Impact on adherence and sustained virological response of psychiatric side effects during peginterferon and ribavirin therapy for chronic hepatitis C

Summary

Background

The psychiatric side effects of interferon, often responsible for dose reduction or treatment discontinuation, represent a major limitation in the treatment of chronic hepatitis C (CHC).

Aim

To prospectively assess the impact on adherence and sustained virological response (SVR) of the occurrence of psychiatric side effects during peginterferon and ribavirin therapy for CHC.

Methods

Ninety‐eight consecutive treatment‐naïve CHC patients receiving a standard course of peginterferon plus ribavirin were systematically screened for psychiatric side effects, using DSM‐IV, at baseline and both during and after treatment.

Results

Psychiatric side effects occurred in 38 patients (39%), mostly within the first 12 weeks (87%), and always consisted of mood disorders. Overall, 68% of patients achieved an SVR (71% of patients with mood disorders and 68% of those without; P = N.S.). Peginterferon and ribavirin dose reductions did not differ between patients with mood disorders and those without (46% vs. 37%, respectively; P = N.S. and 13% vs. 22%, respectively; P = N.S.). Anti‐viral therapy had to be discontinued in four patients (nonresponse: two, hyperthyroidism: one, psychiatric event: one).

Conclusion

Early detection and appropriate management of psychiatric side effects during peginterferon and ribavirin therapy for CHC allow optimizing adherence and virological efficacy.

     

Sustained virological response to peginterferon plus ribavirin in chronic hepatitis C genotype 1 patients is associated with a persistent Th1 immune response

Summary

Background

An impairment of cellular immune response may contribute to the persistency of hepatitis C virus infection.

Aim

To analyse the Th1/Th2 cytokine profile in peripheral blood CD4+ and CD8+ T cells from patients with chronic hepatitis C (CHC) during treatment with pegylated interferon‐α2a plus ribavirin and to correlate the Th1/Th2 balance with virological response (SVR).

Methods

Prospective longitudinal study: 44 naïve genotype 1 CHC patients received PEG‐IFNα2a plus ribavirin for 48 weeks: 26 (59.1%) achieved a SVR, 13 relapsed (29.5%) and 5 (11.4%) were non‐responders. Sixteen healthy controls were analysed. The production of IL‐4, IFNγ and TNFα by CD4+ and CD8+ T cells was measured using flow cytometry, both in resting and phorbol‐ester‐stimulated cells.

Results

First three months of treatment: the synthesis of TNFα by phorbol‐ester‐stimulated‐CD4+ T cells was higher in patients with SVR (P < 0.01). At the end of treatment, SVR was associated with higher intracellular expression of IFNγ by stimulated‐CD4+ and CD8+ T cells (P < 0.05). At the end of follow‐up, a higher intracellular expression of IFNγ by CD4+ T cells was associated with a SVR.

Conclusions

A Th1‐type immune response was associated with achievement of a SVR, as indicated by the persistent elevation of intracellular IFNγ and TNFα.

     

Meta-analysis: the adjuvant role of thymopentin on immunological response to hepatitis B virus vaccine in end-stage renal disease

Summary

Background

It has been calculated that 30–40% of dialysis patients fail to produce antibodies to HBsAg antigen after vaccination towards hepatitis B virus. Several authors have reported on the benefit of thymopentin (TP5) as adjuvant to vaccine against hepatitis B virus in patients receiving regular dialysis. However, consistent information on this issue is still lacking.

Aims

To evaluate efficacy and safety of thymopentin as adjuvant to hepatitis B vaccine in dialysis patients by performing a systematic review with a meta‐analysis of clinical trials.

Methods

We used the random effects model of DerSimonian and Laird, with heterogeneity and sensitivity analyses.

Results

We identified 11 studies involving 272 unique patients with end‐stage renal disease. Only prospective, controlled trials were included. Pooling of study results did not show a significant increase in seroresponse rate among study (thymopentin plus hepatitis B virus vaccine) vs. control (hepatitis B virus vaccine alone) patients; the pooled odds ratio of failure to respond to hepatitis B virus vaccine was 0.677 (95% confidence intervals: 0.285–1.605); no heterogeneity was found (P = 0.0001). Thymopentin significantly improved the seroresponse rate in the subgroup of trials based on greater thymopentin doses (OR: 0.184; 95% CI: 0.085–0.398).

