Background & Aims A new generation of oral anticoagulants (nOAC), which includes thrombin and factor Xa inhibitors, has been shown to be effective, but little is known about whether these drugs ...increase patients’ risk for gastrointestinal bleeding (GIB). Patients who require OAC therapy frequently have significant comorbidities and may also take aspirin and/or thienopyridines. We performed a systematic review and meta-analysis of the risk of GIB and clinically relevant bleeding in patients taking nOAC. Methods We queried MEDLINE, EMbase, and the Cochrane library (through July 2012) without language restrictions. We analyzed data from 43 randomized controlled trials (151,578 patients) that compared nOAC (regardless of indication) with standard care for risk of bleeding (19 trials on GIB). Odds ratios (ORs) were estimated using a random-effects model. Heterogeneity was assessed with the Cochran Q test and the Higgins I2 test. Results The overall OR for GIB among patients taking nOAC was 1.45 (95% confidence interval CI, 1.07−1.97), but there was substantial heterogeneity among studies (I2 , 61%). Subgroup analyses showed that the OR for atrial fibrillation was 1.21 (95% CI, 0.91−1.61), for thromboprophylaxis after orthopedic surgery the OR was 0.78 (95% CI, 0.31−1.96), for treatment of venous thrombosis the OR was 1.59 (95% CI, 1.03−2.44), and for acute coronary syndrome the OR was 5.21 (95% CI, 2.58−10.53). Among the drugs studied, the OR for apixaban was 1.23 (95% CI, 0.56−2.73), the OR for dabigatran was 1.58 (95% CI, 1.29−1.93), the OR for edoxaban was 0.31 (95% CI, 0.01−7.69), and the OR for rivaroxaban was 1.48 (95% CI, 1.21−1.82). The overall OR for clinically relevant bleeding in patients taking nOAC was 1.16 (95% CI, 1.00−1.34), with similar trends among subgroups. Conclusions Studies on treatment of venous thrombosis or acute coronary syndrome have shown that patients treated with nOAC have an increased risk of GIB, compared with those who receive standard care. Better reporting of GIB events in future trials could allow stratification of patients for therapy with gastroprotective agents.
Background Proton pump inhibitor (PPI) use has been associated with hypomagnesemia in case reports and hospital-based cohort studies. Our objective was to determine whether PPI use is associated with ...hypomagnesemia in the general population and whether this is also found in histamine 2 receptor antagonist (H2RA) users. Study Design Prospective cohort study. Setting & Participants 9,818 individuals from the general population (Rotterdam Study). Predictor PPI use and H2RA use compared to no use. Outcomes & Measurements Serum magnesium and hypomagnesemia (serum magnesium ≤ 1.44 mEq/L). Analyses were adjusted for age, sex, body mass index, kidney function, comorbid conditions, and alcohol and diuretic use. Results Serum magnesium level was 0.022 mEq/L lower in PPI users (n = 724; 95% CI, −0.032 to −0.014 mEq/L) versus those with no use. PPI use was associated with increased risk of hypomagnesemia (n = 36; OR, 2.00; 95% CI, 1.36-2.93) compared to no use. Effect modification was found between the use of PPIs and loop diuretics; in participants using loop diuretics (n = 270), PPI use was associated with a further increased risk of hypomagnesemia (n = 5; OR, 7.22; 95% CI, 1.69-30.83) compared to no use. The increased risk with PPIs was only seen after prolonged use (range, 182-2,618 days; OR, 2.99; 95% CI, 1.73-5.15). Including dietary magnesium intake into the model did not alter results (available for 2,504 participants, including 231 PPI users). H2RA users (n = 250) also had a lower serum magnesium level (−0.016 95% CI, −0.032 to −0.002 mEq/L) and increased risk of hypomagnesemia (n = 12; OR, 2.00; 95% CI, 1.08-3.72) compared to those with no use, but no interaction with loop diuretics. Limitations Cross-sectional analysis with single serum magnesium measurement. Conclusions PPI use is associated with hypomagnesemia in the general population. Prolonged PPI use and concomitant loop diuretic use are associated with a stronger risk increase. Similar but weaker associations were found in H2RA users, except for interaction with loop diuretics.
Non-variceal upper gastrointestinal bleeding remains an important emergency condition, leading to significant morbidity and mortality. As endoscopic therapy is the ’gold standard' of management, ...treatment of these patients can be considered in three stages: pre-endoscopic treatment, endoscopic haemostasis and post-endoscopic management. Since publication of the Asia-Pacific consensus on non-variceal upper gastrointestinal bleeding (NVUGIB) 7 years ago, there have been significant advancements in the clinical management of patients in all three stages. These include pre-endoscopy risk stratification scores, blood and platelet transfusion, use of proton pump inhibitors; during endoscopy new haemostasis techniques (haemostatic powder spray and over-the-scope clips); and post-endoscopy management by second-look endoscopy and medication strategies. Emerging techniques, including capsule endoscopy and Doppler endoscopic probe in assessing adequacy of endoscopic therapy, and the pre-emptive use of angiographic embolisation, are attracting new attention. An emerging problem is the increasing use of dual antiplatelet agents and direct oral anticoagulants in patients with cardiac and cerebrovascular diseases. Guidelines on the discontinuation and then resumption of these agents in patients presenting with NVUGIB are very much needed. The Asia-Pacific Working Group examined recent evidence and recommends practical management guidelines in this updated consensus statement.
