Gastrointestinal bleeding risk of non-vitamin K oral anticoagulants is similar to warfarin - a Japanese retrospective cohort study
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BACKGROUND AND AIM: Although several non-vitamin K oral anticoagulants have been developed to prevent cardiogenic thrombosis, the status of hemorrhagic complications in the clinical setting among Asian populations, including Japan, remains unclear. We conducted this retrospective cohort study to clarify the current status of hemorrhagic events during antithrombotic therapy with non-vitamin K oral anticoagulants, with particular focus on gastrointestinal bleeding. METHODS: Medical charts of 475 patients prescribed dabigatran, rivaroxaban, or apixaban between April 2011 and September 2014 were reviewed to examine whether any hemorrhagic events occurred, compared with 135 patients who received warfarin between April 2009 and March 2011. RESULTS: Incidences of total and actionable hemorrhage in patient taking non-vitamin K oral anticoagulants were 13.8% per year and 4.6% per year, respectively, showing no significant differences from those in warfarin users (9.3% per year and 5.0% per year, respectively). In addition, actionable gastrointestinal hemorrhage occurred at similar rates in non-vitamin K oral anticoagulants users (2.1% per year) and warfarin users (1.5% per year). Most hemorrhages were from the lower gastrointestinal tract, and considerable events involved perianal bleeding. Multiple regression analysis showed that age, concomitant dual antiplatelet therapy, and concomitant nonsteroidal anti-inflammatory drug therapy were significant factors related to actionable gastrointestinal bleeding. CONCLUSIONS: Risk of gastrointestinal hemorrhage in patients taking non-vitamin K oral anticoagulants was similar to that in patients taking warfarin. The dominant bleeding site was the lower gastrointestinal tract.
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[Selective serotonin reuptake inhibitor and gastrointestinal hemorrhage].

Selective serotonin reuptake inhibitors (SSRI) are widely used antidepressants characterized by less-frequent adverse effects compared with classical anti-depressive agents. On the other hand, SSRI can cause hemorrhagic events more due to impaired platelet aggregation induced by a depletion of serotonin in the peripheral platelet. Epidemiological studies have indicated that patients taking SSRI are predisposed to gastrointestinal hemorrhage, especially in case that nonsteroidal anti-inflammatory drugs are prescribed concomitantly. Here we describe a risk of the gastrointestinal hemorrhage in patients taking SSRI.

[Treatment and prevention of NSAIDs-induced gastrointestinal injury--the role of gastroenterologist].

According to many clinical researches, it is obvious that patients taking NSAIDs including low-dose aspirin have upper GI injury frequently than those without. Recently, the GI event of those medicines becomes more serious clinical problem in Japan in which aging population is getting larger year by year. Evaluation of GI risk and appropriate use of anti -ulcer drugs, especially proton-pump inhibitors, are recommended for the prevention. Additionally, the close communication and cooperation between doctors who prescribe the medicines and gastroenterologists is essential for minimizing such adverse reaction. Here we describe on the role of gastroenterologists on the prevention of GI event caused by NSAIDs and aspirin.

Prevalence of erosive esophagitis among Japanese patients taking low-dose aspirin.

BACKGROUND AND AIM: The risk for erosive esophagitis (EE) with low-dose aspirin (ASA) remains unknown, especially among Japanese patients. We conducted the present study to compare the risk of EE with that of gastroduodenal mucosal injury among Japanese patients taking ASA. METHODS: From 5555 patients undergoing upper gastrointestinal endoscopy from January 2005 to December 2006 at Teikyo University Hospital, Tokyo, Japan, 159 patients (76 males and 83 females, mean age: 69.3 +/- 11 years) fulfilling the following conditions were selected: (i) taking ASA (less than 100 mg/day) continuously; (ii) not taking acid suppressants; and (iii) no history of gastrointestinal tract surgery, malignancies, severe cardiac failure, or liver cirrhosis. Age- and sex-matched patients not taking aspirin were randomly chosen as controls (n = 159). Two well-experienced endoscopic examiners evaluated endoscopic records to determine the presence or absence of esophageal hiatal hernia, EE, and gastroduodenal ulcers. RESULTS: The prevalence of EE in patients taking aspirin (9.4%) was not different from that of the controls (6.3%, odds ratio [OR]: 1.5, 95% confidence interval [CI]: 0.7-3.2), whereas peptic ulcers were found more frequently in the aspirin group (14%) than in the control group (4%, OR: 3.6, 95% CI: 1.5-8.8). CONCLUSION: In Japanese patients taking ASA, EE was not as common as peptic ulcers.

