{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,30]],"date-time":"2026-10-30T18:40:42Z","timestamp":1793385642734,"version":"4.5.0"},"reference-count":69,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2024,4,27]],"date-time":"2024-04-27T00:00:00Z","timestamp":1714176000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2024,4,27]],"date-time":"2024-04-27T00:00:00Z","timestamp":1714176000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Nat Commun"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Proton pump inhibitors (PPIs) are commonly used for gastric acid-related disorders, but their safety profile and risk stratification for high-burden diseases need further investigation. Analyzing over 2 million participants from five prospective cohorts from the US, the UK, and China, we found that PPI use correlated with increased risk of 15 leading global diseases, such as ischemic heart disease, diabetes, respiratory infections, and chronic kidney disease. These associations showed dose-response relationships and consistency across different PPI types. PPI-related absolute risks increased with baseline risks, with approximately 82% of cases occurring in those at the upper 40% of the baseline predicted risk, and only 11.5% of cases occurring in individuals at the lower 50% of the baseline risk. While statistical association does not necessarily imply causation, its potential safety concerns suggest that personalized use of PPIs through risk stratification might guide appropriate decision-making for patients, clinicians, and the public.<\/jats:p>","DOI":"10.1038\/s41467-024-48007-8","type":"journal-article","created":{"date-parts":[[2024,4,27]],"date-time":"2024-04-27T13:02:28Z","timestamp":1714222948000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":32,"title":["Individualized prevention of proton pump inhibitor related adverse events by risk stratification"],"prefix":"10.1038","volume":"15","author":[{"given":"Bin","family":"Xia","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qiangsheng","family":"He","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fang Gao","family":"Smith","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2061-091X","authenticated-orcid":false,"given":"V. Georgios","family":"Gkoutos","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6816-1279","authenticated-orcid":false,"given":"Krishnarajah","family":"Nirantharakumar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zi Chong","family":"Kuo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Danni","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qi","family":"Feng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eddie C.","family":"Cheung","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3003-8910","authenticated-orcid":false,"given":"Lunzhi","family":"Dai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2382-4443","authenticated-orcid":false,"given":"Junjie","family":"Huang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuanyuan","family":"Yu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9355-0225","authenticated-orcid":false,"given":"Wenbo","family":"Meng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6573-1953","authenticated-orcid":false,"given":"Xiwen","family":"Qin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7947-2646","authenticated-orcid":false,"given":"Jinqiu","family":"Yuan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2024,4,27]]},"reference":[{"key":"48007_CR1","unstructured":"Brown, T. & Smith, M. W. The 10 most-prescribed and top-selling medications. https:\/\/www.webmd.com\/drug-medication\/news\/20150508\/most-prescribed-top-selling-drugs (2022)."