• Assessment of energy availability and associated risk factors in professional female soccer players

      Moss, Samantha L.; Randell, Rebecca K.; Burgess, Darren; Ridley, Stephanie; ÓCairealláin, Cairbre; Allison, Richard; Rollo, Ian (Informa UK Limited, 2020-08-06)
    • Assessment of energy availability and associated risk factors in professional female soccer players.

      Moss, Samantha L; Randell, Rebecca K; Burgess, Darren; Ridley, Stephanie; ÓCairealláin, Caibre; Allison, Richard; Rollo, Ian (2020-07-07)
      This study aimed to assess energy availability (EA), alongside possible risk factors of reduced or low EA of professional female soccer players during a competitive season. Thirteen players (age: 23.7 ± 3.4 y, stature: 1.69 ± 0.08 m, body mass: 63.7 ± 7.0 kg) engaged in a 5-day (two rest days, one light training, heavy training and match day) monitoring period. Energy intake (EI) and expenditure during exercise (EEE) were measured. EA was calculated and categorised as optimal, reduced or low (≥45, 31-44, ≤30 kcal·kg FFM ·day , respectively). Relationships between EA and bone mineral density, resting metabolic rate (RMR), plasma micronutrient status, biochemical markers and survey data were assessed. EA was optimal for 15%, reduced for 62% and low for 23% of players. Higher EA was observed on rest days compared to others ( <0.05). EA was higher for the light compared to the heavy training day ( <0.001). EEE differed significantly between days ( <0.05). EI (2124 ± 444 kcal), carbohydrate (3.31 ± 0.64 g·kg·day ) and protein (1.83 ± 0.41 g·kg·day ) intake remained similar ( >0.05). Survey data revealed 23% scored ≥ 8 on the Low Energy Availability in Females Questionnaire and met criteria for low RMR (ratio <0.90). Relationships between EA and risk factors were inconclusive. Most players displayed reduced EA and did not alter EI or carbohydrate intake to training or match demands. Although cases of low EA were identified, further work is needed to investigate possible long-term effects and risk factors of low and reduced EA separately to inform player recommendations.
    • Association of apolipoprotein E gene polymorphisms with blood lipids and their interaction with dietary factors

      Shatwan, Israa M.; Winther, Kristian H.; Ellahi, Basma; Elwood, Peter; Ben-Shlomo, Yoav; Givens, Ian; Rayman, Margaret P.; Lovegrove, Julie A.; Vimaleswaran, Karani S.; University of Reading; King Abdulaziz University; University Hospital Denmark; University of Chester; University Hospital of Wales; University of Bristol; University of Surrey (BioMed Central, 2018-04-30)
      Background: Several candidate genes have been identified in relation to lipid metabolism, and among these, lipoprotein lipase (LPL) and apolipoprotein E (APOE) gene polymorphisms are major sources of genetically determined variation in lipid concentrations. This study investigated the association of two single nucleotide polymorphisms (SNPs) at LPL, seven tagging SNPs at the APOE gene, and a common APOE haplotype (two SNPs) with blood lipids, and examined the interaction of these SNPs with dietary factors. Methods: The population studied for this investigation included 660 individuals from the Prevention of Cancer by Intervention with Selenium (PRECISE) study who supplied baseline data. The findings of the PRECISE study were further replicated using 1238 individuals from the Caerphilly Prospective cohort (CaPS). Dietary intake was assessed using a validated food-frequency questionnaire (FFQ) in PRECISE and a validated semi-quantitative FFQ in the CaPS. Interaction analyses were performed by including the interaction term in the linear regression model adjusted for age, body mass index, sex and country. Results: There was no association between dietary factors and blood lipids after Bonferroni correction and adjustment for confounding factors in either cohort. In the PRECISE study, after correction for multiple testing, there was a statistically significant association of the APOE haplotype (rs7412 and rs429358; E2, E3, and E4) and APOE tagSNP rs445925 with total cholesterol (P = 4 × 10− 4 and P = 0.003, respectively). Carriers of the E2 allele had lower total cholesterol concentration (5.54 ± 0.97 mmol/L) than those with the E3 (5.98 ± 1.05 mmol/L) (P = 0.001) and E4 (6.09 ± 1.06 mmol/L) (P = 2 × 10− 4) alleles. The association of APOE haplotype (E2, E3, and E4) and APOE SNP rs445925 with total cholesterol (P = 2 × 10− 6 and P = 3 × 10− 4, respectively) was further replicated in the CaPS. Additionally, significant association was found between APOE haplotype and APOE SNP rs445925 with low density lipoprotein cholesterol in CaPS (P = 4 × 10− 4 and P = 0.001, respectively). After Bonferroni correction, none of the cohorts showed a statistically significant SNP-diet interaction on lipid outcomes. Conclusion: In summary, our findings from the two cohorts confirm that genetic variations at the APOE locus influence plasma total cholesterol concentrations, however, the gene-diet interactions on lipids require further investigation in larger cohorts.
    • Autologous chondrocyte implantation-derived synovial fluids display distinct responder and non-responder proteomic profiles

