Complications of Proton Pump Inhibitor Therapy
TL;DR: Many of the proposed adverse consequences of PPI therapy are reviewed and established criteria for the determination of causation are applied and the potential contribution of residual confounding in many of the reported studies are considered.
About: This article is published in Gastroenterology.The article was published on 2017-07-01 and is currently open access. It has received 318 citations till now.
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Population Health Research Institute1, University of Würzburg2, University of Washington Medical Center3, Brigham and Women's Hospital4, Katholieke Universiteit Leuven5, National University of Ireland, Galway6, Semmelweis University7, Bayer8, Catholic University of Korea9, Paris Diderot University10, Centra11, Charles University in Prague12, University of Washington13, University College London14, Karolinska Institutet15, University of the Philippines16, University of La Frontera17, University of Cape Town18, Aalborg University19, University of Glasgow20, Jagiellonian University21, Monash University22, Universiti Teknologi MARA23, University of Edinburgh24
TL;DR: In a large placebo-controlled randomized trial, it is found that pantoprazole is not associated with any adverse event when used for 3 years, with the possible exception of an increased risk of enteric infections.
266 citations
McGill University1, Erasmus University Medical Center2, Yale University3, The Chinese University of Hong Kong4, McMaster University5, Mayo Clinic6, Carlos III Health Institute7, University of British Columbia8, Technion – Israel Institute of Technology9, University of Western Ontario10, University of California, Los Angeles11, University of Liverpool12, University of São Paulo13, George Washington University14, Brigham and Women's Hospital15
TL;DR: This update focuses on resuscitation and risk assessment; preendoscopic, endoscopic, and pharmacologic management; and secondary prophylaxis for recurrent UGIB, as well as assessing the methodological quality of existing systematic reviews.
Abstract: This guideline updates the 2010 International Consensus Recommendations on Management of Patients With Nonvariceal Upper Gastrointestinal Bleeding.
260 citations
Cites background from "Complications of Proton Pump Inhibi..."
...An analysis of factors, such as consistency, specificity, temporality, and biological plausibility, as well as confounding factors, showed that the evidence for causality is very weak (110)....
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TL;DR: Future approaches to treatment of GERD include potassium-competitive acid blockers, reflux-reducing agents, bile acid binders, injection of inert substances into the esophagogastric junction, and electrical stimulation of the lower esophageal sphincter.
194 citations
TL;DR: In this article, the authors provide updated, evidence-based recommendations and practical guidance for the evaluation and management of Gastroesophageal reflux disease, including pharmacologic, lifestyle, surgical, and endoscopic management.
163 citations
TL;DR: Evidence of an independent, dose-response relationship between the use of antisecretory medications and COVID-19 positivity is found; individuals taking PPIs twice daily have higher odds for reporting a positive test when compared with those using lower-dose PPIs up to once daily, and those taking the less potent histamine-2 receptor antagonists are not at increased risk.
151 citations
Cites background from "Complications of Proton Pump Inhibi..."
...3) (1), suggesting that bias alone might not entirely explain that degree of effect size, the aOR of 2....
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...INTRODUCTION Proton pump inhibitors (PPIs) are among the most commonly usedmedications in theUnited States andhave been linked to side effects including bone fracture, chronic kidney disease, and gastrointestinal (GI) infections, among others (1)....
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...This effect is likely related to PPI-induced hypochlorhydria, which impairs the body’s proximal defense against ingested bacteria and viruses (1), and may also occur because prolonged use of PPIs reduces microbial diversity in the gut (7), an effect believed to enable colonization of some enteric pathogens (8)....
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...Moreover, unlike many studies that use retrospective data to examine potential PPI side effects (1), we prospectively constructed this online survey to test an a priori hypothesis....
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...Thus, although most hypothesized complications from PPIs have not withstood the test of time (1), enteric infection is one adverse event supported by both metaanalyses and randomized controlled trial data....
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References
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TL;DR: The criteria outlined in "The Environment and Disease: Association or Causation?" help identify the causes of many diseases, including cancers of the reproductive system.
