Epidemiology,clinical and economic outcomes of admission hyponatremia among hospitalized patients

ABSTRACT

Background: Hyponatremia, the most frequent electrolyte derangement identified among hospitalized patients, is associated with worsened outcomes in patients with pneumonia, heart failure and other disorders.

Research design and methods: We performed a retrospective cohort study of hospitalized patients to quantify the attributable influence of admission hyponatremia on hospital costs and outcomes. Data were derived from a large administrative database with laboratory components, representing 198,281 discharges from 39 US hospitals from January 2004 to December 2005. Hyponatremia was defined as admission serum [Na⁺]?<?135?mEq/L.

Results: The incidence of hyponatremia at admission was 5.5?%?(n?=?10,899). Patients with hyponatremia were older (65.7?±?19.6 vs. 61.5?±?21.8, p?<?0.001) and had a higher Deyo-Charlson Comorbidity Index score (1.8?±?2.1 vs. 1.3?±?1.8, p?<?0.001) than those with normal [Na⁺]. A higher proportion of hyponatremic patients required intensive care unit (ICU) (17.3?%?vs. 10.9?%?, p?<?0.001) and mechanical ventilation (MV) (5.0?%?vs. 2.8?%?, p?<?0.001) within 48?hours of hospitalization. Hospital mortality (5.9?%?vs. 3.0?%?, p?<?0.001), mean length of stay (HLOS, 8.6?±?8.0 vs. 7.2?±?8.2 days, p?<?0.001) and costs ($16,502?±?$28,984 vs. $13,558?±?$24,640, p?<?0.001) were significantly greater among patients with hyponatremia than those without. After adjusting for confounders, hyponatremia was independently associated with an increased need for ICU (OR 1.64, 95?%?CI 1.56–1.73) and MV (OR 1.68, 95?%?CI 1.53–1.84), and higher hospital mortality (OR 1.55, 95?%?CI 1.42–1.69). Hyponatremia also contributed an increase in HLOS of 1.0 day and total hospital costs of $2,289.

Conclusions: Hyponatremia is common at admission among hospitalized patients and is independently associated with a 55?%?increase in the risk of death, substantial hospital resource utilization and costs. Potential for bias inherent in the retrospective cohort design is the main limitation of our study. Studies are warranted to explore how prompt normalization of [Na⁺] may impact these outcomes.     

The impact of pre-endoscopy proton pump inhibitor use on the classification of non-erosive reflux disease and erosive oesophagitis

Aliment Pharmacol Ther 2010; 32: 1266–1274

Summary

Background Factors associated with non‐erosive reflux disease (NERD) and erosive oesophagitis (EO) are incompletely understood and the overlap between the two entities is debated. Aim To compare clinical, demographic, and endoscopic findings in a large cohort of NERD and EO patients. Methods After they completed a validated GERD questionnaire, patients who presented for index endoscopy were enrolled and categorized as NERD or EO. Analysis was performed using Chi‐square, Mann–Whitney U‐test and multivariate logistic regression. Results A total of 696 GERD patients [455 (65.4%) NERD; 241 (34.6%) EO]; mean age 57 years; 92% men and 82% Caucasian were prospectively enrolled. Using logistic regression, patients on PPI were more likely to be classified as NERD (OR: 3.2; P < 0.001). NERD patients were older (OR: 1.50; P = 0.05), less likely to have nocturnal symptoms (OR: 0.63; P = 0.04) and hiatal hernia (OR: 0.32; P < 0.001). Compared with PPI‐naïve NERD patients, those on PPI were more likely to have nocturnal symptoms (69% vs. 29%, P = 0.048) and less likely to have mild‐moderate symptoms (63% vs. 79%, P < 0.001) – similar to the EO group. Conclusions Pre‐endoscopy PPI usage contributes significantly to the classification of GERD patients into the NERD‐phenotype. NERD patients on PPI therapy demonstrate some features that are significantly different from PPI‐naïve patients, but similar to EO patients. This observation supports the notion that some PPI NERD patients are actually healed EO patients, and that an overlap does exist between the GERD phenotypes.     