},{"key":"48007_CR2","doi-asserted-by":"publisher","first-page":"213","DOI":"10.1016\/S0140-6736(19)31236-X","volume":"394","author":"A Knuppel","year":"2019","unstructured":"Knuppel, A., Papier, K., Key, T. J. & Travis, R. C. EAT-Lancet score and major health outcomes: the EPIC-Oxford study. Lancet 394, 213\u2013214 (2019).","journal-title":"Lancet"},{"key":"48007_CR3","doi-asserted-by":"publisher","first-page":"129","DOI":"10.1111\/apt.16407","volume":"54","author":"EM Salvo","year":"2021","unstructured":"Salvo, E. M., Ferko, N. C., Cash, S. B., Gonzalez, A. & Kahrilas, P. J. Umbrella review of 42 systematic reviews with meta-analyses: the safety of proton pump inhibitors. Aliment Pharm. Ther. 54, 129\u2013143 (2021).","journal-title":"Aliment Pharm. Ther."},{"key":"48007_CR4","doi-asserted-by":"publisher","first-page":"2021","DOI":"10.1002\/hep.31914","volume":"74","author":"H Kamal","year":"2021","unstructured":"Kamal, H., Sadr-Azodi, O., Engstrand, L. & Brusselaers, N. Association between proton pump inhibitor use and biliary tract cancer risk: a Swedish population-based cohort study. Hepatology 74, 2021\u20132031 (2021).","journal-title":"Hepatology"},{"key":"48007_CR5","doi-asserted-by":"publisher","first-page":"2265","DOI":"10.1136\/gutjnl-2020-321052","volume":"69","author":"J Xiong","year":"2020","unstructured":"Xiong, J., Wang, Y., Chen, G. & Jin, L. Proton pump inhibitors and the risk of gallbladder cancer: a hospital-based case-control study. Gut 69, 2265\u20132267 (2020).","journal-title":"Gut"},{"key":"48007_CR6","doi-asserted-by":"publisher","first-page":"449","DOI":"10.1111\/apt.15834","volume":"52","author":"J Yuan","year":"2020","unstructured":"Yuan, J. et al. Regular use of proton pump inhibitor and risk of rheumatoid arthritis in women: a prospective cohort study. Aliment Pharm. Ther. 52, 449\u2013458 (2020).","journal-title":"Aliment Pharm. Ther."},{"key":"48007_CR7","doi-asserted-by":"publisher","first-page":"1842","DOI":"10.1053\/j.gastro.2021.08.005","volume":"161","author":"B Xia","year":"2021","unstructured":"Xia, B. et al. Regular use of proton pump inhibitor and the risk of inflammatory bowel disease: pooled analysis of 3 prospective cohorts. Gastroenterology 161, 1842\u20131852.e1810 (2021).","journal-title":"Gastroenterology"},{"key":"48007_CR8","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2021.813587","volume":"12","author":"M Yang","year":"2021","unstructured":"Yang, M. et al. Association between regular use of gastric acid suppressants and subsequent risk of cholelithiasis: a prospective cohort study of 0.47 million participants. Front. Pharm. 12, 813587 (2021).","journal-title":"Front. Pharm."},{"key":"48007_CR9","doi-asserted-by":"publisher","first-page":"e069211","DOI":"10.1136\/bmj-2021-069211","volume":"379","author":"B Farrell","year":"2022","unstructured":"Farrell, B., Lass, E., Moayyedi, P., Ward, D. & Thompson, W. Reduce unnecessary use of proton pump inhibitors. BMJ 379, e069211 (2022).","journal-title":"BMJ"},{"key":"48007_CR10","doi-asserted-by":"publisher","first-page":"1334","DOI":"10.1053\/j.gastro.2021.12.247","volume":"162","author":"LE Targownik","year":"2022","unstructured":"Targownik, L. E., Fisher, D. A. & Saini, S. D. AGA clinical practice update on de-prescribing of proton pump inhibitors: expert review. Gastroenterology 162, 1334\u20131342 (2022).","journal-title":"Gastroenterology"},{"key":"48007_CR11","doi-asserted-by":"publisher","first-page":"e2","DOI":"10.1161\/HYPERTENSIONAHA.116.08249","volume":"69","author":"KN Karmali","year":"2017","unstructured":"Karmali, K. N. & Lloyd-Jones, D. M. Global risk assessment to guide blood pressure management in cardiovascular disease prevention. Hypertension 69, e2\u2013e9 (2017).","journal-title":"Hypertension"},{"key":"48007_CR12","doi-asserted-by":"publisher","first-page":"2402","DOI":"10.1161\/CIRCULATIONAHA.119.040625","volume":"142","author":"V Bittner","year":"2020","unstructured":"Bittner, V. The new 2019 AHA\/ACC guideline on the primary prevention of cardiovascular disease. Circulation 142, 2402\u20132404 (2020).","journal-title":"Circulation"},{"key":"48007_CR13","doi-asserted-by":"publisher","DOI":"10.1186\/s12916-021-02180-5","volume":"19","author":"M Yang","year":"2021","unstructured":"Yang, M. et al. Regular use of proton-pump inhibitors and risk of stroke: a population-based cohort study and meta-analysis of randomized-controlled trials. BMC Med. 19, 316 (2021).","journal-title":"BMC Med."},{"key":"48007_CR14","doi-asserted-by":"publisher","first-page":"524","DOI":"10.1177\/10600280211039240","volume":"56","author":"X Xun","year":"2022","unstructured":"Xun, X., Yin, Q., Fu, Y., He, X. & Dong, Z. Proton pump inhibitors and the risk of community-acquired pneumonia: an updated meta-analysis. Ann. Pharmacother. 56, 524\u2013532 (2022).","journal-title":"Ann. Pharmacother."},{"key":"48007_CR15","doi-asserted-by":"publisher","first-page":"115","DOI":"10.1093\/qjmed\/hcy245","volume":"112","author":"K Lapumnuaypol","year":"2019","unstructured":"Lapumnuaypol, K., Thongprayoon, C., Wijarnpreecha, K., Tiu, A. & Cheungpasitporn, W. Risk of fall in patients taking proton pump inhibitors: a meta-analysis. QJM 112, 115\u2013121 (2019).","journal-title":"QJM"},{"key":"48007_CR16","doi-asserted-by":"publisher","first-page":"46","DOI":"10.1016\/j.cegh.2017.12.008","volume":"7","author":"S Hussaina","year":"2019","unstructured":"Hussaina, S., Singhb, A., Habibc, A. & Najmid, A. K. Proton pump inhibitors use and risk of chronic kidney disease: evidence-based meta-analysis of observational studies. Clin. Epidemiol. Glob. Health 7, 46\u201352 (2019).","journal-title":"Clin. Epidemiol. Glob. Health"},{"key":"48007_CR17","doi-asserted-by":"crossref","unstructured":"D\u2019Silva, K. M. et al. Proton pump inhibitor use and risk for recurrent Clostridioides difficile infection: a systematic review and meta-analysis. Clin. Microbiol. Infect. 27, 697\u2013703 (2021).","DOI":"10.1016\/j.cmi.2021.01.008"},{"key":"48007_CR18","doi-asserted-by":"publisher","first-page":"607","DOI":"10.3389\/fphar.2020.00607","volume":"11","author":"YT Wang","year":"2020","unstructured":"Wang, Y. T., Tsai, M. C., Wang, Y. H. & Wei, J. C. Association between proton pump inhibitors and asthma: a population-based cohort study. Front. Pharm. 11, 607 (2020).","journal-title":"Front. Pharm."},{"key":"48007_CR19","doi-asserted-by":"publisher","first-page":"824","DOI":"10.3390\/jpm12050824","volume":"12","author":"TK Lin","year":"2022","unstructured":"Lin, T. K., Tsai, C. F., Huang, J. Y., Pan, L. F. & Jong, G. P. Exposure to proton pump inhibitors and the risk of incident asthma in patients with coronary artery diseases: a population-based cohort study. J. Pers. Med. 12, 824 (2022).","journal-title":"J. Pers. Med."},{"key":"48007_CR20","doi-asserted-by":"publisher","first-page":"1551","DOI":"10.1111\/bcp.15103","volume":"88","author":"SK Veettil","year":"2022","unstructured":"Veettil, S. K. et al. Association of proton-pump inhibitor use with adverse health outcomes: a systematic umbrella review of meta-analyses of cohort studies and randomised controlled trials. Br. J. Clin. Pharm. 88, 1551\u20131566 (2022).","journal-title":"Br. J. Clin. Pharm."