|
1
|
Eladawy RM, Ahmed LA, Salem MB, Hammam OA, Mohamed AF, Salem HA, El-Sayed RM. Impact of different gastric acid suppressants on chronic unpredictable mild stress-induced cognitive impairment in rats: A possible involvement of gut dysbiosis. Toxicol Appl Pharmacol 2024; 492:117126. [PMID: 39406336 DOI: 10.1016/j.taap.2024.117126] [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: 05/06/2024] [Revised: 10/08/2024] [Accepted: 10/10/2024] [Indexed: 10/18/2024]
Abstract
Recently, clinical evidence indicates that gastric acid suppressants are associated with an increased risk of the development of cognitive impairment and dementia, especially in elderly patients and those with mild cognitive impairment. Therefore, the aim of this research was to explore the impact of different gastric acid suppressants use, famotidine (Famo), esomeprazole (Esome) and vonoprazan (Vono) in the absence or the presence of chronic unpredictable mild stress (CUMS) on several memory tasks with examination of the role of gut dysbiosis. In the present study, rats received famotidine (3.7 mg/kg/day, p.o.) or esomeprazole (3.7 mg/kg/day, p.o.) or vonoprazan (1.85 mg/kg/day, p.o.) for 7 weeks with or without exposure to CUMS. Remarkably, CUMS with different acid suppressants caused a significant decrease in all memory tasks in late CUMS in the current investigation. CUMS with acid suppressants also revealed a marked alteration in the fecal Firmicutes/Bacteroidetes ratio compared to CUMS alone. This gut microbiome alteration was associated with an alteration in gut membrane integrity, as revealed by colonic histopathology and an elevation of systemic inflammatory markers. Besides, upregulation of hippocampal amyloid β and p-tau proteins and modification of brain histopathology were noticed. Our findings support the detrimental effect of gastric acid suppressants, especially proton pump inhibitors, on cognitive impairment in the presence of stress, with the possible involvement of gut dysbiosis.
Collapse
Affiliation(s)
- Reem M Eladawy
- Pharmacology & Toxicology Department, Faculty of Pharmacy, Sinai University - Arish Branch, Arish 45511, Egypt.
| | - Lamiaa A Ahmed
- Pharmacology & Toxicology Department, Faculty of Pharmacy, Cairo University, Cairo, Egypt.
| | - Maha B Salem
- Pharmacology Department, Theodor Bilharz Research Institute, Giza, Egypt
| | - Olfat A Hammam
- Pathology Department, Theodor Bilharz Research Institute, Giza, Egypt
| | - Ahmed F Mohamed
- Pharmacology & Toxicology Department, Faculty of Pharmacy, Cairo University, Cairo, Egypt; Faculty of Pharmacy, King Salman International University (KSIU), South Sinai 46612, Egypt
| | - Hesham A Salem
- Pharmacology & Toxicology Department, Faculty of Pharmacy, Cairo University, Cairo, Egypt
| | - Rehab M El-Sayed
- Pharmacology & Toxicology Department, Faculty of Pharmacy, Sinai University - Arish Branch, Arish 45511, Egypt
| |
Collapse
|
|
2
|
Alanazi AS, Almutairi H, Gupta JK, Mohanty D, Rath D, AlOdan AA, Mahal A, Khatib MN, Gaidhane S, Zahiruddin QS, Rustagi S, Satapathy P, Serhan HA. Osseous implications of proton pump inhibitor therapy: An umbrella review. Bone Rep 2024; 20:101741. [PMID: 38348455 PMCID: PMC10859261 DOI: 10.1016/j.bonr.2024.101741] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/07/2023] [Revised: 01/29/2024] [Accepted: 01/31/2024] [Indexed: 02/15/2024] Open
Abstract
Background Proton pump inhibitors (PPIs) are among the most commonly prescribed medications worldwide for acid-related disorders. While their short-term efficacy and safety are well-established, concerns regarding their long-term effects on bone health have emerged. This umbrella review aimed to synthesize the available findings on the associations between PPI use and bone metabolism outcomes. Methods An electronic search was conducted using PubMed, Web of Science, Embase, and the Cochrane Database up to September 16, 2023. Systematic reviews and meta-analyses of randomized controlled trials (RCTs) and observational studies that evaluated the relationship between PPIs and bone metabolism outcomes were included. Data extraction, quality appraisal, and synthesis were performed in line with the Joanna Briggs Institute and PRISMA guidelines. The strength of the evidence was graded using the GRADE criteria. Statistical analysis was performed in R version 4.3. Results Out of 299 records, 27 studies met the inclusion criteria. The evidence indicated a statistically significant increased risk of fractures, notably hip, spine, and wrist fractures, in PPI users. PPI use was associated with changes in Bone Mineral Density (BMD) across various bones, though the clinical relevance of these changes remains uncertain. Furthermore, PPI-induced hypomagnesemia, which can influence bone health, was identified. A notable finding was the increased risk of dental implant failures in PPI users. However, the certainty of most of the evidence ranged from very low to low based on GRADE criteria. Conclusion The long-term use of PPIs may be associated with adverse bone health outcomes, including increased fracture risk, alterations in BMD, hypomagnesemia, and dental implant failure. While these findings highlight potential concerns for long-term PPI users, the current evidence's low certainty underscores the need for robust, high-quality research to clarify these associations.
Collapse
Affiliation(s)
- Abdullah S. Alanazi
- Department of Clinical Pharmacy, College of Pharmacy, Jouf University, Al-Jouf, Saudi Arabia
| | - Hadiah Almutairi
- Department of Pharmacy Practice, College of Pharmacy, University of Hafr Albatin, Saudi Arabia
| | | | - Dibyalochan Mohanty
- Centre for Nano Medicine, Department of Pharmaceutics, School of Pharmacy, Anurag University, Hyderabad, India
| | - Deepankar Rath
- Department of Pharmacology, School of Pharmacy and Life Sciences, Centurion University of Technology and Management, Odisha, India
| | - Ali A. AlOdan
- Department of Family Medicine, Security Forces Hospital, Riyadh, Saudi Arabia
| | - Ahmed Mahal
- Department of Medical Biochemical Analysis, College of Health Technology, Cihan University-Erbil, Erbil, Kurdistan Region, Iraq
| | - Mahalaqua Nazli Khatib
- Division of Evidence Synthesis, Global Consortium of Public Health and Research, Datta Meghe Institute of Higher Education, Wardha, India
| | - Shilpa Gaidhane
- One Health Centre (COHERD), Jawaharlal Nehru Medical College, Datta Meghe Institute of Higher Education, Wardha, India
| | - Quazi Syed Zahiruddin
- South Asia Infant Feeding Research Network (SAIFRN), Division of Evidence Synthesis, Global Consortium of Public Health and Research, Datta Meghe Institute of Higher Education, Wardha, India
| | - Sarvesh Rustagi
- School of Applied and Life Sciences, Uttaranchal University, Dehradun, Uttarakhand, India
| | - Prakasini Satapathy
- Center for Global Health Research, Saveetha Medical College and Hospital, Saveetha Institute of Medical and Technical Sciences, Saveetha University, Chennai, India
- School of Pharmacy, Graphic Era Hill University, Dehradun, India
- Medical Laboratories Techniques Department, AL-Mustaqbal University, 51001 Hillah, Babil, Iraq
| | | |
Collapse
|
|
3
|
Narula N, Chang NH, Mohammad D, Wong ECL, Ananthakrishnan AN, Chan SSM, Carbonnel F, Meyer A. Food Processing and Risk of Inflammatory Bowel Disease: A Systematic Review and Meta-Analysis. Clin Gastroenterol Hepatol 2023; 21:2483-2495.e1. [PMID: 36731590 DOI: 10.1016/j.cgh.2023.01.012] [Citation(s) in RCA: 42] [Impact Index Per Article: 21.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/03/2022] [Revised: 12/29/2022] [Accepted: 01/12/2023] [Indexed: 02/04/2023]
Abstract
BACKGROUND & AIMS Several studies have been published on the association between food processing and risks of Crohn's disease (CD) and ulcerative colitis (UC), with some variability in results. We performed a systematic literature review and meta-analysis to study this association. METHODS From PubMed, Medline, and Embase until October 2022, we identified cohort studies that studied the association between food processing and the risk of CD or UC. Risk of bias of the included studies was assessed by the Newcastle-Ottawa scale. We computed pooled hazard ratios (HRs) and 95% confidence intervals (CIs) using random-effects meta-analysis based on estimates and standard errors. RESULTS A total of 1,068,425 participants were included (13,594,422 person-years) among 5 cohort studies published between 2020 and 2022. Four of the 5 included studies were scored as high quality. The average age of participants ranged from 43 to 56 years; 55%-83% were female. During follow-up, 916 participants developed CD, and 1934 developed UC. There was an increased risk for development of CD for participants with higher consumption of ultra-processed foods compared with those with lower consumption (HR, 1.71; 95% CI, 1.37-2.14; I2 = 0%) and a lower risk of CD for participants with higher consumption of unprocessed/minimally processed foods compared with those with lower consumption (HR, 0.71; 95% CI, 0.53-0.94; I2 = 11%). There was no association between risk of UC and ultra-processed foods (HR, 1.17; 95% CI, 0.86-1.61; I2 = 74%) or unprocessed/minimally processed foods (HR, 0.84; 95% CI, 0.68-1.02; I2 = 0%). CONCLUSIONS Higher ultra-processed food and lower unprocessed/minimally processed food intakes are associated with higher risk of CD but not UC.
Collapse
Affiliation(s)
- Neeraj Narula
- Department of Medicine (Division of Gastroenterology) and Farncombe Family Digestive Health Research Institute, McMaster University, Hamilton, ON, Canada.
| | - Nicole H Chang
- Department of Medicine (Division of Gastroenterology) and Farncombe Family Digestive Health Research Institute, McMaster University, Hamilton, ON, Canada
| | - Danah Mohammad
- Department of Medicine (Division of Gastroenterology) and Farncombe Family Digestive Health Research Institute, McMaster University, Hamilton, ON, Canada
| | - Emily C L Wong
- Department of Medicine (Division of Gastroenterology) and Farncombe Family Digestive Health Research Institute, McMaster University, Hamilton, ON, Canada
| | - Ashwin N Ananthakrishnan
- Division of Gastroenterology, Massachusetts General Hospital, and Harvard Medical School, Boston, Massachusetts
| | - Simon S M Chan
- Department of Gastroenterology, Norfolk and Norwich University Hospital and Norwich Medical School, University of East Anglia, Norwich, United Kingdom
| | - Franck Carbonnel
- Department of Gastroenterology, University Hospital of Bicêtre, Assistance Publique-Hôpitaux de Paris and Université Paris-Saclay, Le Kremlin Bicêtre, France
| | - Antoine Meyer
- Department of Gastroenterology, University Hospital of Bicêtre, Assistance Publique-Hôpitaux de Paris and Université Paris-Saclay, Le Kremlin Bicêtre, France
| |
Collapse
|
|
4
|
Nguyen-Soenen J, Rat C, Gaultier A, Schirr-Bonnans S, Tessier P, Fournier JP. Effectiveness of a multi-faceted intervention to deprescribe proton pump inhibitors in primary care: protocol for a population-based, pragmatic, cluster-randomized controlled trial. BMC Health Serv Res 2022; 22:219. [PMID: 35177042 PMCID: PMC8851828 DOI: 10.1186/s12913-022-07496-3] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/20/2021] [Accepted: 01/13/2022] [Indexed: 02/07/2023] Open
Abstract
Background Inappropriately using proton pump inhibitors (PPI) is associated with severe adverse drug reactions and may have major consequences on healthcare costs. Deprescribing (the process by which a healthcare professional supervises the withdrawal of an inappropriate medication, to manage polypharmacy and improve outcomes) should be considered when an inappropriate PPI prescription is identified. Deprescribing interventions directed solely to prescribers have limited efficacy and are rarely targeted to patients. The aim of this trial is to assess the efficacy of a multi-faceted intervention with patients and general practitioners (GPs) to deprescribe PPI. Methods We will conduct a pragmatic, cluster-randomized, population-based, controlled trial in two regions of Western France. GPs with practices with over 100 patients, and their adult patient to whom over 300 defined daily doses (DDD) of PPIs have been dispensed in the year before baseline will be included. A total of 1300 GPs and 33,000 patients will be cluster-randomized by GPs practices. Three arms will be compared: i) a multi-faceted intervention associating a) a patient education brochure about PPI deprescribing sent directly to patients (the brochure was designed using a mixed-methods study), and b) a personalized letter with the Bruyere’s PPI deprescribing algorithm sent to their respective GPs, or ii) a single intervention where only the GPs received the letter and algorithm, or iii) no intervention. The primary outcome will be PPI deprescribing, defined as the proportion of patients achieving at least a 50% decrease in the amount of PPI dispensed to them (DDD/year) at 12 months compared to baseline. Secondary outcomes will include incremental cost-utility ratio (using EQ-5D-5L scale and National Health Insurance’s database), acid rebound (using the Gastroesophageal Reflux Disease Impact Scale), and the patients’ attitudes towards deprescribing (using the French rPATD). Discussion Based on previous trials, we anticipate more than 10% “successful PPI deprescribing” in the multi-faceted intervention compared to the single intervention on GPs and the control arm. The study has been funded through a national grant and will be launched in autumn 2020, for early results by the end of 2022. Trial registration Clinicaltrials.gov NCT04255823; first registered on February 5, 2020. Supplementary Information The online version contains supplementary material available at 10.1186/s12913-022-07496-3.
Collapse
Affiliation(s)
- Jérôme Nguyen-Soenen
- Département de Médecine Générale, Faculté de Médecine, Université de Nantes, Nantes, France. .,SPHERE - UMR INSERM 1246, Université de Nantes, Université de Tours, Nantes, France.
| | - Cédric Rat
- Département de Médecine Générale, Faculté de Médecine, Université de Nantes, Nantes, France
| | - Aurélie Gaultier
- Département de Médecine Générale, Faculté de Médecine, Université de Nantes, Nantes, France.,Direction de la recherche, Plateforme de Méthodologie et Biostatistique, CHU Nantes, Nantes, France
| | - Solène Schirr-Bonnans
- CHU de Nantes, Service Évaluation Économique et Développement des Produits de Santé, Nantes Université, Nantes, France
| | - Philippe Tessier
- SPHERE - UMR INSERM 1246, Université de Nantes, Université de Tours, Nantes, France.,CHU de Nantes, Service Évaluation Économique et Développement des Produits de Santé, Nantes Université, Nantes, France
| | - Jean-Pascal Fournier
- Département de Médecine Générale, Faculté de Médecine, Université de Nantes, Nantes, France.,SPHERE - UMR INSERM 1246, Université de Nantes, Université de Tours, Nantes, France
| |
Collapse
|
|
5
|
ACG Clinical Guideline for the Diagnosis and Management of Gastroesophageal Reflux Disease. Am J Gastroenterol 2022; 117:27-56. [PMID: 34807007 PMCID: PMC8754510 DOI: 10.14309/ajg.0000000000001538] [Citation(s) in RCA: 396] [Impact Index Per Article: 132.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/04/2021] [Accepted: 08/30/2021] [Indexed: 01/30/2023]
Abstract
Gastroesophageal reflux disease (GERD) continues to be among the most common diseases seen by gastroenterologists, surgeons, and primary care physicians. Our understanding of the varied presentations of GERD, enhancements in diagnostic testing, and approach to patient management have evolved. During this time, scrutiny of proton pump inhibitors (PPIs) has increased considerably. Although PPIs remain the medical treatment of choice for GERD, multiple publications have raised questions about adverse events, raising doubts about the safety of long-term use and increasing concern about overprescribing of PPIs. New data regarding the potential for surgical and endoscopic interventions have emerged. In this new document, we provide updated, evidence-based recommendations and practical guidance for the evaluation and management of GERD, including pharmacologic, lifestyle, surgical, and endoscopic management. The Grading of Recommendations, Assessment, Development, and Evaluation system was used to evaluate the evidence and the strength of recommendations. Key concepts and suggestions that as of this writing do not have sufficient evidence to grade are also provided.
