Systematic review: the treatment of noncardiac chest pain with antidepressants.

Aliment Pharmacol Ther. 2012 Jan 13;

Authors: Nguyen TM, Eslick GD

Abstract
BACKGROUND: Noncardiac chest pain (NCCP) is a common condition, affecting approximately 25% of the general population. The cause of NCCP can be classified as gastro-oesophageal reflux disease (GERD)-related NCCP, where antireflux therapy is the main treatment modality or alternatively as non-GERD-related NCCP, where pain modulators, including antidepressants, are utilised. AIM: To provide a systematic review evaluating the evidence for the use of antidepressants in the treatment of non-GERD-related NCCP. METHODS: A computerised literature and manual search was conducted to identify relevant randomised, placebo-controlled studies, published in any language for the evaluation of the effectiveness of antidepressant as a therapeutic intervention for NCCP. RESULTS: Six randomised placebo-controlled trials of antidepressant treatment for NCCP were identified. The medications included were selective serotonin reuptake inhibitors [paroxetine (n = 2), sertraline (n = 1)], tricyclic antidepressant [impramine (n = 1)], serotonin-norepinephrine reuptake inhibitor [venlafaxine (n = 1)] and a triazolopyridine [trazodone (n = 1)]. The percentage reduction in chest pain was statistically significant with venlafaxine (50% vs. 10%; P < 0.001), sertraline (63% vs. 15%; P = 0.02) and imipramine (52% vs. 1%; P = 0.03). The improvement in chest pain symptoms was independent of improvement in depression scores. Clinical global improvement also significantly improved in patients on venlafaxine, sertraline, paroxetine and trazodone. The percentage of patients in treatment groups reporting adverse effects were relatively high compared with those in placebo groups, although majority were statistically insignificant or significance was not reported. Nonetheless, adverse events were the reported reason for discontinuation of trials in 53% of patients from the antidepressant groups compared with 29% from the placebo group. CONCLUSIONS: There is modest evidence for the benefit of antidepressants in reducing NCCP and improving patients' general health. However, there is significant heterogeneity amongst the studies with several study limitations to warrant more rigorous trials and to assess the usefulness of low-dose antidepressants in non-GERD NCCP.

PMID: 22239853 [PubMed - as supplied by publisher]

Outcomes in community-acquired Clostridium difficile infection.

Aliment Pharmacol Ther. 2012 Jan 10;

Authors: Khanna S, Pardi DS, Aronson SL, Kammer PP, Baddour LM

Abstract
BACKGROUND: Community-acquired Clostridium difficile infection (CA-CDI) is an increasingly appreciated condition. It is being described in populations lacking traditional predisposing factors that have been previously considered at low-risk for this infection. As most studies of CDI are hospital-based, outcomes in these patients are not well known. AIM: To examine outcomes and their predictors in patients with CA-CDI. METHODS: A sub-group analysis of a population-based epidemiological study of CDI in Olmsted county, Minnesota from 1991-2005 was performed. Data regarding outcomes, including severity, treatment response, need for hospitalisation and recurrence were analysed. RESULTS: Of 157 CA-CDI cases, the median age was 50 years and 75.3% were female. Among all CA-CDI cases, 40% required hospitalisation, 20% had severe and 4.4% had severe-complicated infection, 20% had treatment failure and 28% had recurrent CDI. Patients who required hospitalisation were significantly older (64 years vs. 44 years, P < 0.001), more likely to have severe disease (33.3% vs. 11.7%, P = 0.001), and had higher mean Charlson comorbidity index scores (2.06 vs. 0.84, P = 0.001). They had similar treatment failure and recurrence rates as patients who did not require hospitalisation. CONCLUSIONS: Community-acquired Clostridium difficile infection can be associated with complications and poor outcomes, including hospitalisation and severe Clostridium difficile infection. As the incidence of community-acquired Clostridium difficile infection increases, clinicians should be aware of risk factors (increasing age, comorbid conditions and disease severity) that predict the need for hospitalisation and complications in patients with community-acquired Clostridium difficile infection.

PMID: 22229532 [PubMed - as supplied by publisher]

Systematic review: the treatment of noncardiac chest pain.

