Validation and analysis of prognostic scoring systems for critically ill patients with cirrhosis admitted to ICU.

INTRODUCTION: The number of patients admitted to ICU who have liver cirrhosis is rising. Current prognostic scoring tools to predict ICU mortality have performed poorly in this group. In previous research from a single centre, a novel scoring tool which modifies the Child-Turcotte Pugh score by adding Lactate concentration, the CTP + L score, is strongly associated with mortality. This study aims to validate the use of the CTP + L scoring tool for predicting ICU mortality in patients admitted to a general ICU with cirrhosis, and to determine significant predictive factors for mortality with this group of patients. This study will also explore the use of the Royal Free Hospital (RFH) score in this cohort. METHODS: A total of 84 patients admitted to the Glasgow Royal Infirmary ICU between June 2012 and Dec 2013 with cirrhosis were included. An additional cohort of 115 patients was obtained from two ICUs in London (St George's and St Thomas') collected between October 2007 and July 2009. Liver specific and general ICU scoring tools were calculated for both cohorts, and compared using area under the receiver operating characteristic (ROC) curves. Independent predictors of ICU mortality were identified by univariate analysis. Multivariate analysis was utilised to determine the most predictive factors affecting mortality within these patient groups. RESULTS: Within the Glasgow cohort, independent predictors of ICU mortality were identified as Lactate (p < 0.001), Bilirubin (p = 0.0048), PaO2/FiO2 Ratio (p = 0.032) and PT ratio (p = 0.012). Within the London cohort, independent predictors of ICU mortality were Lactate (p < 0.001), PT ratio (p < 0.001), Bilirubin (p = 0.027), PaO2/FiO2 Ratio (p = 0.0011) and Ascites (p = 0.023). The CTP + L and RFH scoring tools had the highest ROC value in both cohorts examined. CONCLUSION: The CTP + L and RFH scoring tool are validated prognostic scoring tools for predicting ICU mortality in patients admitted to a general ICU with cirrhosis.

Recurrent early-onset severe obstetric cholestasis in a patient with two variants in the ABCB4 gene.

A 36-year-old patient presented with severe early-onset obstetric cholestasis on a background of having pre-term induction of labor at 33 weeks during her only previous pregnancy. The patient had significantly abnormal liver biochemistry with a bilirubin of 78 µmol/L, ALP of 318 u/L, ALT of 280 µmol/L, and bile acid levels of 420 µmol/L. The patient received ursodeoxycholic acid 750 mg 3 times a day, rifampicin 500 mg twice a day, aspirin 150 mg once a day, and metformin 500 mg 3 times a day. However, despite this, the patient still suffered from intractable pruritus and her bile acid level was still above the 100 µmol/L target that the obstetrics team was aiming for to avoid early delivery at 32 weeks. Due to the nature and severity of her cholestasis, the patient had a number of investigations done postnatally including genetic analysis, which confirmed that the patient was heterozygous for a pathogenic variant of the ATP-binding cassette subfamily B member 4 gene (c.959C>T [p.Ser320Phe]) and also a variant of unknown significance (c.1679C>T [p.Thr560Met]).

From a documented past of the Jersey breed in Africa to a profit index linked future.

The paper reports on the prevalence and performance of the Jersey cattle breed in Africa, highlighting its geographic distribution and describing the reported performance and other related characteristics from the early 1900s to the present day. The review examines the contribution of Jersey cattle in increasing the volume and efficiency of milk production across the continent. Data relating to the Jersey cattle breed has been reported in more than 30 African countries based on available material published between 1964 and 2020. A key encompassing parameter of any reference was a well-described consideration of the Jersey cattle breed (as pure or crossbred with other exotic and/or indigenous breeds) with reported performance within a variety of production systems and agro-ecologies in Africa. The main focus was on breed and performance parameters, breed types, percentage of different breed types in specific environments, reproduction method and fertility; survival and longevity; disease incidence; and production efficiency metrics such as: feed efficiency (milk unit per dry matter intake, DMI) and milk yield (MY) per unit of body weight (BW). The main performance descriptors identified were based on observations on resilience under both abiotic (heat, nutrition) and biotic (incidences of pests and diseases) stressors, milk production, BW, nutrition and utilisation of feed resources. From the literature consulted, we grouped key dairy cattle performance characteristics reported in each country under the following areas to aid comparisons; a. Milk production (Milk nutrient value, daily MY, lifetime MY and annual MY); b. Fertility traits and AFC; c. Survival and longevity, d. Production efficiency (Feed efficiency, milk per unit BW and milk per unit DMI and e. Disease incidences. Results of the review showed that the smaller stature and lower maintenance nutrient requirements of the Jersey breed means that it is better suited to tolerate the tropical production conditions in the African small-scale dairy farming sector. Detailed analyses on MY and survival showed that Jersey crosses with exotic and African indigenous breeds performed better than purebred cattle with strong evidence to support the suitability of the Jersey breed in crossbreeding with indigenous breeds for use in smallholder production systems.

