Association Between Vonoprazan and the Risk of Gastric Cancer After Helicobacter pylori Eradication.

BACKGROUND & AIMS: Potassium-competitive acid blockers (PCABs) have been increasingly used to treat upper gastrointestinal disorders, replacing proton pump inhibitors (PPIs). Whereas PPIs are associated with an increased risk of gastric cancer (GC) after Helicobacter pylori (Hp) eradication, it is uncertain whether PCABs carry the same risk. METHODS: Using a population-based claims database in Japan, we identified patients who were prescribed a clarithromycin-based first regimen of Hp eradication between 2015 and 2018. Patients who failed this regimen and those diagnosed with GC before or within 1 year after Hp eradication were excluded. We compared GC incidence between PCAB users and histamine type-2 receptor antagonist (H2RA) users, matching them on the basis of propensity scores calculated with considerations for age, sex, smoking, alcohol consumption, comorbidities, and co-administered medications. PCABs included only vonoprazan in this study. RESULTS: Among 54,055 patients, 568 (1.05%) developed GC during the follow-up period (mean, 3.65 years). The cumulative incidence of GC was 1.64% at 3 years, 2.02% at 4 years, and 2.36% at 5 years in PCAB users and 0.71% at 3 years, 1.04% at 4 years, and 1.22% at 5 years in H2RA users. The use of PCABs was associated with a higher GC risk (matched hazard ratio, 1.92; 95% confidence interval, 1.13-3.25; P = .016). Longer PCAB use and high-dose PCAB use were significantly associated with higher incidence of GC. Sensitivity analyses showed the risk of GC incidence among PCAB users was comparable with that of PPI users. CONCLUSIONS: The use of PCABs was associated with an increased risk of GC among Hp-eradicated patients, with duration/dose response effects.

Association Between Acid-Suppressive Drugs and Risk of Rosacea: Retrospective Study Using the Korean National Health Insurance Service-National Sample Cohort.

BACKGROUND: Rosacea is a common inflammatory skin disease with multiple etiologies. Proton pump inhibitors (PPIs) and histamine-2 receptor antagonists (H2RA) are acid suppressive drugs widely used for gastrointestinal (GI) diseases, and long-term use has been reported to be associated with dysbiosis which is a potential risk for development of rosacea. This study aimed to study the association between rosacea and acid suppressants in the Korean national cohort. METHODS: We used Korean National Health Insurance Service-National Sample Cohort data of 749,166 patients with upper GI diseases between 2001 and 2013. Duration of acid suppressants was compared between patients with and without rosacea together with other sociodemographic characteristics and hazard ratios were estimated. RESULTS: Longer use of acid suppressants was significantly associated with increased risk of rosacea. After adjustment for possible confounders, increased cumulative defined daily dose was significantly associated with risk of rosacea (odds ratio [OR], 1.55; 95% confidence interval [CI], 1.20-2.00; P = 0.001). Other factors significantly associated with risk of rosacea include residing in the rural area (OR, 2.58; 95% CI, 2.18-3.06; P < 0.001), greater Charlson Comorbidity Index score (OR, 1.45; 95% CI, 1.15-1.83; P = 0.002), and comorbidities (malignancy, thyroid disease, and depression). CONCLUSION: Results from our study indicate that H2RA or PPI is associated with the occurrence of rosacea among patients with GI diseases in the Korean population. The risk was increased in dose-dependent manner, even after adjusting for confounding variables. Clinicians should be aware of risks associated with prolonged use of acid suppressive drugs.

Association between Acid-Lowering Agents, Metformin, and Vitamin B12 among Boston-Area Puerto Ricans.

