Half-dose clarithromycin-containing bismuth quadruple therapy is effective and economical in treating Helicobacter pylori infection: A single-center, open-label, randomized trial.

BACKGROUND: Clarithromycin-containing bismuth quadruple therapy has been recommended as the first-line therapy for H pylori infection in China. However, its expensive cost and high antibiotic-related adverse reactions are always haunting us. To find a safer, more cost-effective, and high eradicative strategy for Helicobacter treatment, we investigated the efficacy of 14-day bismuth quadruple therapy and different doses of clarithromycin in the first-line treatment. METHOD: A total of 210 patients with H pylori infection were recruited and randomly assigned to half-dose clarithromycin group (esomeprazole 20 mg bid, amoxicillin 1 g bid, clarithromycin 250 mg bid, and bismuth potassium citrate 0.6 g bid) for 14 days or standard-dose clarithromycin group (esomeprazole 20 mg bid, amoxicillin 1 g bid, clarithromycin 500 mg bid, and bismuth potassium citrate 0.6 g bid) for 14 days. A 13 C-urea breath test (13 C-UBT) was performed at least 4 weeks after treatment. The eradication rate of H pylori, the incidence of side effects, and the cost-effectiveness of regimens were evaluated in this study. RESULTS: The eradication frequencies were 86.67% for both groups in the intention-to-treat analysis, while the per-protocol eradication rates were 91% vs. 91.92% (p=0.817). The incidence of adverse events was higher in standard dose group (54.21% vs. 34.29%; p=0.004), especially bitter taste symptom. There was a higher level of costs per person associated with the standard-dose group as compared with half-dose group (ï¿¥804.3 vs ï¿¥654.36). The cost-effectiveness ratio of the half dose was less than that of the standard dose (7.55 vs 9.16 CNY per percent). CONCLUSIONS: A 14-day half-dose clarithromycin-containing bismuth quadruple regimen is as effective as the standard bismuth quadruple therapy at eradicating H pylori, which is better tolerated and more economical. (ChiCTR-ROC-15007406).

Suitability assessment of a continuous process combining thermo-mechano-chemical and bio-catalytic action in a single pilot-scale twin-screw extruder for six different biomass sources.

A process has been validated for the deconstruction of lignocellulose on a pilot scale installation using six types of biomass selected for their sustainability, accessibility, worldwide availability, and differences of chemical composition and physical structure. The process combines thermo-mechano-chemical and bio-catalytic action in a single twin-screw extruder. Three treatment phases were sequentially performed: an alkaline pretreatment, a neutralization step coupled with an extraction-separation phase and a bioextrusion treatment. Alkaline pretreatment destructured the wall polymers after just a few minutes and allowed the initial extraction of 18-54% of the hemicelluloses and 9-41% of the lignin. The bioextrusion step induced the start of enzymatic hydrolysis and increased the proportion of soluble organic matter. Extension of saccharification for 24h at high consistency (20%) and without the addition of new enzyme resulted in the production of 39-84% of the potential glucose.

Assessment of integrated process based on hydrothermal and alkaline treatments for enzymatic saccharification of sweet sorghum stems.

In this study, sweet sorghum stem was subjected to hydrothermal pretreatment (HTP) and alkaline post-treatment to enhance its saccharification ratio by reducing its recalcitrance. The results showed that the HTP (110-210°C, 0.5-2.0h) significantly degraded hemicelluloses, and the pretreatment at the temperature higher than 190°C led to the partial degradation of the cellulose. As compared to the sole HTP, the integrated process removed most of lignin and hemicelluloses, which incurred a higher cellulose saccharification ratio. Under an optimum condition evaluated (HTP at 170°C for 0.5h and subsequent 2% NaOH treatment), 77.5% saccharification ratio was achieved, which was 1.8, 2.0 and 5.5 times as compared to the only HTP pretreated substrates, alkaline treated substrates alone and the raw material without pretreatment, respectively. Clearly, the integrated process can be considered as a promising approach to achieve an efficient conversion of lignocellulose to fermentable glucose.

