-risk HPV and using cytology as triage. An HPV-positive result can have an adverse psychological impact, at least in the short term. In this paper, we explore the psychological impact of primary HPV screening over 12 months.Methods: Women were surveyed soon after receiving their results (n=1133) and 6 (n=762) and 12 months (n=537) later. Primary outcomes were anxiety (Short-Form State Anxiety Inventory-6) and distress (General Health Questionnaire-12). Secondary outcomes included concern, worry about cervical cancer and reassurance. Mixed-effects regression models were used to explore differences at each time point and change over time across four groups according to their baseline result: control (HPV negative/HPV cleared/normal cytology and not tested for HPV); HPV positive with normal cytology; HPV positive with abnormal cytology; and HPV persistent (ie, second consecutive HPV-positive result).Results: Women who were HPV positive with abnormal cytology had the highest anxiety scores at baseline (mean=42.2, SD: 15.0), but this had declined by 12 months (mean=37.0, SD: 11.7) and was closer to being within the 'normal' range (scores between 34 and 36 are considered 'normal'). This group also had the highest distress at baseline (mean=3.3, SD: 3.8, scores of 3+ indicate case-level distress), but the lowest distress at 12 months (mean=1.9, SD: 3.1). At 6 and 12 months, there were no between-group differences in anxiety or distress for any HPV-positive result group when compared with the control group. The control group were less concerned and more reassured about their result at 6 and 12 months than the HPV-positive with normal cytology group.Conclusions: Our findings suggest the initial adverse impact of an HPV-positive screening result on anxiety and distress diminishes over time. Specific concerns about the result may be longer lasting and efforts should be made to address them. [ABSTRACT FROM AUTHOR]

Background/aim: Web 2.0 internet technology has great potential in promoting physical activity. This trial investigated the effectiveness of a Web 2.0-based intervention on physical activity behaviour, and the impact on website usage and engagement.Methods: 504 (328 women, 126 men) insufficiently active adult participants were randomly allocated to one of two web-based interventions or a paper-based Logbook group. The Web 1.0 group participated in the existing 10 000 Steps programme, while the Web 2.0 group participated in a Web 2.0-enabled physical activity intervention including user-to-user interaction through social networking capabilities. ActiGraph GT3X activity monitors were used to assess physical activity at four points across the intervention (0, 3, 12 and 18 months), and usage and engagement were assessed continuously through website usage statistics.Results: Treatment groups differed significantly in trajectories of minutes/day of physical activity (p=0.0198), through a greater change at 3 months for Web 2.0 than Web 1.0 (7.3 min/day, 95% CI 2.4 to 12.3). In the Web 2.0 group, physical activity increased at 3 (mean change 6.8 min/day, 95% CI 3.9 to 9.6) and 12 months (3.8 min/day, 95% CI 0.5 to 7.0), but not 18 months. The Logbook group also increased physical activity at 3 (4.8 min/day, 95% CI 1.8 to 7.7) and 12 months (4.9 min/day, 95% CI 0.7 to 9.1), but not 18 months. The Web 1.0 group increased physical activity at 12 months only (4.9 min/day, 95% CI 0.5 to 9.3). The Web 2.0 group demonstrated higher levels of website engagement (p=0.3964).Conclusions: In comparison to a Web 1.0 intervention, a more interactive Web 2.0 intervention, as well as the paper-based Logbook intervention, improved physical activity in the short term, but that effect reduced over time, despite higher levels of engagement of the Web 2.0 group.Trial Registration Number: ACTRN12611000157976. [ABSTRACT FROM AUTHOR]

Twenty five patients with right cerebral hemisphere damage and neglect participated in a series of bisection experiments. As expected, long lines were bisected to the right of true midpoint. By contrast, large circles and long white paper strips were bisected accurately, or with leftward errors. Small objects were less sensitive to stimulus properties: short lines and paper strips, and small circles, were bisected to the left of true midpoint, and these leftward errors were equally common as rightward errors with long lines. When asked to draw a perpendicular line of the same length as the presented horizontal line, patients overestimated the length of short lines but underestimated that of long lines. Presenting lines in near and far extrapersonal space selectively affected bisection of short lines. The results suggest that two opposing, independent mechanisms determine bisection performance in left neglect. [ABSTRACT FROM AUTHOR]

The Sustainable Development Goals, Global Strategy for Women's, Children's and Adolescents' Health (2016-2030) and Nurturing Care Framework all include targets to ensure children thrive However, many projects to support early childhood development (ECD) do not 'scale well' and leave large numbers of children unreached. This paper is the fifth in a series examining effective scaling of ECD programmes. This qualitative study explored experiences of scaling-up among purposively recruited implementers of ECD projects in low- and middle-income countries. Participants were sampled, by means of snowball sampling, from existing networks notably through Saving Brains®, Grand Challenges Canada®. Findings of a recent literature review on scaling-up frameworks, by the WHO, informed the development of a semistructured interview schedule. All interviews were conducted in English, via Skype, audio recorded and transcribed verbatim. Interviews were analysed using framework analysis. Framework analysis identified six major themes based on a standard programme cycle: planning and strategic choices, project design, human resources, financing and resource mobilisation, monitoring and evaluation, and leadership and partnerships. Key informants also identified an overarching theme regarding what scaling-up means. Stakeholders have not found existing literature and available frameworks helpful in guiding them to successful scale-up. Our research suggests that rather than proposing yet more theoretical guidelines or frameworks, it would be better to support stakeholders in developing organisational leadership capacity and partnership strategies to enable them to effectively apply a practical programme cycle or systematic process in their own contexts. [ABSTRACT FROM AUTHOR]

