Peptic ulcer bleeding in patients with or without cirrhosis: different diseases but the same prognosis?

Aliment Pharmacol Ther. 2012 May 20;

Authors: Rudler M, Rousseau G, Benosman H, Massard J, Deforges L, Lebray P, Poynard T, Thabut D

Abstract
BACKGROUND: Physiopathology and prognosis of peptic ulcer bleeding (PUB) have never been described in cirrhotic patients. AIM: To assess risk factors and outcome of PUB in two groups of patients with PUB with or without cirrhosis. METHODS: We included prospectively all patients with PUB referred to our ICU of Hepatology and Gastroenterology between January 2008 and March 2011. All patients were treated according to international recommendations. Diagnosis of cirrhosis was based on clinical, biological and morphological exams. Aetiologies, characteristics and outcomes of PUB were compared in cirrhotic vs. noncirrhotic patients. RESULTS: A total of 203 patients with PUB were included prospectively. Twenty-nine patients had cirrhosis (group Cirr+), and 174 patients had no cirrhosis (group Cirr-). Demographic data were similar between the two groups except for age and alcohol consumption. Aetiology of cirrhosis was alcohol in 97% of cirrhotic patients. Characteristics of PUB were not different between the two groups. Ninety-three per cent of patients with cirrhosis had endoscopic portal hypertension. Aetiology of PUB was different between the group Cirr+ and Cirr- (Helicobacter pylori = 10.3% vs. 48.8%, P < 0.0001; NSAID's = 17.2% vs. 54.0%, P < 0.0001; idiopathic PUB = 79.3% vs. 23.8%, P < 0.0001). Outcome was comparable concerning re-bleeding (7.0% vs. 6.9%, P = 0.31), need for arterial embolisation (10.3 vs. 8.6%, P = 0.76), need for salvage surgery (0 vs. 1.7%, P = 0.31) and mortality (3.0% vs. 1.1%, P = 0.87). CONCLUSIONS: Physiopathology of PUB seems to be different in patients with cirrhosis. In cirrhotic patients, PUB occurs almost only in alcoholics. In our series, prognosis was similar to general population. PUB in cirrhosis might be related to portal hypertension and/or alcohol.

PMID: 22607536 [PubMed - as supplied by publisher]

Meta-analysis: probiotics in antibiotic-associated diarrhoea.

Aliment Pharmacol Ther. 2012 Apr 24;

Authors: Videlock EJ, Cremonini F

Abstract
BACKGROUND: Diarrhoea is a common occurrence in association with antibiotic administration. Earlier studies and meta-analyses have suggested that probiotic administration reduces the incidence of antibiotic-associated diarrhoea (AAD). AIM: To estimate the reduction in risk of AAD with administration of probiotics in randomised placebo-controlled trials and to identify factors associated with such reduction. METHODS: Meta-analysis of randomised, double-blinded, placebo-controlled trials including patients treated with antibiotics and administered a probiotic for at least the duration of the antibiotic treatment. The outcome was incidence of diarrhoea irrespective of the presence of C lostridium difficile or the development of pseudomembranous colitis. Meta-analysis and meta-regression methods were used to synthesise data and to assess influence of: mean age, duration of antibiotics, risk of bias and incidence of diarrhoea in the placebo group on outcomes. Subgroup analyses explored effects of different probiotic species, patient populations and treatment indications. RESULTS: A total of 34 studies were included with 4138 patients. The pooled relative risk (RR) for AAD in the probiotic group vs. placebo was 0.53 (95% CI 0.44-0.63), corresponding to a number needed to treat (NNT) of 8 (95% CI 7-11). The preventive effect of probiotics remained significant when grouped by probiotic species, population age group, relative duration of antibiotics and probiotics, study risk of bias and probiotic administered. The pooled RR for AAD during treatment for H elicobacter pylori (H. pylori) was 0.37 (95% CI 0.20-0.69), corresponding to a NNT of 5 (95% CI 4-10). CONCLUSIONS: This updated meta-analysis confirms earlier results supporting the preventive effects of probiotics in AAD.

