Antisecretory Drugs Research Articles

CURRENT MANAGEMENTS AND OUTCOMES OF PEPTIC AND ARTIFICIAL ULCER BLEEDING IN JAPAN

The recent trend of gastroduodenal ulcer bleeding in Japan has not been elucidated in detail and the data for a new categorized type, artificial ulcer bleeding, is completely lacking. The purpose of this paper is to elucidate current managements and outcomes of peptic and artificial ulcer bleeding in Japan. A retrospective multicenter study of consecutive case series was carried out during one year at nine departments of high-volume hospitals in Japan. The study included 325 consecutive patients (239 with peptic ulcers and 86 with artificial ulcers) with bleeding nonmalignant gastroduodenal ulcers that were revealed by emergency endoscopy between January 2008 and December 2008. Hemostasis was carried out mainly using endoscopic treatments. Rates of successful initial hemostasis, rebleeding, transfer to surgery, and death were recorded according to peptic and artificial ulcer bleeding. Additionally, preferred endoscopic methods, concomitant use of antisecretory drugs, and timing of second-look endoscopy were also measured. A total of 227 (99.1%) of 229 peptic ulcer patients with endoscopic treatment and all (100%) 84 artificial ulcer patients underwent successful tentative hemostasis. Rebleeding occurred in 23 peptic ulcer patients (10.1%) and 10 artificial ulcer patients (11.9%). One peptic ulcer patient and two artificial ulcer patients had final surgical rescue due to rebleeding. No death was observed. Monotherapy was predominant (around 65% of cases) in both types of ulcers. The coagulation forceps method was more frequently applied in artificial ulcers (P < 0.05). A per oral proton pump inhibitor was more frequently used in artificial ulcers (P < 0.05), although an intravenous proton pump inhibitor was used in the majority of patients in both types of ulcers. The frequency of second-look endoscopy in peptic ulcers (88%) was significantly higher than that in artificial ulcers (71%) (P < 0.05). There seemed to be no rule as to the timing of second-look endoscopy, although it was most frequently performed on the day after hemostasis. The recent outcomes of endoscopic treatment for nonmalignant gastroduodenal bleeding in Japan were excellent in both peptic and artificial ulcers with similar efficacies. Although they were minor findings, some differences in applied endoscopic methods, concomitant use of antisecretory drugs, and presence of second-look endoscopy were observed.

PWE-078 Intragastric ph holding time of pH &lt;4 predicts low erosive esophagitis healing rate

<h3>Introduction</h3> We have previously proposed a linear relationship between the degree and duration of suppression of 24-h intragastric acidity and the healing rate of erosive esophagitis (EE) with the best predictor as per cent time pH ≥4. Poor response to PPI is an increasingly important concern. Simply reporting time pH &lt;4 may not reflect the extent of acid exposure because of the log scale of pH (1 unit pH change is a 10-fold change in [H+ ion] and a 100-fold increase if pH falls from 4 to 2). Indeed, in healthy volunteers ∼40% of the 24-h is pH ≤4 after 5 days esomeprazole 40 mg om and pH is &lt;2 for 42% of the time between midnight and 0700.1 We aimed to investigate the relationship of time pH &lt;4 in the 24-h and the EE healing rate at 4 and 8 weeks with antisecretory drugs, since time pH &lt;4 is the only widely available pH parameter. <h3>Methods</h3> A meta-analysis was performed to provide 24-h intragastric pH values at steady state (day 5–8) in healthy volunteers and the EE healing rate at 4 or 8 weeks, by searching the English-language literature up to June 2009 in MEDLINE and EMBASE. For pH data, a weighted mean is only possible by using the sample size of each arm ((mean×n from each study)/Σ treated N). A regimen was excluded if &lt;20 subjects provided pH data. For EE data, the pooled healing rate was calculated by weighting the sample size (random effect model) using StatsDirect®2.6.3. Here also a regimen was excluded if &lt;30 subjects per arm provided EE data. Standard linear regression was performed by SPSS® 17.0, with the pooled EE healing rate at 4 weeks or 8 weeks as the dependent variable and mean per cent time pH &lt;4 in 24-h of the corresponding treatment regimen as the independent variable. <h3>Result</h3> 95 studies (411 arms) provided intragastric pH data and 109 studies (243 arms) provided EE healing data for 3 H2-RAs, 5 PPIs and placebo. The commonly reported pH parameter in the pH-EE model was mean per cent time pH &lt;4, which was used in the model. At 4 weeks, the model for the EE (all grades) healing rate = 110.52−1.01* mean per cent time pH &lt;4 in 24 h (R=0.862, p&lt;0.001). At 8 weeks. The model for EE (all grades) healing rate=124.88−1.02* mean per cent time pH &lt;4 in 24 h (R=0.887, p&lt;0.001). <h3>Conclusion</h3> Any increase in the time intragastric pH is pH &lt;4 in the 24 h at steady state in healthy volunteers is associated with a decrease in the EE healing rate at 4 and 8 weeks. The per cent time that intragastric pH &lt;4 is a significant predictor for EE non-healing. Although, not usually reported, a better predictor is likely to be the time pH is &lt;3 or better pH &lt;2, especially during the night-time period.