Conclusions

Our meta‐analysis showed that thymopentin significantly improved the seroresponse rate towards hepatitis B vaccine only in dialysis patients treated with higher thymopentin doses. The limited number of patients precluded definitive conclusions.

     

Comparison of simple tests for the non-invasive diagnosis of clinically silent cirrhosis in chronic hepatitis C

Summary

Background

Biopsy is the gold standard for assessing cirrhosis in patients with chronic hepatitis C virus infection, but it is expensive and at risk of complications. Alternative non‐invasive methods have been developed but their usefulness remains uncertain.

Aim

To compare the accuracy of five non‐invasive scores in detecting cirrhosis.

Methods

We reviewed the charts and liver biopsies of 228 consecutive, treatment‐naïve, hepatitis C virus‐positive patients, 13.2% of whom with histological diagnosis of cirrhosis. The five alternative scores were age‐platelet index, cirrhosis discriminant score, aspartate transaminases to platelet ratio index, Pohl's index, and aspartate transaminases/alanine transaminases ratio.

Results

The specificities of the scores were good (87–100%), but not so their sensitivities (17–67%). Accordingly positive likelihood ratios were generally good but negative likelihood ratios were suboptimal. Combinations of the scores independently related to cirrhosis only slightly change this diagnostic accuracy. Using double cut‐offs to exclude/diagnoses cirrhosis, cirrhosis discriminant score classified 21% of patients without misdiagnoses and aspartate transaminases to platelet ratio index classified 85% of case with 9% of misdiagnoses.

Conclusions

The five scores showed variable sensitivities and specificities in detecting liver cirrhosis, both individually and in combination. The use of double cut‐off points may make the cirrhosis discriminant score and aspartate transaminases to platelet ratio index useful to reduce the number of patients submitted to liver biopsy.

     

Evaluating the cost of sustained virologic response in naïve chronic hepatitis C patients treated à la carte

Summary

Background

There is a tendency to individualize treatment in chronic hepatitis C patients depending on viral load and rapid clearance of HCV‐RNA.

Aim

To evaluate the cost (€, 2006) per sustained virologic response in naïve patients with therapy à la carte compared with standard combination therapy.

Methods

A decision analysis model was used to compare standard therapy with peginterferon alpha and ribavirin for 24 weeks for genotype (G) 2/3, and 48 weeks for G1 and therapy à la carte with the same drugs but different durations: G1 high viral load for 48 weeks, G1 low viral load with rapid virologic response for 24 weeks, and without rapid virologic response for 48 weeks, and G2/3 with rapid virologic response for 12 weeks, and without rapid virologic response for 24 weeks.

Results

Sustained virologic response was similar in both strategies. The cost per successfully treated patient for standard therapy is €17 812 and for therapy à la carte€12 313. Assuming that 13 309 patients with standard therapy and 14 450 patients with therapy à la carte achieve sustained virologic response, therapy à la carte has an overall cost‐saving of €59.13 million.

Conclusion

Therapy à la carte is a cost‐saving strategy for chronic hepatitis C infection compared to standard therapy, with lower investment requirement per patient to achieve sustained virologic response.

     

Interferon alpha with ribavirin for the treatment of chronic hepatitis C in non-responders or relapsers to interferon monotherapy

Background:

A more effective therapy for chronic hepatitis C virus-infected patients is needed.

Aim:

To evaluate the efficacy, tolerance and timing of response to interferon alpha plus ribavirin in 60 patients with no response or reactivation after interferon alpha alone.

Methods:

Sixty patients, 42 non-responders and 18 relapsers, received 3 million units three times weekly of interferon alpha-2b plus 1–1.2 g ribavirin daily, for 6 months. Basal biochemical and virological (HCV RNA and genotype) parameters were determined. Clinical examination, recording adverse effects, and laboratory tests, including viraemia, were carried out at 1, 2, 3 and 6 months.