Effects of a single dose of rabeprazole 20 mg and pantoprazole 40 mg on 24‐h intragastric acidity and oesophageal acid exposure: a randomized study in gastro‐oesophageal reflux disease patients with a history of nocturnal heartburn

Aliment Pharmacol Ther 31 , 991–1000

Summary

Background Nocturnal heartburn is common in patients with gastro‐oesophageal reflux disease (GERD). Aim To compare the effects of single doses of rabeprazole 20 mg and pantoprazole 40 mg on 24‐h intragastric acidity and oesophageal acid exposure (OAE). Methods A total of 52 subjects with GERD and a ≥6‐month history of heartburn were randomized into a blinded, 2 × 2 crossover trial. Subjects’ intragastric pH was monitored in two 48‐h study periods with 6‐ to 13‐day washout between periods. Patients received placebo on day 1, a single dose of rabeprazole 20 mg or pantoprazole 40 mg on day 2, and standardized meals throughout. Results The mean percentage time with intragastric pH >4 was significantly greater with rabeprazole vs. pantoprazole for the 24‐h postdose interval (44.0% vs. 32.8%; P < 0.001). Significant differences were observed in the daytime (51.0% vs. 42.2%; P < 0.001) and nighttime (32.0% vs. 16.9%; P < 0.001). Rabeprazole was also significantly superior in other intragastric pH parameters. There was no statistical difference for OAE between treatments. Conclusions In GERD patients with nocturnal heartburn, rabeprazole 20 mg was significantly more effective than pantoprazole 40 mg in percentage time with intragastric pH >4 during the nighttime, daytime, and 24‐h periods. Differences between treatments in OAE were not demonstrated. This trial is registered with http://clinicaltrials.gov , number NCT00237367.     

Increased oesophageal acid exposure at the beginning of the recumbent period is primarily a recumbent‐awake phenomenon

Background A significant increase in oesophageal acid exposure during early recumbent period has been demonstrated. Aim To determine if acid reflux during the early recumbent period occurs in the recumbent‐asleep or recumbent‐awake period using a novel integrative actigraphy and pH programme. Method Thirty‐nine subjects with heartburn at least three times a week were included. Subjects underwent pH testing concomitantly with actigraphy. Simultaneously recorded actigraphy and pH data were incorporated using a novel integrative technique to determine sleep and awake periods. Characteristics of acid reflux were compared between the recumbent‐awake and recumbent‐asleep periods. Results Seventeen (44.7%) subjects had acid reflux events during recumbent‐awake period as compared to seven (18.4%) in the corresponding recumbent‐asleep period (P = 0.046). The mean number of acid reflux events in recumbent‐awake period was significantly higher than in the corresponding recumbent‐asleep period (8.1 ± 4.4 vs. 3.2 ± 1.5, P < 0.001). In the recumbent‐awake period, 38.4% of acid reflux events were associated with GERD‐related symptoms as compared with 3.7% of acid reflux events during the corresponding recumbent‐asleep period (P = 0.01). Conclusion Increased acid reflux in the early recumbent period occurs primarily during the recumbent‐awake and not during the recumbent‐asleep period.     

Insulin resistance is a major determinant of sustained virological response in genotype 1 chronic hepatitis C patients receiving peginterferon alpha-2b plus ribavirin

Background Cross‐sectional studies suggest insulin resistance is strongly associated with hepatic steatosis and fibrosis in patients with chronic hepatitis C (CHC), which might affect the efficacy of antiviral therapy. Aim To investigate retrospectively the impact of insulin resistance on treatment response in Chinese genotype 1 CHC patients receiving a 24‐week course therapy with peginterferon α‐2b/ribavirin. Methods A total of 133 biopsy‐proven CHC patients were enrolled for analyses. Insulin resistance was evaluated by homeostasis model assessment of insulin resistance (HOMA‐IR). Hepatic fibrosis was graded by the METAVIR scoring system. Results Mean HOMA‐IR progressively elevated along with the severity of hepatic fibrosis (F1–F2 fibrosis: 2.55 ± 0.16 vs. F3–F4 fibrosis: 3.61 ± 0.20, P < 0.001). Compared with patients with sustained virological response (SVR), patients without SVR had significantly higher percentages of F3–F4 fibrosis (62.2% vs. 21.6%, P < 0.001) and baseline high viral load (≥600 000 IU/mL; 64.4% vs. 35.6%, P = 0.038). In addition, patients without SVR had significantly higher plasma levels of insulin (15.03 ± 0.89 vs. 10.19 ± 0.55 μU/mL, P < 0.001) and HOMA‐IR values (3.76 ± 0.23 vs. 2.50 ± 0.15, P < 0.001). Multivariate analyses showed that F1–F2 fibrosis (odds ratio: 4.49, P = 0.001), HOMA‐IR < 2 (odds ratio: 7.15, P = 0.005) and pre‐treatment hepatitis C virus RNA < 600 000 IU/mL (odds ratio: 3.26, P = 0.012) were the independent factors associated with SVR. Conclusions Insulin resistance is a major determinant of SVR in genotype 1 CHC patients receiving peginterferon α‐2b/ribavirin. Strategies to modify insulin resistance may be effective in enhancing SVR before or during anti‐viral therapy.     