An economic approach for L-(+) lactic acid fermentation by Lactobacillus amylophilus GV6 using inexpensive carbon and nitrogen sources.

AIMS: Development of cost-effective production medium by applying statistical designs for single-step fermentation of starch (corn flour - CF) to L-(+) lactic acid, using inexpensive nitrogen sources as substitutes for peptone and yeast extract in MRS medium by amylolytic Lactobacillus amylophilus GV6. METHODS AND RESULTS: A two-level Plackett-Burman design was employed for screening various available crude starches (flours) for L-(+) lactic acid production by Lact. amylophilus GV6 using red lentil flour (RL) and bakers yeast cells (YC) as substitutes for commercial peptone and yeast extract in MRS medium in anaerobic submerged fermentation. Of all the tested flours, CF was found to be the most significant. Central composite rotatable design was employed to determine maximum production of L-(+) lactic acid at optimum values of process variables, CF, RL, YC, CaCO(3) and incubation period (IP). minitab analyses showed that lactic acid production was significantly affected by the linear terms CF, RL, CaCO(3) and IP. The interactions of CF-RL, CF-YC, CF-CaCO(3), RL-YC and RL-CaCO(3) and the square terms CF and IP were significant. The maximum lactic acid production of 29 g/37 g of starch present in 50 g of CF was obtained at optimized concentrations of CF 5%, RL 0.7%, YC 0.8%, CaCO(3) 0.8% and IP 2.9 days. CONCLUSIONS: Successful application of Plackett-Burman design helped in identifying CF as the best carbon source among the tested flours for L-(+) lactic acid production using inexpensive nitrogen sources. Further optimization of the process variables by response surface methods (RSMs) led to maximum production of lactic acid (29 g lactic acid from 37 g of starch present in 50 g of flour). SIGNIFICANCE AND IMPACT OF THE STUDY: Lactobacillus amylophilus GV6 showed 78.4% lactic acid production efficiency (g lactic acid produced/g starch taken) and 96% lactic acid yield efficiency (g lactic acid produced/g starch utilized). Information from the present studies provides a better understanding on production of L-(+) lactic acid on fermentation of CF using inexpensive nitrogen sources and on changes in the production as a response from interaction of factors. Use of inexpensive nitrogen sources and starch as substrate in MRS medium for single-step fermentation of lactic acid can become an efficient, economic and viable process. This report is on optimization of inexpensive nitrogen sources completely replacing peptone and yeast extract in single-step submerged fermentation of starch (present in CF) to lactic acid with high production efficiency.

Comparison of two management strategies for Helicobacter pylori treatment: clinical study and cost-effectiveness analysis.

BACKGROUND: First-line proton pump inhibitor-based triple and quadruple therapies for Helicobacter pylori eradication present similar levels of efficacy. Cross-over treatment (quadruple following triple failure, and triple following quadruple failure) seems the most sensible approach to treatment failures, but the two strategies -'quadruple first' versus 'triple first'- have not been previously compared. The aims of our study were to assess the usefulness and the cost-effectiveness of the two treatment strategies. MATERIAL AND METHODS: Forty-nine out of 344 patients included in a previous study comparing triple therapy - 7 days of omeprazole, amoxicillin and clarithromycin twice a day - with quadruple therapy - 7 days of omeprazole twice a day, plus tetracycline, metronidazole and bismuth subcitrate three times a day - failed initial treatment and were assigned to cross-over therapy. Cure was determined by urea breath test. A decision analysis was performed to compare the two eradication strategies. RESULTS: Intention to treat cure rates were 46% (10/22 patients; 95% CI 24-68%) for second-line triple therapy and 63% (17/27 patients; 95% CI 42-81%) for second-line quadruple therapy. Per protocol cure rates were 71% and 85%, respectively. Intention to treat cure rates were 87% (95% CI 81-92%) for the 'triple first' versus 86% (95% CI 80-91%) for the 'quadruple first' strategy (p = .87). The 'quadruple first' strategy was more cost-effective. The incremental cost of 'triple first' strategy per person was 19 in the low-cost area and 65 US dollars in the high-cost area. CONCLUSIONS: The effectiveness of 'triple first' and 'quadruple first' strategies is similar, although the latter seems slightly more cost-effective.