Clinical Practice: Diagnosis and Evaluation of Dyspepsia

The main issue regarding the approach to the patient with uninvestigated dyspepsia is whether the symptoms are the result of an important clinical illness, which then determines the appropriate management strategy for the treatment of the symptoms. An initial trial of empiric antisecretory drugs is recommended for those without Helicobacter pylori infection and no alarm symptoms, whereas H. pylori eradication is recommended for those with an active H. pylori infection. Treatment expectations for H. pylori infections should theoretically be similar to other common infectious diseases. In most regions, clarithromycin resistance has undermined traditional triple therapy so that it is no longer a suitable choice as an empiric therapy. Four drug therapies, such as sequential, concomitant, and bismuth-quadruple therapy are generally still acceptable choices as empiric therapies. Posteradication testing is highly recommended to provide early identification of otherwise unrecognized increasing antimicrobial resistance. However, despite the ability to successfully cure H. pylori infections, a symptomatic response can be expected in only a minority of those with dyspepsia not associated with ulcers (so called nonulcer dyspepsia). Overall, from the patients stand point, symptomatic relief is often difficult to achieve and physicians must rely on reassurance along with empiric and individualized care.

Role of stereotactic radiosurgery in the management of pituitary adenomas

Trans-sphenoidal neurosurgery is the gold standard treatment for pituitary adenomas, but it can be contraindicated or ineffective. Stereotactic radiosurgery is a procedure aimed at controlling hormone hypersecretion and tumor size of pituitary adenomas. This Review discusses the long-term efficacy and adverse effects of stereotactic radiosurgery with the Gamma Knife((R)) in secreting and nonsecreting pituitary adenomas. Long-term data confirm the antisecretory efficacy of the procedure (about 50% remission in hypersecreting tumors) but also a previously unknown low risk of recurrence (2-10% of cases). The time to remission is estimated to range from 12 to 60 months. The antitumoral efficacy of this treatment against nonsecreting tumors is observed in about 90% of cases. Hypopituitarism is the main adverse effect, observed in 20-40% of cases. Comparisons with conventional fractionated radiotherapy reveal a lower rate of remission with Gamma Knife((R)) radiosurgery, counterbalanced by a more rapid efficacy and a lower rate of hypopituitarism. Short-term follow-up results on stereotactic fractionated radiotherapy suggest a risk of hypopituitarism similar to the one observed with radiosurgery. Therefore, stereotactic radiosurgery is probably still useful to treat some cases of pituitary adenoma, despite the fact that antisecretory drugs, particularly for acromegaly and prolactinomas, are becoming more effective and are well tolerated, thus increasing the probability of success with nonsurgical therapy.

Hypochlorhydric stomach: a risk condition for calcium malabsorption and osteoporosis?

Malabsorption of dietary calcium is a cause of osteoporosis. Dissolution of calcium salts (e.g. calcium carbonate) in the stomach is one step in the proper active and passive absorption of calcium as a calcium ion (Ca2+) in the proximal small intestine. Stomach acid markedly increases dissolution and ionization of poorly soluble calcium salts. If acid is not properly secreted, calcium salts are minimally dissolved (ionized) and, subsequently, may not be properly and effectively absorbed. Atrophic gastritis, gastric surgery, and high-dose, long-term use of antisecretory drugs markedly reduce acid secretion and may, therefore, be risk conditions for malabsorption of dietary and supplementary calcium, and may thereby increase the risk of osteoporosis in the long term.