Abstract: In 1965, Austin Bradford Hill published the article "The Environment and Disease: Association or Causation?" in the Proceedings of the Royal Society of Medicine. In the article, Hill describes nine criteria to determine if an environmental factor, especially a condition or hazard in a work environment, causes an illness. The article arose from an inaugural presidential address Hill gave at the 1965 meeting of the Section of Occupational Medicine of the Royal Society of Medicine in London, England. The criteria he established in the article became known as the Bradford Hill criteria and the medical community refers to them when determining whether an environmental condition causes an illness. The criteria outlined in "The Environment and Disease: Association or Causation?" help identify the causes of many diseases, including cancers of the reproductive system.
6,992 citations
TL;DR: The antiplatelet agent clopidogrel has beneficial effects in patients with acute coronary syndromes without ST-segment elevation, however, the risk of major bleeding is increased among patients treated with clopIDogrel.
Abstract: Background: Despite current treatments, patients who have acute coronary syndromes without ST-segment elevation have high rates of major vascular events. We evaluated the efficacy and safety of the antiplatelet agent clopidogrel when given with aspirin in such patients. Methods: We randomly assigned 12,562 patients who had presented within 24 hours after the onset of symptoms to receive clopidogrel (300 mg immediately, followed by 75 mg once daily) (6259 patients) or placebo (6303 patients) in addition to aspirin for 3 to 12 months. Results: The first primary outcome -- a composite of death from cardiovascular causes, nonfatal myocardial infarction, or stroke -- occurred in 9.3 percent of the patients in the clopidogrel group and 11.4 percent of the patients in the placebo group (relative risk with clopidogrel as compared with placebo, 0.80; 95 percent confidence interval, 0.72 to 0.90; P<0.001). The second primary outcome -- the first primary outcome or refractory ischemia -- occurred in 16.5 percent of the patients in the clopidogrel group and 18.8 percent of the patients in the placebo group (relative risk, 0.86, P<0.001). The percentages of patients with in-hospital refractory or severe ischemia, heart failure, and revascularization procedures were also significantly lower with clopidogrel. There were significantly more patients with major bleeding in the clopidogrel group than in the placebo group (3.7 percent vs. 2.7 percent; relative risk, 1.38; P=0.001), but there were not significantly more patients with episodes of life-threatening bleeding (2.1 percent vs. 1.8 percent, P=0.13) or hemorrhagic strokes. Conclusions: The antiplatelet agent clopidogrel has beneficial effects in patients with acute coronary syndromes without ST-segment elevation. However, the risk of major bleeding is increased among patients treated with clopidogrel. (N Engl J Med 2001;345:494-502.) Copyright (C) 2001 Massachusetts Medical Society.
5,977 citations
Journal Article•
TL;DR: This paper contrasts Bradford Hill’s approach with a currently fashionable framework for reasoning about statistical associations – the Common Task Framework – and suggests why following Bradford Hill, 50+ years on, is still extraordinarily reasonable.
Abstract: In 1965, Sir Austin Bradford Hill offered his thoughts on: “What aspects of [an] association should we especially consider before deciding that the most likely interpretation of it is causation?” He proposed nine means for reasoning about the association, which he named as: strength, consistency, specificity, temporality, biological gradient, plausibility, coherence, experiment, and analogy. In this paper, we look at what motivated Bradford Hill to propose we focus on these nine features. We contrast Bradford Hill’s approach with a currently fashionable framework for reasoning about statistical associations – the Common Task Framework. And then suggest why following Bradford Hill, 50+ years on, is still extraordinarily reasonable.
5,542 citations
TL;DR: Following PCI, long-term clopidogrel therapy significantly reduced the risk of adverse ischemic events and subgroup analyses suggest that longer intervals between the loading dose and PCI may reduce events.
