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PPI evidence

The following is evidence that may be used in a new chapter exploring risks and benefits of PPI drugs:

Are Acid suppressant drugs harmful?

Proton Pump Inhibitor Usage and the Risk of Myocardial Infarction in the General Population

our data-mining study supports the association of PPI exposure with risk for MI in the general population”

Risk of acute myocardial infarction in patients with gastroesophageal reflux disease: A nationwide population-based study

“PPIs use only achieved marginal significance in reducing the occurrence of AMI in GERD patients “

PPIs and CV Safety: Good Science to the Rescue

Two recent reports put into perspective some of these potential risks for clinicians and patients. The first report[1] provides evidence that the association of PPIs with myocardial infarction (MI) should not be a concern, and the second study[2] reports no association with stroke. “

Systematic review with meta-analysis: risk of adverse cardiovascular events with proton pump inhibitors independent of clopidogrel. - PubMed - NCBI

"There is no clear evidence of an association between PPI monotherapy and increased cardiovascular risk."

Proton Pump Inhibitor Use and the Risk of Chronic Kidney Disease

“Proton pump inhibitor use is associated with a higher risk of incident CKD “

How Real Is the Link Between PPI Use and Kidney Disease?

"  I don't think the renal issue is a significant one when co-adjusted for all of the multiple risks"

Proton Pump Inhibitors and Risk of Hepatocellular Carcinoma in Patients with Chronic Hepatitis B or C. - PubMed - NCBI

"Based on a retrospective, nationwide population-based cohort study in Taiwan, where the prescription of PPI is tightly regulated, PPI use is not associated with the risk of developing HCC among patients with chronic HBV or HCV infections."

Association of Proton Pump Inhibitors With Risk of Dementia

“avoidance of PPI medication may prevent the development of dementia “

Proton Pump Inhibitors and Dementia: Cause for Concern?

"The authors adjusted for some variables, but certainly not all confounders. They adjusted for age, gender, polypharmacy, stroke history, depression, ischemic heart disease, and diabetes.

They didn't adjust for some very important risk factors for dementia, including alcohol use, family history of dementia, and hypertension. These are well-known risk factors for dementia, and for some reason, these weren't included in the analysis. Thus, we're missing a tremendous amount of potential risk factors that might account for the imbalance of incident dementia between PPI users and nonusers."

Proton Pump Inhibitors and Risk of Mild Cognitive Impairment and Dementia - Goldstein - 2017 - Journal of the American Geriatrics Society - Wiley Online Library

Proton pump inhibitors were not associated with greater risk of dementia or of AD “

Lack of Association Between Proton Pump Inhibitor Use and Cognitive Decline - Clinical Gastroenterology and Hepatology

"We conclude that there was no association between chronic PPI use and cognitive score or cognitive decline in this large population-based study of middle-aged and older Danish twins."

Proton Pump Inhibitor Use and Risk of Developing Alzheimer's Disease or Vascular Dementia: A Case-Control Analysis. - PubMed - NCBI

"In this large, case-control analysis, we did not find any evidence for an increased risk of either AD or VaD related to PPI or H2RA use."

ProtonPump Inhibitor and Histamine–2 Receptor Antagonist Use and Risk of Liver Cancer

"We found some evidence that PPI use was associated with liver cancer. Whether this association is causal or reflects residual confounding or reverse causation requires additional research."

Association of Gastric Acid Suppression With Recurrent Clostridium difficile Infection

A Systematic Review and Meta-analysis

"  Meta-analyses of observational studies suggest that patients who receive gastric acid suppressants may be at increased risk for recurrent CDI. These data should be interpreted with caution because they may be confounded owing to the observational design of the individual studies."

Withholding Proton Pump Inhibitors to Prevent Recurrent Clostridium difficile: Time for a Randomized Trial | Gastroenterology | JAMA Internal Medicine | JAMA Network

"patients who take gastric acid suppressants are different from, and most likely sicker than, those who do not take gastric acid suppressants"

Proton Pump Inhibitors: Risks and Rewards and Emerging Consequences to the Gut Microbiome.