Results:

A significant (P < 0.001) progressive decrease of HCV RNA and alanine transaminase (ALT) levels was observed during treatment. On finalizing the sixth month, 42 patients (70%) had normal ALT and 26 (43.3%) were HCV RNA negative. Of these 26 complete responders, in 20 the viraemia was undetectable by the third month, while a late clearance at the sixth month of treatment was observed in six patients. Response rates were higher in previous responders to interferon alone (P < 0.05). Mild adverse effects appeared in 46 patients (79.6%), but only three were withdrawn due to serious side-effects. Significantly (P < 0.001), haemoglobin and leucocytes decreased, and bilirubin, ferritin and uric acid increased in the first month of treatment, with no changes thereafter.

Conclusions:

Interferon alpha plus ribavirin progressively decreased HCV RNA and ALT levels, achieving a complete response in the six months of treatment in 26 (43.3%) patients. This combined therapy was well tolerated.

     

Soluble adhesion molecules correlate with liver inflammation and fibrosis in chronic hepatitis C treated with interferon-α

Background:

In chronic hepatitis C the relation of circulating adhesion molecules to disease features before, during and after therapy has not been completely established.

Aim:

To analyse the basal levels of circulating adhesins and the changes induced by interferon in these patients.

Methods:

We studied, using ELISA assays, the serum levels of soluble intercellular adhesion molecule-1 (sICAM-1) and vascular cell adhesion molecule-1 (sVCAM-1) in 52 patients with chronic hepatitis C on entry, prior to finalizing a 6-month course of interferon-α therapy and at the end of the follow-up. Correlations with clinical, virological and histological features, including inflammation and fibrosis, were calculated by Pearson’s r-test.

Results:

Liver necroinflammation was more closely related to sICAM-1 (r = 0.54, P = 0.0000) than to sVCAM-1 (r = 0.32, P = 0.02). Fibrosis, both as serum pIIIP and histological scoring, was, however, clearly related to sVCAM-1 (1071 ± 291 in patients who scored 0–2 vs. 1870 ± 458 in patients who scored 3–4; P = 0.0000). Severe fibrosis was never found below a sVCAM-1 cut-off threshold of 1300 ng/mL. Levels of both adhesins did not correlate with viraemia and were comparable among 1b and non-1b genotypes. Sustained response to interferon was significantly related to low viraemia (P = 0.03), non-1b type (P = 0.04) and low sICAM-1 (P = 0.04), but not to sVCAM-1. On finalizing therapy, patients with normal transaminases had reduced sICAM-1 (P = 0.0005), but not sVCAM-1 levels.

Conclusions:

In chronic hepatitis C, sICAM-1 was a marker of liver necroinflammation while sVCAM-1 reflected fibrosis. Both low sVCAM-1 and pIIIP serum concentrations were strictly linked, suggesting that measuring sVCAM-1 could give information on the degree of liver fibroplasia.

     

Colchicine in chronic hepatitis B: a pilot study

Rationale:

Because of its antifibrotic and anti-inflammatory effects, colchicine has been proposed as a treatment for liver disease. Early in vitro studies have demonstrated that colchicine blocks mitosis in the metaphase and inhibits DNA synthesis.

Aim:

A pilot study of hepatitis B virus (HBV)-related/HBV-DNA+ve chronic liver disease.

Patients:

Nine biopsy-proven chronic hepatitis patients (three with cirrhosis) entered the study. Two of them were HBeAg+ve and seven were antiHBe+. All patients were HBV-DNA+ve/antiHBc IgM+ve (index values of anti-HBc IgM ranged from 0.370 to 1.200). All of them had a major contraindication to interferon therapy or refused antiviral treatment. The known persistence of positive HBsAg ranged from 2 to 21 years.

Methods:

After informed consent, the patients received 1 mg colchicine a day orally for 5 days-a-week over 6 months. Testing for liver enzymes and viral markers was performed at the baseline and after 3 and 6 months.

Results:

None of the patients experienced side-effects during the treatment. The two HBeAg+ve patients seroconverted to anti-HBe with a normalization of AST/ALT during therapy. Among the seven antiHBe+ve patients, four had a complete normalization of transaminases (one patient cleared the HBsAg with seroconversion to anti-HBs). Six of the nine patients were HBV-DNA-ve at the end of therapy and were still negative after 12 months of follow-up.

Conclusion:

These preliminary results suggest that colchicine might have an antiviral activity in HBV-DNA+ve chronic liver disease, and it could be regarded as an alternative therapy to interferon.