PMID: 22531096 [PubMed - as supplied by publisher]

Meta-analysis: vasoactive medications for the management of acute variceal bleeds.

Aliment Pharmacol Ther. 2012 Apr 8;

Authors: Wells M, Chande N, Adams P, Beaton M, Levstik M, Boyce E, Mrkobrada M

Abstract
BACKGROUND: Vasoactive medications such as vasopressin, somatostatin and their analogues (terlipressin, vapreotide and octreotide) are commonly used for the treatment of acute variceal bleeding. However, the risks and benefits of these interventions are not well understood. AIM: To undertake a meta-analysis of the efficacy of vasoactive medications in patients having acute variceal bleeds. METHODS: Randomised controlled trials (RCTs) of vasopressin, somatostatin and their analogues, administered to patients with acute variceal bleeds were identified based on systematic searches of nine electronic databases and multiple sources of grey literature. RESULTS: The search identified 3011 citations, and 30 trials with a total of 3111 patients met eligibility criteria. The use of vasoactive agents was associated with a significantly lower risk of 7-day mortality (RR 0.74; 95% CI 0.57-0.95; P = 0.02; I(2)  = 0%; moderate quality of evidence), and a significant improvement in haemostasis (RR 1.21, 95% CI 1.13-1.30; P < 0.001; I(2)  = 28%; very low quality of evidence), lower transfusion requirements (pooled mean difference -0.70 units of blood transfused, 95% CI -1.01 to -0.38; P < 0.001; I(2)  = 82%; moderate quality of evidence), and a shorter duration of hospitalisation (pooled mean difference -0.71 days; 95% CI -1.23 to -0.19; P = 0.007; I(2)  = 0%; low quality of evidence). Studies comparing different vasoactive agents did not show a difference in efficacy, although the quality of evidence was very low. CONCLUSIONS: The use of vasoactive agents was associated with a significantly lower risk of acute all-cause mortality and transfusion requirements, and improved control of bleeding and shorter hospital stay. Studies comparing different vasoactive medications failed to demonstrate a difference in efficacy.

PMID: 22486630 [PubMed - as supplied by publisher]

Emergence of spontaneous bacterial peritonitis due to enterococci - risk factors and outcome in a 12-year retrospective study.

Aliment Pharmacol Ther. 2012 Mar 26;

Authors: Reuken PA, Pletz MW, Baier M, Pfister W, Stallmach A, Bruns T

Abstract
BACKGROUND: Third-generation cephalosporins (TGC) constitute the empirical first-line therapy for spontaneous bacterial peritonitis (SBP). Hospitalisation, invasive procedures and use of antibiotics may challenge this concept due to an increase in enterococci and other TGC-resistant microorganisms. AIM: To determine prevalence, risk factors and outcome of ascitic fluid infections caused by enterococci. METHODS: All independent episodes of culture-positive ascitic fluid between 2000 and 2011 in a German tertiary centre were analysed retrospectively. RESULTS: Out of 244 positive ascitic fluid cultures, 90 episodes of monomicrobial SBP and 25 episodes of monomicrobial bacterascites (BA) in patients with decompensated cirrhosis were identified. Enterococcus spp. were isolated in 32 (28%) episodes. We noticed a profound increase in the frequency of enterococcal infection over the study period from 11% to 35% (P = 0.007). Univariate risk factors for enterococcal SBP/BA included nosocomial infection (OR = 4.56; 95% CI 1.90-10.97), previous use of antibiotics (OR = 5.63; 95% CI 1.81-17.49) and recent gastrointestinal endoscopy (OR = 3.17; 95% CI 1.33-7.54). Nosocomial infection (OR = 3.29; P = 0.011) and recent antibiotic therapy (OR = 3.88; P = 0.025) remained independent risk factors for enterococcal infection in multivariate logistic regression and these factors contributed also to the model when only SBP cases were considered. In subjects with monomicrobial SBP who were treated with TGC or ciprofloxacin, the probability of 90-day survival was 12% in enterococcal infection compared to 50% in non-enterococcal SBP (P = 0.022 in log-rank test). CONCLUSION: Because of the increasing prevalence of enterococcal spontaneous bacterial peritonitis and its poor prognosis when treated inappropriately, clinicians should consider empirical therapy with anti-enterococcal antibiotics for patients with risk factors.