Objectives: This paper aims to estimate the percentage of European men who have sex with men (MSM) who may benefit from pre-exposure prophylaxis (PrEP), applying the three most widely used HIV risk indices for MSM (MSM Risk Index, Menza score, San Diego Early Test (SDET) score) and drawing on a large-scale multisite bio-behavioural survey (Sialon II).Methods: The Sialon II study was a bio-behavioural survey among MSM implemented in 13 European cities using either time-location sampling or respondent-driven sampling. Biological and behavioural data from 4901 MSM were collected. Only behavioural data of HIV-negative individuals were considered. Three widely used risk indices to assess HIV acquisition risk among MSM were used to estimate individual HIV risk scores and PrEP eligibility criteria.Results: 4219 HIV-negative MSM were considered. Regardless the HIV risk score used and the city, percentages of MSM eligible for PrEP were found to range between 5.19% and 73.84%. Overall, the MSM Risk Index and the Menza score yielded broadly similar percentages, whereas the SDET Index provided estimates constantly lower across all cities. Although all the three scores correlated positively (r>0.6), their concordance was highly variable (0.01Conclusion: Our findings showed the impact of different scoring systems on the estimation of the percentage of MSM who may benefit from PrEP in European cities. Although our primary aim was not to compare the performance of different HIV risk scores, data show that a considerable percentage of MSM in each city should be offered PrEP in order to reduce HIV infections. As PrEP is highly effective at preventing HIV among MSM, our findings provide useful, practical guidance for stakeholders in implementing PrEP at city level to tackle HIV infections in Europe. [ABSTRACT FROM AUTHOR]

The study aimed to develop evidence-based recommendations regarding the evaluation and use of biosimilars to treat rheumatological diseases. The task force comprised an expert group of specialists in rheumatology, dermatology and gastroenterology, and pharmacologists, patients and a regulator from ten countries. Four key topics regarding biosimilars were identified through a process of discussion and consensus. Using a Delphi process, specific questions were then formulated to guide a systematic literature review. Relevant English-language publications through November 2016 were searched systematically for each topic using Medline; selected papers and pertinent reviews were examined for additional relevant references; and abstracts presented at the 2015 and 2016 American College of Rheumatology (ACR) and European League Against Rheumatism (EULAR) annual scientific meetings were searched for those about biosimilars. The experts used evidence obtained from these studies to develop a set of overarching principles and consensus recommendations. The level of evidence and grade of recommendation were determined for each. By the search strategy, 490 references were identified. Of these, 29 full-text papers were included in the systematic review. Additionally, 20 abstracts were retrieved from the ACR and EULAR conference abstract databases. Five overarching principles and eight consensus recommendations were generated, encompassing considerations regarding clinical trials, immunogenicity, extrapolation of indications, switching between bio-originators and biosimilars and among biosimilars, and cost. The level of evidence and grade of recommendation for each varied according to available published evidence. Five overarching principles and eight consensus recommendations regarding the evaluation and use of biosimilars to treat rheumatological diseases were developed using research-based evidence and expert opinion. [ABSTRACT FROM AUTHOR]

Objective: Increasingly the views of young people are sought when improving healthcare; however, it is unclear how they shape policy or practice. This paper presents a consultation with young people commissioned by the National Institute for Health and Care Excellence (NICE) to inform clinical guidelines for paediatric palliative care (end-of-life care for infants, children and young people).Methods: The consultation involved qualitative thematic analysis of data from 14 young people (aged 12-18 years) with a life-limiting or life-threatening condition who took part in focus groups or interviews. The topics explored were predefined by NICE: information and communication; care planning; place of care; and psychological care. Data collection consisted of discussion points and activities using visual cues and was informed by a pilot consultation group with five young adults (aged 19-24 years). Findings were shared with participants, and feedback helped to interpret the findings.Results: Four overarching themes were identified, cutting across the predetermined topic areas: being treated as individuals with individual needs and preferences; quality of care more important than place; emotional well-being; and living as a young person. Importantly, care planning was viewed as a tool to support living well and facilitate good care, and the young people were concerned less about where care happens but who provides this.Conclusion: Young people's priorities differ from those of parents and other involved adults. Incorporating their priorities within policy and practice can help to ensure their needs and preferences are met and relevant research topics identified. [ABSTRACT FROM AUTHOR]

The purpose of this study was to develop a formula to determine and compare the compressibility of selected sport balls. Six balls (basketball, volleyball, soccer ball, baseball, handball, golf ball) were dropped ten times from each of four different heights onto a smooth solid surface overlaid with a white sheet of typing paper, overlaid with a sheet of carbon paper. The diameter of the area of contact of each ball imprinted onto the typing paper was measured in millimetres with calipers. From the data, the distance (d) that each ball compressed for each velocity (v) was calculated. It was found that a linear relationship existed between velocity at impact and the distance for each ball studied. The compressibility coefficient (c) for each ball was calculated and a formula was developed to determine the distance each ball would compress at a given velocity. When velocity is measured in metres per second and the distance a ball compresses is measured in millimetres, the formula to determine d for selected balls, in order of compressibility is: basketball d = 3.07v, volleyball d = 2.90v, soccer ball d = 2.80v, baseball d = 0.77v, handball d = 0.53v, and golf ball d = 0.17v. [ABSTRACT FROM PUBLISHER]

Two rheumatologists made judgments about 'current disease activity' in real patients and 'paper patients' with rheumatoid arthritis. Analysis of each set of judgments provides a model of judgment policy which contains only 3 clinical variables but explains over 94% of the variance in judgments. The judgment policy models differ markedly from each other and from the clinicians' own perceptions of their behaviour. Judgment policy modelling offers a means of improving co-ordination between clinical investigators within and between centres. [ABSTRACT FROM PUBLISHER]

Background: It is current practice to use a single diagnostic sleep study in the diagnostic workup of obstructive sleep apnoea (OSA). However, a relevant night-to-night variability (NtNV) of respiratory events has been reported.Methods: We evaluated the NtNV of respiratory events in adults with suspected or already diagnosed OSA who underwent more than one diagnostic sleep study. Data sources were PubMed, Cochrane and Embase up to 23 January 2019. Random-effects models were used for evidence synthesis. For moderator analysis, mixed-effects regression analysis was performed. The study was registered with PROSPERO (CRD42019135277).Results: Of 2143 identified papers, 24 studies, comprising 3250 participants, were included. The mean Apnoea-Hypopnoea Index (AHI) difference between the first and second night was -1.70/hour (95% CI -3.61 to 0.02). REM time differences (first to second night) were significantly positive associated with differences in mean AHI (β coefficient 0.262 (95% CI 0.096 to 0.428). On average, 41% (95% CI 27% to 57%) of all participants showed changes of respiratory events >10/hour from night to night. Furthermore, 49% (95% CI 32% to 65%) of participants changed OSA severity class (severity thresholds at 5/hour, 15/hour and 30/hour) at least once in sequential sleep studies. Depending on the diagnostic threshold (5/hour, 10/hour or 15/hour), on average 12% (95% CI 9% to 15%), 12% (95% CI 8% to 19%) and 10% (95% CI 8% to 13%) of patients would have been missed during the first night due to single night testing.Conclusion: While there was no significant difference between mean AHI in two sequential study nights on a group level, there was a remarkable intraindividual NtNV of respiratory events, leading to misdiagnosis and misclassification of patients with suspected OSA. [ABSTRACT FROM AUTHOR]