Review article: alginate-raft formulations in the treatment of heartburn and acid reflux.

Alginate-based raft-forming formulations have been marketed word-wide for over 30 years under various brand names, including Gaviscon. They are used for the symptomatic treatment of heartburn and oesophagitis, and appear to act by a unique mechanism which differs from that of traditional antacids. In the presence of gastric acid, alginates precipitate, forming a gel. Alginate-based raft-forming formulations usually contain sodium or potassium bicarbonate; in the presence of gastric acid, the bicarbonate is converted to carbon dioxide which becomes entrapped within the gel precipitate, converting it into a foam which floats on the surface of the gastric contents, much like a raft on water. Both in vitro and in vivo studies have demonstrated that alginate-based rafts can entrap carbon dioxide, as well as antacid components contained in some formulations, thus providing a relatively pH-neutral barrier. Several studies have demonstrated that the alginate raft can preferentially move into the oesophagus in place, or ahead, of acidic gastric contents during episodes of gastro-oesophageal reflux; some studies further suggest that the raft can act as a physical barrier to reduce reflux episodes. Although some alginate-based formulations also contain antacid components which can provide significant acid neutralization capacity, the efficacy of these formulations to reduce heartburn symptoms does not appear to be totally dependent on the neutralization of bulk gastric contents. The strength of the alginate raft is dependant on several factors, including the amount of carbon dioxide generated and entrapped in the raft, the molecular properties of the alginate, and the presence of aluminium or calcium in the antacid components of the formulation. Raft formation occurs rapidly, often within a few seconds of dosing; hence alginate-containing antacids are comparable to traditional antacids for speed of onset of relief. Since the raft can be retained in the stomach for several hours, alginate-based raft-forming formulations can additionally provide longer-lasting relief than that of traditional antacids. Indeed, clinical studies have shown Gaviscon is superior to placebo, and equal to or significantly better than traditional antacids for relieving heartburn symptoms. Alginate-based, raft-forming formulations have been used to treat reflux symptoms in infants and children, and in the management of heartburn and reflux during pregnancy. While Gaviscon is effective when used alone, it is compatible with, and does not interfere with the activity of antisecretory agents such as cimetidine. Even with the introduction of new antisecretory and promotility agents, alginate-rafting formulations will continue to have a role in the treatment of heartburn and reflux symptoms. Their unique non-systemic mechanism of action provides rapid and long-duration relief of heartburn and acid reflux symptoms.

Pharmacological therapy of Helicobacter pylori infection.

Helicobacter pylori has been associated with several diseases including peptic ulcer disease and gastric cancer. Eradication of H pylori not only results in ulcer healing, but reduces recurrences essentially curing peptic ulcer disease. Eradicating H pylori can be difficult. There are several reasons for antimicrobial failure, and the resistance rates for several antibiotics are increasing. The most common drugs used to treat this infection include amoxicillin, clarithromycin, tetracycline, bismuth, and omeprazole and lansoprazole. Dual therapy using a proton pump inhibitor and a single antibiotic gives a suboptimal eradication rate. Triple therapy using at least two antibiotics and either bismuth or a proton pump inhibitor gives satisfactory eradication rates of 90%. However, these regimens are complicated and have significant side effects and compliance problems. The ideal regimen has yet to be developed. In the future, we will prevent infection with immunization. Several vaccines are being developed.

Helicobacter pylori infection. The importance of eradication in patients with gastric disease.

