S D Ryder

Nottingham University Hospitals NHS Trust, Nottigham, England, United Kingdom

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Publications (77)550.15 Total impact

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    ABSTRACT: Tenofovir alafenamide, a phosphonate prodrug of tenofovir with greater plasma stability than tenofovir disoproxil fumarate, provides efficient delivery of active drug to hepatocytes at reduced systemic tenofovir exposures.
    Journal of Hepatology 10/2014; · 10.40 Impact Factor
  • Stephen Ryder, John Dillon
    The Health service journal. 05/2014; 124(6397):21-3.
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    ABSTRACT: Chronic infection with hepatitis C virus (HCV) is a leading indicator for liver disease. New treatment options are becoming available, and there is a need to characterize the epidemiology and disease burden of HCV. Data for prevalence, viremia, genotype, diagnosis and treatment were obtained through literature searches and expert consensus for 16 countries. For some countries, data from centralized registries were used to estimate diagnosis and treatment rates. Data for the number of liver transplants and the proportion attributable to HCV were obtained from centralized databases. Viremic prevalence estimates varied widely between countries, ranging from 0.3% in Austria, England and Germany to 8.5% in Egypt. The largest viremic populations were in Egypt, with 6 358 000 cases in 2008 and Brazil with 2 106 000 cases in 2007. The age distribution of cases differed between countries. In most countries, prevalence rates were higher among males, reflecting higher rates of injection drug use. Diagnosis, treatment and transplant levels also differed considerably between countries. Reliable estimates characterizing HCV-infected populations are critical for addressing HCV-related morbidity and mortality. There is a need to quantify the burden of chronic HCV infection at the national level.
    Journal of Viral Hepatitis 05/2014; 21 Suppl 1:5-33. · 3.08 Impact Factor
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    ABSTRACT: The number of hepatitis C virus (HCV) infections is projected to decline while those with advanced liver disease will increase. A modeling approach was used to forecast two treatment scenarios: (i) the impact of increased treatment efficacy while keeping the number of treated patients constant and (ii) increasing efficacy and treatment rate. This analysis suggests that successful diagnosis and treatment of a small proportion of patients can contribute significantly to the reduction of disease burden in the countries studied. The largest reduction in HCV-related morbidity and mortality occurs when increased treatment is combined with higher efficacy therapies, generally in combination with increased diagnosis. With a treatment rate of approximately 10%, this analysis suggests it is possible to achieve elimination of HCV (defined as a >90% decline in total infections by 2030). However, for most countries presented, this will require a 3-5 fold increase in diagnosis and/or treatment. Thus, building the public health and clinical provider capacity for improved diagnosis and treatment will be critical.
    Journal of Viral Hepatitis 05/2014; 21 Suppl 1:60-89. · 3.08 Impact Factor
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    ABSTRACT: The disease burden of hepatitis C virus (HCV) is expected to increase as the infected population ages. A modelling approach was used to estimate the total number of viremic infections, diagnosed, treated and new infections in 2013. In addition, the model was used to estimate the change in the total number of HCV infections, the disease progression and mortality in 2013-2030. Finally, expert panel consensus was used to capture current treatment practices in each country. Using today's treatment paradigm, the total number of HCV infections is projected to decline or remain flat in all countries studied. However, in the same time period, the number of individuals with late-stage liver disease is projected to increase. This study concluded that the current treatment rate and efficacy are not sufficient to manage the disease burden of HCV. Thus, alternative strategies are required to keep the number of HCV individuals with advanced liver disease and liver-related deaths from increasing.