Clinical trial: esomeprazole for moderate‐to‐severe nighttime heartburn and gastro‐oesophageal reflux disease‐related sleep disturbances

Aliment Pharmacol Ther 2010; 32: 182–190

Summary

Background Nighttime heartburn, common among patients with gastro‐oesophageal reflux disease (GERD), is associated with substantial clinical effects. GERD‐related sleep disturbances are underappreciated and undertreated. Aim To evaluate the efficacy of esomeprazole on GERD‐related nighttime heartburn and associated sleep disturbances. Methods In this multicentre, randomized, double‐blind, placebo‐controlled study, patients with moderate‐to‐severe nighttime heartburn and GERD‐related sleep disturbances (endoscopies not required) received esomeprazole 20 mg or placebo each morning for 4 weeks. Heartburn symptoms and GERD‐related sleep disturbances were evaluated using the validated Pittsburgh Sleep Quality Index and validated Work Productivity and Activity Impairment Questionnaire. Results The analysis included 262 patients (esomeprazole, n = 137; placebo, n = 125). Significantly more patients receiving esomeprazole achieved nighttime heartburn relief (primary end point) than those receiving placebo (34.3% vs. 10.4%; P < 0.0001). Secondary end points such as relief of GERD‐related sleep disturbances (P = 0.006), days without GERD‐related sleep disturbances (P = 0.0003) and complete resolution of sleep disturbances (P < 0.0001) favoured esomeprazole over placebo. Sleep quality, work productivity and regular daily activities also improved significantly with esomeprazole vs. placebo. Conclusions Esomeprazole 20 mg is effective for patients with moderate‐to‐severe nighttime heartburn and GERD‐related sleep disturbances, improving heartburn symptoms, sleep quality, work productivity and functionality.

     

Systematic review: persistent reflux symptoms on proton pump inhibitor therapy in primary care and community studies

Background Persistent gastro‐oesophageal reflux disease (GERD) symptoms can occur despite proton pump inhibitor (PPI) therapy. Aim To assess the prevalence and potential determinants of persistent GERD symptoms in primary care and community‐based studies. Methods Studies were identified by systematic PubMed and Embase searches; pooled prevalence data are shown as sample‐size weighted means and 95% confidence intervals. Results Nineteen studies in individuals with GERD taking a PPI were included. In interventional, nonrandomized primary care trials, the prevalence of persistent troublesome heartburn and regurgitation was 17% (6–28%) and 28% (26–30%) respectively; in randomized trials, it was 32% (25–39%) and 28% (26–30%), respectively. In observational primary care and community‐based studies, 45% (30–60%) of participants reported persistent GERD symptoms. Overall, persistent GERD symptoms despite PPI treatment were more likely in studies with a higher proportion of female participants [>60% vs. <50%, risk ratio (RR): 3.66; P < 0.001], but less likely in studies from Europe than in those from the USA (RR: 0.71; P < 0.001), and were associated with decreased psychological and physical well‐being. Conclusions Persistent GERD symptoms despite PPI treatment are common in the primary care and community setting. Alternative approaches to management are required.     

Eosinophilic oesophagitis in patients presenting with dysphagia--a prospective analysis

Background Eosinophilic oesophagitis (EoO) may be a common finding in adults presenting with dysphagia. Aim To identify the risk factors and prevalence of EoO in an adult population with dysphagia. Methods All patients with dysphagia referred for an upper endoscopy (EGD) were asked to participate. Patients completed a detailed questionnaire followed by EGD with four quadrant biopsies in the distal and mid‐oesophagus. Primary endpoint was the prevalence of EoO; secondary endpoints included age, gender, asthma, food allergies, gastro‐oesophageal reflux disease/dysphagia score and endoscopic findings. Results Two hundred and sixty‐one patients enrolled between December 2005 and January 2007. Thirty‐one patients (12%) met pathological criteria for EoO. There was no difference in EoO prevalence within each gender. Mean age of EoO patients was 42 ± 15 vs. 61 ± 15 for non‐EoO patients (P < 0.001). EoO was diagnosed in 35% of patients <50 years of age. EoO was present in 22% of asthmatics vs. 9% non‐asthmatics (P < 0.01). EoO was present in 36.8% of patients with self‐reported food allergies vs. 9.3% those without allergy (P < 0.001). A 13/31(42%) of EoO patients did not have the classic EGD findings (rings ± furrows) and would have been missed without oesophageal biopsies. Conclusions Eosinophilic oesophagitis was diagnosed in 12% of the patients presenting with dysphagia with relative risk of 9.5 if age <50 years. Oesophageal biopsies are warranted in patients presenting with dysphagia especially in the younger population. Patients may not present with classic endoscopic findings and EoO can be missed without biopsies.     