Discovery of Helicobacter pylori infection in patients with peptic ulcer disease has completely transformed the approach to the disease. Implications of this discovery for healthcare in general and for medical economics are only now being appreciated. Noninvasive and invasive methods of establishing the presence of infection are currently available, and clinical introduction of the recently approved urea breath test in the near future will add another method for documenting both active infection and successful eradication. Patients with initial presentation or recurrence of gastric or duodenal ulcer disease and those with previous disease who are receiving maintenance therapy should be treated for H pylori infection. Treatment regimens, which consist of combinations of antibiotics, bismuth salts, and proton pump inhibitors, can result in cure rates of 90%, with prevention of recurrence. Understanding of the infection continues to grow rapidly, and current recommendations regarding diagnosis and treatment will evolve as new methods are developed.

In vitro assessment of antacid efficacy using a computer-controlled 'artificial stomach-duodenum' model reproducing gastroduodenal flux regulation.

We have developed an artificial stomach-duodenum model made up of three compartments representing the stomach, (including a fragment of hog gastric mucosa), the proximal duodenum, and the distal duodenum. Gastroduodenal flow rates are controlled by a microcomputer capable of (1) adjusting gastric emptying and alkaline secretion in the proximal duodenum according to intragastric pH; (2) adjusting pancreatic alkaline secretion according to proximal duodenum pH; and (3) simulating acid response to food ingestion. Antacid drugs were added 90 min after simulated food ingestion in near-physiological or duodenal ulcer conditions. Aluminum phosphate-containing antacids resulted in a persistent antacid effect, due to their adsorption to the gastric mucosa; this prolonged the buffering capacity at pH 2.4 to 120 min. Aluminum+magnesium hydroxides and calcium+magnesium carbonate combinations mainly exerted neutralizing activity, inducing an increase in the gastric emptying rate. In the duodenal ulcer simulation, the pH of the gastric contents was lower and the antacid effect was shorter than in the 'physiological' simulation.

Efficacy, safety, and cost issues in managing patients with gastroesophageal reflux disease.

The phases of therapy for gastroesophageal reflux disease (GERD) and the efficacy, safety, and cost of the various drugs used are discussed. The therapeutic goals for patients with GERD are to relieve pain, promote healing, avoid complications, and prevent recurrence. Sustained inhibition of gastric acid secretion is necessary to facilitate healing of eroded esophageal mucosa. Phase 1 treatment involves lifestyle changes to remove factors that may help to precipitate reflux, such as overeating, alcohol, and tobacco. Phase 2 involves pharmacologic manipulation of the secretion, concentration, and transport of gastric acid. The drugs used are antacids, alginic acid, the histamine H2-receptor antagonists, the prokinetic agents, sucralfate, and omeprazole. While all of these agents may provide symptomatic relief, only the H2 antagonists and omeprazole have been convincingly shown to relieve symptoms and promote healing. The H2 antagonists differ in potency, pharmacodynamic effect, pharmacokinetics in certain patient groups, drug interactions, and adverse effects. The H2 antagonists may not be effective at standard dosages in patients who secrete especially large quantities of gastric acid. Because of its mechanism of action, omeprazole provides greater inhibition of gastric acid than any other antisecretory drug. Omeprazole may also be the most cost-effective treatment. The availability of omeprazole may reduce the number of patients for whom clinicians must resort to phase 3 treatment, surgery. Although many drugs provide symptomatic relief in patients with GERD, the healing that is necessary to break the cycle of damage and symptoms is promoted only by the H2 antagonists and omeprazole.

Pharmacokinetic considerations in quinolone therapy.

It is advisable to switch patients from parenteral to oral therapy as soon as practical. High volumes of distribution, coupled with relatively low protein binding, indicate that the quinolones are widely distributed outside extracellular fluid. Interactions with aluminum- or magnesium-containing antacids may be avoided by administering the antacids at least 2 hours after quinolone dosing. Some quinolones with high bioavailability (e.g., ofloxacin) are absorbed as reliably and completely after oral administration as when given parenterally, and dosage adjustments for these agents are unnecessary after sequential therapy. Treatment strategies may differ according to the route of drug elimination, and dosage adjustments are required in patients with renal failure who receive quinolones excreted primarily by the kidneys. Theophylline interactions may be more problematic in patients given quinolones that are primarily metabolized by the liver. Quinolones, which have concentration-dependent killing and a long postantibiotic effect, should be administered in the highest tolerated dosage. A method to assess the relative antibacterial efficacy of the quinolones uses the ratio of the Cmax:MIC90 of the organism, compared with a ratio derived from the NCCLS breakpoints for susceptibility.