PMID: 22449290 [PubMed - as supplied by publisher]

Meta-analysis: banding ligation and medical interventions for the prevention of rebleeding from oesophageal varices.

Aliment Pharmacol Ther. 2012 Mar 26;

Authors: Thiele M, Krag A, Rohde U, Gluud LL

Abstract
BACKGROUND: In patients with oesophageal varices, the combination of endoscopic variceal ligation (EVL) and medical therapy is recommended as standard of care for prevention of rebleeding. The results of previous meta-analyses on this topic are equivocal. AIM: To assess the effects of EVL plus medical therapy vs. monotherapy (EVL or medical therapy alone) for secondary prevention in oesophageal varices. METHODS: Electronic and manual searches were combined. The primary outcome measures were overall rebleeding (variceal and nonvariceal) and mortality. Random-effects meta-analyses were performed with subgroup, sensitivity, regression and sequential analyses to identify sources of intertrial heterogeneity and the robustness of the results. RESULTS: Nine randomised trials were included. In total, 442 patients were randomised to combination therapy and 513 to monotherapy. Combination therapy reduced rebleeding (RR = 0.68; 95% CI = 0.54-0.85; number needed to treat eight patients). The result was confirmed in sequential and regression analyses, but not when limiting the analysis to trials with adequate selection bias control. No effect on overall mortality was identified (RR = 0.89; 95% CI = 0.65-1.21). Combination therapy reduced bleeding-related mortality (RR = 0.52; 95% CI 0.27-0.99; number needed to treat 33 patients) and the risk of rebleeding from oesophageal varices. Combination therapy increased the risk of serious adverse events in fixed, but not in random-effects meta-analyses. CONCLUSIONS: The combination of endoscopic variceal ligation and medical therapy reduce the risk of rebleeding, but not overall mortality. Additional research is needed to determine why reduced rebleeding rates do not lead to reduced mortality.

PMID: 22449261 [PubMed - as supplied by publisher]

Randomised clinical trial: the safety and efficacy of long-acting octreotide in patients with portal hypertension.

Aliment Pharmacol Ther. 2012 Mar 1;

Authors: Chandok N, Kamath PS, Blei A, Bosch J, Carey W, Grace N, Kowdley KV, Benner K, Groszmann RJ

Abstract
BACKGROUND: It remains unclear whether a long-acting preparation of octreotide (Sandostatin LAR) can be safely used for portal hypertension in patients with compensated cirrhosis. AIM: To determine the safety and efficacy of LAR among patients with Child Pugh Class A or B cirrhosis and small oesophageal varices. METHODS: A randomised, double-blind, placebo-controlled study was conducted in 39 patients with cirrhosis and small oesophageal varices. Safety was based on frequency and severity of adverse events. Efficacy was determined by hepatic vein pressure gradient (HVPG) measured at baseline and day 84 following administration of LAR 10 mg (n = 15), 30 mg (n = 10) or saline (n = 14). Fasting and postprandial portal blood flow (PBF), superior mesenteric artery pulsatility index (SMA-PI), glucagon and octreotide levels were measured. An intention-to-treat analysis was performed. RESULTS: Four patients in the LAR 30 group (40%) withdrew from the study due to serious adverse events. No patient in the LAR 10 or control group had serious adverse events. There was no statistically significant decrease between HVPG at day 84 and baseline with LAR 30 mg (11.8 ± 2.3 mmHg vs. 14.1 ± 3.2), LAR 10 mg (15.3 ± 4.8 mmHg vs. 15.1 ± 3.8), or saline (13.3 ± 3.8 mmHg vs. 15.1 ± 4.3) (P = 0.26). Neither PBF, SMA-PI nor plasma glucagon levels were significantly decreased from baseline (P = 0.56). CONCLUSIONS: The absence of significant haemodynamic benefit, as well as the high frequency of severe adverse events associated with use of LAR, do not support the use of this agent in the treatment of portal hypertension.