Depression and treatment with antidepressants are associated with the development of gastro‐oesophageal reflux disease

Aliment Pharmacol Ther 31 , 1132–1140

Summary

Background The roles of depression and antidepressants in triggering reflux symptoms remain unclear. Aim To compare the incidence of gastro‐oesophageal reflux disease (GERD) in individuals with and without a depression diagnosis and to evaluate risk factors for a GERD diagnosis. The relationship between antidepressant treatment and GERD was also assessed. Methods The Health Improvement Network UK primary care database was used to identify patients with incident depression and an age‐ and sex‐matched control cohort with no depression diagnosis. Incident GERD diagnoses were identified during a mean follow‐up of 3.3 years. Furthermore, we performed nested case‐control analyses where odds ratios (OR) with 95% confidence intervals (CI) were estimated by unconditional logistic regression in multivariable models. Results The incidence of GERD was 14.2 per 1000 person‐years in the depression cohort and 8.3 per 1000 person‐years in the control cohort. The hazard ratio of GERD in patients with depression compared with controls was 1.72 (95% CI: 1.60–1.85). Among patients with depression, tricyclic antidepressant use was associated with an increased risk of GERD (OR: 1.71; 95% CI: 1.34–2.20), while selective serotonin reuptake inhibitors were not associated with GERD. Conclusions A depression diagnosis is associated with an increased risk of a subsequent GERD diagnosis, particularly in individuals using tricyclic antidepressants.     

Elevated plasma Pim‐1 and its clinical significance in patients with pulmonary arterial hypertension

This study was aimed to determine plasma Pim‐1 levels in patients with pulmonary arterial hypertension (PAH) and to estimate the clinical value of Pim‐1 as a biomarker of PAH. This was a single‐centre retrospective study in 111 patients with congenital heart disease (CHD) and idiopathic PAH (IPAH). Those CHD patients were divided into two groups: PAH associated with CHD (PAH‐CHD) and CHD without PAH (nPAH‐CHD). Plasma Pim‐1 levels were measured by enzyme‐linked immunosorbent assay. (a) Plasma Pim‐1 levels were significantly increased in patients with PAH‐CHD and IPAH compared with the healthy control group (27.81 ± 11.34 ng/mL vs 13.02 ± 5.30 ng/mL; 32.81 ± 12.28 ng/mL vs 13.02 ± 5.30 ng/mL, P < 0.05) and nPAH‐CHD (27.81 ± 11.34 ng/mL vs 17.33 ± 7.99 ng/mL; 32.81 ± 12.28 ng/mL vs 17.33 ± 7.99 ng/mL, P < 0.05). Pim‐1 levels were substantially increased in patients with severe PAH‐CHD compared with mild‐to‐moderate PAH‐CHD (19.12 ± 6.70 ng/mL vs 8.54 ± 3.71 ng/mL, P < 0.05). (b) Pim‐1 levels were correlated positively with the mean pulmonary artery pressure (mPAP) and pulmonary vascular resistance (PVR) (r = 0.582, 0.516; P < 0.001, respectively), while negatively with tricuspid annular plane systolic excursion (TAPSE), tricuspid annular plane systolic velocity (S’) and right ventricular fractional area changes (RVFAC) (r = ?0.375, ?0.354, ?0.507; P < 0.05, respectively). (c) PAH‐CHD and severe PAH‐CHD was identified by plasma Pim‐1 with a cutoff value of 16.8 ng/mL (P < 0.001) with a sensitivity of 87.3% and a specificity of 65%, and a cutoff value of 20.53 ng/mL (P < 0.001) with a sensitivity of 87.3% and a specificity of 52%, respectively. Plasma Pim‐1 levels were significantly higher in patients with PAH‐CHD and IPAH. Plasma Pim‐1 may represent an effectively biomarker in patients with PAH.     

Hypergastrinaemia during long-term omeprazole therapy: influences of vagal nerve function, gastric emptying and Helicobacter pylori infection

Aim:

To elucidate the mechanisms that lead to severe hypergastrinaemia during long-term omeprazole therapy for gastro-oesophageal reflux disease (GERD).