Traveling Internationally: Avoiding and Treating Travelers' Diarrhea

Traveling Internationally: Avoiding and Treating Travelers' Diarrhea

Performance of acidified 14C‐urea capsule breath test during pantoprazole and ranitidine treatment

Urea breath test (UBT) results could be false negative in patients taking antisecretory drugs. This effect would be prevented by citric acid administration during UBT. We prospectively investigated whether acidified 14C-urea capsule prevents false negative UBT results in patients taking antisecretory drugs and show interference with the duration of medications. Sixty Helicobacter pylori positive patients were included. Pantoprazole (40 mg/day) was given to 27 patients for 28 days and ranitidine (300 mg. o.d.) to 33 patients for 60 days. Urea breath tests were repeated on days 14 and 28 in both groups and on day 60 in the ranitidine group. The baseline mean breath counts of two groups did not show any significant difference. Pantoprazole led to a significant decrease in mean breath counts on day 14 (P < 0.005). Six of 27 and 3 of 25 patients taking pantoprazole developed negative or equivocal UBT results on days 14 and 28, respectively. Two of 32, 2 of 32 and 3 of 21 patients taking ranitidine developed negative or equivocal UBT results on days 14, 28 and 60, respectively. The use of acidified 14C-urea capsule did not prevent false negative UBT results in patients taking pantoprazole and ranitidine, and the duration of medication does not affect the test results.

Long-Term Results of Stereotactic Radiosurgery in Secretory Pituitary Adenomas

To date, no study reported long-term follow-up results of gamma knife stereotactic radiosurgery (SR). The aim of the study was to determine long-term efficacy and adverse effects of SR in secreting pituitary adenomas. We conducted a retrospective study of patients treated by SR in the center of Marseille, France, with a follow-up of at least 60 months. A total of 76 patients were treated by SR for acromegaly (n = 43), Cushing's disease (CD; n = 18), or prolactinoma (n = 15) as a primary (n = 27) or adjunctive postsurgical treatment (n = 49). After withdrawal of antisecretory drugs, patients were considered in remission if they had mean GH levels below 2 ng/ml and normal IGF-I (acromegaly), normal 24-h urinary free cortisol, and cortisol less than 50 nmol/liter after low-dose dexamethasone test (CD) or two consecutive normal samplings of prolactin levels (prolactinoma). After a mean follow-up of 96 months, 44.7% of the patients were in remission. Mean time to remission was 42.6 months. Twelve patients presented late remission at least 48 months after SR. Two patients with CD presented late recurrence 72 and 96 months after SR. Forty percent of patients treated primarily with SR were in remission. Target volume and initial hormone levels were significant predictive factors of remission in univariate analysis. Radiation-induced hypopituitarism was observed in 23% patients; in half of them, hypopituitarism was observed after a mean time of 48 to 96 months. Twenty-four patients were followed for more than 120 months; rates of remission and hypopituitarism were similar to the whole cohort. SR is an effective and safe primary or adjunctive treatment in selected patients with secreting pituitary adenomas.

M1895 Long-Term Treatment Patterns in Children and Adolescents with a New Diagnosis of Gastroesophageal Reflux Disease

the predicted and reported EE healing rate at 8 weeks. This pH-EE healing model provides a tool to predict the healing response of EE with antisecretory drugs based on parameters of acid inhibition. This will be especially useful for new anti-secretory drugs.

Influence of generics in prescribing dynamics of proton pump inhibitors in general practice