    Journal of Viral Hepatitis 05/2014; 21 Suppl 1:34-59. · 3.08 Impact Factor
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    ABSTRACT: Background Therapeutic options for the management of hepatitis C virus (HCV) infection have evolved rapidly over the past two decades, with a consequent improvement in cure rates. Novel therapeutic agents are an area of great interest in the research community, with a number of these agents showing promise in the clinical setting.AimsTo assess and present the available evidence for the use of novel therapeutic agents for the treatment of HCV, updating previous guidelines.Methods All Phase 2 and 3 studies, as well as abstract presentations from international Hepatology meetings were identified and reviewed for suitable inclusion, based on studies of new therapies in HCV. Treatment-naïve and experienced individuals, as well as cirrhotic and co-infected individuals were included.ResultsSofosbuvir, simeprevir and faldaprevir, along with pegylated interferon and ribavirin, have a role in the treatment of chronic HCV infection. The precise regimens are largely dependent on the patient characteristics, patient and physician preferences, and cost implication.Conclusions Therapies for chronic HCV have evolved dramatically in recent years. Interferon-free regimens are now possible without compromise in the rate of sustained viral response. The decision as to which regimen is most appropriate is multifactorial, and based on efficacy, safety and cost.
    Alimentary Pharmacology & Therapeutics 04/2014; · 4.55 Impact Factor
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    ABSTRACT: Alcoholic hepatitis is the most florid presentation of alcohol-related liver disease. In its severe form, defined by a Maddrey's discriminant function (DF) >=32, the 28-day mortality rate is approximately 35%. A number of potential treatments have been subjected to clinical trials, of which two, corticosteroids and pentoxifylline, may have therapeutic benefit. The role of corticosteroids is controversial as trial results have been inconsistent, whereas the role of pentoxifylline requires confirmation as only one previous placebo-controlled trial has been published.Methods/design: STOPAH is a multicentre, double-blind, factorial (2 x 2) trial in which patients are randomised to one of four groups:1.Group A: placebo / placebo2.Group B: placebo / prednisolone3.Group C: pentoxifylline / placebo4.Group D: pentoxifylline / prednisoloneThe trial aims to randomise 1,200 patients with severe alcoholic hepatitis, in order to provide sufficient power to determine whether either of the two interventions is effective. The primary endpoint of the study is mortality at 28 days, with secondary endpoints being mortality at 90 days and 1 year. STOPAH aims to be a definitive study to resolve controversy around the existing treatments for alcoholic hepatitis. Eligibility criteria are based on clinical parameters rather than liver biopsy, which are aligned with standard clinical practice in most hospitals. The use of a factorial design will allow two treatments to be evaluated in parallel, with efficient use of patient numbers to achieve high statistical power.Trial registration: EudraCT reference number: 2009-013897-42ISRCTN reference number: ISRCTN88782125.
    Trials 08/2013; 14(1):262. · 2.12 Impact Factor
  • Journal of Hepatology 04/2013; 58:S253. · 10.40 Impact Factor
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    ABSTRACT: Background. Through migration, diversity of chronic hepatitis B virus (HBV) infection has changed which may impact on disease burden and control. We describe clinical and viral characteristics of chronic HBV in the UK.Methods. 698 individuals with chronic HBV infection were recruited from referral liver centres. Demographic, clinical, and laboratory data were collected.Results. 61% were male, 80% were non UK-born. Largest ethnicity was East/South East Asian (36%). 22% were HBeAg seropositive. 20.4% (59/289) had cirrhosis on liver biopsy and 10 (1.7%) had HCC. Genotype D was most common (31%) followed by A, C, B and E (20%, 20%, 19%, and 9%). Genotype was significantly associated with country of birth, length of time in UK, HBe status, precore and basal core promoter mutations. One third were on treatment with men independently more likely than women to be treated. Only 18% of those on treatment were on recommended first line therapies and 30% were on 3TC monotherapy. 27% of treated individuals had antiviral drug resistance. Testing for HIV, HCV and delta co-infections was low.Conclusions. We have demonstrated diversity of chronic HBV infections in UK patients, suggesting that optimal management requires awareness of the variable patterns of chronic HBV in countries of origin. We also found less than optimal clinical management practices, possible gender based treatment bias and the need to improve testing for co-infections.