Background: The National Institute for Health and Care Excellence (NICE) neonatal jaundice guidance recommends a urine culture for investigation of babies with prolonged jaundice. However, the evidence cited for this guidance is limited. We aimed to review local data and the existing literature to identify evidence to either support or refute this guidance.Method: We retrospectively reviewed 3 years of urine cultures from our outpatient prolonged jaundice clinic. We then conducted literature review with meta-analysis of studies presenting original data on urine tract infection (UTI) rates in jaundiced and prolonged jaundiced babies.Results: From our local data, none of the 279 patients met our unit clinical criteria for UTI. Literature review revealed considerable differences worldwide in UTI rates in both jaundiced and prolonged jaundiced cases. Using pooled data from our literature review and our local population, the incidence of UTI in prolonged jaundiced babies is 0.21% (95% CI 0.0% to 0.73%) in the UK. This is significantly lower than the figure indicated from the data from elsewhere in the world, 8.21% (95% CI 4.36% to 13.0%).Conclusions: The findings both from our local data and the current literature do not support the practice of routine screening for urine infection in well babies with prolonged jaundice. In view of the above, we no longer include urine culture in screening of well infants with prolonged jaundice. We hope that NICE will re-examine the evidence and recommend changes to their guidance on the role of routine screening for urine infection in babies with prolonged jaundice. [ABSTRACT FROM AUTHOR]

Ninety diabetic children each provided at least one 24-hour blood glucose profile at home using an impregnated filter paper strip. The mean 24-hour blood glucose level correlated significantly with urine control, height velocity, and Hb A1. The correlation coefficient for individual blood glucose values (r = 0.61) and for mean 24-hour blood glucose values (r = 0.73) repeated within 14 days showed an acceptable degree of reproducibility for the blood glucose profiles. Mean 24-hour blood glucose values fell significantly overall (11.4 to 9.8 mmol/l; 205 to 176 mg/100 ml) in 47 children who had repeated profiles more than 2 weeks apart. Unrecognised nocturnal hypoglycaemia (less than 3.0 mmol/l; 54 mg/100 ml) was found in 19% of children on twice-daily Semitard insulin. The study shows that children over age 7 years manage home blood glucose monitoring without difficulty. It shows that the results are reproducible and correlate with other indices of control, and that it provides a practical basis for the improvement of diabetic control. [ABSTRACT FROM AUTHOR]

Although many different beta blockers are now in clinical use, there is very little information concerning their relative efficacy, and it is still not clear what clinical importance should be attached to properties such as positive inotropic stimulation (intrinsic sympathomimetic activity or ISA) and membrane stabilizing action ("local anaesthetic effect" or "quinidine-like effect"). In this report we compare the ability of patients with angina to exercise on a bicycle ergometer while receiving a series of commonly used beta blockers, and attempt to determine the importance of ISA. The investigation is in four parts with the drugs given orally or intravenously: statistical analysis of the results was carried out using standard methods, both parametric and non-parametric (Friedmann analysis of variance, Wilcoxon matched pairs signed ranks test) by two independent statisticians. The relevant properties of drugs included in this paper are summarized in Table I. Laboratory reports using many different animal preparations may differ from this assessment under specific conditions, and the Table is intended only as a guide to the generally accepted properties of these drugs when used clinically. Results for sotalol are included for reference in the first part of this paper but the drug was withdrawn from clinical use and was not studied further. [ABSTRACT FROM PUBLISHER]

It is often argued that the continuity of the processes of embryo development precludes the establishment of morally significant boundaries, once development is under way. These arguments typically claim that marking out any moral boundaries requires identifying particular significant events, and that in such circumstances this is either impossible or arbitrary. In this paper it is argued that arguments of this kind are not cogent. The paper concludes by indicating where the real problems lie. [ABSTRACT FROM PUBLISHER]

A method for making clinico-anatomical correlations by computer superimposition of brain maps derived from CT scan images, described in a companion paper, was tested in 19 patients with an uncomplicated left hemiparesis due to acute stroke. Eight patients with an isolated left hemiparesis had small lesions in the most rostral part of the right internal capsule. The composite lesion maps of 11 patients whose left hemiparesis was complicated only by spinothalamic sensory loss showed a larger area of damage more caudally in the posterior part of the posterior limb of the capsule, abutting the thalamus. The close correlation between the results obtained by this method and those obtained in previous clinico-pathological studies of patients with uncomplicated strokes, confirms the validity of this mapping technique. [ABSTRACT FROM AUTHOR]

The increasing use of electrical stimulation of the brain for relief of pain, spasticity and epilepsy has introduced unfamiliar techniques into clinical neurological and neurosurgical practice. In view of the evidence that excessive levels of stimulation can damage brain tissue, it is of great importance to monitor the dose of stimulation. A review of recent clinical papers suggests that many centres do not measure the dose accurately, relying on arbitrary dial settings on external transmitters. This paper reviews that factors that affect the dose received by the patient and suggests methods of measuring them, at operation and subsequently, which should routinely be employed by clinicians implanting stimulators. [ABSTRACT FROM AUTHOR]

