PPI Use Warnings

There is a lot of fear mongering going on out there concerning PPI use warnings in the treatment of baby reflux. This article is going to address those studies and shed some light on how they were done so you can draw your own conclusions and how the really apply to the treatment of baby reflux “disease”. Because as we’ve stated time and time again, “Medications such as H2 blockers and proton pump inhibitors should only be considered when the reflux symptoms become a disease. Check out this page for the medical definition of GERD.

MOST Recent Releases of Long Term Use of PPI Medications.

In a 2018 abstract: Proton pump inhibitors (PPIs) potently inhibit gastric acid secretion and are widely used for treatment of acid-related diseases including gastroesophageal reflux disease and secondary prevention of aspirin/NSAID-induced ulcers. Although clinically important adverse effects of PPIs can occur, just as with other drugs, those are not frequently observed during or after administration. Thus, PPIs are regarded as relatively safe and considered to be clinically beneficial. Recently, PPIs have become frequently administered to patients with functional gastrointestinal diseases or primary prevention of drug-related gastroduodenal damage, Although several PPI-related adverse effects have been reported, their clinical relevance is not yet clear, since the evidence reported in those studies is not at a high enough level, as the majority are based on retrospective observational studies and the reported hazard ratios are low. It is important to administer PPIs only for patients who will gain a substantial clinical benefit.

In a March 2019 study: Proton pump inhibitors (PPIs) are used worldwide for the treatment of gastroesophageal reflux disease (GERD) and peptic ulcer disease (PUD). Although considered to be widely safe, PPIs have been associated with the potential risk of adverse effects such as infections including pneumonia and Clostridium difficile, malabsorption of vitamins and minerals, dementia and more recently with chronic kidney disease (CKD). Evidence including large cohort studies suggests that there is a greater risk of developing CKD in chronic users of PPIs. However, the association of CKD with PPI use reported in these studies is weak and does not establish a clear causality. This review aims to further investigate the association of CKD with PPI use by including studies with various study designs.
A literature search of published articles with no start date restrictions was undertaken in May 2018 in three electronic databases (PubMed, ScienceDirect, Google Scholar). Search terms included ‘Proton Pump Inhibitors’, ‘chronic kidney disease’, and ‘association’. Both observational and randomized controlled trials (RCTs) investigating the association of CKD with PPI use were eligible for inclusion.
Ten observational studies with 1,005,899 patients contributed to the review. No experimental study was available for inclusion in the review. Of the included studies, six used a retrospective study design, while the rest were prospective (two) or a case-controlled studies (two). A large prospective cohort study with 144,032 patients conducted in the USA reported that PPI use compared to no PPI use was associated with an increased risk of CKD Hazard ratio [HR] 1.28; 95% Confidence Interval [CI] 1.22–1.34. However, the observational study design of this study together with other studies included in the review suggests that the strength of evidence associating PPI use with CKD is weak and does not establish true causality.
The current evidence related to the potential association of CKD with PPI use remains inconclusive in establishing true causality. Further prospective studies including randomized controlled trials and cohort studies would be required to confirm the findings reported in this review and to draw any conclusions.

The list can go on but I think it’s important to understand why these studies don’t validate any dangers associated with long term PPI use. That comes with understanding the difference between prospective and retrospective studies.

Retrospective Study

Retrospective Study: Is a study that is not designed to show that one thing caused another thing (causation) HOW PPI USE STUDIES WERE CONDUCTED!
1. What is a Retrospective Study?
A retrospective study is a backwards looking evaluation (they look at already existing information). The review of this type of information cannot establish causality.  This is because the subjects of the study have already been treated and there is low-level control of other variables that may make a difference in the outcome being evaluated.
2. Advantages and Disadvantages
    •    Useful for rare diseases or unusual exposures. (Provides some initial information for other studies)
    •    Smaller sample sizes.
    •    Studies take less time, because the data is readily available (it just has to be collected and analyzed).
    •    Costs are generally lower.
    •    Missing data: Exposure status may not be clear, because important data may not have been collected in the first place. For example, if the study is investigating occupational lung cancer rates, information about worker’s smoking habits may not be available.
    •    Recall bias: Participants may not be able to remember if they were exposed or not.
    •    Confounding variables are difficult or impossible to measure.
    •    Retrospective studies are considered to be inferior to prospective studies, so prospective studies should always be used if there is a choice.
    •    As this is a relatively weak type of study, you cannot make causal statements, although correlations are okay (correlation finds that 2 things happen over a specific time, but not that one caused the other). For instance: You got up in the morning and brushed your teeth. But getting up did not cause you to brush your teeth. They are 2 independent actions. Therefore, getting the study read and/or published may be difficult.


Prospective Study Information

What is a prospective study?
A prospective study is a study that looks forward from a time point. There are a number of different types of prospective studies. Some do not attempt to control the treatment of a disease or condition, but rather just follow along whatever happens to the subjects of the study. The opposite is a retrospective study, were the researchers evaluate already existing information (as mentioned above).

Study participants typically have to meet certain criteria to be involved in the study. For example, they may have to be of a certain age, profession, or race. Once the participants are enrolled, they are followed for a period of time to see who gets the outcome in question (and who doesn’t). Usually, the research is conducted with a goal in mind and participants are periodically checked for progress, using the same questions for each person in the study. Follow ups might include:
    •    Email questionnaires
    •    Phone, internet, or in-person interviews,
    •    Physical exams,
    •    Imaging or laboratory tests.
Participants are followed for years and data is collected on the factors of interest, which might include:
    •    When the subject develops the condition,
    •    When they drop out of the study or become “lost,”
    •    When their exposure status changes,
    •    When they die.
Advantages and Disadvantages
    1.    Disease outcomes and prevalence are easy to calculate.
    2.    Multiple disease and conditions can be studied at the same time.
    3.    Researchers don’t have to deal with ethical issues like who receives which treatment (or none at all).
    1.    All cohort studies can be expensive and time consuming.
    2.    Confounding variables can be a larger problem with this type of study.
    3.    Sample sizes are typically very large.
    4.    Selection bias may be an issue.