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Mohan M, Mannan A, Singh S, Singh TG. Unlocking the cellular mystery: how proton pump inhibitors may alter the dementia landscape. Brain Res 2025; 1861:149702. [PMID: 40368227 DOI: 10.1016/j.brainres.2025.149702] [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: 03/27/2025] [Revised: 04/30/2025] [Accepted: 05/10/2025] [Indexed: 05/16/2025]
Abstract
Proton pump inhibitors (PPIs) have become virtually the sole class of histamine-2 receptor antagonists due to their greater effectiveness and general availability. However, concern has been increasing about long-term use and some possible neurological adverse effects, including a link with dementia. Several studies indicate that long-term use of PPIs can raise the risk for both Alzheimer's disease (AD) and non-Alzheimer's dementia, though there is opposing evidence. Neurological side effects of PPIs are cognitive impairment, neuropathies, depression, anxiety, and hallucinations. The mechanisms are unknown but could be due to PPIs crossing the BBB and interfering with neuronal function or causing systemic deficiencies, e.g., vitamin B12 deficiency. Vitamin B12 is essential for cognitive function, and its deficiency has been linked to dementia. PPIs also cause B12 deficiency by inhibiting gastric acid secretion, which is required for B12 absorption. B12 deficiency causes hyperhomocysteinemia, which facilitates tau hyperphosphorylation and amyloid-β (Aβ) deposition, major pathological hallmarks of AD. PPIs have also been found to disrupt amyloid precursor protein processing, mitochondrial function, and neuroinflammation, further enhancing neurodegenerative processes. Experimental evidence indicates that PPIs affect brain homeostasis through inhibition of vacuolar ATPases, modulation of microglial Aβ phagocytosis, and induction of synaptic dysfunction. While the specific molecular mechanisms are unknown, findings suggest that long-term PPI exposure could contribute to neurodegeneration, especially in elderly patients. With increasing dementia prevalence, additional clinical research is needed to ascertain whether PPIs are a causative agent or a contributing factor to cognitive impairment.
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Affiliation(s)
- Maneesh Mohan
- Chitkara College of Pharmacy, Chitkara University, Rajpura, 140401, Punjab, India.
| | - Ashi Mannan
- Chitkara College of Pharmacy, Chitkara University, Rajpura, 140401, Punjab, India.
| | - Shareen Singh
- Chitkara College of Pharmacy, Chitkara University, Rajpura, 140401, Punjab, India.
| | - Thakur Gurjeet Singh
- Chitkara College of Pharmacy, Chitkara University, Rajpura, 140401, Punjab, India.
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Khadivi A, Amiri F, Radnia P, Salehi-Pourmehr H, Mirzaei Bavil F, Pakkhesal S, Hamzehzadeh S, Moghaddam YJ, Naseri A. Proton pump inhibitors and risk of hearing loss; a systematic review. NAUNYN-SCHMIEDEBERG'S ARCHIVES OF PHARMACOLOGY 2025:10.1007/s00210-025-04241-5. [PMID: 40343450 DOI: 10.1007/s00210-025-04241-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 03/07/2025] [Accepted: 04/28/2025] [Indexed: 05/11/2025]
Abstract
Proton pump inhibitors (PPIs) are widely used medications for the treatment of gastroesophageal reflux disease (GERD) and other conditions requiring acid suppression. While generally considered safe, concerns have emerged regarding potential long-term adverse effects of PPIs, such as ototoxicity. To systematically synthesize the evidence regarding the association between PPIs usage and the risk of hearing loss. This systematic review followed PRISMA guidelines. PubMed/Medline, Embase, Scopus, and Web of Science databases were searched in May 2024 and further updated using a handsearching in December 2024. Clinical original studies evaluating the relationship between PPI usage and any type of hearing impairments were included. Exclusion criteria include non-human studies, non-English language publications, reviews, case reports, book chapters, conference abstracts, and retracted studies. Risk of bias was assessed using the Joanna Briggs Institute (JBI) critical appraisal tools. The initial database search yielded 661 records. Four studies (total n = 208,956 participants) proceeded to full-text review and were included in the qualitative synthesis. All of the included studies demonstrated a statistically significant association between PPI use and an increased risk of hearing impairments; even after adjusting for possible confounders; however, one study found no independent association after adjusting for GERD symptoms. The findings of this systematic review reveal inconclusive results regarding the association between PPI use and hearing loss. While the limited available evidence suggests a possible increased risk, further research is needed to dissect the possible causal relationship and elucidate the underlying mechanisms.
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Affiliation(s)
- Amin Khadivi
- Department of Otolaryngology, Imam Reza General Hospital, School of Medicine, Tabriz University of Medical Sciences, Golgasht Street, Tabriz, 5166/15731, Iran
| | - Fatemeh Amiri
- Student Research Committee, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Parastoo Radnia
- Student Research Committee, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Hanieh Salehi-Pourmehr
- Research Center for Evidence-Based Medicine, Iranian EBM Centre: A Joanna Briggs Institute (JBI) Center of Excellence, Tabriz University of Medical Sciences, Golgasht Street, Tabriz, East Azerbaijan, 5166/15731, Iran
| | - Fariba Mirzaei Bavil
- Department of Physiology, School of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Sina Pakkhesal
- Student Research Committee, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Sina Hamzehzadeh
- Research Center for Evidence-Based Medicine, Iranian EBM Centre: A Joanna Briggs Institute (JBI) Center of Excellence, Tabriz University of Medical Sciences, Golgasht Street, Tabriz, East Azerbaijan, 5166/15731, Iran
| | - Yalda Jabbari Moghaddam
- Department of Otolaryngology, Imam Reza General Hospital, School of Medicine, Tabriz University of Medical Sciences, Golgasht Street, Tabriz, 5166/15731, Iran.
| | - Amirreza Naseri
- Research Center for Evidence-Based Medicine, Iranian EBM Centre: A Joanna Briggs Institute (JBI) Center of Excellence, Tabriz University of Medical Sciences, Golgasht Street, Tabriz, East Azerbaijan, 5166/15731, Iran.
- Clinical Research Development Unit of Tabriz Valiasr Hospital, Tabriz University of Medical Sciences, Tabriz, Iran.
- Tabriz USERN Office, Universal Scientific Education and Research Network (USERN), Tabriz, Iran.
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Zhan Z, Li J, Zhang W, Huang S, Fang X. Multidimensional Assessment of Psychiatric Adverse Events Related to Proton Pump Inhibitors: A Real-World, Pharmacovigilance Study. CNS Neurosci Ther 2025; 31:e70436. [PMID: 40365732 PMCID: PMC12076120 DOI: 10.1111/cns.70436] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/02/2025] [Revised: 04/18/2025] [Accepted: 04/30/2025] [Indexed: 05/15/2025] Open
Abstract
INTRODUCTION Limited research has been conducted on the association between proton pump inhibitors (PPIs) use and psychiatric adverse events (AEs), leaving the understanding of PPIs-related psychiatric AEs in real-world settings unclear. OBJECTIVES We aim to identify psychiatric AEs highly relevant to five commonly prescribed PPIs and to delve into the clinical characteristics of the population experiencing psychiatric AEs, as well as the time-to-onset pattern of the reported AEs. METHODS We performed disproportionality analysis to evaluate the PPI-related psychiatric AEs risk signal using data from the FDA adverse event reporting system. Linkage disequilibrium score regression, high-definition likelihood, and Bidirectional MR analyses were employed to evaluate genetic correlations and causality for the pairwise traits between indications for PPI therapy and three common psychiatric disorders. RESULTS Psychiatric AEs were reported in 12.83% of all AE reports on PPIs. Disproportionality analysis identified multiple PPI-related psychiatric AE risk signals such as depressive disorder, bipolar disorder, and sleep disorder, with Omeprazole exhibiting the highest number of positive signals and cases (N = 386) and Rabeprazole the fewest (N = 28). Notably, we detected positive signals for suicide or self-injury-related AEs in three types of PPIs. Significant genetic correlations were revealed in peptic ulcer with major depressive disorder, peptic ulcer with schizophrenia, and gastroesophageal reflux disease (GERD) with major depressive disorder. Bidirectional MR analyses identified significant causal relationships between MDD and peptic ulcer, and a potential bidirectional causal association between GERD and MDD. CONCLUSIONS PPI-related psychiatric AEs may represent a non-negligible portion of overall PPI-related AEs. It is recommended to monitor and evaluate the safety of long-term PPI use in relation to psychiatric AEs.
