drug adverse effects of proton pump inhibitors (PPI)
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Adverse effects
- most common
- headache, diarrhea, abdominal pain, constipation
- switching to another PPI is generally sufficient to reduce or eliminate the adverse effect(s)[21]
- increased risk of C difficile colitis[1][10][18][20][38] RR=1.7
- increased risk of community-acquired pneumonia (0.05%)[2]
- especially recent initiation of use[4]
- risk* may be greater for
- elderly
- COPD
- asthma
- immunocompromised
- not associated with increased risk of community-acquired pneumonia[35]
- increased risk of nosocomial pneumonia (HR=2.5)[7][8][16]
- increased risk of nosocomial pneumonia in stroke patients[26]
- increased risk of serious infection, including severe or fatal COVID-19 (RR=1.46)[56], hepatic encephalopathy & bacterial peritonitis in cirrhotic patients with ascites[6][34]
- H2 receptor antagonists apparently safe[6]
- increased risk for multidrug-resistant organisms[55]
- increased risk of fracture:[3][12][19][22]
- fracture risk increased at higher PPI doses & for duration of therapy > 1 year[21]
- association with risk of hip fracture is inconsistent[21]
- not associated with increased risk of hip fracture[49]
- wrist fracture, vertebral fracture[3][22]
- not associated with changes in bone mineral density[36]
- no increase in risk of colorectal cancer[5]
- rebound gastric hyperacidity may occur in patients when proton pump inhibitor is stopped after 1-2 months of use; best managed with antacids[9][14]
- risk of birth defects
- within 1st 4 weeks prior to conception (HR 1.39); risk lowest for omeprazole
- not associated with when taken by pregnant women during 1st trimester[15]
- hypomagnesemia[17][21]
- acute interstitial nephritis[21][25][30] (hypersensitivity)
- increased risk for chronic renal failure (14.2 vs 10.7 per 1000 person-years, RR=1.3)[28]
- number needed to harm: 286 for 1 year to cause 1 case of chronic renal failure
- RR=1.3 for 2-fold increase in serum creatinine or 30% decrease in eGFR[40]
- 0.5% excess absolute risk for >50% reduction in GFR within 5 years[42]
- 2-fold increase in cardiovascular mortality with PPI use
- increased risk in MI (RR=1.16)[27]
- no increased risk in MI[46]
- H2-blockers not associated with increased risk
- increased risk of stroke within 180 days of initiation of PPI therapy (RR=1.28, RR=1.77 within 30 days)[39]
- not associated with increased risk of stroke[47]
- increase risk of all-cause mortality relative to use of H2-blockers or no acid suppression (RR=1.25)[41]
- excess mortality from CV disease & chronic kidney disease[52]
- increased risk of dementia in the elderly (RR=1.44)[29]
- increased risk for dementia (RR=1.85)[60]
- no increased risk for Alzheimer's disease[43]
- PPI use associated with diminished risk of cognitive impairment[44]
- no increased risk of dementia[48][54]
- increased risk of fundic gland polyps (RR=2.46)[33]
- increased risk of gastric cancer
- 2-fold independent of prior H pylori infection[45]
- RR=1.45, number needed to harm 2100 in 5 years[57]
- increased risk of iron-deficiency anemia (RR=2.5)[37]
- increased risk of vitamin B12 deficiency[21]
- long-term use of PPIs is associated with increased risk of type 2 diabetes[59]
- long-term use of PPIs is associated with increased risk of NAFLD non-alcoholic fatty liver disease (RR=2.0 for use > 5 years)[58]
- use during the 1st 6 months of life associated with increased risk for food allergy during childhood (RR=2.6)[50] 23] increased risk for allergy
* Low pH of stomach acid is antimicrobial. In the absence of acid, refluxed & aspirated gastric contents may contain pathogen that causes pneumonia.
