|
1
|
Harris AB, Agarwal AR, Hegde V, Oni JK, Khanuja HS. Routine Prescription of Proton Pump Inhibitors in the Perioperative Period is Associated With Decreased Rates of 2-Year Revision Surgery After Total Hip and Knee Arthroplasty. J Arthroplasty 2025; 40:597-601.e1. [PMID: 39233100 DOI: 10.1016/j.arth.2024.08.042] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/05/2024] [Revised: 08/23/2024] [Accepted: 08/27/2024] [Indexed: 09/06/2024] Open
Abstract
BACKGROUND Proton pump inhibitors (PPIs) are often prescribed in conjunction with nonsteroidal anti-inflammatory drugs after total hip arthroplasty (THA) and total knee arthroplasty (TKA) due to their gastroprotective effects. In animal studies, it has been suggested that PPIs have immunosuppressive effects and impair fracture healing; however, the association between PPI use and adverse events following THA and TKA has not been well-studied. METHODS An administrative claims database was queried for patients who underwent elective THA from 2010 to 2019. The experimental group consisted of patients who did not have a prior history of gastrointestinal bleeding or gastroesophageal reflux disease and who received a PPI prescription in the perioperative period. A 1:1 propensity score matching was used to create control cohorts of patients who did not have any PPI prescription filled, also matching for age, sex, and the Charlson Comorbidity Index. This same cohort selection and matching procedure was then repeated for patients undergoing elective TKA. In total, 11,450 patients were studied (3,103 TKA + PPI, 2,622 THA + PPI, 3,103 TKA controls, and 2,622 THA controls). The mean age was 64 years (range, 38 to 94), and 57% were women. Significance was considered at P < 0.05. RESULTS Perioperative PPI prescription in TKA patients was associated with significantly lower rates of all-cause revision (3.0 versus 4.1%, P < 0.01) and periprosthetic joint infection (1.0 versus 1.8%, P < 0.01). In THA patients, PPI prescription was associated with a lower all-cause revision rate (2.8 versus 4.0%, P = 0.02). No significant differences were found between PPI and non-PPI groups for aseptic loosening, periprosthetic fracture, gastrointestinal bleeding, or surgical site infection in either cohort. CONCLUSIONS Patients receiving routine PPI prescriptions in the perioperative period surrounding TKA and THA have a lower risk of all-cause revision surgery, and perioperative PPI use is associated with a decreased risk of PJI in patients undergoing TKA. As these results conflict with the few previous studies performed on this topic, additional controlled studies are warranted to fully elucidate the relationship between PPI use and adverse events after THA and TKA.
Collapse
Affiliation(s)
- Andrew B Harris
- Department of Orthopaedic Surgery, The Johns Hopkins University School of Medicine, Baltimore, Maryland
| | - Amil R Agarwal
- Department of Orthopaedic Surgery, Virginia Commonwealth University Medical Center, Richmond, Virginia
| | - Vishal Hegde
- Department of Orthopaedic Surgery, The Johns Hopkins University School of Medicine, Baltimore, Maryland
| | - Julius K Oni
- Department of Orthopaedic Surgery, The Johns Hopkins University School of Medicine, Baltimore, Maryland
| | - Harpal S Khanuja
- Department of Orthopaedic Surgery, The Johns Hopkins University School of Medicine, Baltimore, Maryland
| |
Collapse
|
|
2
|
Gramont B, Fayolle S, Beltramin D, Bidat N, Boudet J, Chaux R, Grange L, Barrau M, Gagneux-Brunon A, Cathébras P, Killian M, Botelho-Nevers E, Célarier T. Proton pump inhibitors and risk of severe COVID-19 in older people. Age Ageing 2024; 53:afae082. [PMID: 38619123 DOI: 10.1093/ageing/afae082] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/23/2023] [Revised: 12/11/2023] [Indexed: 04/16/2024] Open
Abstract
INTRODUCTION Severe acute respiratory syndrome coronavirus 2 is a viral respiratory infection that can cause systemic disorders and lead to death, particularly in older people. Proton pump inhibitors (PPIs) increase the risk of enteric and lung infections. Considering the broad use of PPIs in older people, the potential role of PPIs in COVID-19 could be of dramatic significance. The objective of our study was to evaluate the link between PPIs and severe COVID-19 in older people. METHOD We performed a retrospective cohort study, including all patients aged ≥65, hospitalised for a diagnosis of COVID-19. Epidemiological, clinical and biological data were extracted and we performed an Inverse Probability of Treatment Weighing method based on a propensity score. RESULTS From March 2020 to February 2021, a total of 834 patients were included, with a median age of 83 and 52.8% were male. A total of 410 patients had a PPIs prescription, 358 (87.3%) were long-term PPIs-users and 52 (12.7%) were recent PPIs-users. Among PPIs-users, 163 (39.8%) patients developed severe COVID-19 versus 113 (26.7%) in PPIs-non users (odds ratio (OR) = 1.59 [1.18-2.14]; P < 0.05). Moreover, the double dose PPI-users had a higher risk of developing severe COVID-19 (OR = 3.36 [1.17-9.66]; P < 0.05) than the full dose PPI-users (OR = 2.15 [1.22-3.76]; P < 0.05) and the half dose PPI-users (OR = 1.64 [1.13-2.37]; P < 0.05). CONCLUSION Our study reports evidence that the use of PPIs was associated with an increased risk of severe COVID-19 in older people.
Collapse
Affiliation(s)
- Baptiste Gramont
- Department of Internal Medicine, Saint-Etienne University Hospital, Saint-Etienne, France
- Team GIMAP, CIRI-Centre International de Recherche en Infectiologie, Université de Lyon, Université Jean Monnet, Université Claude Bernard Lyon 1, INSERM, U1111, Centre National de la Recherche Scientifique (CNRS), UMR530, F42023 Saint-Etienne, France
| | - Sophie Fayolle
- Department of General Practice, Université Jean Monnet, Saint-Etienne, France
| | - Diva Beltramin
- Department of Public Health and Medical Information, Saint-Etienne University Hospital, Saint-Etienne, France
| | - Nisrine Bidat
- Department of General Practice, Université Jean Monnet, Saint-Etienne, France
| | - Julie Boudet
- Department of General Practice, Université Jean Monnet, Saint-Etienne, France
| | - Robin Chaux
- Department of Public Health and Medical Information, Saint-Etienne University Hospital, Saint-Etienne, France
| | - Lucile Grange
- Department of Internal Medicine, Saint-Etienne University Hospital, Saint-Etienne, France
| | - Mathilde Barrau
- Team GIMAP, CIRI-Centre International de Recherche en Infectiologie, Université de Lyon, Université Jean Monnet, Université Claude Bernard Lyon 1, INSERM, U1111, Centre National de la Recherche Scientifique (CNRS), UMR530, F42023 Saint-Etienne, France
- Department of Gastroenterology, Saint-Etienne University Hospital, Saint-Etienne, France
| | - Amandine Gagneux-Brunon
- Team GIMAP, CIRI-Centre International de Recherche en Infectiologie, Université de Lyon, Université Jean Monnet, Université Claude Bernard Lyon 1, INSERM, U1111, Centre National de la Recherche Scientifique (CNRS), UMR530, F42023 Saint-Etienne, France
- Infectious Disease Department, Saint-Etienne University Hospital, Saint-Etienne, France
| | - Pascal Cathébras
- Department of Internal Medicine, Saint-Etienne University Hospital, Saint-Etienne, France
| | - Martin Killian
- Department of Internal Medicine, Saint-Etienne University Hospital, Saint-Etienne, France
- Team GIMAP, CIRI-Centre International de Recherche en Infectiologie, Université de Lyon, Université Jean Monnet, Université Claude Bernard Lyon 1, INSERM, U1111, Centre National de la Recherche Scientifique (CNRS), UMR530, F42023 Saint-Etienne, France
| | - Elisabeth Botelho-Nevers
- Team GIMAP, CIRI-Centre International de Recherche en Infectiologie, Université de Lyon, Université Jean Monnet, Université Claude Bernard Lyon 1, INSERM, U1111, Centre National de la Recherche Scientifique (CNRS), UMR530, F42023 Saint-Etienne, France
- Infectious Disease Department, Saint-Etienne University Hospital, Saint-Etienne, France
| | - Thomas Célarier
- Department of Clinical Gerontology, Saint-Etienne University Hospital, Saint-Etienne, France
- Chaire Santé des Ainés, Université Jean Monnet, Saint-Etienne, France
- Gérontopôle Auvergne-Rhône-Alpes, Saint-Etienne, France
| |
Collapse
|
|
3
|
Mekhail A, Young P, Mekhail AM, Tinawi G, Haran C, Clayton N, Galvin S. Stress Ulcer Prophylaxis in Cardiac Surgery: A Retrospective Cohort Study to Analyze the Effects of SUP Cessation. J Intensive Care Med 2023; 38:917-921. [PMID: 37093762 DOI: 10.1177/08850666231171327] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 04/25/2023]
Abstract
INTRODUCTION Upper gastrointestinal bleeding (UGIB) is an important complication among critically ill adults, especially those having cardiac surgery as management is complicated by the requirement for antiplatelet/anticoagulant therapy. As a result, stress ulcer prophylaxis (SUP) has become routine practice in many centers, utilizing either proton pump inhibitors (PPIs) or histamine-2 receptor blockers (H2RBs). Recent evidence from the PEPTIC trial indicated an increase in mortality risk among cardiac surgery patients receiving PPIs compared to H2RBs. Considering these findings, alongside practical difficulties surrounding the transition to H2RBs as a prophylactic agent in New Zealand, Wellington Hospital intensive care unit elected to discontinue routine PPI use for SUP in cardiac surgery patients. A retrospective study was conducted to assess patient outcomes following the discontinuation of routine SUP. METHOD A retrospective cohort study was conducted of all adult patients who underwent cardiac surgery at Wellington Hospital between February/2018 and January/2022, and divided patients into cohorts before and after the discontinuation of routine use of SUP on the 31st of January 2020. The primary outcomes were the rate of UGIB, oesophagogastroduodenoscopy (OGD) and 180-day postoperative mortality. Secondary outcomes included rates of postoperative Clostridium difficile enteritis, pneumonia, deep sternal wound infection, and length of stay of the index admission. RESULTS The rate of UGIB statistically significantly increased since the cessation of routine SUP in January 2020 (2.4% vs 5.4%, P-value = .004). This finding was mirrored with the increased rates of OGD (1.9% vs 4.0%, P-value = .005). There were no significant changes in 180-day mortality, hospital length of stay, or any of the postoperative infective complications analyzed, pneumonia, deep sternal wound infection, or C difficile enteritis. CONCLUSION This study suggests an association between routine use of SUP and reduced rates of clinically significant UGIB and OGD requirements in cardiac surgery patients without increasing risk of infective complications or postoperative mortality.
Collapse
Affiliation(s)
- Andrew Mekhail
- Department of Cardiothoracic Surgery, Wellington Hospital, Wellington, New Zealand
| | - Paul Young
- Department of Intensive Care Medicine, Wellington Hospital, Wellington, New Zealand
| | - Ann-Marie Mekhail
- Department of Intensive Care Medicine, Wellington Hospital, Wellington, New Zealand
| | - Georges Tinawi
- Department of Cardiothoracic Surgery, Wellington Hospital, Wellington, New Zealand
| | - Cheyaanthan Haran
- Department of Cardiothoracic Surgery, Wellington Hospital, Wellington, New Zealand
| | - Nicholas Clayton
- Department of Cardiothoracic Surgery, Wellington Hospital, Wellington, New Zealand
| | - Sean Galvin
- Department of Cardiothoracic Surgery, Wellington Hospital, Wellington, New Zealand
| |
Collapse
|
|
4
|
Uğraklı M, Koçak MZ, Dinç G, Genç TB, Çağlayan M, Uğraklı S, Hendem E, Er MM, Çağlayan D, Eryılmaz MK, Araz M, Geredeli Ç, Tatlı AM, Eren OÖ, Artaç M. The effect of concomitant proton pump inhibitor use on survival outcomes of Nivolumab-treated renal cell carcinoma patients: a multicenter study. J Cancer Res Clin Oncol 2023; 149:9183-9189. [PMID: 37184681 DOI: 10.1007/s00432-023-04844-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/07/2023] [Accepted: 05/07/2023] [Indexed: 05/16/2023]
Abstract
AIM We aimed to evaluate the effect of concomitant proton pump inhibitors (PPI) use with nivolumab on survival outcomes in metastatic renal cell carcinoma (mRCC) in second-line setting. METHODS The study was designed as a multicenter and retrospective involving patients with metastatic renal cell carcinoma receiving second-line nivolumab therapy. One hundred and nine patients with mRCC were divided into two groups based on whether they use PPI concomitantly with nivolumab: concomitant PPI users and non-users. Overall survival (OS) and progression-free survival (PFS) were compared between the groups with and without concurrent PPIs. RESULTS Of 109 patients in our study, 59 were not using PPI concomitantly with nivolumab and 50 were using PPI concomitantly. The median PFS was 6.37 (5.2-7.5) months in the concomitant PPI group and 9.7 (4.5-15) months in the non-users (p = 0.03). The median OS was 14.6 (7.1-22.1) months in patients on PPI concurrently with nivolumab and 29.9 (17.1-42.7) months in the non-users (p = 0.01). Accordingly, PPI use for PFS (Non-use vs. Use = HR: 0.44, 95%Cl 0.28-0.96, p = 0.014) and PPI use for OS (Non-use vs. Use = HR: 0.68, 95%Cl 0.22-0.88, p = 0.01) were found to be as independent risk factors. CONCLUSIONS Concomitant use of PPIs is associated with worse survival outcomes in patients with mRCC treated with nivolumab. Clinicians should carefully consider the concomitant use of PPIs in such patients.
