Patient understanding and experience of non-invasive imaging diagnostic techniques and the liver patient pathway.

BACKGROUND: Clinical and patient-reported outcomes are positively affected when efforts to increase patient understanding of underlying diseases and foster patient participation are part of care pathways. The prevalence of liver diseases is increasing globally, and successful communication of results from liver diagnostic tests will be important for physicians to ensure patient engagement and encourage adherence to lifestyle changes and therapy. Here, we aimed to explore the impact of non-invasive liver tests on patient experience and patient comprehension of liver disease in chronic liver disease diagnostic pathways typically managed with liver biopsies. RESULTS: 101 participants diagnosed with a range of liver disease aetiologies (90 patients, 11 caregivers) underwent a multiparametric magnetic resonance imaging (MRI) test. A subset of 33 participants was subjected to transient elastography (TE) with FibroScan® in addition to multiparametric MRI. MRI results were analysed using LiverMultiScan™. Participants received results on their liver-health status followed by a semi-structured interview to assess the scan procedure experience, comprehension of the results, and experiences of liver disease. A subset of participants (N = 5) was also engaged in the design, execution, and thematic analysis of the interview transcripts of the study. Analysis of semi-structured interviews revealed: (1) Presentation and discussion of the LiverMultiScan visual report by a physician was an effective contributor to better patient experience and increased comprehension of liver disease. (2) Patients demonstrated preference for non-invasive tests over biopsy for management of liver disease. (3) Patients reported positive experiences with the MRI test during the path for liver disease management. CONCLUSIONS: Patients presented with visual reports of liver test results developed increased understanding of liver disease care which may have contributed to an overall more positive experience. Patients reported that clinical information obtained through non-invasive methods and transmitted through visual reports contributed to clarity, understanding and overall increased satisfaction. We conclude that a shift toward non-invasive testing and visual reporting of clinical information (e.g. picture of liver with visual scale) when possible are likely to contribute to improved physician engagement with patients and lead to better outcomes in the management of chronic liver diseases. Evidence suggests that patient experience and understanding can affect several aspects of clinical care and patient well-being. In this study, 101 patients and patient caregivers affected by liver diseases were recruited to determine how patient experiences of liver disease were affected with the introduction of non-invasive evaluation of the liver with an MRI or ultrasound-based elastography. All 101 participants received an MRI followed by a LiverMultiScan report. 33 participants received an additional FibroScan and report. Following the reports, participants were interviewed and asked to reflect on factors which affected their experience of the procedure and the understanding of their results. We focused on factors related to the layout of the standardised report and the delivery of its results. The interviews were transcribed and analysed for common themes and patterns. Patients and patient advocacy groups were involved in the design and conduct of the study, and analysis of the interview transcripts. Here, we report the perception of patients and patient caregivers on the quality of care and diagnostic experience. Trial registration ClinicalTrials.gov identifier-NCT02877602.

Cost-effectiveness and social outcomes of a community-based treatment for podoconiosis lymphoedema in the East Gojjam zone, Ethiopia.

BACKGROUND: Podoconiosis is a disease of the lymphatic vessels of the lower extremities that is caused by chronic exposure to irritant soils. It results in leg swelling, commonly complicated by acute dermatolymphangioadenitis (ADLA), characterised by severe pain, fever and disability. METHODS: We conducted cost-effectiveness and social outcome analyses of a pragmatic, randomised controlled trial of a hygiene and foot-care intervention for people with podoconiosis in the East Gojjam zone of northern Ethiopia. Participants were allocated to the immediate intervention group or the delayed intervention group (control). The 12-month intervention included training in foot hygiene, skin care, bandaging, exercises, and use of socks and shoes, and was supported by lay community assistants. The cost-effectiveness analysis was conducted using the cost of productivity loss due to acute dermatolymphangioadenitis. Household costs were not included. Health outcomes in the cost-effectiveness analysis were: the incidence of ADLA episodes, health-related quality of life captured using the Dermatology Life Quality Index (DLQI), and disability scores measured using the WHO Disability Assessment Schedule 2.0 (WHODAS 2.0). RESULTS: The cost of the foot hygiene and lymphoedema management supplies was 529 ETB (69 I$, international dollars) per person per year. The cost of delivery of the intervention as part of the trial, including transportation, storage, training of lay community assistants and administering the intervention was 1,890 ETB (246 I$) per person. The intervention was effective in reducing the incidence of acute dermatolymphangioadenitis episodes and improving DLQI scores, while there were no significant improvements in the disability scores measured using WHODAS 2.0. In 75% of estimations, the intervention was less costly than the control. This was due to improved work productivity. Subgroup analyses based on income group showed that the intervention was cost-effective (both less costly and more effective) in reducing the number of acute dermatolymphangioadenitis episodes and improving health-related quality of life in families with monthly income <1,000 ETB (130 I$). For the subgroup with family income ≥1,000 ETB, the intervention was more effective but more costly than the control. CONCLUSIONS: Whilst there is evident benefit of the intervention for all, the economic impact would be greatest for the poorest.

