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People with type 1 and type 2 diabetes are at risk of developing progressive chronic kidney disease (CKD) and end-stage kidney failure. Hypertension is a major, reversible risk factor in people with diabetes for development of albuminuria, impaired kidney function, end-stage kidney disease and cardiovascular disease. Blood pressure control has been shown to be beneficial in people with diabetes in slowing progression of kidney disease and reducing cardiovascular events. However, randomised controlled trial evidence differs in type 1 and type 2 diabetes and different stages of CKD in terms of target blood pressure. Activation of the renin-angiotensin-aldosterone system (RAAS) is an important mechanism for the development and progression of CKD and cardiovascular disease. Randomised trials demonstrate that RAAS blockade is effective in preventing/ slowing progression of CKD and reducing cardiovascular events in people with type 1 and type 2 diabetes, albeit differently according to the stage of CKD. Emerging therapy with sodium glucose cotransporter-2 (SGLT-2) inhibitors, non-steroidal selective mineralocorticoid antagonists and endothelin-A receptor antagonists have been shown in randomised trials to lower blood pressure and further reduce the risk of progression of CKD and cardiovascular disease in people with type 2 diabetes. This guideline reviews the current evidence and makes recommendations about blood pressure control and the use of RAAS-blocking agents in different stages of CKD in people with both type 1 and type 2 diabetes. [ABSTRACT FROM AUTHOR]

The clinical utility of molecular diagnostic approaches in allergy investigation is being recognized increasingly to play a significant role in the management of allergic patients. Determining the sensitization pattern, which is best achieved through the use of component resolved diagnostics (CRD), allows effective risk stratification, appropriate treatment and patient selection for immunotherapy. In order to assess the diagnostic service provisions for in-vitro allergy testing across Europe, a survey was carried out via the total immunoglobulin (Ig)E and specific IgE external quality assurance schemes run by UK National External Quality Assessment Service (NEQAS) Immunology, Immunochemistry and Allergy. This survey assessed allergy testing, and in particular allergen components offered by the laboratories, and found a wide variability in service provision, particularly between the United Kingdom and other European Union (EU) countries. Furthermore, there was lack of standardization for acquisition of clinical information to aid allergen (and component) selection, gating strategy, testing algorithms and clinical interpretation. Interestingly, a significant proportion of laboratories (the majority from EU) stated that they 'used' the results for peanut components for risk stratification. However, the vast majority of participants were unaware of guidelines relating to the use of allergen component testing, and agreed that further education would assist in reaching a common platform. Hence, this survey has highlighted that although CRD has been adopted into routine diagnostics across Europe, it is potentially compromised by lack of standardized protocols and guidance sources. Consequently, there is a need for local or national standards and education through External Quality Assurance services on the performance and application of CRD into allergy investigation. [ABSTRACT FROM AUTHOR]

Immunoglobulin (Ig)G4 disease can have apparently 'normal' levels of IgG4 due to antigen excess conditions. IgG4 measurement therefore appears falsely low. UK National External Quality Assurance Scheme (UK NEQAS) data and other reports have suggested that this problem occurred despite pre-existing antigen excess detection steps. To determine the clinical relevance of the problem, we examined the prevalence and characteristics of prozoning in our laboratory and patient cohorts. We establish that the prevalence of raised IgG4 in routine IgG4 analysis is low (< 1%) using one of the two routine methods in use in the United Kingdom. We show that subsequent assay modification appears to have reduced the likelihood of misleading readings. However, the original version of the assay prozoned to low levels (below 0·64 g/l) in 41% of high IgG4 samples in our patients. This may explain the previous reports of low sensitivity of raised IgG4 for IgG4RD, and predictive values should be re-evaluated in this disease using modified prozone-resistant protocols. All laboratories providing IgG4 measurements should verify that their assays are fit for the clinical quality requirement of detection raised IgG4 levels and must verify the upper limit of their reference ranges and freedom from prozoning. [ABSTRACT FROM AUTHOR]