Summary Acute upper gastrointestinal bleeding is a common medical emergency worldwide, a major cause of which are bleeding peptic ulcers. Endoscopic treatment and acid suppression with proton-pump ...inhibitors are cornerstones in the management of the disease, and both treatments have been shown to reduce mortality. The role of emergency surgery continues to diminish. In specialised centres, radiological intervention is increasingly used in patients with severe and recurrent bleeding who do not respond to endoscopic treatment. Despite these advances, mortality from the disorder has remained at around 10%. The disease often occurs in elderly patients with frequent comorbidities who use antiplatelet agents, non-steroidal anti-inflammatory drugs, and anticoagulants. The management of such patients, especially those at high cardiothrombotic risk who are on anticoagulants, is a challenge for clinicians. We summarise the published scientific literature about the management of patients with bleeding peptic ulcers, identify directions for future clinical research, and suggest how mortality can be reduced.
Proton pump inhibitor (PPI)-induced hypomagnesemia has been recognized since 2006. Our aim was to further characterize the clinical consequences and possible mechanisms of this electrolyte disorder ...using 4 cases. Two men (aged 63 and 81 years) and 2 women (aged 73 and 62 years) had been using a PPI (esomeprazole, pantoprazole, omeprazole, and rabeprazole, 20-40 mg) for 1-13 years. They developed severe hypomagnesemia (magnesium, 0.30 ± 0.28 mEq/L; reference, 1.40-2.10 mEq/L) with hypocalcemia (calcium, 6.4 ± 1.8 mg/dL), relative hypoparathyroidism (parathyroid hormone, 43 ± 6 pg/mL), and extremely low urinary calcium and magnesium excretion. One patient was admitted with postanoxic encephalopathy after a collapse likely caused by arrhythmia. The others had electrocardiogram abnormalities (prolonged QT interval, ST depression, and U waves). Concomitant hypokalemia (potassium, 2.8 ± 0.1 mEq/L) was considered the trigger for these arrhythmias. Hypomagnesemia-induced kaliuresis (potassium excretion, 65 ± 24 mEq/L) was identified as the cause of hypokalemia. This series of PPI-induced hypomagnesemia shows that this is a generic effect. It also indicates that hypomagnesemia may occur within 1 year of PPI therapy initiation and can have serious clinical consequences, likely triggered by the associated hypokalemia. A high index of suspicion is required in PPI users for unexplained hypomagnesemia, hypocalcemia, hypokalemia, or associated symptoms.
Gastric cancer remains a prevalent disease worldwide with a poor prognosis.
Helicobacter pylori
plays a major role in gastric carcinogenesis.
H. pylori
colonization leads to chronic gastritis, which ...predisposes to atrophic gastritis, intestinal metaplasia, dysplasia, and eventually gastric cancer. Screening, treatment, and prevention of
H. pylori
colonization can reduce the incidence of gastric cancer. Other interventions that may yield a similar effect, although of smaller magnitude, include promotion of a healthy lifestyle including dietary measures, non-smoking, low alcohol intake, and sufficient physical activity. This chapter reviews interventions that can lead to a decline in gastric cancer incidence in high and low incidence countries.
Gastric intestinal metaplasia (GIM), which denotes conversion of gastric mucosa into an intestinal phenotype, can occur in all regions of the stomach, including cardiac, fundic, and pyloric mucosa. ...Since the earliest description of GIM, its association with gastric cancer of the differentiated (intestinal) type has been a well-recognized concern. Many epidemiologic studies have confirmed GIM to be significantly associated with subsequent gastric cancer development. Helicobacter pylori, the principal etiologic factor for gastric cancer, plays the most important role in predisposing to GIM. Although the role of GIM in the stepwise progression model of gastric carcinogenesis (the so-called "Correa cascade") has come into question recently, we review the scientific evidence that strongly supports this long-standing model and propose a new progression model that builds on the Correa cascade. Eradication of H pylori is the most important method for preventing gastric cancer globally, but the effect of eradication on established GIM, is limited, if any. Endoscopic surveillance for GIM may, therefore, be necessary, especially when there is extensive corpus GIM. Recent advances in image-enhanced endoscopy with integrated artificial intelligence have facilitated the identification of GIM and neoplastic lesions, which will impact preventive strategies in the near future.