Collapse
|
|
6
|
Abstract
Gastroesophageal reflux disease (GERD) continues to be among the most common diseases seen by gastroenterologists, surgeons, and primary care physicians. Our understanding of the varied presentations of GERD, enhancements in diagnostic testing, and approach to patient management have evolved. During this time, scrutiny of proton pump inhibitors (PPIs) has increased considerably. Although PPIs remain the medical treatment of choice for GERD, multiple publications have raised questions about adverse events, raising doubts about the safety of long-term use and increasing concern about overprescribing of PPIs. New data regarding the potential for surgical and endoscopic interventions have emerged. In this new document, we provide updated, evidence-based recommendations and practical guidance for the evaluation and management of GERD, including pharmacologic, lifestyle, surgical, and endoscopic management. The Grading of Recommendations, Assessment, Development, and Evaluation system was used to evaluate the evidence and the strength of recommendations. Key concepts and suggestions that as of this writing do not have sufficient evidence to grade are also provided.
Collapse
|
|
7
|
Use of acid-suppressive drugs and risk of fracture in children and young adults: a meta-analysis of observational studies. Eur J Clin Pharmacol 2021; 78:365-373. [PMID: 34705066 DOI: 10.1007/s00228-021-03245-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/09/2021] [Accepted: 10/21/2021] [Indexed: 10/20/2022]
Abstract
BACKGROUND Acid-suppressive drugs (ASDs) are being used by increasing number of children and young adults. However, evidence for a relationship between ASD use and the risk of fracture in these groups of patients is conflicting. We conducted a meta-analysis to evaluate the risk of fracture in children and young adults exposed to ASDs. METHODS A literature search was performed using the PUBMED, EMBASE, and Cochrane Library databases from inception to November 2020. Pooled relative risks (RRs) and 95% confidence intervals (CIs) were calculated to determine the relationship of ASD use with fracture risk in children and young adults. RESULTS Six studies reporting the outcomes of more than 900,000 children and young adults with ASD use were included in the meta-analysis. The pooled RR for fracture with the use of proton pump inhibitors (PPIs) versus non-use of these medications was 1.17 (95% CI = 1.1-1.25; P < 0.001) in children and 1.2 (95% CI = 0.87-1.65; P = 0.272) in young adults. By contrast, the use of histamine H2-receptor antagonists (H2RAs) was not significantly associated with fracture risk in children (RR, 1.08, 95% CI = 0.99-1.17; P = 0. 083) or young adults (RR, 1.08, 95% CI = 0.82-1.42; P = 0.589). Significant statistical and clinical heterogeneity among studies were determined for the main analysis and most of the subgroup analyses. CONCLUSIONS Our study provides evidence linking PPI use to an increased risk of fracture in children. Thus, the use of PPIs in these patients should be carefully considered. However, randomized controlled studies are needed to determine causality and the role of unmeasured/residual confounding factors in this association.
Collapse
|
|
8
|
Li J, Xie X, Liu W, Gu F, Zhang K, Su Z, Wen Q, Sui Z, Zhou P, Yu T. Acid-Suppressive Drugs and Risk of Fracture in Children and Young Adults: A Meta-Analysis of Observational Studies. Front Pharmacol 2021; 12:712939. [PMID: 34421609 PMCID: PMC8378906 DOI: 10.3389/fphar.2021.712939] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/21/2021] [Accepted: 06/30/2021] [Indexed: 01/11/2023] Open
Abstract
Background: Recent studies have suggested that proton pump inhibitors (PPIs) and histamine type 2 receptor antagonists (H2RAs) may increase the risk of fracture. We performed a meta-analysis to evaluate the risk of fracture with PPIs and H2RAs use in children and young adults. Methods: PubMed, EMBASE database, Cochrane Library, and Web of Science for relevant articles published before May 2021 were searched. We included all the observational studies reporting on the risk of fracture with acid-suppressive drug (PPIs and H2RAs) use in children and young adults. We calculated pooled risk ratios (RRs) for fracture using random-effects models and conducted subgroup analyses. Results: A total of six studies were included in our analysis. Pooled analysis of PPIs use showed significant risk for fracture (RR = 1.23; 95% CI, 1.12–1.34; I2 = 79.3), but not significant for PPIs combined with H2RAs use (RR = 1.22; 95% CI, 0.94–1.60; I2 = 44.0%), as well as for H2RAs use alone (RR = 1.08; 95% CI, 0.94-1.24; I2 = 84.1%). Grouping of studies by region showed a significantly increased fracture risk with PPIs use in North America (RR = 1.24; 95% CI, 1.16–1.32; I2 =0.0%) than in Europe (RR = 1.23; 95% CI, 1.00–1.52; I2 = 94.6%) and Asia (RR = 1.10; 95% CI, 0.96–1.25). However, there was no significant association between the H2RAs use and the fracture risk in North America (RR = 1.08; 95% CI, 1.00–1.09; I2 = 0.0%). Moreover, PPIs use showed an increased risk of fracture in women (RR = 1.13; 95% CI, 1.07–1.19; I2 = 0.0%), whereas there was no significant association between the PPIs use and the risk of fracture in men (RR = 0.93; 95% CI, 0.66–1.31; I2 = 0.0%). Conclusion: PPIs use alone could increase the risk of fracture in children and young adults, but not for PPIs combined with H2RAs use or H2RAs use alone. Clinicians should exercise caution when prescribing PPIs for patients.
Collapse
Affiliation(s)
- Jiangbi Li
- Department of Orthopedics, The First Hospital of Jilin University, Changchun, China
| | - Xiaoping Xie
- Department of Orthopedics, The First Hospital of Jilin University, Changchun, China
| | - Weibing Liu
- Department of Orthopedics, The First People's Hospital of Yunnan Province, Kunming, China
| | - Feng Gu
- Department of Orthopedics, The First Hospital of Jilin University, Changchun, China
| | - Ke Zhang
- Department of Orthopedics, The First Hospital of Jilin University, Changchun, China
| | - Zilong Su
- Department of Orthopedics, The First Hospital of Jilin University, Changchun, China
| | - Qiangqiang Wen
- Department of Orthopedics, The First Hospital of Jilin University, Changchun, China
| | - Zhenjiang Sui
- Department of Orthopedics, The First Hospital of Jilin University, Changchun, China
| | - Pengcheng Zhou
- Department of Orthopedics, The First Hospital of Jilin University, Changchun, China
| | - Tiecheng Yu
- Department of Orthopedics, The First Hospital of Jilin University, Changchun, China
| |
Collapse
|
|
9
|
Pizzorno J, Pizzorno L. Commonly Prescribed and Over-the-Counter Drugs as Secondary Causes of Osteoporosis-Part Two. Integr Med (Encinitas) 2021; 20:8-14. [PMID: 34377095 PMCID: PMC8325506] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 06/13/2023]
Abstract
In this second of a 2-part editorial, we continue our discussion of the importance of being aware that some clinically important prescription drugs can impair bone metabolism. While obviously most critical for women (and men) with osteopenia or osteoporosis, the guidance here is directly relevant to all patients as many are already experiencing decreased bone regeneration even if not severe enough for a formal diagnosis. Part One covered aromatase inhibitors, gonadotropin-releasing hormone agonists, anticonvulsants, benzodiazepines, antidepressants, insulin sensitizers, and NSAIDs and acetaminophen. Part Two covers opioids, glucocorticoids, calcineurin inhibitors, gastric acid blockers, diuretics, anti-coagulants, thyroid hormone medications, and contraceptives.
Collapse
|
|
10
|
Proton Pump Inhibitors, But Not H2-receptor Antagonists, Are Associated With Incident Fractures Among Kidney Transplant Recipients. Transplantation 2021; 104:2609-2615. [PMID: 32058466 DOI: 10.1097/tp.0000000000003178] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/12/2023]
Abstract
BACKGROUND Fractures are a common and burdensome problem among kidney transplant recipients (KTRs). Proton pump inhibitors (PPIs) are frequently used after kidney transplantation and have been associated with increased fracture risk in the general population. This study aimed to determine whether PPI use is associated with incidence of major fractures in KTRs. METHODS Using the Wisconsin Allograft Recipient Database, we identified 155 KTRs with a major fracture that occurred at least 12 months after transplantation. Controls were selected using incidence-density sampling. Use of PPIs and histamine 2-receptor antagonists (H2RA) during the year before the index date were identified. RESULTS A total of 155 cases were matched to 685 controls. Within 1 year before the index date, 68% of cases and 52% of controls used a PPI, and 16% of cases and 11% of controls used an H2RA. PPI use was associated with higher incidence of major fractures in unadjusted analysis (odds ratio [OR], 2.4; 95% CI, 1.6-3.5) and in adjusted analyses controlling for demographic and transplant-related covariates and use of corticosteroids, bisphosphonates, vitamin D and calcium supplements (OR, 1.9; 95% CI, 1.2-3.1). H2RA use was not associated with incidence of major fractures in adjusted analyses (OR, 1.0; 95% CI, 0.5-1.8). The associations between PPI use and fractures remained similar in analyses limited to spine and hip fractures. CONCLUSIONS Use of PPIs, but not H2RAs, is associated with a higher risk of major fractures among KTRs. Clinicians should individualize PPI use in KTRs, evaluating the risks and benefits of prescribing and continuing PPIs in KTRs.
Collapse
|
|
11
|
Fisher L, Fisher A, Smith PN. Helicobacter pylori Related Diseases and Osteoporotic Fractures (Narrative Review). J Clin Med 2020; 9:E3253. [PMID: 33053671 PMCID: PMC7600664 DOI: 10.3390/jcm9103253] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/21/2020] [Revised: 09/28/2020] [Accepted: 10/07/2020] [Indexed: 02/06/2023] Open
Abstract
Osteoporosis (OP) and osteoporotic fractures (OFs) are common multifactorial and heterogenic disorders of increasing incidence. Helicobacter pylori (H.p.) colonizes the stomach approximately in half of the world's population, causes gastroduodenal diseases and is prevalent in numerous extra-digestive diseases known to be associated with OP/OF. The studies regarding relationship between H.p. infection (HPI) and OP/OFs are inconsistent. The current review summarizes the relevant literature on the potential role of HPI in OP, falls and OFs and highlights the reasons for controversies in the publications. In the first section, after a brief overview of HPI biological features, we analyze the studies evaluating the association of HPI and bone status. The second part includes data on the prevalence of OP/OFs in HPI-induced gastroduodenal diseases (peptic ulcer, chronic/atrophic gastritis and cancer) and the effects of acid-suppressive drugs. In the next section, we discuss the possible contribution of HPI-associated extra-digestive diseases and medications to OP/OF, focusing on conditions affecting both bone homeostasis and predisposing to falls. In the last section, we describe clinical implications of accumulated data on HPI as a co-factor of OP/OF and present a feasible five-step algorithm for OP/OF risk assessment and management in regard to HPI, emphasizing the importance of an integrative (but differentiated) holistic approach. Increased awareness about the consequences of HPI linked to OP/OF can aid early detection and management. Further research on the HPI-OP/OF relationship is needed to close current knowledge gaps and improve clinical management of both OP/OF and HPI-related disorders.
Collapse
Affiliation(s)
- Leon Fisher
- Department of Gastroenterology, Frankston Hospital, Peninsula Health, Melbourne 3199, Australia
| | - Alexander Fisher
- Department of Geriatric Medicine, The Canberra Hospital, ACT Health, Canberra 2605, Australia;
- Department of Orthopedic Surgery, The Canberra Hospital, ACT Health, Canberra 2605, Australia;
- Australian National University Medical School, Canberra 2605, Australia
| | - Paul N Smith
- Department of Orthopedic Surgery, The Canberra Hospital, ACT Health, Canberra 2605, Australia;
- Australian National University Medical School, Canberra 2605, Australia
| |
Collapse
|
|
12
|
January SE, Progar K, Nesselhauf NM, Hagopian JC, Malone AF. Choice of Acid Suppressant Therapy and Long-Term Graft Outcomes After Kidney Transplantation. Pharmacotherapy 2020; 40:1082-1088. [PMID: 33037663 DOI: 10.1002/phar.2470] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/29/2022]
Abstract
STUDY OBJECTIVE The purpose of this study was to comprehensively evaluate the long-term adverse effects of proton pump inhibitors (PPIs) compared with histamine-2 receptor antagonists (H2RAs) in kidney transplant recipients. METHODS This retrospective cohort compared 582 patients treated with PPI with 705 patients treated with H2RA and evaluated adverse effects throughout their course of acid suppressant therapy to a maximum of nine years posttransplant. The primary outcome of interest was renal function at 1 year posttransplant; secondary outcomes included renal function at 30 days, 3, 5, and 9 years posttransplant as well as rejection, electrolyte and laboratory abnormalities, osteoporosis, pneumonia, and Clostridium difficile infections. RESULTS Renal function did not significantly differ at any timepoint posttransplant. Rejection rates and Clostridium difficile infections were similar between groups; osteoporosis and pneumonia rates were numerically higher in the PPI treated arm but did not reach statistical significance. Proton pump inhibitor (PPI) treated patients were more likely to experience hypomagnesemia requiring supplementation. High dose PPI treated patients had significantly higher rates of pneumonia and osteoporosis compared with H2RA treated patients. Patients were maintained on PPI therapy for an average of 5 years and H2RA therapy for 3 years posttransplant, the majority without a clear indication for therapy. CONCLUSIONS There was no difference in renal function, rejection, or graft loss between PPI and H2RA treated patients. The majority of patients were maintained on PPI therapy for several years posttransplant without a clear indication; critical evaluation of ongoing need for acid suppressant therapy in the posttransplant course should be an area of future focus.
