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Aims Sudden cardiac death (SCD) is the most common mode of death in paediatric hypertrophic cardiomyopathy (HCM). This study describes the implant and programming strategies with clinical outcomes following implantable cardioverter-defibrillator (ICD) insertion in a well-characterized national paediatric HCM cohort. Methods and results Data from 90 patients undergoing ICD insertion at a median age 13 (±3.5) for primary (n = 67, 74%) or secondary prevention (n = 23, 26%) were collected from a retrospective, longitudinal multi-centre cohort of children ( Conclusion In a large national cohort of paediatric HCM patients with an ICD, device and programming strategies varied widely. No particular strategy was associated with inappropriate therapies, missed/delayed therapies, or lead complications.

Background and Aims At least 80% of children with steroid sensitive nephrotic syndrome (SSNS) have relapses and many are triggered by upper respiratory tract infections (URTIs). Previous small studies (4 studies, 232 patients in total), mostly in children already taking maintenance corticosteroid in countries where URTI epidemiology is different to Europe, showed that giving daily low-dose prednisolone for 5-7 days during an URTI reduces the risk of relapse. The objective of the PREDNOS 2 trial was to determine if these findings were replicated in a large UK population of children with relapsing SSNS on different background medication or none. Method A randomised, double-blind, placebo-controlled trial, including a model-based economic evaluation was carried out in 122 UK paediatric departments. Between February 2013 and January 2019, 365 children with relapsing SSNS (mean age: 7.6 ± 3.5 y) were recruited from 91 sites and randomised (1:1) according to a minimisation algorithm based on background treatment (no background treatment; low-dose prednisolone only; low-dose prednisolone and other immunosuppression; other immunosuppression only). At the start of an URTI, children received 6 days of prednisolone 15 mg/m2 or matching preparation of placebo. Those already taking alternate day prednisolone rounded their daily dose using trial medication to the equivalent of 15 mg/m2 or their alternate-day dose, whichever was the greater. The primary outcome was the incidence of first URTI-related relapse (URR) following any URTI over 12 months. Secondary outcomes were the overall rate of relapse, changes in background treatment, cumulative dose of prednisolone, rates of serious adverse events, incidence of corticosteroid adverse effects, change in Achenbach Child Behaviour Checklist score and quality of life. Analysis was by intention to treat. The economic evaluation used trial data and a decision-analytic model to estimate Quality-Adjusted-Life-Years (QALYs) and costs at 1-year, which were then extrapolated over 16 years. Results 80 children completed 12 m follow-up without an URTI. Consent was withdrawn for 32 children, 14 prior to an URTI, leaving a modified intention to treat analysis population of 271 children (134 and 137 in prednisolone and placebo arms respectively). There were 384 URTIs and 82 URRs in the prednisolone arm, and 407 URTIs and 82 URRs in the placebo arm. The number of patients experiencing a URR was 56 (42.7%) and 58 (44.3%) in the prednisolone and placebo arms respectively (adjusted risk difference: -0.024, 95% CI: -0.14 to 0.095; P=0.7). There was no evidence that the treatment effect differed when data were analysed according to background treatment. There were no significant differences in secondary outcomes between treatment arms. A post-hoc subgroup analysis assessing primary outcome in 58 children of South Asian ethnicity (RR 0.66, 95% CI: 0.396 to 1.105) versus 213 of other ethnicity (RR 1.11, 95% CI: 0.806 to 1.535) showed possible efficacy of intervention in those of South Asian ethnicity (test for interaction P=0.09). Giving daily prednisolone at the time of an URTI was found to increase QALYs and decrease overall costs, when compared to standard care, a finding that was robust to sensitivity analysis. Conclusion In a large and methodologically-robust study, PREDNOS 2 has shown that giving 6 days of daily low-dose prednisolone at the time of an URTI does not reduce the risk of relapse of nephrotic syndrome in UK children, but could offer a cost-effective use of health care resources. Further work is needed to investigate inter-ethnic differences in treatment response, and the pathogenesis of individual viral infections and their effect on nephrotic syndrome.

Background This study focused on evaluating the fumigation scheme and identifying problems encountered during the operation in the Bangkok Metropolitan Administration area. Methods Ten district health officers working in different fumigation teams of the dengue outbreak control programme around Bangkok had participated in an in-depth interview. Five predetermined themes, including (i) dengue surveillance and control strategy, (ii) quality and availability of equipment, (iii) delays, (iv) human resources, and (v) area coverage, and other emerging themes were addressed during the interviews. Results Although the staff seemed to know the operation protocol of the dengue surveillance and control programmes well, they encountered some difficulties in accessing households for proper spraying, and a lack of human and material resources, especially during an outbreak. Other emerging themes concerned inefficient communications among the sectors from hospital to district offices, leading to inaccurate or missing patient addresses for spraying, and the lack of community networks and public cooperation for the dengue control programmes. Conclusions The findings suggest that coordination among the relevant health sectors to acquire accurate and timely information about dengue cases is essential. Involving community networks should help to improve public engagement with and participation in the surveillance and outbreak control programmes.

