Burden of illness of progressive familial intrahepatic cholestasis in the US, UK, France, and Germany: study rationale and protocol of the PICTURE study.

Background: Progressive familial intrahepatic cholestasis (PFIC) is an ultra-rare disease with a considerable burden on pediatric patients and their caregivers, impacting quality of life (QoL). The mortality rates highlight a significant need for efficacious treatments. Real-world data on associated costs and QoL are needed to gauge the potential impact of new pharmacological treatments.Methods: Clinical and socio-economic burden of PFIC on patients/caregivers, health systems, and society will be assessed. Patient/caregiver- and physician-level retrospective cross-sectional data will be collected from the US, UK, France, and Germany, for PFIC types 1, 2, 3.A representative sample of physicians will provide clinical and resource utilization information using an electronic Case Report Form (eCRF). Patient/caregiver surveys will collect socio-economic and QoL data, enabling assessment of PFIC impact on QoL. Mean costs (direct medical/non-medical, indirect) will be calculated.The study materials were reviewed by medical professionals and patient representatives and received ethical approval from the University of Chester.Discussion: The study aims to reveal the unmet medical need, disease burden, resource utilization, and costs of PFIC, to raise awareness with policymakers and healthcare professionals, and provide support for the patient/caregiver community. As novel PFIC therapies recently emerged, this study will yield quantifiable data for health technology assessments.

Disease burden and costs from excess alcohol consumption, obesity, and viral hepatitis: fourth report of the Lancet Standing Commission on Liver Disease in the UK.

This report contains new and follow-up metric data relating to the eight main recommendations of the Lancet Standing Commission on Liver Disease in the UK, which aim to reduce the unacceptable harmful consequences of excess alcohol consumption, obesity, and viral hepatitis. For alcohol, we provide data on alcohol dependence, damage to families, and the documented increase in alcohol consumption since removal of the above-inflation alcohol duty escalator. Alcoholic liver disease will shortly overtake ischaemic heart disease with regard to years of working life lost. The rising prevalence of overweight and obesity, affecting more than 60% of adults in the UK, is leading to an increasing liver disease burden. Favourable responses by industry to the UK Government's soft drinks industry levy have been seen, but the government cannot continue to ignore the number of adults being affected by diabetes, hypertension, and liver disease. New direct-acting antiviral drugs for the treatment of chronic hepatitis C virus infection have reduced mortality and the number of patients requiring liver transplantation, but more screening campaigns are needed for identification of infected people in high-risk migrant communities, prisons, and addiction centres. Provision of care continues to be worst in regions with the greatest socioeconomic deprivation, and deficiencies exist in training programmes in hepatology for specialist registrars. Firm guidance is needed for primary care on the use of liver blood tests in detection of early disease and the need for specialist referral. This report also brings together all the evidence on costs to the National Health Service and wider society, in addition to the loss of tax revenue, with alcohol misuse in England and Wales costing £21 billion a year (possibly up to £52 billion) and obesity costing £27 billion a year (treasury estimates are as high as £46 billion). Voluntary restraints by the food and drinks industry have had little effect on disease burden, and concerted regulatory and fiscal action by the UK Government is essential if the scale of the medical problem, with an estimated 63 000 preventable deaths over the next 5 years, is to be addressed.

Getting it right: Culturally safe approaches to health partnership work in low to middle income countries.

Many health professionals become engaged in international health and education work in low to middle income countries, often as part of health partnerships. This type of work, increasingly popular in an age of global health, can present a number of challenges. Many of these involve cultural factors which are often acknowledged in the literature on overseas health work but rarely explored in depth. This paper aims to illustrate the key cultural considerations to be made by those currently engaged in or considering overseas health and education work in a low to middle income country. A comprehensive literature review methodology was used to examine data through the lens of Cultural Safety Theory and as a result provide guidance for professionals working with international colleagues. Recommendations for practice are based on the importance of gaining an understanding of the host country's history and social context and of professionals examining their own individual worldviews.

Renal artery and parenchymal changes after renal denervation: assessment by magnetic resonance angiography.