Objective: This systematic review aimed to establish the relative incidence of new postoperative brain MRI findings following paediatric congenital cardiac surgery.Design: To distinguish perioperative changes from pre-existing MR findings, our systematic search strategy focused on identifying original research studies reporting both presurgery and postsurgery brain MRI scans. Patient demographics, study methods and brain MR findings were extracted.Results: Twenty-one eligible publications, including two case-control and one randomised controlled trial, were identified. Pre-existing brain MRI findings were noted in 43% (513/1205) of neonates prior to surgery, mainly white matter injuries (WMI). Surgery was performed at a median age of 8 days with comparison of preoperative and postoperative MR scans revealing additional new postoperative findings in 51% (550/1075) of patients, mainly WMI. Four studies adopted a brain injury scoring system, but the majority did not indicate the severity or time course of findings. In a subgroup analysis, approximately 32% of patients with pre-existing lesions went on to develop additional new lesions postsurgery. Pre-existing findings were not found to confer a higher risk of acquiring brain lesions postoperatively. No evidence was identified linking new MR findings with later neurodevelopmental delay.Conclusion: This systematic review suggests that surgery approximately doubles the number of patients with new brain lesions. [ABSTRACT FROM AUTHOR]

This paper describes urinary tract infections (UTI) from the perspective of a disturbed balance between bacterial virulence and host defence. In some children, a UTI is caused by a virulent Escherichia coli, while in other cases children with abnormal renal tracts can get infected by almost any bacteria. Such knowledge can help in guiding treatment, investigations and follow-up of a child with a UTI. [ABSTRACT FROM AUTHOR]

Objective: In 2014, the European Society of Cardiology (ESC) recommended the use of a novel risk prediction model (HCM Risk-SCD) to guide use of implantable cardioverter defibrillators (ICD) for the primary prevention of sudden cardiac death (SCD) in patients with hypertrophic cardiomyopathy (HCM). We sought to determine the performance of HCM Risk-SCD by conducting a systematic review and meta-analysis of articles reporting on the prevalence of SCD within 5 years of evaluation in low, intermediate and high-risk patients as defined by the 2014 guidelines (predicted risk <4%, 4%-<6% and ≥6%, respectively).Methods: The protocol was registered with PROSPERO (registration number: CRD42017064203). MEDLINE and manual searches for papers published from October 2014 to December 2017 were performed. Longitudinal, observational cohorts of unselected adult patients, without history of cardiac arrest were considered. The original HCM Risk-SCD development study was included a priori. Data were pooled using a random effects model.Results: Six (0.9%) out of 653 independent publications identified by the initial search were included. The calculated 5-year risk of SCD was reported in 7291 individuals (70% low, 15% intermediate; 15% high risk) with 184 (2.5%) SCD endpoints within 5 years of baseline evaluation. Most SCD endpoints (68%) occurred in patients with an estimated 5-year risk of ≥4% who formed 30% of the total study cohort. Using the random effects method, the pooled prevalence of SCD endpoints was 1.01% (95% CI 0.52 to 1.61) in low-risk patients, 2.43% (95% CI 1.23 to 3.92) in intermediate and 8.4% (95% CI 6.68 to 10.25) in high-risk patients.Conclusions: This meta-analysis demonstrates that HCM Risk-SCD provides accurate risk estimations that can be used to guide ICD therapy in accordance with the 2014 ESC guidelines.Registration Number: PROSPERO CRD42017064203;Pre-results. [ABSTRACT FROM AUTHOR]

Objectives: Trichomoniasis is the most prevalent curable STI globally, with the highest incidence and prevalence in sub-Saharan Africa (sSA). STIs have largely been associated with an increase in HIV acquisition. Our objective was to assess the existing literature available in English regarding the association of Trichomoniasis and HIV-1 acquisition.Methods: The review protocol was registered at the International Prospective Register of Systematic Reviews (PROSPERO) under number CRD42018082702. We searched MEDLINE, Embase and Scopus databases to collect articles measuring the association of Trichomonas vaginalis infection and HIV acquisition and performed a meta-analysis and qualitative synthesis of the literature.Results: We identified 1806 unduplicated citations, of which 18 papers and 1 conference abstract were eligible for inclusion in the review after applying our inclusion and exclusion criteria. All the studies included in the systematic review had been carried out in sSA. The articles reported various measures of effects, namely: HRs, rate ratios, risk ratios and ORs. In a meta-analysis restricted to 11 studies reporting HR, individuals infected with T. vaginalis were 1.5 times more likely to acquire HIV compared with individuals not infected with T. vaginalis (95% CI 1.3 to 1.7; p<0.001).Conclusions: T. vaginalis is an important factor in HIV acquisition especially in sSA where the prevalence of both T. vaginalis and HIV-1 are high. This systematic review and meta-analysis confirms the evidence that infection with T. vaginalis augments HIV acquisition with 50%. Diagnosis and treatment of T. vaginalis infection in both high-risk and low-risk individuals may be a potential tool to reduce new HIV infections.Trial Registration Number: CRD42018082702. [ABSTRACT FROM AUTHOR]

This paper is part of a series of expert consensus documents covering all aspects of aviation cardiology. In this manuscript, we focus on the broad aviation medicine considerations that are required to optimally manage aircrew with established coronary artery disease in those without myocardial infarction or revascularisation (both pilots and non-pilot aviation professionals). We present expert consensus opinion and associated recommendations. It is recommended that in aircrew with non-obstructive coronary artery disease or obstructive coronary artery disease not deemed haemodynamically significant, nor meeting the criteria for excessive burden (based on plaque morphology and aggregate stenosis), a return to flying duties may be possible, although with restrictions. It is recommended that aircrew with haemodynamically significant coronary artery disease (defined by a decrease in fractional flow reserve) or a total burden of disease that exceeds an aggregated stenosis of 120% are grounded. With aggressive cardiac risk factor modification and, at a minimum, annual follow-up with routine non-invasive cardiac evaluation, the majority of aircrew with coronary artery disease can safely return to flight duties. [ABSTRACT FROM AUTHOR]