Clostridium difficile-associated disease acquired in the cardiothoracic intensive care unit.

OBJECTIVES: To determine the prevalence, severity, and outcome associated with Clostridium difficile-associated disease (CDAD) acquired while in the cardiothoracic intensive care unit (CTICU). DESIGN: A 5-year retrospective study. SETTING: The CTICU. PARTICIPANTS: All CTICU patients with a positive C difficile stool toxin assay 48 hours after admission. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The results of all CTICU patients with a positive C difficile stool toxin assay were obtained from the Microbiology Department. Each patient's medical notes and charts then were reviewed in turn. A total of 27 of 5,199 (0.5%) CTICU patients acquired CDAD. The median age was 74 years (IQR 68-77), and 17 (63%) patients were male. There were 21 (78%) surgical patients; 13 (62%) were elective admissions. The most frequent diagnosis on admission was valvular heart disease (10 [37%] patients). Sixteen (59%) patients underwent coronary artery bypass graft (CABG) surgery and/or valvular heart surgery. The median interval between CTICU admission and CDAD diagnosis was 10 days (IQR 5-18). Previously identified risk factors for ICU-acquired CDAD included age >65 years (23), antibiotic use (26), and medical device requirements (27). At the time of diagnosis, 14 (52%) patients had moderate CDAD. After treatment initiation, 8 (30%) patients developed worsening CDAD. The 30-day in-hospital mortality rate for CTICU-acquired CDAD was 26% (7 patients). CONCLUSIONS: C difficile-associated disease rarely is acquired in the CTICU. Approximately one third of patients may experience disease progression, and just over a quarter may die within 30 days of diagnosis. The implementation of recommended severity definitions and treatment algorithms may reduce complication rates and merits prospective evaluation.

Palliative Long-Term Abdominal Drains Versus Large Volume Paracentesis in Refractory Ascites Due to Cirrhosis (REDUCe Study): Qualitative Outcomes.

CONTEXT: Palliative care remains suboptimal in end-stage liver disease (ESLD). OBJECTIVES: We report qualitative outcomes from the REDUCe study. We aimed to explore and contrast experiences/perceptions/care pathways of patients with refractory ascites due to ESLD randomized to either palliative long-term abdominal drains (LTADs) (allow home drainage) vs. large volume paracentesis (LVP) (hospital drainage). METHODS: Concurrent embedded qualitative study in a 12-week feasibility randomized controlled trial. Telephone interviews were conducted, data being recorded, transcribed verbatim, and analyzed using applied thematic analysis, considered in terms of a pathway approach toward accessing health care. Quantitative outcomes were collected (integrated palliative outcome scale, short-form liver disease quality of life, EQ-5D-5 L, Zarit Burden Interview-12). RESULTS: Fourteen patients (six allocated LTAD and eight LVP) and eight nurses participated in the qualitative study. The patient journey in the LVP group could be hindered by challenges along the entire care pathway, from recognizing the need for drainage to a lengthy wait in hospital for drainage and/or to be discharged. These issues also impacted upon caregivers. In contrast, LTADs appeared to transform this care pathway at all levels across the patient's journey by removing the need for hospital drainage. Additional benefits included personalized care, improved symptom control of ascites, being at home, and regular support from community nurses. Nurses also viewed the LTAD favorably, though expressed the need for additional support should this become standard of care. CONCLUSION: Patients and nurses expressed acceptability of palliative LTAD in ESLD and preference for this approach in enabling care at home. Proceeding to a definitive trial is feasible. TRIAL REGISTRATION: ISRCTN30697116, date assigned: 07/10/2015.