Patients and methods:

A total of 26 GERD patients were studied during omeprazole maintenance therapy. Twelve patients with severe hypergastrinaemia (gastrin > 400 ng/L) were compared with 14 control patients (gastrin < 300 ng/L). Helicobacter pylori serology and a laboratory screen were obtained in all patients. Gastric emptying was scored by the evidence of food remnants upon endoscopy 12 h after a standardized meal. Gastric antrum and corpus biopsies were analysed for histological parameters, as well as somatostatin and gastrin concentrations. All patients underwent a meal-stimulated gastrin test and the hypergastrinaemia patients also underwent a vagal nerve integrity assessment by pancreatic polypeptide testing (PPT).

Results:

Severe hypergastrinaemia patients had a longer duration of treatment (80 vs. 55 months; P = 0.047) and were characterized by a higher prevalence of H. pylori infection (9/12 vs. 2/14, P = 0.004), corpus mucosal inflammation and atrophic gastritis (P < 0.04). This was reflected in lower serum pepsinogen A concentrations (mean ± S.E.M. 53.6 ± 17.9 vs. 137 ± 16.0 mg/L, P = 0.03), pepsinogen A/C ratio (1.8 ± 0.3 vs. 4.1 ± 0.6, P = 0.005) and mucosal somatostatin concentrations (2.75 ± 0.60 vs. 4.48 ± 1.08 mg/g protein, P = 0.038). Two patients in the hypergastrinaemia group had signs of delayed gastric emptying, but none in the normogastrinaemia group did (P = N.S.). In addition, both groups had a normal meal-stimulated gastrin response.

Conclusion:

Severe hypergastrinaemia during omeprazole maintenance therapy for GERD is associated with the duration of therapy and H. pylori infection, but not with abnormalities of gastric emptying or vagal nerve integrity.

     

Development and validation of a disease‐specific quality of life questionnaire for gastro‐oesophageal reflux disease: the GERD‐QOL questionnaire

Aliment Pharmacol Ther 31 , 452–460

Summary

Background A simple and meaningful health‐related quality of life (HRQoL) questionnaire for gastro‐oesophageal reflux disease (GERD) patients is lacking. Aim To develop and validate a disease‐specific HRQoL instrument (GERD‐QOL) for GERD patients. Methods An 18‐item questionnaire was generated to measure the impact of GERD on sleep, exercise, diet, need for medication, sex life, work, social activity and psychological well‐being. GERD patients were invited to complete the GERD‐QOL, a visual analogue scale (VAS) and a validated Chinese generic QoL (SF‐36) questionnaire before and after esomeprazole treatment. Factor analysis was performed for item selection and psychometric properties were measured. An English version was developed by a forward‐backward translation process. Results A final 16‐item GERD‐QOL questionnaire was developed. The items were grouped into four subscales (Daily activity, Treatment effect, Diet, and Psychological well‐being) after factor analysis. GERD‐QOL had good item‐internal consistency (Cronbach’s alpha: 0.64–0.88), high test‐retest reliability (intraclass correlation coefficient: 0.73–0.94, P < 0.001). Its subscale scores were correlated with SF‐36 and VAS, which demonstrated high construct validity (P < 0.001). Discriminant validity was verified by correlating GERD‐QOL scores with symptom severity (P < 0.001). Responsiveness after esomeprazole treatment was significant (paired‐t‐test P < 0.001). An English version of GERD‐QOL was developed. Conclusion The instrument, GERD‐QOL, is valid and reliable.     

Randomised clinical trial: high-dose acid suppression for chronic cough - a double-blind, placebo-controlled study

Aliment Pharmacol Ther 2011; 33: 225–234

Summary

Background Cough may be a manifestation of gastro‐oesophageal reflux disease (GERD). The utility of acid suppression in GERD‐related cough is uncertain. Aim To assess the impact of high‐dose acid suppression with proton pump inhibitors (PPI) on chronic cough in subjects with rare or no heartburn. Methods Subjects were nonsmokers without history of asthma, with chronic cough for >8 weeks. All subjects underwent a baseline 24‐h pH/impedance study, methacholine challenge test and laryngoscopy. Subjects were randomised to either 40 mg of esomeprazole twice daily or placebo for 12 weeks. The primary outcome measure was the Cough‐Specific Quality of Life Questionnaire (CQLQ). Secondary outcomes were response on Fisman Cough Severity/Frequency scores and change in laryngeal findings. Results Forty subjects were randomised (22 PPI, 18 placebo) and completed the study. There was no difference between PPI and placebo in CQLQ (mean improvement 9.8 vs. 5.9 respectively, P = 0.3), or Fisman Cough Severity/Frequency scores. Proportion of patients who improved by >1 s.d. on the CQLQ was 27.8% (five of 18) and 31.8% (seven of 22) in the placebo and PPI groups respectively. Conclusion In subjects with chronic cough and rare or no heartburn, high‐dose proton pump inhibitor does not improve cough‐related quality of life or symptoms.     