Collapse
Affiliation(s)
- Muzaffer Uğraklı
- Meram Faculty of Medicine Department of Medical Oncology, Necmettin Erbakan University, 14280, Konya, Turkey.
| | - Mehmet Zahid Koçak
- Meram Faculty of Medicine Department of Medical Oncology, Necmettin Erbakan University, 14280, Konya, Turkey
| | - Gülhan Dinç
- Department of Medical Oncology, Okmeydani Training and Research Hospital, Istanbul, Turkey
| | | | - Melek Çağlayan
- Department of Medical Oncology, Selçuk University, Konya, Turkey
| | - Selin Uğraklı
- Department of Medical Microbiology, Necmettin Erbakan University, Konya, Turkey
| | - Engin Hendem
- Meram Faculty of Medicine Department of Medical Oncology, Necmettin Erbakan University, 14280, Konya, Turkey
| | - Muhammed Muhiddin Er
- Meram Faculty of Medicine Department of Medical Oncology, Necmettin Erbakan University, 14280, Konya, Turkey
| | - Dilek Çağlayan
- Meram Faculty of Medicine Department of Medical Oncology, Necmettin Erbakan University, 14280, Konya, Turkey
| | - Melek Karakurt Eryılmaz
- Meram Faculty of Medicine Department of Medical Oncology, Necmettin Erbakan University, 14280, Konya, Turkey
| | - Murat Araz
- Meram Faculty of Medicine Department of Medical Oncology, Necmettin Erbakan University, 14280, Konya, Turkey
| | - Çağlayan Geredeli
- Department of Medical Oncology, Okmeydani Training and Research Hospital, Istanbul, Turkey
| | - Ali Murat Tatlı
- Department of Medical Oncology, Akdeniz University, Antalya, Turkey
| | - Orhan Önder Eren
- Department of Medical Oncology, Selçuk University, Konya, Turkey
| | - Mehmet Artaç
- Meram Faculty of Medicine Department of Medical Oncology, Necmettin Erbakan University, 14280, Konya, Turkey
| |
Collapse
|
|
5
|
Kiecka A, Szczepanik M. Proton pump inhibitor-induced gut dysbiosis and immunomodulation: current knowledge and potential restoration by probiotics. Pharmacol Rep 2023:10.1007/s43440-023-00489-x. [PMID: 37142877 PMCID: PMC10159235 DOI: 10.1007/s43440-023-00489-x] [Citation(s) in RCA: 30] [Impact Index Per Article: 15.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/22/2023] [Revised: 04/20/2023] [Accepted: 04/21/2023] [Indexed: 05/06/2023]
Abstract
Proton pump inhibitors (PPIs) are the most commonly prescribed drugs for the treatment of non-erosive reflux disease (NERD), ulcers associated with non-steroidal anti-inflammatory drugs (NSAIDs), esophagitis, peptic ulcer disease (PUD), Zollinger-Ellison syndrome (ZES), gastroesophageal reflux disease (GERD), non-ulcer dyspepsia, and Helicobacter pylori eradication therapy. The drugs have the effect of inhibiting acid production in the stomach. According to research, PPIs can affect the composition of gut microbiota and modulate the immune response. Recently, there has been a problem with the over-prescription of such drugs. Although PPIs do not have many side effects, their long-term use can contribute to small intestinal bacterial overgrowth (SIBO) or C. difficile and other intestinal infections. Probiotic supplementation during PPIs therapy may provide some hope in the reduction of emerging therapy side effects. This review aims to present the most important effects of long-term PPI use and provides critical insights into the role of probiotic intervention in PPI therapy.
Collapse
Affiliation(s)
- Aneta Kiecka
- Chair of Biomedical Sciences, Institute of Physiotherapy, Faculty of Health Sciences, Jagiellonian University Medical College, Kopernika 7a, 31-034, Kraków, Poland.
| | - Marian Szczepanik
- Chair of Biomedical Sciences, Institute of Physiotherapy, Faculty of Health Sciences, Jagiellonian University Medical College, Kopernika 7a, 31-034, Kraków, Poland
| |
Collapse
|
|
6
|
Zhang Y, Li J, Chen Z, Liu L, Zhan X, Peng F, Zhou Q, Wu X, Zeng Y, Zhu L, Xie Y, Lai X, Wang Z, Wen Y, Feng X, Liang J. Proton pump inhibitor usage associates with higher risk of first episodes of pneumonia and peritonitis in peritoneal dialysis patients. Ren Fail 2022; 44:1623-1631. [PMID: 36195979 PMCID: PMC9542879 DOI: 10.1080/0886022x.2022.2129064] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/03/2022] Open
Abstract
Background A large number of studies have shown that proton pump inhibitors (PPIs) are associated with infection events. Therefore, we retrospectively evaluated the association of PPI therapy with the occurrence of first pneumonia and peritoneal dialysis(PD)-related peritonitis events in the maintenance PD patients. Methods We collected PD patients in two large hospitals from January 1, 2012 to December 31, 2016, and divided them into the PPI group and the non-PPI group. Multivariate Cox proportional hazards models were applied to evaluate the cumulative incidence and hazard ratios (HRs). Inverse probability of treatment weight (IPTW) method was used to adjust for covariate imbalance between the two groups and further confirm our findings. Results Finally, 656 PD patients were included for data analysis, and the results showed that PPI usage was associated with an increased risk of pneumonia [HR 1.71; 95% CI 1.06-2.76; p = 0.027] and peritonitis [HR 1.73; 95% CI 1.24-2.40; p = 0.001]. IPTW-adjusted HRs for the association of PPIs with pneumonia and peritonitis were 1.58 (95% CI:1.18-2.12; p = 0.002) and 2.33 (95% CI:1.91-2.85; p < 0.001), respectively. Moreover, the competitive risk model proved that under the conditions of competition for other events(including transfer to hemodialysis therapy, kidney transplant, transfer from our research center, loss to follow-up, and death), the differences in endpoints events between the two groups were still statistically significant (p = 0.009, p < 0.001, respectively). Conclusions PPIs was associated with an increased risk of first pneumonia and PD-related peritonitis events in PD patients, which reminds clinicians to be cautious when prescribing acid-suppressing drugs for PD patients.
Collapse
Affiliation(s)
- Yujing Zhang
- Department of Nephrology, The Second Affiliated Hospital Guangzhou Medical University, Guangzhou, China
| | - Jiao Li
- Department of Nephrology, The Second Affiliated Hospital Guangzhou Medical University, Guangzhou, China.,Department of Cardiology, The Second Affiliated Hospital Guangzhou Medical University, Guangzhou, China
| | - Zijun Chen
- Department of Nephrology, Affiliated Dongguan People's Hospital Southern Medical University, Guangdong, China
| | - Lingling Liu
- Department of General Medicine, The Third Affiliated Hospital Sun Yat-sen University, Guangzhou, China
| | - Xiaojiang Zhan
- Department of Nephrology, The First Affiliated Hospital of Nanchang University, Nanchang, China
| | - Fenfen Peng
- Department of Nephrology, Zhujiang Hospital Southern Medical University, Guangzhou, China
| | - Qian Zhou
- Department of Medical Statistics, Clinical Trials Unit, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
| | - Xianfeng Wu
- Department of Nephrology, Affiliated Sixth People's Hospital Shanghai Jiao Tong University, Shanghai, China
| | - Yingsi Zeng
- Department of Nephrology, The Second Affiliated Hospital Guangzhou Medical University, Guangzhou, China
| | - Liya Zhu
- Department of Nephrology, The Second Affiliated Hospital Guangzhou Medical University, Guangzhou, China
| | - Yuxin Xie
- Department of Nephrology, The Second Affiliated Hospital Guangzhou Medical University, Guangzhou, China
| | - Xiaochun Lai
- Department of Nephrology, The Second Affiliated Hospital Guangzhou Medical University, Guangzhou, China
| | - Zebin Wang
- Department of Nephrology, The Second Affiliated Hospital Guangzhou Medical University, Guangzhou, China
| | - Yueqiang Wen
- Department of Nephrology, The Second Affiliated Hospital Guangzhou Medical University, Guangzhou, China
| | - Xiaoran Feng
- Department of Nephrology, Jiujiang NO.1 people's Hospital, Jiujiang, China
| | - Jianbo Liang
- Department of Nephrology, The Second Affiliated Hospital Guangzhou Medical University, Guangzhou, China
| |
Collapse
|
|
7
|
Zhang L, Chen C, Chai D, Li C, Kuang T, Liu L, Dong K, Deng W, Wang W. Effects of PPIs use on clinical outcomes of urothelial cancer patients receiving immune checkpoint inhibitor therapy. Front Pharmacol 2022; 13:1018411. [PMID: 36225582 PMCID: PMC9549125 DOI: 10.3389/fphar.2022.1018411] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/13/2022] [Accepted: 09/07/2022] [Indexed: 11/30/2022] Open
Abstract
Objective: Immune checkpoint inhibitors (ICIs) have recently demonstrated promising performance in improving the prognosis of urological cancer patients. The goal of this meta-analysis was to determine the impact of PPI use on the clinical outcomes of urological cancer patients receiving ICI therapy. Methods: Before 6 May 2022, the eligible literature was searched using PubMed, EMBASE, Cochrane Library, and Google Scholar. The clinical outcomes were overall survival (OS), progression-free survival (PFS), and objective response rate (ORR). Results: A total of six articles met the inclusion criteria, and of the 1980 patients with advanced or metastatic urothelial cancers (UC) included. The meta-analysis displayed that PPI use could increase the risk of progression by 50.7% (HR: 1.507, 95% CI: 1.327–1.711, p < 0.001) and death by 58.7% (HR: 1.587, 95% CI: 1.367–1.842, p < 0.001), and reduce the ORR (OR: 0.503, 95% CI: 0.360–0.703, p < 0.001) in UC patients receiving ICIs. No significant heterogeneity and publication bias existed. Sensitivity analysis proved that the results were stable and reliable. Conclusion: The meta-analysis indicated that concomitant PPI use was significantly associated with low clinical benefit in UC patients.
Collapse
|
|
8
|
Rizzo A, Santoni M, Mollica V, Ricci AD, Calabrò C, Cusmai A, Gadaleta-Caldarola G, Palmiotti G, Massari F. The Impact of Concomitant Proton Pump Inhibitors on Immunotherapy Efficacy Among Patients with Urothelial Carcinoma: A Meta-Analysis. J Pers Med 2022; 12:jpm12050842. [PMID: 35629263 PMCID: PMC9145929 DOI: 10.3390/jpm12050842] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/28/2022] [Revised: 05/17/2022] [Accepted: 05/19/2022] [Indexed: 02/06/2023] Open
Abstract
Background. Immune checkpoint inhibitors (ICIs) have recently represented a breakthrough in urothelial carcinoma (UC). Proton pump inhibitors (PPIs) are routinely used for extended time periods in UC patients, with these agents having potentially and frequently undervalued effects on ICIs efficacy. Methods. We performed a meta-analysis aimed at investigating the impact of concomitant PPI administration on progression-free survival (PFS) and overall survival (OS) among patients receiving immunotherapy for metastatic UC. Results. Two studies encompassing a total of 1015 patients were included. The pooled Hazard Ratios (HRs) for OS and PFS were 1.55 (95% CI, 1.31–1.84) and 1.43 (95% CI, 1.23–1.66), respectively, suggesting that the administration of PPIs was negatively associated with PFS and with OS in UC patients treated with ICIs. Conclusions. The current meta-analysis represents the first study to provide a systematic evaluation of the impact of concomitant PPI use in UC patients treated with ICIs. Further studies are warranted on this topic to clarify the relationship between gut microbiome, antiacid exposure, and cancer immunotherapy. In the current era of medical oncology, progress in this setting will require the collaboration of basic science and clinical research to optimize systemic treatment and to improve the outcomes of UC patients receiving ICIs.
Collapse
Affiliation(s)
- Alessandro Rizzo
- Struttura Semplice Dipartimentale di Oncologia Medica per la Presa in Carico Globale del Paziente Oncologico “Don Tonino Bello”, Istituto di Ricerca e Cura a Carattere Scientifico (IRCCS), Istituto Tumori Giovanni Paolo II-Bari, Viale Orazio Flacco 65, 70124 Bari, Italy; (A.C.); (G.P.)
- Correspondence: ; Tel.: +39-051-2144078; Fax: +39-051-6364037
| | - Matteo Santoni
- Oncology Unit, Macerata Hospital, 62100 Macerata, Italy;
| | - Veronica Mollica
- Medical Oncology, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Via Albertoni-15, 40138 Bologna, Italy; (V.M.); (F.M.)
| | - Angela Dalia Ricci
- Departmental Unit of Medical Oncology, ‘San Paolo’ Hospital, ASL BA, 70123 Bari, Italy;
| | - Concetta Calabrò
- S.C. Farmacia e U.Ma.C.A., Istituto di Ricerca e Cura a Carattere Scientifico (IRCCS), Istituto Tumori Giovanni Paolo-Bari, 70124 Bari, Italy;
| | - Antonio Cusmai
- Struttura Semplice Dipartimentale di Oncologia Medica per la Presa in Carico Globale del Paziente Oncologico “Don Tonino Bello”, Istituto di Ricerca e Cura a Carattere Scientifico (IRCCS), Istituto Tumori Giovanni Paolo II-Bari, Viale Orazio Flacco 65, 70124 Bari, Italy; (A.C.); (G.P.)
| | - Gennaro Gadaleta-Caldarola
- Medical Oncology Unit, ‘Mons. R. Dimiccoli’ Hospital, Azienda Sanitaria Locale Barletta, 76121 Barletta, Italy;
| | - Gennaro Palmiotti
- Struttura Semplice Dipartimentale di Oncologia Medica per la Presa in Carico Globale del Paziente Oncologico “Don Tonino Bello”, Istituto di Ricerca e Cura a Carattere Scientifico (IRCCS), Istituto Tumori Giovanni Paolo II-Bari, Viale Orazio Flacco 65, 70124 Bari, Italy; (A.C.); (G.P.)
| | - Francesco Massari
- Medical Oncology, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Via Albertoni-15, 40138 Bologna, Italy; (V.M.); (F.M.)