* pharmacy guidelines require reassessment of need after 8 weeks of therapy
More general terms
References
- ↑ 1.0 1.1 Prescriber's Letter 11(8): 2004 Proton Pump Inhibitors Associated with Increased Risk of Clostridium difficile Diarrhea Detail-Document#: http://prescribersletter.com/(5bhgn1a4ni4cyp2tvybwfh55)/pl/ArticleDD.aspx?li=1&st=1&cs=&s=PRL&pt=3&fpt=25&dd=200804&pb=PRL (subscription needed) http://www.prescribersletter.com
Dial S et al, Use of gastric acid-suppressive agents and the risk of commumity-acquired Clostridium difficile-associated disease. JAMA 2005; 294:2989 PMID: https://www.ncbi.nlm.nih.gov/pubmed/16414946 - ↑ 2.0 2.1 Prescriber's Letter 11(12): 2004 Community-Acquired Pneumonia Risk with Acid-Suppressive Drugs Detail-Document#: http://prescribersletter.com/(5bhgn1a4ni4cyp2tvybwfh55)/pl/ArticleDD.aspx?li=1&st=1&cs=&s=PRL&pt=3&fpt=25&dd=201207&pb=PRL (subscription needed) http://www.prescribersletter.com
Laheij RJ, Sturkenboom MC, Hassing RJ, Dieleman J, Stricker BH, Jansen JB. Risk of community-acquired pneumonia and use of gastric acid- suppressive drugs. JAMA. 2004 Oct 27;292(16):1955-60. PMID: https://www.ncbi.nlm.nih.gov/pubmed/15507580 - ↑ 3.0 3.1 3.2 Yang YX, Lewis JD, Epstein S, Metz DC. Long-term proton pump inhibitor therapy and risk of hip fracture. JAMA. 2006 Dec 27;296(24):2947-53. PMID: https://www.ncbi.nlm.nih.gov/pubmed/17190895
Prescriber's Letter 14(2): 2007 Proton pump inhibitors and risk of hip fracture Detail-Document#: http://prescribersletter.com/(5bhgn1a4ni4cyp2tvybwfh55)/pl/ArticleDD.aspx?li=1&st=1&cs=&s=PRL&pt=3&fpt=25&dd=230202&pb=PRL (subscription needed) http://www.prescribersletter.com
FDA MedWatch: Proton Pump Inhibitors (PPI): Class Labeling Change Drug Safety Communication Possible Increased Risk of Bone Fractures With Certain Antacid Drugs - FDA http://www.fda.gov/Safety/MedWatch/SafetyInformation/SafetyAlertsforHumanMedicalProducts/ucm213321.htm - ↑ 4.0 4.1 Gulmez SE et al, Use of proton pump inhibitors and the risk of community- acquired pneumonia: A population-based case-control study. Arch Intern Med 2007, 167:950 PMID: https://www.ncbi.nlm.nih.gov/pubmed/17502537
- ↑ 5.0 5.1 Yang Y-X et al, Chronic proton pump inhibitor therapy and the risk of colorectal cancer. Gastroenterology 2007, 133:748 PMID: https://www.ncbi.nlm.nih.gov/pubmed/17698926
Robertson DJ et al, Proton Pum inhibitor use and risk of colorectal cancer: A polulation-based, case-control study. Gastroenterology 2007, 133:755 PMID: https://www.ncbi.nlm.nih.gov/pubmed/17698921 - ↑ 6.0 6.1 6.2 Bajaj JS et al Association of proton pump inhibitor therapy with spontaneous bacterial peritonitis in cirrhotic patients with ascites. Am J Gastroenterol 2009 May; 104:1130. PMID: https://www.ncbi.nlm.nih.gov/pubmed/19337238
Bajaj JS et al. Proton pump inhibitors are associated with a high rate of serious infections in veterans with decompensated cirrhosis. Aliment Pharmacol Ther 2012 Sep 11 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/22966967 <Internet> http://onlinelibrary.wiley.com/doi/10.1111/apt.12045/abstract;jsessionid=63AAEC22827345E993522335B4680B03.d02t03 - ↑ 7.0 7.1 Herzig SJ et al, Acid-Suppressive Medication Use and the Risk for Hospital- Acquired Pneumonia JAMA. 2009;301(20):2120-2128 PMID: https://www.ncbi.nlm.nih.gov/pubmed/19470989
- ↑ 8.0 8.1 Prescriber's Letter 16(7): 2009 Overuse of Acid Suppressing Drugs in the Hospital Detail-Document#: http://prescribersletter.com/(5bhgn1a4ni4cyp2tvybwfh55)/pl/ArticleDD.aspx?li=1&st=1&cs=&s=PRL&pt=3&fpt=25&dd=250720&pb=PRL (subscription needed) http://www.prescribersletter.com