 "current data suggest that PPI use is not associated with an increased risk of bone fractures, community-acquired pneumonia, cardiovascular events, hypocalcemia, and gastric malignancies. A mild increased risk of vitamin B12 deficiency and chronic kidney disease, and a moderate increase in the risk of rebound hypersecretion, small intestinal bacterial overgrowth, and enteric infections, including Clostridium difficile, has been noted with PPI therapy"

Doctors: Be wary of new PPI studies linking drug to health problems,148602

"These studies are observational studies. These are not considered to be the cause-all factor. It's not definitely directly linked,"

Is it safe to take PPIs? A gastroenterologist explains the risks

“PPIs have become the go-to because they are very effective.“With 30 years of use by tens of millions of people, they’ve been shown to be very safe.”

When It Comes to PPIs, Why All the 'Mayhem'?

"Let's go through the different concerns and talk about best practice recommendations."

Proton pump inhibitors: Risks of long‐term use

"We have reviewed the most recent literature reporting possible associations between long‐term PPI treatment and adverse effects and discussed the mechanisms through which these complications might develop. ... In most cases and based on the available evidence, PPIs benefits seem to outweigh potential adverse effects."

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Do acid suppressants prevent cancer?

The case against

Proton pump inhibitor use may not prevent high-grade dysplasia and oesophageal adenocarcinoma in Barrett's oesophagus: a nationwide study of 9883 p... - PubMed - NCBI

No cancer-protective effects from PPI's were seen. In fact, high-adherence and long-term use of PPI were associated with a significantly increased risk of adenocarcinoma or high-grade dysplasia. “

Maintenance proton pump inhibition therapy and risk of oesophageal cancer - ScienceDirect

"The long term use of PPIs is associated with increased risk of oesophageal adenocarcinoma in the absence of other risk factors. Long term use of PPIs should be addressed with caution."

The case for

Acid-suppressive medications and risk of oesophageal adenocarcinoma in patients with Barrett's oesophagus: a systematic review and meta-analysis | Gut

Based on meta-analysis of observational studies, the use of PPIs is associated with a decreased risk of OAC and/or BO-HGD in patients with BO. None of the studies showed an increased risk of OAC “

PPIs Protective for Esophageal Cancer - Gastroenterology & Endoscopy News

The present study provides relatively good evidence that PPI use prevents progression to EAC in BE patients,”[Same study as above]

Proton Pump Inhibitors Display Antitumor Effects in Barrett's Adenocarcinoma Cells

Our results showed that esomeprazole, especially at high concentrations (50, 100, and 200 μM) increased apoptosis of EAC cells “ “In conclusion, the present study demonstrates that PPI exerts antineoplastic effects on EAC in vitro “

Letter: proton pump inhibitor usage still seems to reduce the risk of high‐grade dysplasia and/or oesophageal adenocarcinoma in Barrett's oesophagus - Aydin - 2014 - Alimentary Pharmacology & Therapeutics - Wiley Online Library

Even with the addition of the negative result study of Hvid‐Jensen et al. to the meta‐analysis, we can conclude that PPI usage still seems to reduce the risk of OAC and/or HGD in BO “

Acid suppression medications reduce risk of oesophageal adenocarcinoma in Barrett's oesophagus: a nested case‐control study in US male veterans

"In summary, we found PPI use to be associated with 41% lower risk, and H2RA use with 30% lower risk of Barrett's oesophagus progression to OAC after adjusting for multiple confounders"

Taking aspirin and anti-acid reflux medication prevents oesophageal cancer in high risk patients | Cancer Research UK

"people who took this combination for at least seven years were 20% less likely to develop oesophageal cancer than if they had been untreated"

The proton pump inhibitor pantoprazole disrupts protein degradation systems and sensitizes cancer cells to death under various stresses | Cell Death & Disease

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