BACKGROUND: Vitamin B12 involves several physiological functions, and malabsorption is reported with medication use. OBJECTIVES: Studies have reported an inverse association between the use of metformin or acid-lowering agents (ALAs), such as proton pump inhibitors, histamine 2 receptor antagonists, and blood vitamin B12 concentration, because of malabsorption. The concomitant use of these medications is underreported. We sought to examine these associations in a cohort of Boston-area Puerto Rican adults. METHODS: This analysis was conducted within the Boston Puerto Rican Health Study (BPRHS), an ongoing longitudinal cohort that enrolled 1499 Puerto Rican adults aged 45-75 y at baseline. Our study comprised 1428, 1155, and 782 participants at baseline, wave2 (2.2 y from baseline), and wave3 (6.2 y from baseline), respectively. Covariate-adjusted linear and logistic regression was used to examine the association between baseline medication use and vitamin B12 concentration or deficiency (vitamin B12 <148 pmol/L or methylmalonic acid >271 nmol/L), and long-term medication use (continuous use for ∼6.2 y) and wave3 vitamin B12 concentration and deficiency. Sensitivity analyses were done to examine these associations in vitamin B12 supplement users. RESULTS: At baseline, we observed an association between metformin use (ß = -0.069; P = 0.03) and concomitant ALA and metformin use (ß = -0.112; P = 0.02) and vitamin B12 concentration, but not a deficiency. We did not observe associations between ALA, proton pump inhibitors, or histamine 2 receptor antagonists, individually, with vitamin B12 concentration or deficiency. CONCLUSIONS: These results suggest an inverse relationship between metformin, concomitant ALA, metformin use, and serum vitamin B12 concentration.

Association of proton pump inhibitor and histamine H2-receptor antagonists with restless legs syndrome.

Restless legs syndrome (RLS) is a common sensorimotor disorder, which can disrupt sleep and is thought to be caused in part by low cellular iron stores. Proton pump inhibitors (PPI) and histamine H2-receptor antagonists (H2A) are among the most commonly used drugs worldwide and show evidence of causing iron deficiency. We conducted a case/non-case observational study of blood donors in the United States (N = 13,403; REDS-III) and Denmark (N = 50,323; Danish Blood Donor Study, DBDS), both of which had complete blood count measures and a completed RLS assessment via the Cambridge-Hopkins RLS questionnaire. After adjusting for age, sex, race, BMI, blood donation frequency, smoking, hormone use, and iron supplement use, PPI/H2A use was associated with RLS (odds ratio [OR] = 1.41; 95% confidence interval [CI], 1.13-1.76; p = 0.002) in REDS-III for both PPI (OR = 1.43; CI, 1.03-1.95; p = 0.03) and H2A (OR = 1.56; CI, 1.10-2.16; p = 0.01). DBDS exhibited a similar association with PPIs/H2As (OR = 1.29; CI, 1.20-1.40; p < 0.001), and for PPIs alone (OR = 1.27; CI, 1.17-1.38; p < 0.001), but not H2As alone (OR = 1.18; CI, 0.92-1.53; p = 0.2). We found no evidence of blood iron stores mediating this association. The association of PPI, and possibly H2A, consumption with RLS independent of blood iron status and other factors which contribute to RLS risk suggest the need to re-evaluate use of PPI/H2A in populations at particular risk for RLS.

Efficacy and safety of traditional Chinese herbal formula combined with western medicine for gastroesophageal reflux disease: A protocol for systematic review and meta-analysis.

BACKGROUND: The combined therapy of Chinese herbal formula and western medicine against gastroesophageal reflux disease (GERD) could significantly improve the clinical effect, reduce the recurrence rate and the side effects of western medicine, and even reduce the dosage and course of treatment of western medicine. This study tried to systematically evaluate the efficacy and safety traditional Chinese herbal formula combined with western medicine in the treatment of GERD. METHODS: Randomized controlled trials of traditional Chinese herbal formula combined with western medicine for GERD patients will be systematically searched using the PubMed, Embase, Medline, Cochrane Library, China National Knowledge Infrastructure (CNKI), Wanfang database, Chongqing VIP Chinese Science and Technology Periodical Database, and Chinese Biological and Medical database (CMB) until Aug. 28, 2020. Two researchers will perform data extraction and risk of bias assessment independently. Statistical analysis will be conducted in RevMan 5.3. RESULTS: This study will summarize the present evidence by exploring the efficacy and safety of traditional Chinese herbal formula combined with western medicine in the treatment of GERD. CONCLUSIONS: The findings of the study will help to determine potential benefits of traditional Chinese herbal formula combined with western medicine against GERD. ETHICS AND DISSEMINATION: The private information from individuals will not be published. This systematic review also will not involve endangering participant rights. Ethical approval is not required. The results may be published in a peer-reviewed journal or disseminated in relevant conferences. OSF REGISTRATION NUMBER: DOI 10.17605/OSF.IO/RSAVF.