},{"key":"48007_CR21","doi-asserted-by":"crossref","first-page":"1","DOI":"10.37796\/2211-8039.1110","volume":"10","author":"SW Lai","year":"2020","unstructured":"Lai, S. W., Liao, K. F., Lin, C. L. & Lin, C. H. Association between Parkinson\u2019s disease and proton pump inhibitors therapy in older people. Biomedicine 10, 1\u20134 (2020).","journal-title":"Biomedicine"},{"key":"48007_CR22","doi-asserted-by":"publisher","first-page":"327","DOI":"10.3390\/ph15030327","volume":"15","author":"JH Kim","year":"2022","unstructured":"Kim, J. H. et al. Association between proton pump inhibitor use and Parkinson\u2019s disease in a Korean population. Pharmaceuticals 15, 327 (2022).","journal-title":"Pharmaceuticals"},{"key":"48007_CR23","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-022-24244-z","volume":"12","author":"P Fong","year":"2022","unstructured":"Fong, P. et al. Association of suicidal ideation and depression with the use of proton pump inhibitors in adults: a cross-sectional study. Sci. Rep. 12, 19539 (2022).","journal-title":"Sci. Rep."},{"key":"48007_CR24","doi-asserted-by":"publisher","first-page":"153","DOI":"10.1017\/S1041610217001715","volume":"30","author":"A Laudisio","year":"2018","unstructured":"Laudisio, A. et al. Use of proton-pump inhibitors is associated with depression: a population-based study. Int. Psychogeriatr. 30, 153\u2013159 (2018).","journal-title":"Int. Psychogeriatr."},{"key":"48007_CR25","doi-asserted-by":"publisher","first-page":"e0219213","DOI":"10.1371\/journal.pone.0219213","volume":"14","author":"YQ Song","year":"2019","unstructured":"Song, Y. Q., Li, Y., Zhang, S. L., Gao, J. & Feng, S. Y. Proton pump inhibitor use does not increase dementia and Alzheimer\u2019s disease risk: an updated meta-analysis of published studies involving 642305 patients. PLoS ONE 14, e0219213 (2019).","journal-title":"PLoS ONE"},{"key":"48007_CR26","doi-asserted-by":"publisher","first-page":"2157","DOI":"10.1007\/s00384-020-03717-5","volume":"35","author":"T Ma","year":"2020","unstructured":"Ma, T., Wu, M., Jia, S. & Yang, L. Proton pump inhibitors and the risk of colorectal cancer: a systematic review and meta-analysis of observational studies. Int. J. Colorectal Dis. 35, 2157\u20132169 (2020).","journal-title":"Int. J. Colorectal Dis."},{"key":"48007_CR27","doi-asserted-by":"publisher","first-page":"1437","DOI":"10.1007\/s00228-020-02927-8","volume":"76","author":"HJ Song","year":"2020","unstructured":"Song, H. J., Jeon, N. & Squires, P. The association between acid-suppressive agent use and the risk of cancer: a systematic review and meta-analysis. Eur. J. Clin. Pharm. 76, 1437\u20131456 (2020).","journal-title":"Eur. J. Clin. Pharm."},{"key":"48007_CR28","doi-asserted-by":"publisher","first-page":"943","DOI":"10.5588\/ijtld.18.0585","volume":"23","author":"HJ Song","year":"2019","unstructured":"Song, H. J., Park, H. & Seo, H. J. Association between use of proton pump inhibitors and tuberculosis risk: a systematic review. Int J. Tuberc. Lung Dis. 23, 943\u2013951 (2019).","journal-title":"Int J. Tuberc. Lung Dis."},{"key":"48007_CR29","doi-asserted-by":"publisher","first-page":"475","DOI":"10.1097\/COC.0000000000000949","volume":"45","author":"ML Zhang","year":"2022","unstructured":"Zhang, M. L. et al. Proton pump inhibitors and cancer risk: an umbrella review and meta-analysis of observational studies. Am. J. Clin. Oncol. 45, 475\u2013485 (2022).","journal-title":"Am. J. Clin. Oncol."},{"key":"48007_CR30","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-019-53622-3","volume":"9","author":"T Makunts","year":"2019","unstructured":"Makunts, T., Alpatty, S., Lee, K. C., Atayee, R. S. & Abagyan, R. Proton-pump inhibitor use is associated with a broad spectrum of neurological adverse events including impaired hearing, vision, and memory. Sci. Rep. 9, 17280 (2019).","journal-title":"Sci. Rep."