Aliment Pharmacol Ther. 2011 Nov 13;

Authors: Hershcovici T, Achem SR, Jha LK, Fass R

Abstract
Background? Treatment of noncardiac chest pain (NCCP) remains a challenge. This is in part due to the heterogenous nature of this disorder. Several conditions are associated with NCCP including gastro-oesophageal reflux disease (GERD), oesophageal dysmotility, oesophageal hypersensitivity as well as others. Aim  To determine the currently available therapeutic modalities for NCCP. Methods? We performed a systematic review of the literature that was published between January, 1980 and March, 2011. We identified 734 studies; 68 of them met entry criteria. Results? Patients with GERD-related NCCP should receive proton pump inhibitors (PPI) twice daily for at least 8?weeks. Smooth muscle relaxants are only recommended for temporary relief of NCCP with motility disorders. Botulinum toxin injection of the distal oesophagus may be effective in the treatment of NCCP and spastic oesophageal motility disorders. Studies assessing the value of tricyclic antidepressants, trazodone and selective serotonine reuptake inhibitors in NCCP are relatively small, but suggest an oesophageal analgesic effect in NCCP patients that is limited by their side effects profile. The usage of theophylline to treat patients with non-GERD-related NCCP should be weighed against its potential toxicity. Use of complementary medicine has been scarcely studied in NCCP. Patients with coexisting psychological morbidity or those not responding to any medical therapy should be considered for psychological intervention. Cognitive behavioural therapy and hypnotherapy may be useful in the treatment of NCCP. Conclusions? Patients with GERD-related noncardiac chest pain should be treated with at least double dose PPI. The primary treatment for non-GERD-related noncardiac chest pain, regardless if oesophageal dysmotility is present, is pain modulators.

PMID: 22077344 [PubMed - as supplied by publisher]

Concomitant use of clopidogrel and proton pump inhibitors is not associated with major adverse cardiovascular events following coronary stent implantation.

Aliment Pharmacol Ther. 2011 Nov 4;

Authors: Schmidt M, Johansen MB, Robertson DJ, Maeng M, Kaltoft A, Jensen LO, Tilsted HH, Bøtker HE, Sørensen HT, Baron JA

Abstract
Background? Cytochrome P450 inhibition by proton pump inhibitors (PPIs) may attenuate the effectiveness of clopidogrel. Aim? To examine whether PPI use modifies the association between clopidogrel use and major adverse cardiovascular events (MACE) after percutaneous coronary intervention (PCI) with stent implantation, using time-varying drug exposure ascertainment. Methods? We conducted this population-based cohort study in Western Denmark (population 3?million) using medical databases. We identified all 13?001 patients with coronary stent implantation between 2002 and 2005 and ascertained their reported comorbidities. During the recommended 12-month postintervention treatment period, we tracked use of clopidogrel and PPI and the rate of MACE. We used Cox regression to compute hazard ratios (HRs), controlling for potential confounders. Results? During follow-up, one or more prescriptions were redeemed by 91% of patients for clopidogrel and by 21% of patients for PPIs. Of the patients, 15% experienced a MACE. The adjusted HR for MACE comparing clopidogrel use with non-use was 0.57 [95% confidence interval (CI): 0.44-0.74] among PPI users and 0.47 (95% CI: 0.42-0.53) among PPI non-users, yielding an interaction effect (i.e. relative rate increase) of 1.20 (95% CI: 0.91-1.58). PPI users treated from before PCI had a 25% increased rate of MACE compared to PPI non-users, independent of clopidogrel use [adjusted HR?=?1.24 (95% CI: 0.97-1.58) for clopidogrel users and 1.26 (95% CI: 0.97-1.63) for clopidogrel non-users]. Conclusions? The use of PPIs as a class did not modify the protective effect of clopidogrel, but its use was associated with major adverse cardiovascular events itself, particularly among patients having used PPIs before percutaneous coronary intervention.

PMID: 22050009 [PubMed - as supplied by publisher]

Review article: the aetiology, investigation and management of diarrhoea in the HIV-positive patient.