A study of muscle tissue oxygenation and peripheral microcirculatory dysfunction in cirrhosis using near infrared spectroscopy.

BACKGROUND: The circulatory dysfunction associated with cirrhosis is well described. Reduced systemic vascular resistance and high cardiac output are the main features of the hyperdynamic state, but involvement of the peripheral microcirculation in this process is poorly understood. Near infrared spectroscopy (NIRS) has been used to assess muscle tissue oxygenation (StO(2)) in haemorrhagic and septic shock. Vascular occlusion testing (VOT) can produce dynamic changes in StO(2) which represent tissue oxygen extraction, delivery, and hence, surrogate markers of microvascular function. AIMS: We aimed to investigate dynamic StO(2) changes in the peripheral microcirculation of patients with cirrhosis. METHODS: Thirty-five subjects were examined (25 cirrhosis, 10 healthy volunteers) with an InSpectra 650 StO(2) monitor and 15 mm thenar probe. Brachial VOT was applied at systolic blood pressure +50 mmHg for 3 min, in triplicate. Dynamic StO(2) parameters are reported for baseline, downslope, upslope, area over ischaemic curve, overshoot, area under recovery curve and recovery time. RESULTS: Patients with cirrhosis demonstrated significantly larger post-occlusive hyperaemic variables compared with volunteers: overshoot (17 vs 15%, P=0.009), area under recovery curve (25.1 vs 16.3 %/min, P<0.001) and recovery time (3.0 vs 2.2 min, P<0.001). Magnitude of change was also seen to increase with disease stage as defined by Child-Pugh score. Serial VOT revealed microcirculatory ischaemic adaptation in volunteers, which was absent in cirrhosis. CONCLUSIONS: NIRS can identify dynamic changes in muscle tissue oxygenation in cirrhosis which are compatible with microcirculatory vasodilatation. Ischaemic adaptation was seen in controls but not in patients with cirrhosis. NIRS techniques offer a novel approach to the assessment of peripheral vascular dysfunction in cirrhosis.

Clostridium difficile infection and inflammatory bowel disease.

The importance of Clostridium difficile (C. difficile) infection amongst patients with inflammatory bowel disease (IBD) is increasingly being recognized. Recent studies have demonstrated a concerning trend towards increased rates of infection, morbidity, mortality and health costs, and guidelines now promote testing for C. difficile in IBD patients experiencing a relapse. This critical review focuses on the epidemiology, risk factors, pathogenesis, treatment options and outcomes associated with C. difficile infection in patients with IBD.

Randomised clinical trial: palliative long-term abdominal drains vs large-volume paracentesis in refractory ascites due to cirrhosis.

BACKGROUND: Palliative care remains suboptimal in end-stage liver disease. AIM: To inform a definitive study, we assessed palliative long-term abdominal drains in end-stage liver disease to determine recruitment, attrition, safety/potential effectiveness, questionnaires/interview uptake/completion and make a preliminary cost comparison. METHODS: A 12-week feasibility nonblinded randomised controlled trial comparing large-volume paracentesis vs long-term abdominal drains in refractory ascites due to end-stage liver disease with fortnightly home visits for clinical/questionnaire-based assessments. Study success criteria were attrition not >50%, <10% long-term abdominal drain removal due to complications, the long-term abdominal drain group to spend <50% ascites-related study time in hospital vs large-volume paracentesis group and 80% questionnaire/interview uptake/completion. RESULTS: Of 59 eligible patients, 36 (61%) were randomised, 17 to long-term abdominal drain and 19 to large-volume paracentesis. Following randomisation, median number (IQR) of hospital ascitic drains (long-term abdominal drain group vs large-volume paracentesis group) were 0 (0-1) vs 4 (3-7); week 12 serum albumin (g/L) and serum creatinine (µmol/L) were 29 (26.5-32.5) vs 30 (25-35) and 104.5 (81-115.5) vs 127 (63-158) respectively. Total attrition was 42% (long-term abdominal drain group 47%, large-volume paracentesis group 37%). Median (IQR) fortnightly community/hospital/social care ascites-related costs and percentage study time in hospital were lower in the long-term abdominal drain group, £329 (253-580) vs £843 (603-1060) and 0% (0-0.74) vs 2.75% (2.35-3.84) respectively. Self-limiting cellulitis/leakage occurred in 41% (7/17) in the long-term abdominal drain group vs 11% (2/19) in the large-volume paracentesis group; peritonitis incidence was 6% (1/17) vs 11% (2/19) respectively. Questionnaires/interview uptake/completion were ≥80%; interviews indicated that long-term abdominal drains could transform the care pathway. CONCLUSIONS: The REDUCe study demonstrates feasibility with preliminary evidence of long-term abdominal drain acceptability/effectiveness/safety and reduction in health resource utilisation. TRIAL REGISTRATION: ISRCTN30697116, date assigned: 07/10/2015.