      Hulme, Charlotte H.; Wilson, Emma L.; Peffers, Mandy J.; Roberts, Sally; Simpson, Deborah M.; Richardson, James B.; Gallacher, Pete; Wright, Karina T.; Keele University; Robert Jones and Agnes Hunt Orthopaedic Hospital; University of Chester; University of Liverpool (BioMed Central, 2017-06-30)
      Background Autologous chondrocyte implantation (ACI) can be used in the treatment of focal cartilage injuries to prevent the onset of osteoarthritis (OA). However, we are yet to understand fully why some individuals do not respond well to this intervention. Identification of a reliable and accurate biomarker panel that can predict which patients are likely to respond well to ACI is needed in order to assign the patient to the most appropriate therapy. This study aimed to compare the baseline and mid-treatment proteomic profiles of synovial fluids (SFs) obtained from responders and non-responders to ACI. Methods SFs were derived from 14 ACI responders (mean Lysholm improvement of 33 (17–54)) and 13 non-responders (mean Lysholm decrease of 14 (4–46)) at the two stages of surgery (cartilage harvest and chondrocyte implantation). Label-free proteome profiling of dynamically compressed SFs was used to identify predictive markers of ACI success or failure and to investigate the biological pathways involved in the clinical response to ACI. Results Only 1 protein displayed a ≥2.0-fold differential abundance in the preclinical SF of ACI responders versus non-responders. However, there is a marked difference between these two groups with regard to their proteome shift in response to cartilage harvest, with 24 and 92 proteins showing ≥2.0-fold differential abundance between Stages I and II in responders and non-responders, respectively. Proteomic data has been uploaded to ProteomeXchange (identifier: PXD005220). We have validated two biologically relevant protein changes associated with this response, demonstrating that matrix metalloproteinase 1 was prominently elevated and S100 calcium binding protein A13 was reduced in response to cartilage harvest in non-responders. Conclusions The differential proteomic response to cartilage harvest noted in responders versus non-responders is completely novel. Our analyses suggest several pathways which appear to be altered in non-responders that are worthy of further investigation to elucidate the mechanisms of ACI failure. These protein changes highlight many putative biomarkers that may have potential for prediction of ACI treatment success.
    • Biomechanical measures of short-term maximal cycling on an ergometer: a test-retest study

      Burnie, Louise; Barratt, Paul; Davids, Keith; orcid: 0000-0003-1398-6123; Worsfold, Paul; Wheat, Jon; orcid: 0000-0002-1107-6452 (Informa UK Limited, 2020-08-11)
    • Biomechanical measures of short-term maximal cycling on an ergometer: a test-retest study.

      Burnie, Louise; Barratt, Paul; Davids, Keith; orcid: 0000-0003-1398-6123; Worsfold, Paul; Wheat, Jon; orcid: 0000-0002-1107-6452 (2020-08-11)
      An understanding of test-retest reliability is important for biomechanists, such as when assessing the longitudinal effect of training or equipment interventions. Our aim was to quantify the test-retest reliability of biomechanical variables measured during short-term maximal cycling. Fourteen track sprint cyclists performed 3 × 4 s seated sprints at 135 rpm on an isokinetic ergometer, repeating the session 7.6 ± 2.5 days later. Joint moments were calculated via inverse dynamics, using pedal forces and limb kinematics. EMG activity was measured for 9 lower limb muscles. Reliability was explored by quantifying systematic and random differences within- and between-session. Within-session reliability was better than between-sessions reliability. The test-retest reliability level was typically moderate to excellent for the biomechanical variables that describe maximal cycling. However, some variables, such as peak knee flexion moment and maximum hip joint power, demonstrated lower reliability, indicating that care needs to be taken when using these variables to evaluate biomechanical changes. Although measurement error (instrumentation error, anatomical marker misplacement, soft tissue artefacts) can explain some of our reliability observations, we speculate that biological variability may also be a contributor to the lower repeatability observed in several variables including ineffective crank force, ankle kinematics and hamstring muscles' activation patterns.
    • BOOK REVIEWS