- ↑ 9.0 9.1 Reimer C et al. Proton-pump inhibitor therapy induces acid-related symptoms in healthy volunteers after withdrawal of therapy. Gastroenterology 2009 Jul; 137:80. PMID: https://www.ncbi.nlm.nih.gov/pubmed/19362552
McColl KEL and Gillen D. Evidence that proton-pump inhibitor therapy induces the symptoms it is used to treat. Gastroenterology 2009 Jul; 137:20. PMID: https://www.ncbi.nlm.nih.gov/pubmed/19482105
Prescriber's Letter 16(9): 2009 Proton Pump Inhibitors and Rebound Acid Hypersecretion Detail-Document#: http://prescribersletter.com/(5bhgn1a4ni4cyp2tvybwfh55)/pl/ArticleDD.aspx?li=1&st=1&cs=&s=PRL&pt=3&fpt=25&dd=250920&pb=PRL (subscription needed) http://www.prescribersletter.com - ↑ 10.0 10.1 Howell MD et al Iatrogenic Gastric Acid Suppression and the Risk of Nosocomial Clostridium difficile Infection Arch Intern Med. 2010;170(9):784-790. <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/20458086 <Internet> http://archinte.ama-assn.org/cgi/content/abstract/170/9/784
Yachimski PS et al Proton Pump Inhibitors for Prophylaxis of Nosocomial Upper Gastrointestinal Tract Bleeding Arch Intern Med. 2010;170(9):779-783. <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/20458085 <Internet> http://archinte.ama-assn.org/cgi/content/short/170/9/779
Katz MH Failing the Acid Test: Benefits of Proton Pump Inhibitors May Not Justify the Risks for Many Users Arch Intern Med. 2010;170(9):747-748. <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/20458079 <Internet> http://archinte.ama-assn.org/cgi/content/short/170/9/747 - ↑ Wang CH et al. High-dose vs non-high-dose proton pump inhibitors after endoscopic treatment in patients with bleeding peptic ulcer: A systematic review and meta-analysis of randomized controlled trials. Arch Intern Med 2010 May 10; 170:751 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/20458081 <Internet> http://dx.doi.org/10.1001/archinternmed.2010.100
- ↑ 12.0 12.1 Gray SL et al. Proton pump inhibitor use, hip fracture, and change in bone mineral density in postmenopausal women: Results from the Women's Health Initiative. Arch Intern Med 2010 May 10; 170:765. <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/20458083 <Internet> http://dx.doi.org/10.1001/archinternmed.2010.94
Corley DA, Kubo A, Zhao W, Quesenberry C. Proton pump inhibitors and histamine-2 receptor antagonists are associated with hip fractures among at-risk patients. Gastroenterology 2010; 139(1):93-101. Epub 2010 Mar 27. PMID: https://www.ncbi.nlm.nih.gov/pubmed/20353792 - ↑ Linsky A et al. Proton pump inhibitors and risk for recurrent Clostridium difficile infection. Arch Intern Med 2010 May 10; 170:772. <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/20458084 <Internet> http://dx.doi.org/10.1001/archinternmed.2010.73
- ↑ 14.0 14.1 Niklasson A et al. Dyspeptic symptom development after discontinuation of a proton pump inhibitor: A double-blind placebo-controlled trial. Am J Gastroenterol 2010 Jul; 105:1531. PMID: https://www.ncbi.nlm.nih.gov/pubmed/20332770
- ↑ 15.0 15.1 Pasternak B et al Use of Proton-Pump Inhibitors in Early Pregnancy and the Risk of Birth Defects N Engl J Med 2010; 363:2114-2123November 25, 2010 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/21105793 <Internet> http://www.nejm.org/doi/full/10.1056/NEJMoa1002689