},{"key":"48007_CR31","doi-asserted-by":"publisher","first-page":"80","DOI":"10.1016\/j.ejim.2022.09.021","volume":"106","author":"M Nolde","year":"2022","unstructured":"Nolde, M. et al. Proton pump inhibitors and the risk of cardiovascular events and cardiovascular mortality: a systematic review and meta-analysis of observational studies. Eur. J. Intern. Med. 106, 80\u201389 (2022).","journal-title":"Eur. J. Intern. Med."},{"key":"48007_CR32","first-page":"497","volume":"33","author":"Y Chen","year":"2022","unstructured":"Chen, Y. et al. Will proton pump inhibitors increase the risk of diabetes mellitus? A systemic review and meta-analysis. Turk. J. Gastroenterol. 33, 497\u2013504 (2022).","journal-title":"Turk. J. Gastroenterol."},{"key":"48007_CR33","doi-asserted-by":"publisher","first-page":"8739","DOI":"10.3390\/ijerph19148739","volume":"19","author":"HY Kuo","year":"2022","unstructured":"Kuo, H. Y. et al. Dose-dependent proton pump inhibitor exposure and risk of type 2 diabetes: a nationwide nested case-control study. Int J. Environ. Res. Public Health 19, 8739 (2022).","journal-title":"Int J. Environ. Res. Public Health"},{"key":"48007_CR34","first-page":"1687","volume":"71","author":"SH Loosen","year":"2022","unstructured":"Loosen, S. H. et al. Long-term use of proton pump inhibitors (PPIs) is associated with an increased risk of type 2 diabetes. Gut 71, 1687\u20131688 (2022).","journal-title":"Gut"},{"key":"48007_CR35","doi-asserted-by":"publisher","first-page":"e2671","DOI":"10.1210\/clinem\/dgac231","volume":"107","author":"S Ciardullo","year":"2022","unstructured":"Ciardullo, S. et al. Prolonged use of proton pump inhibitors and risk of type 2 diabetes: results from a large population-based nested case-control study. J. Clin. Endocrinol. Metab. 107, e2671\u2013e2679 (2022).","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"48007_CR36","doi-asserted-by":"publisher","first-page":"2718","DOI":"10.1111\/bcp.15182","volume":"88","author":"P Czarniak","year":"2022","unstructured":"Czarniak, P. et al. Proton pump inhibitors are associated with incident type 2 diabetes mellitus in a prospective population-based cohort study. Br. J. Clin. Pharm. 88, 2718\u20132726 (2022).","journal-title":"Br. J. Clin. Pharm."},{"key":"48007_CR37","doi-asserted-by":"publisher","first-page":"99","DOI":"10.1007\/s10147-022-02253-2","volume":"28","author":"TR Peng","year":"2023","unstructured":"Peng, T. R., Wu, T. W. & Li, C. H. Association between proton-pump inhibitors and the risk of gastric cancer: a systematic review and meta-analysis. Int J. Clin. Oncol. 28, 99\u2013109 (2023).","journal-title":"Int J. Clin. Oncol."},{"key":"48007_CR38","doi-asserted-by":"publisher","first-page":"175628482110514","DOI":"10.1177\/17562848211051463","volume":"14","author":"D Segna","year":"2021","unstructured":"Segna, D., Brusselaers, N., Glaus, D., Krupka, N. & Misselwitz, B. Association between proton-pump inhibitors and the risk of gastric cancer: a systematic review with meta-analysis. Ther. Adv. Gastroenterol. 14, 17562848211051463 (2021).","journal-title":"Ther. Adv. Gastroenterol."},{"key":"48007_CR39","doi-asserted-by":"publisher","first-page":"749","DOI":"10.1136\/gutjnl-2015-310861","volume":"65","author":"MA Jackson","year":"2016","unstructured":"Jackson, M. A. et al. Proton pump inhibitors alter the composition of the gut microbiota. Gut 65, 749\u2013756 (2016).","journal-title":"Gut"},{"key":"48007_CR40","doi-asserted-by":"publisher","first-page":"i5813","DOI":"10.1136\/bmj.i5813","volume":"355","author":"F Othman","year":"2016","unstructured":"Othman, F., Crooks, C. J. & Card, T. R. Community acquired pneumonia incidence before and after proton pump inhibitor prescription: population based study. BMJ 355, i5813 (2016).","journal-title":"BMJ"},{"key":"48007_CR41","doi-asserted-by":"publisher","first-page":"75","DOI":"10.1007\/s00281-019-00775-y","volume":"42","author":"K Hufnagl","year":"2020","unstructured":"Hufnagl, K., Pali-Scholl, I., Roth-Walter, F. & Jensen-Jarolim, E. Dysbiosis of the gut and lung microbiome has a role in asthma. Semin. Immunopathol. 