     

Liver stiffness diminishes with antiviral response in chronic hepatitis C

Aliment Pharmacol Ther 2011; 34: 656–663

Summary

Background Transient elastography measures liver stiffness, which correlates with the hepatic fibrosis stage and has excellent accuracy for the diagnosis of cirrhosis in patients with chronic hepatitis C. Aim To assess prospectively the kinetics of liver stiffness in treated patients with chronic hepatitis C and compare them with the viral kinetics on treatment and with the final outcome of therapy. Methods 91 patients with chronic hepatitis C with significant fibrosis (>7.0 kPa) at baseline were included. They received therapy with pegylated interferon‐α and ribavirin. The kinetics of liver stiffness were characterized during therapy and thereafter by means of Fibroscan, and compared with the virological responses at weeks 4, 12, 24, end of treatment and 12 and 24 weeks after. Results A significant liver stiffness decrease was observed during therapy, which continued after treatment only in patients who achieved a sustained virological response. In this group, the median intra‐patient decrease relative to baseline at the end of follow‐up was ?3.4 kPa, vs?1.8 kPa in the patients who did not achieve an SVR. Similar dynamics were observed in cirrhotic and non‐cirrhotic patients. In multivariate analysis, only the SVR was associated with long‐term improvement of liver stiffness (odds ratio: 3.10; 95% confidence interval: 1.20–8.02, P = 0.019). Conclusions In patients with advanced fibrosis at the start of therapy, liver stiffness is significantly reduced during treatment, but improvement continues off treatment only in patients who achieve a sustained virological response. Liver stiffness assessment earlier than 6 months after the end of therapy does not appear to be clinically meaningful.

     

Effect of hiatal hernia on proximal oesophageal acid clearance in gastro-oesophageal reflux disease patients

Summary

Background

Proximal acid reflux is common in gastro‐oesophageal reflux disease and is a determinant of symptoms. Patients with hiatal hernia complain of more symptoms than those without and are less responsive to proton‐pump inhibitors.

Aim

To evaluate the role of hiatal hernia on spatiotemporal characteristics of acid reflux.

Methods

Thirty seven consecutive gastro‐oesophageal reflux disease patients underwent endoscopy, videofluoroscopy, manometry and multichannel 24‐h pH test. Data were compared with those of 15 asymptomatic controls. Multivariate linear regression was used for statistical analysis.

Results

At videofluoroscopy, hiatal hernia was found in 16 of 37 patients. The mean size of hiatal hernia was 3.4 cm. Patients showed significantly prolonged acid clearance time, both at proximal and distal oesophagus, compared with controls. Hiatal hernia patients showed a significantly delayed acid clearance, along the oesophageal body, compared with non‐hiatal hernia patients. The prolonged acid exposure was maintained during upright and supine position. The presence of hiatal hernia significantly predicted acid clearance delay in the distal and proximal oesophagus [at 10 cm below upper oesophageal sphincter: Δ + 2.5 min (95% confidence interval: 0.4–4.5); P < 0.02].

Conclusions

The presence of hiatal hernia is a strong predictor of more prolonged proximal oesophageal acid exposure and clearance. Hiatal hernia is likely to play a role in the pathophysiology of gastro‐oesophageal reflux disease symptoms, and should be taken into greater consideration in the treatment strategies of the disease.

     

Effect of MDR1 C3435T polymorphism on cure rates of Helicobacter pylori infection by triple therapy with lansoprazole, amoxicillin and clarithromycin in relation to CYP 2C19 genotypes and 23S rRNA genotypes of H. pylori

Summary

Background

Polymorphism in MDR1 is associated with variation in the plasma level of a proton pump inhibitor.

Aim

To investigate whether MDR1 polymorphism is associated with eradication rates of Helicobacter pylori by a triple therapy with lansoprazole, amoxicillin and clarithromycin in relation to CYP2C19 genotype status and bacterial susceptibility to clarithromycin.

Methods

A total of 313 patients infected with H. pylori completed the treatment with lansoprazole 30 mg b.d., clarithromycin 200 mg b.d. and amoxicillin 750 mg b.d. for 1 week. MDR1 C3435T polymorphism and CYP2C19 genotypes of patients and sensitivity of H. pylori to clarithromycin were determined.