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Affiliation(s)
- Zhi‐Qing Zhan
- Division of Gastroenterology and Hepatology, NHC Key Laboratory of Digestive Diseases, State Key Laboratory for Oncogenes and Related Genes, Shanghai Institute of Digestive Disease, School of Medicine, Renji HospitalShanghai Jiao Tong UniversityShanghaiChina
| | - Jia‐Xin Li
- Department of Gastroenterology and Hepatology, West China HospitalSichuan UniversityChengduChina
| | - Wei‐Gang Zhang
- Division of Gastroenterology and Hepatology, NHC Key Laboratory of Digestive Diseases, State Key Laboratory for Oncogenes and Related Genes, Shanghai Institute of Digestive Disease, School of Medicine, Renji HospitalShanghai Jiao Tong UniversityShanghaiChina
| | - Shu‐Yi Huang
- The Affiliated Brain HospitalGuangzhou Medical UniversityGuangzhouChina
- Key Laboratory of Neurogenetics and Channelopathies of Guangdong Province and the Ministry of Education of ChinaGuangzhou Medical UniversityGuangzhouChina
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Wang JH, Han SY, Lee K, Han U, Cho SK, Kim H. Antibiotic Cocktail Exacerbates Esomeprazole-Induced Intestinal Dysmotility While Ameliorating Gastric Dyspepsia in Mice. Antibiotics (Basel) 2025; 14:442. [PMID: 40426509 DOI: 10.3390/antibiotics14050442] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/26/2025] [Revised: 04/24/2025] [Accepted: 04/26/2025] [Indexed: 05/29/2025] Open
Abstract
Background/Objectives: Esomeprazole, a proton pump inhibitor (PPI), is commonly prescribed for gastric-acid-related disorders but has been associated with impaired gastrointestinal (GI) motility with long-term use. However, the effect of concurrent antibiotic administration on this dysfunction remains unclear. Therefore, this study aimed to investigate the effects of antibiotics on esomeprazole-induced GI motility dysfunction and explore the underlying mechanisms in a mouse model. Methods: Male C57BL/6 mice were orally administered esomeprazole (160 mg/kg) five times per week for 4 weeks. Three days before initiating esomeprazole treatment, a broad-spectrum antibiotic cocktail (ABX) consisting of ampicillin (1 g/kg), neomycin (1 g/kg), metronidazole (1 g/kg), and vancomycin (0.5 g/kg) was provided in drinking water and maintained throughout the experimental period. Mosapride (3 mg/kg), a prokinetic agent, was used as a positive control. Results: Neither esomeprazole alone nor in combination with ABX affected body weight or food intake. Compared to normal controls, esomeprazole treatment significantly delayed both intestinal transit and gastric emptying. However, ABX co-administration further pronounced intestinal transit time and improved gastric motility. The potential mechanisms may involve interactions among gastric H+/K+-ATPase, CYP3A11, gastrointestinal hormones (secretin and motilin), and the gut microbiome. Conclusions: Long-term esomeprazole use can impair both gastric and intestinal motility, and ABX co-treatment further exacerbates intestinal transit delay while paradoxically enhancing gastric emptying. These findings highlight the critical role of the gut microbiota in esomeprazole-induced GI motility dysfunction and suggest that antibiotic use should be approached with caution, particularly when combined with PPI therapy.
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Affiliation(s)
- Jing-Hua Wang
- Institute of Oriental Medicine, Dongguk University, 32 Dongguk-ro, Goyang-si 10326, Gyeonggi-do, Republic of Korea
- Department of Rehabilitation Medicine of Korean Medicine, Dongguk University, 32 Dongguk-ro, Ilsandong-gu, Goyang-si 10326, Gyeonggi-do, Republic of Korea
| | - Song-Yi Han
- Department of Rehabilitation Medicine of Korean Medicine, Dongguk University, 32 Dongguk-ro, Ilsandong-gu, Goyang-si 10326, Gyeonggi-do, Republic of Korea
| | - Kyungjae Lee
- College of Korean Medicine, Dongguk University, 32 Dongguk-ro, Ilsandong-gu, Goyang-si 10326, Gyeonggi-do, Republic of Korea
| | - Uijeong Han
- Department of Biological and Environmental Science, Dongguk University, 32 Dongguk-ro, Ilsandong-gu, Goyang-si 10326, Gyeonggi-do, Republic of Korea
| | - Si-Kyung Cho
- Department of Biological and Environmental Science, Dongguk University, 32 Dongguk-ro, Ilsandong-gu, Goyang-si 10326, Gyeonggi-do, Republic of Korea
| | - Hojun Kim
- Department of Rehabilitation Medicine of Korean Medicine, Dongguk University, 32 Dongguk-ro, Ilsandong-gu, Goyang-si 10326, Gyeonggi-do, Republic of Korea
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Balkrishna A, Sinha S, Shukla S, Bhattacharya K, Varshney A. Anti-ulcerogenic activity of the marine-pearl derived medicine mukta Pishti in Rat model of pylorus ligation-induced peptic ulcer. JOURNAL OF ETHNOPHARMACOLOGY 2025; 342:119378. [PMID: 39828143 DOI: 10.1016/j.jep.2025.119378] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 10/30/2024] [Revised: 01/15/2025] [Accepted: 01/16/2025] [Indexed: 01/22/2025]
Abstract
ETHNOPHARMACOLOGICAL RELEVANCE Mukta Pishti (MKP) is a traditional Ayurvedic medicine described in classical textbook 'Rasatarangini' and synthesized from marine pearls following classical methodology. MKP is used as therapeutic medicine against hyperacidity, irritable bowel syndrome, and gastric ulcers. AIM OF THE STUDY Here, we explored the therapeutic properties of MKP in alleviating peptic ulcer in male Wistar rat model of pylorus ligation. METHODS Physicochemical properties of MKP were explored using scanning electron microscope, electron dispersive X-ray, dynamic light scattering, and Fourier-transform-infrared (FTIR)-spectroscopy analysis. Animals were orally treated twice daily with dosages of MKP, over a period of 15 days. The animals underwent 6 h pylorus ligation for the induction of peptic ulcers and analyzed for biochemical changes in gastric content, gross and histopathological changes in the stomach region. RESULTS Physicochemical analysis showed 0.1-30 μm particles size for MKP, with elemental composition of oxygen, calcium, silica, carbon, phosphorus, and sodium. FTIR-spectroscopy indicated presence of aragonite crystals in MKP with capability of physically binding to gastric mucin molecules. Additionally, MKP treatment modulated gastric pH in simulated digestion model but did not affect the overall gastric content and total/free acidity levels in the in vivo pylorus ligation model. However, MKP treatment in rats significantly reduced ulcer index in stomach region and protected it against epithelial damages, hemorrhages and edema induced by pylorus ligation. CONCLUSION MKP alleviated peptic ulcer induced by pylorus ligation in the male Wistar rats. Further research is warranted to elucidate the precise mode of action and long-term safety of Mukta Pishti.
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Affiliation(s)
- Acharya Balkrishna
- Drug Discovery and Development Division, Patanjali Research Foundation, Haridwar, 249 405, Uttarakhand, India; Department of Allied and Applied Sciences, University of Patanjali, Patanjali Yog Peeth, Haridwar, 249 405, Uttarakhand, India; Patanjali Yog Peeth (UK) Trust, 40 Lambhill Street, Kinning Park, Glasgow, G41 1AU, UK
| | - Sandeep Sinha
- Drug Discovery and Development Division, Patanjali Research Foundation, Haridwar, 249 405, Uttarakhand, India
| | - Sunil Shukla
- Drug Discovery and Development Division, Patanjali Research Foundation, Haridwar, 249 405, Uttarakhand, India
| | - Kunal Bhattacharya
- Drug Discovery and Development Division, Patanjali Research Foundation, Haridwar, 249 405, Uttarakhand, India
| | - Anurag Varshney
- Drug Discovery and Development Division, Patanjali Research Foundation, Haridwar, 249 405, Uttarakhand, India; Special Centre for Systems Medicine, Jawaharlal Nehru University, New Delhi 110 067, India.
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Nayda NC, Delaney CL, Thomas JM, Miller MD. Biochemical validation of a food frequency questionnaire measuring immune modulating nutrient intake in patients with peripheral arterial disease. Nutr Metab Cardiovasc Dis 2025:103934. [PMID: 40089391 DOI: 10.1016/j.numecd.2025.103934] [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: 04/16/2024] [Revised: 02/19/2025] [Accepted: 02/21/2025] [Indexed: 03/17/2025]
Abstract
BACKGROUND AND AIMS Peripheral arterial disease (PAD) is a cardiovascular disease affecting approximately 6 % of the population. The condition is associated with claudication, non-healing ischemic ulceration, and a systemic pro-inflammatory and pro-oxidative state. Recently, nutrition therapy is exploring immunonutrition as a novel dietary strategy to reduce the progression of atherosclerosis. A 21-item food frequency questionnaire (FFQ) has been developed and previously validated in the PAD population against a dietitian collected seven-day diet history method showing good agreement. The aim of this study was to determine whether the FFQ accurately predicts serum levels of six routinely analysed immune-modulating nutrients (vitamins A, C, D, and E, zinc, iron). METHODS AND RESULTS Dietary intake measured by the validated FFQ was compared to fasting serum blood levels of their respective biomarkers. Correlation coefficients and quartile agreements were performed to determine the relationship between dietary intake and serum levels. The mean age of participants (n = 100) was 75 years with 76 % being male. Correlation coefficients and quartile agreements indicated poor agreement between intake measured by FFQ and serum biomarkers and were not statistically significant. CONCLUSION These results suggest that intake measured by the FFQ is not an accurate reflection of serum levels of these immune-modulating nutrients in this population, possibly due to endogenous physiological processes specific to PAD. Further research into the utilisation of nutrients is warranted to inform dietary recommendations in this population.
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Affiliation(s)
- Nicole C Nayda
- Caring Futures Institute, College of Nursing and Health Sciences, Flinders University, Bedford Park, SA, 5042, Australia
| | - Christopher L Delaney
- Department of Vascular and Endovascular Surgery, Flinders Medical Centre, Bedford Park, SA, 5042, Australia; College of Medicine and Public Health, Flinders University, Bedford Park, SA, 5042, Australia
| | - Jolene M Thomas
- Caring Futures Institute, College of Nursing and Health Sciences, Flinders University, Bedford Park, SA, 5042, Australia
| | - Michelle D Miller
- Caring Futures Institute, College of Nursing and Health Sciences, Flinders University, Bedford Park, SA, 5042, Australia.
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Song B, Liu L, Dong S, Wang S. Drug-induced hypokalemia: an analytical study based on real-world drug monitoring data. Expert Opin Drug Saf 2025:1-9. [PMID: 39977281 DOI: 10.1080/14740338.2025.2468861] [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: 06/08/2024] [Accepted: 11/08/2024] [Indexed: 02/22/2025]
Abstract
BACKGROUND Drug-induced hypokalemia is often associated with adverse clinical outcomes, and unfortunately, the inability to fully understand the drugs that cause hypokalemia puts us in a passive position. This study applies pharmacovigilance data to present a panorama of suspected medications associated with hyperkalemia. RESEARCH DESIGN AND METHODS This study used disproportionality analysis to mine adverse events in OpenFDA, identified all suspected drugs that caused hypokalemia, and coded and classified the suspected drugs according to the Anatomical Therapeutic Chemical (ATC) classification system. RESULTS There are 19755 reports related to drug-induced hypokalemia. The majority of individuals with hypokalemia are females, with a concentrated age range of 65 to 84 years old. After the occurrence of hypokalemia, 8.02% died due to hypokalemia. This study identified 1141 suspected drugs, and among the top 50 drugs, 32 drugs did not include hypokalemia in their instructions. All suspected drugs can be categorized into 73 subgroups according to the ATC classification system. CONCLUSIONS By mining the OpenFDA database, we have identified all suspected drugs that cause hypokalemia and conducted a comprehensive evaluation. The instructions for most of the suspected drugs do not focus on hypokalemia. When the treatment regimen includes other drugs that can directly/indirectly cause a decrease in blood potassium, we recommend actively monitoring blood potassium when using suspected drugs.