Proton Pump Inhibitors, But Not H2-receptor Antagonists, Are Associated With Incident Fractures Among Kidney Transplant Recipients.

BACKGROUND: Fractures are a common and burdensome problem among kidney transplant recipients (KTRs). Proton pump inhibitors (PPIs) are frequently used after kidney transplantation and have been associated with increased fracture risk in the general population. This study aimed to determine whether PPI use is associated with incidence of major fractures in KTRs. METHODS: Using the Wisconsin Allograft Recipient Database, we identified 155 KTRs with a major fracture that occurred at least 12 months after transplantation. Controls were selected using incidence-density sampling. Use of PPIs and histamine 2-receptor antagonists (H2RA) during the year before the index date were identified. RESULTS: A total of 155 cases were matched to 685 controls. Within 1 year before the index date, 68% of cases and 52% of controls used a PPI, and 16% of cases and 11% of controls used an H2RA. PPI use was associated with higher incidence of major fractures in unadjusted analysis (odds ratio [OR], 2.4; 95% CI, 1.6-3.5) and in adjusted analyses controlling for demographic and transplant-related covariates and use of corticosteroids, bisphosphonates, vitamin D and calcium supplements (OR, 1.9; 95% CI, 1.2-3.1). H2RA use was not associated with incidence of major fractures in adjusted analyses (OR, 1.0; 95% CI, 0.5-1.8). The associations between PPI use and fractures remained similar in analyses limited to spine and hip fractures. CONCLUSIONS: Use of PPIs, but not H2RAs, is associated with a higher risk of major fractures among KTRs. Clinicians should individualize PPI use in KTRs, evaluating the risks and benefits of prescribing and continuing PPIs in KTRs.

Proton Pump Inhibitors, H2-Receptor Antagonists, Metformin, and Vitamin B-12 Deficiency: Clinical Implications.

There is clear evidence that proton-pump inhibitors (PPIs), H2-receptor antagonists (H2RAs), and metformin can reduce serum vitamin B-12 concentrations by inhibiting the absorption of the vitamin. However, it is unclear if the effects of these drugs on serum vitamin B-12 are associated with increased risk of biochemical or functional deficiency (as is indicated by elevated blood concentrations of homocysteine and methylmalonic acid) or clinical deficiency (including megaloblastic anemia and neurologic disorders such as peripheral neuropathy and cognitive dysfunction). This review provides an overview of vitamin B-12 absorption and biochemistry and the mechanisms by which PPIs, H2RAs, and metformin affect these functions. It also summarizes the literature relating the use of these drugs to the risk of vitamin B-12 deficiency. Also discussed is that strategies for assessing vitamin B-12 status and diagnosing vitamin B-12 deficiency have evolved in recent years beyond solely measuring serum total vitamin B-12. Multiple analyte testing, a strategy in which ≥2 of 4 biomarkers of vitamin B-12 status-serum total vitamin B-12, holotranscobalamin, homocysteine, and methylmalonic acid-are measured, increases sensitivity and specificity for diagnosing vitamin B-12 deficiency. It is concluded that randomized controlled trials are now needed that use the strategy of multiple analyte testing to determine if PPIs, H2RAs, and metformin do indeed increase the risk of vitamin B-12 deficiency. Until these studies are conducted, a reasonable recommendation for physicians and their patients who are taking these drugs is to monitor vitamin B-12 status and to provide vitamin B-12 supplements if altered blood biomarkers or clinical signs consistent with low or deficient vitamin B-12 status develop.