- Department of Experimental, Diagnostic and Specialty Medicine, University of Bologna, 40138 Bologna, Italy
| |
Collapse
|
|
9
|
Rizzo A, Cusmai A, Giovannelli F, Acquafredda S, Rinaldi L, Misino A, Montagna ES, Ungaro V, Lorusso M, Palmiotti G. Impact of Proton Pump Inhibitors and Histamine-2-Receptor Antagonists on Non-Small Cell Lung Cancer Immunotherapy: A Systematic Review and Meta-Analysis. Cancers (Basel) 2022; 14:cancers14061404. [PMID: 35326555 PMCID: PMC8945985 DOI: 10.3390/cancers14061404] [Citation(s) in RCA: 88] [Impact Index Per Article: 29.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/20/2022] [Revised: 03/04/2022] [Accepted: 03/07/2022] [Indexed: 02/07/2023] Open
Abstract
Simple Summary The current meta-analysis highlighted that proton pump inhibitors (PPIs) and histamine-2-receptor antagonists (H2RAs) could impact immune checkpoint inhibitors (ICIs) efficacy in NSCLC patients, highlighting the need for a deeper comprehension of factors involved in treatment response or resistance. Since the number of indications and NSCLC patients receiving ICIs is supposed to increase further soon, identifying the impact of these agents on NSCLC immunotherapy represents a compelling and urgent need regarding NSCLC. Abstract (1) Background: In recent years, immunotherapy has revolutionized the treatment landscape of non-small cell lung cancer (NSCLC), representing a therapeutic breakthrough in this field. Antacid agents such as proton pump inhibitors (PPIs) and histamine-2-receptor antagonists (H2RAs) are commonly prescribed for extended periods in NSCLC patients, and these drugs have the potential to modify the efficacy of immune checkpoint inhibitors (ICIs). (2) Materials and Methods: Herein, we conducted a systematic review and meta-analysis to investigate the impact of PPIs and H2RAs on progression-free survival (PFS) and overall survival (OS) among patients receiving immunotherapy for metastatic NSCLC. Effect measures for OS were Hazard Ratios (HRs) and 95% Confidence Intervals (CIs), which were extracted from available studies. Forest plots were used to assess HRs to describe the relationship between treatment and OS in the specified cohorts of patients. (3) Results: Six studies were included in the analysis, involving 2267 patients. The pooled HRs for OS and PFS were 1.4 (95% CI, 1.25–1.58) and 1.29 (95% CI, 1.17–1.43), respectively, suggesting that PPIs and H2RAs administration was negatively associated with PFS and OS. (4) Conclusion: Concomitant antacid use could modify the activity of ICIs in NSCLC patients.
Collapse
Affiliation(s)
- Alessandro Rizzo
- Struttura Semplice Dipartimentale di Oncologia Medica per la Presa in Carico Globale del Paziente Oncologico “Don Tonino Bello”, I.R.C.C.S. Istituto Tumori “Giovanni Paolo II”, Viale Orazio Flacco 65, 70124 Bari, Italy; (A.C.); (F.G.); (S.A.); (L.R.); (A.M.); (E.S.M.); (G.P.)
- Correspondence: ; Tel.: +39-0-512-144-078
| | - Antonio Cusmai
- Struttura Semplice Dipartimentale di Oncologia Medica per la Presa in Carico Globale del Paziente Oncologico “Don Tonino Bello”, I.R.C.C.S. Istituto Tumori “Giovanni Paolo II”, Viale Orazio Flacco 65, 70124 Bari, Italy; (A.C.); (F.G.); (S.A.); (L.R.); (A.M.); (E.S.M.); (G.P.)
| | - Francesco Giovannelli
- Struttura Semplice Dipartimentale di Oncologia Medica per la Presa in Carico Globale del Paziente Oncologico “Don Tonino Bello”, I.R.C.C.S. Istituto Tumori “Giovanni Paolo II”, Viale Orazio Flacco 65, 70124 Bari, Italy; (A.C.); (F.G.); (S.A.); (L.R.); (A.M.); (E.S.M.); (G.P.)
| | - Silvana Acquafredda
- Struttura Semplice Dipartimentale di Oncologia Medica per la Presa in Carico Globale del Paziente Oncologico “Don Tonino Bello”, I.R.C.C.S. Istituto Tumori “Giovanni Paolo II”, Viale Orazio Flacco 65, 70124 Bari, Italy; (A.C.); (F.G.); (S.A.); (L.R.); (A.M.); (E.S.M.); (G.P.)
| | - Lucia Rinaldi
- Struttura Semplice Dipartimentale di Oncologia Medica per la Presa in Carico Globale del Paziente Oncologico “Don Tonino Bello”, I.R.C.C.S. Istituto Tumori “Giovanni Paolo II”, Viale Orazio Flacco 65, 70124 Bari, Italy; (A.C.); (F.G.); (S.A.); (L.R.); (A.M.); (E.S.M.); (G.P.)
| | - Andrea Misino
- Struttura Semplice Dipartimentale di Oncologia Medica per la Presa in Carico Globale del Paziente Oncologico “Don Tonino Bello”, I.R.C.C.S. Istituto Tumori “Giovanni Paolo II”, Viale Orazio Flacco 65, 70124 Bari, Italy; (A.C.); (F.G.); (S.A.); (L.R.); (A.M.); (E.S.M.); (G.P.)
| | - Elisabetta Sara Montagna
- Struttura Semplice Dipartimentale di Oncologia Medica per la Presa in Carico Globale del Paziente Oncologico “Don Tonino Bello”, I.R.C.C.S. Istituto Tumori “Giovanni Paolo II”, Viale Orazio Flacco 65, 70124 Bari, Italy; (A.C.); (F.G.); (S.A.); (L.R.); (A.M.); (E.S.M.); (G.P.)
| | - Valentina Ungaro
- S.C. Farmacia e U.Ma.C.A., Istituto di Ricerca e Cura a Carattere Scientifico (IRCCS), Istituto Tumori Giovanni Paolo II-Bari, 70124 Bari, Italy;
| | - Mariagrazia Lorusso
- Unità Operativa Complessa Chirurgia Toracica, Istituto di Ricerca e Cura a Carattere Scientifico (IRCCS), Istituto Tumori Giovanni Paolo II-Bari, 70124 Bari, Italy;
| | - Gennaro Palmiotti
- Struttura Semplice Dipartimentale di Oncologia Medica per la Presa in Carico Globale del Paziente Oncologico “Don Tonino Bello”, I.R.C.C.S. Istituto Tumori “Giovanni Paolo II”, Viale Orazio Flacco 65, 70124 Bari, Italy; (A.C.); (F.G.); (S.A.); (L.R.); (A.M.); (E.S.M.); (G.P.)
| |
Collapse
|
|
10
|
Bruin MM, Deijkers RLM, Bazuin R, Elzakker EPM, Pijls BG. Proton-pump inhibitors are associated with increased risk of prosthetic joint infection in patients with total hip arthroplasty: a case-cohort study. Acta Orthop 2021; 92:431-435. [PMID: 33977828 PMCID: PMC8382017 DOI: 10.1080/17453674.2021.1920687] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/31/2023] Open
Abstract
Background and purpose - Proton-pump inhibitors (PPI) have previously been associated with an increased risk of infections such as community-acquired pneumonia, gastrointestinal infections and central nervous system infection. Therefore, we evaluated a possible association between proton-pump inhibitor use and prosthetic joint infection (PJI) in patients with total hip arthroplasty (THA), because they can be stopped perioperatively or switched to a less harmful alternative.Patients and methods - A cohort of 5,512 primary THAs provided the base for a case-cohort design; cases were identified as patients with early-onset PJI. A weighted Cox proportional hazard regression model was used for the study design and to adjust for potential confounders.Results - There were 75 patients diagnosed with PJI of whom 32 (43%) used PPIs perioperatively compared with 75 PPI users (25%) in the control group of 302 patients. The risk of PJI was 2.4 times higher (95% CI 1.4-4.0) for patients using PPI. This effect remained after correction for possible confounders.Interpretation - The use of PPIs was associated with an increased risk of developing PJI after THA. Hence, the use of a PPI appears to be a modifiable risk factor for PJI.
Collapse
Affiliation(s)
- Maarten M Bruin
- Department of Orthopedic Surgery, HagaZiekenhuis, Den Haag
- Department of Orthopedic Surgery, LUMC, Leiden, The Netherlands
| | | | - Roos Bazuin
- Department of Orthopedic Surgery, HagaZiekenhuis, Den Haag
| | | | - Bart G Pijls
- Department of Orthopedic Surgery, HagaZiekenhuis, Den Haag
- Department of Orthopedic Surgery, LUMC, Leiden, The Netherlands
| |
Collapse
|
|
11
|
Elfiky A, Alsheikh M, Hosry J, Aqsa A, Yassine AA, Deeb L. Is the Use of Proton Pump Inhibitors a Predisposing Factor for Pyogenic Liver Abscesses? Gastroenterology Res 2021; 14:184-189. [PMID: 34267834 PMCID: PMC8256900 DOI: 10.14740/gr1404] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/28/2021] [Accepted: 06/02/2021] [Indexed: 02/02/2023] Open
Abstract
Background Proton pump inhibitors (PPIs) increase gastric pH by reducing acid production. The resulting alkaline milieu in the stomach increases the risk of bacterial translocation. This study aimed to investigate if there is a correlation between PPI use and developing pyogenic liver abscesses. Methods In this retrospective case-control analysis, we studied adult patients diagnosed with cryptogenic liver abscess at Northwell hospitals between 2015 and 2019. Adult patients with the diagnosis of liver abscess were included. We excluded patients with history of liver abscess prior to admission, biliary disease, hepatobiliary malignancy, or intra-abdominal infections. A group of randomly selected patients without liver abscess from the same hospitals’ database were enrolled as the control group. A multivariate logistic regression analysis was performed to adjust for potential confounding factors. Results We identified 277 patients diagnosed with first episode of pyogenic liver abscess. Cases were compared to 554 controls. Klebsiella pneumonia was the most common pathogen. PPI use was associated with an increased risk of developing a first episode of pyogenic liver abscess in univariate (odds ratio (OR): 2.36, 95% confidence interval (CI): 1.70 - 3.27), and multivariate analysis (adjusted OR: 2.27, 95% CI: 1.55 - 3.32). Conclusion This study is the first US population-based analysis to demonstrate that PPI use is associated with increased risk of developing pyogenic liver abscesses. Further prospective studies are needed to shed more light on this association and better evaluate the impact of dose and duration of PPI exposure.
Collapse
Affiliation(s)
- Ahmed Elfiky
- Department of Internal Medicine, Staten Island University Hospital-Northwell Health, Staten Island, NY, USA
| | - Mira Alsheikh
- Department of Gastroenterology, Staten Island University Hospital-Northwell Health, Staten Island, NY, USA
| | - Jeff Hosry
- Department of Internal Medicine, Staten Island University Hospital-Northwell Health, Staten Island, NY, USA
| | - Anum Aqsa
- Department of Internal Medicine, Staten Island University Hospital-Northwell Health, Staten Island, NY, USA
| | - Ahmad Abou Yassine
- Department of Internal Medicine, Staten Island University Hospital-Northwell Health, Staten Island, NY, USA
| | - Liliane Deeb
- Department of Gastroenterology, Staten Island University Hospital-Northwell Health, Staten Island, NY, USA
| |
Collapse
|
|
12
|
van der Sande LJTM, Jöbsis Q, Bannier MAGE, van de Garde EMW, Coremans JJM, de Vries F, Dompeling E, Driessen JHM. The risk of community-acquired pneumonia in children using gastric acid suppressants. Eur Respir J 2021; 58:13993003.03229-2020. [PMID: 33737412 DOI: 10.1183/13993003.03229-2020] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/21/2020] [Accepted: 02/21/2021] [Indexed: 12/13/2022]
Abstract
BACKGROUND With the increased use of acid suppressants, significant potential complications such as community-acquired pneumonia (CAP) are becoming more apparent. Paradoxically, in spite of an increased focus on potential complications, there is an increased use of acid suppressants in children and a lack of data specifically targeting the association between acid suppressants and CAP. Our main objective was to evaluate the risk of CAP in children using acid suppressants (proton pump inhibitors (PPIs) and/or histamine-2 receptor antagonists (H2RAs)). METHODS We performed a cohort study using data from the UK Clinical Practice Research Datalink. All patients aged 1 month to 18 years with a prescription of acid suppressants were included and matched to up to four unexposed children. Time-varying Cox proportional hazards models were used to estimate the risk of CAP. The cohort consisted of 84 868 exposed and 325 329 unexposed children. RESULTS Current use of PPIs and H2RAs was associated with an increased risk of CAP (adjusted hazard ratio 2.05 (95% CI 1.90-2.22) and 1.80 (95% CI 1.67-1.94), respectively). The risk was even greater in patients with respiratory disease. Long-term use (≥211 days) of PPIs and H2RAs led to a significantly greater risk of CAP compared with short-term use (<31 days). After cessation of therapy, the risk remained increased for the following 7 months. CONCLUSION The use of acid suppressants in children was associated with a doubled risk of CAP. This risk increased with chronic use and respiratory disease, and remained increased after discontinuation of therapy.