Objectives: Viral load and sexual risk behaviour contribute to HIV transmission risk. High HIV viral loads present greater transmission risk than transient viral 'blips' above an undetectable level. This paper therefore characterises sexual risk behaviour among patients with HIV in care with viral loads>1500 copies/mL and associated demographic characteristics.Methods: This cross-sectional study was conducted at six HIV outpatient clinics in USA. The study sample comprises 1315 patients with HIV with a recent viral load >1500 copies/mL. This study sample was drawn from a larger sample of individuals with a recent viral load >1000 copies/mL who completed a computer-assisted self-interview (CASI) regarding sexual risk practices in the last 2 months. The study sample was 32% heterosexual men, 38% men who have sex with men (MSM) and 30% women.Results: Ninety per cent of the sample had their viral load assay within 60 days of the CASI. Thirty-seven per cent reported being sexually active (vaginal or anal intercourse) in the last 2 months. Most of the sexually active participants reported always using condoms (56.9%) or limiting condomless sex to seroconcordant partners (serosorting; 29.2% overall and 42.9% among MSM). Among sexually active participants who reported condomless anal or vaginal sex with an at-risk partner (14%), most had viral loads>10 000 copies/mL (62%).Conclusions: A relatively small number of patients with HIV in care with viral loads above 1500 copies/mL reported concurrent sexual transmission risk behaviours. Most of the individuals in this small group had markedly elevated viral loads, increasing the probability of transmission. Directing interventions to patients in care with high viral loads and concurrent risk behaviour could strengthen HIV prevention and reduce HIV infections.Trial Registration Number: NCT02044484, completed. [ABSTRACT FROM AUTHOR]

Background: Being married is associated with healthier lifestyle behaviours and lower mortality and may reduce risk for dementia due to life-course factors. We conducted a systematic review and meta-analysis of studies of the association between marital status and the risk of developing dementia.Methods: We searched medical databases and contacted experts in the field for relevant studies reporting the relationship, adjusted for age and sex, between marital status and dementia. We rated methodological quality and conducted random-effects meta-analyses to summarise relative risks of being widowed, divorced or lifelong single, compared with being married. Secondary stratified analyses with meta-regression examined the impact of clinical and social context and study methodology on findings.Results: We included 15 studies with 812 047 participants. Compared with those who are married, lifelong single (relative risk=1.42 (95% CI 1.07 to 1.90)) and widowed (1.20 (1.02 to 1.41)) people have elevated risk of dementia. We did not find an association in divorced people.Further analyses showed that less education partially confounds the risk in widowhood and worse physical health the elevated risk in lifelong single people. Compared with studies that used clinical registers for ascertaining dementia diagnoses, those which clinically examined all participants found higher risk for being unmarried.Conclusions: Being married is associated with reduced risk of dementia than widowed and lifelong single people, who are also underdiagnosed in routine clinical practice. Dementia prevention in unmarried people should focus on education and physical health and should consider the possible effect of social engagement as a modifiable risk factor. [ABSTRACT FROM AUTHOR]

Objectives: A community level randomised controlled trial of a Community Popular Opinion Leader (C-POL) intervention to reduce bacterial and viral sexually transmitted infections (STIs) and unprotected extramarital sex was carried out over 2 years in five countries. The main study results did not find significant intervention effects. This paper presents a sub-analysis examining the differential intervention impacts among high-risk and low-risk participants in the China site.Methods: From 2002-2006, 3912 migrant market vendors aged 18 and 49 years were recruited at an urban site in China. Markets were randomly assigned to the C-POL intervention (N=20 markets; n=1979) or standard-care control condition (N=20; n=1933). Both study condition venues received HIV/STI education, free condoms, STI testing and treatment, and training for pharmacists in antibiotic treatments. In intervention markets, C-POLs were identified and trained to diffuse messages regarding safer sex, STI treatment and partner discussions of sex. The primary biological outcome was incidence of new STIs (chlamydia, gonorrhoea, syphilis, trichomonas, herpes or HIV). The primary sexual behaviour risk outcome was any unprotected extramarital sex in the prior 3 months.Results: In unadjusted analyses, women had significantly lower rates of STI infection at 24 months in the C-POL intervention (5.7%) compared to controls (8.3%; p = 0.043). In mixed-effects regression models, intervention participants with STIs at previous assessments were about half as likely to have STIs at 24 months (OR 0.47, 95% CI 0.25 to 0.90) compared to controls.Conclusions: The C-POL intervention lowers HIV risk among those at highest risk (i.e., with a STI or engaging in high-risk sexual activities) rather than the general population. [ABSTRACT FROM AUTHOR]

Background: During the transition to rheumatoid arthritis (RA) many patients pass through a phase characterised by the presence of symptoms without clinically apparent synovitis. These symptoms are not well-characterised. This taskforce aimed to define the clinical characteristics of patients with arthralgia who are considered at risk for RA by experts based on their clinical experience.Methods: The taskforce consisted of 18 rheumatologists, 1 methodologist, 2 patients, 3 health professionals and 1 research fellow. The process had three phases. In phase I, a list of parameters considered characteristic for clinically suspect arthralgia (CSA) was derived; the most important parameters were selected by a three-phased Delphi approach. In phase II, the experts evaluated 50 existing patients on paper, classified them as CSA/no-CSA and indicated their level of confidence. A provisional set of parameters was derived. This was studied for validation in phase III, where all rheumatologists collected patients with and without CSA from their outpatient clinics.Results: The comprehensive list consisted of 55 parameters, of which 16 were considered most important. A multivariable model based on the data from phase II identified seven relevant parameters: symptom duration <1 year, symptoms of metacarpophalangeal (MCP) joints, morning stiffness duration ≥60 min, most severe symptoms in early morning, first-degree relative with RA, difficulty with making a fist and positive squeeze test of MCP joints. In phase III, the combination of these parameters was accurate in identifying patients with arthralgia who were considered at risk of developing RA (area under the receiver operating characteristic curve 0.92, 95% CI 0.87 to 0.96). Test characteristics for different cut-off points were determined.Conclusions: A set of clinical characteristics for patients with arthralgia who are at risk of progression to RA was established. [ABSTRACT FROM AUTHOR]