An Analysis of the Inclusion of Medications Considered Potentially Inappropriate in Older Adults in Chemotherapy Templates for Hematologic Malignancies: One Recommendation for All?

BACKGROUND: There remains a paucity of data regarding the use of potentially inappropriate medications (PIMs) in the supportive management of older adults undergoing chemotherapy. Raising awareness among healthcare providers regarding the frequency of their use and potential toxicities may help to minimize the risks to patients. OBJECTIVE: The aim of this study was to evaluate the frequency of six specific classes of medications considered PIMs by the American Geriatrics Society Beers Criteria that are commonly included in the National Comprehensive Cancer Network (NCCN) chemotherapy order templates for hematologic malignancies. The six PIMs evaluated are first-generation antihistamines, benzodiazepines, corticosteroids, H2-receptor antagonists, metoclopramide, and antipsychotics. METHODS: A total of 311 unique chemotherapy order templates published online by the NCCN for the treatment of hematologic malignancies were reviewed to determine the frequency that these six specific PIMs were recommended for supportive care. RESULTS: Approximately 45% of the NCCN chemotherapy templates for hematologic malignancies specifically recommended the use of at least one of the six PIMs examined. The remainder of the templates evaluated referred exclusively to the NCCN Guidelines® on Oncology for Antiemesis, which also included the use of at least one of the six PIMs evaluated. CONCLUSIONS: These findings demonstrate that PIMs are frequently used as supportive therapy in the treatment of hematologic malignancies. Increasing healthcare provider awareness of their potential side effects may minimize the risks associated with their use in older adults with hematologic malignancies undergoing chemotherapy.

Exposure to Gastric Acid Inhibitors Increases the Risk of Infection in Preterm Very Low Birth Weight Infants but Concomitant Administration of Lactoferrin Counteracts This Effect.

OBJECTIVE: To investigate whether exposure to inhibitors of gastric acidity, such as H2 blockers or proton pump inhibitors, can independently increase the risk of infections in very low birth weight (VLBW) preterm infants in the neonatal intensive care unit. STUDY DESIGN: This is a secondary analysis of prospectively collected data from a multicenter, randomized controlled trial of bovine lactoferrin (BLF) supplementation (with or without the probiotic Lactobacillus rhamnosus GG) vs placebo in prevention of late-onset sepsis (LOS) and necrotizing enterocolitis (NEC) in preterm infants. Inhibitors of gastric acidity were used at the recommended dosages/schedules based on the clinical judgment of attending physicians. The distribution of days of inhibitors of gastric acidity exposure between infants with and without LOS/NEC was assessed. The mutually adjusted effects of birth weight, gestational age, duration of inhibitors of gastric acidity treatment, and exposure to BLF were controlled through multivariable logistic regression. Interaction between inhibitors of gastric acidity and BLF was tested; the effects of any day of inhibitors of gastric acidity exposure were then computed for BLF-treated vs -untreated infants. RESULTS: Two hundred thirty-five of 743 infants underwent treatment with inhibitors of gastric acidity, and 86 LOS episodes occurred. After multivariate analysis, exposure to inhibitors of gastric acidity remained significantly and independently associated with LOS (OR, 1.03; 95% CI, 1.008-1.067; P = .01); each day of inhibitors of gastric acidity exposure conferred an additional 3.7% odds of developing LOS. Risk was significant for Gram-negative (P < .001) and fungal (P = .001) pathogens, but not for Gram-positive pathogens (P = .97). On the test for interaction, 1 additional day of exposure to inhibitors of gastric acidity conferred an additional 7.7% risk for LOS (P = .003) in BLF-untreated infants, compared with 1.2% (P = .58) in BLF-treated infants. CONCLUSION: Exposure to inhibitors of gastric acidity is significantly associated with the occurrence of LOS in preterm VLBW infants. Concomitant administration of BLF counteracts this selective disadvantage. TRIAL REGISTRATION: isrctn.org: ISRCTN53107700.