Mitchell AA Proton-Pump Inhibitors and Birth Defects - Some Reassurance, but More Needed N Engl J Med 2010; 363:2161-2163November 25, 2010 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/21105800 <Internet> http://www.nejm.org/doi/full/10.1056/NEJMe1009631 - ↑ 16.0 16.1 Eom C-S et al. Use of acid-suppressive drugs and risk of pneumonia: Systematic review and meta-analysis. CMAJ 2010 Dec 20 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/21173070 <Internet> http://www.cmaj.ca/cgi/content/abstract/cmaj.092129v1
- ↑ 17.0 17.1 FDA MedWatch, Feb 3, 2011 Proton Pump Inhibitor drugs (PPIs): Drug Safety Communication
Low Magnesium Levels Can Be Associated With Long-Term Use http://www.fda.gov/Safety/MedWatch/SafetyInformation/SafetyAlertsforHumanMedicalProducts/ucm245275.htm
Prescriber's Letter 18(11): 2011 Comparison of Oral Magnesium Salts Detail-Document#: http://prescribersletter.com/(5bhgn1a4ni4cyp2tvybwfh55)/pl/ArticleDD.aspx?li=1&st=1&cs=&s=PRL&pt=3&fpt=25&dd=271111&pb=PRL (subscription needed) http://www.prescribersletter.com - ↑ 18.0 18.1 FDA MedWatch: 02/08/2012 Proton Pump Inhibitors (PPIs) - Drug Safety Communication: Clostridum Difficile-Associated Diarrhea (CDAD) Can be Associated With Stomach Acid Drugs http://www.fda.gov/Safety/MedWatch/SafetyInformation/SafetyAlertsforHumanMedicalProducts/ucm290838.htm
- ↑ 19.0 19.1 Khalili H et al. Use of proton pump inhibitors and risk of hip fracture in relation to dietary and lifestyle factors: A prospective cohort study. BMJ 2012 Jan 31; 344:e372. PMID: https://www.ncbi.nlm.nih.gov/pubmed/22294756
- ↑ 20.0 20.1 Janarthanan S et al. Clostridium difficile-associated diarrhea and proton pump inhibitor therapy: A meta-analysis. Am J Gastroenterol 2012 Jul; 107:1001. PMID: https://www.ncbi.nlm.nih.gov/pubmed/22710578
Kwok CS et al. Risk of Clostridium difficile infection with acid suppressing drugs and antibiotics: Meta-analysis. Am J Gastroenterol 2012 Jul; 107:1011 PMID: https://www.ncbi.nlm.nih.gov/pubmed/22525304 - ↑ 21.0 21.1 21.2 21.3 21.4 21.5 21.6 Medical Knowledge Self Assessment Program (MKSAP) 16, 17, 18. American College of Physicians, Philadelphia 2012, 2015, 2018.
- ↑ 22.0 22.1 22.2 Geriatric Review Syllabus, 8th edition (GRS8) Durso SC and Sullivan GN (eds) American Geriatrics Society, 2013
- ↑ Eom CS, Park SM, Myung SK, Yun JM, Ahn JS. Use of acid-suppressive drugs and risk of fracture: a meta-analysis of observational studies. Ann Fam Med. 2011 May-Jun;9(3):257-67. doi:http://dx.doi.org/ 10.1370/afm.1243. PMID: https://www.ncbi.nlm.nih.gov/pubmed/21555754
- ↑ Heidelbaugh JJ. PPI therapy: when to worry about fracture risk. J Fam Pract. 2011 May;60(5):255-60. PMID: https://www.ncbi.nlm.nih.gov/pubmed/21544271
- ↑ 25.0 25.1 Blank ML et al A nationwide nested case-control study indicates an increased risk of acute interstitial nephritis with proton pump inhibitor use. Kidney Int 2014 Oct; 86:837 PMID: https://www.ncbi.nlm.nih.gov/pubmed/24646856
Muriithi AK et al. Biopsy-proven acute interstitial nephritis, 1993 - 2011: A case series. Am J Kidney Dis 2014 Oct; 64:558 PMID: https://www.ncbi.nlm.nih.gov/pubmed/24927897 - ↑ 26.0 26.1 Herzig SJ et al. Acid-suppressive medication use in acute stroke and hospital- acquired pneumonia. Ann Neurol 2014 Nov; 76:712 PMID: https://www.ncbi.nlm.nih.gov/pubmed/25164323
- ↑ 27.0 27.1 Shah NH, LePendu P, Bauer-Mehren A et al Proton Pump Inhibitor Usage and the Risk of Myocardial Infarction in the General Population. PLOS One. Published: June 10, 2015 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/26061035 <Internet> http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0124653
- ↑ 28.0 28.1 Lazarus B, Chen Y, Wilson FP et al Proton Pump Inhibitor Use and the Risk of Chronic Kidney Disease. JAMA Intern Med. Published online January 11, 2016 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/26752337 <Internet> http://archinte.jamanetwork.com/article.aspx?articleid=2481157