Collapse
Affiliation(s)
- Spenser E January
- Department of Pharmacy, Barnes-Jewish Hospital, Saint Louis, Missouri, USA
| | - Kristin Progar
- Department of Pharmacy, Barnes-Jewish Hospital, Saint Louis, Missouri, USA
| | | | | | - Andrew F Malone
- Division of Nephrology, Washington University Physicians, Saint Louis, Missouri, USA
| |
Collapse
|
|
13
|
Wei J, Chan AT, Zeng C, Bai X, Lu N, Lei G, Zhang Y. Association between proton pump inhibitors use and risk of hip fracture: A general population-based cohort study. Bone 2020; 139:115502. [PMID: 32593677 DOI: 10.1016/j.bone.2020.115502] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/11/2020] [Revised: 06/15/2020] [Accepted: 06/19/2020] [Indexed: 12/29/2022]
Abstract
Previous studies comparing risk of fracture among Proton Pump Inhibitors (PPIs) users with that among non-users were susceptible to confounding by indication. Epidemiologic studies of this association using an active medication as a comparator would appropriately address this bias. We conducted a propensity-score matched cohort study to compare the risk of incident fracture over five years among initiators of PPIs with initiators of histamine 2 receptor antagonist (H2RA) using data collected from The Health Improvement Network (THIN) database in the United Kingdom (2000-2016). The prevalence of PPIs prescription increased 3.8-fold from 2000 (7.9%) to 2012 (30.3%) and remained stable since then. Of the 50,265 propensity-score matched participants in each cohort (mean age was 65 years, and 57% were women), 370 (1.9/1000 person-years) incident hip fracture occurred in the PPIs initiators and 294 (1.5/1000 person-years) in the H2RA initiators during the follow-up period. The rate difference of incident hip fracture for PPIs initiation was 0.4 (95% confidence interval [CI]: 0.2-0.7)/1000 person-years compared with H2RA initiation and the corresponding hazard ratio (HR) was 1.27 (95%CI: 1.09-1.48). Compared with non-PPI use, multivariable-adjusted odds ratios (ORs) of hip fracture were 1.17 (95%CI: 0.94-1.46), 1.55 (95%CI: 1.23-1.96), and 1.67 (95%CI: 1.33-2.10) for 1-2, 3-9 and ≥ 10 prescriptions of PPIs, respectively (P for trend = 0.001). We found that PPIs prescription has been increasing rapidly over the past decade in the United Kingdom, and the initiation of PPIs was associated with a higher risk of hip fracture than initiation of H2RA.
Collapse
Affiliation(s)
- Jie Wei
- Health Management Center, Xiangya Hospital, Central South University, Changsha, Hunan, China; Division of Rheumatology, Allergy, and Immunology, Department of Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA
| | - Andrew T Chan
- Division of Gastroenterology, Department of Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA; Clinical and Translational Epidemiology Unit, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA; Department of Immunology and Infectious Diseases, Harvard T. H. Chan School of Public Health, Harvard Medical School, Boston, MA, USA
| | - Chao Zeng
- Division of Rheumatology, Allergy, and Immunology, Department of Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA; Department of Orthopaedics, Xiangya Hospital, Central South University, Changsha, Hunan, China; Hunan Key Laboratory of Joint Degeneration and Injury, Changsha, Hunan, China
| | - Xiaochun Bai
- Department of Orthopedics, Academy of Orthopedics Guangdong Province, Orthopedic Hospital of Guangdong Province, Guangdong Provincial Key Laboratory of Bone and Joint Degenerative Diseases, The Third Affiliated Hospital of Southern Medical University, Guangzhou, China; Department of Cell Biology, Key Laboratory of Mental Health of the Ministry of Education, School of Basic Medical Sciences, Southern Medical University, Guangzhou, China
| | - Na Lu
- Arthritis Research Canada, Richmond, Canada
| | - Guanghua Lei
- Department of Orthopaedics, Xiangya Hospital, Central South University, Changsha, Hunan, China; Hunan Key Laboratory of Joint Degeneration and Injury, Changsha, Hunan, China; National Clinical Research Center of Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, Hunan, China.
| | - Yuqing Zhang
- Division of Rheumatology, Allergy, and Immunology, Department of Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
| |
Collapse
|
|
14
|
Dhar A, Maw F, Dallal HJ, Attwood S. Side effects of drug treatments for gastro-oesophageal reflux disease: current controversies. Frontline Gastroenterol 2020; 13:45-49. [PMID: 34966532 PMCID: PMC8666855 DOI: 10.1136/flgastro-2019-101386] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/07/2020] [Revised: 07/28/2020] [Accepted: 07/28/2020] [Indexed: 02/06/2023] Open
Abstract
The two main drugs used in the treatment of gastro-oesophageal reflux disease are proton pump inhibitors and histamine-2 receptor antagonists and both these agents have been implicated in a number of adverse effects, leading to considerable controversies related to their long-term use. This paper is aimed at a critical review of the published literature and the clinical significance of these reported side effects, most of which are associations rather than causal.
Collapse
Affiliation(s)
- Anjan Dhar
- Gastroenterology, County Durham & Darlington NHS Foundation Trust, Darlington, UK
| | - Frances Maw
- Pharmacy, County Durham and Darlington NHS Foundation Trust, Darlington, Darlington, UK
| | - Helen Jane Dallal
- Gastroenterology, County Durham & Darlington NHS Foundation Trust, Darlington, UK
| | | |
Collapse
|
|
15
|
Kim JJ, Jang EJ, Park J, Sohn HS. Association between proton pump inhibitor use and risk of fracture: A population-based case-control study. PLoS One 2020; 15:e0235163. [PMID: 32730257 PMCID: PMC7392283 DOI: 10.1371/journal.pone.0235163] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/03/2019] [Accepted: 06/10/2020] [Indexed: 12/17/2022] Open
Abstract
Objectives The purpose of this study was to reconfirm the association between the risk of fracture and proton pump inhibitor use and to establish evidence for defining a high-risk group of patients among proton pump inhibitor users. Methods A nested case-control study was performed using data from the National Health Insurance Sharing Service database from the period January 2007 to December 2017. The study population included elderly women aged ≥65 years with claims for peptic ulcer or gastro-esophageal reflux disease. The cases were all incidental osteoporotic fractures, and up to two controls were matched to each case by age, osteoporosis, and Charlson comorbidity index. Conditional logistic regression was used to calculate the adjusted odds ratio and 95% confidence interval (CI). Results A total of 21,754 cases were identified, and 43,508 controls were matched to the cases. The adjusted odds ratio of osteoporotic fractures related to the use of proton pump inhibitors was 1.15 (95% CI: 1.11–1.20). There was a statistically significant interaction between proton pump inhibitor and bisphosphonate use (p<0.01). The risk of fracture in patients using proton pump inhibitors was 1.15 (95% CI: 1.08–1.92) in bisphosphonate users and 1.11 (95% CI: 1.03–1.20) in bisphosphonate non-users. Conclusion Concomitant use of bisphosphonates and proton pump inhibitors will likely increase the risk of osteoporotic fractures in women aged 65 and over, and caution should be exercised in this high-risk group of patients.
Collapse
Affiliation(s)
- Jong Joo Kim
- Pharmaceutical Information Research Institute, Cha University, Gyeonggi-do, Republic of Korea
| | - Eun Jin Jang
- College of Natural Science, Andong National University, Gyeongsangbuk-do, Republic of Korea
| | - Jiwon Park
- College of Natural Science, Kyungpook National University, Daegu-si, Republic of Korea
| | - Hyun Soon Sohn
- College of Pharmacy, Cha University, Gyeonggi-do, Republic of Korea
- * E-mail:
| |
Collapse
|
|
16
|
Effects of Pistacia lentiscus and Coriander Triphala on Adult Gastroesophageal Reflux Disease: A Randomized Double-Blinded Clinical Trial. IRANIAN RED CRESCENT MEDICAL JOURNAL 2020. [DOI: 10.5812/ircmj.102260] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
Background: The cardinal symptoms of gastroesophageal reflux disease include heartburn (pyrosis) and regurgitation. Conventional treatment is done by proton pump inhibitors. In Persian traditional medicine, several herbs (single or combined) have been used to treat gastrointestinal disorders. Objectives: This study aimed to assess the effects of Pistacia lentiscus (mastic) and Coriander Triphala on reflux symptoms compared to omeprazole in a double-blinded randomized clinical trial. Methods: In a double-blinded, multicenter, randomized clinical trial, we assessed the effects of Pistacia lentiscus L., Coriander Triphala, and omeprazole on the symptoms of GERD in Tabriz, Iran, in 2018 - 2019. Thus, 105 patients with GERD symptoms were assigned randomly to three groups as group A (Pistacia lentiscus L., 1000 mg/TDS), group B (Coriander Triphala, 1000 mg/TDS), and group C (omeprazole, 20 mg/day plus five placebo capsules per day). The assessments were done at the beginning and the end of the study using FSSG, VAS, RS, and GERD-HRQL questionnaires. Results: In the beginning, no significant differences were observed between the groups in the background characteristics. There was no statistically significant difference between Pistacia lentiscus, Coriander Triphala, and omeprazole in the improvement of FSSG, VAS, GERD-HRQL, and reflux scores. In all groups, the FFSG, VAS, reflux, and GERD-HRQL scores significantly decreased and improved after four weeks of intervention compared to the respective baselines. The FSSG score improvements after four weeks of intervention were 73.68%, 83.33%, and 68.62%, in groups A, B, and C, respectively. The VAS score improvements were 66.66%, 75.00%, and 62.50% in groups A, B, and C, respectively. Improvements in GERD-HRQL were 90.00%, 91.28%, and 82.00%, in groups A, B, and C, respectively. Reflux improvements were 66.66%, 80.00%, and 66.66% in groups A, B, and C, respectively. Conclusions: The results showed that Pistacia lentiscus and Coriander Triphala are as effective as omeprazole in the treatment of GERD.
Collapse
|
|
17
|
Suitability of patient education materials on proton-pump inhibitors deprescribing: a focused review. Eur J Clin Pharmacol 2019; 76:17-21. [PMID: 31690956 DOI: 10.1007/s00228-019-02779-x] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/28/2019] [Accepted: 09/26/2019] [Indexed: 12/17/2022]
Abstract
PURPOSE Engaging patients in the process of deprescribing is a necessity. Several patient education materials have been developed for this purpose. The aim of this study was to assess the suitability of the existing patient education materials for proton-pump inhibitors deprescribing. METHODS We conducted a targeted inventory of the available materials on scientific literature and known repositories. We evaluated their suitability with the Suitability Assessment of Materials (SAM) instrument. Materials were rated independently by two researchers and then discussed until consensus was reached. RESULTS Seven patient education materials were identified. Three materials (42.9%) were deemed "superior" and 4 (57.1%) were deemed "adequate". Ratings were generally good in the categories of content, learning stimulation, motivation, typography and layout. The major weaknesses included the use of inappropriate graphics and the too demanding required reading grade level. These may decrease patient attention and comprehension and therefore the effectiveness of education materials. CONCLUSIONS Suitability of the patient education materials on proton-pump inhibitors deprescribing is overall satisfactory. Greater attention on readability, graphics and inclusion of summaries will be needed for development of future materials.
Collapse
|
|
18
|
Emeny RT, Chang CH, Skinner J, O’Malley AJ, Smith J, Chakraborti G, Rosen CJ, Morden NE. Association of Receiving Multiple, Concurrent Fracture-Associated Drugs With Hip Fracture Risk. JAMA Netw Open 2019; 2:e1915348. [PMID: 31722031 PMCID: PMC6902800 DOI: 10.1001/jamanetworkopen.2019.15348] [Citation(s) in RCA: 15] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/03/2023] Open
Abstract
IMPORTANCE Many prescription drugs increase fracture risk, which raises concern for patients receiving 2 or more such drugs concurrently. Logic suggests that risk will increase with each additional drug, but the risk of taking multiple fracture-associated drugs (FADs) is unknown. OBJECTIVE To estimate hip fracture risk associated with concurrent exposure to multiple FADs. DESIGN, SETTING, AND PARTICIPANTS This cohort study used a 20% random sample of Medicare fee-for-service administrative data for age-eligible Medicare beneficiaries from 2004 to 2014. Sex-stratified Cox regression models estimated hip fracture risk associated with current receipt of 1, 2, or 3 or more of 21 FADs and, separately, risk associated with each FAD and 2-way FAD combination vs no FADs. Models included sociodemographic characteristics, comorbidities, and use of non-FAD medications. Analyses began in November 2018 and were completed April 2019. EXPOSURE Receipt of prescription FADs. MAIN OUTCOMES AND MEASURES Hip fracture hospitalization. RESULTS A total of 11.3 million person-years were observed, reflecting 2 646 255 individuals (mean [SD] age, 77.2 [7.3] years, 1 615 613 [61.1%] women, 2 136 585 [80.7%] white, and 219 579 [8.3%] black). Overall, 2 827 284 person-years (25.1%) involved receipt of 1 FAD; 1 322 296 (11.7%), 2 FADs; and 954 506 (8.5%), 3 or more FADs. In fully adjusted, sex-stratified models, an increase in hip fracture risk among women was associated with the receipt of 1, 2, or 3 or more FADs (1 FAD: hazard ratio [HR], 2.04; 95% CI, 1.99-2.11; P < .001; 2 FADs: HR, 2.86; 95% CI, 2.77-2.95; P < .001; ≥3 FADs: HR, 4.50; 95% CI, 4.36-4.65; P < .001). Relative risks for men were slightly higher (1 FAD: HR, 2.23; 95% CI, 2.11-2.36; P < .001; 2 FADs: HR, 3.40; 95% CI, 3.20-3.61; P < .001; ≥3 FADs: HR, 5.18; 95% CI, 4.87-5.52; P < .001). Among women, 2 individual FADs were associated with HRs greater than 3.00; 80 pairs of FADs exceeded this threshold. Common, risky pairs among women included sedative hypnotics plus opioids (HR, 4.90; 95% CI, 3.98-6.02; P < .001), serotonin reuptake inhibitors plus benzodiazepines (HR, 4.50; 95% CI, 3.76-5.38; P < .001), and proton pump inhibitors plus opioids (HR, 4.00; 95% CI, 3.56-4.49; P < .001). Receipt of 1, 2, or 3 or more non-FADs was associated with a small, significant reduction in fracture risk compared with receipt of no non-FADs among women (1 non-FAD: HR, 0.93; 95% CI, 0.90-0.96; P < .001; 2 non-FADs: HR, 0.84; 95% CI, 0.81-0.87; P < .001; ≥3 non-FADs: HR, 0.74; 95% CI, 0.72-0.77; P < .001). CONCLUSIONS AND RELEVANCE Among older adults, FADs are commonly used and commonly combined. In this cohort study, the addition of a second and third FAD was associated with a steep increase in fracture risk. Many risky pairs of FADs included potentially avoidable drugs (eg, sedatives and opioids). If confirmed, these findings suggest that fracture risk could be reduced through tighter adherence to long-established prescribing guidelines and recommendations.