Geomorphological and sedimentological evidence of former glaciation in the Bizzle valley in the Cheviot Hills of northern England and southern Scotland was used to reconstruct the dimensions of a small topographically constrained glacier with an equilibrium line altitude (ELA) of 535 m. This was interpreted as having formed during Younger Dryas cooling; this is the only glacier to have been described from the area and is the most easterly site of Younger Dryas glaciation in the British Isles. Whilst glaciation at this time was extensive in the Lake District to the southwest, the restricted nature of Cheviot ice cover suggests that a steep west-east precipitation gradient existed in this region during the Younger Dryas. [ABSTRACT FROM AUTHOR]

Abstract Objectives A routine review of hepatitis A travel vaccination recommendations was brought forward in June 2017 due to hepatitis A vaccine shortages and a concurrent outbreak in men who have sex with men (MSM). There were three objectives: first, to document the review process for changing the recommendations for the UK travellers in June 2017. Second, to study the impact of these changes on prescribing in general practice in 2017 compared with the previous 5 years. Third, to study any changes in hepatitis A notifications in June–October 2017 compared with the previous 5 years. Study design This is an observational study. Methods Travel vaccination recommendations for countries with either low-risk (<20%) or high-risk (>90%) status according to child hepatitis A seroprevalence were not changed. A total of 67 intermediate-risk countries with existing recommendations for most travellers and with new data on rural sanitation levels were shortlisted for the analysis. Data on child hepatitis A seroprevalence, country income status, access to sanitation in rural areas and traveller volumes were obtained. Information about the vaccine supply was obtained from Public Health England. Changes to the existing classification were made through expert consensus, based on countries' hepatitis A seroprevalence, sanitation levels, level of income, volume of travel and hepatitis A traveller cases. Data on the number of combined and monovalent hepatitis A–containing vaccines prescribed in England, 2012–2017, were obtained from the National Health Service Business Service Authorities. The number of monthly prescriptions for January–September 2017 was compared with the mean number of prescriptions for the same month in the previous 5 years (t -test, α = 5%, df = 4). The number of hepatitis A cases notified in June–October 2017 not related to the MSM outbreak was compared with the number of notifications in the same months in previous years. Results A total of 36 countries were downgraded based on good access (80+% of population) to sanitation in rural areas and the intermediate-risk status in terms of child hepatitis A seroprevalence. For these countries, vaccination would only be recommended to travellers staying long term, visiting friends and relatives or staying in areas without good sanitation. There was a significant decline in hepatitis A vaccine prescriptions in June–September 2017, and there was no increase in the number of notifications. Conclusions Hepatitis A vaccination recommendations for travel were revised in 2017 following a systematic approach to maintain continuity of supply after a hepatitis A vaccine shortage and increased hepatitis A vaccine demand related to a large outbreak. Improved access to good sanitation in rural areas and low seroprevalence estimates among children have led to 36 countries to no longer require vaccination for most travellers. These changes do not seem to have impacted on hepatitis A notifications in England, although further research will be needed to quantify the impact more precisely. Highlights • Hepatitis A travel vaccination recommendations were revised in response to vaccine supply issues. • A decrease in GP travel vaccination followed the change in recommendations. • The changes do not seem to have impacted hepatitis A notifications. [ABSTRACT FROM AUTHOR]

Introduction and Objectives: No definitive management guidelines exist for Spitz-type lesions; recommendations in the UK favour a 'safe' approach with a low threshold for excision. We aimed to describe Spitz-type lesions in children to further clarify the clinical features and outcomes., Methods: We conducted a retrospective cohort study in Addenbrooke's Hospital, Cambridge, UK, and reviewed all patients aged ≤18 years with histologically confirmed Spitz-type lesions from November 2014 to September 2020. Information collected included patient demographics, lesion details, follow-up, outcomes and recurrence., Results: Ninety-one children (male: female 42: 49; mean age at diagnosis: 9.4 years, SD: 4.6 years) were identified. Among them, 64 (70.3%) had classic Spitz or spitzoid naevi, 26 (28.6%) atypical Spitz tumours and 1 (1.1%) had spitzoid malignant melanoma based on histological features. On assessing the clinical features, where documented, we found that 22.0% (20/91) had amelanosis, 44.0% (40/91) had a raised bump, 12.1% (11/91) displayed bleeding, 25.0% (20/80) had non-uniform colour, 96.7% (88/91) were de novo lesions, 55.1% (43/78) were evolving in size and 35.9% (28/78) were evolving in colour. Fifty-nine patients (64.8%) were discharged without the need for follow-up, and the other 32 had a median follow-up time of 4 months. After confirmed excision, no incidences of local recurrence, distant metastases or mortality have been reported to date in all patients., Conclusions: The outcomes for paediatric Spitz-type lesions continue to be exceptionally good, remaining a low-risk lesion, which is more likely to be benign in children. Hence, we do not advocate aggressive management strategies for paediatric patients with clinically banal Spitz-type lesions., (Copyright © 2024 British Association of Plastic, Reconstructive and Aesthetic Surgeons. Published by Elsevier Ltd. All rights reserved.)