Collapse
Affiliation(s)
- Linda J T M van der Sande
- Dept of Pediatric Pulmonology, School for Public Health and Primary Care (CAPHRI), Maastricht University Medical Center (MUMC+), Maastricht, The Netherlands
| | - Quirijn Jöbsis
- Dept of Pediatric Pulmonology, School for Public Health and Primary Care (CAPHRI), Maastricht University Medical Center (MUMC+), Maastricht, The Netherlands
| | - Michiel A G E Bannier
- Dept of Pediatric Pulmonology, School for Public Health and Primary Care (CAPHRI), Maastricht University Medical Center (MUMC+), Maastricht, The Netherlands
| | - Ewoudt M W van de Garde
- Dept of Pharmaceutical Sciences, Division of Pharmacoepidemiology and Clinical Pharmacology, University of Utrecht, Utrecht, The Netherlands
| | - Jan J M Coremans
- Dept of Clinical Pharmacy and Toxicology, Maastricht University Medical Center (MUMC+), Maastricht, The Netherlands
| | - Frank de Vries
- Dept of Pharmaceutical Sciences, Division of Pharmacoepidemiology and Clinical Pharmacology, University of Utrecht, Utrecht, The Netherlands.,Dept of Clinical Pharmacy and Toxicology, Maastricht University Medical Center (MUMC+), Maastricht, The Netherlands.,School for Nutrition and Translational Research in Metabolism (NUTRIM), Maastricht University, Maastricht, The Netherlands
| | - Edward Dompeling
- Dept of Pediatric Pulmonology, School for Public Health and Primary Care (CAPHRI), Maastricht University Medical Center (MUMC+), Maastricht, The Netherlands.,E. Dompeling and J.H.M. Driessen are joint senior authors
| | - Johanna H M Driessen
- Dept of Pharmaceutical Sciences, Division of Pharmacoepidemiology and Clinical Pharmacology, University of Utrecht, Utrecht, The Netherlands.,Dept of Clinical Pharmacy and Toxicology, Maastricht University Medical Center (MUMC+), Maastricht, The Netherlands.,School for Nutrition and Translational Research in Metabolism (NUTRIM), Maastricht University, Maastricht, The Netherlands.,E. Dompeling and J.H.M. Driessen are joint senior authors
| |
Collapse
|
|
13
|
Young PJ, Bagshaw SM, Forbes AB, Nichol AD, Wright SE, Bailey M, Bellomo R, Beasley R, Brickell K, Eastwood GM, Gattas DJ, van Haren F, Litton E, Mackle DM, McArthur CJ, McGuinness SP, Mouncey PR, Navarra L, Opgenorth D, Pilcher D, Saxena MK, Webb SA, Wiley D, Rowan KM. Effect of Stress Ulcer Prophylaxis With Proton Pump Inhibitors vs Histamine-2 Receptor Blockers on In-Hospital Mortality Among ICU Patients Receiving Invasive Mechanical Ventilation: The PEPTIC Randomized Clinical Trial. JAMA 2020; 323:616-626. [PMID: 31950977 PMCID: PMC7029750 DOI: 10.1001/jama.2019.22190] [Citation(s) in RCA: 142] [Impact Index Per Article: 28.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/18/2022]
Abstract
IMPORTANCE Proton pump inhibitors (PPIs) or histamine-2 receptor blockers (H2RBs) are often prescribed for patients as stress ulcer prophylaxis drugs in the intensive care unit (ICU). The comparative effect of these drugs on mortality is unknown. OBJECTIVE To compare in-hospital mortality rates using PPIs vs H2RBs for stress ulcer prophylaxis. DESIGN, SETTING, AND PARTICIPANTS Cluster crossover randomized clinical trial conducted at 50 ICUs in 5 countries between August 2016 and January 2019. Patients requiring invasive mechanical ventilation within 24 hours of ICU admission were followed up for 90 days at the hospital. INTERVENTIONS Two stress ulcer prophylaxis strategies were compared (preferential use with PPIs vs preferential use with H2RBs). Each ICU used each strategy sequentially for 6 months in random order; 25 ICUs were randomized to the sequence with use of PPIs and then use of H2RBs and 25 ICUs were randomized to the sequence with use of H2RBs and then use of PPIs (13 436 patients randomized by site to PPIs and 13 392 randomized by site to H2RBs). MAIN OUTCOMES AND MEASURES The primary outcome was all-cause mortality within 90 days during index hospitalization. Secondary outcomes were clinically important upper gastrointestinal bleeding, Clostridioides difficile infection, and ICU and hospital lengths of stay. RESULTS Among 26 982 patients who were randomized, 154 opted out, and 26 828 were analyzed (mean [SD] age, 58 [17.0] years; 9691 [36.1%] were women). There were 26 771 patients (99.2%) included in the mortality analysis; 2459 of 13 415 patients (18.3%) in the PPI group died at the hospital by day 90 and 2333 of 13 356 patients (17.5%) in the H2RB group died at the hospital by day 90 (risk ratio, 1.05 [95% CI, 1.00 to 1.10]; absolute risk difference, 0.93 percentage points [95% CI, -0.01 to 1.88] percentage points; P = .054). An estimated 4.1% of patients randomized by ICU site to PPIs actually received H2RBs and an estimated 20.1% of patients randomized by ICU site to H2RBs actually received PPIs. Clinically important upper gastrointestinal bleeding occurred in 1.3% of the PPI group and 1.8% of the H2RB group (risk ratio, 0.73 [95% CI, 0.57 to 0.92]; absolute risk difference, -0.51 percentage points [95% CI, -0.90 to -0.12 percentage points]; P = .009). Rates of Clostridioides difficile infection and ICU and hospital lengths of stay were not significantly different by treatment group. One adverse event (an allergic reaction) was reported in 1 patient in the PPI group. CONCLUSIONS AND RELEVANCE Among ICU patients requiring mechanical ventilation, a strategy of stress ulcer prophylaxis with use of proton pump inhibitors vs histamine-2 receptor blockers resulted in hospital mortality rates of 18.3% vs 17.5%, respectively, a difference that did not reach the significance threshold. However, study interpretation may be limited by crossover in the use of the assigned medication. TRIAL REGISTRATION anzctr.org.au Identifier: ACTRN12616000481471.
Collapse
Affiliation(s)
| | - Paul J Young
- Medical Research Institute of New Zealand, Wellington
- Intensive Care Unit, Wellington Hospital, Wellington, New Zealand
| | - Sean M Bagshaw
- Department of Critical Care Medicine, University of Alberta Hospital, Edmonton, Canada
| | | | - Alistair D Nichol
- Intensive Care Unit, Alfred Hospital, Melbourne, Australia
- Australian and New Zealand Intensive Care Research Centre, Monash University, Melbourne, Australia
- University College Dublin-Clinical Research Centre, St Vincent's Hospital, Dublin, Ireland
| | - Stephen E Wright
- Intensive Care Unit, Freeman Hospital, Newcastle upon Tyne, England
| | - Michael Bailey
- Australian and New Zealand Intensive Care Research Centre, Monash University, Melbourne, Australia
- University of Melbourne, Melbourne, Australia
| | - Rinaldo Bellomo
- Australian and New Zealand Intensive Care Research Centre, Monash University, Melbourne, Australia
- University of Melbourne, Melbourne, Australia
- Intensive Care Unit, Austin Hospital, Heidelberg, Australia
| | | | - Kathy Brickell
- University College Dublin-Clinical Research Centre, St Vincent's Hospital, Dublin, Ireland
| | | | - David J Gattas
- Intensive Care Unit, Royal Prince Alfred Hospital, Camperdown, Australia
- George Institute for Global Health, University of New South Wales, Sydney, Australia
| | | | - Edward Litton
- Intensive Care Unit, Fiona Stanley Hospital, Murdoch, Australia
| | | | - Colin J McArthur
- Medical Research Institute of New Zealand, Wellington
- Department of Critical Care Medicine, Auckland City Hospital, Auckland, New Zealand
| | - Shay P McGuinness
- Medical Research Institute of New Zealand, Wellington
- Cardiothoracic and Vascular Intensive Care Unit, Auckland City Hospital, Auckland, New Zealand
| | - Paul R Mouncey
- Intensive Care National Audit and Research Centre, London, England
| | | | - Dawn Opgenorth
- Department of Critical Care Medicine, University of Alberta Hospital, Edmonton, Canada
| | - David Pilcher
- Intensive Care Unit, Alfred Hospital, Melbourne, Australia
- Australian and New Zealand Intensive Care Research Centre, Monash University, Melbourne, Australia
- Australian and New Zealand Intensive Care Society Centre for Outcome and Resource Evaluation, Camberwell, Australia
| | - Manoj K Saxena
- George Institute for Global Health, University of New South Wales, Sydney, Australia
- Intensive Care Unit, Bankstown Hospital, Bankstown, Australia
| | - Steve A Webb
- Intensive Care Unit, Royal Perth Hospital, Perth, Australia
| | - Daisy Wiley
- Intensive Care National Audit and Research Centre, London, England
| | - Kathryn M Rowan
- Intensive Care National Audit and Research Centre, London, England
| |
Collapse
|
|
14
|
Song HJ, Park H, Park S, Kwon JW. The association between proton pump inhibitor use and the risk of tuberculosis: A case-control study. Pharmacoepidemiol Drug Saf 2019; 28:830-839. [PMID: 30920070 DOI: 10.1002/pds.4773] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/14/2018] [Revised: 01/13/2019] [Accepted: 02/11/2019] [Indexed: 02/01/2023]
Abstract
PURPOSE Few studies have reported an association between proton pump inhibitor (PPI) use and tuberculosis. Tuberculosis incidence is relatively high in Asian people, and an increase in PPI prescriptions has been reported in South Korea. Thus, we investigated the association between PPI use and tuberculosis development. METHODS We conducted a case-control study on 25 672 newly diagnosed tuberculosis patients using the National Health Insurance Service-National Sample Cohort (NHIS-NSC) database (2002-2013). We selected a control group without tuberculosis using 1:1 exact matching based on age, sex, index year, insurance type, and income level. We investigated PPI exposure 2 years prior to the index date and classified the subjects into nonuser, continuous user, recent user, and former user groups. Odds ratios (ORs) and 95% confidence intervals (CIs) for tuberculosis development were calculated using conditional logistic regression. RESULTS A total of 51 344 cases and controls were analyzed. Recent PPI use (adjusted odds ratio [aOR], 1.28; 95% CI, 1.18-1.39) and continuous PPI use (aOR, 1.13; 95% CI 1.10-1.28) were significantly associated with tuberculosis development, compared with nonuse of PPIs. An increased tuberculosis incidence was not observed in the former use group compared with the nonuse group (aOR 1.05, 95% CI 0.95-1.17). CONCLUSIONS In this case-control study, we found that recent PPI use and continuous PPI use were associated with increased tuberculosis development. Although further investigation is needed, the tuberculosis risk accompanying PPI treatment should be considered.
Collapse
Affiliation(s)
- Hyun Jin Song
- School of Pharmacy, Sungkyunkwan University, Suwon, South Korea.,College of Pharmacy, University of Florida, Gainesville, FL, USA
| | - Haesuk Park
- College of Pharmacy, University of Florida, Gainesville, FL, USA
| | - Susan Park
- College of Pharmacy and Research Institute of Pharmaceutical Sciences, Kyungpook National University, Daegu, South Korea
| | - Jin-Won Kwon
- College of Pharmacy and Research Institute of Pharmaceutical Sciences, Kyungpook National University, Daegu, South Korea
| |
Collapse
|
|
15
|
Hayek S, Bekaddour N, Besson L, Alves de Sousa R, Pietrancosta N, Viel S, Smith N, Jacob Y, Nisole S, Mandal R, Wishart DS, Walzer T, Herbeuval JP, Vidalain PO. Identification of Primary Natural Killer Cell Modulators by Chemical Library Screening with a Luciferase-Based Functional Assay. SLAS DISCOVERY 2018; 24:25-37. [PMID: 30184441 DOI: 10.1177/2472555218797078] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/08/2023]
Abstract
Natural killer (NK) cells are essential players of the innate immune response that secrete cytolytic factors and cytokines such as IFN-γ when contacting virus-infected or tumor cells. They represent prime targets in immunotherapy as defects in NK cell functions are hallmarks of many pathological conditions, such as cancer and chronic infections. The functional screening of chemical libraries or biologics would greatly help identify new modulators of NK cell activity, but commonly used methods such as flow cytometry are not easily scalable to high-throughput settings. Here we describe an efficient assay to measure the natural cytotoxicity of primary NK cells where the bioluminescent enzyme NanoLuc is constitutively expressed in the cytoplasm of target cells and is released in co-culture supernatants when lysis occurs. We fully characterized this assay using either purified NK cells or total peripheral blood mononuclear cells (PBMCs), including some patient samples, as effector cells. A pilot screen was also performed on a library of 782 metabolites, xenobiotics, and common drugs, which identified dextrometorphan and diphenhydramine as novel NK cell inhibitors. Finally, this assay was further improved by developing a dual-reporter cell line to simultaneously measure NK cell cytotoxicity and IFN-γ secretion in a single well, extending the potential of this system.