Collapse
Affiliation(s)
- Rebecca T. Emeny
- The Dartmouth Institute for Health Policy and Clinical Practice, Geisel School of Medicine, Dartmouth College, Lebanon, New Hampshire
| | - Chiang-Hua Chang
- Division of Geriatric and Palliative Medicine, Internal Medicine, Institute of Healthcare Policy and Innovation, University of Michigan, Ann Arbor
| | - Jonathan Skinner
- The Dartmouth Institute for Health Policy and Clinical Practice, Geisel School of Medicine, Dartmouth College, Lebanon, New Hampshire
| | - A. James O’Malley
- The Dartmouth Institute for Health Policy and Clinical Practice, Geisel School of Medicine, Dartmouth College, Lebanon, New Hampshire
| | - Jeremy Smith
- The Dartmouth Institute for Health Policy and Clinical Practice, Geisel School of Medicine, Dartmouth College, Lebanon, New Hampshire
| | - Gouri Chakraborti
- The Dartmouth Institute for Health Policy and Clinical Practice, Geisel School of Medicine, Dartmouth College, Lebanon, New Hampshire
| | - Clifford J. Rosen
- Center for Clinical and Translational Research, Maine Medical Center Research Institute, Scarborough
| | - Nancy E. Morden
- The Dartmouth Institute for Health Policy and Clinical Practice, Geisel School of Medicine, Dartmouth College, Lebanon, New Hampshire
- now with Microsoft Artificial Intelligence and Research, Healthcare NeXT, Redmond, Washington
| |
Collapse
|
|
19
|
Folwarczna J, Konarek N, Freier K, Karbowniczek D, Londzin P, Janas A. Effects of loratadine, a histamine H 1 receptor antagonist, on the skeletal system of young male rats. DRUG DESIGN DEVELOPMENT AND THERAPY 2019; 13:3357-3367. [PMID: 31576110 PMCID: PMC6767469 DOI: 10.2147/dddt.s215337] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 05/11/2019] [Accepted: 07/26/2019] [Indexed: 01/03/2023]
Abstract
Background Histamine H1 receptor antagonists are widely used in the treatment of allergic diseases. H1 receptors are expressed on bone cells and histamine takes part in regulation of bone metabolism. Loratadine is often prescribed to children. Purpose The aim of the present study was to investigate the effects of loratadine on the skeletal system of young rats. Material and methods Loratadine (0.5, 5, and 50 mg/kg p.o. daily) was administered for 4 weeks to male Wistar rats, 6-week-old at the start of the experiment. Bone mass, mass of bone mineral, calcium, and phosphorus content in the bone mineral of the tibia, femur, and L-4 vertebra, histomorphometric parameters of the femur, mechanical properties of the proximal tibial metaphysis, femoral diaphysis and femoral neck, and serum levels of bone turnover markers were examined. Results Loratadine at 0.5 and 5 mg/kg did not significantly affect the skeletal system of young rats. At 50 mg/kg, loratadine decreased the femoral length, increased content of calcium and phosphorus in the bone mineral of the vertebra, and tended to improve mechanical properties of the tibial metaphysis. Conclusion High-dose loratadine slightly but significantly affected development of the skeletal system in rapidly growing rats.
Collapse
Affiliation(s)
- Joanna Folwarczna
- Department of Pharmacology, School of Pharmacy with the Division of Laboratory Medicine in Sosnowiec, Medical University of Silesia, Katowice, Sosnowiec 41-200, Poland
| | - Natalia Konarek
- Department of Pharmacology, School of Pharmacy with the Division of Laboratory Medicine in Sosnowiec, Medical University of Silesia, Katowice, Sosnowiec 41-200, Poland
| | - Karolina Freier
- Department of Pharmacology, School of Pharmacy with the Division of Laboratory Medicine in Sosnowiec, Medical University of Silesia, Katowice, Sosnowiec 41-200, Poland
| | - Dawid Karbowniczek
- Department of Pharmacology, School of Pharmacy with the Division of Laboratory Medicine in Sosnowiec, Medical University of Silesia, Katowice, Sosnowiec 41-200, Poland
| | - Piotr Londzin
- Department of Pharmacology, School of Pharmacy with the Division of Laboratory Medicine in Sosnowiec, Medical University of Silesia, Katowice, Sosnowiec 41-200, Poland
| | - Aleksandra Janas
- Department of Pharmacology, School of Pharmacy with the Division of Laboratory Medicine in Sosnowiec, Medical University of Silesia, Katowice, Sosnowiec 41-200, Poland
| |
Collapse
|
|
20
|
Mester A, Apostu D, Ciobanu L, Piciu A, Lucaciu O, Campian RS, Taulescu M, Bran S. The impact of proton pump inhibitors on bone regeneration and implant osseointegration. Drug Metab Rev 2019; 51:330-339. [PMID: 31055956 DOI: 10.1080/03602532.2019.1610767] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
Proton pump inhibitors (PPIs) have become known for the treatment of gastric-acid related disorders. Similar to any other drugs, PPIs have possible adverse reactions, being associated with bone fractures, infections, kidney disease, mineral deficiency, dementia, and pneumonia. Multiple analyses have stated that PPIs therapy may affect bone regeneration and osseointegration process, causing an increased risk of bone fracture, deterioration of bone metabolism and impaired bone healing. In this review, we emphasized the current literature regarding the influence of proton pump inhibitors in the bone regeneration process. Results from the studies suggest a link between PPIs intake and bone regeneration, but several concerns are raised regarding inadequate recipient bone, surgical trauma, limitations on the titanium surface, comorbidities or interference with other pharmacological agents. Further studies are needed to determine whether the impaired bone regeneration process is due to PPI or coexisting factors.
Collapse
Affiliation(s)
- Alexandru Mester
- Department of Oral Rehabilitation, Oral Health and Dental Office Management, University of Medicine and Pharmacy "Iuliu Hatieganu" , Cluj-Napoca , Romania
| | - Dragos Apostu
- Department of Orthopedics and Traumatology, University of Medicine and Pharmacy "Iuliu Hatieganu" , Cluj-Napoca , Romania
| | - Lidia Ciobanu
- Department of Gastroenterology and Hepatology, University of Medicine and Pharmacy "Iuliu Hatieganu" , Cluj-Napoca , Romania
| | - Andra Piciu
- Department of Medical Oncology, University of Medicine and Pharmacy "Iuliu Hatieganu" , Cluj-Napoca , Romania
| | - Ondine Lucaciu
- Department of Oral Rehabilitation, Oral Health and Dental Office Management, University of Medicine and Pharmacy "Iuliu Hatieganu" , Cluj-Napoca , Romania
| | - Radu Septimiu Campian
- Department of Oral Rehabilitation, Oral Health and Dental Office Management, University of Medicine and Pharmacy "Iuliu Hatieganu" , Cluj-Napoca , Romania
| | - Marian Taulescu
- Department of Pathology, University of Agricultural Sciences and Veterinary Medicine , Cluj-Napoca , Romania
| | - Simion Bran
- Department of Maxillofacial Surgery and Implantology, University of Medicine and Pharmacy "Iuliu Hatieganu" , Cluj-Napoca , Romania
| |
Collapse
|
|
21
|
Influence of oral magnesium-containing supplement and antacid administration on hypomagnesemia induced by panitumumab. Cancer Chemother Pharmacol 2019; 83:673-679. [PMID: 30661095 DOI: 10.1007/s00280-019-03772-y] [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: 08/28/2018] [Accepted: 01/06/2019] [Indexed: 12/21/2022]
Abstract
PURPOSE Hypomagnesemia is a common side effect of panitumumab. The effect of magnesium-containing supplement as a laxative and concomitant antacid (proton pump inhibitor and histamine H2 antagonist) administration on panitumumab-induced hypomagnesemia was retrospectively investigated. METHODS Patients with advanced or recurrent colorectal cancer who received panitumumab were included in this study. Serum magnesium levels were extracted from the electronic medical records of 1753 administrations in 221 patients who received panitumumab. Serum magnesium levels in patients with or without oral magnesium-containing supplement and antacid treatment were compared using analysis of covariance as the number of panitumumab administration up to 16 times for covariates. RESULTS The mean serum magnesium levels were significantly decreased with increasing number of panitumumab administrations (2.13 mg/dL at 1st vs. 1.55 mg/dL at 16th, p < 0.001). The use of oral magnesium-containing supplement significantly inhibited the decline in mean serum magnesium level (1.98 mg/dL vs. 1.78 mg/dL, p < 0.001). However, antacid use in patients receiving oral magnesium-containing supplement significantly decreased the effectiveness of the magnesium supplement on serum magnesium level (2.02 mg/dL vs. 1.93 mg/dL, p < 0.05). CONCLUSION The use of oral magnesium-containing supplement might function as magnesium supplement based on the finding that use of oral magnesium-containing supplement during panitumumab administration decreased hypomagnesemia. However, combination of antacid decreased the supplemental effect of oral magnesium on hypomagnesemia. These results suggest the possibility that use of antacids during anti-EGFR antibody administration may promote hypomagnesemia.
Collapse
|
|
22
|
Bardou M, Fortinsky KJ, Chapelle N, Luu M, Barkun A. An update on the latest chemical therapies for reflux esophagitis in children. Expert Opin Pharmacother 2018; 20:231-239. [DOI: 10.1080/14656566.2018.1549224] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
Affiliation(s)
- Marc Bardou
- Centre d’Investigations Cliniques CIC1432, CHU de Dijon, Dijon Cedex, France
- Gastroenterology Department, CHU de Dijon, Dijon Cedex, France
| | - Kyle J. Fortinsky
- Department of Medicine, University of Toronto, Toronto General Hospital, Toronto, Ontario, Canada
| | | | - Maxime Luu
- Centre d’Investigations Cliniques CIC1432, CHU de Dijon, Dijon Cedex, France
| | - Alan Barkun
- Gastroenterology department, McGill University Health Centre, Montréal, Québec, Canada
| |
Collapse
|
|
23
|
Ayele HT, Dormuth CR, Filion KB. Long-Term Use of Proton Pump Inhibitors and Community-Acquired Pneumonia: Adverse Effect or Bias? J Am Geriatr Soc 2018; 66:2427-2428. [PMID: 30325006 DOI: 10.1111/jgs.15575] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/13/2018] [Accepted: 07/13/2018] [Indexed: 12/27/2022]
Affiliation(s)
- Henok Tadesse Ayele
- Centre for Clinical Epidemiology Lady Davis Institute Jewish General Hospital, Montreal, Quebec, Canada.,Department of Epidemiology, Biostatistics, and Occupational Health, McGill University, Montreal, Quebec, Canada
| | - Colin R Dormuth
- Department of Anesthesiology, Pharmacology, and Therapeutics, University of British Columbia, Vancouver, British Columbia, Canada
| | - Kristian B Filion
- Centre for Clinical Epidemiology Lady Davis Institute Jewish General Hospital, Montreal, Quebec, Canada.,Department of Epidemiology, Biostatistics, and Occupational Health Department of Medicine, McGill University, Montreal, Quebec, Canada
| |
Collapse
|
|
24
|
Doell A, Walus A, To J, Bell A. Quantifying Candidacy for Deprescribing of Proton Pump Inhibitors among Long-Term Care Residents. Can J Hosp Pharm 2018; 71:302-307. [PMID: 30401996 PMCID: PMC6209507] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 06/08/2023]
Abstract
BACKGROUND Proton pump inhibitors (PPIs) are a commonly prescribed drug class used to inhibit gastric acid secretion. They are prescribed for both treatment and prophylaxis of several gastrointestinal conditions. Although PPIs can be used safely in the short term, several serious adverse effects have been reported following long-term use, including increased risk of falls and fragility fractures. Long-term care home (LTCH) residents represent a population in which the long-term adverse effects of PPIs can be significant and PPI deprescribing should be considered when appropriate. OBJECTIVES To determine the proportion of LTCH residents with PPI prescriptions who were eligible for PPI deprescribing, and to examine vitamin B12 deficiencies and fall risk in the study population. METHODS This cross-sectional, multisite chart review involved LTCH residents who had an active PPI prescription during October 2016. A convenience sample of 150 charts was randomly selected, and the appropriateness of PPI deprescribing was determined using Canadian guidelines. Descriptive statistics were used to examine demographic characteristics, PPI dosing and indication, vitamin B12 supplementation, fall history, and fall risk. RESULTS Three of the selected charts were excluded because of missing information. Of the 147 residents included in the chart review, 93 (63%) were candidates for deprescribing. PPI use for gastroesophageal reflux disease for more than 8 weeks without a deprescribing attempt in the past year was the most frequently observed opportunity for deprescribing (49/93 [53%]). Twenty-nine residents (20%) had no documented indication for PPI use. Thirteen residents (9%) had had a fall within the past 30 days, and 53 (36%) had a prescription for vitamin B12 supplements and/or had low serum vitamin B12 levels. CONCLUSIONS A majority of the residents whose charts were reviewed were candidates for PPI deprescribing. This finding suggests an opportunity for clinicians who care for LTCH residents to increase their deprescribing efforts.
Collapse
Affiliation(s)
- Alanna Doell
- , BScPharm, ACPR, is a Staff Pharmacist with Seven Oaks General Hospital of the Winnipeg Regional Health Authority, Winnipeg, Manitoba
| | - Ashley Walus
- , BScPharm, ACPR, is a Clinical Resource Pharmacist with the Winnipeg Regional Health Authority, Winnipeg, Manitoba
| | - Jaclyn To
- , BScPharm, ACPR, is a Staff Pharmacist with the Victoria General Hospital of the Winnipeg Regional Health Authority, Winnipeg, Manitoba
| | - Allison Bell
- , BScPharm, is the Pharmacy Manager with the Long Term Care Program of the Winnipeg Regional Health Authority, Winnipeg, Manitoba
| |
Collapse
|
|
25
|
Zirk‐Sadowski J, Masoli JA, Delgado J, Hamilton W, Strain WD, Henley W, Melzer D, Ble A. Proton-Pump Inhibitors and Long-Term Risk of Community-Acquired Pneumonia in Older Adults. J Am Geriatr Soc 2018; 66:1332-1338. [PMID: 29676433 PMCID: PMC6099478 DOI: 10.1111/jgs.15385] [Citation(s) in RCA: 38] [Impact Index Per Article: 5.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/20/2017] [Revised: 02/16/2018] [Accepted: 02/28/2018] [Indexed: 02/06/2023]
Abstract
OBJECTIVES To estimate associations between long-term use of proton pump inhibitors (PPIs) and pneumonia incidence in older adults in primary care. DESIGN Longitudinal analyses of electronic medical records. SETTING England PARTICIPANTS: Individuals aged 60 and older in primary care receiving PPIs for 1 year or longer (N=75,050) and age- and sex-matched controls (N=75,050). MEASUREMENTS Net hazard ratios for pneumonia incidence in Year 2 of treatment were estimated using the prior event rate ratio (PERR), which adjusts for pneumonia incidence differences before initiation of treatment. Inverse probability weighted models adjusted for 78 demographic, disease, medication, and healthcare usage measures. RESULTS During the second year after initiating treatment, PPIs were associated with greater hazard of incident pneumonia (PERR-adjusted hazard ratio=1.82, 95% confidence interval=1.27-2.54), accounting for pretreatment pneumonia rates. Estimates were similar across age and comorbidity subgroups. Similar results were also obtained from propensity score- and inverse probability-weighted models. CONCLUSION In a large cohort of older adults in primary care, PPI prescription was associated with greater risk of pneumonia in the second year of treatment. Results were robust across alternative analysis approaches. Controversies about the validity of reported short-term harms of PPIs should not divert attention from potential long-term effects of PPI prescriptions on older adults.