Results

Logistic regression analysis revealed that the MDR1 polymorphism as well as CYP2C19 genotypes of patients and clarithromycin‐resistance of H. pylori were significantly associated with successful eradication. Eradication rates for H. pylori were 82% (83/101: 95% CI = 73–89), 81% (112/139: CI = 73–87), and 67% (44/73: CI = 48–72) in patients with the MDR1 3435 C/C, C/T and T/T genotype, respectively (P = 0.001).

Conclusions

Polymorphism of MDR1 is one of the determinants of successful eradication of H. pylori by the triple therapy with lansoprazole, amoxicillin and clarithromycin, together with CYP2C19 genotype and bacterial susceptibility to clarithromycin.

     

Three-year oral pantoprazole administration is effective for patients with Zollinger-Ellison syndrome and other hypersecretory conditions

Summary

Background

Zollinger–Ellison syndrome and idiopathic hypersecretion are gastrointestinal hypersecretory conditions requiring long‐term maintenance.

Aims

The safety and efficacy data for short‐term (6‐month) treatment of Zollinger–Ellison syndrome and idiopathic hypersecretion with oral pantoprazole were previously published. This study extends the initial observations to 3 years.

Methods

The primary efficacy end point for this report was the control of gastric acid secretion in the last hour before the next dose of oral pantoprazole (acid output of <10 mmol/h; <5 mmol/h in subjects with prior acid‐reducing surgery). Dose titration was permitted to a maximum of 240 mg per 24 h.

Results

Twenty‐four subjects completed the study. The acid output of 28 of 34 subjects was controlled at initial enrolment. The mean acid output rates were <10 mmol/h throughout the 36 months of treatment for 90–100% of the patients. The majority of the patients were controlled with b.d. doses of 40 or 80 mg pantoprazole at 36 months (acid output was controlled in 24 of 24 subjects). Pantoprazole was generally well tolerated with minimal adverse events reported.

Conclusions

Maintenance oral pantoprazole therapy up to 3 years at dosages of 40–120 mg b.d. was effective and well tolerated in patients with Zollinger–Ellison syndrome and other hypersecretory conditions.

     

Patterns of gastritis and the effect of eradicating Helicobacter pylori on gastro-oesophageal reflux disease in Western patients with non-ulcer dyspepsia

Summary

Background

The effect of Helicobacter pylori eradication on the development of gastro‐oesophageal reflux disease is controversial.

Aim

To determine the incidence of symptoms of reflux disease and of erosive oesophagitis, and the relationship to changes in histological gastritis, in patients with non‐ulcer dyspepsia over 12 months.

Methods

Six hundred and ninety‐three patients in two similar randomized placebo controlled trials of H. pylori eradication in non‐ulcer dyspepsia were studied. Symptoms were assessed using the validated Gastrointestinal Symptom Rating Scale during a 1‐week run‐in period, at 6 months and 12 months. Endoscopy was performed at baseline to exclude patients with pathology and at 3 months and 12 months to determine if oesophagitis was present. Gastric biopsies were scored using the modified Sydney Classification.

Results

Patients without predominant heartburn, oesophagitis or ulcers at endoscopy were randomized to active (n = 297, omeprazole, amoxicillin and clarithromycin) treatment or to placebo/omeprazole (n = 306) for 1 week. The eradication rate was 82% in the active treatment group. Antrum‐predominant gastritis (55%) was more frequently found than corpus‐predominant gastritis (6%). In patients with antrum‐predominant gastritis, heartburn and regurgitation scores improved significantly 12 months after eradication. Erosive oesophagitis developed in 15/232 patients in the eradication group (7%) compared with 2/227 (2%) in the control group, but there was no significant difference when adjusted for oesophagitis present at baseline.

Conclusions

Antrum‐predominant gastritis is the most common pattern of gastritis seen in non‐ulcer dyspepsia in Western populations. Heartburn and regurgitation improve after eradication therapy or placebo in patients with non‐ulcer dyspepsia; the development of oesophagitis is uncommon.

     

Oesophageal acid exposure and altered neurocardiac function in patients with GERD and idiopathic cardiac dysrhythmias

Summary

Background

Oesophageal sensory stimuli alter neurocardiac function through autonomic reflexes.

Aim

To evaluate in patients with idiopathic supraventricular cardiac dysrhythmias and gastro‐oesophageal reflux disease (GERD) whether GE reflux alters neurocardiac function and the effect of acid suppression on cardiac symptoms.