    Clinical Infectious Diseases 12/2012; · 9.42 Impact Factor
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    ABSTRACT: INTRODUCTION: Early insertion of transjugular intrahepatic portosystemic shunt (TIPS) in high-risk patients with acute variceal haemorrhage reduces rebleeding and mortality. However, the economic benefit of utilizing this approach remains unclear. We evaluated the economic implications of introducing early TIPS into routine algorithms for the management of variceal bleeding. METHODS: Consecutive patients admitted in 2009 with variceal haemorrhage to two liver units and eligible for early TIPS insertion were identified retrospectively. The costs of a 12-month follow-up from index bleeding admission were calculated - the actual cost of follow-up and rebleeding in this cohort was compared with the theoretical 12-month follow-up costs of instead inserting an early TIPS at index admission. Our findings were subjected to a sensitivity analysis to assess the cost effectiveness of early TIPS insertion compared with standard care. RESULTS: In 2009, 78 patients were admitted to our units with variceal haemorrhage; 27 patients (35%) were eligible for early TIPS insertion. The actual cost of a 12-month follow-up was £138 473.50. Early TIPS insertion, assuming a 3.2% rebleeding rate, would save £534.70 per patient per year (P<0.0001). On sensitivity analysis, early TIPS dominated standard care up to an early TIPS rebleeding rate of 6% and remained cost-effective up to a rebleeding rate of 12%. CONCLUSION: Early TIPS insertion for high-risk patients with acute variceal bleeding is a cost-efficient intervention. This has important implications for the introduction of early TIPS as standard care and the organization of interventional radiology services.
    European journal of gastroenterology & hepatology 10/2012; · 1.66 Impact Factor
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    ABSTRACT: BACKGROUND/AIMS: There is substantial evidence suggesting transient elastography (TE) is a useful tool in assessing liver fibrosis. We aimed to determine whether TE has incremental diagnostic value over clinical acumen and routinely available tests. METHODS: We performed a retrospective study of 130 patients to assess the ability of hepatologists to predict severity of fibrosis using clinical acumen; clinical acumen with routine tests; and elastography in patients with chronic liver disease. The incremental diagnostic benefit was assessed using the area under the ROC curve (AUC) and the Net Reclassification Index (NRI). RESULTS: Using universally available tests, including clinical acumen, the AUCs for detection of cirrhosis ranged from 0.70 to 0.80 for the four hepatologists. Elastography led to statistically non-significant improvements in AUC statistics (range 0.83-0.89; P > 0.01). The detection of significant fibrosis using clinical acumen and routine tests was less accurate, with AUCs of 0.52-0.59. Elastography had incremental diagnostic value (AUC performance range 0.76-0.82; P < 0.01). The NRI indicated that 39-58% were correctly reclassified using elastography, especially with respect to sensitivity. CONCLUSIONS: Our study suggests that the diagnostic value of clinical acumen and routine tests is acceptable for detection of cirrhosis, but not significant fibrosis. Elastography detects significant fibrosis or cirrhosis with acceptable accuracy and offered incremental diagnostic value in detecting significant fibrosis, but not cirrhosis. These findings have implications for determining the diagnostic value of tests over and above routine clinical assessment, which will aid incorporation of novel tests into clinical algorithms.
    Liver international: official journal of the International Association for the Study of the Liver 10/2012; · 4.41 Impact Factor
  • Journal of Hepatology 05/2012; 56, Supplement 2:S423 -. · 10.40 Impact Factor
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    ABSTRACT: The nonstructural 3 serine protease inhibitors (PIs), boceprevir and telaprevir, represent the first in a new generation of directly acting antivirals against genotype 1 hepatitis C (HCV) infection. When used in combination with pegylated interferon and ribavirin, these drugs greatly improve sustained virological response rates in both treatment-naïve patients and patients who have had previous virological failure on treatment. However, the addition of these new agents will increase the complexity of therapeutic regimens, the rates of side-effects and costs. To review concisely the current evidence and to suggest current best practice, for the use of telaprevir and boceprevir in the management of chronic genotype 1 HCV infection. These guidelines for the use of boceprevir and telaprevir have been formulated following extensive review of the current literature, are based on the consensus opinion of a panel of national experts, and have been openly discussed and debated at a national meeting of HCV care providers. We have made recommendations on a number of the key practical issues facing HCV care providers: (i) Which patients to treat?; (ii) Standards for the provision of care; (iii) Pre-treatment considerations; (iv) Which treatment regimens to use?; (v) Stopping rules; and (vi) Management of adverse effects. Finally, we have produced suggested algorithms for the assessment and treatment of these patients. These UK Consensus guidelines indicate the current best practice for the use of boceprevir and telaprevir in the management of genotype 1 chronic HCV infection.