Gastro-oesophageal reflux disease: beyond proton pump inhibitor therapy.

Gastro-oesophageal reflux disease (GORD or GERD) is a very common disorder, and advancement in drug development over the years has markedly improved disease management. Proton pump inhibitors (PPIs) remain the mainstay of treatment for GERD due to their profound and consistent inhibitory effect on acid secretion. However, PPIs do not reduce the number of reflux events and do not provide long-term cure for GERD. In addition, although the safety profile of PPIs is excellent, recent population-based studies have suggested that long-term PPI use may be associated with a variety of adverse events. They include osteoporosis-related hip and spine fractures, community-acquired and nosocomial pneumonia, various enteric and non-enteric infections, fundic gland polyps and many others. Consequently, there is growing interest by patients and physicians alike in current, as well as future, non-PPI-related therapeutic strategies for GERD. This includes repositioning histamine H(2) receptor antagonists and prokinetics in our current GERD therapeutic algorithms and a resurgence of non-medical therapeutic modalities for GERD, such as anti-reflux surgery, endoscopic treatment, alternative and complementary medicine and psychological interventions. Furthermore, there will be renewed efforts in further developing new medical and non-medical therapeutic modalities for GERD.

Use of proton pump inhibitors and H2 blockers and risk of pneumonia in older adults: a population-based case-control study.

PURPOSE: To examine whether use of proton pump inhibitors (PPIs) and H2 blockers is associated with increased pneumonia risk. METHODS: We conducted a population-based, nested case-control study within Group Health, an integrated healthcare delivery system. Among community-dwelling, immunocompetent adults aged 65-94, we identified presumptive cases of ambulatory and hospitalized community-acquired pneumonia in 2000-2003 from ICD-9 codes and validated them by medical record review (N = 1125). Controls were selected, matched to cases on age, sex, and calendar year (N = 2235). Current PPI or H2 blocker use was ascertained from computerized pharmacy records. Comorbid illnesses and other characteristics were ascertained by medical record review. Multivariable conditional logistic regression was used to examine the association between medication use and pneumonia risk. We conducted sensitivity analyses using only administrative and pharmacy data to assess how these results differed from our primary results. RESULTS: The prevalence of PPI or H2 blocker use was 21% (241/1125) for pneumonia cases and 16% (350/2235) for controls (adjusted odds ratio [OR] 1.03, 95% CI 0.86-1.24, compared to nonuse). No increased risk was seen for recent initiation. The prevalence of PPI use was 12% (132/1125) for cases and 7% (160/2235) for controls (adjusted OR 1.13, 95% CI 0.88-1.44). Analyses using only administrative and pharmacy data yielded risk estimates farther from the null (adjusted OR 1.32, 95% CI 1.17-1.49, for current PPI use versus nonuse). CONCLUSIONS: Use of PPIs and H2 blockers is not associated with increased pneumonia risk in older adults. The increased risk observed in some prior studies may reflect confounding.

Proton pump inhibitors and histamine-2 receptor antagonists are associated with hip fractures among at-risk patients.