Methods

Thirty‐two patients (13 females and 19 males; age: 20–69 years) with dysrhythmias plus GERD, and nine patients (five females and four males; age: 43–58 years) with GERD only, underwent simultaneous 24‐h pH‐metry and ECG monitoring. Power spectrum analysis of heart rate variability (PSHRV) was obtained with both its low frequency (LF, sympathetic modulation) and high frequency (HF, vagal modulation) components. Hourly mean oesophageal pH and LF/HF ratio were correlated. A 3 months full‐dosage PPI therapy (esomeprazole 40 mg/day) was prescribed.

Results

In 18 (56%) of the 32 patients with dysrhythmia and in none with GERD only, a significant (P < 0.05) correlation between oesophageal pH and LF/HF ratio (oesophagus–heart correlation) was observed. A significant reduction of cardiac symptoms after PPI therapy was observed only in these patients (13/16 vs. 4/11, P < 0.01).

Conclusions

This study has identified a subgroup of dysrhythmic patients in whom the oesophageal acid stimulus elicited cardiac autonomic reflexes. In these patients acid suppression seems to improve GERD and cardiac symptoms.

     

Review article: overview of medical treatments in unresectable hepatocellular carcinoma—an impossible meta-analysis?

Background:

Controversies surrounding medical treatment in patients with unresectable hepatocellular carcinoma continue to persist.

Aim:

To perform a meta-analysis of therapeutic modalities which had been evaluated in two or more randomized trials.

Methods:

Fifty-two randomized trials were studied; only 30 were included. This overview identified seven therapeutic modalities which had been evaluated in two or more trials: adriamycin, 5-fluorouracil, interferon, percutaneous ethanol injection, transarterial chemotherapy, the combination of lipiodol with transarterial chemotherapy, and tamoxifen.

Results:

Comparisons of survival between control groups showed substantial heterogeneity. There was no survival benefit at 1 year with adriamycin (mean difference 4%), 5-fluorouracil (mean difference ?3%), percutaneous ethanol injection (mean difference 6%) or transarterial chemotherapy (mean difference ?2%). For interferon, the survival benefit was significant with the Der Simonian & Laird method (mean difference 9%, 95% CI = 1–18%, P = 0.04) but not with the Peto et al. method (2.4 mean odds ratio, 95% CI = O.9–6.8). The meta-analysis of tamoxifen showed a borderline survival benefit (mean difference 25%, 95% CI = 0–49%, P = 0.05). However, in sensitivity analyses, the survival benefit of tamoxifen was no longer significant.

Conclusions:

No treatment has clearly proven efficacy in survival. 5-Fluorouracil, adriamycin and transarterial chemotherapy were not associated with survival benefit at 1 year. The number of randomized controlled trials was insufficient to enable a conclusion to be reached for interferon and percutaneous ethanol injection. Controversy persists concerning tamoxifen efficacy. Interferon and tamoxifen require new randomized controlled trials on a larger population of patients.

     

There are some benefits for eradicating Helicobacter pylori in patients with non-ulcer dyspepsia

Background

: The relationship between Helicobacter pylori infection and non‐ulcer dyspepsia is not established.

Aim

: To determine whether eradication of H. pylori might be of benefit in non‐ulcer dyspepsia patients.

Methods

: We randomly assigned 129 H. pylori infected patients with severe epigastric pain, without gastro‐oesophageal reflux symptoms, to receive twice daily treatment with 300 mg of ranitidine, 1000 mg of amoxicillin, and 500 mg of clarithromycin for 7 days and 124 such patients to receive identical‐appearing placebos.

Results

: Treatment was successful (decrease of symptoms at 12 months) in 62% of patients in the active‐treatment group and in 60% of the placebo group (N.S.). At 12 months, the rate of eradication of H. pylori was 69% in the active‐treatment group and 18% in the placebo group (P < 0.001). Complete relief of symptoms occurred significantly more frequently in patients on the active treatment (43%) than in placebo‐treated patients (31%, P=0.048). Within the active‐treatment group, therapeutic success was significantly more frequent in the non‐infected patients (84% vs. 64%, P=0.04).