Studying patients during the end of life is important, as it has the potential to lead to improvements in care for the dying. For patients who die after a controlled withdrawal of life-sustaining therapies in the intensive care unit, information about the natural history of death and the process of removing life support has additionally led to advances in practice for deceased organ donation. However, this unique population of severely critically ill and imminently dying patients has been difficult to study, largely due to assumptions made by research teams and ethics boards alike about the logistical difficulties of obtaining consent and completing research procedures before or during the process of withdrawal of life-sustaining therapies. In this paper, we describe the ethics substudy of the first prospective observational research study in Canada to obtain consent and collect clinical data on patients during the process of withdrawal of life-sustaining therapies in the intensive care unit. We describe in detail the process of protocol development, review by five institutional research ethics boards and bedside staff satisfaction with the study. We conclude that prospective research on a critically ill and imminently dying population is feasible and can be conducted in an ethical manner. Further information is needed about the experiences and motivations of families and substitute decision makers who provide consent for research on critically ill intensive care unit patients at the end of life. [ABSTRACT FROM AUTHOR]

Background: Young people's advisory groups (YPAGs) for research are comprised of children or adolescents who work with researchers to shape different stages of the research process. Their involvement is expected to ensure studies better reflect the preferences and needs of targeted youth populations. However, despite their increasing use in health research, there is little systematic evidence on the methods and impacts associated with YPAGs.Method: To address this gap, we conducted a scoping review of YPAGs in youth-focused health studies. We systematically searched MEDLINE for empirical studies in populations between 12 years and 18 years of age published in 2019. If a potential YPAG was identified, authors were contacted for additional information about the activities and level of involvement of the YPAG.Findings: Of all studies that collected primary data from persons aged 12-18 years, only 21 studies reported using youth advice during their research. This represents less than 1% of all published empirical child and adolescent studies. There was variation in the type of research activity undertaken by YPAGs and their level of involvement. Most studies involved YPAGs in co-production of research design and/or in dissemination activities. The majority of authors that responded were positive about the impact of YPAGs.Interpretation: Recommendations for consistent reporting of YPAG involvement in empirical studies include reporting on the match between YPAG and study populations, frequency/format of meetings, and the nature and level of involvement. [ABSTRACT FROM AUTHOR]

This paper reports a longitudinal study of 19 patients diagnosed as having pseudodementia more than a decade earlier. In only one patient was the earlier diagnosis changed to definite dementia and, in this patient, there were strong indicators that such a diagnosis should have been made initially. In a second patient, dementia could not be excluded. The remaining patients did not show evidence of a dementing illness and the courses of the illnesses resembled the primary psychiatric disorders responsible for the pseudodementia. The results validate the clinical utility of the term "pseudodementia". [ABSTRACT FROM AUTHOR]

The site of lesions responsible for horizontal gaze palsy and various types of internuclear ophthalmoplegia (INO) was established by identifying the common areas where the abnormal MRI signals from patients with a given ocular-motor disorder overlapped. Patients with unilateral gaze palsy had lesions in the paramedian area of the pons, including the abducens nucleus, the lateral part of the nucleus reticularis pontis caudalis and the nucleus reticularis pontis oralis. Patients with abducens nucleus lesions showed additional clinical signs of lateral rectus weakness. Lesions responsible for bilateral gaze palsy involved the pontine tegmental raphe. Since this region contains the saccadic omnipause neurons, this finding suggests that damage to omnipause cells produces slowing of saccades rather than opsoclonus, as previously proposed. All INOs, regardless of the presence of impaired abduction or convergence, had similar MRI appearances. Frequently the lesions in patients with INO, were not confined to the medial longitudinal fasciculus (MLF) but also involved neighbouring structures at the pontine and mid-brain levels. There was a statistically significant association between the clinical severity of the INO and the presence of abnormal abduction or convergence. The findings suggest that the lesions outside the MLF, which may affect abducens, gaze or convergence pathways, are responsible for the presence of features additional to INO, depending on the magnitude of functional disruption they produce. [ABSTRACT FROM AUTHOR]

Background: Manual analysis of sleep, breathing, and oxygenation records is the "gold standard" for diagnosing sleep abnormalities but is time consuming and cumbersome. The accuracy and cost of a computerised sleep analysis system have therefore been investigated.Methods: Manual and computerised (CNS Sleep Lab) scores from 43 consecutive clinical sleep studies were prospectively compared for accuracy and the time and costs were recorded.Results: There were good correlations and no systematic differences between manual and computer scoring for total sleep time, sleep onset latency, and duration of REM sleep. There was a small but clinically insignificant systematic difference in breathing pattern analysis, the number of hypopnoeas/hour being lower with manual than with computer scoring (13 (SE 3) v 15 (SE 3)/hour). There was no difference between computer and manual scoring of the frequency of apnoeas, so the frequency of apnoeas + hypopnoeas was clinically insignificantly higher with computer scoring with a highly significant correlation between the two techniques. The time taken to perform the analyses was not different between the two methods (manual 83 (SE 8) v computer 86 (SE 8) minutes). The computer system was six times more expensive than the manual system and annual running costs, including full maintenance contract and 15% depreciation, were twice as great.Conclusion: The CNS Sleep Lab is sufficiently accurate for use in clinical sleep studies but is significantly more expensive and does not save technician time. [ABSTRACT FROM AUTHOR]

The psychosocial morbidity associated with HIV infection and responses to such infection may exceed morbidity associated with medical sequelae of such infection. This paper argues that negative judgements on those with HIV infection or in groups associated with such infection will cause avoidable psychological and social distress. Moral judgements made regarding HIV infection may also harm the common good by promoting conditions which may increase the spread of HIV infection. This paper examines these two lines of argument with regard to the ethical aspects of psychological bases of health care, clinical contact, public perceptions of AIDS and the comparative perspective. It is concluded that the psychosocial aspects of HIV infection impose ethical psychological, as well as medical, obligations to reduce harm and prevent the spread of infection. [ABSTRACT FROM PUBLISHER]