BACKGROUND & AIMS: Drugs that inhibit gastric acid might increase the risk of hip fracture. However, little long-term exposure data exist and no large studies have been conducted in the United States. METHODS: We conducted a case-control study using data from an integrated health services organization. We evaluated 33,752 patients with incident diagnoses of hip/femur fractures (cases), 130,471 matched members without fractures (controls), prescription data for use of proton pump inhibitors (PPIs) or histamine-2 receptor antagonists (H2RAs) (up to 10 years' cumulative duration), and confounders. RESULTS: Patients with hip fractures were more likely than controls to have previously received a > or =2-year supply of PPIs (odds ratio [OR], 1.30; 95% confidence interval [CI], 1.21-1.39) or H2RAs (OR, 1.18; 95% CI, 1.08-1.29). The risk was reduced after discontinuation of medication (OR of 1.30 [95% CI, 1.21-1.41] for current PPI users vs OR of 1.09 [95% CI, 0.64-1.85] for patients who received their last prescription 2-2.9 years ago). Higher dosages (but not increasing cumulative durations) were associated with increased risk (eg, > or =1.5 pills/day: OR, 1.41 [95% CI, 1.21-1.64]; <0.74 pills/day: OR, 1.12 [95% CI, 0.94-1.33]). Excess fracture risk for PPI use was only present among persons with at least one other fracture risk factor. CONCLUSIONS: Use of drugs that inhibit gastric acid is associated with an increased risk of hip fracture; however, this association was only found among persons with at least one other risk factor for hip fracture. Acid inhibition might therefore be associated with fracture risk in persons already at risk for osteoporosis, although other confounding cannot be excluded.

Colorectal cancer risk in relation to use of acid suppressive medications.

PURPOSE: Acid suppressants are commonly prescribed medications. Laboratory studies suggest a mechanism by which they could increase colorectal cancer (CRC) risk. A few epidemiologic studies have investigated acid suppressant use and CRC risk; none has documented an overall association. We sought to investigate whether acid suppressants are associated with CRC risk. METHODS: We conducted a case-control study among members of an integrated healthcare delivery system in Washington State. Cases (N = 641) were diagnosed with CRC between 2000 and 2003; controls (N = 641) were randomly selected from enrollees and matched to cases on age, sex, and length of enrollment. We used conditional logistic regression to estimate the odds ratios (ORs) and 95% confidence intervals (CI) for CRC associated with the use of any acid suppressive medication, proton pump inhibitors (PPIs) only, histamine receptor antagonists (H2 blockers) only, or both PPIs and H2 blockers in relation to the use of neither PPIs nor H2 blockers. RESULTS: Use of PPIs exclusively was modestly associated with an increased risk of CRC, however this finding was consistent with chance and based on a small number of patients exposed (OR = 1.7; 95%CI = 0.8, 4.0). H2 blocker use alone was not related to CRC risk (OR = 0.8; 95%CI = 0.6, 1.1). CONCLUSIONS: PPI use may be modestly associated with CRC risk; further research should be conducted in populations with long-term PPI use.

Do acid-lowering agents affect vitamin B12 status in older adults?

OBJECTIVE: To examine the relationship between serum vitamin B12 levels in older adults on histamine(2) receptor antagonists (H2 blockers) or proton-pump inhibitors (PPI) over 6 years. PARTICIPANTS: A cross-sectional sample of 659 adults, 60 to 102 years, from long-term care facilities and community ambulatory care (C) in the Bronx. MEASUREMENTS: Patient demographics, serum B12 levels, use and duration of use of H2 blockers, PPIs, antacids, multivitamin/minerals, liquid dietary supplements, oral vitamin B12 supplementation, oral or intramuscular B12 therapy, and recent lab chemistries. RESULTS: Acid-lowering agents (ALA) were used by 54% (PPIs by 26% and H2 blockers by 28%), duration averaged 18.2 +/- 16.0 (SD) months. NH and C subjects had similar ages (P = .9971), gender distributions (P = .625), durations of ALA use (P = .1227), and rates of PPI use (P = .130); NH subjects used more H2 blockers (P < .0005) and had less low B12 status (P = .037). H2 blocker use did not influence serum B12 status (P = .1036) while PPI use was associated with diminished serum B12 levels (P < .00005). Concomitant oral B12 supplementation slowed but did not prevent the decline in B12 status during prolonged PPI use (P = .0125). CONCLUSIONS: B12 status declines during prolonged PPI use in older adults, but not with prolonged H2 blocker use; supplementation with RDA amounts of B12 do not prevent this decline. This report reinforces that B12 deficiency is common in the elderly and suggests that it appears prudent to monitor periodically B12 status while on prolonged PPI use, to enable correction before complications ensue.