Collapse
Affiliation(s)
- Jan Zirk‐Sadowski
- Epidemiology and Public Health Group, Medical SchoolUniversity of ExeterExeterUnited Kingdom
- Medicines Policy Research Unit, Centre for Big Data Research in HealthUniversity of New South WalesSydneyAustralia
| | - Jane A. Masoli
- Epidemiology and Public Health Group, Medical SchoolUniversity of ExeterExeterUnited Kingdom
- Department of Healthcare for Older PeopleRoyal Devon and Exeter National Health Service Foundation TrustExeterUnited Kingdom
| | - Joao Delgado
- Epidemiology and Public Health Group, Medical SchoolUniversity of ExeterExeterUnited Kingdom
| | - Willie Hamilton
- Primary Care Diagnostics, Medical School, St Luke's CampusUniversity of ExeterExeterUnited Kingdom
| | - W. David Strain
- Department of Healthcare for Older PeopleRoyal Devon and Exeter National Health Service Foundation TrustExeterUnited Kingdom
- Diabetes and Vascular Medicine, Medical SchoolUniversity of ExeterExeterUnited Kingdom
| | - William Henley
- Health Statistics Group, Institute of Health Research, Medical School, St Luke's CampusUniversity of ExeterExeterUnited Kingdom
| | - David Melzer
- Epidemiology and Public Health Group, Medical SchoolUniversity of ExeterExeterUnited Kingdom
| | - Alessandro Ble
- Epidemiology and Public Health Group, Medical SchoolUniversity of ExeterExeterUnited Kingdom
| |
Collapse
|
|
26
|
Law CCY, Narula A, Lightner AL, McKenna NP, Colombel JF, Narula N. Systematic Review and Meta-Analysis: Preoperative Vedolizumab Treatment and Postoperative Complications in Patients with Inflammatory Bowel Disease. J Crohns Colitis 2018; 12:538-545. [PMID: 29718245 DOI: 10.1093/ecco-jcc/jjy022] [Citation(s) in RCA: 67] [Impact Index Per Article: 9.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/28/2017] [Accepted: 02/22/2018] [Indexed: 02/08/2023]
Abstract
BACKGROUND AND AIMS The impact of vedolizumab, a gut-selective monoclonal antibody, on postoperative outcomes is unclear. This study aimed to assess the impact of preoperative vedolizumab treatment on the rate of postoperative complications in patients with inflammatory bowel disease [IBD] undergoing abdominal surgery. METHODS A systematic search of multiple electronic databases from inception until May 2017 identified studies reporting rates of postoperative complications in vedolizumab-treated IBD patients compared to no biologic exposure or anti-tumor necrosis factor (anti-TNF) treated IBD patients. Outcomes of interest included postoperative infectious complications and overall postoperative complications. Pooled risk ratios and 95% confidence intervals were estimated using the random-effects model. RESULTS Five studies comprising 307 vedolizumab-treated IBD patients, 490 anti-TNF-treated IBD patients and 535 IBD patients not exposed to preoperative biologic therapy were included. The risk of postoperative infectious complications (risk ratio [RR] 0.99, 95% confidence interval [CI] 0.37-2.65) and overall postoperative complications [RR 1.00, 95% CI 0.46-2.15] were not significantly different between vedolizumab-treated patients and those who received no preoperative biologic therapy. In addition, the risk of postoperative infectious complications [RR 0.99, 95% CI 0.34-2.90] and overall postoperative complications [RR 0.92, 95% CI 0.44-1.92] were not significantly different between vedolizumab-treated vs anti-TNF-treated patients. CONCLUSIONS Preoperative vedolizumab treatment in IBD patients does not appear to be associated with an increased risk of postoperative infectious or overall postoperative complications compared to either preoperative anti-TNF therapy or no biologic therapy. Future prospective studies which include perioperative drug level monitoring are needed to confirm these findings.
Collapse
Affiliation(s)
- Cindy C Y Law
- Division of Internal Medicine, Department of Medicine, McMaster University, Hamilton, ON, Canada
| | - Alisha Narula
- Division of Gastroenterology, Department of Medicine, Farncombe Family Digestive Health Research Institute, McMaster University, Hamilton, ON, Canada
| | - Amy L Lightner
- Division of Colon and Rectal Surgery, Mayo Clinic, Rochester, MN, USA
| | | | - Jean-Frederic Colombel
- Division of Gastroenterology, Icahn School of Medicine at Mount Sinai, New York, NY, USA
| | - Neeraj Narula
- Division of Gastroenterology, Department of Medicine, Farncombe Family Digestive Health Research Institute, McMaster University, Hamilton, ON, Canada
| |
Collapse
|
|
27
|
Kumar S, Drake MT, Schleck C, Johnson ML, Alexander JA, Katzka DA, Iyer PG. Incidence and predictors of osteoporotic fractures in patients with Barrett's oesophagus: a population-based nested case-control study. Aliment Pharmacol Ther 2017; 46:1094-1102. [PMID: 28980336 PMCID: PMC5683094 DOI: 10.1111/apt.14345] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/07/2017] [Revised: 06/30/2017] [Accepted: 09/07/2017] [Indexed: 12/13/2022]
Abstract
BACKGROUND Proton pump inhibitors (PPI) are inconsistently associated with osteoporotic fractures. Barrett's oesophagus (BO) patients are treated with high PPI doses for prolonged periods, but there are limited data on the incidence of osteoporosis and fractures in this group pf patients. AIM To estimate the incidence of (and risk factors for) low bone mass (osteoporosis and/or osteopenia) related fractures in a population-based BO cohort. METHODS All subjects with BO and a diagnosis of osteoporosis and fractures were identified using Rochester Epidemiology Project resources. The incidence rates of all and osteoporotic fractures in these subjects were compared to an age- and gender similar population in Olmsted County to determine standardised incidence ratios (SIR). Predictors were assessed using Cox proportional hazards models. RESULTS Five hundred and twenty-one patients were included (median [IQR] age 61 [52, 72] years; 398 [76%] men) of whom 113 (21.7%) had fractures, and 46 (8.8%) had osteoporotic fractures. The incidence of all fractures and osteoporotic fractures was comparable to that of an age- and gender-matched population (SIR 1.09; 95% CI 0.92-1.29: SIR 1.05; 95% CI 0.85-1.29). PPI use, dose or duration of use was not associated with osteoporotic fracture risk (HR 0.87; 95% CI 0.12-6.39). Independent risk factors for osteoporotic fractures included older age, female gender and higher co-morbidity index. CONCLUSIONS The incidence of osteoporotic fractures was not increased in BO patients compared to the general population. In addition, PPI use was not associated with increased fracture risk regardless of the duration of therapy or dose.
Collapse
Affiliation(s)
- Swarup Kumar
- Division of Gastroenterology, Rochester, Minnesota
| | - Matthew T. Drake
- Division of Endocrinology, Metabolism & Diabetes, Rochester, Minnesota
| | - Cathy Schleck
- Division of Biostatistics, Mayo Clinic, Rochester, Minnesota
| | | | | | | | | |
Collapse
|
|
28
|
Abstract
Proton pump inhibitors (PPIs) are widely prescribed and many people remain on them for years. In some, there may be good justification for long-term use; for example, in those with oesophageal stricture, Barrett's oesophagus or a history of a bleeding gastrointestinal ulcer, or to provide gastroprotection in those at high risk of gastrointestinal complications from taking NSAIDs. However, PPIs are often not used in line with clinical guidelines.1,2 In addition, there are concerns that many people take them for long periods to manage less serious conditions (e.g. indigestion) and may prefer taking them to addressing factors such as diet, obesity or alcohol that may be contributing to their symptoms. Although PPIs are well-tolerated, there is increasing evidence that they may be associated with a range of long-term adverse effects. Here, we review the safety of PPIs and consider whether long-term prescribing needs to be reassessed.
Collapse
|
|
29
|
Trifan A, Stanciu C, Girleanu I, Stoica OC, Singeap AM, Maxim R, Chiriac SA, Ciobica A, Boiculese L. Proton pump inhibitors therapy and risk of Clostridium difficile infection: Systematic review and meta-analysis. World J Gastroenterol 2017; 23:6500-6515. [PMID: 29085200 PMCID: PMC5643276 DOI: 10.3748/wjg.v23.i35.6500] [Citation(s) in RCA: 183] [Impact Index Per Article: 22.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/13/2017] [Revised: 08/11/2017] [Accepted: 08/25/2017] [Indexed: 02/06/2023] Open
Abstract
AIM To perform a systematic review and meta-analysis on proton pump inhibitors (PPIs) therapy and the risk of Clostridium difficile infection (CDI). METHODS We conducted a systematic search of MEDLINE/PubMed and seven other databases through January 1990 to March 2017 for published studies that evaluated the association between PPIs and CDI. Adult case-control and cohort studies providing information on the association between PPI therapy and the development of CDI were included. Pooled odds ratios (ORs) estimates with 95% confidence intervals (CIs) were calculated using the random effect. Heterogeneity was assessed by I2 test and Cochran's Q statistic. Potential publication bias was evaluated via funnel plot, and quality of studies by the Newcastle-Otawa Quality Assessment Scale (NOS). RESULTS Fifty-six studies (40 case-control and 16 cohort) involving 356683 patients met the inclusion criteria and were analyzed. Both the overall pooled estimates and subgroup analyses showed increased risk for CDI despite substantial statistical heterogeneity among studies. Meta-analysis of all studies combined showed a significant association between PPI users and the risk of CDI (pooled OR = 1.99, CI: 1.73-2.30, P < 0.001) as compared with non-users. The association remained significant in subgroup analyses: by design-case-control (OR = 2.00, CI: 1.68-2.38, P < 0.0001), and cohort (OR = 1.98, CI: 1.51-2.59, P < 0.0001); adjusted (OR = 1.95, CI: 1.67-2.27, P < 0.0001) and unadjusted (OR = 2.02, CI: 1.41-2.91, P < 0.0001); unicenter (OR = 2.18, CI: 1.72-2.75, P < 0.0001) and multicenter (OR = 1.82, CI: 1.51-2.19, P < 0.0001); age ≥ 65 years (OR = 1.93, CI: 1.40-2.68, P < 0.0001) and < 65 years (OR = 2.06, CI: 1.11-3.81, P < 0.01). No significant differences were found in subgroup analyses (test for heterogeneity): P = 0.93 for case-control vs cohort, P = 0.85 for adjusted vs unadjusted, P = 0.24 for unicenter vs multicenter, P = 0.86 for age ≥ 65 years and < 65 years. There was significant heterogeneity across studies (I2 = 85.4%, P < 0.001) as well as evidence of publication bias (funnel plot asymmetry test, P = 0.002). CONCLUSION This meta-analysis provides further evidence that PPI use is associated with an increased risk for development of CDI. Further high-quality, prospective studies are needed to assess whether this association is causal.
Collapse
Affiliation(s)
- Anca Trifan
- Institute of Gastroenterology and Hepatology, “St. Spiridon” Hospital, “Grigore T. Popa” University of Medicine and Pharmacy, 700111 Iasi, Romania
| | - Carol Stanciu
- Institute of Gastroenterology and Hepatology, “St. Spiridon” Hospital, 700111 Iasi, Romania
| | - Irina Girleanu
- Institute of Gastroenterology and Hepatology, “St. Spiridon” Hospital, “Grigore T. Popa” University of Medicine and Pharmacy, 700111 Iasi, Romania
| | - Oana Cristina Stoica
- Institute of Gastroenterology and Hepatology, “St. Spiridon” Hospital, “Grigore T. Popa” University of Medicine and Pharmacy, 700111 Iasi, Romania
| | - Ana Maria Singeap
- Institute of Gastroenterology and Hepatology, “St. Spiridon” Hospital, “Grigore T. Popa” University of Medicine and Pharmacy, 700111 Iasi, Romania
| | - Roxana Maxim
- Institute of Gastroenterology and Hepatology, “St. Spiridon” Hospital, “Grigore T. Popa” University of Medicine and Pharmacy, 700111 Iasi, Romania
| | - Stefan Andrei Chiriac
- Institute of Gastroenterology and Hepatology, “St. Spiridon” Hospital, “Grigore T. Popa” University of Medicine and Pharmacy, 700111 Iasi, Romania
| | - Alin Ciobica
- Department of Research, Faculty of Biology, “Alexandru Ioan Cuza” University of Iasi, 700506 Iasi, Romania
| | - Lucian Boiculese
- Department of Preventive Medicine and Interdisciplinarity, “Grigore. T. Popa” University of Medicine and Pharmacy, 700111 Iasi, Romania
| |
Collapse
|
|
30
|
Maes ML, Fixen DR, Linnebur SA. Adverse effects of proton-pump inhibitor use in older adults: a review of the evidence. Ther Adv Drug Saf 2017; 8:273-297. [PMID: 28861211 PMCID: PMC5557164 DOI: 10.1177/2042098617715381] [Citation(s) in RCA: 135] [Impact Index Per Article: 16.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/24/2016] [Indexed: 12/17/2022] Open
Abstract
Proton-pump inhibitors (PPIs) are a widely prescribed class of medications used to treat acid-related disorders and use has significantly increased over the last few decades. PPIs are often inappropriately prescribed and since they have been on the market, a number of post-marketing studies have been published demonstrating associations between longer duration of PPI therapy and a number of adverse effects that are a concern in older adults. The objective of this review is to discuss the existing literature of potential adverse effects with long-term PPI use in older adults and to summarize the implications in clinical practice. A PubMed search was conducted to identify studies evaluating the potential long-term adverse effects of PPI therapy in older adults, and publications were selected based on relevant criteria. PPIs have been associated with an increased risk of a number of adverse effects including osteoporotic-related fractures, Clostridium difficile infection, community-acquired pneumonia, vitamin B12 deficiency, kidney disease, and dementia, demonstrated by a number of case-control, cohort studies, and meta-analyses. Older adults should be periodically evaluated for the need for continued use of PPI therapy given the number of potential adverse effects associated with long-term use.