Abstract: ContextFollowing percutaneous coronary intervention (PCI), short-term clopidogrel
therapy in addition to aspirin leads to greater protection from thrombotic
complications than aspirin alone. However, the optimal duration of combination
oral antiplatelet therapy is unknown. Also, although current clinical data
suggest a benefit for beginning therapy with a clopidogrel loading dose prior
to PCI, the practical application of this therapy has not been prospectively
studied.ObjectivesTo evaluate the benefit of long-term (12-month) treatment with clopidogrel
after PCI and to determine the benefit of initiating clopidogrel with a preprocedure
loading dose, both in addition to aspirin therapy.Design, Setting, and ParticipantsThe Clopidogrel for the Reduction of Events During Observation (CREDO)
trial, a randomized, double-blind, placebo-controlled trial conducted among
2116 patients who were to undergo elective PCI or were deemed at high likelihood
of undergoing PCI, enrolled at 99 centers in North America from June 1999
through April 2001.InterventionsPatients were randomly assigned to receive a 300-mg clopidogrel loading
dose (n = 1053) or placebo (n = 1063) 3 to 24 hours before PCI. Thereafter,
all patients received clopidogrel, 75 mg/d, through day 28. From day 29 through
12 months, patients in the loading-dose group received clopidogrel, 75 mg/d,
and those in the control group received placebo. Both groups received aspirin
throughout the study.Main Outcome MeasuresOne-year incidence of the composite of death, myocardial infarction
(MI), or stroke in the intent-to-treat population; 28-day incidence of the
composite of death, MI, or urgent target vessel revascularization in the per-protocol
population.ResultsAt 1 year, long-term clopidogrel therapy was associated with a 26.9%
relative reduction in the combined risk of death, MI, or stroke (95% confidence
interval [CI], 3.9%-44.4%; P = .02; absolute reduction,
3%). Clopidogrel pretreatment did not significantly reduce the combined risk
of death, MI, or urgent target vessel revascularization at 28 days (reduction,
18.5%; 95% CI, −14.2% to 41.8%; P = .23). However,
in a prespecified subgroup analysis, patients who received clopidogrel at
least 6 hours before PCI experienced a relative risk reduction of 38.6% (95%
CI, −1.6% to 62.9%; P = .051) for this end
point compared with no reduction with treatment less than 6 hours before PCI.
Risk of major bleeding at 1 year increased, but not significantly (8.8% with
clopidogrel vs 6.7% with placebo; P = .07).ConclusionsFollowing PCI, long-term (1-year) clopidogrel therapy significantly
reduced the risk of adverse ischemic events. A loading dose of clopidogrel
given at least 3 hours before the procedure did not reduce events at 28 days,
but subgroup analyses suggest that longer intervals between the loading dose
and PCI may reduce events.
2,977 citations
Centers for Disease Control and Prevention1, Colorado Department of Public Health and Environment2, Oregon Health Authority3, University of Rochester4, Veterans Health Administration5, Yale University6, University of New Mexico7, Maryland Department of Health8, University of California, San Francisco9
TL;DR: In this article, the authors used regression models to calculate estimates of national incidence and total number of infections, first recurrences, and deaths within 30 days after the diagnosis of C. difficile infection.
Abstract: Background The magnitude and scope of Clostridium difficile infection in the United States continue to evolve. Methods In 2011, we performed active population- and laboratory-based surveillance across 10 geographic areas in the United States to identify cases of C. difficile infection (stool specimens positive for C. difficile on either toxin or molecular assay in residents ≥1 year of age). Cases were classified as community-associated or health care–associated. In a sample of cases of C. difficile infection, specimens were cultured and isolates underwent molecular typing. We used regression models to calculate estimates of national incidence and total number of infections, first recurrences, and deaths within 30 days after the diagnosis of C. difficile infection. Results A total of 15,461 cases of C. difficile infection were identified in the 10 geographic areas; 65.8% were health care–associated, but only 24.2% had onset during hospitalization. After adjustment for predictors of disease incidence, the estimated number of incident C. difficile infections in the United States was 453,000 (95% confidence interval [CI], 397,100 to 508,500). The incidence was estimated to be higher among females (rate ratio, 1.26; 95% CI, 1.25 to 1.27), whites (rate ratio, 1.72; 95% CI, 1.56 to 2.0), and persons 65 years of age or older (rate ratio, 8.65; 95% CI, 8.16 to 9.31). The estimated number of first recurrences of C. difficile infection was 83,000 (95% CI, 57,000 to 108,900), and the estimated number of deaths was 29,300 (95% CI, 16,500 to 42,100). The North American pulsed-field gel electrophoresis type 1 (NAP1) strain was more prevalent among health care–associated infections than among community-associated infections (30.7% vs. 18.8%, P<0.001) Conclusions C. difficile was responsible for almost half a million infections and was associated with approximately 29,000 deaths in 2011. (Funded by the Centers for Disease Control and Prevention.)
2,209 citations