Effects of proton pump inhibitors on gastric emptying: a systematic review.

The proton pump inhibitor (PPI) is widely used for the treatment of gastroesophageal reflux disease, peptic ulcer diseases, and functional dyspepsia. The pathogenesis of these acid-related and/or functional upper gastrointestinal disorders is potentially associated with abnormal gastric emptying. To date, variable effects of PPIs on gastric emptying have been reported. Therefore, it is relevant to gather and analyze published information on this topic. A systematic literature search has been performed, showing that the delaying effect of PPIs on gastric emptying of solid meals is consistent, whereas the effect of PPIs on the emptying of liquids is inconsistent. The underlying mechanisms whereby PPIs may affect gastric emptying have been discussed, most of which still remain hypothetic. Gastric emptying of solids involves a process of peptic hydrolysis. PPIs impair the hydrolytic digestion by inhibiting acid-dependent peptic activity, thereby delaying the solid emptying. Gastric emptying of liquids largely depends on volume and energy density of intragastric contents. PPIs variably modify the volume and the energy density by reducing gastric fluid secretion, thereby modifying the liquid emptying in an unpredictable manner. Hypergastrinemia has been considered to delay gastric emptying, but it seems of minor importance in the regulation of gastric emptying during PPI use. The delayed emptying of solids due to PPI therapy may have clinical implications in the management of gastroesophageal reflux disease, functional dyspepsia, as well as diabetes.

No relationship between plasma desacyl-ghrelin levels and rabeprazole-related delay in gastric emptying : controlled study in healthy volunteers.

BACKGROUND AND OBJECTIVE: Recent studies have indicated that rabeprazole, a proton pump inhibitor, delays gastric emptying. However, the mechanism of action remains unclear. We conducted this study to clarify whether desacyl-ghrelin (the inactive form of the endogenous growth hormone secretagogue receptor ghrelin) is involved in rabeprazole-induced changes in gastric motor function. METHODS: Twelve healthy males underwent (13)C-acetate breath tests to evaluate gastric emptying of a liquid meal twice after administration of rabeprazole 20 mg/day for 3 days or no medication (control). Gastric emptying was evaluated by two parameters: half-emptying time and time to peak (13)CO(2) excretion. Plasma desacyl-ghrelin levels were measured in blood samples collected at three time points: immediately pre-test and 1 and 2 hours after ingestion of the test meal. RESULTS: Rabeprazole significantly delayed gastric emptying of the liquid meal. However, plasma desacyl-ghrelin levels after ingestion of the liquid meal showed little difference before or after rabeprazole administration. CONCLUSION: The results indicate that desacyl-ghrelin was not associated with changes in gastric emptying caused by rabeprazole.

Reliability of the time to maximal [13CO2] excretion and the half-[13CO2] excretion time as a gastric emptying parameter: assessments using the Wagner-Nelson method.

In the [(13)C]-octanoate breath test, two popular parameters have been used to quantify gastric emptying rates, namely the time to the maximal [(13)CO(2)] excretion (T(max)) and the time to the half-[(13)CO(2)] recovery (T(1/2b)). Although each of T(max) and T(1/2b) is closely correlated with the scintigraphic half-emptying time, the two parameters occasionally indicate different judgments on a gastric emptying rate. In this study, to clarify which of the two parameters is more reliable, T(max) and T(1/2b) were compared to the "reference" parameters calculated using the Wagner-Nelson method, which allows accurate estimation of a time-course of gastric emptying from breath data. Ten healthy male volunteers underwent the breath test after ingestion of a muffin meal (320 kcal) containing 100 mg [(13)C]-octanoate. Breath samples were collected at 15-min intervals for 6 h. According to the conventional analytical algorithm, T(max) and T(1/2b) were mathematically calculated. By applying Wagner-Nelson analysis to the breath test, the time-percent gastric retention curve was generated and the half-emptying time (T(1/2WN)) was determined. T(1/2WN) was more closely correlated with T(max) (r=0.954, P<0.0001) than with T(1/2b) (r=0.782, P=0.008). T(max) was significantly correlated with the percent gastric retention value in the early (t=0.25 and 0.5 h), the middle (t=1.0 and 1.5 h), and the late (t=2.0 h) postprandial phase. T(1/2b) was significantly correlated with the gastric retention value in the middle and the late phase, but not with the gastric retention value in the early phase. The present results show that T(1/2b) has limited capability to reflect gastric emptying in the early postprandial period, suggesting that T(max) is more reliable than T(1/2b) as a gastric emptying parameter.