Hospitalization rates before and after initiation of paliperidone ER in patients with schizophrenia: results from open-label extensions of the US double-blind trials

ABSTRACT

Objective: To assess differences in the number of days hospitalized among schizophrenic patients receiving paliperidone extended-release (paliperidone ER) during the open-label extension (OLE) phases, compared to a similar time period prior to the screening for entry into the double-blind (DB) trials conducted in the United States.

Methods: Mental health-related hospital days during the 52 weeks before entering the DB trials and during the OLE phases were compared. The mean number of hospital days per person per year in the pre- and post-periods was calculated and the statistical significance of pre-post differences was assessed using bootstrap resampling methods. Total person-years were also calculated for the pre- and post-periods to account for different lengths of observation.

Results: Patients' (n = 215) mean (?±?SD) age was 41.2 (?±?11.0) years; most were male (73.0?%?); and black (52.1 vs. 45.1?%?white). The mean (?±?SD) paliperidone ER treatment duration during the OLE phase was 167.0 (?±?145.0) days and the mean (?±?SD) daily dose was 10.5 (?±?2.0) mg. Overall, paliperidone ER patients spent an average (?±?SD) of 13.2 (?±?1.6) and 3.1 (?±?0.7) hospital days per person-year in the pre-and post-periods, respectively (mean?±?SD change 10.0?±?1.8, 95?%?CI 6.5, 13.4, p?<?0.001). Using the 2007 Federal Per Diem Base Rate (i.e., $595.09 per day), this reduction in hospital days would result in an average (?±?SD) cost savings of $5951 (?±?1071) per person per year.

Conclusions: Patients had significantly fewer hospital days in the OLE phase compared to the 1-year period prior to entering the DB trial. Paliperidone ER may play a role in reducing mental health-related hospital days and associated costs. Important study limitations include the lack of a control group, the pre-post design comparing historical data with data collected in the trials which could create a bias due to the mismatch in settings, and patients having more frequent contact with treating physicians and investigators during the trial period, which could favor the outcomes in the OLE phase. Further studies are needed to confirm these findings.     

Trimetazidine Limits the Effects of Myocardial Ischaemia During Percutaneous Coronary Angioplasty

Summary

This open-label, randomised, controlled study is aimed at assessing the effect of pre-treatment with the metabolic agent trimetazidine on the degree of ischaemia during percutaneous transluminal coronary angioplasty (PTCA).

Overall 44 patients with one-vessel coronary artery stenosis (>70%) in the medial part of the left anterior descending artery were included. One group (n?=?22) was pre-treated with oral trimetazidine. The other group (n?=?22) was the control. All patients (n?=?44) were administered aspirin and conventional treatment.

All patients underwent PTCA; stents were implanted in 11 trimetazidine patients and in seven control patients.

The mean ST-segment elevation during all balloon inflations was significantly lower in the trimetazidine group than in the control group (?1.66?±?1.50?mm vs. 3.29?±?1.59?mm, p?=?0.001). Maximal ST-segment elevations and

mean ST elevation values during sequential balloon inflations were also significantly lower with trimetazidine (p?=?0.018). The mean amplitude of the T-wave alterations during all balloon inflations was significantly lower with trimetazidine (3.09?±?2.39?mm vs. 6.83?±?4.31?mm; p?=?0.001). Similarly, the maximal amplitude of the T-wave alterations was 4.50?±?2.90?mm with trimetazidine vs. 9.25?±?4.97?mm in control patients (p?=?0.0005). Angina and rhythm disturbances were more frequent in the control group. Time from balloon inflation to onset of angina was 50?±?26.2s with trimetazidine vs. 32?±?15.0s, for control group (p?=?0.03). The time to pain relief after deflation was 19.3?±?11.4s with trimetazidine vs. 28.2?±?16.8s (p?=?0.001).

Trimetazidine administered a few days before PTCA appears to be a cardioprotective agent for the prevention of myocardial ischaemia.     