42, 75\u201393 (2020).","journal-title":"Semin. Immunopathol."},{"key":"48007_CR42","doi-asserted-by":"publisher","first-page":"172","DOI":"10.1016\/j.canep.2018.02.004","volume":"53","author":"N Brusselaers","year":"2018","unstructured":"Brusselaers, N., Engstrand, L. & Lagergren, J. Maintenance proton pump inhibition therapy and risk of oesophageal cancer. Cancer Epidemiol. 53, 172\u2013177 (2018).","journal-title":"Cancer Epidemiol."},{"key":"48007_CR43","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-017-00796-x","volume":"8","author":"C Llorente","year":"2017","unstructured":"Llorente, C. et al. Gastric acid suppression promotes alcoholic liver disease by inducing overgrowth of intestinal Enterococcus. Nat. Commun. 8, 837 (2017).","journal-title":"Nat. Commun."},{"key":"48007_CR44","doi-asserted-by":"publisher","first-page":"120","DOI":"10.4239\/wjd.v14.i2.120","volume":"14","author":"YR Guo","year":"2023","unstructured":"Guo, Y. R., Liu, X. M. & Wang, G. X. Exposure to proton pump inhibitors and risk of diabetes: a systematic review and meta-analysis. World J. Diabetes 14, 120\u2013129 (2023).","journal-title":"World J. Diabetes"},{"key":"48007_CR45","doi-asserted-by":"publisher","first-page":"2262","DOI":"10.3390\/jcm12062262","volume":"12","author":"CC Wu","year":"2023","unstructured":"Wu, C. C., Liao, M. H., Kung, W. M. & Wang, Y. C. Proton pump inhibitors and risk of chronic kidney disease: evidence from observational studies. J. Clin. Med 12, 2262 (2023).","journal-title":"J. Clin. Med"},{"key":"48007_CR46","doi-asserted-by":"publisher","first-page":"625","DOI":"10.1016\/S1474-4422(15)00007-1","volume":"14","author":"A Fasano","year":"2015","unstructured":"Fasano, A., Visanji, N. P., Liu, L. W., Lang, A. E. & Pfeiffer, R. F. Gastrointestinal dysfunction in Parkinson\u2019s disease. Lancet Neurol. 14, 625\u2013639 (2015).","journal-title":"Lancet Neurol."},{"key":"48007_CR47","doi-asserted-by":"publisher","first-page":"62","DOI":"10.1159\/000485190","volume":"87","author":"WS Huang","year":"2018","unstructured":"Huang, W. S. et al. Use of proton pump inhibitors and risk of major depressive disorder: a nationwide population-based study. Psychother. Psychosom. 87, 62\u201364 (2018).","journal-title":"Psychother. Psychosom."},{"key":"48007_CR48","doi-asserted-by":"publisher","first-page":"10733","DOI":"10.3390\/ijms231810733","volume":"23","author":"E Lespessailles","year":"2022","unstructured":"Lespessailles, E. & Toumi, H. Proton pump inhibitors and bone health: an update narrative review. Int. J. Mol. Sci. 23, 10733 (2022).","journal-title":"Int. J. Mol. Sci."},{"key":"48007_CR49","doi-asserted-by":"publisher","first-page":"845","DOI":"10.1161\/CIRCULATIONAHA.113.003602","volume":"128","author":"YT Ghebremariam","year":"2013","unstructured":"Ghebremariam, Y. T. et al. Unexpected effect of proton pump inhibitors: elevation of the cardiovascular risk factor asymmetric dimethylarginine. Circulation 128, 845\u2013853 (2013).","journal-title":"Circulation"},{"key":"48007_CR50","doi-asserted-by":"publisher","first-page":"682","DOI":"10.1053\/j.gastro.2019.05.056","volume":"157","author":"P Moayyedi","year":"2019","unstructured":"Moayyedi, P. et al. Safety of proton pump inhibitors based on a large, multi-year, randomized trial of patients receiving rivaroxaban or aspirin. Gastroenterology 157, 682\u2013691 e682 (2019).","journal-title":"Gastroenterology"},{"key":"48007_CR51","first-page":"CD011969","volume":"3","author":"TA Boghossian","year":"2017","unstructured":"Boghossian, T. A. et al. Deprescribing versus continuation of chronic proton pump inhibitor use in adults. Cochrane Database Syst. Rev. 3, CD011969 (2017).","journal-title":"Cochrane Database Syst. Rev."