PMID: 22380529 [PubMed - as supplied by publisher]

Systematic review: faecal transplantation for the treatment of Clostridium difficile-associated disease.

Aliment Pharmacol Ther. 2012 Feb 23;

Authors: Guo B, Harstall C, Louie T, Veldhuyzen van Zanten S, Dieleman LA

Abstract
BACKGROUND: Management of recurrent Clostridium difficile-associated disease (CDAD), particularly in elderly patients, remains clinically challenging. Faecal transplantation (FT) may restore normal microbiota and break the cycle of recurrent CDAD. AIM: To critically appraise the clinical research evidence on the safety and effectiveness of FT compared with standard care in the treatment of patients with CDAD. METHODS: A comprehensive literature search was conducted by a research librarian to identify relevant studies published between 2000 and 2011. The Cochrane Library, PubMed, EMBASE, CINAHL, Biological Abstracts, BIOSIS Previews and Web of Science were searched using the following Medical Subject Headings (MeSH) terms and keywords, alone or in combination: Clostridium infections/Clostridium difficile/pseudomembranous/colitis/faeces/rectal/colon flora/gastrointestinal/nasogastric tube/enema/donor/transplant/infusion/bacteriotherapy/human probiotic infusion. Methodological quality of the included case series studies was assessed in terms of patient selection criteria, consecutive recruitment, prospective data collection, reporting of lost to follow-up, and follow-up rates. RESULTS: No controlled studies were found. Based on the weak evidence from seven full-text case series studies of 124 patients with recurrent/refractory CDAD, FT appears to be a safe and effective procedure. In most cases (83%) symptoms improved immediately after the first FT procedure, and some patients stayed diarrhoea free for several months or years. CONCLUSIONS: Although these results appear to be promising, the treatment effects of faecal transplantation cannot be determined definitively in the absence of a control group. Results from randomised controlled trials that compare faecal transplantation to oral vancomycin without or with a taper regimen will help to better define the role of faecal transplantation in the management of recurrent CDAD.

PMID: 22360412 [PubMed - as supplied by publisher]

Overnight glucose infusion suppresses renal ammoniagenesis and reduces hyperammonaemia induced by a simulated bleed in cirrhotic patients.

Aliment Pharmacol Ther. 2012 Feb 23;

Authors: Mpabanzi L, Deutz N, Hayes PC, Dejong CH, Olde Damink SW, Jalan R

Abstract
BACKGROUND: A simulated upper gastrointestinal (UGI) bleed in cirrhotic patients has been shown to induce hyperammonaemia. The kidney was the site of this exaggerated ammoniagenesis with alanine as substrate. Administration of alanine to decompensated cirrhotic patients did not change hepatic gluconeogenesis, but resulted in increased ammoniagenesis. We hypothesise that reduced hepatic glycogen stores result in hyperglucagonaemia which may drive increased renal gluconeogenesis and therefore alanine uptake and renal ammoniagenesis. AIM: To determine whether an overnight glucose infusion lowers renal ammoniagenesis by reducing hyperglucagonaemia and renal ammoniagenesis. METHODS: Patients with decompensated cirrhosis were studied in a cross-over design. An UGI bleed was simulated via intragastric administration of an amino acids mixture mimicking the haemoglobin molecule after a 12-h overnight fast (F-group) or after a 12-h treatment with 20% glucose solution (G-group). RESULTS: Before the simulated bleed the glucagon levels were 21 (15-31) pmol/L in the F-group and 15 (9-21) pmol/L in the G-group (P < 0.01). After the simulated bleed, arterial ammonia levels increased in both groups [F-group: 73-118 ?mol/L (P = 0.01); G-group 64-87 ?mol/L (P = 0.01)]. The enhancement of hyperammonaemia was significantly higher in the F-group (45 [19-71] ?mol/L) compared with the G-group (23 [13-39] ?mol/L) (P = 0.01). The difference in renal ammoniagenesis during the simulated bleed in the F-group was 399 (260-655) nmol/kg/bwt/min and was significantly higher than in the G-group 313 (1-498) nmol/kg/bwt/min (P = 0.05). CONCLUSIONS: Overnight glucose infusion results in reduced renal ammoniagenesis and attenuates ammonia levels. These observations have implications for the development of nutritional strategies in hyperammonaemic patients.