In recent years several different methods have been developed to assess mechanical exposures, which are related to musculoskeletal disorders in ergonomic epidemiology. Each of these methods is capable of measuring one or more aspects of risk factors, but has drawbacks as well. Improper application of methods might result in biased exposure estimates, which has serious consequences for risk estimates arising from epidemiological studies. The aim of this paper was to systematically evaluate the usefulness of different measurement methods in terms of accuracy and applicability. Assessment of external exposure measures by subjective judgements (from experts or self reports from workers), observational methods (on site or afterwards from video recordings), and direct measurements methods (at work or during laboratory simulations) are discussed for each of the dimensions of exposure level, duration, and frequency. It is concluded that expert judgements and self reports give only limited insight into the occurrence of tasks and activities. Further information can be obtained from observations, which can best be combined with direct measurements of exposure to posture, movement, and exerted forces to achieve exposure profiles by occupational task. Internal exposures estimated by biomechanical modelling mostly consider the low back and require information on postures of the different body segments and exerted forces, completed with movement data in the case of dynamic models. Moreover, electromyography (EMG) and measurements of intra-abdominal pressure might be used for this purpose. Both biomechanical models and EMG are useful methods to assess internal exposure, but biomechanical models should not be restricted to the level of compressive forces on the lower back. Finally, current problems and future directions in measurement strategies and methods are discussed. [ABSTRACT FROM AUTHOR]

Objectives: This paper describes a study that was carried out in the primary nickel production industry to investigate the levels of personal exposure to aerosols containing nickel and the impact on exposure assessment of introducing new personal sampling techniques with performance consistent with the latest particle size-selective criteria.Methods: Experiments were carried out at workplaces in mining, milling, smelting, and refining works to investigate the effect of changing from the current method of total aerosol (with the widely used 37 mm filter holder) to the new method of measuring inhalable aerosol (with the Institute of Occupational Medicine (IOM) inhalable aerosol sampler).Results: The results show that inhalable aerosol exposure concentrations--for both overall aerosol and for total nickel--were consistently and significantly higher than the corresponding total aerosol concentrations. Weighted least squares linear regression yielded IOM/37 mm factors ranging from about 1.2 to 4.0. The exposure data for each company process were found to be log-normally distributed.Conclusions: The results suggest the possibility of generating a single pragmatic factor for each company process for converting current total aerosol exposures to new exposures based on the inhalability concept contained in the latest particle size-selective criteria for aerosol exposure assessment. Such data may be important in determining new occupational exposure limits for nickel. [ABSTRACT FROM AUTHOR]

Eighty nine British and Australian rheumatologists took part in a study to discover how accurately they could describe their procedures for measuring disease severity in rheumatoid arthritis. The relative importance they attached to different clinical and laboratory variables showed a very wide variation, and these stated policies were generally poor at predicting their actual judgments when assessing 'paper patients' (r2 = 39%). Policies based on equal weighting of all variables, while also poor predictors (r2 = 41%), were nevertheless superior to their stated policies for 49 respondents. Policies calculated by judgment (linear regression) analysis were much more successful predictors (R2 = 73%). Unhurried, detailed interviews with four experienced rheumatologists provided carefully considered statements of assessment policy, but these also were poor predictors of routine assessments of outpatients (r2 = 34%) compared with policies calculated by clinical judgment analysis, even when these were applied to new data (R2 = 88%). [ABSTRACT FROM PUBLISHER]

Denzimol, a new anticonvulsant drug, is currently undergoing clinical evaluation. In this paper we report its use in six patients who were also taking carbamazepine and two patients taking phenytoin. There was a striking elevation of serum carbamazepine, carbamazepine-10, 11 epoxide and phenytoin concentrations in all patients on the addition of denzimol therapy. The interaction with carbamazepine is greater in severity than any other reported to date and denzimol's interaction with both carbamazepine and phenytoin is likely to prove of major clinical significance. [ABSTRACT FROM AUTHOR]

Background: Engaging patients and the public as collaborators in research is increasingly recognised as important as such partnerships can help improve research relevance and acceptability. Young Persons' Advisory Groups (YPAGs) provide a forum for clinical researchers and triallists to engage with children and young people on issues relevant to the design, conduct and translation of paediatric clinical trials. Until fairly recently, there was very little information available to guide the successful development and operation of YPAGs.Objective: To develop an evidence-based tool to guide clinical researchers and triallists in the establishment and operation of a YPAG.Methods: An online needs assessment survey was conducted using SurveyMonkey with 60 known paediatric drug researchers to identify knowledge gaps around YPAG engagement, development and operation. Semistructured interviews with founders and coordinators of five well-established existing YPAGs and a review of the literature were performed to identify best-practice processes for starting up and operating YPAG.Results: The majority of 12 survey respondents (20%) from 12 different centres indicated that while they felt YPAGs could benefit their research, guidance on how to develop and operate a YPAG was needed. Most preferred a web-based guidance tool. Ten core steps in starting up and operating a YPAG were identified and developed into an online YPAG guidance tool, now freely accessible for use by paediatric clinical researchers worldwide. Plans to evaluate the impact are in place.Conclusions: This novel tool, developed with an internationally based group of public involvement leads working across paediatric clinical research areas, provides harmonised guidance for researchers seeking to develop and operate YPAGs to help improve the quality and impact of paediatric clinical research studies. [ABSTRACT FROM AUTHOR]

Objectives: To assess evidence supporting the view that 'low fibre causes childhood constipation'.Design: Triangulation integrated three approaches: a systematic review NICE guideline CG99 examining effectiveness of increasing fibre; a cohort study, Avon Longitudinal Study of Parents and Children (ALSPAC), to assess if constipation (or hard stools) can precede fibre intake at weaning; and a literature search for twin studies to calculate heredity.Setting: CG99 examined the literature regarding the effectiveness of increasing fibre. ALSPAC asked parents about: hard stools at 4 weeks, 6 months and 2.5 years and constipation at age 4-10 years, as well as fibre intake at 2 years. Twin studies and data from ALSPAC were pooled to calculate concordance of constipation comparing monozygotic and dizygous twin pairs.Participants: CG99 reported six randomised controlled trials (RCTs). ALSPAC hard stool data from 6796 children at 4 weeks, 9828 at 6 months and 9452 at 2.5 years plus constipation data on 8401 at 4-10 years were compared with fibre intake at 2 years. Twin studies had 338 and 93 twin pairs and ALSPAC added a further 45.Results: Increasing fibre did not effectively treat constipation. Hard stools at 4 weeks predated fibre and at 6 months predicted lower fibre intake at 2 years (p=0.003). Heredity explained 59% of constipation.Conclusions: RCTs indicate that increasing fibre is not an effective treatment for constipation in children. Hard stools can precede and predict later fibre intake. Genetic inheritance explains most childhood constipation. Extended treatment with stool softeners may improve fibre intake and limit long-term damaging sequelae of constipation. [ABSTRACT FROM AUTHOR]