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Affiliation(s)
- Bo Song
- Department of Pharmacy, Children's Hospital of Nanjing Medical University, Nanjing, Jiangsu, China
| | - Liheng Liu
- Department of Pharmacy, Children's Hospital of Nanjing Medical University, Nanjing, Jiangsu, China
| | - Shichao Dong
- Department of Pharmacy, The Second Hospital of Tianjin Medical University, Tianjin, China
| | - Shanshan Wang
- Department of Pharmacy, Children's Hospital of Nanjing Medical University, Nanjing, Jiangsu, China
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Mostafavi SA. Potential Antidepressant Effects of Omeprazole Introduced Through Network Analysis and Systems Biology Should Be Interpreted with Caution in the Clinical Environment. IRANIAN JOURNAL OF PSYCHIATRY 2025; 20:1-2. [PMID: 40093520 PMCID: PMC11904747 DOI: 10.18502/ijps.v20i1.17407] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Received: 11/27/2024] [Revised: 12/03/2024] [Accepted: 12/03/2024] [Indexed: 03/19/2025]
Abstract
The Article Abstract is not available.
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Affiliation(s)
- Seyed-Ali Mostafavi
- Psychiatry and Psychology Research Center, Tehran University of Medical Sciences, Tehran, Iran
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Feng Y, Zhong Y. Proton pump inhibitor use and risk of stroke: A systematic review and meta-analysis. Pak J Med Sci 2024; 40:2432-2440. [PMID: 39554645 PMCID: PMC11568727 DOI: 10.12669/pjms.40.10.10409] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/13/2024] [Revised: 06/28/2024] [Accepted: 09/05/2024] [Indexed: 11/19/2024] Open
Abstract
Objective To explore a link between the use of proton pump inhibitor (PPI) and the risk of stroke. Methods Comprehensive literature search in PubMed, EMBASE, and Cochrane CENTRAL Library databases was carried out for observational studies establishing the link between PPI and a risk of stroke. Data extraction and quality assessment were performed by two reviewers. Pooled hazard ratios (HRs) with 95% confidence intervals (CIs) using random-effects models were plotted. Subgroup analyses were conducted based on age, gender, PPI type, duration of follow-up, and propensity score matching (PSM). Results The analysis included 12 studies, with considerable heterogeneity (I2 = 95%). PPI use did not affect the incidence of ischemic stroke (HR: 1.11, 95% CI: 0.98-1.26). Subgroup analyses revealed that PPI use correlated with the risk of ischemic stroke, in particular in patients<65 years old (HR: 1.25, 95% CI: 1.07-1.45), both males (HR: 1.12, 95% CI: 1.02-1.24) and females (HR: 1.21, 95% CI: 1.10-1.33). The correlation varied depending on the PPI type, with pantoprazole showing elevated risk (HR: 1.66, 95% CI: 1.43-1.93). Duration of follow-up or propensity score matching (PSM) did not impact the association. Conclusion PPI use may be linked with ischemic stroke, particularly in individuals <65 years old and of all genders. The specific PPI type may also influence the risk. However, the cumulative analysis did not find any statistically significant association, and heterogeneity among studies was substantial.
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Affiliation(s)
- Yaoyao Feng
- Yaoyao Feng Department of Neurology, Huzhou Third Municipal Hospital, The Affiliated Hospital of Huzhou University, Huzhou, Zhejiang Province 313000, P.R. China
| | - Ying Zhong
- Ying Zhong Department of Geriatrics, Huzhou Third Municipal Hospital, The Affiliated Hospital of Huzhou University, Huzhou, Zhejiang Province 313000, P.R. China
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Dimas-Benedicto C, Albasanz JL, Bermejo LM, Castro-Vázquez L, Sánchez-Melgar A, Martín M, Martínez-García RM. Impact of Iron Intake and Reserves on Cognitive Function in Young University Students. Nutrients 2024; 16:2808. [PMID: 39203944 PMCID: PMC11356983 DOI: 10.3390/nu16162808] [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: 07/31/2024] [Revised: 08/19/2024] [Accepted: 08/20/2024] [Indexed: 09/03/2024] Open
Abstract
Iron is a key nutrient for cognitive function. During periods of high academic demand, brain and cognitive activity increase, potentially affecting iron intake and reserves. The present study aimed to investigate the impact of iron levels on cognitive function in a university sample, considering the influence of gender. A cross-sectional study was conducted with 132 university students (18-29 years) from the University of Castilla-La Mancha (Spain). A dietary record was formed through a questionnaire to analyze iron consumption, and blood and anthropometric parameters were measured. The Wechsler Adult Intelligence Scale-IV was used to determine the Intelligence Quotient (IQ), as well as the Verbal Comprehension Index (VCI), Working Memory Index (WMI), Processing Speed Index (PSI), and Perceptual Reasoning Index (PRI), to assess cognitive abilities. Among women, the prevalence of iron deficiency (ID) and iron deficiency anemia (IDA) was 21% and 4.2%, respectively. No ID or IDA was found in men. The impact of iron intake on IQ and cognitive abilities was mainly associated with the female population, where a positive association between iron intake, serum ferritin, and total IQ was revealed. In conclusion, low iron intake is related to poorer intellectual ability, suggesting that an iron-rich diet is necessary to maintain the academic level of university students.
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Affiliation(s)
- Carmen Dimas-Benedicto
- NUTRI-SAF Research Group, Departamento de Enfermería, Fisioterapia y Terapia Ocupacional, Facultad de Enfermería, University of Castilla-La Mancha, 16071 Cuenca, Spain; (C.D.-B.); (R.M.M.-G.)
| | - José Luis Albasanz
- GNCR Research Group, Departamento de Química Inorgánica, Orgánica y Bioquímica, Facultad de Medicina de Ciudad Real, Instituto de Biomedicina de la UCLM, IDISCAM, University of Castilla-La Mancha, 13071 Ciudad Real, Spain;
| | - Laura M. Bermejo
- VALORNUT Research Group, Departamento de Nutrición y Ciencias de los Alimentos, Facultad de Farmacia, Universidad Complutense de Madrid, 28040 Madrid, Spain;
- San Carlos Health Research Institute (IdISSC), 28040 Madrid, Spain
| | - Lucía Castro-Vázquez
- NUTRI-SAF Research Group, Departamento de Química Analítica y Tecnología de los Alimentos, Facultad de Farmacia, University of Castilla-La Mancha, 02071 Albacete, Spain;
| | - Alejandro Sánchez-Melgar
- GNCR Research Group, Departamento de Química Inorgánica, Orgánica y Bioquímica, Facultad de Enfermeria de Ciudad Real, Instituto de Biomedicina de la UCLM, IDISCAM, University of Castilla-La Mancha, 13071 Ciudad Real, Spain;
| | - Mairena Martín
- GNCR Research Group, Departamento de Química Inorgánica, Orgánica y Bioquímica, Facultad de Medicina de Ciudad Real, Instituto de Biomedicina de la UCLM, IDISCAM, University of Castilla-La Mancha, 13071 Ciudad Real, Spain;
- GNCR Research Group, Departamento de Química Inorgánica, Orgánica y Bioquímica, Facultad de Enfermeria de Ciudad Real, Instituto de Biomedicina de la UCLM, IDISCAM, University of Castilla-La Mancha, 13071 Ciudad Real, Spain;
| | - Rosa M. Martínez-García
- NUTRI-SAF Research Group, Departamento de Enfermería, Fisioterapia y Terapia Ocupacional, Facultad de Enfermería, University of Castilla-La Mancha, 16071 Cuenca, Spain; (C.D.-B.); (R.M.M.-G.)
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Ito T, Ramos-Alvarez I, Jensen RT. Long-Term Proton Pump Inhibitor-Acid Suppressive Treatment Can Cause Vitamin B 12 Deficiency in Zollinger-Ellison Syndrome (ZES) Patients. Int J Mol Sci 2024; 25:7286. [PMID: 39000391 PMCID: PMC11242121 DOI: 10.3390/ijms25137286] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/31/2024] [Revised: 06/26/2024] [Accepted: 06/28/2024] [Indexed: 07/16/2024] Open
Abstract
Whether the long-term treatment of patients with proton pump inhibitors (PPIs) with different diseases [GERD, Zollinger-Ellison syndrome (ZES), etc.] can result in vitamin B12 (VB12) deficiency is controversial. In this study, in 175 patients undergoing long-term ZES treatment with anti-acid therapies, drug-induced control acid secretory rates were correlated with the presence/absence of VB12 deficiency, determined by assessing serum VB12 levels, measurements of VB12 body stores (blood methylmalonic acid (MMA) and total homocysteine[tHYC]), and other features of ZES. After a mean of 10.2 yrs. of any acid treatment (5.6 yrs. with PPIs), 21% had VB12 deficiency with significantly lower serum and body VB12 levels (p < 0.0001). The presence of VB12 deficiency did not correlate with any feature of ZES but was associated with a 12-fold lower acid control rate, a 2-fold higher acid control pH (6.4 vs. 3.7), and acid control secretory rates below those required for the activation of pepsin (pH > 3.5). Over a 5-yr period, the patients with VB12 deficiency had a higher rate of achlorhydria (73% vs. 24%) and a lower rate of normal acid secretion (0% vs. 49%). In conclusion, in ZES patients, chronic long-term PPI treatment results in marked acid hyposecretion, resulting in decreased serum VB12 levels and decreased VB12-body stores, which can result in VB12 deficiency.