Use of antisecretory drugs has greatly increased in recent years in Italy. After the launching of generic lansoprazole (early 2006), several Italian Regional Health Authorities have introduced measures to favour the prescription of less expensive PPI. The aim of this study is to evaluate general practitioners’ prescription (GPs) of different Proton Pump Inhibitors (PPIs) in the period between 2005 to 2008. Analysis has been performed on a database of 99 medical practitioners that have managed an average of 150,000 inhabitants. We evaluate the PPIs prescriptions from Jan 2005 to Dec 2008. Evaluations performed are the following: 1) PPI prescription (total and separately for lansoprazole, esomeprazole, pantoprazole, rabeprazole, and omeprazole); 2) prevalence of the reimbursement purpose (Gastroprotection – G; Acid-Related Disease – ARD); 3) PPI prescriptions separately for ARD diagnostic codes. Data were expressed as Compound Annual Growth Rate (CAGR). PPI consumption were quantified using Defined Daily Dose system (DDD). The total volume of PPI’s prescribing increased progressively over the 4 years (CAGR +15%). The proportion of defined daily doses accounted for by lansoprazole increased from 12.0% in 2005 to 30.9% in 2008. The prescription of omeprazole decreased from 42.2% to 26.7%, while that of esomeprazole remained costant. The reimbursement purpose was higher for G (CAGR +43%) than for ARD (CAGR +7%). We found an increase of lansoprazole prescriptions especially for heartburn (CAGR +52.4%), gastroesophageal reflux (CAGR 34,5%) and upper abdominal pain (CAGR 37,2%). Generic PPIs has unexpectedly increased the prescription of whole drug class during the period 2005-2008. Our data suggest that the appropriateness of PPI prescription after generic PPI introduction should be carefully monitored to distinguish between cost-effective from cost-ineffective PPI treatment.

Cyclooxygenase-inhibiting nitric oxide donators for osteoarthritis

Nonsteroidal anti-inflammatory drugs (NSAIDs) remain the most commonly used medications for the treatment of the symptoms of many chronic inflammatory diseases, including osteoarthritis. Unfortunately, the toxicity of NSAIDs substantially limits their long-term use. Some newer NSAIDs, namely selective cyclooxygenase (COX)-2 inhibitors, exhibit greater gastrointestinal safety, and concomitant use of anti-secretory drugs can also reduce NSAID-induced gastropathy. However, NSAIDs also adversely affect the cardiovascular system. A new class of anti-inflammatory drugs, COX-inhibiting nitric oxide donators (CINODs), has been designed to exert similar anti-inflammatory effects as NSAIDs, but with an improved safety profile. CINODs release nitric oxide, providing protective effects in the gastrointestinal tract and attenuating the detrimental effects on blood pressure normally associated with NSAIDs. We provide an outline of the rationale for CINODs and their activity, in addition to an overview of the pre-clinical and clinical profile of the most advanced CINOD, naproxcinod.

Upper Gastrointestinal Bleeding in Patients Receiving Dual Antiplatelet Therapy after Coronary Stenting

We investigated the risk of upper gastrointestinal (UGI) bleeding and the protective effect of concomitant anti-secretory drugs during dual antiplatelet therapy administered following implantation of drug-eluting stents (DES) for coronary heart disease. Because proton pump inhibitors (PPIs) are reported to decrease the platelet inhibitory effects of clopidogrel, we also assessed cardiovascular outcomes in patients taking thienopyridine derivatives with or without anti-secretory drug. We retrospectively analyzed 243 patients, who underwent DES implantation between January 2006 and December 2007 and were receiving dual anti-platelet therapy post-surgery. The main outcome measurement was the presence of UGI bleeding. Cardiovascular outcomes were assessed by follow-up coronary angiography (CAG) findings. Data were collected from medical records. Eight cases of UGI bleeding were observed during the follow-up period, none of whom were taking anti-secretory drugs. Among the 243 cases, 108 cases were taking anti-secretory drugs: a PPI (67 cases), and an H2 receptor antagonist (41 cases). No UGI bleeding was observed among patients who were taking concomitant anti-secretory drugs. The 1- and 2-year cumulative incidences of UGI bleeding among patients who were not taking anti-secretory drugs were 4.5% and 9.2%, respectively. When CAG findings were compared between patients not taking any anti-secretory drug, taking PPI, or taking H2RA, significantly more stenotic lesions of the coronary artery were observed in the PPI-treatment group. Concomitant use of an anti-secretory agent was associated with a reduced risk of UGI bleeding. Use of PPI may be associated with an attenuation of the effect of dual antiplatelet therapy.