Collapse
Affiliation(s)
- Simon Hayek
- 1 Chimie & Biologie, Modélisation et Immunologie pour la Thérapie (CBMIT), Université Paris Descartes, CNRS, UMR8601, Paris, France
| | - Nassima Bekaddour
- 1 Chimie & Biologie, Modélisation et Immunologie pour la Thérapie (CBMIT), Université Paris Descartes, CNRS, UMR8601, Paris, France
| | - Laurie Besson
- 2 Centre International de Recherche en Infectiologie, CIRI, Inserm, U1111, Université Claude Bernard Lyon 1, CNRS, UMR5308, École Normale Supérieure de Lyon, University of Lyon, Lyon, France.,3 Laboratoire d'Immunologie, Hospices Civils de Lyon, Centre Hospitalier Lyon Sud, Pierre-Bénite, France
| | - Rodolphe Alves de Sousa
- 1 Chimie & Biologie, Modélisation et Immunologie pour la Thérapie (CBMIT), Université Paris Descartes, CNRS, UMR8601, Paris, France
| | - Nicolas Pietrancosta
- 1 Chimie & Biologie, Modélisation et Immunologie pour la Thérapie (CBMIT), Université Paris Descartes, CNRS, UMR8601, Paris, France
| | - Sébastien Viel
- 2 Centre International de Recherche en Infectiologie, CIRI, Inserm, U1111, Université Claude Bernard Lyon 1, CNRS, UMR5308, École Normale Supérieure de Lyon, University of Lyon, Lyon, France.,3 Laboratoire d'Immunologie, Hospices Civils de Lyon, Centre Hospitalier Lyon Sud, Pierre-Bénite, France
| | - Nikaia Smith
- 1 Chimie & Biologie, Modélisation et Immunologie pour la Thérapie (CBMIT), Université Paris Descartes, CNRS, UMR8601, Paris, France
| | - Yves Jacob
- 4 CNRS, UMR3569, Unité de Génétique Moléculaire des Virus à ARN, Institut Pasteur, Université Paris Diderot, Paris, France
| | - Sébastien Nisole
- 5 Institut de Recherche en Infectiologie de Montpellier, CNRS, UMR9004, Université de Montpellier, Montpellier, France
| | - Rupasri Mandal
- 6 Departments of Biological Sciences and Computing Science, University of Alberta, Edmonton, Alberta, Canada
| | - David S Wishart
- 6 Departments of Biological Sciences and Computing Science, University of Alberta, Edmonton, Alberta, Canada
| | - Thierry Walzer
- 2 Centre International de Recherche en Infectiologie, CIRI, Inserm, U1111, Université Claude Bernard Lyon 1, CNRS, UMR5308, École Normale Supérieure de Lyon, University of Lyon, Lyon, France
| | - Jean-Philippe Herbeuval
- 1 Chimie & Biologie, Modélisation et Immunologie pour la Thérapie (CBMIT), Université Paris Descartes, CNRS, UMR8601, Paris, France
| | - Pierre-Olivier Vidalain
- 1 Chimie & Biologie, Modélisation et Immunologie pour la Thérapie (CBMIT), Université Paris Descartes, CNRS, UMR8601, Paris, France
| |
Collapse
|
|
16
|
Hamai K, Iwamoto H, Ohshimo S, Wakabayashi Y, Ihara D, Fujitaka K, Hamada H, Ono K, Hattori N. Use of proton pump inhibitors is associated with increased mortality due to nosocomial pneumonia in bedridden patients receiving tube feeding. Geriatr Gerontol Int 2018; 18:1215-1218. [PMID: 29785745 DOI: 10.1111/ggi.13450] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/16/2017] [Revised: 04/18/2018] [Accepted: 04/25/2018] [Indexed: 01/27/2023]
Abstract
AIM To investigate the association between the use of proton pump inhibitors (PPI) and nosocomial pneumonia and gastrointestinal bleeding in bedridden patients receiving tube feeding. METHODS A total of 116 bedridden hospitalized patients receiving tube feeding, of which 80 were supported by percutaneous endoscopic gastrostomy and 36 by nasogastric tube, were included in the present study. The patients were divided into two groups: 62 patients treated with PPI (PPI group) and 54 patients without PPI (non-PPI group). Mortality due to nosocomial pneumonia was evaluated using the Kaplan-Meier approach and the log-rank test. RESULTS A total of 36 patients (31%) died of nosocomial pneumonia during the observation period; the mortality rate due to nosocomial pneumonia was significantly higher in the PPI group than in the non-PPI group (P = 0.0395). Cox proportional hazard analysis showed that the use of PPI and lower levels of serum albumin were independent predictors of 2-year mortality due to nosocomial pneumonia. Gastrointestinal bleeding was observed in four patients in the non-PPI group (7.7%) and in one patient in the PPI group (1.6%); there was no significant difference between the two groups. CONCLUSION The use of PPI in bedridden tube-fed patients was independently associated with mortality due to nosocomial pneumonia, and the PPI group had a non-significant lower incidence of gastrointestinal bleeding than the non-PPI group. Geriatr Gerontol Int 2018; 18: 1215-1218.
Collapse
Affiliation(s)
- Kosuke Hamai
- Department of Respiratory Medicine, Hiroshima Prefectural Hospital, Hiroshima, Japan.,Department of Internal Medicine, Rikita Hospital, Hiroshima, Japan.,Department of Molecular and Internal Medicine, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan
| | - Hiroshi Iwamoto
- Department of Molecular and Internal Medicine, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan
| | - Shinichiro Ohshimo
- Department of Emergency and Critical Care Medicine, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan
| | - Yu Wakabayashi
- Department of Internal Medicine, Rikita Hospital, Hiroshima, Japan.,Department of Molecular and Internal Medicine, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan
| | - Daisuke Ihara
- Department of Internal Medicine, Rikita Hospital, Hiroshima, Japan.,Department of Respiratory Medicine, Hiroshima City Hiroshima Citizens Hospital, Hiroshima, Japan
| | - Kazunori Fujitaka
- Department of Molecular and Internal Medicine, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan
| | - Hironobu Hamada
- Department of Molecular and Internal Medicine, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan
| | - Koichi Ono
- Department of Internal Medicine, Rikita Hospital, Hiroshima, Japan
| | - Noboru Hattori
- Department of Molecular and Internal Medicine, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan
| |
Collapse
|
|
17
|
Haas CM, Maywald M, Goetzenich A, Stoppe C, Rink L. Proton-pump inhibitors elevate infection rate in cardiothoracic surgery patients by influencing PMN function in vitro and in vivo. J Leukoc Biol 2018; 103:777-788. [PMID: 29350834 DOI: 10.1002/jlb.5a0417-143r] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/10/2017] [Revised: 11/29/2017] [Accepted: 12/19/2017] [Indexed: 11/09/2022] Open
Abstract
Proton-pump inhibitors (PPI) as pantoprazole are highly effective acid suppressive agents that belong to the world's most sold medication. However, they are pronounced to have immunosuppressive aspects. In our study, a negative influence of PPI on functions of polymorphonuclear cells in vitro like phagocytosis, oxidative burst, chemotaxis, and killing activity was shown, whereas formation of neutrophil extracellular traps (NET)osis remained unaffected. Pantoprazole stimulation additionally reduced the production of the proinflammatory cytokine IL-1β in whole blood assay as well as the production of IL-2 and IFN-γ after whole blood stimulation with phytohaemagglutinin. Moreover, IFN-γ feedback mechanisms and signaling by STAT-1 was impaired by PPI. Cardiac surgery is accompanied by developing systemic inflammatory response syndrome with immunosuppressive aspects. We exhibited reduced oxidative burst analyzing cardiac surgery patients' samples receiving or not receiving PPI. Furthermore, a higher rate of infections in patients receiving permanent PPI medication in retrospective analysis was uncovered. Patients undergoing cardiac surgery with cardiopulmonary bypass and regular PPI medication developed significant more infections retrospectively indicating a clinical impact of the immunosuppressive influence of PPI.
Collapse
Affiliation(s)
- Carolin Maria Haas
- Faculty of Medicine, Institute of Immunology, RWTH Aachen University, University Hospital, Aachen, Germany
| | - Martina Maywald
- Faculty of Medicine, Institute of Immunology, RWTH Aachen University, University Hospital, Aachen, Germany
| | - Andreas Goetzenich
- Department of Thoracic and Cardiovascular Surgery, Faculty of Medicine, RWTH Aachen University, University Hospital, Aachen, Germany
| | - Christian Stoppe
- Department of Intensive Care Medicine, Faculty of Medicine, RWTH Aachen University, University Hospital, Aachen, Germany
| | - Lothar Rink
- Faculty of Medicine, Institute of Immunology, RWTH Aachen University, University Hospital, Aachen, Germany
| |
Collapse
|
|
18
|
Hsu WT, Lai CC, Wang YH, Tseng PH, Wang K, Wang CY, Chen L. Risk of pneumonia in patients with gastroesophageal reflux disease: A population-based cohort study. PLoS One 2017; 12:e0183808. [PMID: 28837700 PMCID: PMC5570340 DOI: 10.1371/journal.pone.0183808] [Citation(s) in RCA: 35] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/13/2017] [Accepted: 08/13/2017] [Indexed: 12/23/2022] Open
Abstract
PURPOSE The prevalence of gastroesophagel reflux disease (GERD) has steadily increased. However, the association between GERD itself and the risk of pneumonia remains unclear. This study aimed to investigate the association between GERD and long-term risk of pneumonia and to identify the major risk factors for pneumonia in GERD patients. METHODS Using the Taiwan National Health Insurance Research Database, we identified patients who were newly diagnosed with GERD and treated with proton pump inhibitors (PPIs) from January 1, 2004 through December 31, 2010. Two groups comprising 15,715 GERD cases and 15,715 non-GERD matched controls were generated using propensity score matching, thereby making the differences in basic demographics, concomitant medication use, and comorbidities between the two groups inconsiderable. RESULTS Cumulative incidence of pneumonia was significantly higher in the patients with GERD than that in the non-GERD matched controls, with an adjusted HR of 1.48 (95% confidence interval [CI] = 1.31-1.67; P < 0.001) within 6-year follow-ups. Multivariate stratified analyses revealed similar results in many subgroups, with a highest risk in individuals younger than 40 years of age (HR = 2.17, 95% CI = 1.48-3.19). Crucially, patients with GERD using PPIs longer than 4 months were at a significantly increased risk of pneumonia than those who did not use PPIs or took PPIs less than 4 months. CONCLUSIONS GERD was significantly associated with long-term risk of pneumonia, especially in GERD with PPI use longer than 4 months or in the young population. Further prospective longitudinal studies should be conducted for validation and implementing clinical practice guidelines.
Collapse
Affiliation(s)
- Wan-Tseng Hsu
- School of Pharmacy, National Taiwan University, Taipei, Taiwan
| | - Chih-Cheng Lai
- Department of Intensive Care Medicine, Chi Mei Medical Center, Liouying, Tainan, Taiwan
| | - Ya-Hui Wang
- Medical Research Center, Cardinal Tien Hospital and School of Medicine, College of Medicine, Fu Jen Catholic University, New Taipei City, Taiwan
| | - Ping-Huei Tseng
- Department of Internal Medicine, College of Medicine, National Taiwan University Hospital, Taipei, Taiwan
| | - Kun Wang
- Department of Internal Medicine, Cardinal Tien Hospital and School of Medicine, College of Medicine, Fu Jen Catholic University, New Taipei City, Taiwan
| | - Cheng-Yi Wang
- Department of Internal Medicine, Cardinal Tien Hospital and School of Medicine, College of Medicine, Fu Jen Catholic University, New Taipei City, Taiwan
| | - Likwang Chen
- Institute of Population Health Sciences, National Health Research Institutes, Zhunan, Miaoli County, Taiwan
| |
Collapse
|
|
19
|
Abstract
This narrative review summarises the benefits, risks and appropriate use of acid-suppressing drugs (ASDs), proton pump inhibitors and histamine-2 receptor antagonists, advocating a rationale balanced and individualised approach aimed to minimise any serious adverse consequences. It focuses on current controversies on the potential of ASDs to contribute to infections-bacterial, parasitic, fungal, protozoan and viral, particularly in the elderly, comprehensively and critically discusses the growing body of observational literature linking ASD use to a variety of enteric, respiratory, skin and systemic infectious diseases and complications (Clostridium difficile diarrhoea, pneumonia, spontaneous bacterial peritonitis, septicaemia and other). The proposed pathogenic mechanisms of ASD-associated infections (related and unrelated to the inhibition of gastric acid secretion, alterations of the gut microbiome and immunity), and drug-drug interactions are also described. Both probiotics use and correcting vitamin D status may have a significant protective effect decreasing the incidence of ASD-associated infections, especially in the elderly. Despite the limitations of the existing data, the importance of individualised therapy and caution in long-term ASD use considering the balance of benefits and potential harms, factors that may predispose to and actions that may prevent/attenuate adverse effects is evident. A six-step practical algorithm for ASD therapy based on the best available evidence is presented.
Collapse
Affiliation(s)
- Leon Fisher
- Frankston Hospital, Peninsula Health, Melbourne, Australia.
| | - Alexander Fisher
- The Canberra Hospital, ACT Health, Canberra, Australia
- Australian National University Medical School, Canberra, Australia
| |
Collapse
|
|
20
|
Correlation between proton pump inhibitors and risk of pyogenic liver abscess. Eur J Clin Pharmacol 2017; 73:1019-1025. [PMID: 28434021 DOI: 10.1007/s00228-017-2256-9] [Citation(s) in RCA: 37] [Impact Index Per Article: 4.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/22/2016] [Accepted: 04/18/2017] [Indexed: 02/06/2023]
Abstract
BACKGROUND/OBJECTIVE Little is known about the relationship between proton pump inhibitors use and pyogenic liver abscess. The objective of this study was to evaluate the correlation between proton pump inhibitors use and pyogenic liver abscess in Taiwan. METHODS This was a population-based case-control study using the database of the Taiwan National Health Insurance Program since 2000 to 2011. Subjects aged 20 to 84 who experienced their first episode of pyogenic liver abscess were enrolled as the case group (n = 1372). Randomly selected subjects aged 20 to 84 without pyogenic liver abscess were enrolled as the control group (n = 1372). Current use, early use, and late use of proton pump inhibitors was defined as subjects whose last one tablet for proton pump inhibitors was noted ≤30 days, between 31 to 90 days and ≥91 days before the date of admission for pyogenic liver abscess. Subjects who never received a prescription for proton pump inhibitors were defined as nonusers of proton pump inhibitors. A multivariable unconditional logistic regression model was used to measure the odds ratio and 95% confidence interval to evaluate the correlation between proton pump inhibitors use and pyogenic liver abscess. RESULTS After adjusting for confounders, the adjusted odds ratio of pyogenic liver abscess was 7.59 for subjects with current use of proton pump inhibitors (95% confidence interval 5.05, 11.4), when compared with nonusers. CONCLUSIONS Current use of proton pump inhibitors is associated with a greater risk of pyogenic liver abscess.