Repeatability and reproducibility of multiparametric magnetic resonance imaging of the liver.

As the burden of liver disease reaches epidemic levels, there is a high unmet medical need to develop robust, accurate and reproducible non-invasive methods to quantify liver tissue characteristics for use in clinical development and ultimately in clinical practice. This prospective cross-sectional study systematically examines the repeatability and reproducibility of iron-corrected T1 (cT1), T2*, and hepatic proton density fat fraction (PDFF) quantification with multiparametric MRI across different field strengths, scanner manufacturers and models. 61 adult participants with mixed liver disease aetiology and those without any history of liver disease underwent multiparametric MRI on combinations of 5 scanner models from two manufacturers (Siemens and Philips) at different field strengths (1.5T and 3T). We report high repeatability and reproducibility across different field strengths, manufacturers, and scanner models in standardized cT1 (repeatability CoV: 1.7%, bias -7.5ms, 95% LoA of -53.6 ms to 38.5 ms; reproducibility CoV 3.3%, bias 6.5 ms, 95% LoA of -76.3 to 89.2 ms) and T2* (repeatability CoV: 5.5%, bias -0.18 ms, 95% LoA -5.41 to 5.05 ms; reproducibility CoV 6.6%, bias -1.7 ms, 95% LoA -6.61 to 3.15 ms) in human measurements. PDFF repeatability (0.8%) and reproducibility (0.75%) coefficients showed high precision of this metric. Similar precision was observed in phantom measurements. Inspection of the ICC model indicated that most of the variance in cT1 could be accounted for by study participants (ICC = 0.91), with minimal contribution from technical differences. We demonstrate that multiparametric MRI is a non-invasive, repeatable and reproducible method for quantifying liver tissue characteristics across manufacturers (Philips and Siemens) and field strengths (1.5T and 3T).

Measurement of liver iron by magnetic resonance imaging in the UK Biobank population.

The burden of liver disease continues to increase in the UK, with liver cirrhosis reported to be the third most common cause of premature death. Iron overload, a condition that impacts liver health, was traditionally associated with genetic disorders such as hereditary haemochromatosis, however, it is now increasingly associated with obesity, type-2 diabetes and non-alcoholic fatty liver disease. The aim of this study was to assess the prevalence of elevated levels of liver iron within the UK Biobank imaging study in a cohort of 9108 individuals. Magnetic resonance imaging (MRI) was undertaken at the UK Biobank imaging centre, acquiring a multi-echo spoiled gradient-echo single-breath-hold MRI sequence from the liver. All images were analysed for liver iron and fat (expressed as proton density fat fraction or PDFF) content using LiverMultiScan. Liver iron was measured in 97.3% of the cohort. The mean liver iron content was 1.32 ± 0.32 mg/g while the median was 1.25 mg/g (min: 0.85 max: 6.44 mg/g). Overall 4.82% of the population were defined as having elevated liver iron, above commonly accepted 1.8 mg/g threshold based on biochemical iron measurements in liver specimens obtained by biopsy. Further analysis using univariate models showed elevated liver iron to be related to male sex (p<10(-16), r2 = 0.008), increasing age (p<10(-16), r2 = 0.013), and red meat intake (p<10(-16), r2 = 0.008). Elevated liver fat (>5.6% PDFF) was associated with a slight increase in prevalence of elevated liver iron (4.4% vs 6.3%, p = 0.0007). This study shows that population studies including measurement of liver iron concentration are feasible, which may in future be used to better inform patient stratification and treatment.

Lymphoedema management to prevent acute dermatolymphangioadenitis in podoconiosis in northern Ethiopia (GoLBeT): a pragmatic randomised controlled trial.