Background: Robust preanalytical and analytical processes are critical for the detection of cryoproteins. There is significant variation in practice in the detection, analysis and reporting. Results: A survey in 2018 of 137 laboratories participating in the UK National External Quality Assessment Service (UK NEQAS) (6) quality control program showed significant variation in the laboratory processes which highlighted the need for standardisation of the detection, analysis and reporting of cryoglobulins. Conclusion: The first available EQA scheme aiming to harmonise practice for cryoprotein testing has been developed by UK NEQAS and laboratories should participate in an appropriate EQA scheme to fulfil requirements for ISO accreditation., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Objective: Implementing teleophthalmology into the optometric referral pathway may ease the current pressures on hospital eye services caused by over-referrals from some optometrists. This study aimed to understand the practical implications of implementing teleophthalmology by analysing lived experiences and perceptions of teleophthalmology in the optometric referral pathway for suspected retinal conditions., Design: Qualitative in-depth interview study SETTING: Fourteen primary care optometry practices and four secondary care hospital eye services from four NHS Foundation Trusts across the UK., Participants: We interviewed 41 participants: patients (17), optometrists (18), and ophthalmologists (6) who were involved in the HERMES study. Through thematic analysis, we collated and present their experiences of implementing teleophthalmology., Results: All participants interviewed were positive towards teleophthalmology as it could enable efficiencies in the referral pathway and improve feedback and communication between patients and healthcare professionals. Concerns included setup costs for optometrists and anxieties from patients about not seeing an ophthalmologist face to face. However, reducing unnecessary visits and increasing the availability of resources and capacity were seen as significant benefits., Conclusions: Overall, we report positive experiences of implementing teleophthalmology into the optometric referral pathway for suspected retinal conditions. Successful implementation will require appropriate investment to set up and integrate new technology and remunerate services, and continued evaluation to ensure timely feedback to patients and between healthcare professionals is received., Trial Registration Number: ISRCTN18106677., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY. Published by BMJ.)

Treatment advances have greatly improved survival, but myeloma is among the worst of all cancers for delayed diagnosis, causing serious morbidities and early deaths. This delay is largely because the symptom profile of myeloma has very low specificity, and in primary care, myeloma is rare. However, initiating the journey to diagnosis simply requires considering myeloma and sending blood to test for monoclonal immunoglobulin. Laboratory tests reliably detect monoclonal immunoglobulin, which is present in 99% of myeloma cases, so why do health care systems have such a problem with delayed diagnosis? The Myeloma UK early diagnosis programme has brought together diverse expertise to investigate this problem, and this article was prepared by the programme's working group for laboratory best practice. It reviews evidence for test requesting, analysis and reporting, for which there is large variation in practice across the United Kingdom. It presents a 'GP Myeloma diagnostic tool' and how it can be integrated into laboratory practice alongside a laboratory best practice tool. It proposes improved requesting and integration with haematology services for reporting and interpretation. Here the laboratory has a central role in creating efficient and cost-effective pathways for appropriate and timely bone marrow examination for myeloma diagnosis., (© 2024 The Authors. British Journal of Haematology published by British Society for Haematology and John Wiley & Sons Ltd.)