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Affiliation(s)
- Tetsuhide Ito
- Neuroendocrine Tumor Centra, Fukuoka Sanno Hospital, International University of Health and Welfare, 3-6-45 Momochihama, Sawara-Ku, Fukuoka 814-0001, Japan
| | | | - Robert T Jensen
- Digestive Diseases Branch, NIDDK, NIH, Bethesda, MD 20892-1804, USA
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Vieira de Sousa JP, Santos-Sousa H, Vieira S, Nunes R, Nogueiro J, Pereira A, Resende F, Costa-Pinho A, Preto J, Sousa-Pinto B, Carneiro S, Lima-da-Costa E. Assessing Nutritional Deficiencies in Bariatric Surgery Patients: A Comparative Study of Roux-en-Y Gastric Bypass versus Sleeve Gastrectomy. J Pers Med 2024; 14:650. [PMID: 38929871 PMCID: PMC11204764 DOI: 10.3390/jpm14060650] [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: 04/27/2024] [Revised: 06/09/2024] [Accepted: 06/14/2024] [Indexed: 06/28/2024] Open
Abstract
Obesity is a worldwide epidemic, and bariatric surgery is considered the primary treatment for long-term weight loss and managing obesity-related health issues. Sleeve gastrectomy (SG) and Roux-en-Y gastric bypass (RYGB) are the most performed procedures. Nutritional deficiencies are a significant concern following bariatric surgery and can have serious consequences. This study aims to compare the incidence of nutritional deficiencies in patients undergoing RYGB and SG. A retrospective analysis was conducted on the nutritional status of 505 consecutive patients who underwent either RYGB or SG between January and December 2019. Data were collected regarding vitamin B12, folic acid, vitamin D, calcium, PTH, magnesium, hemoglobin, iron, ferritin, and transferrin at preoperative, 6-month, and 12-month intervals post-surgery. The RYGB group showed significantly higher excess weight loss. Vitamin B12, hemoglobin, and ferritin levels were consistently higher in the SG group throughout the study. Vitamin D deficiency was prevalent, with no significant difference between the groups. Vitamin B12 deficiency was significantly more common in the RYGB group (6 months: 17.46% vs. 4.69%, p < 0.001; 12 months: 16.74% vs. 0.93%, p < 0.001). Despite differences in their mechanisms, bariatric surgeries were associated with nutritional deficiencies. It is crucial to efficiently assess, prevent, and manage these deficiencies tailored to each surgical procedure.
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Affiliation(s)
- José P. Vieira de Sousa
- Faculty of Medicine, University of Porto, 4200-319 Porto, Portugal; (J.P.V.d.S.); (S.V.); (R.N.); (J.N.); (A.P.); (F.R.); (A.C.-P.); (B.S.-P.); (S.C.); (E.L.-d.-C.)
- Surgery Department, São João University Medical Center, 4200-319 Porto, Portugal
| | - Hugo Santos-Sousa
- Faculty of Medicine, University of Porto, 4200-319 Porto, Portugal; (J.P.V.d.S.); (S.V.); (R.N.); (J.N.); (A.P.); (F.R.); (A.C.-P.); (B.S.-P.); (S.C.); (E.L.-d.-C.)
- Obesity Integrated Responsibility Unit (CRI-O), São João University Medical Center, 4200-319 Porto, Portugal;
| | - Sofia Vieira
- Faculty of Medicine, University of Porto, 4200-319 Porto, Portugal; (J.P.V.d.S.); (S.V.); (R.N.); (J.N.); (A.P.); (F.R.); (A.C.-P.); (B.S.-P.); (S.C.); (E.L.-d.-C.)
| | - Rita Nunes
- Faculty of Medicine, University of Porto, 4200-319 Porto, Portugal; (J.P.V.d.S.); (S.V.); (R.N.); (J.N.); (A.P.); (F.R.); (A.C.-P.); (B.S.-P.); (S.C.); (E.L.-d.-C.)
| | - Jorge Nogueiro
- Faculty of Medicine, University of Porto, 4200-319 Porto, Portugal; (J.P.V.d.S.); (S.V.); (R.N.); (J.N.); (A.P.); (F.R.); (A.C.-P.); (B.S.-P.); (S.C.); (E.L.-d.-C.)
- Surgery Department, São João University Medical Center, 4200-319 Porto, Portugal
| | - André Pereira
- Faculty of Medicine, University of Porto, 4200-319 Porto, Portugal; (J.P.V.d.S.); (S.V.); (R.N.); (J.N.); (A.P.); (F.R.); (A.C.-P.); (B.S.-P.); (S.C.); (E.L.-d.-C.)
- Surgery Department, São João University Medical Center, 4200-319 Porto, Portugal
| | - Fernando Resende
- Faculty of Medicine, University of Porto, 4200-319 Porto, Portugal; (J.P.V.d.S.); (S.V.); (R.N.); (J.N.); (A.P.); (F.R.); (A.C.-P.); (B.S.-P.); (S.C.); (E.L.-d.-C.)
- Obesity Integrated Responsibility Unit (CRI-O), São João University Medical Center, 4200-319 Porto, Portugal;
| | - André Costa-Pinho
- Faculty of Medicine, University of Porto, 4200-319 Porto, Portugal; (J.P.V.d.S.); (S.V.); (R.N.); (J.N.); (A.P.); (F.R.); (A.C.-P.); (B.S.-P.); (S.C.); (E.L.-d.-C.)
- Obesity Integrated Responsibility Unit (CRI-O), São João University Medical Center, 4200-319 Porto, Portugal;
| | - John Preto
- Obesity Integrated Responsibility Unit (CRI-O), São João University Medical Center, 4200-319 Porto, Portugal;
| | - Bernardo Sousa-Pinto
- Faculty of Medicine, University of Porto, 4200-319 Porto, Portugal; (J.P.V.d.S.); (S.V.); (R.N.); (J.N.); (A.P.); (F.R.); (A.C.-P.); (B.S.-P.); (S.C.); (E.L.-d.-C.)
- MEDCIDS—Department of Community Medicine, Information and Health Decision Sciences, Faculty of Medicine, University of Porto, 4200-450 Porto, Portugal
- CINTESIS—Center for Health Technology and Services Research, 4200-450 Porto, Portugal
| | - Silvestre Carneiro
- Faculty of Medicine, University of Porto, 4200-319 Porto, Portugal; (J.P.V.d.S.); (S.V.); (R.N.); (J.N.); (A.P.); (F.R.); (A.C.-P.); (B.S.-P.); (S.C.); (E.L.-d.-C.)
- Surgery Department, São João University Medical Center, 4200-319 Porto, Portugal
| | - Eduardo Lima-da-Costa
- Faculty of Medicine, University of Porto, 4200-319 Porto, Portugal; (J.P.V.d.S.); (S.V.); (R.N.); (J.N.); (A.P.); (F.R.); (A.C.-P.); (B.S.-P.); (S.C.); (E.L.-d.-C.)
- Obesity Integrated Responsibility Unit (CRI-O), São João University Medical Center, 4200-319 Porto, Portugal;
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Amidon S, Mistry A, Haque R. Use of Betaine HCl with Pepsin in Esophageal Cancer Patient: A Case Report. J Med Food 2024; 27:460-465. [PMID: 38695854 DOI: 10.1089/jmf.2023.0174] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 05/31/2024] Open
Abstract
The principal mechanisms surrounding gastrointestinal (GI) side effects due to chemotherapy are unclear, whereas the information regarding symptom management of patients with esophageal cancer post-esophagectomy is lacking. Esophagectomy patients are left with significant anatomical changes to the GI tract, including the cutting of the vagus nerve, which regulates gastric secretions, gastric acid pH, and motility. A 76-year-old male patient self-referred himself to the clinical dietitian for nutritional management of chronic nausea, fatigue, weight loss, and dumping syndrome 9 months post-esophagectomy, which was not responsive to medications. A physical functional nutritional assessment with evaluation of diet history and elimination suggested gastric hypochlorhydria. Gastric acid is needed for the active absorption of iron, zinc, B complex vitamins, especially B12, and digestion of consumed proteins. A digestive supplement, betaine hydrochloric acid with pepsin (BHClP), was introduced, and the patient ingested 1 capsule containing 500 mg betaine hydrochloride and 23.5 mg pepsin prior to protein-containing meals and reported a substantial decrease in GI symptoms while eating a regular diet with no limitations. He gained necessary weight and energy for daily activities. After a few months, the patient discontinued BHClP, and GI symptoms and dumping syndrome returned, leading to a loss of 7.5% of his body weight. The patient reinitiated the supplement and GI symptoms dissipated, and weight was restored. BHClP provided metabolic therapeutic benefit to optimize the patient's oral intake, preventing further complications and malnutrition. The success with BHClP for this patient case suggests that more research is needed to fully realize the mechanisms and clinical usage.
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Affiliation(s)
- Sarah Amidon
- Root and Fruit Nutrition, Indianapolis, Indiana, USA
| | | | - Rubina Haque
- Eastern Michigan University, Ypsilanti, Michigan, USA
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14
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Ferah Okkay I, Okkay U, Cicek B, Karatas O, Yilmaz A, Yesilyurt F, Hacimuftuoglu A. Syringic acid guards against indomethacin-induced gastric ulcer by alleviating inflammation, oxidative stress and apoptosis. Biotech Histochem 2024; 99:147-156. [PMID: 38644776 DOI: 10.1080/10520295.2024.2344477] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 04/23/2024] Open
Abstract
The purpose of this study was to evaluate the effects of syringic acid, an anti-oxidant, on indomethacin induced gastric ulcers in rats. Experimental groups were control, ulcer, ulcer treated with 20 mg/kg esomeprazole (a proton pump inhibitor that reduces acid secretion), and ulcer treated with 100 mg/kg syringic acid. Rats were pretreated with esomeprazole or syringic acid two weeks before ulcer induction. Our histopathological observations showed that either syringic acid or esomeprazole attenuated the severity of gastric mucosal damage. Moreover, syringic acid and esomeprazole pretreatments alleviated indomethacin-induced damage by regulating oxidative stress, inflammatory response, the level of transforming growth factor-β (TGF-β), expressions of COX and prostaglandin E2, cell proliferation, apoptosis and regulation of the NF-κB signaling pathway. We conclude that either esomeprazole or syringic acid administration protected the gastric mucosa from harmful effects of indomethacin. Syringic acid might, therefore be a potential therapeutic agent for preventing and treating indomethacin-induced gastric damage.