Aortic stenosis (AS) is a common valve disorder in an ageing population in western countries, and women, with longer life expectancy, comprise a substantial percentage of elderly patients with AS. Compared with men, women exhibit distinctive characteristics at the level of stenotic valve leaflets and subsequent compensatory responses of the left ventricle to chronic pressure overload, and in clinical presentation, consequences and response to intervention. Randomised controlled trials of transcatheter aortic valve implantation have yielded new evidence of sex differences in both short-term and long-term outcomes after intervention. A comprehensive knowledge of the existing evidence may inform our understanding of gender differences during assessment and treatment of patients with AS. In this paper, we review the available evidence regarding sex differences in AS in terms of symptoms, clinical presentation, anatomical differences and pathophysiological progression, management and outcomes after aortic valve replacement. Implications for further research are suggested. [ABSTRACT FROM AUTHOR]

Background: Sickle cell disease (SCD) is a multisystem disease characterised by vaso-occlusive crisis, chronic anaemia and a shorter lifespan. More patients with SCD are living till reproductive age and contemplating pregnancy. Pulmonary complications in pregnancy are significant causes of maternal morbidity and mortality but yet this has not been systematically quantified. A systematic review and meta-analysis were conducted to quantify the association between SCD and pulmonary complications in pregnancy.Methods: MEDLINE, EMBASE, Web of Science, Cochrane and Maternity and Infant Care databases were searched for publications between January 1998 and April 2019. Observational studies involving at least 30 participants were included. Random-effects models were used for statistical meta-analysis.Findings: Twenty-two studies were included in the systematic review and 18 in the quantitative analysis. The meta-analysis included 3964 pregnancies with SCD and 336 559 controls. Compared with women without SCD, pregnancies complicated by SCD were at increased risk of pulmonary thromboembolism (relative risk (RR) 7.74; 95% CI 4.65 to 12.89). The estimated prevalence of acute chest syndrome and pneumonia was 6.46% (95% CI 4.66% to 8.25%), with no significant difference between the HbSS and HbSC genotypes (RR 1.42; 95% CI 0.90 to 2.23).Interpretation: This meta-analysis highlighted a strong association between SCD and maternal pulmonary complications. Understanding the risks of and the factors associated with pulmonary complications would aid preconceptual counselling and optimal management of the condition in pregnancy, thereby reducing associated maternal morbidity and mortality.Prospero Registration Number: CRD42019124708. [ABSTRACT FROM AUTHOR]

Objectives: Despite a recent fall in the incidence of HIV within the UK, men who have sex with men (MSM) continue to be disproportionately affected. As biomedical prevention technologies including pre-exposure prophylaxis are increasingly taken up to reduce transmission, the role of HIV testing has become central to the management of risk. Against a background of lower testing rates among older MSM, this study aimed to identify age-related factors influencing recent (≤12 months) HIV testing.Methods: Cross-sectional subpopulation data from an online survey of sexually active MSM in the Celtic nations-Scotland, Wales, Northern Ireland and Ireland (n=2436)-were analysed to compare demographic, behavioural and sociocultural factors influencing HIV testing between MSM aged 16-25 (n=447), 26-45 (n=1092) and ≥46 (n=897).Results: Multivariate logistic regression demonstrated that for men aged ≥46, not identifying as gay (OR 0.62, CI 0.41 to 0.95), location (Wales) (OR 0.49, CI 0.32 to 0.76) and scoring higher on the personalised Stigma Scale (OR 0.97, CI 0.94 to 1.00) significantly reduced the odds for HIV testing in the preceding year. Men aged 26-45 who did not identify as gay (OR 0.61, CI 0.41 to 0.92) were also significantly less likely to have recently tested for HIV. For men aged 16-25, not having a degree (OR 0.48, CI 0.29 to 0.79), location (Republic of Ireland) (OR 0.55, CI 0.30 to 1.00) and scoring higher on emotional competence (OR 0.57, CI 0.42 to 0.77) were also significantly associated with not having recently tested for HIV.Conclusion: Key differences in age-related factors influencing HIV testing suggest health improvement interventions should accommodate the wide diversities among MSM populations across the life course. Future research should seek to identify barriers and enablers to HIV testing among the oldest and youngest MSM, with specific focus on education and stigma. [ABSTRACT FROM AUTHOR]

Background: Understanding donor, government and out-of-pocket funding for early child development (ECD) is important for tracking progress. We aimed to estimate a baseline for the WHO, UNICEF and World Bank Nurturing Care Framework (NCF) with a special focus on childhood disability.Methods: To estimate development assistance spending, the Organisation for Economic Cooperation and Development's Creditor Reporting System (OECD-CRS) database was searched for 2007-2016, using key words derived from domains of the NCF (good health, nutrition and growth, responsive caregiving, security and safety, and early learning), plus disability. Associated funds were analysed by domain, donor, recipient and region. Trends of ECD/NCF were compared with reproductive, maternal, newborn and child health (RMNCH) disbursements. To assess domestic or out-of-pocket expenditure for ECD, we searched electronic databases of indexed and grey literature.Results: US$79.1 billion of development assistance were disbursed, mostly for health and nutrition (US$61.9 billion, 78% of total) and least for disability (US$0.7 billion, 2% of total). US$2.3 per child per year were disbursed for non-health ECD activities. Total development assistance for ECD increased by 121% between 2007 and 2016, an average increase of 8.3% annually. Per child disbursements increased more in Africa and Asia, while minimally in Latin America and the Caribbean and Oceania. We could not find comparable sources for domestic funding and out-of-pocket expenditure.Conclusions: Estimated international donor disbursements for ECD remain small compared with RMNCH. Limitations include inconsistent donor terminology in OECD data. Increased investment will be required in the poorest countries and for childhood disability to ensure that progress is equitable. [ABSTRACT FROM AUTHOR]