      Clough, David; Brown, Jennifer; Ward, Frances; Gorringe, Tim; Higginson, Richard; Foster-Gilbert, Claire; Woodward, James; Mursell, Gordon; Brierley, Michael; Korpel, Marjo; et al. (Liverpool University Press, 2020-07)
    • Brief Engagement and Acceptance Coaching for Community and Hospice Settings (the BEACHeS Study): Protocol for the development and pilot testing of an evidence-based psychological intervention to enhance wellbeing and aid transition into palliative care

      Hulbert-Williams, Nicholas J.; orcid: 0000-0001-9041-5485; email: n.hulbertwilliams@chester.ac.uk; Norwood, Sabrina; email: s.norwood@chester.ac.uk; Gillanders, David; email: david.gillanders@ed.ac.uk; Finucane, Anne; email: anne.finucane@mariecurie.org.uk; Spiller, Juliet; email: juliet.spiller@mariecurie.org.uk; Strachan, Jenny; email: jenny.strachan@mariecurie.org.uk; Millington, Sue; email: sue.millington@btopenworld.com; Swash, Brooke; email: b.swash@chester.ac.uk (BioMed Central, 2019-08-20)
      Abstract: Background: Cancer affects millions of individuals globally, with a mortality rate of over eight million people annually. Although palliative care is often provided outside of specialist services, many people require, at some point in their illness journey, support from specialist palliative care services, for example, those provided in hospice settings. This transition can be a time of uncertainty and fear, and there is a need for effective interventions to meet the psychological and supportive care needs of people with cancer that cannot be cured. Whilst Acceptance and Commitment Therapy (ACT) has been shown to be effective across diverse health problems, robust evidence for its effectiveness in palliative cancer populations is not extensive. Method: This mixed-methods study uses a single-case experimental design with embedded qualitative interviews to pilot test a novel intervention for this patient group. Between 14 and 20 patients will be recruited from two hospices in England and Scotland. Participants will receive five face-to-face manualised sessions with a psychological therapist. Sessions are structured around teaching core ACT skills (openness, awareness and engagement) as a way to deal effectively with challenges of transition into specialist palliative care services. Outcome measures include cancer-specific quality of life (primary outcome) and distress (secondary outcome), which are assessed alongside measures of psychological flexibility. Daily diary outcome assessments will be taken for key measures, alongside more detailed weekly self-report, through baseline, intervention and 1-month follow-up phases. After follow-up, participants will be invited to take part in a qualitative interview to understand their experience of taking part and acceptability and perceived effectiveness of the intervention and its components. Discussion: This study is the first investigation of using ACT with terminally ill patients at the beginning of their transition into palliative treatment. Using in-depth single-case approaches, we will refine and manualise intervention content by the close of the study for use in follow-up research trials. Our long-term goal is then to test the intervention as delivered by non-psychologist specialist palliative care practitioners thus broadening the potential relevance of the approach. Trial registration: Open Science Framework, 46033. Registered 19 April 2018.
    • British prisoners of war in First World War Germany

      Grady, Tim (Informa UK Limited, 2020-05-29)
    • Building the capacity for psycho-Oncology research: a survey of the research barriers and training needs within the International Psycho-Oncology Society.