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Affiliation(s)
- Irmak Ferah Okkay
- Department of Pharmacology, Faculty of Pharmacy, Ataturk University, Erzurum, Turkey
| | - Ufuk Okkay
- Department of Medical Pharmacology, Faculty of Medicine, Ataturk University, Erzurum, Turkey
| | - Betul Cicek
- Department of Physiology, Faculty of Medicine, Erzincan Binali Yildirim University, Erzincan, Turkey
| | - Ozhan Karatas
- Department of Pathology, Faculty of Veterinary Medicine, Sivas Cumhuriyet University, Sivas, Turkey
| | - Aysegul Yilmaz
- Department of Medical Pharmacology, Faculty of Medicine, Ataturk University, Erzurum, Turkey
| | - Fatma Yesilyurt
- Department of Medical Pharmacology, Faculty of Medicine, Ataturk University, Erzurum, Turkey
| | - Ahmet Hacimuftuoglu
- Department of Medical Pharmacology, Faculty of Medicine, Ataturk University, Erzurum, Turkey
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15
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Elsabaawy M, Alhaddad O. Forgettable in the care of liver cirrhosis: the unseen culprits of progression from bad to worse. PRZEGLAD GASTROENTEROLOGICZNY 2024; 19:6-17. [PMID: 38571544 PMCID: PMC10985753 DOI: 10.5114/pg.2024.136361] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Received: 07/10/2023] [Accepted: 11/20/2023] [Indexed: 04/05/2024]
Abstract
Patients with liver cirrhosis constitute a critically ill and unique population, and their stability relies on a well-coordinated multidisciplinary team with a carefully structured plan. Overlooking any aspect of this plan can expedite disease progression, leading to severe complications. The lack of disease-specific nutritional guidance, the prevalent sedentary lifestyle among patients, and insufficient screening for hepatocellular carcinoma, oesophageal varices, sarcopaenia, minimal hepatic encephalopathy, and diabetes mellitus, along with fibrosis progression and cirrhosis decompensation, can add further complexities. Additionally, devaluing the impact of obesity in triggering liver cirrhosis can be disadvantageous. Prolonged and inappropriate use of proton pump inhibitors also poses a significant challenge with a wide range of complications. These often-unheeded aspects in the care of liver cirrhosis patients represents the unseen culprits of progression from bad to worse and warrant serious consideration.
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Affiliation(s)
- Maha Elsabaawy
- Department of Hepatology and Gastroenterology, National Liver Institute, Menoufia University, Shebin Elkom, Menoufia, Egypt
| | - Omkosoum Alhaddad
- Department of Hepatology and Gastroenterology, National Liver Institute, Menoufia University, Shebin Elkom, Menoufia, Egypt
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16
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Ali F, Mouzaki M. Nutritional deficiencies in children. Curr Opin Gastroenterol 2024; 40:106-111. [PMID: 38190349 DOI: 10.1097/mog.0000000000000998] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/10/2024]
Abstract
PURPOSE OF REVIEW The purpose of this review is to summarize commonly encountered nutritional deficiencies in children and their implications. Considering data suggesting that the majority of children with the United States consume unhealthy diets, the growing interest in the consumption of limiting diets, as well as the insidious clinical presentation of nutritional deficiencies, this is a timely and highly relevant review. RECENT FINDINGS The underlying socioeconomic and medical circumstances that predispose to nutritional deficiencies in the Western world are covered. The high index of suspicion required to recognize nutritional deficiencies and the limitations of available testing are also discussed. Finally, the need for the development of accurate nutritional biomarkers is presented as a future research priority. SUMMARY Nutritional deficiencies are not uncommon, even in high resource countries. Clinicians should remain vigilant and include nutritional deficiencies in the differential diagnoses of patients presenting with nonspecific symptoms.
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Affiliation(s)
- Farhana Ali
- Primary Children's Hospital, University of Utah
| | - Marialena Mouzaki
- Cincinnati Children's Hospital Medical Center, University of Cincinnati College of Medicine, Cincinnati, Ohio, USA
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17
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Weh KM, Howard CL, Zhang Y, Tripp BA, Clarke JL, Howell AB, Rubenstein JH, Abrams JA, Westerhoff M, Kresty LA. Prebiotic proanthocyanidins inhibit bile reflux-induced esophageal adenocarcinoma through reshaping the gut microbiome and esophageal metabolome. JCI Insight 2024; 9:e168112. [PMID: 38329812 PMCID: PMC11063939 DOI: 10.1172/jci.insight.168112] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/16/2022] [Accepted: 02/02/2024] [Indexed: 02/10/2024] Open
Abstract
The gut and local esophageal microbiome progressively shift from healthy commensal bacteria to inflammation-linked pathogenic bacteria in patients with gastroesophageal reflux disease, Barrett's esophagus, and esophageal adenocarcinoma (EAC). However, mechanisms by which microbial communities and metabolites contribute to reflux-driven EAC remain incompletely understood and challenging to target. Herein, we utilized a rat reflux-induced EAC model to investigate targeting the gut microbiome-esophageal metabolome axis with cranberry proanthocyanidins (C-PAC) to inhibit EAC progression. Sprague-Dawley rats, with or without reflux induction, received water or C-PAC ad libitum (700 μg/rat/day) for 25 or 40 weeks. C-PAC exerted prebiotic activity abrogating reflux-induced dysbiosis and mitigating bile acid metabolism and transport, culminating in significant inhibition of EAC through TLR/NF-κB/TP53 signaling cascades. At the species level, C-PAC mitigated reflux-induced pathogenic bacteria (Streptococcus parasanguinis, Escherichia coli, and Proteus mirabilis). C-PAC specifically reversed reflux-induced bacterial, inflammatory, and immune-implicated proteins and genes, including Ccl4, Cd14, Crp, Cxcl1, Il6, Il1b, Lbp, Lcn2, Myd88, Nfkb1, Tlr2, and Tlr4, aligning with changes in human EAC progression, as confirmed through public databases. C-PAC is a safe, promising dietary constituent that may be utilized alone or potentially as an adjuvant to current therapies to prevent EAC progression through ameliorating reflux-induced dysbiosis, inflammation, and cellular damage.
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Affiliation(s)
- Katherine M. Weh
- Department of Surgery, Section of Thoracic Surgery, and
- Rogel Comprehensive Cancer Center, University of Michigan, Ann Arbor, Michigan, USA
| | - Connor L. Howard
- Department of Surgery, Section of Thoracic Surgery, and
- Rogel Comprehensive Cancer Center, University of Michigan, Ann Arbor, Michigan, USA
| | - Yun Zhang
- Department of Surgery, Section of Thoracic Surgery, and
- Rogel Comprehensive Cancer Center, University of Michigan, Ann Arbor, Michigan, USA
| | | | - Jennifer L. Clarke
- Department of Statistics, Department of Food Science Technology, Quantitative Life Sciences Initiative, University of Nebraska-Lincoln, Lincoln, Nebraska, USA
| | - Amy B. Howell
- Marucci Center for Blueberry and Cranberry Research, Rutgers University, Chatsworth, New Jersey, USA
| | - Joel H. Rubenstein
- Division of Gastroenterology, Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan, USA
- LTC Charles S. Kettles Veterans Affairs Medical Center, Ann Arbor, Michigan, USA
| | - Julian A. Abrams
- Department of Medicine, Columbia University Irving Medical Center, New York, New York, USA
| | - Maria Westerhoff
- Department of Pathology, University of Michigan, Ann Arbor, Michigan, USA
| | - Laura A. Kresty
- Department of Surgery, Section of Thoracic Surgery, and
- Rogel Comprehensive Cancer Center, University of Michigan, Ann Arbor, Michigan, USA
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18
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Prabhoo RY, Pai UA, Wadhwa A, Pillai BV, D'souza C, Wadhawan M, Bhatnagar M, Prabhoo MR, Shetty S, Seshadri VP, Bhatnagar S, Manchanda SC, Kher V. Multidisciplinary Consensus for Rationalizing the Use of Acid Suppressants in Children and Adults: CONFOR. Euroasian J Hepatogastroenterol 2024; 14:99-119. [PMID: 39022200 PMCID: PMC11249898 DOI: 10.5005/jp-journals-10018-1430] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/02/2024] [Accepted: 04/22/2024] [Indexed: 07/20/2024] Open
Abstract
The use of acid suppression therapy (AST) is a common approach for managing a wide spectrum of acid peptic disorders. Histamine type 2-receptor antagonists (H2RAs) and proton pump inhibitors (PPIs) are the most widely prescribed AST in routine clinical practice. However, an exponential surge in the prescriptions of PPIs, such as Omeprazole, Esomeprazole, Pantoprazole, Lansoprazole in recent years and their associated adverse effects have raised concern about their inappropriate and overuse, both in children and adults. To address these issues, a three-step modified Delphi polling process was employed to establish best practice consensus statements for rationalizing the use of acid suppressants. A multidisciplinary expert panel of 13 health professionals across medical specialties, including gastroenterologists, hepatologists, pediatric gastroenterologists, pediatricians, otolaryngologists, cardiologists, nephrologists, gynecologist and orthopedists actively contributed to this collaborative process of consensus development. The expert panel proposed 21 consensus statements providing best practice points on the general use and safety of acid suppressants based on a comprehensive review of scientific literature and clinical expertise. The panel also collaboratively developed a PPI deprescribing algorithm. Altogether, this consensus paper offers evidence-based recommendations and guidance for the rational use of acid suppressants with a blueprint for deprescribing PPIs. This consensus paper contributes to aiding primary care practitioners in improving patient outcomes and minimizing healthcare costs. Additionally, it enhances patient safety and curtail inappropriate usage. How to cite this article Prabhoo RY, Pai UA, Wadhwa A, et al. Multidisciplinary Consensus for Rationalizing the Use of Acid Suppressants in Children and Adults: CONFOR. Euroasian J Hepato-Gastroenterol 2024;14(1):99-119.