Assessment of antacid characteristics of drugs containing a combination of aluminium and magnesium salts using the "artificial stomach" model.

Antacid characteristics of three drugs containing aluminium and magnesium salts (combination of clay with aluminium and magnesium hydroxides, aluminium and magnesium hydroxide mixture and hydrotalcite) have been studied in a dynamic situation simulated by the "artificial stomach" model, simultaneously taking into account both gastric fluxes, a constant secretory flux and variable emptying fluxes. Therapeutic doses of the drugs were added 1. to 100 ml of 0.1 N HCl, without or with 1% or 5% meat extract, and 2. 100 ml of pooled human gastric juice (96 mmol/l, pH 1.1). In addition, antacid activity of 0.5 g aluminium and magnesium hydroxides, taken alone or in combination, were evaluated when added to 100 ml of 0.1 N HCl. In aqueous HCl solution or in human gastric juice, the three antacid drugs exhibited 1. a neutralising activity characterised by pH-rise and 2. a buffering capacity close to pH 3.8. In addition, hydrotalcite exhibited also buffering capacity at pH 1.2. The antacid-induced capacity, expressed as H+ mmol, to recover initial pH were very similar, indicating that antacid physiochemical properties are similar in HCl solution or in gastric juice. H+ consumption depended upon emptying fluxes. The same antacid characteristics were observed when antacids were mixed with 1% meat extract while 5% meat extract resulted in a modification of antacid characteristics. Therefore the antacid capacities of respective mixtures were of smaller magnitude (50-60%) than the sum of the activities of antacids plus meat extracts.(ABSTRACT TRUNCATED AT 250 WORDS)

A comparative study of the neutralising capacity of eight brands of antacids.

Eight brands of antacid tablets commonly available in the private market in Kenya were subjected to in-vitro tests for neutralizing capacity. The neutralizing capacity per gram and per tablet of the products was compared. The neutralizing capacity in millilitres of 0.1 M HC1 per gram ranged from 103.10 for Gelusil to 225.13 for Maalox, with others ranging between +/- 18.1% and -12% about the average. The neutralizing capacity per tablet ranged from 64.90 ml for Magnesium trisilicate Co tablets B.P. to 263.15 ml for Maalox, with the others ranging between +/- 24.9% and -33.1% about the average. This shows high variation in the neutralizing capacities of the different brands available especially in relations to the neutralizing capacities per tablet due to the high variation in the tablet weight.

Relative effectiveness and costs of antiulcer medications as a basis for rational prescribing.

To be maximally effective, antiulcer medications should relieve ulcer symptoms rapidly and promote rapid healing of an ulcer crater; after the cessation of a course of treatment the ulcer should not recur. A wide variety of agents is available. These are of similar efficiency in the control of ulcer symptoms and in the acceleration of the healing of the ulcer crater. However, evidence exists of differences in the rate of the recurrence of duodenal ulcers on the cessation of these drugs. Surface-active agents (bismuth complexes, sucralfate, prostaglandins and carbenoxolone) are consistently superior to H2-histamine receptor antagonist drugs (cimetidine and ranitidine). A high relapse rate produces more patients with active disease at any one time, hence more patients will be exposed to the complications of the disease, and will require active investigation and therapy. Because of the increased rate of relapse, the use of H2-receptor antagonist drugs as first-line intermittent healing therapy can be shown to be associated with an eight-fold (800%) increase in cost of pharmaceutical agents as compared with first-line treatment with bismuth salts; a four-fold increase compared with the cost of using antacid drugs; and a two-fold increase compared with the cost of using sucralfate. When maintenance therapy with H2-receptor antagonist agents is given instead of intermittent therapy with bismuth complexes, a 14-fold increase in pharmaceutical costs is incurred, with inferior results that have already been demonstrated under the conditions of a controlled clinical trial. These considerations of efficacy and cost suggest that H2-receptor antagonist drugs ought not to be first-line therapy for duodenal ulcers; rather, surface-active agents such as colloidal bismuth or sucralfate should be prescribed initially.