Reliability of rapid urinary test for antibody to Helicobacter pylori in adult patients with proteinuria.

A urinary test for detecting the anti-H. pylori antibody using immunochromatography (RAPIRAN) is considered suitable for the screening purpose. However, this may yield spurious results in the presence of proteinuria. The present study was conducted to evaluate the diagnostic performance of RAPIRAN in patients with proteinuria. Urine and serum samples of adult inpatients with proteinuria were used for analyses. The diagnosis of H. pylori infection was made based on the seropositivity of anti-H. pylori antibody using 2 different serum tests. Fifty-one subjects were eligible for analyses. The serum tests showed negative and positive in 25 and 26 patients, respectively. Two of 25 seropositive patients had a negative result in RAPIRAN, and 1 provided invalid data. All of seronegative patients showed negative in RAPIRAN. The overall accuracy was 95.0%. The present study showed that RAPIRAN has diagnostic quality enough to use clinically also in patients with proteinuria.

Assessment of the gastric emptying velocity by the 13C-octanoate breath test: deconvolution versus a Wagner-Nelson analysis.

BACKGROUND: The dynamic change in gastric emptying on a minute-by-minute basis (gastric velocity) is evaluated by the 13C-octanoate breath test with deconvolution analysis. However, deconvolution is impractical, because it requires dual experiments to obtain 13CO2 excretion profiles following intraduodenal and oral administration of 13C-octanoate. We investigated whether the Wagner-Nelson method, used in drug absorption studies, can determine the velocity profile based on a single experiment as accurately as deconvolution, and whether the velocity assessed by the Wagner-Nelson method is sensitive enough to detect subtle changes in gastric emptying induced by butylscopolamine. METHODS: Five male volunteers underwent a 4-h breath test twice, after intraduodenal administration of 20 ml normal saline containing 100 mg 13C-octanoate and after ingestion of a 320-kcal muffin containing 100 mg 13C-octanoate. Deconvolution determined the velocity profile by subtracting duodenal from oral data, and the Wagner-Nelson method produced it from only oral data. The velocity profiles were compared between the two methods. Another six male subjects underwent the breath test by ingesting a muffin twice, once with and once without 20 mg oral butylscopolamine. The velocity profiles generated by the Wagner-Nelson analysis and the conventional 13CO2 excretion curves were compared between the two occasions. RESULTS: The two techniques yielded identical velocity profiles. The velocity profile detected a significant change in the emptying pattern induced by butylscopolamine (initial acceleration with subsequent deceleration), while the conventional breath curves failed to detect this change. CONCLUSIONS: Velocity assessment by a Wagner-Nelson analysis can precisely describe altered gastric emptying, based on a single experiment.

Effect of cigarette smoking on gastric emptying of solids in Japanese smokers: a crossover study using the 13C-octanoic acid breath test.

BACKGROUND: Cigarette smoking is associated with an increased risk of peptic ulcer and gastroesophageal reflux disease. Gastric emptying disorders may play a role in the development of these upper gastrointestinal diseases. Thus, studies examining a link between smoking and gastric emptying disorders have clinical relevance. This study was conducted to investigate the effect of smoking on gastric emptying of solids in Japanese smokers. METHODS: The (13)C-octanoic acid breath test was performed in eight male habitual smokers on two randomized occasions (either sham smoking or actively smoking). The time vs (13)CO(2) excretion rate curve was mathematically fitted to a conventional formula of y (t) = m*k*beta*e(-k*t)*(1 - e(-k*t))(beta-1), and the parameters of k and beta were determined: under the crossover protocol, a larger (smaller) beta indicates slower (faster) emptying in the early phase, and a larger (smaller) k indicates faster (slower) emptying in the later phase. The half (13)CO(2) excretion time (t(1/2b) = -[ln(1 - 2(-1/beta))]/k) and the time of maximal (13)CO(2) excretion rate (t(max) = [lnbeta]/k) were also calculated. Between the two occasions, k, beta, t(1/2b), and t(max) were compared by the Wilcoxon signed-rank test. RESULTS: After smoking, k was significantly increased. No significant differences were found in beta, t(1/2), and t(max) between the two occasions. CONCLUSIONS: The increase in k suggests the acceleration of gastric emptying in the later phase. For the first time, this study has revealed that acute smoking speeds the gastric emptying of solids in Japanese habitual smokers.