Aliment Pharmacol Ther. 2011 Jul 20;

Authors: Feasey NA, Healey P, Gordon MA

Background? Diarrhoea is a common presentation throughout the course of HIV disease. Aims? To review the literature relating to aetiology, investigation and management of diarrhoea in the HIV-infected adult. Methods? The PubMed database was searched using major subject headings 'AIDS' or 'HIV' and 'diarrhoea' or 'intestinal parasite'. The search was limited to adults and to studies with >10 patients. Results? Diarrhoea affects 40-80% of HIV-infected adults untreated with antiretroviral therapy (ART). First-line investigation is by stool microbiology. Reported yield varies with geography and methodology. Molecular and immunological methods and special stains have improved diagnostic yield. Endoscopy is diagnostic in 30-70% of cases of pathogen-negative diarrhoea and evidence supports flexible sigmoidoscopy as a first line screening procedure (80-95% sensitive for CMV colitis), followed by colonoscopy and terminal ileoscopy. Radiology is useful to assess severity, distribution, complications and to diagnose HIV-related malignancies. Side effects and compliance with ART are important considerations in assessment. There is a good evidence base for many specific therapies, but optimal treatment of cryptosporidiosis is unclear and only limited data support symptomatic treatments. Conclusions? The immunological response to HIV infection and ART remains incompletely understood. ART regimens need to be optimised to suppress HIV while minimising side effects. Effective agents for management of cryptosporidiosis are lacking. There is an urgent need for enhanced regional diagnostic facilities in countries with a high prevalence of HIV. The ongoing roll-out of ART in low-resource settings will continue to change the aetiology and management of this problem, necessitating ongoing surveillance and study.

PMID: 21777262 [PubMed - as supplied by publisher]

Randomised clinical trial: rabeprazole plus aspirin is not inferior to rabeprazole plus clopidogrel for the healing of aspirin-related peptic ulcer.

Aliment Pharmacol Ther. 2011 Jul 5;

Authors: Luo JC, Huang KW, Leu HB, Chen LC, Hou MC, Li CP, Lu CL, Lin HC, Lee FY, Lee SD

Background? Clopidogrel does not inhibit prostaglandin synthesis. As a result, clopidogrel's incidence of peptic ulcer disease (PUD) and ulcer bleeding is lower than aspirin's. Aim? To compare the healing rate in aspirin-related dyspeptic ulcer patients who were given proton pump inhibitor (PPI) plus aspirin or PPI plus clopidogrel. Methods? Patients with aspirin-related nonbleeding symptomatic ulcers were randomised to receive rabeprazole (20?mg/day) plus aspirin (100?mg/day) or rabeprazole (20?mg/day) plus clopidogrel (75?mg/day) for 12?weeks. The primary endpoint was the successful treatment of PUD as characterised by intention-to-treat at the end of therapy. Results? Two hundred and eighteen patients (109 in the aspirin group and 109 in the clopidogrel group) were enrolled. There were no statistical demographic differences between the group that received aspirin and the group that received clopidogrel. The PUD treatment success rate was also statistically equal between the clopidogrel and aspirin groups (86.2% vs. 90.0%, P?=?0.531). Neither group experienced ulcer-related bleeding. Multivariate logistic regression analysis showed that large ulcer size (>10?mm) (OR: 6.29, 95% CI: 2.58-15.37) and past history of PUD (OR: 3.69, 95% CI: 1.24-10.97) were important predictors of unsuccessful therapy for aspirin-related PUD. Conclusions? Rabeprazole plus aspirin is not inferior to rabeprazole plus clopidogrel in treating aspirin-related symptomatic PUD. Large ulcer size (>10?mm) and past history of PUD are important predictors of unsuccessful therapy (NCT 01037491).

PMID: 21726257 [PubMed - as supplied by publisher]

Review article: the diagnosis and investigation of obscure gastrointestinal bleeding.