Increased mortality in prostate carcinoma and smoking-related disease after parietal cell vagotomy: A long-term follow-up study

Objective. There is an increased risk of gastrointestinal carcinoma and smoking-related diseases after partial gastrectomy for peptic ulcer disease. The purpose of this study was to evaluate long-term cancer incidence and mortality after parietal cell vagotomy (PCV), a surgical method with a low rate of side effects, but creating hypochlorhydria in the stomach mimicking long-term treatment with antisecretory drugs. Material and methods. Data on 383 ulcer patients operated on with PCV during 1971–80 at Lund University Hospital were compared with the national registers for cause of death and cancer incidence for selected diagnoses. Median follow-up was 28 years and 31 years, respectively. Standardized mortality ratios (SMRs) and standardized incidence ratios (SIRs) were calculated. Results. An increased incidence of cancer in the respiratory organs (SIR 1.97, 95% CI: 1.08–3.31) and prostate carcinoma (SIR 1.85, 95% CI: 1.22–2.69) was found, and among men also an increased mortality in prostate carcinoma (SMR 3.85, 95% CI: 1.41–8.38) and chronic respiratory disease (SMR 2.76, 95% CI: 1.01–6.02). Overall mortality was similar to that of the background population and no increased risk of gastrointestinal malignancies was observed. Conclusions. Patients with peptic ulcer operated on with PCV have a long-term increased risk of smoking-related diseases, but PCV does not seem to increase the risk of gastrointestinal carcinoma. An increased risk of, and mortality in prostate carcinoma was found, a cancer previously not found to be related to smoking. This might be the result of surgery-induced hypochlorhydria, which warrants further investigation in patients on long-term proton-pump inhibitors.

Increased risk of exacerbating gastrointestinal disease among elderly patients following treatment with calcium channel blockers

Calcium channel blockers (CCBs) have been widely used for the treatment of hypertension and angina pectoris. It is presumed that CCBs decrease the lower esophageal sphincter pressure and as a result, the risk of gastrointestinal disease may be increased. Since the prevalence of gastrointestinal diseases has increased in elderly patients, it is possible that treatment with CCBs may have contributed to this increase. Therefore, we considered that the risk of exacerbating gastrointestinal disease among elderly patients by CCBs can be estimated by using the prescription ratio of antisecretory drugs as an outcome. We hypothesized that patients who are prescribed CCBs would increase the use of antisecretory drugs involving H(2)-receptor antagonists and proton pump inhibitors (PPIs). From January 2001 to December 2005, a dynamic retrospective cohort study was performed at three community pharmacies in Nagasaki city, Japan, to assess the use of antisecretory drugs following treatment with CCBs among elderly patients. The correlation of initiation of antisecretory drugs treatment to maintenance therapy with PPIs was determined by the Cox proportional hazards model. The proposed study includes 303 patients prescribed CCBs and 258 controls. During the study period, 138 patients prescribed CCBs and 66 controls were initiated by giving antisecretory drugs; the hazard ratio was 1.40 (95% confidence interval 1.21-1.63). Eighty two patients taking CCBs and 32 controls were initiated by the maintenance therapy with PPIs; the hazard ratio was 1.48 (95% confidence interval 1.21-1.83). Patients who simultaneously initiated the use of antisecretory drugs with CCBs could not be found. Therefore, antisecretory drugs have not been used to prevent the gastrointestinal diseases caused by CCBs. The results obtained in this study suggest that the risk of gastrointestinal disease could be increased by long-term treatment with CCBs for elderly patients.

CNS or Classic Drugs for the Treatment of Pain in Functional Dyspepsia? A Systematic Review and Meta-Analysis of the Literature

Recent evidence has suggested that pain in functional dyspepsia (FD) is associated with nervous system dysfunction; indicating that therapies aimed at nervous system modulation might be associated with pain relief in FD. To conduct a systematic review and meta-analysis to quantify the efficacy of drugs targeting the central nervous system (antidepressants and antianxiety agents - referred as "CNS drugs") and drugs targeting gastric modulation (antisecretory and prokinetic - referred as "classic drugs") for the treatment of pain in FD and, in an exploratory way, compare these 2 modalities of treatment. MEDLINE and reference lists were examined for relevant articles. We included prospective studies that evaluated the effects of either CNS drugs or classic drugs (subdivided in prokinetic and antisecretory drugs) on the symptoms of FD. Seven studies for CNS drugs and 11 studies for gastric drugs met our inclusion criteria. The analyses of these drugs showed that the 2 groups of drugs are associated with a significant reduction in dyspeptic symptoms. The pooled effect size (standardized mean difference between pre-treatment versus post-treatment means) from the random effects model was 1.25 (95% C.I., 0.83, 1.67) for CNS; 1.63 (95% C.I., 1.28, 1.97) for prokinetic, and 0.93 (95% C.I., 0.57, 1.29) for antisecretory drugs. The exploratory comparison between classes of drugs revealed no significant difference in dyspeptic symptoms reduction between CNS and prokinetic drugs; however CNS drugs were associated with a larger reduction in symptoms as compared with antisecretory drugs. The results show that both CNS and classic drugs are associated with a significant pain reduction in functional dyspepsia.