      Lambert, Sylvie D; Coumoundouros, Chelsea; Hulbert-Williams, Nick J; Shaw, Joanne; Schaffler, Jamie (2020-07-28)
      The International Psycho-Oncology Society (IPOS) is a multidisciplinary professional network that aims to improve psychosocial care for individuals impacted by cancer. IPOS encourages research activity, recognizing that a high-quality evidence base is essential to provide best-practice, data-driven clinical care. This study aimed to determine the barriers to research involvement and the training needs and priorities of IPOS members, with the goal of facilitating the development of training resources tailored to the needs of IPOS members. A link to an online, cross-sectional survey was disseminated to all registered members of IPOS via email. The online survey platform SimpleSurvey was used, and questions included demographic characteristics and items related to research interests, involvement, and training needs. High priority research training needs were identified as research tasks respondents rated as highly important, yet possessed a low perceived skill level in. Thirty-two percent of IPOS members (n = 142) completed the survey. Participants represented 49 countries and were at a variety of career stages. Overall, participants reported spending an average of 17.3 hours per week on research (range 0-80 hours per week), with 69% of respondents wanting to increase their research involvement. The main barriers to research participation included lack of research funding (80%) and lack of protected time (63%). IPOS members identified 5 high-priority training needs: preparing successful grant applications; preparing research budgets; community-based participatory research; working with decision makers; and finding collaborators or expert consultants. Participants suggested funding access, statistical advisors, and networking and mentorship opportunities as ways to enhance research involvement. Members preferred online training modules (39%) and mentorship programs (19%) as methods by which IPOS could provide research support. IPOS was viewed as being able to contribute to many aspects of research capacity building such as networking, training, and dissemination of research findings. IPOS has an important role in encouraging research capacity building among members. This survey provides an agenda for workshops and training opportunities. Mainly, for respondents it was less about training in research methods and more about training in how to prepare successful grant applications, including budgets, and receiving mentorship on this as well as having opportunities to collaborate with other researchers. [Abstract copyright: Copyright © 2020 The Authors. Published by Wolters Kluwer Health Inc., on behalf of the International Psycho-Oncology Society.]
    • Challenges and issues facing ethnic minority small business owners

      Rahman, Md Zillur; Ullah, Farid; Thompson, Piers (SAGE Publications, 2018-01-23)
      Studies investigating the challenges and barriers faced by ethnic minority entrepreneurs have often concentrated on areas where there is a large supportive ethnic minority community. Less work has been conducted on the experience of those entrepreneurs operating in cities where such ethnic resources may be less widely available. Considered from the perspective of mixed embeddedness framework, this study uses face-to-face interviews with 25 ethnic minority entrepreneurs to gain a greater understanding of the constraints experienced by the starting and running businesses in one such location, the Scottish city of Aberdeen in the United Kingdom. Although issues found by previous studies such as access to funding remain an issue, the entrepreneurs indicated problems with access to labour as United Kingdom Border Agency’s immigration rules and tightening of the Post Study Work visa have had a profound effect on these entrepreneurs. The results imply that the weakening of the ethnic resource microsphere has not opened up opportunities which are exploited by the entrepreneurs, but they have still been exposed to external forces from the regulatory macrosphere. Both entrepreneurs and policymakers need to think carefully about the retention, training and recruitment of staff. In particular, the wider ramifications of immigration rule changes need to be considered, but also whether entrepreneurs need to be more open to the potential of recruiting non-ethnic employees and if so what support is required to achieve this.
    • Comparing physician associates and foundation year two doctors-in-training undertaking emergency medicine consultations in England: a mixed-methods study of processes and outcomes

      Halter, Mary; orcid: 0000-0001-6636-0621; Drennan, Vari; orcid: 0000-0002-8915-5185; Wang, Chao; Wheeler, Carly; Gage, Heather; Nice, Laura; de Lusignan, Simon; orcid: 0000-0001-5613-6810; Gabe, Jonathan; Brearley, Sally; Ennis, James; et al. (BMJ Publishing Group, 2020-09-01)
      Objectives: To compare the contribution of physician associates to the processes and outcomes of emergency medicine consultations with that of foundation year two doctors-in-training. Design: Mixed-methods study: retrospective chart review using 4 months’ anonymised clinical record data of all patients seen by physician associates or foundation year two doctors-in-training in 2016; review of a subsample of 40 records for clinical adequacy; semi-structured interviews with staff and patients; observations of physician associates. Setting: Three emergency departments in England. Participants: The records of 8816 patients attended by 6 physician associates and 40 foundation year two doctors-in-training; of these n=3197 had the primary outcome recorded (n=1129 physician associates, n=2068 doctor); 14 clinicians and managers and 6 patients or relatives for interview; 5 physician associates for observation. Primary and secondary outcome measures: The primary outcome was unplanned re-attendance at the same emergency department within 7 days. Secondary outcomes: consultation processes, clinical adequacy of care, and staff and patient experience. Results: Re-attendances within 7 days (n=194 (6.1%)) showed no difference between physician associates and foundation year two doctors-in-training (OR 0.87, 95% CI 0.61 to 1.24, p=0.437). If seen by a physician associate, patients were more likely receive an X-ray investigation (OR 2.10, 95% CI 1.72 to 4.24), p<0.001), after adjustment for patient characteristics, triage severity of condition and statistically significant clinician intraclass correlation. Clinical reviewers found almost all patients’ charts clinically adequate. Physician associates were evaluated as assessing patients in a similar way to foundation year two doctors-in-training and providing continuity in the team. Patients were positive about the care they had received from a physician associate, but had poor understanding of the role. Conclusions: Physician associates in emergency departments in England treated patients with a range of conditions safely, and at a similar level to foundation year two doctors-in-training, providing clinical operational efficiencies.
    • Comparing physician associates and foundation year two doctors-in-training undertaking emergency medicine consultations in England: a mixed-methods study of processes and outcomes.