Famotidine versus omeprazole, in combination with amoxycillin and tinidazole, for eradication of Helicobacter pylori infection.

BACKGROUND: Eradication regimens combining two antibiotics with a proton pump inhibitor have been studied intensively. In contrast, only a few studies have focused on the possible role of H2-receptor antagonists in eradication therapy. The mechanism involved in the synergy between antibiotics and proton pump inhibitors is still controversial. OBJECTIVES: To compare the results of two triple-therapy regimens, different only in the antisecretory drugs used, in patients with Helicobacter pylori infection, and to assess the impact of primary resistance to metronidazole on treatment outcome. METHODS: A total of 120 patients with peptic ulcer and non-ulcer dyspepsia were randomly assigned to a 2-week course of either: famotidine 40 mg twice a day, amoxycillin 1 g twice a day and tinidazole 500 mg twice a day (FAT group; n = 60); or omeprazole 20 mg twice a day, amoxycillin 1 g twice a day and tinidazole 500 mg twice a day (OAT group; n = 60). Upper endoscopy was performed prior to treatment and at least 4 weeks after completion of treatment and discontinuation of the antisecretory therapy. H. pylori status was assessed by a biopsy urease test, histology and culture. RESULTS: In the intention-to-treat analysis, eradication of H. pylori was achieved in 48 of the 60 patients (80%; 95% confidence interval: 70-90%) in the FAT group, compared to 50 of the 60 patients (83.3%; 95% confidence interval: 74-93%) in the OAT group. In the per protocol analysis, eradication therapy was achieved in 48 out of 53 patients (90.6%; 95% confidence interval: 83-98%) treated with FAT and 50 out of 57 patients (87.7%; 95% confidence interval: 79-96%) treated with OAT (not significant). The primary metronidazole resistance was present in 28.8% of strains. Overall, per protocol eradication rates in strains resistant and susceptible to metronidazole were 83.3% and 91.3% respectively (P > 0.05). CONCLUSIONS: Two-week courses of either high-dose famotidine or omeprazole, both combined with amoxycillin and tinidazole, are equally effective for eradication of H. pylori infection. In a 2-week triple therapy, metronidazole resistance has no significant impact on eradication rates.

Changes in serum interferon-gamma, interleukin-4, and interleukin-12 cytokine levels in anti-histamine type 2-treated allergic rhinitis patients.

OBJECTIVES/HYPOTHESIS: Markedly elevated immunoglobulin E (IgE) synthesis characterizes allergic diseases. Interferon-gamma (IFN-gamma) and interleukin-4 (IL-4) regulate IgE synthesis. It has been shown that immunotherapy and histamine type 2 (H2) receptor antagonists induce a clinical improvement, decrease IgE antibodies, and increase T-cell subsets, which express a suppressor function. In addition, immunotherapy brings about a reduction in the amount of IL-4 in T-cell clones of allergic individuals. The purpose of this study was to investigate the profile of cytokines IFNgamma and IL-4 that occurs in vivo in anti-H2-treated patients with allergic rhinitis (AR). METHODS: Enrolled were 65 AR patients with sensitivity to a single allergen, the Parietaria, 36 of whom were randomly assigned to treatment with ranitidine at a dosage of 1 mg/kg per day intravenously for 20 days, and 29 to placebo treatment. RESULTS: A comparison of the serum cytokine values recorded before and after anti-H2 treatment showed a significant increase in INF-gamma serum level (P = .003) and a decrease in IL-4 (P = .016). Negligible variations were found in the placebo-treated group. CONCLUSION: H2 antagonists probably induce their effects by enhancing the amount of IFN-gamma and by reducing IL-4 cytokines, which, respectively, induce a decrease and an increase in the IgE synthesis.

Standard-dose lansoprazole is more effective than high-dose ranitidine in achieving endoscopic healing and symptom relief in patients with moderately severe reflux oesophagitis. The Dutch Lansoprazole Study Group.