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Affiliation(s)
- Ram Y Prabhoo
- Department of Orthopedics, Mukund Hospital, Mumbai, Maharashtra, India
| | - Uday A Pai
- Department of Pediatrics, Sai Kutti Clinic, Mumbai, Maharashtra, India
| | - Arun Wadhwa
- Department of Pediatrics, Arun Wadhwa Clinic, New Delhi, India
| | - Bhanu V Pillai
- Department of Pediatric Gastroenterology, Amrita Institute of Medical Sciences, Kochi, Kerala, India
| | - Chris D'souza
- Department of ENT, Holy Family Hospital, Mumbai, Maharashtra, India
| | - Manav Wadhawan
- Department of Hepatology and Liver Transplant, BLK-Max Super Speciality Hospital, Delhi, India
| | - Manish Bhatnagar
- Department of Gastroenterology, Orchid Mediservices, Ahmedabad, Gujarat, India
| | - Meena R Prabhoo
- Department of Gynecology, Mukund Hospital, Mumbai, Maharashtra, India
| | - Sadanand Shetty
- Department of Cardiology, Somaiya Super Specialty Institute, Mumbai, Maharashtra, India
| | | | - Shrish Bhatnagar
- Department of Pediatric Gastroenterology, Era's Lucknow Medical College and Hospital, Lucknow, Uttar Pradesh, India
| | | | - Vijay Kher
- Department of Nephrology and Transplant Medicine, Epitome Kidney and Urology Institute, New Delhi, India
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Khan Z, Mehan S, Saifi MA, Das Gupta G, Narula AS, Kalfin R. Proton Pump Inhibitors and Cognitive Health: Review on Unraveling the Dementia Connection and Co-morbid Risks. Curr Alzheimer Res 2024; 20:739-757. [PMID: 38424433 PMCID: PMC11107432 DOI: 10.2174/0115672050289946240223050737] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/28/2023] [Revised: 01/28/2024] [Accepted: 01/31/2024] [Indexed: 03/02/2024]
Abstract
Dementia, an international health issue distinguished by the impairment of daily functioning due to cognitive decline, currently affects more than 55 million people worldwide, with the majority residing in low-income and middle-income countries. Globally, dementia entails significant economic burdens in 2019, amounting to a cost of 1.3 trillion US dollars. Informal caregivers devote considerable hours to providing care for those affected. Dementia imposes a greater caregiving and disability-adjusted life-year burden on women. A recent study has established a correlation between prolonged Proton Pump Inhibitor (PPI) usage and dementia, in addition to other neurodegenerative conditions. PPIs are frequently prescribed to treat peptic ulcers and GERD (gastroesophageal reflux disease) by decreasing stomach acid secretion. They alleviate acid-related symptoms through the inhibition of acid-secreting H+-K+ ATPase. In a number of observational studies, cognitive decline and dementia in the elderly have been linked to the use of PPIs. The precise mechanism underlying this relationship is unknown. These drugs might also alter the pH of brain cells, resulting in the accumulation of amyloid-beta (Aβ) peptides and the development of Alzheimer's disease (AD). Despite the compelling evidence supporting the association of PPIs with dementia, the results of studies remain inconsistent. The absence of a correlation between PPI use and cognitive decline in some studies emphasizes the need for additional research. Chronic PPI use can conceal underlying conditions, including cancer, celiac disease, vitamin B12 deficiency, and renal injury, highlighting dementia risk and the need for further investigations on cognitive health.
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Affiliation(s)
- Zuber Khan
- Division of Neuroscience, Department of Pharmacology, ISF College of Pharmacy, Moga, Punjab, India (Affiliated to IK Gujral Punjab Technical University), Jalandhar, Punjab, 144603, India;
| | - Sidharth Mehan
- Division of Neuroscience, Department of Pharmacology, ISF College of Pharmacy, Moga, Punjab, India (Affiliated to IK Gujral Punjab Technical University), Jalandhar, Punjab, 144603, India;
| | - Mohd. Anas Saifi
- Department of Medical Elementology and Toxicology, School of Chemical and Life Sciences, Jamia Hamdard, New Delhi-110062, India;
| | - Ghanshyam Das Gupta
- Department of Pharmaceutics, ISF College of Pharmacy, Moga, Punjab, India (Affiliated to IK Gujral Punjab Technical University), Jalandhar, Punjab, 144603, India;
| | - Acharan S. Narula
- Narula Research, LLC, 107 Boulder Bluff, Chapel Hill, NC 27516, USA;
| | - Reni Kalfin
- Institute of Neurobiology, Bulgarian Academy of Sciences, Acad. G. Bonchev St., Block 23, Sofia 1113, Bulgaria;
- Department of Healthcare, South-West University “NeofitRilski”, Ivan Mihailov St. 66, Blagoevgrad 2700, Bulgaria
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20
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Sugandhi VV, Pangeni R, Vora LK, Poudel S, Nangare S, Jagwani S, Gadhave D, Qin C, Pandya A, Shah P, Jadhav K, Mahajan HS, Patravale V. Pharmacokinetics of vitamin dosage forms: A complete overview. Food Sci Nutr 2024; 12:48-83. [PMID: 38268871 PMCID: PMC10804103 DOI: 10.1002/fsn3.3787] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/25/2023] [Revised: 10/07/2023] [Accepted: 10/11/2023] [Indexed: 01/26/2024] Open
Abstract
Vitamins are crucial for sustaining life because they play an essential role in numerous physiological processes. Vitamin deficiencies can lead to a wide range of severe health issues. In this context, there is a need to administer vitamin supplements through appropriate routes, such as the oral route, to ensure effective treatment. Therefore, understanding the pharmacokinetics of vitamins provides critical insights into absorption, distribution, and metabolism, all of which are essential for achieving the desired pharmacological response. In this review paper, we present information on vitamin deficiencies and emphasize the significance of understanding vitamin pharmacokinetics for improved clinical research. The pharmacokinetics of several vitamins face various challenges, and thus, this work briefly outlines the current issues and their potential solutions. We also discuss the feasibility of enhanced nanocarrier-based pharmaceutical formulations for delivering vitamins. Recent studies have shown a preference for nanoformulations, which can address major limitations such as stability, solubility, absorption, and toxicity. Ultimately, the pharmacokinetics of pharmaceutical dosage forms containing vitamins can impede the treatment of diseases and disorders related to vitamin deficiency.
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Affiliation(s)
| | - Rudra Pangeni
- Department of PharmaceuticsVirginia Commonwealth UniversityRichmondVirginiaUSA
| | | | - Sagun Poudel
- Department of PharmaceuticsVirginia Commonwealth UniversityRichmondVirginiaUSA
| | - Sopan Nangare
- Department of PharmaceuticsH. R. Patel Institute of Pharmaceutical Education and ResearchShirpurMaharashtraIndia
| | - Satveer Jagwani
- KLE College of PharmacyKLE Academy of Higher Education and ResearchBelagaviKarnatakaIndia
| | - Dnyandev Gadhave
- Department of PharmaceuticsSinhgad Technical Education SocietySinhgad Institute of PharmacyPuneMaharashtraIndia
| | - Chaolong Qin
- Department of PharmaceuticsVirginia Commonwealth UniversityRichmondVirginiaUSA
| | - Anjali Pandya
- Department of Pharmaceutical Sciences and TechnologyInstitute of Chemical TechnologyMumbaiIndia
| | - Purav Shah
- Thoroughbred Remedies ManufacturingTRM Industrial EstateNewbridgeIreland
| | - Kiran Jadhav
- KLE College of PharmacyKLE Academy of Higher Education and ResearchBelagaviKarnatakaIndia
| | - Hitendra S. Mahajan
- Department of PharmaceuticsR. C. Patel Institute of Pharmaceutical Education and ResearchShirpurMaharashtraIndia
| | - Vandana Patravale
- Department of Pharmaceutical Sciences and TechnologyInstitute of Chemical TechnologyMumbaiIndia
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21
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Murthy JJ, Hughes S, Travis C, Chalia A, Khan S, Ang-Rabanes M, Mogallapu R. Chronic Use of Proton Pump Inhibitors: A Potential Link to Amino Acid Deficiency and the Development of Depression. Cureus 2023; 15:e51067. [PMID: 38269224 PMCID: PMC10807343 DOI: 10.7759/cureus.51067] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 12/25/2023] [Indexed: 01/26/2024] Open
Abstract
In recent years, the gut-brain axis (GBA) has been implicated in several vital physiological processes, including digestion, immunity, inflammation, and mood regulation. Disruption of this network is tied to the development of several pathological conditions, including mood disorders, inflammatory bowel diseases, and dementia. Proton pump inhibitors (PPI) are among the most utilized and easily accessible medications worldwide. Although they are effective at treating conditions, including gastroesophageal reflux disorder (GERD), peptic ulcer disease, Zollinger-Ellison syndrome, and erosive esophagitis, PPIs have several mechanisms that may precipitate protein and, thus, amino acid malnutrition. Our patient is a 34-year-old female with a longstanding history of GERD treated with proton-pump inhibitors who presented to the psychiatry clinic complaining of a six-month history of depression without extraneous psychosocial factors. Although the patient refused psychiatric intervention, she desired an answer for her symptoms, leading to the discovery of a severe tyrosine deficiency. As tyrosine is critical in the process of neurotransmitter synthesis, replenishment of the amino acid along with discontinuation of proton-pump inhibitors was found to relieve her depressive symptoms within a few short months. In this report, we seek to establish a link between the chronic use of proton-pump inhibitor medications and the development of mood disorders.