BACKGROUND: Podoconiosis (also known as endemic, non-filarial elephantiasis) affects about 4 million subsistence farmers in tropical Africa. Poor awareness of the condition and inadequate evidence for the efficacy of treatment mean that no government in an endemic country yet offers lymphoedema management for patients with podoconiosis. Among patients with filarial lymphoedema, trials suggest that limb care is effective in reducing the most disabling sequelae: episodes of acute dermatolymphangioadenitis. We aimed to test the hypothesis that a simple, inexpensive lymphoedema management package would reduce the incidence of acute dermatolymphangioadenitis in adult patients with podoconiosis in northern Ethiopia. METHODS: We did a pragmatic randomised controlled trial at health posts and health centres in 18 sub-districts of Aneded woreda (district) in Amhara, northern Ethiopia. Participants were adults aged 18 years and older, had a diagnosis of at least stage 2 podoconiosis (persistent lymphoedema) and a negative antigen test for filariasis, and intended to remain within Aneded woreda for the duration of the trial. Patients were randomly assigned (1:1) to either receive a package containing instructions for foot hygiene, skin care, bandaging, exercises, and use of socks and shoes, with support by lay Community Podoconiosis Agents at monthly meetings (intervention group) or to receive no intervention (control group). Participants were aware of their group assignment, but researchers doing all analyses were masked to treatment group. The primary outcome was incidence of acute dermatolymphangioadenitis episodes in the total period of observation of each participant, measured by use of validated patient self-reported pictorial diaries. This trial was registered with the International Standard Randomised Controlled Trials Number Register, number ISRCTN67805210. FINDINGS: Between Dec 1, 2014, and June 30, 2015, 1339 patients were screened, and 696 patients were enrolled and randomly allocated to treatment groups. We allocated 350 patients to the intervention group and 346 patients to the control group. 321 (92%) patients from the intervention group and 329 (95%) patients from the control group provided follow-up results at 12 months. During the 12 months of follow-up, 16 550 new episodes of acute dermatolymphangioadenitis occurred during 765·2 person-years. The incidence of acute dermatolymphangioadenitis was 19·4 episodes per person-year (95% CI 18·9-19·9) in the intervention group and 23·9 episodes per person-year (23·4-24·4) in the control group. The ratio of incidence rate in the intervention group to that of the control group was 0·81 (0·74 to 0·89; p<0·0001), with a rate difference of -4·5 (-5·1 to -3·8) episodes per person-year. No serious adverse events related to the intervention were reported. INTERPRETATION: A simple, inexpensive package of lymphoedema self-care is effective in reducing the frequency and duration of acute dermatolymphangioadenitis. We recommend its implementation by the governments of endemic countries. FUNDING: Joint Global Health Trials scheme (from the Wellcome Trust, the UK Medical Research Council, and UK Aid).

Podoconiosis treatment in northern Ethiopia (GoLBet): study protocol for a randomised controlled trial.

BACKGROUND: Podoconiosis is one of the forgotten types of leg swelling (elephantiasis) in the tropics. Unlike the other, better-known types of leg swelling, podoconiosis is not caused by any parasite, virus or bacterium, but by an abnormal reaction to minerals found in the clay soils of some tropical highland areas. Non-governmental Organizations (NGOs) have been responsible for the development of simple treatment methods without systematic evaluation of its effectiveness. It is essential that a large scale, fully controlled, pragmatic trial of the intervention is conducted. We aim to test the hypothesis that community-based treatment of podoconiosis lymphoedema reduces the frequency of acute dermatolymphangioadenitis episodes ('acute attacks') and improves other clinical, social and economic outcomes. METHODS/DESIGN: This is a pragmatic, individually randomised controlled trial. We plan to randomly allocate 680 podoconiosis patients from the East Gojjam Zone in northern Ethiopia to one of two groups: 'Standard Treatment' or 'Delayed Treatment'. Those randomised to standard treatment will receive the hygiene and foot-care intervention from May 2015 for one year, whereas those in the control arm will be followed through 2015 and be offered the intervention in 2016. The trial will be preceded by an economic context survey and a Rapid Ethical Assessment to identify optimal methods of conveying information about the trial and the approaches to obtaining informed consent preferred by the community. The primary outcome will be measured by recording patient recall and using a simple, patient-held diary that will be developed to record episodes of acute attacks. Adherence to treatment, clinical stage of disease, quality of life, disability and stigma will be considered secondary outcome measures. Other outcomes will include adverse events and economic productivity. Assessments will be made at baseline and at 3, 6, 9 and 12 months thereafter. DISCUSSION: The evidence is highly likely to inform implementation of the new master plan for integrated control of Neglected Tropical Diseases (NTDs), in which podoconiosis is identified as one of eight NTDs prioritised for control. Potentially, an estimated 3 million patients in Ethiopia will therefore benefit from the results of this trial. TRIAL REGISTRATION: International Standard Randomised Controlled Trial Number. REGISTRATION NUMBER: ISRCTN67805210. Date of registration: 24 January 2013.