BACKGROUND: In the treatment of reflux oesophagitis, H2-receptor antagonists are still widely used in spite of the apparent higher efficacy of proton pump inhibitors. In an attempt to compensate for the lower efficacy, H2-receptor antagonists are now increasingly being used at a higher dose. OBJECTIVE: To assess whether or not standard-dose lansoprazole (30 mg o.d.) is more effective than high-dose ranitidine (300 mg b.d.) in moderately severe reflux oesophagitis (grades II-III). METHODS: Lansoprazole or ranitidine was given to 133 patients for 4-8 weeks in a double-blind, randomized, parallel group, multicentre trial. RESULTS: The percentage of patients with endoscopically-verified healing was significantly higher on lansoprazole than on ranitidine both after 4 weeks (79% vs. 42%) and 8 weeks (91% vs. 66%), though smoking had a negative impact on oesophagitis healing with lansoprazole. Heartburn, retrosternal pain and belching improved significantly better with lansoprazole than with ranitidine, as did the patient-rated overall symptom severity. Relief of heartburn appeared somewhat faster with ranitidine, but was more pronounced with lansoprazole. The number of patients with adverse events was similar in both treatment groups. CONCLUSION: Standard-dose lansoprazole is better than high-dose ranitidine in moderately severe reflux oesophagitis.

[An elderly case with pseudogout exacerbated by the administration of granulocyte-colony stimulating factor during drug-induced granulocytopenia].

A 82-year-old woman was admitted because of dehydration and chronic renal failure. Although her renal function was improved by hydration, granulocytopenia (granulocyte number 645/mm3) occurred. Treatment with a relatively high dose of H2 blocker for one month before admission may have caused the granulocytopenia. To prevent possible infection in the patient, we administered 75 g of granulocyte-colony stimulating factor (G-CSF) for 5 consecutive days but 4 days after commencement of administration of G-CSF, pain in both knee joints suddenly appeared. Synovial fluid aspiration revealed granulocytosis (10,400/mm3) and deposition of calcium pyrophosphate dihydrate in the knee joints. The level of G-CSF in the synovial fluid was increased in the joints (700 pg/ml), compared with the serum concentration (62 pg/ml). Furthermore, the concentrations of interleukin-6 and interleukin-8 were markedly increased in the synovial fluid. The results indicated that her pseudogout exacerbation by G-CSF was at least in part explained by the increased production of cytokines in the knee joints. Because the prevalence of pseudogout and gout is overwhelming in the elderly, the possibility of GCSF induced exacerbation of joint pain should be carefully considered in elderly patients.

The consequences of H2 receptor antagonist--piroxicam coadministration in patients with joint disorders.

A randomised crossover study was performed in subjects with rheumatoid arthritis (or other arthropathies) to investigate if any alteration in the steady pharmacokinetics of the NSAID piroxicam (a drug which is extensively metabolised via cytochrome P450) or its major metabolites occurred as a result of coadministering either cimetidine or nizatidine. Twelve females and 2 males with mean age, weight, and albumin concentrations of 58 years, 61 kg, and 40 g.L-1 respectively, completed the study. Comparisons were made between the following parameters: plasma piroxicam AUCs [AUC0-24(P)], plasma 5-hydroxypiroxicam AUCs [AUC0-24(5-OHP)], the ratio of these i.e. AUC0-24(5-OHP):AUC0-24(p), the % piroxicam daily dose excreted in urine as 5-hydroxypiroxicam (before and after glucuronidase incubation); and the mean of the steady state trough piroxicam, and 5-hydroxypiroxicam concentrations (obtained during each study phase in addition to the wash-out period). A statistically significant difference as a result of initiating either cimetidine or nizatidine was obtained only for the ratio AUC0-23(5-OHP):AUC0-24(P). This was indicative of a weak potential to inhibit piroxicam hydroxylation. No clinically significant alteration in the steady state pharmacokinetics of piroxicam occurred in these subjects as a result of cimetidine or nizatidine coadministration. Consequently it is unlikely that any adverse events would arise from these combinations.