      Halter, Mary; orcid: 0000-0001-6636-0621; email: m.halter@sgul.kingston.ac.uk; Drennan, Vari; orcid: 0000-0002-8915-5185; Wang, Chao; Wheeler, Carly; Gage, Heather; Nice, Laura; de Lusignan, Simon; orcid: 0000-0001-5613-6810; Gabe, Jonathan; Brearley, Sally; Ennis, James; et al. (2020-09-01)
      To compare the contribution of physician associates to the processes and outcomes of emergency medicine consultations with that of foundation year two doctors-in-training. Mixed-methods study: retrospective chart review using 4 months' anonymised clinical record data of all patients seen by physician associates or foundation year two doctors-in-training in 2016; review of a subsample of 40 records for clinical adequacy; semi-structured interviews with staff and patients; observations of physician associates. Three emergency departments in England. The records of 8816 patients attended by 6 physician associates and 40 foundation year two doctors-in-training; of these n=3197 had the primary outcome recorded (n=1129 physician associates, n=2068 doctor); 14 clinicians and managers and 6 patients or relatives for interview; 5 physician associates for observation. The primary outcome was unplanned re-attendance at the same emergency department within 7 days. consultation processes, clinical adequacy of care, and staff and patient experience. Re-attendances within 7 days (n=194 (6.1%)) showed no difference between physician associates and foundation year two doctors-in-training (OR 0.87, 95% CI 0.61 to 1.24, p=0.437). If seen by a physician associate, patients were more likely receive an X-ray investigation (OR 2.10, 95% CI 1.72 to 4.24), p<0.001), after adjustment for patient characteristics, triage severity of condition and statistically significant clinician intraclass correlation. Clinical reviewers found almost all patients' charts clinically adequate. Physician associates were evaluated as assessing patients in a similar way to foundation year two doctors-in-training and providing continuity in the team. Patients were positive about the care they had received from a physician associate, but had poor understanding of the role. Physician associates in emergency departments in England treated patients with a range of conditions safely, and at a similar level to foundation year two doctors-in-training, providing clinical operational efficiencies. [Abstract copyright: © Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY. Published by BMJ.]
    • Coping Style and Early Life Vocalizations in the Common Marmoset ( Callithrix jacchus )

      Díaz, Sergio; email: s.gonzalezdiaz@chester.ac.uk; Sánchez, Susana; Fidalgo, Ana (Springer US, 2020-05-20)
      Abstract: Coping styles describe behavioral differences during stressful or challenging situations. Coping styles are stable over time but little is known about early life manifestation and development of these behavioral differences. We aimed to investigate if differences in the way marmosets produce vocalizations at an early age are related to their coping style in the future. We studied 14 common marmosets (Callithrix jacchus) from three social groups housed at the marmoset colony at Universidad Autónoma de Madrid. We recorded the vocalizations of each marmoset in isolation at 15–17 days of age, analyzing latency to vocalize and calling rate of phee and tsik calls. To measure coping style, we introduced a novel stimulus to the group cages when infants were 3 months old and recorded exploration, headcocking, and approaches to the stimulus. The results showed negative relationships between the latency of phee call (a long-range contact call) at 15–17 days and frequency of exploration and approach to the novel stimulus at 3 months, although both correlations fall above the cut-off points for the false discovery rate. Marmosets that gave long-range calls sooner at 15–17 days of age also showed more exploratory behaviors at 3 months. The results also showed group differences in exploration at 3 months, and twins were more similar to each other than to other infants in the sample. There were no group differences in early vocalizations and no sex differences in any variable. These findings suggest that coping style is stable from as early as 15–17 days after birth and suggest that the group can influence exploration in marmosets.
    • Cost of non-alcoholic steatohepatitis in Europe and the USA: The GAIN study.