Background: Clinical trials should be as inclusive as possible to facilitate equitable access to research and better reflect the population towards which any intervention is aimed. Informed by the UK's National Institute for Health and Care Research (NIHR) Innovations in Clinical Trial Design and Delivery for the Under-served (INCLUDE) guidance, we audited oncology trials conducted by the Clinical Trials and Statistics Unit at The Institute of Cancer Research, London (ICR-CTSU) to identify whether essential documents were overtly excluding any groups and whether sufficient data were collected to assess diversity of trial participants from groups suggested by INCLUDE as under-served by research in the UK., Methods: Thirty cancer clinical trials managed by ICR-CTSU and approved between 2011-2021 were audited. The first ethics approved version of each trial's protocol, patient information sheet, and patient completed questionnaire, together with the first case report forms (CRFs) version were reviewed. A range of items aligned with the INCLUDE under-served groups were assessed, including age, sex and gender, socio-economic and health factors. The scope did not cover trial processes in participating hospitals., Results: Data relating to participants' age, ethnic group and health status were well collected and no upper age limit was specified in any trials' eligibility criteria. 23/30 (77%) information sheets used at least one gendered term to address patients. Most CRFs did not specify whether they were collecting sex or gender and only included male or female categories. The median reading age for information sheets was 15-16 years (IQR: 14-15 - 16-17). Socio-economic factors were not routinely collected and not commonly mentioned in trial protocols., Conclusions: No systemic issues were identified in protocols which would explicitly prevent any under-served group from participating. Areas for improvement include reducing use of gendered words and improving readability of patient information. The challenge of fully assessing adequate inclusion of under-served populations remains, as socio-economic factors are not routinely collected because they fall beyond the data generally required for protocol-specified trial endpoint assessments. This audit has highlighted the need to agree and standardise demographic data collection to permit adequate monitoring of the under-served groups identified by the NIHR., (© 2023. The Author(s).)

Aims: To investigate characteristics of people hospitalized with coronavirus-disease-2019 (COVID-19) and diabetic ketoacidosis (DKA) or hyperosmolar hyperglycaemic state (HHS), and to identify risk factors for mortality and intensive care admission., Materials and Methods: Retrospective cohort study with anonymized data from the Association of British Clinical Diabetologists nationwide audit of hospital admissions with COVID-19 and diabetes, from start of pandemic to November 2021. The primary outcome was inpatient mortality. DKA and HHS were adjudicated against national criteria. Age-adjusted odds ratios were calculated using logistic regression., Results: In total, 85 confirmed DKA cases, and 20 HHS, occurred among 4073 people (211 type 1 diabetes, 3748 type 2 diabetes, 114 unknown type) hospitalized with COVID-19. Mean (SD) age was 60 (18.2) years in DKA and 74 (11.8) years in HHS (p < .001). A higher proportion of patients with HHS than with DKA were of non-White ethnicity (71.4% vs 39.0% p = .038). Mortality in DKA was 36.8% (n = 57) and 3.8% (n = 26) in type 2 and type 1 diabetes respectively. Among people with type 2 diabetes and DKA, mortality was lower in insulin users compared with non-users [21.4% vs. 52.2%; age-adjusted odds ratio 0.13 (95% CI 0.03-0.60)]. Crude mortality was lower in DKA than HHS (25.9% vs. 65.0%, p = .001) and in statin users versus non-users (36.4% vs. 100%; p = .035) but these were not statistically significant after age adjustment., Conclusions: Hospitalization with COVID-19 and adjudicated DKA is four times more common than HHS but both associate with substantial mortality. There is a strong association of previous insulin therapy with survival in type 2 diabetes-associated DKA., (© 2023 The Authors. Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd.)