Collapse
|
|
21
|
Abstract
Chronic obstructive pulmonary disease (COPD) is one of the main causes of human mortalities globally after heart disease and stroke. There is increasing evidence of an aetiological association between COPD and pneumonia, the leading infectious cause of death globally in children under 5 years. In this review, we discuss the known risk factors of COPD that are also shared with pneumonia including smoking, air pollution, age and immune suppression. We review how lung pathology linked to a previous history of pneumonia may heighten susceptibility to the development of COPD in later life. Furthermore, we examine how specific aspects of COPD immunology could contribute to the manifestation of pneumonia. Based on the available evidence, a convergent relationship is becoming apparent with respect to the pathogenesis of COPD and pneumonia. This has implications for the management of both diseases, and the development of new interventions.
Collapse
Affiliation(s)
- Sanjay S Gautam
- a Breathe Well Centre, School of Medicine, University of Tasmania , Hobart , Australia
| | - Ronan F O'Toole
- a Breathe Well Centre, School of Medicine, University of Tasmania , Hobart , Australia
| |
Collapse
|
|
22
|
Lansoprazole Is Associated with Worsening Asthma Control in Children with the CYP2C19 Poor Metabolizer Phenotype. Ann Am Thorac Soc 2016; 12:878-85. [PMID: 25844821 DOI: 10.1513/annalsats.201408-391oc] [Citation(s) in RCA: 21] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/08/2023] Open
Abstract
RATIONALE Gastric acid blockade in children with asymptomatic acid reflux has not improved asthma control in published studies. There is substantial population variability regarding metabolism of and response to proton pump inhibitors based on metabolizer phenotype. How metabolizer phenotype affects asthma responses to acid blockage is not known. OBJECTIVES To determine how metabolizer phenotype based on genetic analysis of CYP2C19 affects asthma control among children treated with a proton pump inhibitor. METHODS Asthma control as measured by the Asthma Control Questionnaire (ACQ) and other questionnaires from a 6-month clinical trial of lansoprazole in children with asthma was analyzed for associations with surrogates of lansoprazole exposure (based on treatment assignment and metabolizer phenotype). Groups included placebo-treated children; lansoprazole-treated extensive metabolizers (EMs); and lansoprazole-treated poor metabolizers (PMs). Metabolizer phenotypes were based on CYP2C19 haplotypes. Carriers of the CYP2C19*2, *3, *8, *9, or *10 allele were PMs; carriers of two wild-type alleles were extensive metabolizers (EMs). MEASUREMENTS AND MAIN RESULTS Asthma control through most of the treatment period was unaffected by lansoprazole exposure or metabolizer phenotype. At 6 months, PMs displayed significantly worsened asthma control compared with EMs (+0.16 vs. -0.13; P = 0.02) and placebo-treated children (+0.16 vs. -0.23; P < 0.01). Differences in asthma control were not associated with changes in gastroesophageal reflux symptoms. Recent upper respiratory infection worsened asthma control, and this upper respiratory infection effect may be more pronounced among lansoprazole-treated PMs. CONCLUSIONS Children with the PM phenotype developed worse asthma control after 6 months of lansoprazole treatment for poorly controlled asthma. Increased exposure to proton pump inhibitor may worsen asthma control by altering responses to respiratory infections. Clinical trial registered with www.clinicaltrials.gov (NCT00604851).
Collapse
|
|
23
|
Merli M, Lucidi C, Di Gregorio V, Giannelli V, Giusto M, Ceccarelli G, Riggio O, Venditti M. The chronic use of beta-blockers and proton pump inhibitors may affect the rate of bacterial infections in cirrhosis. Liver Int 2015; 35:362-9. [PMID: 24836902 DOI: 10.1111/liv.12593] [Citation(s) in RCA: 73] [Impact Index Per Article: 7.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/02/2014] [Accepted: 05/11/2014] [Indexed: 02/07/2023]
Abstract
BACKGROUND & AIMS Bacterial infections are among the most common and life-threatening complications in cirrhosis. Qualitative and quantitative modifications of the gut microbiota, dysfunction of the intestinal barrier and multiple immune defects are factors that contribute to a pathological 'bacterial translocation' (BT), leading to a higher susceptibility to infections in cirrhotic patients. Long-term therapies, commonly adopted in cirrhotic patients, may influence BT and modify the risk of infection in these patients. To investigate the influence of chronic therapies on the prevalence and microbiological characteristics of infections in cirrhosis. METHODS Consecutive cirrhotic patients hospitalised from 2008 to 2013 were enrolled. All previous treatments were carefully recorded. Infections were actively sought out, patients were actively monitored for infection, and possible risk factors were evaluated. RESULTS Four hundred cirrhotic patients were included. The most frequent therapies were proton pump inhibitors (PPIs) (67%), non-absorbable-disaccharides (44%), beta-blockers (BBs) (39%) and non-absorbable-antibiotics (10%). Child-Pugh C (P < 0.001; OR 5; 95%CI: 2.6-9.9) and PPI therapy (P = 0.008; OR 2; 95% CI: 1.2-3.2) were found to be independent predictors of infection, and the use of BBs was a protective factor (P = 0.001; OR 0.46; 95%CI: 0.3-0.7). Cirrhotic patients with bacterial infection showed lower morbidity and mortality when taking BBs. CONCLUSIONS Proton pump inhibitors increase the risk of infection in cirrhosis and should not be prescribed in these patients without specific indications. In contrast, the use of BBs is associated with a lower rate of infection and attenuates the consequences of infections in cirrhotic patients.
Collapse
Affiliation(s)
- Manuela Merli
- Gastroenterology, Department of Clinical Medicine, 'Sapienza' University of Rome, Rome, Italy
| | | | | | | | | | | | | | | |
Collapse
|
|
24
|
Bateman BT, Bykov K, Choudhry NK, Schneeweiss S, Gagne JJ, Polinski JM, Franklin JM, Doherty M, Fischer MA, Rassen JA. Type of stress ulcer prophylaxis and risk of nosocomial pneumonia in cardiac surgical patients: cohort study. BMJ 2013; 347:f5416. [PMID: 24052582 PMCID: PMC3777797 DOI: 10.1136/bmj.f5416] [Citation(s) in RCA: 52] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/29/2022]
Abstract
OBJECTIVE To examine the relation between the type of stress ulcer prophylaxis administered and the risk of postoperative pneumonia in patients undergoing coronary artery bypass grafting. DESIGN Retrospective cohort study. SETTING Premier Research Database. PARTICIPANTS 21,214 patients undergoing coronary artery bypass graft surgery between 2004 and 2010; 9830 (46.3%) started proton pump inhibitors and 11,384 (53.7%) started H2 receptor antagonists in the immediate postoperative period. MAIN OUTCOME MEASURE Occurrence of postoperative pneumonia, assessed using appropriate diagnostic codes. RESULTS Overall, 492 (5.0%) of the 9830 patients receiving a proton pump inhibitor and 487 (4.3%) of the 11,384 patients receiving an H2 receptor antagonist developed postoperative pneumonia during the index hospital admission. After propensity score adjustment, an elevated risk of pneumonia associated with treatment with proton pump inhibitors compared with H2 receptor antagonists remained (relative risk 1.19, 95% confidence interval 1.03 to 1.38). In the instrumental variable analysis, use of a proton pump inhibitor (compared with an H2 receptor antagonist) was associated with an increased risk of pneumonia of 8.2 (95% confidence interval 0.5 to 15.9) cases per 1000 patients. CONCLUSIONS Patients treated with proton pump inhibitors for stress ulcer had a small increase in the risk of postoperative pneumonia compared with patients treated with H2 receptor antagonists; this risk remained after confounding was accounted for using multiple analytic approaches.
Collapse
Affiliation(s)
- Brian T Bateman
- Division of Pharmacoepidemiology and Pharmacoeconomics, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA
| | | | | | | | | | | | | | | | | | | |
Collapse
|
|
25
|
Triadafilopoulos G, Roorda AK, Akiyama J. Indications and safety of proton pump inhibitor drug use in patients with cancer. Expert Opin Drug Saf 2013; 12:659-72. [PMID: 23647006 DOI: 10.1517/14740338.2013.797961] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
INTRODUCTION Although the exact prevalence of proton pump inhibitor (PPI) use in cancer patients is not known, it is generally perceived to be widespread. PPIs are generally well tolerated and carry an excellent safety profile. However, increasing and longer term PPI use has raised concerns about the risk of pneumonia, bone fractures and enteric infections, and a possible interaction with clopidogrel that could increase the risk of cardiovascular events. AREAS COVERED We conducted a PubMed search of English language articles addressing the safety and adverse events associated with PPI use with particular emphasis in cancer patients. EXPERT OPINION PPIs, frequently used in cancer patients, are generally well tolerated and carry an excellent safety profile. PPI-induced acid suppression may increase the risk of Clostridium difficile or other enteric infections, nutritional deficiencies and community acquired pneumonia, all particularly important in cancer patients. The indications for PPI use in cancer patients should be carefully reviewed prior to use.
Collapse
Affiliation(s)
- George Triadafilopoulos
- Stanford University Medical Center, Division of Gastroenterology, 300 Pasteur Drive, # M-211, Stanford, CA 94305, USA.
| | | | | |
Collapse
|
|
26
|
Proton pump inhibitor use and recurrent Clostridium difficile-associated disease: a case-control analysis matched by propensity score. J Clin Gastroenterol 2012; 46:397-400. [PMID: 22298089 DOI: 10.1097/mcg.0b013e3182431d78] [Citation(s) in RCA: 52] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/18/2022]
Abstract
BACKGROUND AND AIM Clostridium difficile has been increasingly diagnosed in hospitalized patients. An association between proton pump inhibitors (PPIs) use and Clostridium difficile-associated disease (CDAD) and between recurrent CDAD has been suggested. The aim of this study is to investigate whether PPI use is associated with the development of recurrent CDAD. METHODS This was a retrospective case-control study of patients with CDAD at Yeungnam University Medical Center, seen from January 2004 to December 2008. C. difficile infection was diagnosed by the presence of C. difficile toxin in the stool. Those with recurrent disease were matched with nonrecurrent controls using multivariate matched sampling methods that incorporated the propensity score. RESULTS Recurrent CDAD developed in 28 (14.1%) of the 198 patients with diarrhea and positive C. difficile stool toxin assays. Multivariate analysis of the total population of recurrent versus nonrecurrent CDAD revealed that additional use of non-C. difficile antimicrobial therapy (concomitant with the treatment or after or both), poor response to therapy with metronidazole or vancomycin, and recent gastrointestinal surgery were risk factors for recurrent CDAD. We were able to match 21 recurrent CDAD subjects with 21 without recurrent CDAD. Among the matched patients only PPI use was associated with recurrent CDAD (ie, 47.6% vs. 4.8%, P=0.004 for recurrent vs. nonrecurrent CDAD, respectively). CONCLUSIONS Among the matched patient groups, only PPI therapy was associated with recurrent CDAD. Prospective studies are needed to clarify whether avoidance of PPIs or specific cotherapies will reduce the incidence of recurrent C. difficile-associated diarrhea.
Collapse
|
|
27
|
FURR M, COHEN ND, AXON JE, SANCHEZ LC, PANTALEON L, HAGGETT E, CAMPBELL R, TENNENT-BROWN B. Treatment with histamine-type 2receptor antagonists and omeprazole increase the risk of diarrhoea in neonatal foals treated in intensive care units. Equine Vet J 2012:80-6. [DOI: 10.1111/j.2042-3306.2011.00499.x] [Citation(s) in RCA: 36] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
|
|
28
|
Viljoen A, Mncwangi N, Vermaak I. Anti-inflammatory iridoids of botanical origin. Curr Med Chem 2012; 19:2104-27. [PMID: 22414102 PMCID: PMC3873812 DOI: 10.2174/092986712800229005] [Citation(s) in RCA: 124] [Impact Index Per Article: 9.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/22/2011] [Revised: 01/07/2012] [Accepted: 01/08/2012] [Indexed: 11/22/2022]
Abstract
Inflammation is a manifestation of a wide range of disorders which include; arthritis, atherosclerosis, Alzheimer's disease, inflammatory bowel syndrome, physical injury and infection amongst many others. Common treatment modalities are usually nonsteroidal anti-inflammatory drugs (NSAIDs) such as aspirin, paracetamol, indomethacin and ibuprofen as well as corticosteroids such as prednisone. These however, may be associated with a host of side effects due to non-selectivity for cyclooxygenase (COX) enzymes involved in inflammation and those with selectivity may be highly priced. Thus, there is a continuing search for safe and effective antiinflammatory molecules from natural sources. Research has confirmed that iridoids exhibit promising anti-inflammatory activity which may be beneficial in the treatment of inflammation. Iridoids are secondary metabolites present in various plants, especially in species belonging to the Apocynaceae, Lamiaceae, Loganiaceae, Rubiaceae, Scrophulariaceae and Verbenaceae families. Many of these ethnobotanicals have an illustrious history of traditional use alluding to their use to treat inflammation. Although iridoids exhibit a wide range of pharmacological activities such as cardiovascular, hepatoprotection, hypoglycaemic, antimutagenic, antispasmodic, anti-tumour, antiviral, immunomodulation and purgative effects this review will acutely focus on their anti-inflammatory properties. The paper aims to present a summary for the most prominent iridoid-containing plants for which anti-inflammatory activity has been demonstrated in vitro and / or in vivo.