    Alimentary Pharmacology & Therapeutics 03/2012; 35(6):647-62. · 4.55 Impact Factor
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    ABSTRACT: A substantial proportion of patients with chronic hepatitis C virus (HCV) cirrhosis fail to eradicate infection and develop liver-related complications. Despite evidence that interferon-α has an antifibrotic effect, clinical trials have demonstrated that low-dose maintenance interferon does not improve outcomes in patients with compensated HCV cirrhosis following a lead-in phase of interferon. In a pilot study, we have investigated the efficacy of an escalating dose of pegylated interferon α-2a (PEG-IFN2a) as compared with standard clinical care in patients with more advanced HCV Child's A or B cirrhosis without a lead-in phase. In a prospective study, 40 patients were randomized to receive either standard clinical care (no further antiviral therapy) or 48 weeks of treatment with PEG-IFN2a starting at 90 mcg and escalating to 180 mcg weekly if tolerated. Patients were thereafter followed for a mean duration of 41 months. The primary outcome variables were liver-related death, all-cause mortality and sustained virological response. The secondary outcomes were 'liver-related events' and health-related quality of life. Both groups were well matched, with treatment well tolerated. The incidences of all-cause mortality (P=0.024) and nononcological liver morbidity (P=0.04) were significantly higher in the control arm after a mean of 47 months of follow-up. A 48-week escalating dose of PEG-IFN2a is associated with a significant reduction in all-cause mortality and nononcological liver-related morbidity in this trial. Further investigation of PEG-IFN2a is warranted for patients with advanced HCV-related cirrhosis for whom there is no other treatment and where transplantation is associated with rapid progression to cirrhosis.
    European journal of gastroenterology & hepatology 02/2012; 24(5):543-50. · 1.66 Impact Factor
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    ABSTRACT: Although liver function tests (LFTs) are routinely measured in primary care, raised levels in patients with no obvious liver disease may trigger a range of subsequent expensive and unnecessary management plans. The aim of this study was to develop and validate a prediction model to guide decision-making by general practitioners, which estimates risk of one year all-cause mortality in patients with no obvious liver disease. In this population-based historical cohort study, biochemistry data from patients in Tayside, Scotland, with LFTs performed in primary care were record-linked to secondary care and prescription databases to ascertain baseline characteristics, and to mortality data. Using this derivation cohort a survival model was developed to predict mortality. The model was assessed for calibration, discrimination (using the C-statistic) and performance, and validated using a separate cohort of Scottish primary care practices. From the derivation cohort (n = 95 977), 2.7% died within one year. Predictors of mortality included: age; male gender; social deprivation; history of cancer, renal disease, stroke, ischaemic heart disease or respiratory disease; statin use; and LFTs (albumin, transaminase, alkaline phosphatase, bilirubin, and gamma-glutamyltransferase). The C-statistic for the final model was 0.82 (95% CI 0.80-0.84), and was similar in the validation cohort (n = 11 653) 0.86 (0.79-0.90). As an example of performance, for a 10% predicted probability cut-off, sensitivity = 52.8%, specificity = 94.0%, PPV = 21.0%, NPV = 98.5%. For the model without LFTs the respective values were 43.8%, 92.8%, 15.6%, 98.1%. The Algorithm for Liver Function Investigations (ALFI) is the first model to successfully estimate the probability of all-cause mortality in patients with no apparent liver disease having LFTs in primary care. While LFTs added to the model's discrimination and sensitivity, the clinical utility of ALFI remains to be established since LFTs did not improve an already high NPV for short term mortality and only modestly improved a very low PPV.