Fulminant type 1 diabetes: The clinical and continuous glucose monitoring characteristics in Chinese patients

The purpose of the current study was to investigate the clinical characteristics of fulminant type 1 diabetes mellitus (FT1DM) in Chinese patients and to further determine their glycaemic profiles through continuous glucose monitoring (CGM). Thirty subjects who were diagnosed with FT1DM according to the 2012 JDS criteria were enrolled. Clinical characteristics were compared to those reported in Japanese FT1DM. All subjects received retrospective CGM for 3 days after being converted to subcutaneous insulin injection therapy. Chinese FT1DM patients presented with a shorter duration of symptoms (2.84 ± 2.42 days vs 4.4 ± 3.1 days, P < 0.01), worse islet function (fasting C‐peptide, 0.09 ± 0.11 ng/mL vs 0.30 ± 0.21 ng/mL; 2‐hour C‐peptide, 0.13 ± 0.14 ng/mL vs 0.30 ± 0.30 ng/mL, both P < 0.01), lower prevalence of flu‐like symptoms (46.7% vs 71.4%, P < 0.05), and a significantly higher GADA positive rate (23.3% vs 5.1%, P < 0.01) when compared with Japanese patients. The CGM results showed that the mean time in range (TIR) of FT1DM patients was 49.8 ± 22.1%, while mean amplitude of glycaemic excursion (MAGE) and standard deviations of sensor glucose (SDSG) were 7.58 ± 3.59 mmol/L and 3.19 ± 1.22 mmol/L, respectively, with nearly 1/3 participants coefficient of variation (CV) > 36% (all are male), suggesting a large glucose fluctuation. The female patients were further divided into pregnancy‐related FT1DM (PF) and non‐PF (NPF) subgroups (both n = 5), and we found that PF patients had a significantly higher TIR than NPF patients (77.0 ± 16.1% vs 41.0 ± 22.4%, P < 0.05). There were heterogeneities in the clinical characteristics of FT1DM patients, and the CGM results indicated a very low TIR and large glucose fluctuation which needs careful attention.     

Clinical trial: endoscopic evaluation of naproxen etemesil,a naproxen prodrug,vs. naproxen – a proof‐of‐concept,randomized, double‐blind,active‐comparator study

Aliment Pharmacol Ther 2010; 32: 1091–1101

Summary

Background Nonsteroidal anti‐inflammatory drugs are associated with upper gastrointestinal mucosal injury. Naproxen etemesil is a lipophilic, non‐acidic, inactive prodrug of naproxen that is hydrolysed to pharmacologically active naproxen once absorbed. We hypothesized that with lesser topical exposure to naproxen from the prodrug, there would be reduced gastroduodenal mucosal injury compared with naproxen. Aim To compare the degree of endoscopic mucosal damage of naproxen etemesil vs. naproxen. Methods This multicentre, randomized, double‐blind, double‐dummy trial compared oral naproxen etemesil 1200 mg twice daily (n = 61) with naproxen 500 mg twice daily (n = 59) for 7.5 days in 120 healthy subjects (45–70 years; mean 51 years; 58% female) with baseline total modified gastroduodenal Lanza score ≤2 (no erosions/ulcers) on endoscopy. The primary endpoint was mean total modified gastroduodenal Lanza score on day 7. A secondary endpoint was incidence of gastric ulcers. Results The day 7 mean total modified gastroduodenal Lanza score was 2.8 ± 1.7 for naproxen etemesil vs. 3.5 ± 2.0 for naproxen (P = 0.03), and significantly fewer naproxen etemesil‐treated subjects (3.3%) developed gastric ulcers compared with naproxen‐treated subjects (15.8%) (P = 0.02). Conclusion In this first proof‐of‐concept study, naproxen etemesil was associated with significantly lower gastroduodenal mucosal injury compared with naproxen after 7 days of exposure (Clinical trial number: NCT00750243).     

Reflux parameters as modified by EsophyX or laparoscopic fundoplication in refractory GERD