Background: Yellow fever (YF) vaccination is the single most important preventative measure against YF infection, however the live attenuated vaccine has associated serious adverse events. All YF vaccinations in England, Wales and Northern Ireland (EWNI) are administered in YF Vaccination Centres and comply with National Travel Health Network and Centre (NaTHNaC) Conditions of Designation and Code of Practice, including reporting of vaccine incidents to NaTHNaC. In this study we evaluated the number and type of YF vaccine incidents in EWNI to identify areas for improvement., Methods: NaTHNaC's telephone advice line database was retrospectively searched from 1st January 2016 to 31st December 2018 for YF vaccine incidents. Calls were categorised and analysed according to incident type., Results: Seventy-eight YF vaccine incidents were reported from a total of 17250 calls. The commonest incident was incorrect timing of measles, mumps and rubella vaccine in relation to YF vaccine, where the recommended 28-day interval was not observed (n = 21). Other incidents included accidental partial vaccination (n = 11), inappropriate vaccination (n = 5) and invalid vaccination due to expiry or cold chain breach (n = 4). Inadvertent vaccination in contraindicated individuals occurred in two travellers with thymectomies (resulting in one death), and five immunocompromised travellers., Conclusions: YF vaccine incidents represent a small proportion of total calls. Similar incidents likely occur with other vaccines, but YF vaccine incidents are of particular concern; whilst most incidents were not harmful, vaccination in contraindicated individuals resulted in one death. These findings helped to inform new guidance and update training for staff in YF vaccination centres., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Background: The true frequency of hospital outbreaks of invasive group B streptococcal (iGBS; Streptococcus agalactiae) disease in infants is unknown. We used whole genome sequencing (WGS) of iGBS isolates collected during a period of enhanced surveillance of infant iGBS disease in the UK and Ireland to determine the number of clustered cases., Methods: Potentially linked iGBS cases from infants with early (<7 days of life) or late-onset (7-89 days) disease were identified from WGS data (HiSeq 2500 platform, Illumina) from clinical sterile site isolates collected between 04/2014 and 04/2015. We assessed time and place of cases to determine a single-nucleotide polymorphism (SNP) difference threshold for clustered cases. Case details were augmented through linkage to national hospital admission data and hospital record review by local microbiologists., Results: Analysis of sequences indicated a cutoff of ≤5 SNP differences to define iGBS clusters. Among 410 infant iGBS isolates, we identified 7 clusters (4 genetically identical pairs with 0 SNP differences, 1 pair with 3 SNP differences, 1 cluster of 4 cases with ≤1 SNP differences) of which 4 clusters were uncovered for the first time. The clusters comprised 16 cases, of which 15 were late-onset (of 192 late-onset cases with sequenced isolates) and 1 an early-onset index case. Serial intervals between cases ranged from 0 to 59 (median 12) days., Conclusions: Approximately 1 in 12 late-onset infant iGBS cases were part of a hospital cluster. Over half of the clusters were previously undetected, emphasizing the importance of routine submission of iGBS isolates to reference laboratories for cluster identification and genomic confirmation., (© Crown copyright 2020.)