Schoenfeld AJ, Grady D Adverse Effects Associated With Proton Pump Inhibitors. JAMA Intern Med. Published online January 11, 2016 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/26751904 <Internet> http://archinte.jamanetwork.com/article.aspx?articleid=2481153 - ↑ 29.0 29.1 Gomm W, von Holt K, Thome F et al Association of Proton Pump Inhibitors With Risk of Dementia. A Pharmacoepidemiological Claims Data Analysis. JAMA Neurol. Published online February 15, 2016 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/26882076 <Internet> http://archneur.jamanetwork.com/article.aspx?articleid=2487379
Kuller LH Do Proton Pump Inhibitors Increase the Risk of Dementia? JAMA Neurol. Published online February 15, 2016 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/26882528 <Internet> http://archneur.jamanetwork.com/article.aspx?articleid=2487375 - ↑ 30.0 30.1 Chang YS. Hypersensitivity reactions to proton pump inhibitors. Curr Opin Allergy Clin Immunol. 2012 Aug;12(4):348-53. Review. PMID: https://www.ncbi.nlm.nih.gov/pubmed/22744268
- ↑ Abrahamsen B, Vestergaard P. Proton pump inhibitor use and fracture risk - effect modification by histamine H1 receptor blockade. Observational case-control study using National Prescription Data. Bone. 2013 Nov;57(1):269-71. PMID: https://www.ncbi.nlm.nih.gov/pubmed/23973557
- ↑ Ngamruengphong S, Leontiadis GI, Radhi S et al Proton pump inhibitors and risk of fracture: a systematic review and meta-analysis of observational studies. Am J Gastroenterol. 2011 Jul;106(7):1209-18; quiz 1219. Review. PMID: https://www.ncbi.nlm.nih.gov/pubmed/21483462
- ↑ 33.0 33.1 Martin FC et al. Systematic review with meta-analysis: Fundic gland polyps and proton pump inhibitors. Aliment Pharmacol Ther 2016 Sep 15 PMID: https://www.ncbi.nlm.nih.gov/pubmed/27634363
- ↑ 34.0 34.1 Dam G, Vilstrup H, Watson H, Jepsen P. Proton pump inhibitors as a risk factor for hepatic encephalopathy and spontaneous bacterial peritonitis in patients with cirrhosis with ascites. Hepatology. 2016 Oct;64(4):1265-72. PMID: https://www.ncbi.nlm.nih.gov/pubmed/27474889
- ↑ 35.0 35.1 Othman F, Crooks CJ, Card TR Community acquired pneumonia incidence before and after proton pump inhibitor prescription: population based study. BMJ 2016;355:i5813 Not indexed in PubMed http://www.bmj.com/content/355/bmj.i5813
Filion KB, Chateau D, Targownik LE et al, CNODES Investigators.. Proton pump inhibitors and the risk of hospitalisation for community-acquired pneumonia: replicated cohort studies with meta-analysis. Gut. 2014 Apr;63(4):552-8. PMID: https://www.ncbi.nlm.nih.gov/pubmed/23856153 Free PMC Article - ↑ 36.0 36.1 Targownik LE et al. Long-term proton pump inhibitor use is not associated with changes in bone strength and structure. Am J Gastroenterol 2016 Nov 15 PMID: https://www.ncbi.nlm.nih.gov/pubmed/27845341
- ↑ 37.0 37.1 Lam JR et al. Proton pump inhibitor and histamine-2 receptor antagonist use and iron deficiency. Gastroenterology 2016 Nov 24 PMID: https://www.ncbi.nlm.nih.gov/pubmed/27890768
- ↑ 38.0 38.1 Tariq R, Singh S, Gupta A, Pardi DS, Khanna S. Association of gastric acid suppression with recurrent Clostridium difficile infection: A systematic review and meta-analysis. JAMA Intern Med 2017 Mar 27 PMID: https://www.ncbi.nlm.nih.gov/pubmed/28346595
- ↑ 39.0 39.1 Wang YF, Chen YT, Luo JC, Chen TJ, Wu JC, Wang SJ. Proton-pump inhibitor use and the risk of first-time ischemic stroke in the general population: A nationwide population- based study. Am J Gastroenterol 2017 Apr 11; PMID: https://www.ncbi.nlm.nih.gov/pubmed/28397874