Reliability of urinary tests for antibody to Helicobacter pylori in patients with pulmonary tuberculosis.

AIM: Although the quality of currently available urinary tests for detecting antibody to Helicobacter pylori (H pylori) have been proved in some populations, the accuracy has not been studied regarding patients who suffer from pulmonary tuberculosis with multi-drug treatments. The present study was conducted to evaluate the accuracy of these urinary tests for antibody to H pylori in these patients. METHODS: Serum samples from 61 inpatients with pulmonary tuberculosis were tested using enzyme immunoassay, and urine samples were assayed by enzyme-linked immunosorbent assay method (URINELISA) and immunochromatography method (RAPIRAN). Medicines prescribed to the patients were recorded for medical charts, to evaluate the influences on the results of urinary tests. RESULTS: The sensitivity, specificity, and consistency of URINELISA against the serum test were 93.1%, 65.6%, and 78.6% respectively, and those of RAPIRAN were 86.2%, 93.7%, and 90.1% respectively, which were almost equal to the data previously reported. Prescribed medicines had little influence on the results. CONCLUSION: The two urinary tests for detecting H pylori antibody have a diagnostic accuracy in patients with pulmonary tuberculosis given multiple anti-tuberculosis drugs.

Early gallbladder carcinoma associated with primary sclerosing cholangitis and ulcerative colitis.

Patients troubled with primary sclerosing cholangitis (PSC) and ulcerative colitis (UC) are at high risk for cholangiocarcinoma, whereas cancer of the gallbladder (GBC) is rarely reported to develop in that population. A Japanese man aged 62 years with a 14-year history of PSC and UC had been found to have a protruding lesion of the gallbladder by screening sonography. The preoperative examination suggested the lesion to be GBC at an early stage. Pathology examination after cholecystectomy proved that the lesion was papillary adenocarcinoma localized in the mucosal layer. Although the prognosis of GBC is poor, the outcome of cholecystectomy against early GBC is relatively good. Early detection of the tumor is required for a better prognosis of patients with GBC. According to the review of the literature, PSC and UC patients are regarded as a high-risk group not only for cholangiocarcinoma but also GBC. It is advocated that clinicians perform repeated radiographic examinations including sonography for patients with PSC and UC even if the diseases are being controlled.

Gastric emptying of liquids is delayed by co-ingesting solids: a study using salivary paracetamol concentrations.

BACKGROUND: Paracetamol concentrations in plasma, a frequently used index of gastric emptying (GE) of liquids, are closely correlated with those in saliva. GE of liquids is delayed by co-ingesting solids. No researchers have used salivary paracetamol concentrations to show this phenomenon. The aim of this study was to elucidate whether salivary paracetamol concentrations can detect the food-induced delay in liquid GE. METHODS: Paracetamol absorption was measured twice in five healthy male volunteers. Following an overnight fast, they received 10 mg/kg paracetamol in 200 ml water alone on one occasion, and received this solution after consuming a 400 kcal-containing cookie on another occasion. After thorough rinsing of the month, 1 ml saliva was obtained, simultaneously with 2 ml blood, at 0, 0.25, 0.5, 0.75, 1.0, 2.0, 3.0, 4.0, and 6.0 h after paracetamol intake. The peak concentration (C(max)), the time to C(max) (t(max)), the area under the curve (AUC), and C(max)/AUC in plasma were calculated. Salivary C(max) and t(max) were also determined. RESULTS: Plasma C(max) and AUC were not significantly different between the two occasions. In contrast, significant differences in plasma t(max) and C(max)/AUC ( P < 0.05) established the food-induced delay in GE. Salivary t(max) could detect the delayed GE, whereas salivary C(max) could not. CONCLUSIONS: Salivary t(max) can document the solid meal-induced delay in liquid GE.