    PLoS ONE 01/2012; 7(12):e50965. · 3.53 Impact Factor
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    ABSTRACT: Alcohol misuse is a common reason for hospital admission. While there is considerable evidence from other areas that provision of specialised alcohol services can reduce alcohol intake, there is currently less evidence for medical departments in an acute hospital setting. Nottingham hospitals initiated such a service in 2002-3 based around two nurse specialists who provided input to inpatients with alcohol-related physical disease and provided links to community-based services for alcohol misuse. This service assessed 3632 patients over five years and has seen a reduction in hospital admissions, violent incidents against staff and primary care attendances. It is believed that this model of care is an effective means of intervening in people with alcohol-related problems.
    Clinical medicine (London, England) 10/2010; 10(5):435-40. · 1.69 Impact Factor
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    ABSTRACT: Assessment of liver fibrosis is important in determining prognosis and evaluating interventions. Due to limitations of accuracy and patient hazard of liver biopsy, non-invasive methods have been sought to provide information on liver fibrosis, including the European liver fibrosis (ELF) test, shown to have good diagnostic accuracy for the detection of moderate and severe fibrosis. Access to independent cohorts of patients has provided an opportunity to explore if this test could be simplified. This paper reports the simplification of the ELF test and its ability to identity severity of liver fibrosis in external validation studies in patients with chronic hepatitis C (CHC). Paired biopsy and serum samples from 347 naïve patients with CHC in three independent cohorts were analysed. Diagnostic performance characteristics were derived (AUROC, sensitivity and specificity, predictive values), and clinical utility modelling performed to determine the proportion of biopsies that could have been avoided if ELF test was used in this patient group. It was possible to simplify the original ELF test without loss of performance and the new algorithm is reported. The simplified ELF test was able to predict severe fibrosis [pooled AUROC of 0.85 (95% CI 0.81-0.89)] and using clinical utility modelling to predict severe fibrosis (Ishak stages 4-6; METAVIR stages 3 and 4) 81% of biopsies could have been avoided (65% correctly). Issues of spectrum effect in diagnostic test evaluations are discussed. In chronic hepatitis C a simplified ELF test can detect severe liver fibrosis with good accuracy.
    Journal of Viral Hepatitis 02/2010; 18(1):23-31. · 3.08 Impact Factor
  • Hepatology 01/2010; 52(4):675A-675A. · 11.19 Impact Factor
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    ABSTRACT: Autoantibodies are commonly detected in chronic hepatitis C (HCV) but their significance remains uncertain. We assessed the prevalence of anti-nuclear (ANA) and anti-smooth muscle (ASM) antibodies within a cohort of 963 treatment-naïve HCV patients. We also assessed for differences between autoantibody-positive and autoantibody-negative patients in demographics, markers of disease activity and response to anti-viral treatment. One hundred and seventy-two patients (17.9%) had at least one autoantibody, of which were 104 (10.8%) ASM, 54 (5.6%) ANA and 14 (1.5%) positive for both. Autoantibody-positive patients were older (43 vs 39 years, P = 0.001) caused by an age-related increase in ANA (but not ASM). There were no differences in gender, alcohol intake, ethnicity or viral genotype. The presence of autoantibodies, and specifically ASM, was associated with an increase in interface hepatitis score amongst men (1.1 vs 0.8, P = 0.005) but no difference in other necroinflammatory measures, liver function tests or immunoglobulins (Ig). There was no difference in initial fibrosis stage or rate of fibrosis progression. Autoantibodies did not affect response to anti-viral treatment. We conclude that autoantibodies are frequent in HCV infection. Anti-nuclear antibodies increase with age, whereas ASM antibodies are associated with interface hepatitis in men. Neither autoantibody carries increased risk of fibrosis progression or failure of therapy.