The assessment of gastric acidity and antacid effect in pregnant women by a non-invasive radiotelemetry technique.

Non-invasive radiotelemetry techniques were used for the in-vivo assessment of gastric acidity and the effect of antacids in non-pregnant women and women in the third trimester of pregnancy. A particulate (magnesium trisilicate mixture) and a non-particulate (sodium citrate) antacid were studied. There was no significant difference in basal gastric acidity and gut transit time between the pregnant and non-pregnant subjects. The median and range of values for the efficacy (defined as the integrated area under the pH/time curves) of sodium citrate was 138.3 pH.min (29.8-520.7) in the non-pregnant and 103.0 pH.min (54.3-375.6) in the pregnant subjects. The median and range of values for the duration of action of sodium citrate were 38.6 (18.1-147.4) min in the non-pregnant and 30.5 (20.0-119.1) min in the pregnant women. Magnesium trisilicate mixture resulted in a greater intragastric pH change and had a greater efficacy than sodium citrate, but the duration of action of the two antacids was similar.

The use of radiotelemetry techniques for the in vivo assessment of antacids.

The use of the pH radio pill for the assessment of antacid effect has been evaluated. The correlation between the pH pill and a conventional pH electrode system was high (r2 = 0.997). The records of in vivo pH against time allow unique measurements of antacid efficacy (defined as the integrated area under the pH against time curve) and duration of action to be obtained. Using a free pill, antacid assessments were performed in 13 subjects in the left lateral position. The effects of repeated antacid administrations were studied in five subjects using a pH pill which was prevented from leaving the stomach by tethering it to the teeth. These longer studies were performed in the sitting position. The efficacy (p less than 0.02) and duration of action (p less than 0.02) of sodium citrate 0.3 M were less in those subjects in whom the pill was tethered. The differences between the results of the studies using either a free or a tethered pill can be attributed to posture. The overall duration of action of sodium citrate 15 ml was short, the mean (SEM) value being 42.4 (4.5) minutes in the left lateral position and 21.2 (4.0) minutes in the upright position.

A comparative assessment of a new antacid formulation based on magaldrate.

A new antacid formulation (Dynese) based on magaldrate, a discrete chemical entity with marked antacid properties, has been compared in vitro with several commercially available antacid preparations. All preparations were tested for their ability to maintain gastric pH within acceptable limits and to effectively bind bile acids. Sodium concentrations were also determined. Dynese was shown to compare very favourably with existing preparations in that it had a prolonged even neutralization profile, efficient bile acid binding properties and a low sodium content.

In vitro evaluation of liquid antacid products.

The in vitro neutralizing capacities, sodium content, and cost of 21 nonprescription antacid products were compared. A 5-ml sample of each antacid product was placed in a beaker using a pipette. The pipette was rinsed three times wtih purified water 5 ml, and the mixture was stirred with a magnetic stirring rod. After one minute, 1.0 N hydrochloride acid 30 ml was added to the mixture and stirring was continued for 15 minutes. The pH was then measured. Using a burette, sufficient 0.5 N sodium hydroxide was added to the mixture to raise the pH stable value to 3.5. Samples were tested in duplicate. Manufacturers were requested to provide sodium content for the antacid products, and costs were obtained based on wholesale prices. Neutralizing capacity of the antacids ranged from 1.3 to 8.7 meq/ml. Of the 21 products, 17 contained at least 90% of the claimed neutralizing capacity, as required by FDA. One product did not qualify as an antacid by FDA standards. Sodium content has been reduced in may preparations and may no longer be a factor in choosing an antacid. Chronic therapy with antacids can be expensive, and it costs more to deliver a given amount of neutralizing capacity with less concentrated antacids.