Aliment Pharmacol Ther. 2011 Jun 21;

Authors: Liu K, Kaffes AJ

Background? Obscure gastrointestinal bleeding (OGIB) is a commonly encountered clinical problem in gastroenterology and is associated with significant morbidity and mortality. The investigation and management of OGIB has changed dramatically over the past decade with the advent of newer gastroenterological and radiological technologies. Aim? To review the current evidence on the diagnosis and investigation of OGIB. Methods? We searched the PubMed database (1985-2010) for full original articles in English-language journals relevant to the investigation of OGIB. The search terms we used were 'gastrointestinal bleeding' or 'gastrointestinal hemorrhage' or 'small bowel bleeding' each in combination with 'obscure', or 'capsule endoscopy', or 'enteroscopy' or 'enterography' or 'enteroclysis'. Results? Capsule endoscopy (CE) or double balloon enteroscopy (DBE) should be first line investigations. They are complimentary procedures with comparable high diagnostic yields. DBE is also able to provide therapeutic intervention. Newer technologies such as single balloon and spiral enteroscopy are currently being evaluated. Radiological and nuclear medicine investigations, such as CT enterography and CT enteroclysis, are alternative diagnostic tools when CE or DBE are contraindicated. Repeating the gastroscopy and/or colonoscopy may be considered in selective situations. An algorithm for investigation of obscure bleeding is proposed. Conclusions? The development of capsule endoscopy and double balloon enteroscopy has transformed the approach to the evaluation and management of obscure gastrointestinal bleeding over the past decade. Older diagnostic modalities still play a complementary, but increasingly selective role.

PMID: 21692820 [PubMed - as supplied by publisher]

Multicentre comparison of the Glasgow Blatchford and Rockall scores in the prediction of clinical end-points after upper gastrointestinal haemorrhage.

Aliment Pharmacol Ther. 2011 Jun 26;

Authors: Stanley AJ, Dalton HR, Blatchford O, Ashley D, Mowat C, Cahill A, Gaya DR, Thompson E, Warshow U, Hare N, Groome M, Benson G, Murray W

Background? The Glasgow Blatchford Score (GBS) is increasingly being used to predict intervention and outcome following upper gastrointestinal haemorrhage (UGIH). Aim? To compare the GBS with both the admission and full Rockall scores in predicting specific clinical end-points following UGIH. Patients and methods? Data on consecutive patients presenting to four UK hospitals were collected. Admission history, clinical and laboratory data, endoscopic findings, treatment and clinical follow-up were recorded. Using ROC curves, we compared the three scores in the prediction of death, endoscopic or surgical intervention and transfusion. Results? A total of 1555 patients (mean age 56.7?years) presented with UGIH during the study period. Seventy-four (4.8%) died, 223 (14.3%) had endoscopic or surgical intervention and 363 (23.3%) required transfusion. The GBS was similar at predicting death compared with both the admission Rockall (area under ROC curve 0.804 vs. 0.801) and full Rockall score (AUROC 0.741 vs. 0.790). In predicting endo-surgical intervention, the GBS was superior to the admission Rockall (AUROC 0.858 vs. 0.705; P?<?0.00005) and similar to the full Rockall score (AUROC 0.822 vs. 0.797). The GBS was superior to both admission Rockall (AUROC 0.944 vs. 0.756; P?<?0.00005) and full Rockall scores (AUROC 0.935 vs. 0.792; P?<?0.00005) in predicting need for transfusion. Conclusions? Despite not incorporating age, the GBS is as effective as the admission and full Rockall scores in predicting death after UGIH. It is superior to both the admission and full Rockall scores in predicting need for transfusion, and superior to the admission Rockall score in predicting endoscopic or surgical intervention.

PMID: 21707681 [PubMed - as supplied by publisher]

Meta-analysis: antibiotic prophylaxis for cirrhotic patients with upper gastrointestinal bleeding - an updated Cochrane review.

Aliment Pharmacol Ther. 2011 Jun 27;

Authors: Chavez-Tapia NC, Barrientos-Gutierrez T, Tellez-Avila F, Soares-Weiser K, Mendez-Sanchez N, Gluud C, Uribe M