      O'Hara, Jamie; Finnegan, Alan; Dhillon, Harpal; Ruiz-Casas, Leonardo; Pedra, Gabriel; Franks, Bethany; Morgan, George; Hebditch, Vanessa; Jönsson, Bengt; Mabhala, Mzwandile; et al. (2020-07-15)
      Non-alcoholic steatohepatitis (NASH) leads to cirrhosis and is associated with a substantial socioeconomic burden, which, coupled with rising prevalence, is a growing public health challenge. However, there are few real-world data available describing the impact of NASH. The Global Assessment of the Impact of NASH (GAIN) study is a prevalence-based burden of illness study across Europe (France, Germany, Italy, Spain, and the UK) and the USA. Physicians provided demographic, clinical, and economic patient information via an online survey. In total, 3,754 patients found to have NASH on liver biopsy were stratified by fibrosis score and by biomarkers as either early or advanced fibrosis. Per-patient costs were estimated using national unit price data and extrapolated to the population level to calculate the economic burden. Of the patients, 767 (20%) provided information on indirect costs and health-related quality of life using the EuroQOL 5-D (EQ-5D; n = 749) and Chronic Liver Disease Questionnaire - Non-Alcoholic Fatty Liver Disease (CLDQ-NAFLD) (n = 723). Mean EQ-5D and CLDQ-NAFLD index scores were 0.75 and 4.9, respectively. For 2018, the mean total annual per patient cost of NASH was €2,763, €4,917, and €5,509 for direct medical, direct non-medical, and indirect costs, respectively. National per-patient cost was highest in the USA and lowest in France. Costs increased with fibrosis and decompensation, driven by hospitalisation and comorbidities. Indirect costs were driven by work loss. The GAIN study provides real-world data on the direct medical, direct non-medical, and indirect costs associated with NASH, including patient-reported outcomes in Europe and the USA, showing a substantial burden on health services and individuals. There has been little research into the socioeconomic burden associated with non-alcoholic steatohepatitis (NASH). The GAIN study provides real-world data on the direct medical, direct non-medical, and indirect costs associated with NASH, including patient-reported outcomes in five European countries (UK, France, Germany, Spain, and Italy) and the USA. Mean total annual per patient cost of NASH was estimated at €2,763, €4,917, and €5,509 for the direct medical, direct non-medical, and indirect cost categories, respectively. [Abstract copyright: © 2020 The Author(s).]
    • The cost of severe haemophilia in Europe: the CHESS study

      O’Hara, Jamie; Hughes, David; Camp, Charlotte; Burke, Tom; Carroll, Liz; Diego, Daniel-Anibal G.; University of Chester; HCD Economics, Daresbury; The Haeomophelia Society, London; FedHemo, Madrid (BioMed Central, 2017-05-31)
      Background Severe haemophilia is associated with major psychological and economic burden for patients, caregivers, and the wider health care system. This burden has been quantified and documented for a number of European countries in recent years. However, few studies have taken a standardised methodology across multiple countries simultaneously, and sought to amalgamate all three levels of burden for severe disease. The overall aim of the ‘Cost of Haemophilia in Europe: a Socioeconomic Survey’ (CHESS) study was to capture the annualised economic and psychosocial burden of severe haemophilia in five European countries. A cross-section of haemophilia specialists (surveyed between January and April 2015) provided demographic and clinical information and 12-month ambulatory and secondary care activity for patients via an online survey. In turn, patients provided corresponding direct and indirect non-medical cost information, including work loss and out-of-pocket expenses, as well as information on quality of life and adherence. The direct and indirect costs for the patient sample were calculated and extrapolated to population level. Results Clinical reports for a total of 1,285 patients were received. Five hundred and fifty-two patients (43% of the sample) provided information on indirect costs and health-related quality of life via the PSC. The total annual cost of severe haemophilia across the five countries for 2014 was estimated at EUR 1.4 billion, or just under EUR 200,000 per patient. The highest per-patient costs were in Germany (mean EUR 319,024) and the lowest were in the United Kingdom (mean EUR 129,365), with a study average of EUR 199,541. As expected, consumption of clotting factor replacement therapy represented the vast majority of costs (up to 99%). Indirect costs are driven by patient and caregiver work loss. Conclusions The results of the CHESS study reflect previous research findings suggesting that costs of factor replacement therapy account for the vast majority of the cost burden in severe haemophilia. However, the importance of the indirect impact of haemophilia on the patient and family should not be overlooked. The CHESS study highlights the benefits of observational study methodologies in capturing a ‘snapshot’ of information for patients with rare diseases.