Conclusions

: Although eradicating H. pylori is not likely to relieve symptoms in the majority of patients with non‐ulcer dyspepsia, a small proportion of H. pylori‐infected patients may benefit from eradication treatment.

     

Prospective study of the risk of Clostridium difficile diarrhoea in elderly patients following treatment with cefotaxime or piperacillin–tazobactam

Background

Rates of Clostridium difficile diarrhoea have recently been rising, with the elderly being at highest risk.

Aim

To compare the incidence of C. difficile colonization and diarrhoea in elderly patients treated for presumed infection with either empirical cefotaxime (CTX) or piperacillin–tazobactam (PT).

Methods

A prospective, ward-based, crossover study was carried out on two well-matched care of the elderly wards at a UK tertiary care hospital, in patients requiring empirical broad-spectrum antibiotic treatment.

Results

There was a highly significant increased incidence of C. difficile colonization (26/34 vs. 3/14, P = 0.001) and diarrhoea (18/34 vs. 1/14, P = 0.006) in patients who received CTX as opposed to PT. DNA fingerprinting suggested that most infections arose from strains acquired from the hospital environment.

Conclusions

Elderly patients are significantly less likely to develop C. difficile diarrhoea after treatment with PT than after CTX. The source of C. difficile appears to be predominantly from the ward environment.

     

Lubiprostone, a locally acting chloride channel activator, in adult patients with chronic constipation: a double-blind, placebo-controlled, dose-ranging study to evaluate efficacy and safety

Summary

Background

Lubiprostone, a locally acting type‐2 chloride channel activator, induces intestinal fluid secretion.

Aim

To assess efficacy and safety of oral lubiprostone at multiple doses for the treatment of chronic constipation.

Methods

A total of 129 patients with chronic constipation were randomized to receive lubiprostone (24, 48 or 72 mcg/day) or placebo for 3 weeks. Spontaneous bowel movement (SBM) frequency, rescue medication use, symptom assessments and adverse events (AEs) were tracked.

Results

Over the double‐blinded period, mean SBM frequencies were higher for lubiprostone groups (5.1–6.1) vs. placebo (3.8) and the overall difference was statistically significant (P = 0.046). SBM frequencies at week 1 were significantly higher in patients taking lubiprostone 48 or 72 mcg/day (P ≤ 0.003) and, at week 2, all three lubiprostone doses yielded significantly higher SBM rates vs. placebo (P ≤ 0.020). Significantly larger proportions of patients taking lubiprostone 48 and 72 mcg/day also experienced a SBM on the first treatment day (P ≤ 0.009). The most common AEs were nausea, headache and diarrhoea.

Conclusions

Lubiprostone improved SBM rates in a dose‐dependent manner. AEs were tolerable for most patients. Increased AE severity at 72 mcg/day did not provide a clear risk‐to‐benefit advantage compared with lubiprostone 48 mcg/day, the dose chosen for subsequent Phase 3 studies.

     

Review article: the management of achalasia - a comparison of different treatment modalities

Summary

Background

Achalasia is an uncommon primary oesophageal motor disorder with an unknown aetiology. Therapeutic options for achalasia are aimed at decreasing the lower oesophageal sphincter pressure, improving the oesophageal empting, and most importantly, relieving the symptoms of achalasia. Modalities for treatment include pharmacologic, endoscopic, pneumatic dilatation and surgical. The decision of which modality to use involves the consideration of multiple clinical and economic factors.

Aim

To review the management strategies currently available for achalasia.

Methods

A Medline search identified the original articles and reviews the published in the English language literature between 1966 and 2006.

Results

The results reveal that pharmacotherapy, injection of botulinum toxin, pneumatic dilatation and minimally invasive surgical oesophagomyotomy are variably effective at controlling the symptoms of achalasia but that each modality has specific strengths and weaknesses which make them each suitable in certain populations. Overall, pharmacologic therapy results in the shortest lived, least durable response followed by botulinum toxin injection, pneumatic dilatation and surgery, respectively.

Conclusion

The optimal treatment for achalasia remains an area of controversy given our lack of complete understanding about the pathophysiology of the disease as well as the high numbers of clinical relapse after treatment. Further research focusing on optimal dosing of botulinum toxin injection and optimal timing of repeated graduated pneumatic dilatations could add to our knowledge regarding long‐term therapy.