},{"key":"48007_CR52","doi-asserted-by":"publisher","first-page":"28","DOI":"10.1136\/gutjnl-2017-314605","volume":"67","author":"KS Cheung","year":"2018","unstructured":"Cheung, K. S. et al. Long-term proton pump inhibitors and risk of gastric cancer development after treatment for Helicobacter pylori: a population-based study. Gut 67, 28\u201335 (2018).","journal-title":"Gut"},{"key":"48007_CR53","doi-asserted-by":"publisher","first-page":"1573","DOI":"10.2105\/AJPH.2016.303338","volume":"106","author":"Y Bao","year":"2016","unstructured":"Bao, Y. et al. Origin, methods, and evolution of the three Nurses\u2019 Health Studies. Am. J. Public Health 106, 1573\u20131581 (2016).","journal-title":"Am. J. Public Health"},{"key":"48007_CR54","doi-asserted-by":"crossref","unstructured":"Rimm, E. B. et al. Reproducibility and validity of an expanded self-administered semiquantitative food frequency questionnaire among male health professionals. Am. J. Epidemiol. 135, 1114\u20131126; discussion 1127-1136 (1992).","DOI":"10.1093\/oxfordjournals.aje.a116211"},{"key":"48007_CR55","unstructured":"Health Professionals Follow-up Study. https:\/\/sites.sph.harvard.edu\/hpfs\/ (2023)."},{"key":"48007_CR56","unstructured":"The Hospital Authority. Hospital authority statistical report 2012\u20132013. http:\/\/www.ha.org.hk\/haho\/ho\/stat\/HASR1415_2.pdf (2023)."},{"key":"48007_CR57","doi-asserted-by":"publisher","first-page":"55","DOI":"10.1111\/apt.14796","volume":"48","author":"KT Tran","year":"2018","unstructured":"Tran, K. T. et al. Proton pump inhibitor and histamine-2 receptor antagonist use and risk of liver cancer in two population-based studies. Aliment Pharm. Ther. 48, 55\u201364 (2018).","journal-title":"Aliment Pharm. Ther."},{"key":"48007_CR58","doi-asserted-by":"publisher","first-page":"e372","DOI":"10.1136\/bmj.e372","volume":"344","author":"H Khalili","year":"2012","unstructured":"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 344, e372 (2012).","journal-title":"BMJ"},{"key":"48007_CR59","doi-asserted-by":"publisher","first-page":"1204","DOI":"10.1016\/S0140-6736(20)30925-9","volume":"396","author":"GBD Diseases","year":"2020","unstructured":"Diseases, G. B. D. & Injuries, C. Global burden of 369 diseases and injuries in 204 countries and territories, 1990-2019: a systematic analysis for the Global Burden of Disease Study 2019. Lancet 396, 1204\u20131222 (2020).","journal-title":"Lancet"},{"key":"48007_CR60","doi-asserted-by":"publisher","first-page":"1475","DOI":"10.1161\/01.CIR.86.5.1475","volume":"86","author":"A Ascherio","year":"1992","unstructured":"Ascherio, A. et al. A prospective study of nutritional factors and hypertension among US men. Circulation 86, 1475\u20131484 (1992).","journal-title":"Circulation"},{"key":"48007_CR61","first-page":"416","volume":"19","author":"OF Wong","year":"2013","unstructured":"Wong, O. F., Ho, P. L. & Lam, S. K. Retrospective review of clinical presentations, microbiology, and outcomes of patients with psoas abscess. Hong Kong Med. J. 19, 416\u2013423 (2013).","journal-title":"Hong Kong Med. J."},{"key":"48007_CR62","doi-asserted-by":"publisher","first-page":"138","DOI":"10.1093\/pubmed\/fdr054","volume":"34","author":"EM Burns","year":"2012","unstructured":"Burns, E. M. et al. Systematic review of discharge coding accuracy. J. Public Health 34, 138\u2013148 (2012).","journal-title":"J. Public Health"},{"key":"48007_CR63","doi-asserted-by":"publisher","first-page":"894","DOI":"10.1093\/oxfordjournals.aje.a114319","volume":"123","author":"GA Colditz","year":"1986","unstructured":"Colditz, G. A. et al. Validation of questionnaire information on risk factors and disease outcomes in a prospective cohort study of women. Am. J. Epidemiol. 