Collapse
Affiliation(s)
- Marina L. Maes
- Department of Clinical Pharmacy, University of Colorado Skaggs School of Pharmacy and Pharmaceutical Sciences, Aurora, CO, USA
- Dr. Maes was a 4th year student at the University of Colorado Skaggs School of Pharmacy and Pharmaceutical Sciences
| | - Danielle R. Fixen
- Department of Clinical Pharmacy, University of Colorado Skaggs School of Pharmacy and Pharmaceutical Sciences, Aurora, CO, USA
- Dr. Maes was a 4th year student at the University of Colorado Skaggs School of Pharmacy and Pharmaceutical Sciences
| | - Sunny Anne Linnebur
- Skaggs School of Pharmacy and Pharmaceutical Sciences, University of Colorado Anschutz Medical Campus, 12850 E. Montview Blvd (C238), Aurora, CO 80045, USA
| |
Collapse
|
|
31
|
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
|
|
32
|
Yu LY, Sun LN, Zhang XH, Li YQ, Yu L, Yuan ZQY, Meng L, Zhang HW, Wang YQ. A Review of the Novel Application and Potential Adverse Effects of Proton Pump Inhibitors. Adv Ther 2017; 34:1070-1086. [PMID: 28429247 PMCID: PMC5427147 DOI: 10.1007/s12325-017-0532-9] [Citation(s) in RCA: 81] [Impact Index Per Article: 10.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/27/2017] [Indexed: 02/07/2023]
Abstract
Proton pump inhibitors (PPIs) are known as a class of pharmaceutical agents that target H+/K+-ATPase, which is located in gastric parietal cells. PPIs are widely used in the treatment of gastric acid-related diseases including peptic ulcer disease, erosive esophagitis and gastroesophageal reflux disease, and so on. These drugs present an excellent safety profile and have become one of the most commonly prescribed drugs in primary and specialty care. Except for gastric acid-related diseases, PPIs can also be used in the treatment of Helicobacter pylori infection, viral infections, respiratory system diseases, cancer and so on. Although PPIs are mainly used short term in patients with peptic ulcer disease, nowadays these drugs are increasingly used long term, and frequently for a lifetime, for instance in patients with typical or atypical symptoms of gastroesophageal reflux disease and in NSAID or aspirin users at risk of gastrotoxicity and related complications including hemorrhage, perforation and gastric outlet obstruction. Long-term use of PPIs may lead to potential adverse effects, such as osteoporotic fracture, renal damage, infection (pneumonia and clostridium difficile infection), rhabdomyolysis, nutritional deficiencies (vitamin B12, magnesium and iron), anemia and thrombocytopenia. In this article, we will review some novel uses of PPIs in other fields and summarize the underlying adverse reactions.
Collapse
|
|
33
|
de la Coba Ortiz C, Argüelles Arias F, Martín de Argila de Prados C, Júdez Gutiérrez J, Linares Rodríguez A, Ortega Alonso A, Rodríguez de Santiago E, Rodríguez-Téllez M, Vera Mendoza MI, Aguilera Castro L, Álvarez Sánchez Á, Andrade Bellido RJ, Bao Pérez F, Castro Fernández M, Giganto Tomé F. Proton-pump inhibitors adverse effects: a review of the evidence and position statement by the Sociedad Española de Patología Digestiva. REVISTA ESPANOLA DE ENFERMEDADES DIGESTIVAS 2017; 108:207-24. [PMID: 27034082 DOI: 10.17235/reed.2016.4232/2016] [Citation(s) in RCA: 32] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
Abstract
INTRODUCTION In the last few years a significant number of papers have related the use of proton-pump inhibitors (PPIs) to potential serious adverse effects that have resulted in social unrest. OBJECTIVE The goal of this paper was to provide a literature review for the development of an institutional position statement by Sociedad Española de Patología Digestiva (SEPD) regarding the safety of long-term PPI use. MATERIAL AND METHODS A comprehensive review of the literature was performed to draw conclusions based on a critical assessment of the following: a) current PPI indications; b) vitamin B12 deficiency and neurological disorders; c) magnesium deficiency; d) bone fractures; e) enteric infection and pneumonia; f) interactions with thienopyridine derivatives; e) complications in cirrhotic patients. RESULTS Current PPI indications have remained unchanged for years now, and are well established. A general screening of vitamin B12 levels is not recommended for all patients on a PPI; however, it does seem necessary that magnesium levels be measured at therapy onset, and then monitored in subjects on other drugs that may induce hypomagnesemia. A higher risk for bone fractures is present, even though causality cannot be concluded for this association. The association between PPIs and infection with Clostridium difficile is mild to moderate, and the risk for pneumonia is low. In patients with cardiovascular risk receiving thienopyridines derivatives it is prudent to adequately consider gastrointestinal and cardiovascular risks, given the absence of definitive evidence regardin potential drug-drug interactions; if gastrointestinal risk is found to be moderate or high, effective prevention should be in place with a PPI. PPIs should be cautiously indicated in patients with decompensated cirrhosis. CONCLUSIONS PPIs are safe drugs whose benefits outweigh their potential side effects both short-term and long-term, provided their indication, dosage, and duration are appropriate.
Collapse
Affiliation(s)
| | | | | | - Javier Júdez Gutiérrez
- Departamento de Gestión del Conocimiento, Sociedad Española de Patología Digestiva SEPD, España
| | | | - Aida Ortega Alonso
- UGC Enfermedades Digestivas, Instituto de Investigación Biomédica de Málaga (IBIMA), Hospital Universitario Virgen de la Victoria, España
| | | | - Manuel Rodríguez-Téllez
- UGC Intercentros de Aparato Digestivo , Hospital Universitario Virgen de la Macarena (HUVM), España
| | | | | | - Ángel Álvarez Sánchez
- Servicio de Aparato Digestivo, Hospital Clínico San Carlos. Universidad Complutense de Madrid., España
| | - Raúl Jesús Andrade Bellido
- Unidad de Gestión Clinica de Aparato Digestivo, Instituto de Investigación Biomédica de Málaga (IBIMA), Hospital Universitario Virgen de la Victoria, España
| | | | | | - Froilán Giganto Tomé
- Servicio de Aparato Digestivo, Hospital Universitario Central de Asturias, España
| |
Collapse
|
|
34
|
Efficacy and Safety of Modified Banxia Xiexin Decoction (Pinellia Decoction for Draining the Heart) for Gastroesophageal Reflux Disease in Adults: A Systematic Review and Meta-Analysis. EVIDENCE-BASED COMPLEMENTARY AND ALTERNATIVE MEDICINE 2017; 2017:9591319. [PMID: 28298938 PMCID: PMC5337392 DOI: 10.1155/2017/9591319] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 10/17/2016] [Revised: 01/07/2017] [Accepted: 01/16/2017] [Indexed: 12/30/2022]
Abstract
Modified Banxia Xiexin decoction (MBXD) is a classical Chinese herbal formula in treating gastroesophageal reflux disease (GERD) for long time, but the efficacy of it is still controversial. This study is to evaluate the efficacy and safety of MBXD for the treatment of GERD in adults. The search strategy was carried out for publications in seven electronic databases. RevMan software version 5.3 and the Cochrane Collaboration's risk of bias tool were performed for this review. Twelve RCTs were included for the analysis. The results of overall clinical efficacy and efficacy under gastroscope demonstrated that MBXD was superior to conventional western medicine. Meanwhile, the results of subgroup analysis showed clinical heterogeneity between the two groups. However, there was no statistically significant difference in acid regurgitation between the two groups. But in the improvement of heartburn and sternalgia, the results showed statistically significant differences for the comparison between two groups. In addition, the adverse reactions of the experiment groups were not different from those of the control groups. This systematic review indicates that MBXD may have potential effects on the treatment of patients with GERD. But because the evidence of methodological quality and sample sizes is weak, further standardized researches are required.
Collapse
|
|
35
|
Tatsuzawa M, Ogawa R, Ohkubo A, Shimojima K, Maeda K, Echizen H, Miyazaki A. Influence of proton pump inhibitors and histamine H 2 receptor antagonists on serum phosphorus level control by calcium carbonate in patients undergoing hemodialysis: a retrospective medical chart review. J Pharm Health Care Sci 2016; 2:34. [PMID: 27895933 PMCID: PMC5120546 DOI: 10.1186/s40780-016-0068-1] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/28/2016] [Accepted: 11/11/2016] [Indexed: 11/10/2022] Open
Abstract
Background Hyperphosphatemia is one of the common complications in patients undergoing hemodialysis. Although calcium carbonate (CaC) is often used to control serum inorganic phosphorus level in dialysis patients, co-administration of gastric acid reducers (ARs) may interfere with the phosphate binding effect of CaC. We performed a retrospective medical chart review to study whether ARs attenuate the hypophosphatemic effect of CaC in patients undergoing hemodialysis. Methods One hundred and eight chronic hemodialysis patients receiving either CaC alone or CaC concomitant with one of the ARs (proton pump inhibitors and histamine H2-receptor antagonists) were retrieved from the medical charts in Juntendo University Nerima Hospital. The patients were subdivided according to the interval between hemodialysis sessions (interdialysis interval of 48 or 72 h). A multivariate analysis was performed to identify clinical covariates associated with the variability of serum inorganic phosphorus levels. The study protocol was approved by the Institutional Review Board before the study was begun. Results Among patients on hemodialysis with a 72-h interdialysis interval, the magnitude of increase in serum inorganic phosphorus concentration in patients receiving CaC and AR was significantly greater than in those receiving CaC alone. While a similar trend was observed among patients with a 48-h interdialysis interval, the difference did not reach a significant level. A multivariate regression analysis revealed that concomitant administration of ARs with CaC and a longer interdialysis interval (72 h) were significantly and independently associated with the magnitude of increase in serum phosphorus concentration between dialysis sessions. No significant differences in albumin-corrected serum calcium concentrations and incidence of pathological fractures were observed between patients receiving CaC alone and those receiving CaC with ARs. Conclusions Concomitant use of ARs with CaC may attenuate the hypophosphatemic effect of CaC in patients undergoing chronic hemodialysis. When hemodialysis patients require prescription of ARs for the prevention of upper gastrointestinal mucosal diseases (such as peptic ulcer), it may be prudent to choose a phosphate binder other than CaC.
Collapse
Affiliation(s)
- Masaomi Tatsuzawa
- Department of Pharmacy, Juntendo University Nerima Hospital, 3-1-10 Takanodai, Nerima-ku, Tokyo, 177-8521 Japan
| | - Ryuichi Ogawa
- Department of Pharmacotherapy, Meiji Pharmaceutical University, 2-522-1 Noshio, Kiyose-shi, Tokyo, 204-8588 Japan
| | - Atsushi Ohkubo
- Department of Pharmacy, Juntendo University Nerima Hospital, 3-1-10 Takanodai, Nerima-ku, Tokyo, 177-8521 Japan
| | - Kazuyo Shimojima
- Department of Pharmacy, Juntendo University Nerima Hospital, 3-1-10 Takanodai, Nerima-ku, Tokyo, 177-8521 Japan
| | - Kunimi Maeda
- Department of Nephrology, Juntendo University Nerima Hospital, 3-1-10 Takanodai, Nerima-ku, Tokyo, 177-8521 Japan
| | - Hirotoshi Echizen
- Department of Pharmacotherapy, Meiji Pharmaceutical University, 2-522-1 Noshio, Kiyose-shi, Tokyo, 204-8588 Japan
| | - Akihisa Miyazaki
- Departments of Gastroenterology and Pharmacy, Juntendo University Nerima Hospital, 3-1-10 Takanodai, Nerima-ku, Tokyo, 177-8521 Japan
| |
Collapse
|
|
36
|
Mössner J. The Indications, Applications, and Risks of Proton Pump Inhibitors. DEUTSCHES ARZTEBLATT INTERNATIONAL 2016; 113:477-83. [PMID: 27476707 PMCID: PMC4973002 DOI: 10.3238/arztebl.2016.0477] [Citation(s) in RCA: 30] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 11/19/2015] [Revised: 03/17/2016] [Accepted: 03/17/2016] [Indexed: 02/07/2023]
Abstract
BACKGROUND Proton pump inhibitors (PPI) are the most effective drugs for inhibiting gastric acid secretion. They have been in clinical use for more than 25 years, In 2014, 3.475 billion daily defined doses (DDD) of PPI were prescribed in Germany. This high number alone calls for a critical analysis of the spectrum of indications for PPI and their potential adverse effects. METHODS This review is based on pertinent publications retrieved by a selective search in the PubMed and Cochrane Library databases, with particular emphasis on randomized, prospective multicenter trials, cohort studies, case-control studies, and meta-analyses. RESULTS The inhibition of gastric acid secretion with PPI is successfully used for the treatment of gastroesophageal reflux disease and of gastric and duodenal ulcers, for the secondary prevention of gastroduodenal lesions that have arisen under treatment with nonsteroidal anti-inflammatory drugs and acetylsalicylic acid, and for the prevention of recurrent hemorrhage from ulcers after successful endoscopic hemostasis. PPI are given along with practically all antibiotic regimens for the eradication of Helicobacter pylori infection. The number of prescriptions for PPI has risen linearly over the past 25 years. As there has been no broadening of indications, one may well ask whether the current, extensive use of PPI is justified. There is evidence that patients taking PPI are at greater risk for fractures. Moreover, the vitamin B12 level should be checked occasionally in all patients taking PPI. CONCLUSION PPI are among the more effective drugs for the treatment of diseases associated with gastric acid. In view of their cost and potential adverse effects, they should only be prescribed for scientifically validated indications.
Collapse
Affiliation(s)
- Joachim Mössner
- Division of Gastroenterology and Rheumatology, Department of Internal Medicine, Neurology and Dermatology, University Hospital of Leipzig, Germany: Mössner
| |
Collapse
|
|
37
|
dos Reis Lívero FA, da Silva LM, Ferreira DM, Galuppo LF, Borato DG, Prando TBL, Lourenço ELB, Strapasson RLB, Stefanello MÉA, de Paula Werner MF, Acco A. Hydroethanolic extract of Baccharis trimera promotes gastroprotection and healing of acute and chronic gastric ulcers induced by ethanol and acetic acid. Naunyn Schmiedebergs Arch Pharmacol 2016; 389:985-98. [DOI: 10.1007/s00210-016-1262-2] [Citation(s) in RCA: 24] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/24/2016] [Accepted: 05/20/2016] [Indexed: 12/11/2022]
|
|
38
|
Abramowitz J, Thakkar P, Isa A, Truong A, Park C, Rosenfeld RM. Adverse Event Reporting for Proton Pump Inhibitor Therapy: An Overview of Systematic Reviews. Otolaryngol Head Neck Surg 2016; 155:547-54. [PMID: 27188706 DOI: 10.1177/0194599816648298] [Citation(s) in RCA: 42] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/20/2016] [Accepted: 04/15/2016] [Indexed: 12/12/2022]
Abstract
OBJECTIVE To assist clinicians in counseling patients regarding the risk of adverse events from proton pump inhibitors (PPIs), by synthesizing evidence from published systematic reviews of antireflux therapy. DATA SOURCES Cochrane Library, CINAHL, PubMed, Web of Knowledge. REVIEW METHODS Overview based on PRISMA reporting standards (preferred reporting items for systematic reviews and meta-analyses) of English-language meta-analyses and systematic reviews of PPI therapy for reflux disease through December 2014. Two independent investigators assessed study eligibility, rated the review quality with AMSTAR criteria (assessing the methodological quality of systematic reviews), and abstracted data for adverse events. RESULTS Thirty-three systematic reviews met inclusion criteria. The most commonly reported adverse events were community-acquired pneumonia (odds ratios, 1.04-1.92), with a greater association noted with shorter duration of therapy and higher doses. Hip fractures were also associated with PPI use (odds ratios, 1.16-1.50), especially with long-term therapy. Last, enteric infection with Clostridium difficile was more common with PPI therapy (odds ratios, 1.69-1.33). Other less commonly reported adverse events included electrolyte and vitamin deficiency. Risk factors for adverse events are reported in the text. CONCLUSION Our overview shows that PPI therapy is associated with significant and potentially serious adverse events that should be discussed with patients. The effect sizes and risk factors provided should facilitate this discussion and promote shared decision making.