- ↑ 40.0 40.1 Klatte DCF, Gasparini A, Xu H et al. Association between proton pump inhibitor use and risk of progression of chronic kidney disease. Gastroenterology 2017 Jun 2 PMID: https://www.ncbi.nlm.nih.gov/pubmed/28583827
- ↑ 41.0 41.1 Xie Y, Bowe B, Li T et al Risk of death among users of Proton Pump Inhibitors: a longitudinal observational cohort study of United States veterans. BMJ Open. 2017 Jul 4;7(6):e015735. <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/28676480 Free Article <Internet> http://bmjopen.bmj.com/content/7/6/e015735
- ↑ 42.0 42.1 Xie Y, Bowe B, Li T, Xian H, Yan Y, Al-Aly Z. Long-term kidney outcomes among users of proton pump inhibitors without intervening acute kidney injury. Kidney Int 2017 Jun; 91:1482. PMID: https://www.ncbi.nlm.nih.gov/pubmed/28237709 Free Article
- ↑ 43.0 43.1 Taipale H, Tolppanen AM, Tiihonen M et al. No association between proton pump inhibitor use and risk of Alzheimer's disease. Am J Gastroenterol 2017 Jul 11 PMID: https://www.ncbi.nlm.nih.gov/pubmed/28695906
Lochhead P, Hagan K, Joshi AD et al. Association between proton pump inhibitor use and cognitive function in women. Gastroenterology 2017 Jul 17; PMID: https://www.ncbi.nlm.nih.gov/pubmed/28728964 - ↑ 44.0 44.1 Goldstein FC, Steenland K, Zhao L et al Proton pump inhibitors and risk of mild cognitive impairment and dementia. J Am Geriatr Soc 2017 Sep; 65:1969-1974 PMID: https://www.ncbi.nlm.nih.gov/pubmed/28590010
- ↑ 45.0 45.1 Brooks M Gastric Cancer Risk Doubled With Long-term PPI Use. Medscape - Oct 31, 2017. https://www.medscape.com/viewarticle/887863
Cheung KS, Chan EW, Wong AYS et al Long-term proton pump inhibitors and risk of gastric cancer development after treatment for Helicobacter pylori: a population-based study. Gut. Nov 2017 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/29089382 <Internet> http://gut.bmj.com/content/early/2017/09/18/gutjnl-2017-314605 - ↑ 46.0 46.1 Landi SN, Sandler RS, Pate V, Lund JL. No increase in risk of acute myocardial infarction in privately insured adults prescribed proton pump inhibitors vs histamine-2 receptor antagonists (2002-2014). Gastroenterology 2017 Nov 6; <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/29122546 <Internet> http://www.gastrojournal.org/article/S0016-5085(17)36330-8/pdf
- ↑ 47.0 47.1 Nguyen LH, Lochhead P, Joshi AD et al. No significant association between proton pump inhibitor use and risk of stroke after adjustment for lifestyle factors and indication. Gastroenterology 2017 Dec 18 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/29269313 <Internet> http://www.gastrojournal.org/article/S0016-5085(17)36710-0/pdf
- ↑ 48.0 48.1 Gray SL, Walker RL, Dublin S et al. Proton pump inhibitor use and dementia risk: Prospective population-based study. J Am Geriatr Soc 2018 Feb; 66:247. PMID: https://www.ncbi.nlm.nih.gov/pubmed/29134629
- ↑ 49.0 49.1 Torvinen-Kiiskinen S, Tolppanen AM, Koponen M et al. Proton pump inhibitor use and risk of hip fractures among community-dwelling persons with Alzheimer's disease - A nested case-control study. Aliment Pharmacol Ther 2018 Apr; 47:1135; PMID: https://www.ncbi.nlm.nih.gov/pubmed/29508411
- ↑ 50.0 50.1 Mitre E, Susi A, Kropp LE, et al Association Between Use of Acid-Suppressive Medications and Antibiotics During Infancy and Allergic Diseases in Early Childhood. JAMA Pediatr. Published online April 2, 2018 PMID: https://www.ncbi.nlm.nih.gov/pubmed/29610864 https://jamanetwork.com/journals/jamapediatrics/fullarticle/2676167