Objective Ventricular hypertrophy (VH) has been observed in children with congenital hyperinsulinism (CHI), a condition of hypoglycaemia characterised by dysregulated insulin secretion, but the prevalence is not known. Patients and methods Cardiac assessment was performed in children (n=49) with CHI at diagnosis and follow-up. Two dimensional and Doppler echocardiography studies were used to assess cardiac structures, while M-mode study was used to measure left ventricular (LV) dimensions, subsequently converted to Z scores. Where possible, LV hypertrophy was confirmed by LV mass index (g/m2.7) >95th centile. Results Cardiac structural lesions were found in 14 (28%) children. At initial echocardiography, VH was present in 31 (65%) children with median (range) LV posterior wall dimension in diastole Z scores of +1.6 (−2.4 to +5.8) and interventricular septal wall dimension in end diastole Z scores of +1.9 (−1.7 to +17.2). At follow-up echocardiography, performed after an interval of 178 (45–390) days, VH persisted in 16 (33%) children. In regression analysis, the presence of VH (odds ratio (95% confidence intervals) 1.1 (1.0–1.2), P=0.04) at initial echocardiography was correlated with maximum glucose requirement at diagnosis, indicating that severity of CHI at presentation may play a role in the pathogenesis of VH. Conclusions A significant proportion of children with CHI have cardiac structural lesions. A majority also have VH, which may be associated with the severity of CHI at diagnosis. VH may persist in some children, which requires careful long-term cardiac review.

Imported malaria has been described as “an infection that was acquired in an endemic area by an individual (either a tourist or indigenous native) but diagnosed in a non‐endemic country after development of the clinical disease.” 1 In the UK, there was an average of 1,965 laboratory‐confirmed reports of imported malaria infections between 1987 and 2006, 2 and this country, together with France, Germany, and Italy, accounts for about three‐quarters of the 10,000 to 12,000 annual cases imported into the World Health Organization European region. 3 The majority of imported malaria infections reported in European countries are caused by Plasmodium falciparum , 3 the Plasmodium species associated with the most severe disease and mortality. Data from TropNetEurop, 4,5 a European sentinel surveillance system, describe how most cases originate from West Africa and affect travelers of African ethnicity. The most commonly reported reason for travel is to visit friends and relatives (VFRs), with 64.5% of all travelers citing this as a reason for travel in malaria reports between 1987 and 2006 to the UK's Malaria Reference Laboratory and 76.4% in reports to TropNetEurop in 2007. 5 Those VFRs who were born and lived for some time in malaria‐endemic countries before moving to Europe will have acquired partial immunity from exposure to malaria during childhood. Without repeated exposure, immunity appears to wane with time, although the time period during which this occurs is unknown. Bouchaud and colleagues 6 have demonstrated that levels of parasitemia and severe disease were lower in African migrants who were resident outside malarious areas for more than 4 years but acquired falciparum malaria on a short visit to a malaria‐endemic area, when compared to patients who had always lived outside these areas. However, a recent study of African migrants in Italy 7suggests that living for more than … Corresponding Author: Penny Neave, MSc, Malaria Reference Laboratory, London School of Hygiene and Tropical Medicine, Keppel Street, London WC1E 7HT, UK. E‐mail: penny.neave{at}lshtm.ac.uk

Caption rate and text reduction are factors that appear to affect the comprehension of captions by people who are deaf or hard of hearing. These 2 factors are confounded in everyday captioning; rate (in words per minute) is slowed by text reduction. In this study, caption rate and text reduction were manipulated independently in 2 experiments to assess any differential effects and possible benefits for comprehension by deaf and hard-of-hearing adults. Volunteers for the study included adults with a range of reading levels, self-reported hearing status, and different communication and language preferences. Results indicate that caption rate (at 130, 180, 230 words per minute) and text reduction (at 84%, 92%, and 100% original text) have different effects for different adult users, depending on hearing status, age, and reading level. In particular, reading level emerges as a dominant factor: more proficient readers show better comprehension than poor readers and are better able to benefit from caption rate and, to some extent, text reduction modifications.

Eve M. D. Smith, Rachel Corkhill, Angela Midgley, Louise Watson, Caroline Jones, Stephen D. Marks, Kjell Tullus, Clarissa Pilkington and Michael W. Beresford Institute of Translational Medicine, University of Liverpool, Liverpool, Department of Nephrolology, Alder Hey Children’s Hospital, Liverpool, Nephrology Unit, Great Ormond Street Hospital, London, Paediatric Rheumatology Department, Great Ormond Street Hospital for Children Hospital, London and Department of Rheumatology, Alder Hey Children’s Hospital, Liverpool, UK Correspondence to: Eve M. D. Smith. E-mail: esmith8@liverpool.ac.uk

Embryonic stem cells hold considerable promise in tissue engineering and regenerative medicine as a source of tissue-specific cells. However, realizing this promise requires novel methods for guiding lineage-specific differentiation of stem cells. In this study, we developed a micropatterned co-culture platform for stimulating hepatic differentiation of mouse embryonic stem cells (mESCs). Studies of mESC and hepatic cell adhesion preferences revealed that mESCs required fibronectin for attachment, while hepatic cells (HepG2) preferred collagen (I) substrate and did not adhere to fibronectin. Printing columns of collagen (I) and fibronectin spots (300 microm diameter), followed by sequential seeding of the two cell types, allowed the positioning of clusters of mESCs adjacent to groups of hepatic cells within the same microarray. These micropatterned co-cultures were maintained for up to two weeks in hepatic differentiation media supplemented. To examine the differentiation, mESCs were selectively extracted from the co-culture using laser microdissection and analyzed using real-time reverse transcriptase (RT)-polymerase chain reaction (PCR). These analyses revealed that mESCs co-cultured with HepG2 cells showed a decrease in pluripotency gene expression concomitant with up-regulation of endodermal genes. In addition, the co-culture format induced a significant increase in the expression of liver genes compared to mESCs cultured alone. In conclusion, micropatterned co-cultures of mESCs and hepatic cells showed a significant promise in driving stem cell differentiation towards hepatic phenotype. In the future, this cell culture platform will be further enhanced to enable efficient conversion of mouse and human ESCs to hepatocytes.