Background? Antibiotic prophylaxis seems to decrease the incidence of bacterial infections in patients with cirrhosis and upper gastrointestinal bleeding and is considered standard of care. However, there is no updated information regarding the effects of this intervention. Aim? To assess the benefits and harms of antibiotic prophylaxis in cirrhotic patients with gastrointestinal bleeding by performing a systematic review of randomised trials. Methods? We searched The Cochrane Hepato-Biliary Group Controlled Trials Register, The Cochrane Central Register of Controlled Trials in The Cochrane Library, MEDLINE, EMBASE and Science Citation Index EXPANDED until June 2010. We statistically combined data calculating relative risk (RR) for dichotomous outcomes and mean difference (MD) for continuous outcomes. Results? Twelve trials (1241 patients) evaluating antibiotic prophylaxis against placebo or no antibiotic prophylaxis were included. Antibiotic prophylaxis was associated with reduced mortality (RR 0.79, 95% CI 0.63-0.98), mortality from bacterial infections (RR 0.43, 95% CI 0.19-0.97), bacterial infections (RR 0.35, 95% CI 0.26-0.47), rebleeding (RR 0.53, 95% CI 0.38-0.74) and days of hospitalisation (MD -1.91, 95% CI -3.80-0.02). Trials analysing rebleeding rate and hospitalisation length are still scarce, thus, caution should be exerted when interpreting the results. Conclusion? Antibiotic prophylaxis in patients with cirrhosis and upper gastrointestinal bleeding significantly reduced bacterial infections, and reduce all-cause mortality, bacterial infection mortality, rebleeding events and hospitalisation length. Novel clinically significant outcomes were included in this meta-analysis. Some benefits are biased and the risks are not yet properly assessed, this encourages future research in this field.

PMID: 21707680 [PubMed - as supplied by publisher]

Review article: faecal transplantation therapy for gastrointestinal disease.

Aliment Pharmacol Ther. 2011 Jun 20;

Authors: Landy J, Al-Hassi HO, McLaughlin SD, Walker AW, Ciclitira PJ, Nicholls RJ, Clark SK, Hart AL

Background? Evidence is emerging regarding the relationship between a dysbiosis of the human gut microbiota and a number of gastrointestinal diseases as well as diseases beyond the gut. Probiotics have been investigated in many gastrointestinal disease states, with variable and often modest outcomes. Faecal transplantation is an alternative approach to manipulate the gut microbiota. Aims? To review the use of faecal transplantation therapy for the management of gastrointestinal disorders. Methods? Available articles on faecal transplantation in the management of gastrointestinal disorders were identified using a Pubmed search and bibliographies of review articles on the subject were collated. Results? A total of 239 patients who had undergone faecal transplantation were reported. Seventeen of 22 studies of faecal transplantation were in fulminant or refractory Clostridium difficile. Studies of faecal transplantation are heterogeneous regarding the patients, donors, screening, methods of administration and definition of response. Faecal transplantation for C. difficile has been demonstrated to be effective in 145/166 (87%) patients. Small numbers of patients are reported to have undergone successful faecal transplantation for irritable bowel syndrome and inflammatory bowel disease. Conclusions? Faecal transplantation has been reported with good outcomes for fulminant and refractory C. difficile. No adverse effects of faecal transplantation have been reported. However, there are no level 1 data of faecal transplantation and reports to date may suffer from reporting bias of positive outcomes and under-reporting of adverse effects. This therapy holds great promise, where a dysbiosis of the gut microbiota is responsible for disease and further studies are necessary to explore this potential.

PMID: 21682755 [PubMed - as supplied by publisher]

Review article: cyclic vomiting syndrome in adults - rediscovering and redefining an old entity.

Aliment Pharmacol Ther. 2011 Jun 12;

Authors: Hejazi RA, McCallum RW

Background? Cyclic vomiting syndrome is a disorder characterised by recurrent episodes of severe nausea and vomiting separated by symptom-free periods. Aims? To review the history, epidemiology, clinical aspects, pathophysiology, diagnosis and treatments of adult cyclic vomiting syndrome as well as to identify areas for further clinical research and the unanswered questions in this field. Methods? We conducted a PubMed search using such keywords as cyclic vomiting syndrome; nausea; vomiting; pathophysiology; diagnosis; treatment; trigger factors; gastric emptying test; autonomic nerve function test; gastrointestinal hormones; outcome and natural history and combined this information with the knowledge and extensive clinical research and publications from the authors. Results? Available data show that in adult cyclic vomiting syndrome, severe epigastric and sometimes diffuse abdominal pain accompanies most cycles of nausea and vomiting interspersed with periods of symptomatic remission. Psychological disorders, specifically anxiety and depression are common, and gastric emptying is actually rapid in approximately 60% of patients and normal in the remainder. There is an impressive and sustained response to high-dose tricyclic antidepressants. In up to 15% who are regarded as poor responders to tricyclic antidepressants, a predictable profile can be identified related to co-existing psychological disorders, marijuana use, poorly controlled migraine headache or chronic narcotic use. Conclusions? Cyclic vomiting syndrome in adults is an entity that is being increasingly recognised, but the need to educate Internists, Gastroenterologists and Emergency Department staff remains an ongoing challenge.