OBJECTIVES: Relatively little is known about the incidence of long-term renal damage after renal denervation (RDN), a potential new treatment for hypertension. In this study the incidence of renal artery and parenchymal changes, assessed with contrast-enhanced magnetic resonance angiography (MRA) after RDN, is investigated. METHODS: This study is an initiative of ENCOReD, a collaboration of hypertension expert centres. Patients in whom an MRA was performed before and after RDN were included. Scans were evaluated by two independent, blinded radiologists. Primary outcome was the change in renal artery morphology and parenchyma. RESULTS: MRAs from 96 patients were analysed. Before RDN, 41 renal anomalies were observed, of which 29 mostly mild renal artery stenoses. After a median time of 366 days post RDN, MRA showed a new stenosis (25-49% lumen reduction) in two patients and progression of pre-existing lumen reduction in a single patient. No other renal changes were observed and renal function remained stable. CONCLUSIONS: We observed new or progressed renal artery stenosis in three out of 96 patients, after a median time of 12 months post RDN (3.1%). Procedural angiographies showed that ablations were applied near the observed stenosis in only one of the three patients. KEY POINTS: • The incidence of vascular changes 12 months post RDN was 3.1%. • No renal vascular or parenchymal changes other than stenoses were observed. • Ablations were applied near the stenosis in only one of three patients.

Improving Outcomes through Transformational Health and Social Care Integration - The Scottish Experience.

The Scottish Parliament recently passed legislation on integrating healthcare and social care to improve the quality and outcomes of care and support for people with multiple and complex needs across Scotland. This ambitious legislation provides a national framework to accelerate progress in person-centred and integrated care and support for the growing number of people who have multiple physical and mental health conditions and complex needs. Additional investment and improvement capacity is helping to commission support and services that are designed and delivered with people in local communities and in partnership with housing, community, voluntary and independent sectors.

Low-density lipoprotein receptor gene familial hypercholesterolemia variant database: update and pathological assessment.

Familial hypercholesterolemia (FH) is caused predominately by variants in the low-density lipoprotein receptor gene (LDLR). We report here an update of the UCL LDLR variant database to include variants reported in the literature and in-house between 2008 and 2010, transfer of the database to LOVDv.2.0 platform (https://grenada.lumc.nl/LOVD2/UCL-Heart/home.php?select_db=LDLR) and pathogenicity analysis. The database now contains over 1288 different variants reported in FH patients: 55% exonic substitutions, 22% exonic small rearrangements (<100 bp), 11% large rearrangements (>100 bp), 2% promoter variants, 10% intronic variants and 1 variant in the 3' untranslated sequence. The distribution and type of newly reported variants closely matches that of the 2008 database, and we have used these variants (n= 223) as a representative sample to assess the utility of standard open access software (PolyPhen, SIFT, refined SIFT, Neural Network Splice Site Prediction Tool, SplicePort and NetGene2) and additional analyses (Single Amino Acid Polymorphism database, analysis of conservation and structure and Mutation Taster) for pathogenicity prediction. In combination, these techniques have enabled us to assign with confidence pathogenic predictions to 8/8 in-frame small rearrangements and 8/9 missense substitutions with previously discordant results from PolyPhen and SIFT analysis. Overall, we conclude that 79% of the reported variants are likely to be disease causing.

Daughters and mothers exercising together: effects of home- and community-based programs.

PURPOSE: This pilot study compares the effectiveness of home- and community-based physical activity interventions that target mothers and daughters to increase physical activity and improve health-related fitness. METHODS: Mothers (45.18 +/- 7.49 yr) and daughters (15.41 +/- 1.33 yr) were randomly assigned to a community-based (CB) (N = 20 participants) or home-based (HB) (N = 14 participants) program. CB participants attended three instructor-led sessions per week for 12 wk. HB participants were asked to participate in 3 sessions per week for 12 wk in a program similar to the CB program. The main difference between the programs was that CB activities were completed at a fitness facility within a university and HB activities were completed in or near the home. Before and after the intervention, changes in health-related fitness and physical activity were assessed. A series of 2 (group assignment) x 2 (time) ANOVAs were conducted to assess changes separately for mothers and daughters. RESULTS: CB participants attended 77% of the sessions, and none of the pairs dropped out. HB participants completed 70% of the recommended sessions, and three pairs dropped out. Mothers and daughters in both groups significantly increased their participation in aerobic, muscular strength, and flexibility activities (P = 0.02 to 0.000). Daughters in both groups significantly improved their muscular endurance (sit-ups,P = 0.000). Mothers in both groups improved their muscular strength (push-ups, P = 0.003), muscular endurance (sit-ups, P = 0.000), flexibility (sit-and-reach, P = 0.008), and aerobic capacity (1-mile walk, P = 0.002). Positive changes in diastolic blood pressure also occurred (P = 0.008). CONCLUSION: Mothers and daughters responded positively to CB and HB physical activity programs. Home-based physical activity programming is a cost-effective means to increase physical activity and improve health-related fitness in these groups.