The National Travel Health Network and Centre (NaTHNaC) offers a telephone advice line for travel health practitioners in the UK. In this study we review clinical incidents concerning vaccines or malaria prophylaxis reported between 2016 and 2018. Two-hundred-and-fifty-one clinical incident calls were recorded, and commonly concerned scheduling or dosing errors. Vaccine scheduling errors accounted for 103 calls (41%), predominantly due to hepatitis A or hepatitis B vaccination either alone or in combination (65/103, 63%). Administration of yellow fever vaccine within 28 days of measles, mumps and rubella accounted for a further 15 (15%) calls. Twenty-six (10%) calls reported administration of a vaccine that was not recommended either for the destination or contraindicated in the traveller. Yellow fever was the commonest single vaccine discussed in 28.4% of vaccine clinical incidents reported. By highlighting common mistakes, we hope to raise awareness of common issues and improve practice in travel health., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Background: Malaria prevention in travellers can be complex and requires consideration of a number of factors. UK healthcare professionals providing pre-travel malaria advice can access specialist support from the National Travel Health Network and Centre (NaTHNaC) telephone advice line. The aim of this study is to characterise queries to the NaTHNaC telephone advice line regarding pre-travel malaria advice., Method: Telephone calls received to NaTHNaC's advice line are recorded using an online data capture form. All calls relating to malaria advice during 2016 were selected and data extracted. Analysis was undertaken using Microsoft Excel and STATA., Results: During 2016, 1803 malaria-related calls were received; the majority from general practice and calls were from across the UK. The most common type of pre-travel malaria query was country-specific followed by travellers with special health needs. Many queries related to pregnant and breastfeeding travellers, children under 5 years and travellers over 60 years., Conclusions: This review presents a large and exceptional dataset and reflects the ambiguity amongst some healthcare professionals regarding malaria advice. We have identified potential knowledge gaps, and as a result will strengthen future guidance, enhance existing malaria maps, and inform the development of future clinical educational activity., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Background: Group B streptococcus is a leading cause of serious infection in young infants in many countries worldwide. We aimed to define the burden and clinical features of invasive group B streptococcal disease in infants younger than 90 days in the UK and Ireland, together with the characteristics of disease-causing isolates., Methods: Prospective, active national surveillance of invasive group B streptococcal disease in infants younger than 90 days was done from April 1, 2014, to April 30, 2015, through the British Paediatric Surveillance Unit, microbiology reference laboratories, and national public health agencies in the UK and Ireland. Early onset was defined as disease in the first 6 days of life and late onset was defined as 7-89 days of life. Incidence was calculated using livebirths in 2014 (after adjustment for the 13-month surveillance period). Isolates were characterised by serotyping, multilocus sequence typing, and antimicrobial susceptibility testing., Findings: 856 cases of group B streptococcus were identified in 2014-15, an incidence of 0·94 per 1000 livebirths (95% CI 0·88-1·00). Incidence for early-onset disease (n=517) was 0·57 per 1000 livebirths (95% CI 0·52-0·62), and for late-onset disease (n=339) was 0·37 per 1000 livebirths (0·33-0·41). 53 infants died (case fatality rate 6·2%), of whom 27 had early-onset disease (case fatality rate 5·2%) and 26 had late-onset disease (case fatality rate 7·7%). The predominant serotypes were III (241 [60%] of 402 serotyped isolates) and Ia (69 [17%]); five serotypes (Ia, Ib, II, III, V) accounted for 377 (94%) of all serotyped isolates., Interpretation: The incidence of invasive infant group B streptococcal disease in the UK and Ireland has increased since a comparable study done in 2000-01. The burden of early-onset disease has not declined despite the introduction of national prevention guidelines. New strategies for prevention are required., Funding: Meningitis Now., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Background: A number of barriers prevent community pharmacists (CPs) from impacting public health (PH) outcomes. Social media (SM) and mobile health apps (MH apps) may offer ways to help the public make positive health decisions., Objectives: To evaluate CP perceptions of their role in PH and the use of SM and MH apps in this regard., Methods: This was a mixed method study using a cross-sectional survey and follow-up interviews. The survey covered: CPs role in PH; CP use of SM; CP use of MH apps; non-identifiable demographic information. Following ethical approval and piloting, responses were collected on paper and online. The study population was CPs in Greater London, UK (n = 2931). A minimum sample size of 340 was calculated (95% confidence interval/5% margin of error). To achieve this, 596 surveys were distributed. Responses (n = 257) were analysed using descriptive statistics. Twenty-five respondents were willing to take part in follow-up one-to-one interviews. Twenty interviews were completed as data saturation was achieved after the 14th. Interviews were transcribed and analysed using framework methodology as described by Ritchie and Spencer in 1994., Results: Survey response rate was 43%. Respondents represented English CPs in terms of age but males and non-whites were over-represented. The majority of CPs accessed SM and MH apps for personal use but did not recommend these in a professional capacity due to lack of awareness and confidentiality/liability concerns. Most would promote an SM health page (78.6%) or MH app (83.7%) if maintained by healthcare professionals (HCPs). Under 35s were more positive about these tools in PH. Two interview themes emerged: The role of CPs in PH; Concerns and opportunities for the use of technology in PH., Conclusions: Most CPs, particularly those under 30, were positive about the use of SM and MH apps in PH. Training on the use of such tools among the pharmacy team, and an awareness of the availability of evidence-based apps will ensure their wider adoption., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Background: The National Bariatric Surgery Registry (NBSR) is the largest bespoke database in the field in the United Kingdom., Objectives: Our aim was to analyze the NBSR to determine whether the effects of obesity surgery on associated co-morbidities observed in small randomized controlled clinical trials could be replicated in a "real life" setting within U.K. healthcare., Setting: United Kingdom., Methods: All NBSR entries for operations between 2000 and 2015 with associated demographic and co-morbidity data were analyzed retrospectively., Results: A total of 50,782 entries were analyzed. The patients were predominantly female (78%) and white European with a mean age of 45 ± 11 years and a mean body mass index of 48 ± 8 kg/m 2 . Over 5 years of follow-up, statistically significant reductions in the prevalence of type 2 diabetes, hypertension, dyslipidemia, sleep apnea, asthma, functional impairment, arthritis, and gastroesophageal reflux disease were observed. The "remission" of these co-morbidities was evident 1 year postoperatively and reached a plateau 2 to 5 years after surgery. Obesity surgery was particularly effective on functional impairment and diabetes, almost doubling the proportion of patients able to climb 3 flights of stairs and halving the proportion of patients with diabetes related hyperglycemia compared with preoperatively. Surgery was safe with a morbidity of 3.1% and in-hospital mortality of .07% and a reduced median inpatient stay of 2 days, despite an increasingly sick patient population., Conclusions: Obesity surgery in the U.K. results not only in weight loss, but also in substantial improvements in obesity-related co-morbidities. Appropriate support and funding will help improve the quality of the NBSR data set even further, thus enabling its use to inform healthcare policy., (Copyright © 2018 American Society for Bariatric Surgery. Published by Elsevier Inc. All rights reserved.)