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Affiliation(s)
- Jeevan J Murthy
- College of Medicine, Eastern Division, West Virginia University School of Medicine, Martinsburg, USA
| | - Sarah Hughes
- College of Medicine, Eastern Division, West Virginia University School of Medicine, Martinsburg, USA
| | - Colin Travis
- College of Medicine, Eastern Division, West Virginia School of Osteopathic Medicine, Martinsburg, USA
| | - Ankit Chalia
- Department of Behavioral Medicine and Psychiatry, West Virginia University School of Medicine, Martinsburg, USA
| | - Samira Khan
- Department of Behavioral Medicine and Psychiatry, West Virginia University School of Medicine, Martinsburg, USA
| | - Michael Ang-Rabanes
- Department of Behavioral Medicine and Psychiatry, West Virginia University School of Medicine, Martinsburg, USA
| | - Raja Mogallapu
- Department of Behavioral Medicine and Psychiatry, West Virginia University School of Medicine, Martinsburg, USA
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22
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Bell V, Rodrigues AR, Antoniadou M, Peponis M, Varzakas T, Fernandes T. An Update on Drug-Nutrient Interactions and Dental Decay in Older Adults. Nutrients 2023; 15:4900. [PMID: 38068758 PMCID: PMC10708094 DOI: 10.3390/nu15234900] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/06/2023] [Revised: 11/20/2023] [Accepted: 11/22/2023] [Indexed: 12/18/2023] Open
Abstract
In recent decades, the global demographic landscape has undergone a discernible shift that has been characterised by a progressive increase in the proportion of elderly individuals, indicative of an enduring global inclination toward extended lifespans. The aging process, accompanied by physiological changes and dietary patterns, contributes to detrimental deviations in micronutrient consumption. This vulnerable aging population faces heightened risks, including dental caries, due to structural and functional modifications resulting from insufficient nutritional sustenance. Factors such as physiological changes, inadequate nutrition, and the prevalence of multiple chronic pathologies leading to polypharmacy contribute to the challenge of maintaining an optimal nutritional status. This scenario increases the likelihood of drug interactions, both between medications and with nutrients and the microbiome, triggering complications such as dental decay and other pathologies. Since the drug industry is evolving and new types of food, supplements, and nutrients are being designed, there is a need for further research on the mechanisms by which drugs interfere with certain nutrients that affect homeostasis, exemplified by the prevalence of caries in the mouths of older adults. Infectious diseases, among them dental caries, exert serious impacts on the health and overall quality of life of the elderly demographic. This comprehensive review endeavours to elucidate the intricate interplay among drugs, nutrients, the microbiome, and the oral cavity environment, with the overarching objective of mitigating the potential hazards posed to both the general health and dental well-being of older adults. By scrutinising and optimising these multifaceted interactions, this examination aims to proactively minimise the susceptibility of the elderly population to a spectrum of health-related issues and the consequences associated with dental decay.
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Affiliation(s)
- Victoria Bell
- Faculty of Pharmacy, University of Coimbra, Pólo das Ciências da Saúde, Azinhaga de Santa Comba, 3000-548 Coimbra, Portugal; (V.B.)
| | - Ana Rita Rodrigues
- Faculty of Pharmacy, University of Coimbra, Pólo das Ciências da Saúde, Azinhaga de Santa Comba, 3000-548 Coimbra, Portugal; (V.B.)
| | - Maria Antoniadou
- Department of Dentistry, School of Health Sciences, National and Kapodistrian University of Athens, GR-15772 Athens, Greece; (M.A.); (M.P.)
- CSAP Executive Mastering Program in Systemic Management, University of Piraeus, GR-18534 Piraeus, Greece
| | - Marios Peponis
- Department of Dentistry, School of Health Sciences, National and Kapodistrian University of Athens, GR-15772 Athens, Greece; (M.A.); (M.P.)
| | - Theodoros Varzakas
- Food Science and Technology, University of the Peloponnese, GR-22100 Kalamata, Greece
| | - Tito Fernandes
- CIISA, Faculty of Veterinary Medicine, University of Lisbon, 1649-004 Lisbon, Portugal
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23
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Ramadoss T, Weimer DS, Mayrovitz HN. Topical Iron Chelator Therapy: Current Status and Future Prospects. Cureus 2023; 15:e47720. [PMID: 38022031 PMCID: PMC10675985 DOI: 10.7759/cureus.47720] [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: 08/22/2023] [Accepted: 10/25/2023] [Indexed: 12/01/2023] Open
Abstract
Systemic iron chelation therapy has long been used for iron overload, providing a role in returning iron levels to proper homeostatic concentrations. Recently, topical iron chelation therapy has emerged as a potential strategy for treating skin damage. This narrative review explores the current status and future prospects of topical iron chelation therapy for treating ultraviolet (UV) and non-UV skin damage, as well as its potential application in wound healing. The review was conducted through a literature search across PubMed, Web of Science, and EMBASE databases, spanning publications from 1990 to 2023. The selection of articles was focused on primary research studies, either experimental or clinical, that explored the implications and formulations of topical iron chelators used alone or in conjunction with another therapeutic agent. The search strategy employed a combination of terms, including "topical iron chelation", "topical deferoxamine", "UV", "wound healing", "skin inflammation", "radiation-induced fibrosis", and "skin cancer". Relevant studies, including methods, intervention strategies, measured outcomes, and findings, are summarized. The review also considered the potential challenges in translating research findings into clinical practice. Results indicate that topical iron chelators, such as deferoxamine, are effective in mitigating UV-induced skin damage, reducing tumorigenesis, and decreasing oxidative damage. In addition, the use of these agents in radiation-induced fibrosis has been shown to significantly increase skin elasticity and reduce dermal fibrosis. Several studies also highlight the use of topical iron chelators in difficult-to-treat chronic wounds, such as diabetic neuropathic ulcers and sickle cell ulcers. In conclusion, topical iron chelation therapy represents a novel and promising approach for skin protection and wound healing. Its potential makes it a promising area of future research.
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Affiliation(s)
- Tanya Ramadoss
- Medical School, Nova Southeastern University Dr. Kiran C. Patel College of Allopathic Medicine, Fort Lauderdale, USA
| | - Derek S Weimer
- Medical School, Nova Southeastern University Dr. Kiran C. Patel College of Allopathic Medicine, Fort Lauderdale, USA
| | - Harvey N Mayrovitz
- Medical Education, Nova Southeastern University Dr. Kiran C. Patel College of Allopathic Medicine, Fort Lauderdale, USA
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24
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Barraquer Comes A, Roy Millán P. Proton Pump Inhibitor Deprescription Prospective Study in Patients Without Indication: Are There Differences in Proportion of Restarts According to Withdrawal Strategy? J Pharm Technol 2023; 39:224-230. [PMID: 37745729 PMCID: PMC10515970 DOI: 10.1177/87551225231195216] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 09/26/2023] Open
Abstract
Background: The increasing utilization of proton pump inhibitors (PPIs) in patients without clear medical indications has raised concerns regarding potential risks, highlighting the importance of deprescription. However, comparative analyses of withdrawal strategies (abrupt vs gradual) in this context remain scarce or of low quality. Aim: This study aimed to evaluate the success rate of deprescribing PPIs in hospitalized patients without a documented indication and compare the proportion of treatment restarts based on withdrawal strategy. Method: An uncontrolled, open-label prospective observational study was conducted on patients receiving PPI treatment during hospital admission between May 2017 and July 2018. Deprescription was recommended for patients without a clear indication. Follow-up continued until discharge, with monitoring for rebound symptoms. The percentage of restarts based on the withdrawal strategy was compared using the chi-square test. Results: A total of 402 patients were reviewed, among whom 27% lacked a medical indication (mean age > 60 years, polymedicated), while 70% were prescribed PPIs electronically. Deprescription was performed in 49% of patients, with 64% undergoing abrupt withdrawal. Rebound symptoms led to treatment restart in 15% of cases. However, the chi-square test revealed no significant differences in restart proportions between the abrupt and gradual withdrawal groups (P = 0.365). Conclusion: Deprescribing PPIs is deemed safe, particularly for polymedicated geriatric patients, as it leads to a low percentage of restarts regardless of the chosen withdrawal strategy. However, the high percentage of PPI prescription without a clear indication underlines the need for periodic reassessment to avoid unnecessary risks and overuse.
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Affiliation(s)
- Anna Barraquer Comes
- Pharmaceutical specialist in hospital Pharmacy, Department manager, Hospital Mare de Déu de la Mercè, Barcelona, Spain
| | - Pedro Roy Millán
- Medical director, Hospital Mare de Déu de la Mercè, Barcelona, Spain
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25
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Tayal R, Yasmin S, Chauhan S, Singh TG, Saini M, Shorog E, Althubyani MM, Alsaadi BH, Aljohani F, Alenazi MA, Abutaily SA, Ansari MY. Are Proton Pump Inhibitors Contributing in Emerging New Hypertensive Population? Pharmaceuticals (Basel) 2023; 16:1387. [PMID: 37895858 PMCID: PMC10609986 DOI: 10.3390/ph16101387] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/04/2023] [Revised: 09/22/2023] [Accepted: 09/28/2023] [Indexed: 10/29/2023] Open
Abstract
Balancing the therapeutic advantages of a medicine with its possible risks and side effects is an important part of medical practice and drug regulation. When a drug is designed to treat a particular disease or medical condition ends up causing additional risks or side effects that lead to the development of other serious health problems, it can have detrimental consequences for patients. This article explores the correlation between persistent proton pump inhibitor (PPI) use and hypertension, a common cardiovascular ailment. While PPIs are beneficial in treating various gastrointestinal problems, their availability without a prescription has resulted in self-medication and long-term use without medical monitoring. Recent findings have revealed a link between long-term PPI usage and increased cardiovascular risks, particularly hypertension. This study investigates the intricate mechanisms underlying PPI's effects, focusing on potential pathways contributing to hypertension, such as endothelial dysfunction, disruption of nitric oxide bioavailability, vitamin B deficiency, hypocalcemia, and hypomagnesemia. The discussion explains how long-term PPI use can disrupt normal endothelial function, vascular control, and mineral balance, eventually leading to hypertension. The article emphasizes the significance of using PPIs with caution and ongoing research to better understand the implications of these medications on cardiovascular health.