123, 894\u2013900 (1986).","journal-title":"Am. J. Epidemiol."},{"key":"48007_CR64","doi-asserted-by":"publisher","first-page":"e010038","DOI":"10.1136\/bmjopen-2015-010038","volume":"6","author":"S Cassidy","year":"2016","unstructured":"Cassidy, S., Chau, J. Y., Catt, M., Bauman, A. & Trenell, M. I. Cross-sectional study of diet, physical activity, television viewing and sleep duration in 233,110 adults from the UK Biobank; the behavioural phenotype of cardiovascular disease and type 2 diabetes. BMJ Open 6, e010038 (2016).","journal-title":"BMJ Open"},{"key":"48007_CR65","doi-asserted-by":"publisher","first-page":"991","DOI":"10.1093\/ije\/23.5.991","volume":"23","author":"AM Wolf","year":"1994","unstructured":"Wolf, A. M. et al. Reproducibility and validity of a self-administered physical activity questionnaire. Int. J. Epidemiol. 23, 991\u2013999 (1994).","journal-title":"Int. J. Epidemiol."},{"key":"48007_CR66","doi-asserted-by":"publisher","first-page":"417","DOI":"10.1002\/jrsm.1303","volume":"9","author":"E Kontopantelis","year":"2018","unstructured":"Kontopantelis, E. A comparison of one-stage vs two-stage individual patient data meta-analysis methods: a simulation study. Res. Synth. methods 9, 417\u2013430 (2018).","journal-title":"Res. Synth. methods"},{"key":"48007_CR67","doi-asserted-by":"publisher","first-page":"557","DOI":"10.1136\/bmj.327.7414.557","volume":"327","author":"JP Higgins","year":"2003","unstructured":"Higgins, J. P., Thompson, S. G., Deeks, J. J. & Altman, D. G. Measuring inconsistency in meta-analyses. BMJ 327, 557\u2013560 (2003).","journal-title":"BMJ"},{"key":"48007_CR68","doi-asserted-by":"publisher","first-page":"1492","DOI":"10.1136\/bmj.319.7223.1492","volume":"319","author":"DG Altman","year":"1999","unstructured":"Altman, D. G. & Andersen, P. K. Calculating the number needed to treat for trials where the outcome is time to an event. BMJ 319, 1492\u20131495 (1999).","journal-title":"BMJ"},{"key":"48007_CR69","doi-asserted-by":"publisher","first-page":"268","DOI":"10.7326\/M16-2607","volume":"167","author":"TJ VanderWeele","year":"2017","unstructured":"VanderWeele, T. J. & Ding, P. Sensitivity analysis in observational research: introducing the E-value. Ann. Intern. Med. 167, 268\u2013274 (2017).","journal-title":"Ann. Intern. Med."}],"container-title":["Nature Communications"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41467-024-48007-8.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41467-024-48007-8","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41467-024-48007-8.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,4,27]],"date-time":"2024-04-27T14:03:30Z","timestamp":1714226610000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41467-024-48007-8"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,4,27]]},"references-count":69,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2024,12]]}},"alternative-id":["48007"],"URL":"https:\/\/doi.org\/10.1038\/s41467-024-48007-8","relation":{},"ISSN":["2041-1723"],"issn-type":[{"value":"2041-1723","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,4,27]]},"assertion":[{"value":"14 June 2023","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"17 April 2024","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"27 April 2024","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare no competing interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"3591"}}