Oncological care was largely derailed due to the reprioritisation of health care services to handle the initial surge of COVID-19 patients adequately. Cancer screening programmes were no exception in ...this reprioritisation. They were temporarily halted in the Netherlands (1) to alleviate the pressure on health care services overwhelmed by the upsurge of COVID-19 patients, (2) to reallocate staff and personal protective equipment to support critical COVID-19 care, and (3) to mitigate the spread of COVID-19. Utilising data from the Netherlands Cancer Registry on provisional cancer diagnoses between 6 January 2020 and 4 October 2020, we assessed the impact of the temporary halt of national population screening programmes on the diagnosis of breast and colorectal cancer in the Netherlands. A dynamic harmonic regression model with ARIMA error components was applied to assess the observed versus expected number of cancer diagnoses per calendar week. Fewer diagnoses of breast and colorectal cancer were objectified amid the early stages of the initial COVID-19 outbreak in the Netherlands. This effect was most pronounced among the age groups eligible for cancer screening programmes, especially in breast cancer (age group 50-74 years). Encouragingly enough, the observed number of diagnoses ultimately reached and virtually remained at the level of the expected values. This finding, which emerged earlier in age groups not invited for cancer screening programmes, comes on account of the decreased demand for critical COVID-19 care since early April 2020, which, in turn, paved the way forward to resume screening programmes and a broad range of non-critical health care services, albeit with limited operating and workforce capacity. Collectively, transient changes in health-seeking behaviour, referral practices, and cancer screening programmes amid the early stages of the initial COVID-19 epidemic in the Netherlands conjointly acted as an accelerant for fewer breast and colorectal cancer diagnoses in age groups eligible for cancer screening programmes. Forthcoming research is warranted to assess whether the decreased diagnostic scrutiny of cancer during the COVID-19 pandemic resulted in stage migration and altered clinical management, as well as poorer outcomes.
A multidisciplinary group of 34 experts from 15 countries developed this update and expansion of the recommendations on the management of acute nonvariceal upper gastrointestinal bleeding (UGIB) from ...2003.
The Appraisal of Guidelines for Research and Evaluation (AGREE) process and independent ethics protocols were used. Sources of data included original and published systematic reviews; randomized, controlled trials; and abstracts up to October 2008. Quality of evidence and strength of recommendations have been rated by using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) criteria.
Recommendations emphasize early risk stratification, by using validated prognostic scales, and early endoscopy (within 24 hours). Endoscopic hemostasis remains indicated for high-risk lesions, whereas data support attempts to dislodge clots with hemostatic, pharmacologic, or combination treatment of the underlying stigmata. Clips or thermocoagulation, alone or with epinephrine injection, are effective methods; epinephrine injection alone is not recommended. Second-look endoscopy may be useful in selected high-risk patients but is not routinely recommended. Preendoscopy proton-pump inhibitor (PPI) therapy may downstage the lesion; intravenous high-dose PPI therapy after successful endoscopic hemostasis decreases both rebleeding and mortality in patients with high-risk stigmata. Although selected patients can be discharged promptly after endoscopy, high-risk patients should be hospitalized for at least 72 hours after endoscopic hemostasis. For patients with UGIB who require a nonsteroidal anti-inflammatory drug, a PPI with a cyclooxygenase-2 inhibitor is preferred to reduce rebleeding. Patients with UGIB who require secondary cardiovascular prophylaxis should start receiving acetylsalicylic acid (ASA) again as soon as cardiovascular risks outweigh gastrointestinal risks (usually within 7 days); ASA plus PPI therapy is preferred over clopidogrel alone to reduce rebleeding.
International guidelines recommend endoscopic surveillance of premalignant gastric lesions. However, the diagnostic yield and preventive effect require further study. We therefore aimed to assess the ...incidence of neoplastic progression and to assess the ability of various tests to identify patients most at risk for progression.
Patients from the Netherlands and Norway with a previous diagnosis of atrophic gastritis (AG), intestinal metaplasia (IM) or dysplasia were offered endoscopic surveillance. All histological specimens were assessed according to the updated Sydney classification and the operative link on gastric intestinal metaplasia (OLGIM) system. In addition, we measured serum pepsinogens (PG) and gastrin-17.
279 (mean age 57.9 years, SD 11.4, male/female 137/142) patients were included and underwent at least one surveillance endoscopy during follow-up. The mean follow-up time was 57 months (SD 36). Four subjects (1.4%) were diagnosed with high-grade adenoma/dysplasia or invasive neoplasia (ie, gastric cancer) during follow-up. Two of these patients were successfully treated with endoscopic submucosal dissection, while the other two underwent a total gastrectomy. Compared with patients with extended AG/IM (PGI/II≤3 and/or OGLIM stage III-IV), patients with limited AG/IM (PG I/II>3 and OLGIM stage 0-II) did not develop high-grade adenoma/dysplasia or invasive neoplasia during follow-up (p=0.02).
In a low gastric cancer incidence area, a surveillance programme can detect gastric cancer at an early curable stage with an overall risk of neoplastic progression of 0.3% per year. Use of serological markers in endoscopic surveillance programmes may improve risk stratification.
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