Collapse
Affiliation(s)
- Jason Abramowitz
- Department of Otolaryngology, SUNY Downstate Medical Center, Brooklyn, New York, USA
| | - Punam Thakkar
- Department of Otolaryngology, SUNY Downstate Medical Center, Brooklyn, New York, USA
| | - Arton Isa
- Department of Otolaryngology, SUNY Downstate Medical Center, Brooklyn, New York, USA
| | - Alan Truong
- Department of Otolaryngology, SUNY Downstate Medical Center, Brooklyn, New York, USA
| | - Connie Park
- Department of Otolaryngology, SUNY Downstate Medical Center, Brooklyn, New York, USA
| | - Richard M Rosenfeld
- Department of Otolaryngology, SUNY Downstate Medical Center, Brooklyn, New York, USA
| |
Collapse
|
|
39
|
Zhou B, Huang Y, Li H, Sun W, Liu J. Proton-pump inhibitors and risk of fractures: an update meta-analysis. Osteoporos Int 2016; 27:339-47. [PMID: 26462494 DOI: 10.1007/s00198-015-3365-x] [Citation(s) in RCA: 174] [Impact Index Per Article: 19.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/11/2015] [Accepted: 10/01/2015] [Indexed: 12/13/2022]
Abstract
UNLABELLED To identify the relationship between proton-pump inhibitors (PPIs) and the risk of fracture, we conducted an update meta-analysis of observational studies. Results showed that PPI use was associated with a modestly increased risk of hip, spine, and any-site fracture. INTRODUCTION Many studies have investigated the association of proton-pump inhibitors (PPIs) with fracture risk, but the results have been inconsistent. To evaluate this question, we performed a meta-analysis of relevant observational studies. METHODS A systematic literature search up to February 2015 was performed in PubMed. We combined relative risks (RRs) for fractures using random-effects models and conducted subgroup and stratified analyses. RESULTS Eighteen studies involving a total of 244,109 fracture cases were included in this meta-analysis. Pooled analysis showed that PPI use could moderately increase the risk of hip fracture [RR = 1.26, 95 % confidence intervals (CIs) 1.16–1.36]. There was statistically significant heterogeneity among studies (p < 0.001; I 2 = 71.9 %). After limiting to cohort studies, there was also a moderate increase in hip fracture risk without evidence of study heterogeneity. Pooling revealed that short-term use (<1 year) and longer use (>1 year) were similarly associated with increased risk of hip fracture. Furthermore, a moderately increased risk of spine (RR = 1.58, 95 % CI 1.38–1.82) and any-site fracture (RR = 1.33, 95 % CI 1.15–1.54) was also found among PPI users. CONCLUSION In this update meta-analysis of observational studies, PPI use modestly increased the risk of hip, spine, and any-site fracture, but no evidence of duration effect in subgroup analysis.
Collapse
|
|
40
|
Connett GJ. Cystic Fibrosis Nutrition--Chewing the Fat. Paediatr Respir Rev 2016; 17:42-4. [PMID: 26527359 DOI: 10.1016/j.prrv.2015.08.006] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/26/2015] [Accepted: 08/28/2015] [Indexed: 10/22/2022]
Abstract
Survival data for successive birth cohorts of cystic fibrosis infants born in the twentieth century have shown consistent improvements. More recent UK and US data suggest a plateau in improvements for clinically relevant outcomes. Better treatment of malnutrition has arguably been the most important advance in CF care, but despite this nearly a half of the UK CF population has a sub-optimal BMI. Nutritional decline typically occurs in late childhood and early adult life. Addressing poor adherence and more targeted multi-disciplinary interventions to prevent or reverse this pattern are key to achieving better outcomes for CF patients in the future.
Collapse
Affiliation(s)
- Gary J Connett
- Consultant in Paediatric Respiratory Medicine, Southampton Children's Hospital, University Hospital Southampton NHS Foundation Trust, Tremona Road, Southampton, SO16 6YD, UK.
| |
Collapse
|
|
41
|
Benmassaoud A, McDonald EG, Lee TC. Potential harms of proton pump inhibitor therapy: rare adverse effects of commonly used drugs. CMAJ 2015; 188:657-662. [PMID: 26598371 DOI: 10.1503/cmaj.150570] [Citation(s) in RCA: 22] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022] Open
Affiliation(s)
- Amine Benmassaoud
- Division of General Internal Medicine (Benmassaoud, McDonald, Lee), Department of Medicine, McGill University Health Centre; McGill Centre for Quality Improvement (McDonald, Lee), Montréal, Que
| | - Emily G McDonald
- Division of General Internal Medicine (Benmassaoud, McDonald, Lee), Department of Medicine, McGill University Health Centre; McGill Centre for Quality Improvement (McDonald, Lee), Montréal, Que
| | - Todd C Lee
- Division of General Internal Medicine (Benmassaoud, McDonald, Lee), Department of Medicine, McGill University Health Centre; McGill Centre for Quality Improvement (McDonald, Lee), Montréal, Que.
| |
Collapse
|
|
42
|
Schonheit C, Le Petitcorps H, Pautas É. [Prescription for proton pump inhibitors in geriatrics]. SOINS. GERONTOLOGIE 2015; 20:39-44. [PMID: 26574132 DOI: 10.1016/j.sger.2015.09.010] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/05/2023]
Abstract
Proton pump inhibitors are widely prescribed, notably for the over 65s, despite there being significant side effects in the geriatric population. It is therefore important that doctors, caregivers and patients are fully aware of the recognised indications of PPIs and on the less well-known problems inherent to their prescription.
Collapse
Affiliation(s)
- Claire Schonheit
- Service de court séjour gériatrique, hôpital Charles-Foix, 7 avenue de la République, 94205 Ivry-sur-Seine cedex, France
| | - Hélène Le Petitcorps
- Service de court séjour gériatrique, hôpital Charles-Foix, 7 avenue de la République, 94205 Ivry-sur-Seine cedex, France
| | - Éric Pautas
- Service de court séjour gériatrique, hôpital Charles-Foix, 7 avenue de la République, 94205 Ivry-sur-Seine cedex, France; UFR de médecine Pierre et Marie-Curie, université Paris 6, 4 place Jussieu, 75005 Paris, France.
| |
Collapse
|
|
43
|
Abstract
Although outcome data for individuals with cystic fibrosis (CF) have shown consistent improvements throughout the twentieth century, more recent national registry data suggests that outcomes have reached a plateau. Median values for nutritional outcomes in CF currently cluster around the fiftieth centile for the normal population. These data suggest that up to half of CF patients have sub-optimal body mass index (BMI) which might have a significant adverse impact on their respiratory status. BMI might be underestimating the extent to which more important lean body mass might also be reduced. Nutritional decline is a particular problem during adolescence and commonly persists into early adult life. Current treatment strategies to optimize nutrition include the use of high energy diets, proton pump inhibitors and optimal use of enzyme preparations including higher strength preparations to decrease pill burden. Whilst these are all of potential benefit, poor adherence to nutritional care recommendations is probably the greatest impediment to future health improvement. More effective strategies to impact on treatment adherence are needed.
Collapse
Affiliation(s)
- Gary J Connett
- Southampton Children's Hospital and UK National Institute for Health Research Southampton Respiratory Biomedical Research Unit, Tremona Road, Southampton, Hampshire SO16 6YD, UK.
| | - Katharine C Pike
- University College London, Institute of Child Health, 30 Guilford Street, London WC1N 1EH, UK.
| |
Collapse
|
|
44
|
Cai D, Feng W, Jiang Q. Acid-suppressive medications and risk of fracture: an updated meta-analysis. Int J Clin Exp Med 2015; 8:8893-8904. [PMID: 26309543 PMCID: PMC4538134] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/13/2015] [Accepted: 05/20/2015] [Indexed: 06/04/2023]
Abstract
BACKGROUND Acid-suppressive medications are widely used for the management of acid-related disorders. It has been reported that acid-suppressive medication users were at increased risk of fracture, but such an association was inconsistent among observational studies. The purpose of our analysis was to assess the relationship between use of antacid drugs and fracture risk. METHODS We systematically searched electronic database and manually examined the reference lists of previous reviews for potentially eligible studies. Given the heterogeneity across studies, random effects models were used to calculate summary estimates. Subgroup analysis and sensitivity analysis were conducted to explore the potential heterogeneity. RESULTS 18 studies met our inclusion criteria. PPI and H2RA were associated with increased risk of hip fracture, with substantial heterogeneity (PPI: 1.216, 1.134-1.304, I(2)=71.3%; H2RA: 1.128, 1.022-1.245, I(2)=72.1%). High risk of spine fracture was observed in PPI users (1.216, 95% CI: 1.134-1.304) but not H2RA users. When considering 5 studies conducted among postmenopausal women, the RR was 1.376, (95% CI: 1.043-1.816) with modest heterogeneity (I(2)=57.7%). Subgroup analysis and sensitivity analysis found consistent association between hip fracture risk and PPI use but not H2RA use. Positive association for H2RA use lost its significance when considering case-control studies and European studies. CONCLUSION Results of this updated meta-analysis provided evidence to support that acid-suppressive medications were associated with increased risk of fracture, especially hip fracture.
Collapse
Affiliation(s)
- Dawei Cai
- Department of Orthopedics, Drum Tower Hospital, Nanjing University Medical School No. 321 Zhongshan Road, Nanjing, China
| | - Wan Feng
- Nanjing University Medical School Nanjing, People's Republic of China
| | - Qing Jiang
- Department of Orthopedics, Drum Tower Hospital, Nanjing University Medical School No. 321 Zhongshan Road, Nanjing, China
| |
Collapse
|
|
45
|
Truter I, Shankar S, Bennie M, Woerkom MV, Godman B. Initiatives in South Africa to enhance the prescribing of generic proton pump inhibitors: findings and implications. J Comp Eff Res 2015; 4:123-31. [DOI: 10.2217/cer.14.70] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/21/2022] Open
Abstract
Background: There have been multiple reforms in South Africa to conserve resources including policies to enhance generic use, such as compulsory generic substitution and copayments. However, there are concerns with the limited knowledge of their impact. Objective: The objective was to determine utilization and expenditure of different proton pump inhibitors (PPIs). Methodology: A retrospective drug utilization study was conducted on a prescription database of a medical aid administrator in 2010. Results: The limited prescribing of single-sourced PPIs accounted for 21.5% of total prescriptions. The limited use of originators omeprazole and lansoprazole accounted for 1.8 and 1.4% of total prescriptions for the molecule, respectively. Generic prices accounted for 36–68% of the originator in 2010. Patients received on average 2.91 PPI prescriptions during the year. Conclusion: Policies to enhance prescribing of generics appear working. Opportunities exist to further lower generic prices given low prices in some European countries.
Collapse
Affiliation(s)
- Ilse Truter
- Drug Utilization Research Unit (DURU), Department of Pharmacy, Nelson Mandela Metropolitan University, Port Elizabeth 6031, South Africa
| | - Sushma Shankar
- Nuffield Department of Surgical Sciences, University of Oxford, John Radcliffe Hospital, Headington, Oxford, OX3 9DU, UK
| | - Marion Bennie
- Strathclyde Institute of Pharmacy & Biomedical Sciences, University of Strathclyde, Glasgow, UK
| | - Menno van Woerkom
- Dutch Institute for Rational Use of Medicines, Utrecht, The Netherlands
| | - Brian Godman
- Strathclyde Institute of Pharmacy & Biomedical Sciences, University of Strathclyde, Glasgow, UK
- Department of Laboratory Medicine, Division of Clinical Pharmacology, Karolinska Institutet, Karolinska University Hospital, Huddinge, SE-141 86 Stockholm, Sweden
- National Institute for Science & Technology on Innovation on Neglected Diseases, Center for Technological Development in Health, Oswaldo Cruz Foundation, Rio de Janeiro, Brazil
| |
Collapse
|
|
46
|
Rossini M, Viapiana O, Adami S, Idolazzi L, Buda S, Veronesi C, Degli Esposti L, Gatti D. Medication use before and after hip fracture: a population-based cohort and case-control study. Drugs Aging 2015; 31:547-53. [PMID: 24825617 DOI: 10.1007/s40266-014-0184-2] [Citation(s) in RCA: 19] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/25/2022]
Abstract
BACKGROUND Osteoporosis, together with age, is the main risk factor for hip fracture, the incidence of which has also been associated with an increased risk of falling or co-morbidities and related pharmacological treatments. OBJECTIVES The aim of this study was to investigate changes in concomitant pharmacological treatments prescribed before and after hip fracture in elderly patients compared with treatments prescribed to a matched cohort of subjects without hospitalisation for fractures. METHODS Data relating to the study population were extracted from a large population-based administrative database of the Italian National Health Authorities. A retrospective analysis was conducted involving female patients (6,431) aged ≥65 years and hospitalised for a hip fracture. The control group comprised age-matched subjects (38,586) not hospitalised for fracture. Changes in drug prescriptions 1 year before and 1 year after hip fracture and differences versus controls were compared. RESULTS Prior to the fracture, patients were taking more anti-Parkinson medications, antidepressants, medications for chronic obstructive pulmonary disease (COPD), bisphosphonates and calcium-vitamin D supplements, although the intake of the routinely monitored drug classes was significantly infrequent. Polypharmacy was less frequent in fractured women before fracture than in controls (22 vs. 25 %, respectively; P < 0.001), but it was more frequent (30 %, P < 0.001) post-fracture. The incidence of fracture was associated with a significant increase in the use of a number of drug classes: insulin, NSAIDs or analgesics, gastroprotectants, loop diuretics, β-blockers, antidepressants, antiparkinson drugs, antiepileptics and drugs for COPD. CONCLUSION Our study confirms a strong association between the use of some drugs (antidepressants, antiparkinson drugs, drugs for COPD) and the risk of hip fracture, but drug use is globally less common than in controls. Hip fracture is associated with a significant increase in drug use, suggesting a global deterioration of health conditions.