    Journal of Viral Hepatitis 06/2009; 16(5):325-31. · 3.08 Impact Factor
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    ABSTRACT: To determine the natural history of abnormalities in liver function tests (LFTs), derive predictive algorithms for liver disease and identify the most cost-effective strategies for further investigation. MEDLINE database from 1966 to September 2006, EMBASE, CINAHL and the Cochrane Library. Population-based retrospective cohort study set in primary care in Tayside, Scotland, between 1989 and 2003. Participants were patients with no obvious signs of liver disease and registered with a general practitioner (GP). The study followed up those with an incident batch of LFTs in primary care to subsequent liver disease or mortality over a maximum of 15 years. The health technologies being assessed were primary care LFTs, viral and autoantibody tests, ultrasound and liver biopsy. Measures used were the epidemiology of liver disease in Tayside (ELDIT) database, time-to-event modelling, predictive algorithms derived using the Weibull survival model, decision analyses from an NHS perspective, cost-utility analyses, and one-way and two-way sensitivity analyses. A total of 95,977 patients had 364,194 initial LFTs, with a median follow-up of 3.7 years. Of these, 21.7% had at least one abnormal liver function test (ALFT) and 1090 (1.14%) developed liver disease. Elevated transaminases were strongly associated with diagnosed liver disease, with hazard ratios (HRs) of 4.23 [95% CI (confidence interval) 3.55-5.04] for mild levels and 12.67 (95% CI 9.74-16.47) for severe levels versus normal. For gamma-glutamyltransferase (GGT), these HRs were 2.54 (95% CI 2.17-2.96) and 13.44 (10.71-16.87) respectively. Low albumin was strongly associated with all cause mortality, with ratios of 2.65 (95% CI 2.47-2.85) for mild levels and 4.99 (95% CI 4.26-5.84) for severe levels. Sensitivity for predicting events over 5 years was low and specificity was high. Follow-up time was split into baseline to 3 months, 3 months to 1 year and over 1 year. All LFTs were predictive of liver disease, and high probability of liver disease was associated with being female, methadone use, alcohol dependency and deprivation. The shorter-term models had overall c-statistics of 0.85 and 0.72 for outcome of liver disease at 3 months and 1 year respectively, and 0.88 and 0.82 for all cause mortality at 3 months and 1 year respectively. Calibration was good for models predicting liver disease. Discrimination was low for models predicting events at over 1 year. In cost-utility analyses, retesting dominated referral as an option. However, using the predictive algorithms to identify the top percentile at high risk of liver disease, retesting had an incremental cost-utility ratio of 7588 pounds relative to referral. GGT should be included in the batch of LFTs in primary care. If the patient in primary care has no obvious liver disease and a low or moderate risk of liver disease, retesting in primary care is the most cost-effective option. If the patient with ALFTs in primary care has a high risk of liver disease, retesting depends on the willingness to pay of the NHS. Cut-offs are arbitrary and in developing decision aids it is important to treat the LFT results as continuous variables.
    Health technology assessment (Winchester, England) 05/2009; 13(25):iii-iv, ix-xi, 1-134. · 5.12 Impact Factor

Publication Stats

1k Citations
550.15 Total Impact Points


  • 2004–2014
    • Nottingham University Hospitals NHS Trust
      Nottigham, England, United Kingdom
  • 2010
    • University of Southampton
      Southampton, England, United Kingdom
  • 2009
    • Centre for Digestive Diseases
      Newtown, New South Wales, Australia
    • University of Dundee
      • Undergraduate Tayside Centre for General Practice
      Dundee, Scotland, United Kingdom
  • 1998–2009
    • University of Nottingham
      • • Nottingham Digestive Diseases Centre
      • • Centre for Sports Medicine
      Nottingham, ENG, United Kingdom
  • 2003–2005
    • The Bracton Centre, Oxleas NHS Trust
      Дартфорде, England, United Kingdom
  • 2001
    • The Queen's Medical Center
      Honolulu, Hawaii, United States
  • 1994–1996
    • King's College London
      • Department of Immunobiology
      Londinium, England, United Kingdom
    • The Peninsula College of Medicine and Dentistry
      Plymouth, England, United Kingdom
  • 1991–1995
    • University of Liverpool
      • School of Medicine
      Liverpool, ENG, United Kingdom
  • 1993
    • Royal Liverpool and Broadgreen University Hospitals NHS Trust
      • Department of Medicine
      Liverpool, England, United Kingdom