Collapse
Affiliation(s)
- A Viljoen
- Department of Pharmaceutical Sciences, Faculty of Science, Tshwane University of Technology, Pretoria, South Africa.
| | | | | |
Collapse
|
|
29
|
Risk of fracture and pneumonia from acid suppressive drugs. World J Methodol 2011; 1:15-21. [PMID: 25237609 PMCID: PMC4145558 DOI: 10.5662/wjm.v1.i1.15] [Citation(s) in RCA: 11] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/12/2011] [Revised: 09/08/2011] [Accepted: 09/19/2011] [Indexed: 02/06/2023] Open
Abstract
A recently published systematic review and meta-analysis, incorporating all relevant studies on the association of acid suppressive medications and pneumonia identified up to August 2009, revealed that for every 200 patients, treated with acid suppressive medication, one will develop pneumonia. They showed the overall risk of pneumonia was higher among people using proton pump inhibitors (PPIs) [adjusted odds ratio (OR) = 1.27, 95% CI: 1.11-1.46, I2 = 90.5%] and Histamine-2 receptor antagonists (H2RAs) (adjusted OR = 1.22, 95% CI: 1.09-1.36, I2 = 0.0%). In the randomized controlled trials, use of H2RAs was associated with an elevated risk of hospital-acquired pneumonia (relative risk 1.22, 95% CI: 1.01-1.48, I2 = 30.6%). Another meta-analysis of 11 studies published between 1997 and 2011 found that PPIs, which reduce stomach acid production, were associated with increased risk of fracture. The pooled OR for fracture was 1.29 (95% CI: 1.18-1.41) with use of PPIs and 1.10 (95% CI: 0.99-1.23) with use of H2RAs, when compared with non-use of the respective medications. Long-term use of PPIs increased the risk of any fracture (adjusted OR = 1.30, 95% CI: 1.15-1.48) and of hip fracture risk (adjusted OR = 1.34, 95% CI: 1.09-1.66), whereas long-term H2RA use was not significantly associated with fracture risk. Clinicians should carefully consider when deciding to prescribe acid-suppressive drugs, especially for patients who are already at risk for pneumonia and fracture. Since it is unnecessary to achieve an achlorhydric state in order to resolve symptoms, we recommend using the only minimum effective dose of drug required to achieve the desired therapeutic goals.
Collapse
|
|
30
|
Fohl AL, Regal RE. Proton pump inhibitor-associated pneumonia: Not a breath of fresh air after all? World J Gastrointest Pharmacol Ther 2011; 2:17-26. [PMID: 21731913 PMCID: PMC3124633 DOI: 10.4292/wjgpt.v2.i3.17] [Citation(s) in RCA: 59] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/15/2011] [Revised: 05/25/2011] [Accepted: 06/02/2011] [Indexed: 02/06/2023] Open
Abstract
Over the past two decades, proton pump inhibitors (PPIs) have emerged as highly effective and relatively safe agents for the treatment of a variety of gastrointestinal disorders. Unfortunately, this desirable pharmacological profile has also contributed to superfluous and widespread use in both the inpatient and outpatient settings. While generally well-tolerated, research published over the last decade has associated these agents with increased risks of Clostridium difficile disease, fractures likely due to calcium malabsorption and both community-acquired (CAP) and hospital-acquired pneumonias (HAP). The mechanism behind PPI-associated pneumonia may be multifactorial, but is thought to stem from compromising the stomach’s “acid mantle” against gastric colonization of acid-labile pathogenic bacteria which then may be aspirated. A secondary postulate is that PPIs, through their inhibition of extra-gastric H+/K+-ATPase enzymes, may reduce the acidity of the upper aerodigestive tract, thus resulting in increased bacterial colonization of the larynx, esophagus and lungs. To date, several retrospective case control studies have been published looking at the association between PPI use and CAP. Some studies found a temporal relationship between PPI exposure and the incidence of pneumonia, but only two could define a dose-response relationship. Furthermore, other studies found an inverse correlation between duration of PPI use and risk of CAP. In terms of HAP, we reviewed two retrospective cohort studies and one prospective study. One retrospective study in a medical ICU found no increased association of HAP in PPI-exposed patients compared to no acid-lowering therapy, while the other in cardiothoracic surgery patients showed a markedly increased risk compared to those receiving H2RAs. The one prospective study in ICU patients showed an increased risk of HAP with PPIs, but not with H2RAs. In conclusion, the current literature shows a slight trend toward an association between PPI use and pneumonia and an increased risk with PPIs over H2RAs, but the findings are not consistent across all studies. Larger controlled trials still need to be done to better identify the risk that PPIs impart towards patients contracting CAP or HAP. Until these are completed, we will have to continue to extrapolate across smaller controlled trials to predict the associated risks in our respective patient populations. In the interim, it appears prudent to limit the use of PPIs to situations where they are clinically indicated and, in such cases, use them at the lowest effective dose. In the case of prescribing for stress ulcer prophylaxis in ICU patients, perhaps H2RAs should be used as the preferred agents over PPIs.
Collapse
Affiliation(s)
- Alexander L Fohl
- Alexander L Fohl, University of Michigan Hospitals and College of Pharmacy, Ann Arbor, MI 48109-5008,, United States
| | | |
Collapse
|
|
31
|
Sheen E, Triadafilopoulos G. Adverse effects of long-term proton pump inhibitor therapy. Dig Dis Sci 2011; 56:931-50. [PMID: 21365243 DOI: 10.1007/s10620-010-1560-3] [Citation(s) in RCA: 196] [Impact Index Per Article: 14.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/01/2010] [Accepted: 12/31/2010] [Indexed: 12/12/2022]
Abstract
Proton pump inhibitors have an excellent safety profile and have become one of the most commonly prescribed class of drugs in primary and specialty care. Long-term, sometimes lifetime, use is becoming increasingly common, often without appropriate indications. This paper is a detailed review of the current evidence on this important topic, focusing on the potential adverse effects of long-term proton pump inhibitor use that have generated the greatest concern: B12 deficiency; iron deficiency; hypomagnesemia; increased susceptibility to pneumonia, enteric infections, and fractures; hypergastrinemia and cancer; drug interactions; and birth defects. We explain the pathophysiological mechanisms that may underlie each of these relationships, review the existing evidence, and discuss implications for clinical management. The benefits of proton pump inhibitor use outweigh its risks in most patients. Elderly, malnourished, immune-compromised, chronically ill, and osteoporotic patients theoretically could be at increased risk from long-term therapy.
Collapse
Affiliation(s)
- Edward Sheen
- Department of Medicine and Division of Gastroenterology and Hepatology, Stanford University School of Medicine, Stanford, CA 94305, USA.
| | | |
Collapse
|
|
32
|
Eom CS, Jeon CY, Lim JW, Cho EG, Park SM, Lee KS. Use of acid-suppressive drugs and risk of pneumonia: a systematic review and meta-analysis. CMAJ 2010; 183:310-9. [PMID: 21173070 DOI: 10.1503/cmaj.092129] [Citation(s) in RCA: 277] [Impact Index Per Article: 18.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022] Open
Abstract
BACKGROUND Observational studies and randomized controlled trials have yielded inconsistent findings about the association between the use of acid-suppressive drugs and the risk of pneumonia. We performed a systematic review and meta-analysis to summarize this association. METHODS We searched three electronic databases (MEDLINE [PubMed], Embase and the Cochrane Library) from inception to Aug. 28, 2009. Two evaluators independently extracted data. Because of heterogeneity, we used random-effects meta-analysis to obtain pooled estimates of effect. RESULTS We identified 31 studies: five case-control studies, three cohort studies and 23 randomized controlled trials. A meta-analysis of the eight observational studies showed that the overall risk of pneumonia was higher among people using proton pump inhibitors (adjusted odds ratio [OR] 1.27, 95% confidence interval [CI] 1.11-1.46, I(2) 90.5%) and histamine(2) receptor antagonists (adjusted OR 1.22, 95% CI 1.09-1.36, I(2) 0.0%). In the randomized controlled trials, use of histamine(2) receptor antagonists was associated with an elevated risk of hospital-acquired pneumonia (relative risk 1.22, 95% CI 1.01-1.48, I(2) 30.6%). INTERPRETATION Use of a proton pump inhibitor or histamine(2) receptor antagonist may be associated with an increased risk of both community- and hospital-acquired pneumonia. Given these potential adverse effects, clinicians should use caution in prescribing acid-suppressive drugs for patients at risk.
Collapse
Affiliation(s)
- Chun-Sick Eom
- Department of Family Medicine, Seoul National University Hospital, Seoul, Republic of Korea
| | | | | | | | | | | |
Collapse
|
|
33
|
Abstract
BACKGROUND Observational studies examining the association between proton pump inhibitor (PPI) use and risk of community-acquired pneumonia are conflicting. AIM To assess systematically the association between risk of community-acquired pneumonia and PPI use in adults. METHODS We searched MEDLINE, EMBASE and CINAHL databases between 1988 and January 2010. Two reviewers independently selected studies based on eligibility criteria and extracted data. Included studies evaluated adults (> or =18 years) who took PPIs as an out-patient. The primary outcome was community-acquired pneumonia. Only observational studies with a comparison arm were included. RESULTS Over 2600 citations were reviewed. Six studies were included. All were nested case-control studies. Meta-analysis found an increased risk of community-acquired pneumonia associated with PPI use [OR 1.36 (95% CI 1.12-1.65)]; significant heterogeneity remained (I(2) 92%, P < 0.001). In exploratory subgroup analysis, short duration of use was associated with an increased odds of community-acquired pneumonia [OR 1.92 (95% CI 1.40-2.63), I(2) 75%, P = 0.003], whereas chronic use was not [OR 1.11 (95% CI 0.90-1.38), I(2) 91%, P < 0.001], a significant interaction (P < 0.005). CONCLUSIONS Heterogeneity precluded interpretation of the summary statistic. Exploratory analysis revealed that duration of PPI use may impact the risk of community-acquired pneumonia, a finding that should be explored in future studies.
Collapse
|
|
34
|
Abstract
Proton pump inhibitors (PPIs) are among the most widely used of prescription drugs. They have revolutionized the management of gastroesophageal reflux disease and other acid-related disorders. Although generally safe, concerns about possible adverse effects continue to arise. Some of these, such as gastric neoplasms, are of theoretical concern only and are related to suppression of gastric acid secretion and consequent hypergastrinemia; these have not been encountered in clinical practice despite millions of patient-years of use. Others are more idiosyncratic, unpredictable, and rare. In general, the therapeutic benefits of PPIs outweigh these potential risks. However, it is important that PPIs are only given for appropriate indications and that, whenever possible, they are used in the lowest effective dose. At present, there is no need for specific monitoring for adverse events during PPI therapy.
Collapse
|
|
35
|
Examination of selected clinical factors and medication use as risk factors for pneumonia during stroke rehabilitation: a case-control study. Am J Phys Med Rehabil 2009; 88:30-8. [PMID: 19096289 DOI: 10.1097/phm.0b013e3181909b73] [Citation(s) in RCA: 36] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/15/2023]
Abstract
OBJECTIVE To assess the association of selected clinical factors and specific medication use (proton pump inhibitors, H2 receptor antagonists [H2 blockers], and angiotensin-converting enzyme inhibitors) with presence of pneumonia in patients with stroke undergoing acute inpatient rehabilitation. DESIGN Matched case-control study in a freestanding urban academic inpatient acute rehabilitation hospital. Participants were 72 stroke survivors, consisting of 36 patients who developed pneumonia during rehabilitation hospitalization individually matched in order of decreasing priority on age, sex, stroke side, depth, and severity with 36 patients with stroke not developing pneumonia. Potential risk factors, including severe dysphagia, dietary interventions, presence of tracheostomy or feeding tube, and specific medications, were assessed for association with pneumonia during rehabilitation using separate univariate and multivariate analyses. Functional change was assessed using the functional independence measure. RESULTS Although pneumonia was associated with proton pump inhibitors or H2 blockers (odds ratio, 3.3; 95% confidence interval, 1.0-13.7), any feeding tube (odds ratio: 5.0; 95% confidence interval, 1.4-27.0), severe dysphagia (odds ratio: 15.0; 95% confidence interval, 2.3-631), and tracheostomy (odds ratio: 10; 95% confidence interval, 1.4-434.0) on univariate evaluation, none of these individual factors was significantly associated with pneumonia in a multivariate model. Risk factors were found to be highly related to each other. Odds of pneumonia did not significantly decrease with angiotensin-converting enzyme inhibitors (odds ratio: 0.9; 95% confidence interval, 0.2-3.0). Patients with pneumonia had a significantly lower functional independence measure score at discharge. CONCLUSIONS A reduction in pneumonia was not found with the use of angiotensin-converting enzyme inhibitors. Although tracheostomies, feeding tubes, proton pump inhibitor or H2 blocker use, and the presence of dysphagia were identified as risk factors for pneumonia on univariate analyses, none of these factors demonstrated an independent association with pneumonia on multivariate analyses. It may be more that the underlying impairment, rather than the assessed interventions, may confer greater risk of pneumonia in the poststroke patient.
