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Effectiveness of management strategies for uninvestigated dyspepsia: systematic review and network meta-analysis

BMJ 2019; 367 doi: https://doi.org/10.1136/bmj.l6483 (Published 11 December 2019) Cite this as: BMJ 2019;367:l6483

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Long term proton pump inhibitor use: An insight in to its complications

Dear Editor,

Since their introduction, prescriptions for proton pump inhibitors (PPIs) have doubled in the United Kingdom and United States. (1,2) More particularly omeprazole makes up for about four fifths of all prescriptions. (1) It is approximated that 90% of the NHS drug budget goes towards treating dyspepsia. (1) However, this can be corrected if medications are limited to advised recommendations. (1) A study conducted revealed that 67% of inpatients in the UK did not meet recommended criteria for receiving PPIs. (1) Studies published in recent years have reported adverse events associated with the use of PPIs alone. A review of the literature revealed the following adverse outcomes:

1. Meta-Analysis of 9 observational studies revealed that 43% of the 109,798 patients were at increased risk of hypomagnesemia. (2)

2. PPIs tend to predispose the patient to small intestinal bacterial overgrowth (SIBO) by decreasing gastric acid production. Meta-Analysis of 11 studies revealed an increased risk of developing SIBO in PPI users when compared with non users (OR, 2.28; 95% CI, 1.24-4.21). (2)

3. Patients receiving PPIs for more than 2 years were at a 65% increased risk of vitamin B12 deficiency. (2) It was also noted that the use of 1.5 pills or more per day was also associated with increased risk of vitamin B12 deficiency (odds ratio [OR], 1.95; 95% CI, 1.77-2.15). (2) This is due to the fact that decreased gastric acid does not facilitate absorption of vitamin B12 in the terminal ileum.

4. PPIs predispose to Clostridium difficile induced colitis. A meta-analysis of 42 observational studies revealed an increased risk of both incident and recurring cases (OR, 1.74; 95% CI, 1.47-2.85 and OR, 2.51; 95% CI, 1.16-5.44, respectively). (1,2) It is also important to note that the H2 receptor antagonists may also cause Clostridium difficile induced colitis, but the risk is relatively lower than with the use of PPIs.

5. Increased risk of dementia because PPIs increase amyloid synthesis and decrease its degradation in the brain. (2) A prospective cohort study of 73,679 individuals by Gomm et al revealed a 44% risk of dementia with the use of PPIs.

6. Multiple studies have also shown increased risk of fractures with the use of PPIs. The highest risk is associated with spine fracture 58% (RR, 1.58; 95% CI, 1.38-1.82). (2) Fracture risk were also reported with any site (33% (RR, 1.33; 95% CI, 1.15-1.54)) and the hip (26% (RR, 1.26; 95% CI, 1.16-1.36)). (2)

7. Greater risk of acquiring both Acute kidney injury (64%) and Chronic kidney disease (50%). (2) Furthermore, a population based study of patients older than 65 years of age found a 2.5-times increase in the risk of developing AKI and three times the risk for acute interstitial nephritis. (2)

8. Several studies have also shown a 27% increased risk of developing community accquired pneumonia with the use of PPIs. (2)

REFERENCES:
1. Forgacs I, Loganayagam A. Overprescribing proton pump inhibitors. BMJ (Clinical Research ed.). 2008 Jan;336(7634):2-3.

2. Nehra AK, Alexander JA, Loftus CG, Nehra V. Proton Pump Inhibitors: Review of Emerging Concerns. Mayo Clinic Proceedings. 2018 Feb;93(2):240-246

Competing interests: No competing interests

19 December 2019
Syed Adeel Hassan
Doctor in Internal Medicine
Ali Akhtar
Dow University of Health Sciences
Ojha Campus , Karachi , Pakistan