PMID: 22360430 [PubMed - as supplied by publisher]

Randomised clinical trial: high-dose vs. standard-dose proton pump inhibitors for the prevention of recurrent haemorrhage after combined endoscopic haemostasis of bleeding peptic ulcers.

Aliment Pharmacol Ther. 2012 Feb 28;

Authors: Chen CC, Lee JY, Fang YJ, Hsu SJ, Han ML, Tseng PH, Liou JM, Hu FC, Lin TL, Wu MS, Wang HP, Lin JT

Abstract
BACKGROUND: The optimal dosage of intravenous proton pump inhibitors (PPIs) for the prevention of peptic ulcer rebleeding remains unclear. AIM: To compare the rebleeding rate of high-dose and standard-dose PPI use after endoscopic haemostasis. METHODS: A total of 201 patients with bleeding ulcers undergoing endoscopic treatment with epinephrine injection and heater probe thermocoagulation were randomised to receive a high-dose regimen (80 mg bolus, followed by pantoprazole 8 mg/h infusion, n = 100) or a standard-dose regimen (pantoprazole 40 mg bolus daily, n = 101). After 72 h, all patients were given 40 mg pantoprazole daily orally for 27 days. RESULTS: There were no statistical differences in mean units of blood transfused, length of hospitalisation ?5 days, surgical or radiological interventions and mortality within 30 days between two groups. Bleeding recurred within 30 days in six patients [6.2%, 95% confidence interval (CI) 1.3-11.1%] in the high-dose group, as compared to five patients (5.2%, 95% CI 0.6-9.7%) in the standard-dose group (P = 0.77). The stepwise Cox regression analysis showed end-stage renal disease, haematemesis, chronic obstructive pulmonary disease (hazard ratio: 37.15, 10.07, 9.12, 95% CI: 6.76-204.14, 2.07-49.01, 1.66-50.00 respectively) were independent risk factors for rebleeding and Helicobacter pylori infection was associated with lower risk of rebleeding (hazard ratio: 0.20, 95% CI: 0.04-0.94). CONCLUSIONS: Following combined endoscopic haemostasis of bleeding ulcers, co-morbidities, haematemesis and H. pylori Status, but not PPI dosage, are associated with rebleeding (http://www.Clinical Trials.gov.ID: NCT00709046).

PMID: 22369682 [PubMed - as supplied by publisher]

Predictors of severe outcomes associated with Clostridium difficile infection in patients with inflammatory bowel disease.