PMID: 21668458 [PubMed - as supplied by publisher]

Abnormal liver tests in people aged 75 and above: prevalence and association with mortality.

Aliment Pharmacol Ther. 2011 Jun 1;

Authors: Fleming KM, West J, Aithal GP, Fletcher AE

Background? Despite their common use the occurrence and consequences of abnormal liver tests remain unclear. Aims? To estimate the prevalence and mortality associated with abnormal liver tests in people aged 75?years and above. Methods? A cohort study on 13?276 people aged 75?years and above, registered with general practices, with a valid measurement of one or more liver test, calculating the prevalence of abnormal aspartate transaminase (AST), alkaline phosphatase (ALP) or bilirubin. Hazard ratios (HRs) were calculated for all-cause and cause-specific mortality comparing elderly patients with abnormal liver tests to elderly patients with normal liver tests. Results? At least one abnormal liver test was found in 2175 subjects (16.1%, 95% CI [15.4%, 16.7%]). The prevalence of a single abnormal liver test was 3.3% (95% CI [3.0%, 3.7%]) for AST, 9.2% (95% CI [8.8%, 9.7%]) for ALP and 5.4% (95% CI [5.1%, 5.9%]) for bilirubin. Abnormal AST, ALP and bilirubin were associated with increased risks of all-cause mortality; adjusted HRs, 1.27(95% CI [1.09, 1.47]), 1.47(95% CI [1.35, 1.61]) and 1.15(95% CI [1.02, 1.30]), respectively. Abnormal AST and ALP were associated with sevenfold and sixfold increased risk of death from liver disease, respectively. Two or more abnormal liver tests were associated with 2-fold and 17-fold increased risk of death from cancer and liver disease, respectively. Of the causes examined, absolute mortality rates were highest for cardiovascular disease in subjects with and without abnormal liver tests. Conclusions? Abnormal liver tests occur commonly in elderly people and are associated with a modest increase in all-cause mortality. There was a strong association with liver disease; however, the majority of deaths were not due to this cause.

PMID: 21631558 [PubMed - as supplied by publisher]

Optimising the care of patients with cirrhosis and gastrointestinal haemorrhage: a quality improvement study.

Aliment Pharmacol Ther. 2011 May 17;

Authors: Johnson EA, Spier BJ, Leff JA, Lucey MR, Said A

Background? Patients with cirrhosis and gastrointestinal haemorrhage are a complex group with high thirty-day mortality rates. Aim? To evaluate the quality of care delivered to patients admitted with gastrointestinal (GI) haemorrhage to a tertiary care centre before and after implementing a quality improvement initiative for better adherence to practice standards. Methods? This is a prospective cohort study. All patients admitted to a tertiary care centre with a GI haemorrhage and known or suspected chronic liver disease were evaluated before and after the quality improvement initiative was implemented. Interventions to improve quality of care included the delivery of educational sessions for medical practitioners, and creation and implementation of standardised admission order sets. Quality of care measures included delivery of prophylactic antibiotics (PAs) within 24?h of admission, delivery of a somatostatin analogue (SA) and use of a proton pump inhibitor (PPI); optimal care was defined as receiving all three. Secondary outcomes included hospital length of stay (LOS) and 30-day readmission rate. Results? In comparing the preintervention and postintervention groups, we found significant gains in delivering PAs (57% vs. 75%, P?=?0.05), SAs (54% vs. 76%, P?=?0.013) and overall optimal care (41% vs. 65%, P?=?0.008). Use of PPIs did not change and remained in accordance with guidelines (90% vs. 87%, P?=?0.67). Hospital LOS remained similar between the two groups (6.8 vs. 7.1, P?=?0.88), whereas the 30-day readmission decreased (41% vs. 13%, P?=?0.001). Conclusion? Implementation of quality improvement initiatives, such as targeted educational efforts and standardised order sets, can improve the quality of care delivered and patient outcomes in patients with cirrhosis and GI haemorrhage.