Collapse
Affiliation(s)
- Maurizio Rossini
- Rheumatology Unit, Department of Medicine, University of Verona, Policlinico Borgo Roma, Piazzale Scuro, 10, 37134, Verona, Italy,
| | | | | | | | | | | | | | | |
Collapse
|
|
47
|
Li H, Zhang HM, Chen LF, Chen YQ, Chen L, Ren H, Hu HD. Prophylactic lamivudine to improve the outcome of HBsAg-positive lymphoma patients during chemotherapy: a systematic review and meta-analysis. Clin Res Hepatol Gastroenterol 2015; 39:80-92. [PMID: 25199680 DOI: 10.1016/j.clinre.2014.07.010] [Citation(s) in RCA: 18] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/21/2014] [Revised: 04/23/2014] [Accepted: 07/23/2014] [Indexed: 02/04/2023]
Abstract
Hepatitis B viral (HBV) reactivation in lymphoma patients undergoing chemotherapy is associated with significant morbidity and mortality. Increasingly, lamivudine is being used to prevent hepatitis B reactivation. To assess the effects of prophylactic lamivudine on reactivation and mortality following chemotherapy in lymphoma patients who are hepatitis B surface antigen (HBsAg)-positive, we searched Medline/PubMed, Ovid MEDLINE, EMBASE, Web of Knowledge and the Cochrane Library for studies through November 2013. Statistical analysis was performed using REVMAN. Fourteen studies consisting of 636 patients were included in the analysis. The rate of HBV reactivation, incidence of hepatitis and incidence of hepatitis due to HBV reactivation in patients with lamivudine prophylaxis was significantly lower than those with no prophylaxis. Risk ratios [RRs] were 0.25 (95% confidence intervals [CI] 0.13-0.51; P=0.0001), 0.40 (95% CI 0.26-0.63; P<0.0001), and 0.21 (95% CI 0.09-0.51; P=0.0005) respectively. In addition, patients given prophylactic lamivudine had significant reductions in overall mortality and mortality attributable to HBV reactivation compared with control group. Risk ratios [RRs] were 0.45 (95% CI 0.29-0.70; P=0.0004) and 0.41 (95% CI 0.20-0.84; P=0.01) respectively. Chemotherapy disruption was not significantly different between the two groups. Risk ratios [RRs] were 0.34 (95% CI 0.09-1.26; P=0.11). Prophylactic therapy with lamivudine for HBsAg-positive lymphoma patients who are undergoing chemotherapy may reduce the risk for HBV reactivation, hepatitis due to HBV reactivation, overall mortality and mortality attributable to HBV reactivation. Additionally, patients with preventive lamivudine had a trend towards the decreased incidence of chemotherapy disruption.
Collapse
Affiliation(s)
- Hong Li
- Department of Infectious Diseases, Institute for Viral Hepatitis, The Second Affiliated Hospital of Chongqing Medical University, 76, Linjiang Road, 400010 Chongqing, China
| | - Hong-Min Zhang
- Department of Infectious Diseases, Institute for Viral Hepatitis, The Second Affiliated Hospital of Chongqing Medical University, 76, Linjiang Road, 400010 Chongqing, China
| | - Li-Fen Chen
- Department of Neurology, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, China
| | - Ya-Qin Chen
- Department of Infectious Diseases, Institute for Viral Hepatitis, The Second Affiliated Hospital of Chongqing Medical University, 76, Linjiang Road, 400010 Chongqing, China
| | - Ling Chen
- Department of Infectious Diseases, Institute for Viral Hepatitis, The Second Affiliated Hospital of Chongqing Medical University, 76, Linjiang Road, 400010 Chongqing, China
| | - Hong Ren
- Department of Infectious Diseases, Institute for Viral Hepatitis, The Second Affiliated Hospital of Chongqing Medical University, 76, Linjiang Road, 400010 Chongqing, China; Institute for Viral Hepatitis of Chongqing Medical University, Chongqing, China; Key Laboratory of Molecular Biology for Infectious Diseases, Ministry of Education, Chongqing Medical University, Chongqing, China
| | - Huai-Dong Hu
- Department of Infectious Diseases, Institute for Viral Hepatitis, The Second Affiliated Hospital of Chongqing Medical University, 76, Linjiang Road, 400010 Chongqing, China; Institute for Viral Hepatitis of Chongqing Medical University, Chongqing, China; Key Laboratory of Molecular Biology for Infectious Diseases, Ministry of Education, Chongqing Medical University, Chongqing, China.
| |
Collapse
|
|
48
|
Zeng W, Finlayson AE, Shankar S, de Bruyn W, Godman B. Prescribing efficiency of proton pump inhibitors in China: influence and future directions. BMC Health Serv Res 2015; 15:11. [PMID: 25609265 PMCID: PMC4308879 DOI: 10.1186/s12913-014-0638-6] [Citation(s) in RCA: 18] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/28/2014] [Accepted: 12/08/2014] [Indexed: 02/04/2023] Open
Abstract
BACKGROUND Pharmaceutical expenditure is currently rising by 16% per annum in China, greater in recent years. Initiatives to moderate growth include drug pricing regulations, essential medicine lists and encouraging generic prescribing. These are principally concentrated in hospitals, which currently account for over 80% of total pharmaceutical expenditure. However, no monitoring of prescribing and perverse incentives encouraging physicians and hospitals to profit from drug procurement encourages irrational prescribing. This includes greater utilisation of originators versus generics as well as injectables when cheaper oral equivalents are available. The objective of the paper is to assess changes in proton pump inhibitor (PPI) utilisation and expenditure in China as more generics become available including injectables. METHODS Observational retrospective study of PPI utilisation and procured expenditure between 2004 and 2013 in the largest teaching hospital in Chongqing District as representative of China. RESULTS Appreciable increase in PPI utilisation during the study period rising 10.4 fold, with utilisation of generics rising faster than originators. Oral generics reached 84% of total oral preparations in 2013 (defined daily dose basis), with generic injectables 93% of total injectables by 2013. Injectables accounted for 42% of total PPI utilisations in 2008 and 2009 before falling to below 30%. Procured prices for oral preparations reduced over time (-34%). Generic oral omeprazole in 2010 was 87% below 2004 originator prices, mirroring reductions seen in Western Europe. Injectable prices also decreased over time (-19%). However, injectables typically 4.3 to 6.8 fold more expensive than equivalent orals - highest for injectable lansoprazole at 13.4 to 18.0 fold. High utilisation of more expensive oral PPIs as well as injectables meant that PPI expenditure increased 10.1 fold during the study period. Lower use of injectables, and only oral generic omeprazole, would result in accumulated savings of CNY249.65 million, reducing total accumulated expenditure by 84%. CONCLUSIONS Encouraging to see high utilisation of generic PPIs and low prices for oral generics. However, considerable opportunities to enhance prescribing efficiency through greater use of oral generic omeprazole.
Collapse
Affiliation(s)
- Wenjie Zeng
- School of Management, Chongqing Jiaotong University, No.66 Xuefu Road, Nan'an District, Chongqing, 400074, China.
| | | | - Sushma Shankar
- Nuffield Department of Surgical Sciences, John Radcliffe Hospital, University of Oxford, Headington, Oxford, OX3 9DU, UK.
| | - Winnie de Bruyn
- Department of Pharmaceutical Sciences, Utrecht University, Utrecht, Netherlands.
| | - Brian Godman
- Department of Laboratory Medicine, Division of Clinical Pharmacology, Karolinska Institutet, Karolinska University Hospital Huddinge, Stockholm, SE-141 86, Sweden. .,Strathclyde Institute of Pharmacy and Biomedical Sciences, University of Strathclyde, Glasgow, UK. .,Liverpool Health Economics Centre, Liverpool University, Chatham Street, Liverpool, L69 7ZH, UK.
| |
Collapse
|
|
49
|
Pinheiro Silva L, Damacena de Angelis C, Bonamin F, Kushima H, José Mininel F, Campaner Dos Santos L, Karina Delella F, Luis Felisbino S, Vilegas W, Regina Machado da Rocha L, Aparecido Dos Santos Ramos M, Maria Bauab T, Toma W, Akiko Hiruma-Lima C. Terminalia catappa L.: a medicinal plant from the Caribbean pharmacopeia with anti-Helicobacter pylori and antiulcer action in experimental rodent models. JOURNAL OF ETHNOPHARMACOLOGY 2015; 159:285-295. [PMID: 25460589 DOI: 10.1016/j.jep.2014.11.025] [Citation(s) in RCA: 33] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 08/22/2014] [Revised: 11/03/2014] [Accepted: 11/13/2014] [Indexed: 06/04/2023]
Abstract
ETHNOPHARMACOLOGICAL RELEVANCE Terminalia catappa L. (Combretaceae) is a medicinal plant listed as a pharmacopeia vegetable from Caribbean to treat gastritis. The objective of this study was to evaluate the gastroprotective and healing effect of the aqueous fraction (FrAq) obtained from the leaves of Terminalia catappa and to determine the antiulcer mechanism of action in experimental rodent models and its activity to Helicobacter pylori. MATERIAL AND METHODS In rodents, the FrAq was challenged by different necrotizing agents, such as absolute ethanol and ischemia-reperfusion injury. The antiulcer mechanism of action of FrAq was assessed and the healing effects of the fraction after seven and 14 days of treatment was evaluated by matrix metalloproteinase activity (MMP-2 and MMP-9). The toxicological effect of subacute treatment with FrAq during 14 days of treatment was also analyzed. The anti-Helicobacter pylori activity was determined by microdilution. The phytochemical study of the fraction was analyzed by experiments with FIA-ESI-IT-MS(n) (Direct Flow Analysis-ionization Electrospray Ion Trap Tandem Mass Spectrometry) and high performance liquid chromatography (HPLC) coupled to a photodiode array (PDA). RESULTS Oral treatment with FrAq (25mg/kg) significantly decreased the number of ulcerative lesions induced by ethanol and ischemia/reperfusion injury. The action of FrAq was mediated by the activation of defensive mucosa-protective factors, such as increases in mucus production, the nitric oxide (NO) pathway and endogenous prostaglandins. Oral treatment with FrAq for seven and 14 days significantly reduced the lesion area (80% and 37%, respectively) compared to the negative control group. Analyses of MMP-9 and MMP-2 activity from gastric mucosa confirmed the accelerated gastric healing effect of FrAq. This extract also presented considerable activity against Helicobacter pylori. The mass spectrum and MS/MS of the aqueous fraction indicates the existence of many different phenolic compounds, including punicalagin, punicalin, and gallagic acid, among others. CONCLUSIONS We concluded that FrAq from Terminalia catappa leaves has excellent preventive and curative effects on acute and chronic induced gastric ulcers and showed an important profile against Helicobacter pylori.
Collapse
Affiliation(s)
- Laísa Pinheiro Silva
- Univ. Estadual Paulista-UNESP - Departamento de Fisiologia, Instituto de Biociências, CEP 18618-970 Botucatu, SP, Brazil
| | - Célio Damacena de Angelis
- Univ. Estadual Paulista-UNESP - Departamento de Fisiologia, Instituto de Biociências, CEP 18618-970 Botucatu, SP, Brazil
| | - Flavia Bonamin
- Univ. Estadual Paulista-UNESP - Departamento de Fisiologia, Instituto de Biociências, CEP 18618-970 Botucatu, SP, Brazil
| | - Hélio Kushima
- Univ. Estadual Paulista-UNESP - Departamento de Fisiologia, Instituto de Biociências, CEP 18618-970 Botucatu, SP, Brazil
| | - Francisco José Mininel
- Univ. Estadual Paulista-UNESP - Departamento de Química Orgânica, Instituto de Química, CEP 14800-900, Araraquara, SP, Brazil
| | - Lourdes Campaner Dos Santos
- Univ. Estadual Paulista-UNESP - Departamento de Química Orgânica, Instituto de Química, CEP 14800-900, Araraquara, SP, Brazil
| | - Flavia Karina Delella
- Univ. Estadual Paulista-UNESP - Departamento de Morfologia, Instituto de Biociências, CEP 18618-970, Botucatu, SP, Brazil
| | - Sergio Luis Felisbino
- Univ. Estadual Paulista-UNESP - Departamento de Morfologia, Instituto de Biociências, CEP 18618-970, Botucatu, SP, Brazil
| | - Wagner Vilegas
- Univ. Estadual Paulista-UNESP - Campus Experimental do Litoral Paulista, CEP 11330-900 São Vicente, SP, Brazil
| | - Lucia Regina Machado da Rocha
- Univ. Estadual Paulista-UNESP - Departamento de Fisiologia, Instituto de Biociências, CEP 18618-970 Botucatu, SP, Brazil
| | - Matheus Aparecido Dos Santos Ramos
- Univ. Estadual Paulista-UNESP - Departamento de Ciências Biológicas, Faculdade de Ciências Farmacêuticas, CEP 14801-902, Araraquara, SP, Brazil
| | - Tais Maria Bauab
- Univ. Estadual Paulista-UNESP - Departamento de Ciências Biológicas, Faculdade de Ciências Farmacêuticas, CEP 14801-902, Araraquara, SP, Brazil
| | - Walber Toma
- Universidade Santa Cecília - Pós-Graduação em Sustentabilidade de Ecossistemas Costeiros e Marinhos, Rua Oswaldo Cruz, 266, Boqueirão, CEP 11045907 Santos, SP, Brazil.
| | - Clelia Akiko Hiruma-Lima
- Univ. Estadual Paulista-UNESP - Departamento de Fisiologia, Instituto de Biociências, CEP 18618-970 Botucatu, SP, Brazil.
| |
Collapse
|
|
50
|
Protective effects of garlic extract, PMK-S005, against nonsteroidal anti-inflammatory drugs-induced acute gastric damage in rats. Dig Dis Sci 2014; 59:2927-34. [PMID: 25283375 DOI: 10.1007/s10620-014-3370-5] [Citation(s) in RCA: 24] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/29/2014] [Accepted: 09/15/2014] [Indexed: 01/25/2023]
Abstract
BACKGROUND PMK-S005 is synthetic s-allyl-L-cysteine (SAC), a sulfur-containing amino acid, which was initially isolated from garlic. The antioxidant and anti-inflammation activities of SAC have been demonstrated in diverse experimental animal models. AIMS The purpose of this study was to investigate the gastroprotective effects of PMK-S005 against NSAIDs-induced acute gastric damage in rats. METHODS Eight-week SD rats were pretreated with PMK-S005 (1, 5, or 10 mg/kg) or rebamipide (50 mg/kg) 1 h before administration of NSAIDs including aspirin (200 mg/kg), diclofenac (80 mg/kg), and indomethacin (40 mg/kg). After 4 h, the gross ulcer index, histological index, and gastric mucus level were determined. Myeloperoxidase (MPO), TNF-α, IL-1β, PGE2, and LTB4 levels were estimated in the gastric mucosal tissue by ELISA. Protein expressions of cPLA2, COX-1, and COX-2 were assessed by Western blot analysis. RESULTS Pretreatment with PMK-S005 significantly attenuated the NSAIDs-induced gastric damage and increased the gastric mucus level. In addition, PMK-S005 attenuated increases in MPO, TNF-α, and IL-1β production. The expressions of cPLA2 and COX-2 induced by NSAIDs were decreased by PMK-S005 pretreatment. PMK-S005 did not cause suppression of PGE2 synthesis induced by NSAIDs, but LTB4 production was significantly suppressed by PMK-S005. The effects of PMK-S005 were consistently maximized at a concentration of 5 mg/kg, which were frequently superior to those of rebamipide. CONCLUSIONS These results strongly suggest that PMK-S005 can be a useful gastroprotective agent against acute gastric mucosal damage by suppressing proinflammatory cytokines, down-regulating cPLA2, COX-2 and LTB4 expression, and increasing the synthesis of mucus.
Collapse
|