- ↑ Moledina DG, Perazella MA. PPIs and kidney disease: from AIN to CKD. J Nephrol. 2016 Oct;29(5):611-6. Review. PMID: https://www.ncbi.nlm.nih.gov/pubmed/27072818
- ↑ 52.0 52.1 Xie Y, Bowe B, Yan Y Estimates of all cause mortality and cause specific mortality associated with proton pump inhibitors among US veterans: cohort study. BMJ 2019;365:l1580 PMID: https://www.ncbi.nlm.nih.gov/pubmed/31147311 https://www.bmj.com/content/365/bmj.l1580
- ↑ Jordakieva G, Kundi M, Untersmayr E et al Country-wide medical records infer increased allergy risk of gastric acid inhibition. Nature Communications. volume 10, Article number: 3298 (2019) PMID: https://www.ncbi.nlm.nih.gov/pubmed/31363098 Free PMC Article https://www.nature.com/articles/s41467-019-10914-6
- ↑ 54.0 54.1 Khan MA, Yuan Y, Iqbal U, et al. No association linking short-term proton pump inhibitor use to dementia: Systematic review and meta-analysis of observational studies. Am J Gastroenterol 2020 Jan 2. PMID: https://www.ncbi.nlm.nih.gov/pubmed/31895707 https://journals.lww.com/ajg/Abstract/publishahead/No_Association_Linking_Short_Term_Proton_Pump.99461.aspx
- ↑ 55.0 55.1 Willems RPJ, van Dijk K, Ket JCF et al. Evaluation of the association between gastric acid suppression and risk of intestinal colonization with multidrug-resistant microorganisms: A systematic review and meta-analysis. JAMA Intern Med 2020 Feb 24; PMID 32091544 https://jamanetwork.com/journals/jamainternalmedicine/fullarticle/2761273
Lee TC, McDonald EG. Deprescribing proton pump inhibitors: Overcoming resistance. JAMA Intern Med 2020 Feb 24; PMID: https://www.ncbi.nlm.nih.gov/pubmed/32091554 https://jamanetwork.com/journals/jamainternalmedicine/fullarticle/2761268 - ↑ 56.0 56.1 Brooks M PPI Use Tied to Increased Risk of Severe or Fatal COVID-19 Outcome in Meta-Analysis. Medscape - Nov 04, 2020. https://www.medscape.com/viewarticle/940390
- ↑ 57.0 57.1 Abrahami D et al. Proton pump inhibitors and risk of gastric cancer: Population-based cohort study. Gut 2022 Jan; 71:16. PMID: https://www.ncbi.nlm.nih.gov/pubmed/34226290 https://gut.bmj.com/content/71/1/16
- ↑ 58.0 58.1 Huang H et al Long-term Use of Proton Pump Inhibitors is Associated With An Increased Risk of Nonalcoholic Fatty Liver Disease. J Clin Gastroenterol. 2023. March 31 Not indexed in PubMed https://journals.lww.com/jcge/Abstract/9900/Long_term_Use_of_Proton_Pump_Inhibitors_is.144.aspx
- ↑ 59.0 59.1 Loosen SH et al. Long-term use of proton pump inhibitors (PPIs) is associated with an increased risk of type 2 diabetes. Gut. 2022. Aug;71(8):1687-1688 PMID: https://www.ncbi.nlm.nih.gov/pubmed/34725199
- ↑ 60.0 60.1 Ahn N, Wawro N, Baumeister SE et al Time-Varying Use of Proton Pump Inhibitors and Cognitive Impairment and Dementia: A Real-World Analysis from Germany. Drug & Aging. 2023. May 13 PMID: https://www.ncbi.nlm.nih.gov/pubmed/37178361 https://link.springer.com/article/10.1007/s40266-023-01031-7
- ↑ 61.0 61.1 George J Dementia Risk Linked With Cumulative Heartburn Med Use, Analysis Suggests. Study adds to the ongoing discussion about proton pump inhibitors and cognition. MedPage Today August 9, 2023 https://www.medpagetoday.com/neurology/dementia/105827
Northuis C, Bell E, Lutsey P et al Cumulative Use of Proton Pump Inhibitors and Risk of Dementia: The Atherosclerosis Risk in Communities Study. Neurology, 2023. August 9. PMID: https://www.ncbi.nlm.nih.gov/pubmed/37558503 https://n.neurology.org/content/early/2023/08/09/WNL.0000000000207747
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