PMID: 21585407 [PubMed - as supplied by publisher]

The systemic inflammatory response syndrome and sequential organ failure assessment scores are effective triage markers following paracetamol (acetaminophen) overdose.

Aliment Pharmacol Ther. 2011 May 10;

Authors: Craig DG, Reid TW, Martin KG, Davidson JS, Hayes PC, Simpson KJ

Background? The systemic inflammatory response syndrome (SIRS) and sequential organ failure assessment (SOFA) scores are widely used as prognostic markers in critical care settings and could improve triage of high-risk paracetamol (acetaminophen) overdose patients. Aim? To evaluate the prognostic accuracy of the SIRS and SOFA scores following single time point paracetamol overdose. Methods? Analysis of 100 single time point paracetamol overdoses admitted to a tertiary liver centre, with subsequent prospective validation of identified thresholds. Individual laboratory samples were correlated with the corresponding clinical parameters in relation to time post-overdose, and the daily SOFA and SIRS scores calculated. Results  A total of 74 (74%) patients developed the SIRS, which occurred significantly earlier in patients who died (n?=?21) compared with spontaneous survivors (n?=?53, P?=?0.05). The SIRS occurred in 70 (70%) patients by 96?h post-overdose, with a 30% mortality rate; compared with 0% mortality in the 30 non-SIRS patients (P?=?0.001). Median SOFA scores were significantly higher in nonsurvivors at 48 (P?=?0.009), 72 (P?<?0.001), and 96?h (P?<?0.001). A SOFA score >7 during the first 96?h post-overdose predicted death/transplantation with a sensitivity of 95.0 (95% CI 78.5-99.1) and specificity of 70.5 (95% CI 66.3-71.6). A validation cohort of 38 single time point paracetamol overdoses confirmed the extremely high negative predictive value of both the SIRS and SOFA thresholds. Conclusions? The absence of either a SOFA score >7 or a SIRS response during the first 96?h following paracetamol overdose could improve triage and reduce transfers of lower risk patients to tertiary liver centres.

PMID: 21554357 [PubMed - as supplied by publisher]

Review article: drug-induced liver injury - its pathophysiology and evolving diagnostic tools.

Aliment Pharmacol Ther. 2011 May 3;

Authors: Au JS, Navarro VJ, Rossi S

Background? Drug-induced liver injury (DILI) is a significant cause of morbidity and mortality accounting for at least 13% of acute liver failure cases in the US. It is the leading cause of acute liver failure among patients referred for liver transplantation and the most common reason that drugs in development do not obtain FDA approval. The incidence of DILI has been reported to be one in 10?000 to one in 100?000 patients; however, the actual incidence is probably higher due in part to the difficulty of diagnosis. Aim? To present a review of the current literature on DILI with a focus on its pathophysiology and evolving diagnostic modalities. Methods? A PubMed literature search was conducted using the terms 'drug induced liver injury', 'pathophysiology', 'causality', 'diagnosis', 'toxicogenomics' and 'pharmacogenetics'. Results? Drug-induced liver injury is an area of ongoing research. From the time it was first recognised, our understanding of the pathophysiology, its classification, diagnosis and reporting by established national networks continues to challenge and evolve. Metabonomics, pharmacogenetics, proteomics and transcriptomics are more recent areas of study that have been applied to further the understanding of DILI. Conclusions? Despite recent advances in our understanding of drug-induced liver injury, many aspects of its pathophysiology and clinical impact remain unclear. In addition, genomic-based studies are evolving concepts, which undoubtedly continue to contribute to our understanding of the underlying mechanisms of drug-induced liver injury.

PMID: 21539586 [PubMed - as supplied by publisher]