Aliment Pharmacol Ther 2011; 34: 67–75

Summary

Background EsophyX is a novel transoral incisionless fundoplication device developed to mimic surgical fundoplication. EsophyX fundoplication improves acid reflux parameters in proton pump inhibitor (PPI)‐responsive GERD patients but its efficacy in refractory GERD has been scarcely studied. Aim To assess reflux parameters before and after EsophyX or laparoscopic fundoplication and their relationship with symptoms in refractory GERD. Methods In an open‐label study, we enrolled prospectively patients with heartburn/regurgitation persisting despite high‐dose PPI therapy. Impedance‐pH monitoring was performed on PPI therapy before intervention and off PPI therapy 3 months after intervention. Results Ten patients chose to undergo EsophyX (EndoGastric Solutions, Redmond, WA, USA) fundoplication while ten chose laparoscopic fundoplication, and the baseline characteristics were comparable. Distal and proximal refluxes were significantly reduced post‐operatively in the surgical but not in the endoscopic group and the median values were significantly lower in the former than in the latter. The oesophageal acid exposure time was normal in 50% of cases after EsophyX and in 100% of cases after surgery (P = 0.033); the number of distal refluxes was normal in 20% and 90% of cases (P = 0.005) and the number of proximal refluxes was normal in 40% and 100% of cases (P = 0.011), respectively. A positive persisting symptom‐reflux association was found post‐operatively in 6/10 patients in the EsophyX group and in 0/10 patients in the surgical group (P = 0.011). Conclusions In patients with refractory GERD, EsophyX fundoplication is significantly less effective than laparoscopic fundoplication in improving reflux parameters and accordingly, in inducing symptom remission.     

Toll‐like receptor 4 D299G polymorphism and the incidence of infections in cirrhotic patients

Aliment Pharmacol Ther 31 , 1192–1199

Summary

Background Toll‐like receptor (TLR) 4 genetic polymorphisms, mainly D299G, have been associated with increased predisposition to infection in several populations. Aim To retrospectively analyse the relationship between the presence of the TLR4 D299G polymorphism and the incidence of bacterial infections in cirrhotic patients. Methods We included 111 consecutive cirrhotic patients hospitalized with ascites and we determined the presence of the TLR4 D299G polymorphism by PCR–RFLP (polymerase chain reaction–restriction fragment length polymorphism) and its relationship with the incidence of previous bacterial infections. Results Ten out of 111 (9%) cirrhotic patients presented with the TLR4 D299G polymorphism. The mean follow‐up from first decompensation of cirrhosis until current admission was longer in D299G polymorphism patients than in wild‐type patients (53.8 ± 40.7 vs. 35.4 ± 48.3 months, P = 0.03). D299G polymorphism patients showed a trend towards a higher incidence of history of previous infections (80% vs. 56.4%, P = 0.19), as well as a higher number of infections (2.8 ± 2.3 vs. 1.0 ± 1.3, P = 0.01) and bacteriaemias (0.4 ± 1.0 vs. 0.04 ± 0.2, P = 0.02) per patient than wild‐type patients. Conclusions Toll‐like receptor 4 D299G polymorphism could influence not only the predisposition to bacterial infections but also the evolution of the disease in cirrhotic patients. Further prospective studies in larger series of patients are warranted.     

Review article: the treatment of functional abdominal bloating and distension

Aliment Pharmacol Ther 2011; 33: 1071–1086

Summary

Background Abdominal bloating and distension are common symptoms in patients with functional gastrointestinal disorders (FGIDs), however, relatively little is known about their treatment. Aim To review the treatment trials for abdominal bloating and distension. Methods A literature review in Medline for English‐language publications through February 2010 of randomised, controlled treatment trials in adults. Study quality was assessed according to Jadad’s score. Results Of the 89 studies reviewed, 18% evaluated patients with functional dyspepsia, 61% with irritable bowel syndrome (IBS), 10% with chronic constipation and 10% with other FGIDs. No studies were conducted in patients diagnosed with functional abdominal bloating. The majority of trials investigated the efficacy of prokinetics or probiotics, although studies are heterogeneous with respect to diagnostic criteria and outcome measures. In general, bloating and/or distension were evaluated as secondary endpoints or as individual symptoms as part of a composite score rather than as primary endpoints. A greater proportion of IBS patients with constipation reported improvement in bloating with tegaserod vs. placebo (51% vs. 40%, P < 0.0001) and lubiprostone (P < 0.001). A greater proportion of nonconstipating IBS patients reported adequate relief of bloating with rifaximin vs. placebo (40% vs. 30%, P < 0.001). Bloating was significantly reduced with the probiotics, Bifidobacterium infantis 35624 (1 × 10⁸ dose vs. placebo: ?0.71 vs. ?0.44, P < 0.05) and B. animalis (live vs. heat‐killed: ?0.56 ± 1.01 vs. ?0.31 ± 0.87, P = 0.03). Conclusions Prokinetics, lubiprostone, antibiotics and probiotics demonstrate efficacy for the treatment of bloating and/or distension in certain FGIDs, but other agents have either not been studied adequately or have shown conflicting results.