Aspectos menos conocidos de la enfermedad por reflujo gastroesofágico: pirosis funcional y reflujo no ácido

Gastroesophageal reflux disease (GERD) is defined as a pathologic condition that develops when reflux of stomach contents produce annoying symptoms and/or complications. According to whether esophagitis is present, GERD is classified as being erosive and non-erosive. Functional pyrosis is defined by the presence of retrosternal burning for at least 6 months in the absence of structural or metabolic alterations, GERD, or motor disorders that could cause the symptoms. Currently, functional pyrosis does not include patients with an acid-sensitive esophagus or those who improve with antisecretory drugs, which differentiates this entity from non-erosive GERD. GERD has usually been identified with acid reflux. However, the availability of new diagnostic methods such as Bilitec and, especially, impedance monitoring has revealed that acid, weakly acidic and gas reflux is able to produce distressing symptoms and complications in some patients.

American Gastroenterological Association Institute Technical Review on the Management of Gastroesophageal Reflux Disease

American Gastroenterological Association Institute Technical Review on the Management of Gastroesophageal Reflux Disease

Helicobacter pylori and Non‐malignant Diseases

In 2007 Helicobacter pylori research continued to deal with some controversies raised in the last decade. The main problems remain unsolved: peptic ulcer disease negative for H. pylori, synergism of H. pylori infection and aspirin and other nonsteroidal anti-inflammatory drugs or cyclooxygenase 2 specific inhibitors, the role of H. pylori eradication in uninvestigated and nonulcer dyspepsia, and the possible protective effect of H. pylori infection against gastroesophageal reflux disease and its complications such as Barrett's esophagus and adenocarcinoma. The incidence and prevalence of peptic ulcer disease as well as ulcer-related mortality are continuing to decline all over the world. The increasing consumption of anti-inflammatory and antisecretory drugs was not found to change the trend over the last period and therefore H. pylori was considered the key factor in causing ulcer-related mortality. Some progress has been achieved in understanding H. pylori-induced immunological processes, and attack mechanisms, as well as specific pathogenesis in uremic and cirrhotic patients. There is still a lot to learn about the bacterium and host factors related to H. pylori infection and its complications.

T1308 Comparison of the Effects of Acid Antisecretory Drugs On Cancer Chemotherapy-Induced Gastrointestinal Mucositis in Rats

T1308 Comparison of the Effects of Acid Antisecretory Drugs On Cancer Chemotherapy-Induced Gastrointestinal Mucositis in Rats

Management of malignant bowel obstruction

Malignant bowel obstruction (MBO) is a common and distressing outcome particularly in patients with bowel or gynaecological cancer. Radiological imaging, particularly with CT, is critical in determining the cause of obstruction and possible therapeutic interventions. Although surgery should be the primary treatment for selected patients with MBO, it should not be undertaken routinely in patients known to have poor prognostic criteria for surgical intervention such as intra-abdominal carcinomatosis, poor performance status and massive ascites. A number of treatment options are now available for patients unfit for surgery. Nasogastric drainage should generally only be a temporary measure. Self-expanding metallic stents are an option in malignant obstruction of the gastric outlet, proximal small bowel and colon. Medical measures such as analgesics according to the W.H.O. guidelines provide adequate pain relief. Vomiting may be controlled using anti-secretory drugs or/and anti-emetics. Somatostatin analogues (e.g. octreotide) reduce gastrointestinal secretions very rapidly and have a particularly important role in patients with high obstruction if hyoscine butylbromide fails. A collaborative approach by surgeons and the oncologist and/or palliative care physician as well as an honest discourse between physicians and patients can offer an individualised and appropriate symptom management plan.