Aliment Pharmacol Ther. 2012 Feb 23;

Authors: Ananthakrishnan AN, Guzman-Perez R, Gainer V, Cai T, Churchill S, Kohane I, Plenge RM, Murphy S

Abstract
BACKGROUND: The increasing incidence of Clostridium difficile (C. difficile) infection (CDI) among patients with inflammatory bowel disease is well recognised. However, most studies have focused on demonstrating that CDI is associated with adverse outcomes in IBD patients. Few have attempted to identify predictors of severe outcomes associated with CDI among IBD patients. AIM: To identify clinical and laboratory factors that predict severe outcomes associated with CDI in IBD patients. METHODS: From a multi-institution EMR database, we identified all hospitalised patients with at least one diagnosis code for C. difficile from among those with a diagnosis of Crohn's disease or ulcerative colitis. Our primary outcome was time to total colectomy or death with follow-up censored at 180 days after CDI. Cox proportional hazards models were used to identify predictors of the primary outcome from among demographic, disease-related, laboratory and medication variables. RESULTS: A total of 294 patients with CDI-IBD were included in our study. Of these, 58 patients (20%) met our primary outcome (45 deaths, 13 colectomy) at a median of 31 days. On multivariate analysis, serum albumin <3 g/dL (HR 5.75, 95% CI 1.34-24.56), haemoglobin below 9 g/dL (HR 5.29, 95% CI 1.58-17.69) and creatinine above 1.5 mg/dL (HR 1.98, 95% CI 1.04-3.79) were independent predictors of our primary outcome. Examining laboratory parameters as continuous variables or shortening our primary outcome to include events within 90 days yielded similar results. CONCLUSION: Serum albumin below 3 g/dL, haemoglobin below 9 g/dL and serum creatinine above 1.5 mg/dL were independent predictors of severe outcomes in hospitalised IBD patients with Clostridium difficile infection.

PMID: 22360370 [PubMed - as supplied by publisher]

Modified-orientation log to assess hepatic encephalopathy.

Aliment Pharmacol Ther. 2012 Feb 21;

Authors: Salam M, Matherly S, Farooq IS, Stravitz RT, Sterling RK, Sanyal AJ, Gibson DP, Wade JB, Thacker LR, Heuman DM, Fuchs M, Puri P, Luketic V, Bickston SJ, Bajaj JS

Abstract
BACKGROUND: The subjectivity of the West-Haven criteria (WHC) hinders hepatic encephalopathy (HE) evaluation. The new HE classification has emphasised assessment of orientation. The modified-orientation log (MO-log, eight questions, scores 0-24; 24 normal) is adapted from a validated brain injury measure. AIM: To validate MO-log for HE assessment in cirrhosis. METHODS: Cirrhotics admitted with/without HE were administered MO-log. We collected cirrhosis/HE details, admission/daily MO-logs and WHC (performed by different examiners), time to reach normal mentation (MO-log ?23) and MO-log/WHC change (?) over day 1. Outcomes were in-hospital mortality, duration to normal mentation and length-of-stay (LOS). Regressions were performed for each outcome. MO-log inter-rater reliability was measured. RESULTS: Ninety-six HE (55 ± 8 years, MELD 21) and 20 non-HE (54 ± 5 years, MELD 19) in-patients were included. In HE patients, median admission WHC was 3 (range 1-4). Mean MO-log was 12 ± 8 (range 0-22). Their LOS was 6 ± 5 days and 13% died. Time to reach normal mentation was 2.4 ± 1.7 days. Concurrent validity: there was a significant negative correlation between admission MO-log and WHC (r = -0.79, P < 0.0001). Discriminant validity: admission MO-logs were significantly lower in those who died (7 vs. 12, P = 0.03) and higher in those admitted without HE (23.6 vs. 12, P < 0.0001). MO-log improved in 69% on day 1 (?MO-log 4 ± 8) which was associated with lower duration to normal mentation (2 vs. 3.5 days, P = 0.03) and mortality (3% vs.43%, P < 0.0001), not ?WHC. Regression models for all outcomes included admission/?MO-log but not WHC as a predictor. Inter-rater reliability: ICC for MO-log inter-rater observations was 0.991. CONCLUSIONS: Modified-orientation log is a valid tool for assessing severity and is better than West-Haven criteria in predicting outcomes in hospitalised hepatic encephalopathy patients.

PMID: 22348593 [PubMed - as supplied by publisher]

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]