Chronic liver disease--an increasing problem: a study of hospital admission and mortality rates in England, 1979-2005, with particular reference to alcoholic liver disease.

AIMS: To determine time trends in hospital admissions for chronic liver disease in England between 1989/1990 and 2002/2003, mortality rates in England and Wales between 1979 and 2005, and the influence of alcohol-related disease on these trends. METHODS: Hospital episode statistics for admissions in England were obtained from the Information Center for Health and Social Care and mortality data for England and Wales from the Office for National Statistics. RESULTS: Hospital admission rates for chronic liver disease increased by 71% in males and 43% in females over the study period. This increase was largely due to alcoholic liver disease, admission rates for which more than doubled between 1989/1990 and 2002/2003. While there was a smaller rise for chronic viral hepatitis B and C, admission rates declined for hepatitis A, autoimmune hepatitis, and primary biliary cirrhosis. Mortality rates for chronic liver disease more than doubled between 1979 and 2005. Two thirds of these deaths were attributable to alcohol-related liver disease in 2005. The highest rate of alcoholic liver disease mortality was in the 45-64 age group, and the largest percentage increase between 1979 and 2005 occurred in the 25-34 age group. CONCLUSIONS: Hospital admissions and mortality in England from chronic liver disease are increasing. The underlying reasons are complex, but alcohol-induced liver disease makes a major contribution. There are clear social and health implications if the trend continues and addressing alcohol-related liver disease should be a public health priority.

Do critically ill liver patients experience negative bias? A web-based survey examining doctors opinions to critical care escalation.

OBJECTIVE: To test the hypothesis that there is negative bias towards escalating levels of care in decompensated cirrhosis, compared with other patient groups. DESIGN: An electronic survey containing eight acute clinical scenarios with equivalent physiological derangement, in which respondents were asked to score the degree to which they would advocate for intensive care unit admission on a scale of 1-10. Scenarios included respiratory, haematology, vascular, renal, gastrointestinal, postoperative and hepatological conditions. Follow-up questions examined the reasons why the patient should or should not be transferred, and enquired about ceilings of care, end-of-life decisions, degree of organ support and healthcare financial rationing. 273 doctors responded. SETTING: Secondary care hospitals in south of England. PATIENTS: None involved. INTERVENTIONS: None. MAIN OUTCOME MEASURES: Advocacy score (1-10) and subsidiary responses. RESULTS: The hepatology patient ranked 4th of 8 with a mean advocacy score of 7.2. There were no significant differences between intensivists and physicians or between grades of seniority. Of those less likely to escalate (score 1-5, n=42), the reasons given were based on unsurvivability or excessive burden of treatment rather than aetiology. One-fifth cited 'lifestyle decision'. 25 (62.5%) respondents not favouring escalation would make the patient DNACPR, 17 (42.5%) would stipulate ward-based care only and a small minority would instigate active palliation. Of those favouring escalation (advocacy score 6-10), 70% (n=122) would consider unlimited organ support. Fifty-four (29.5% of those who answered) said they 'sometimes' or 'frequently' consider resource allocation when making decisions about escalation of care. CONCLUSIONS: When compared with a variety of acute medical scenarios, doctors did not overly appear to exhibit therapeutic nihilism for patients with decompensated liver disease; however, significant variation in interpretation of the data and management approaches was identified.