Collapse
|
|
36
|
Abstract
The aim is to determine whether there is a pattern of allergic and immune abnormalities in children with complex medical problems. The authors retrospectively studied a convenience sample of 69 children in a case management program. Of 69 children, 42 underwent immunologic investigations during the selected time frame. Forty (95%) had 1 or more allergic disorder. Cow's milk sensitivity was present in 32 (76%). Abnormal immunoglobulin levels, IgG, IgA, and IgE were found at a greater frequency than in the general pediatric population (P <.005). Lymphocyte subset percentages were decreased for B cells (CD19) and natural killer cells (CD57, CD16/56; P <.05). Presence of a gastrostomy tube, gastroesophageal reflux disease, gastric acid suppression, and chronic constipation were common and failure to thrive, developmental delay, sleep disturbance, and recurrent otitis media were present in the majority. The authors report a higher than expected prevalence of allergic and immune abnormalities in children with complex medical problems.
Collapse
Affiliation(s)
- Anne Kelly
- Department of Pediatrics, University of Minnesota, Minneapolis, Minnesota 55455, USA
| | | |
Collapse
|
|
37
|
Alkim H, Unal S, Okur H, Imir T. Omeprazole inhibits natural killer cell functions. Dig Dis Sci 2008; 53:347-51. [PMID: 17597410 DOI: 10.1007/s10620-007-9869-2] [Citation(s) in RCA: 11] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/24/2006] [Accepted: 05/08/2007] [Indexed: 12/26/2022]
Abstract
This study was designed to determine the possible effects of omeprazole on human natural killer cells. Peripheral venous blood samples were taken from 20 peptic ulcer patients before and at the 14th and the 28th days of omeprazole treatment. Mononuclear cells were removed from blood and their capability of making conjugation with K562 target cells and lysing K562 target cells was evaluated. A significant decrease was found (P < 0.001) in the 14th and the 28th days compared with the basal value of the capability of the mononuclear cells to conjugate with the K562 target cells and to lyse them. This study demonstrated that omeprazole significantly reduces natural killer cell functions. This finding suggests that omeprazole may also have some effects on the other systems in addition to parietal cell acid secretion.
Collapse
Affiliation(s)
- Huseyin Alkim
- Department of Gastroenterology, Faculty of Medicine, Gazi University, Ankara, Turkey
| | | | | | | |
Collapse
|
|
38
|
Laheij RJF, Van Ijzendoorn MC, Janssen MJR, Jansen JBMJ. Gastric acid-suppressive therapy and community-acquired respiratory infections. Aliment Pharmacol Ther 2003; 18:847-51. [PMID: 14535879 DOI: 10.1046/j.1365-2036.2003.01744.x] [Citation(s) in RCA: 45] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
BACKGROUND Bacteria and viruses have been detected in the stomach of patients during acid-suppressive therapy. AIM To investigate whether subjects using acid-suppressive drugs more often develop community-acquired respiratory infections when compared to those who do not use acid-suppressive drugs. METHODS 700 study subjects were recruited during a single week in December 2002. Information on the prevalence of clinical manifestations of infections and complications in the preceding month was assessed by questionnaire. Furthermore, subjects were asked to report antibiotic therapy and physician visits related to possible infection. RESULTS Questionnaires were returned by 405 subjects (58%). Consumption of acid-suppressive drugs was reported by 91 individuals, of whom 79 used proton-pump inhibitors (20%) and 12 H2-receptor antagonists (3%). Overall, 101 (25%) responders reported clinical manifestations of respiratory infection in the preceding month. Subjects using acid-suppressive drugs were 2.34 times [95% confidence interval (CI) 1.4-4.1] more likely to have clinical manifestations of infection than individuals not using acid-suppressive drugs. Subjects using acid-suppressive drugs visited a physician 3.72 times more often (95% CI 2.1-6.8) for an infection and received antibiotic therapy 4.19 times more often (95% CI 2.2-8.1) in comparison to individuals not using acid-suppressive drugs. CONCLUSIONS Subjects using acid-suppressive drugs more often reported community-acquired respiratory infections in comparison to those who did not use acid-suppressive drugs.
Collapse
Affiliation(s)
- R J F Laheij
- Department of Gastroenterology, University Medical Center St Radboud, Nijmegen, The Netherlands.
| | | | | | | |
Collapse
|
|
39
|
Agastya G, West BC, Callahan JM. Omeprazole inhibits phagocytosis and acidification of phagolysosomes of normal human neutrophils in vitro. Immunopharmacol Immunotoxicol 2000; 22:357-72. [PMID: 10952036 DOI: 10.3109/08923970009016425] [Citation(s) in RCA: 62] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
We postulated omeprazole inhibition of the neutrophil proton pump, impairing phagocytosis and phagolysosomal acidification. Neutrophils from healthy human beings were treated with omeprazole prodrug 0.5 mM/l or acid activated omeprazole 0.5 mM/l, then incubated with killed Saccharomyces cerevisiae stained with bromcresol purple. Wet mounts were done at 10, 30 and 60 minutes. Percent neutrophils phagocytosing, percent yeast phagocytosed, and yeast per phagocytosing neutrophil were significantly decreased in acid activated omeprazole compared to controls and omeprazole prodrug. In contrast, percent acidification of intracellular yeast was significantly lower in both omeprazole prodrug and acid activated omeprazole compared to controls. Over time, control neutrophils showed an increase in percent yeast phagocytosed and yeast per phagocytosing neutrophil. When treated with acid activated omeprazole, the percent of neutrophils phagocytosing progressively decreased over time. We observed 1) omeprazole prodrug does not inhibit neutrophil phagocytosis but does inhibit phagolysosomal acidification, whereas 2) acid activated omeprazole inhibits both neutrophil phagocytosis and phagolysosome acidification. We conclude that omeprazole impairs these neutrophil functions in vitro.
Collapse
Affiliation(s)
- G Agastya
- The Department of Medicine Research Laboratory, Huron Hospital, East Cleveland, OH 44112, USA
| | | | | |
Collapse
|
|
40
|
Sasakii M, Joh T, Yokoyama Y, Seno K, Tsuchida K, Kurokawa T, Itoh M. The therapeutic effect of proton pump inhibitors on Helicobacter pylori-positive gastric ulcers. J Pharm Pharmacol 1999; 51:825-30. [PMID: 10467958 DOI: 10.1211/0022357991773023] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/31/2022]
Abstract
The aim of the present study was to elucidate the risk factors that could delay gastric ulcer healing when either a proton pump inhibitor or an H2-receptor antagonist is used for gastric ulcer treatment. Endoscopically-diagnosed gastric ulcer patients (216 men and 96 women, mean age: 57+/-13 years) were investigated. All patients were consecutively recruited and randomly assigned to receive H2-receptor antagonist (n = 196) or proton pump inhibitor (n = 116) treatment for eight weeks. Chi-squared tests and multivariate analysis to determine factors influencing ulcer healing were used to analyse the patients profiles, endoscopic findings, and Helicobacter pylori-infection status. In the H2-receptor antagonist group, the most important risk factor was a large ulcer size (> 2 cm diam.), followed by a linear shape of the ulcer, undermining tendency of ulcer, previous history of gastric ulcer, and H. pylori infection. In the proton pump inhibitor group, linear shape of the ulcer was the only significant risk factor for slow ulcer healing; other factors, including H. pylori infection, were insignificant. These results indicate that ulcer morphology may be the most important information for predicting ulcer healing, and that H. pylori infection does not delay gastric ulcer healing when proton pump inhibitor treatment is used.
Collapse
Affiliation(s)
- M Sasakii
- Department of Internal Medicine, Nagoya City University Medical School, Aichi, Japan
| | | | | | | | | | | | | |
Collapse
|
|
41
|
Capodicasa E, De Bellis F, Pelli MA. Effect of lansoprazole on human leukocyte function. Immunopharmacol Immunotoxicol 1999; 21:357-77. [PMID: 10319286 DOI: 10.3109/08923979909052768] [Citation(s) in RCA: 27] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/13/2023]
Abstract
Recent findings on the capacity of omeprazole to influence various leukocyte functions, in vitro, raises the question on the potential use of protonic pump inhibitors, commonly used in the treatment of acid-secretion-related disorders, as immunomodulators. The aim of this study was to evaluate the in vitro effect of lansoprazole on human natural killer (NK) cell cytotoxix activity, chemotaxis and superoxide anion (O2*-) generation exerted by polymorphonucleated cells (PMNs). NK cytotoxicity activity was assessed by a 51Cr release assay, PMN chemotaxis was determined by an under agarose method and O2*- generation was analyzed on the basis of reduced cytochrome C. Incubation times with lansoprazole was 30 min for PMNs and 1-4.5 hours for NK cells, respectively. Lansoprazole induced significant dose dependent inhibition of NK cell activity and PMN functions at concentrations ranging from 100 to 1,000 microM. This study demonstrate that lansoprazole, like omeprazole, inhibits several leukocyte functions, in vitro, then suggesting that protonic pump inhibitors are able to provoke these effects, at least at certain doses.
Collapse
Affiliation(s)
- E Capodicasa
- Institute of Internal Medicine and Oncological Sciences, Perugia University, Italy
| | | | | |
Collapse
|
|
42
|
Holm A, Sundqvist T, Oberg A, Magnusson KE. Mechanical manipulation of polymorphonuclear leukocyte plasma membranes with optical tweezers causes influx of extracellular calcium through membrane channels. Med Biol Eng Comput 1999; 37:410-2. [PMID: 10505396 DOI: 10.1007/bf02513321] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/29/2022]
Abstract
Optical tweezers are used mechanically to manipulate the plasma membrane of polymophonuclear leukocytes attached to the bottom of a glass manipulation chamber. The laser trapping beam is dragged across the membrane of cells in calcium-containing and calcium-depleted extracellular medium. This treatment causes a significant rise in the intracellular calcium concentration compared with controls, in cells in calcium-containing medium (239.8 +/- 49.0% against 75.4 +/- 16.4%, respectively), but not in cells in calcium-depleted medium (69.1 +/- 9.6% against 83.4 +/- 18.5%, respectively), indicating that the calcium rise is caused by an influx of calcium from the environment. The rise in calcium concentration is blocked (23.5 +/- 7.1% against 17.1 +/- 4.1%, respectively) by the addition of lansoprazole, indicating that the influx is not due to unspecific membrane damage caused by the mechanical manipulation of the cell. It can therefore be concluded that mechanical manipulation of the neutrophil membrane, in the piconewton force range exerted by the optical tweezer, does not damage the plasma membrane but stimulates a mechanically inducible, membrane channel-mediated influx of extracellular calcium.
Collapse
Affiliation(s)
- A Holm
- Division of Medical Microbiology, Faculty of Health Sciences, Linköping University, Sweden.
| | | | | | | |
Collapse
|
|
43
|
Bolay H, Karabudak R, Aybay C, Candemir H, Varli K, Imir T, Kansu E. Alpha interferon treatment in myasthenia gravis: effects on natural killer cell activity. J Neuroimmunol 1998; 82:109-15. [PMID: 9585806 DOI: 10.1016/s0165-5728(97)00146-x] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
The efficacy of recombinant interferon-alpha (rIFN alpha), on natural killer (NK) cell cytotoxic activity, CD3+, CD4+, CD8+, CD56+, HLA-DR+ lymphocyte counts, anti-acetylcholine receptor antibody (AChR Ab) levels, single fibre electromyography findings (SFEMG) and clinical course were evaluated in patients with myasthenia gravis (MG). During the IFN alpha treatment (3 mu, subcutaneous, 3 times a week), NK cell cytotoxicity and CD4+/8+ ratio increased, NK cell count remarkably decreased, and no significant clinical or SFEMG changes were observed. This preliminary open study in MG patients has demonstrated enhanced NK activity per unit NK cell after IFN alpha therapy. Although lymphocyte phenotypes and NK function approached normal levels during therapy, a higher dose of IFN alpha may be required for a significant clinical response. It has been also concluded that 6 months of IFN alpha therapy seems to be safe in MG, though in patients with malignancy, IFN alpha may cause increased autoimmunity, AChR positivity and MG.
Collapse
Affiliation(s)
- H Bolay
- Department of Neurology, Hacettepe University, School of Medicine, Ankara, Turkey
| | | | | | | | | | | | | |
Collapse
|
|
44
|
Aybay C, Imir T. Tumor necrosis factor (TNF) induction from monocyte/macrophages by Candida species. Immunobiology 1996; 196:363-74. [PMID: 9061377 DOI: 10.1016/s0171-2985(96)80059-3] [Citation(s) in RCA: 20] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/03/2023]
Abstract
Candida albicans was studied for its capacity to induce TNF production from mouse peritoneal macrophages (PM phi). TNF activities in the culture supernatants of Candida-stimulated PM phi and human peripheral blood monocytes were assessed by L 929 bioassay and ELISA respectively. C. albicans induced TNF production from PM phi and human peripheral blood monocytes in a dose-dependent manner. Although the capacity was lesser than live form, heat-killed C. albicans was also found to be capable of stimulating PM phi to induce TNF. The filtered supernatant of 24 h cultured live C. albicans had no effects on TNF production from PM phi. Saccharomyces cerevisiae-extracted mannan, a yeast cell wall antigen, induced TNF production from PM phi in a dose-dependent manner. Thus, the effect of C. albicans on TNF production from PM phi was seemed to be directly related to the presence of the yeast cell wall itself. Compatible with these data, when various candida species (C. albicans, C. tropicalis, C. pseudotropicalis. C. lusitaniae, C. krusei, C. parapsilosis, C. guilliermondii, C. stellatoidea, C. glabrata) and S. cerevisiae were compared to each other, at a concentration of 2 x 10(6) yeast cells/ml from each species, it was observed that TNF inducing capacities varied. Among the species used in this study, C. guilliermondii and C. glabrata, of which the yeast cell size were the smallest ones, were found to be less potent than that of others to induce TNF from PM phi.
Collapse
Affiliation(s)
- C Aybay
- Department of Microbiology & Immunology, Gazi University, Medical School, Ankara, Turkey
| | | |
Collapse
|