Objective: To investigate the feasibility of a full-scale randomised controlled trial of a picture booklet to improve quality of life for people with epilepsy and learning disabilities., Trial Design: A randomised controlled feasibility trial. Randomisation was not blinded and was conducted using a centralised secure database and a blocked 1:1 allocation ratio., Setting: Epilepsy clinics in 1 English National Health Service (NHS) Trust., Participants: Patients with learning disabilities and epilepsy who had: a seizure within the past 12 months, meaningful communication and a carer with sufficient proficiency in English., Intervention: Participants in the intervention group used a picture booklet with a trained researcher, and a carer present. These participants kept the booklet, and were asked to use it at least twice more over 20 weeks. The control group received treatment as usual, and were provided with a booklet at the end of the study., Outcome Measures: 7 feasibility criteria were used relating to recruitment, data collection, attrition, potential effect on epilepsy-related quality of life (Epilepsy and Learning Disabilities Quality of Life Scale, ELDQOL) at 4-week, 12-week and 20-week follow-ups, feasibility of methodology, acceptability of the intervention and potential to calculate cost-effectiveness., Outcome: The recruitment rate of eligible patients was 34% and the target of 40 participants was reached. There was minimal missing data and attrition. An intention-to-treat analysis was performed; data from the outcome measures suggest a benefit from the intervention on the ELDQOL behaviour and mood subscales at 4 and 20 weeks follow-up. The booklet and study methods were positively received, and no adverse events were reported. There was a positive indication of the potential for a cost-effectiveness analysis., Conclusions: All feasibility criteria were fully or partially met, therefore confirming feasibility of a definitive trial., Trial Registration Number: ISRCTN80067039., Competing Interests: Conflicts of Interest: None declared., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.)

Objective: Analysis of long-term (30 years) clinical history and response to treatment of 13 patients with the D374Y mutation of PCSK9 (PCSK9 patients) from 4 unrelated white British families compared with 36 white British patients with heterozygous familial hypercholesterolemia attributable to 3 specific mutations in the low-density lipoprotein (LDL) receptor gene (LDLR) known to cause severe phenotype., Methods and Results: The PCSK9 patients, when compared with the LDLR patients, were younger at presentation (20.8+/-14.7 versus 30.2+/-15.7 years; P=0.003), had higher pretreatment serum cholesterol levels (13.6+/-2.9 versus 9.6+/-1.6 mmol/L; P=0.004) that remained higher during treatment with simvastatin (10.1+/-3.0 versus 6.5+/-0.9 mmol/L; P=0.006), atorvastatin (9.6+/-2.9 versus 6.4+/-1.0 mmol/L; P=0.006), or current lipid-lowering therapy, including LDL apheresis and partial ileal bypass in 2 PCSK9 patients (7.0+/-1.6 versus 5.4+/-1.0 mmol/L; P=0.001), and were affected >10 years earlier by premature coronary artery disease (35.2+/-4.8 versus 46.8+/-8.9 years; P=0.002). LDL from PCSK9 patients competed significantly less well for binding to fibroblast LDL receptors than LDL from either controls or LDLR patients., Conclusions: These British PCSK9 patients with the D374Y mutation have an unpredictably severe clinical phenotype, which may be a unique feature for this cohort, and requires early and aggressive lipid-lowering management to prevent cardiovascular complications.