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Affiliation(s)
- Rohit Tayal
- Chitkara College of Pharmacy, Chitkara University, Rajpura 140401, Punjab, India; (R.T.); (T.G.S.)
| | - Sabina Yasmin
- Department of Pharmaceutical Chemistry, College of Pharmacy, King Khalid University, Abha 61421, Saudi Arabia;
| | - Samrat Chauhan
- Chitkara College of Pharmacy, Chitkara University, Rajpura 140401, Punjab, India; (R.T.); (T.G.S.)
| | - Thakur Gurjeet Singh
- Chitkara College of Pharmacy, Chitkara University, Rajpura 140401, Punjab, India; (R.T.); (T.G.S.)
| | - Monika Saini
- M.M. College of Pharmacy, Maharishi Markandeshwar (Deemed to be) University, Mullana, Ambala 133207, Haryana, India;
- Swami Vivekanand College of Pharmacy, Ramnagar, Banur 140601, Punjab, India
| | - Eman Shorog
- Clinical Pharmacy Department, College of Pharmacy, King Khalid University, Abha 61421, Saudi Arabia;
| | - Maryam M. Althubyani
- Department of Clinical Services, Pharmaceutical Care Services, King Salman Medical City, Ministry of Health MOH, Al Madinah Al Munawwarah 11176, Saudi Arabia; (M.M.A.); (B.H.A.)
| | - Baiaan H. Alsaadi
- Department of Clinical Services, Pharmaceutical Care Services, King Salman Medical City, Ministry of Health MOH, Al Madinah Al Munawwarah 11176, Saudi Arabia; (M.M.A.); (B.H.A.)
| | - Fatimah Aljohani
- Prince Sultan Armed Forces Hospital, Al Madenah Al Monwarah 42375, Saudi Arabia;
| | - Maram A. Alenazi
- Pharmaceutical Care Services, King Salman Specialist Hospital, Ministry of Health (MOH), Hail 55471, Saudi Arabia;
| | - Sarah A. Abutaily
- Ambulatory Care Clinical, Prince Sultan Military Medical City, Riyadh 12233, Saudi Arabia;
| | - Mohammad Yousuf Ansari
- M.M. College of Pharmacy, Maharishi Markandeshwar (Deemed to be) University, Mullana, Ambala 133207, Haryana, India;
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26
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Chang JJ, Gadi SR, Videnovic A, Kuo B, Pasricha TS. Impact of outpatient gastroenterology consult on pharmacotherapy and management of gastrointestinal symptoms in Parkinson's Disease. Clin Park Relat Disord 2023; 9:100215. [PMID: 37700817 PMCID: PMC10493246 DOI: 10.1016/j.prdoa.2023.100215] [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: 05/08/2023] [Revised: 08/14/2023] [Accepted: 08/23/2023] [Indexed: 09/14/2023] Open
Abstract
Background & aims Gastrointestinal (GI) symptoms are common in Parkinson's Disease (PD) patients, and GI dysmotility is thought to induce motor fluctuations, requiring escalation of levodopa therapy. The role of GI consultation in managing such symptoms, however, is unclear. In this study, we investigate the possible association between GI dysmotility symptoms and escalated LEDD therapy, as well as factors associated with GI consultation for PD symptom management. Methods This was a retrospective case-study of 248 PD patients evaluated by outpatient neurology at Massachusetts General Brigham Healthcare from 2018 to 2022. Logistic regression, t-test, and Fisher exact tests were performed to identify factors associated with GI consult, change in LEDD with consult, and association of consultation with GI diagnoses and treatments, respectively. Results Among 248 PD patients, 12.9% received GI consultation despite 96.8% having GI symptoms. Bloating was the primary symptom associated with receiving GI consultation (OR 3.59 [95% CI 1.47-8.88], p = 0.005). GI consultation increased the odds of receiving GI-specific medications (78.2% vs 46.3%, p = 0.001) and specialized GI diagnoses like gastroparesis (9.4% vs 0.46%, p < 0.001) and pelvic floor dysfunction (15.6% vs 0%, p < 0.0001). Interestingly, LEDD tended not to change after GI consultation, and dysmotility symptoms, including bloating, did not predict need for higher LEDD. Conclusions While treating symptoms of dysmotility may not ameliorate levodopa-based motor fluctuations as much as previously thought, GI consultations are underutilized in PD, and patients who receive GI consultation are more likely to have changes in GI diagnosis and treatment.
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Affiliation(s)
| | - Sanjay R.V. Gadi
- Department of Medicine, Duke University Health System, Durham, NC, United States
- Harvard Medical School, Boston, MA, United States
| | - Aleksandar Videnovic
- Neurological Clinical Research Institute, Department of Neurology, Massachusetts General Hospital, Boston, MA, United States
- Harvard Medical School, Boston, MA, United States
| | - Braden Kuo
- Harvard Medical School, Boston, MA, United States
- Center for Neurointestinal Health, Division of Gastroenterology, Department of Medicine, Massachusetts General Hospital, Boston, MA, United States
| | - Trisha S. Pasricha
- Harvard Medical School, Boston, MA, United States
- Center for Neurointestinal Health, Division of Gastroenterology, Department of Medicine, Massachusetts General Hospital, Boston, MA, United States
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27
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Weh KM, Howard CL, Zhang Y, Tripp BA, Clarke JL, Howell AB, Rubenstein JH, Abrams JA, Westerhoff M, Kresty LA. Prebiotic proanthocyanidins inhibit bile reflux-induced esophageal adenocarcinoma through reshaping the gut microbiome and esophageal metabolome. BIORXIV : THE PREPRINT SERVER FOR BIOLOGY 2023:2023.08.22.554315. [PMID: 37662411 PMCID: PMC10473615 DOI: 10.1101/2023.08.22.554315] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 09/05/2023]
Abstract
The gut and local esophageal microbiome progressively shift from healthy commensal bacteria to inflammatory-linked pathogenic bacteria in patients with gastroesophageal reflux disease, Barrett's esophagus and esophageal adenocarcinoma (EAC). However, mechanisms by which microbial communities and metabolites contribute to reflux-driven EAC remain incompletely understood and challenging to target. Herein, we utilized a rat reflux-induced EAC model to investigate targeting the gut microbiome-esophageal metabolome axis with cranberry proanthocyanidins (C-PAC) to inhibit EAC progression. Sprague Dawley rats, with or without reflux-induction received water or C-PAC ad libitum (700 µg/rat/day) for 25 or 40 weeks. C-PAC exerted prebiotic activity abrogating reflux-induced dysbiosis, and mitigating bile acid metabolism and transport, culminating in significant inhibition of EAC through TLR/NF-κB/P53 signaling cascades. At the species level, C-PAC mitigated reflux-induced pathogenic bacteria (Clostridium perfringens, Escherichia coli, and Proteus mirabilis). C-PAC specifically reversed reflux-induced bacterial, inflammatory and immune-implicated proteins and genes including Ccl4, Cd14, Crp, Cxcl1, Il6, Il1β, Lbp, Lcn2, Myd88, Nfkb1, Tlr2 and Tlr4 aligning with changes in human EAC progression, as confirmed through public databases. C-PAC is a safe promising dietary constituent that may be utilized alone or potentially as an adjuvant to current therapies to prevent EAC progression through ameliorating reflux-induced dysbiosis, inflammation and cellular damage.
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28
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Dinesh D, Lee JS, Scott TM, Tucker KL, Palacios N. Proton Pump Inhibitor Use and Cognitive Function in the Boston Puerto Rican Health Study. J Gerontol A Biol Sci Med Sci 2023; 78:1461-1470. [PMID: 36420642 PMCID: PMC10395560 DOI: 10.1093/gerona/glac231] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/17/2022] [Indexed: 08/03/2023] Open
Abstract
BACKGROUND There is a lack of consensus among studies on the association between proton pump inhibitor (PPI) use and cognitive impairment. This association is not well studied among minority populations, including among Puerto Ricans. Therefore, we sought to examine this association among Boston-area Puerto Ricans. METHODS The Boston Puerto Rican Health Study is an ongoing longitudinal cohort that enrolled 1499 Boston-area Puerto Rican adults, aged 45-75 years at baseline. Complete outcome and exposure data was available for 1290 baseline participants. Covariate-adjusted linear regression and linear mixed effects models were used to examine the association between PPI use, and global cognition, executive function, and memory cross-sectionally and longitudinally over ~12.7 years of follow-up. Furthermore, we examined the cross-sectional association between long-term PPI use (continuous use of ~6.2 years) and global cognition, executive function, and memory. RESULTS Among 1 290 participants at baseline, 313 (24.3%) self-reported PPI use. Baseline PPI use was not associated with baseline global cognition, executive function, or memory. Baseline PPI use also did not alter the trajectory of global cognition, executive function, or memory over ~12.7 years of follow-up. Long-term PPI use was not associated with global cognition, executive function, or memory over ~12.7 years of follow-up. CONCLUSION In this study of Boston-area Puerto Ricans, we did not observe an association between PPI use and global cognition, executive function, or memory either cross-sectionally or over 12.7 years of follow-up.
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Affiliation(s)
- Deepika Dinesh
- Center for Population Health, University of Massachusetts Lowell, Lowell, Massachusetts, USA
- Department of Biomedical and Nutritional Sciences, University of Massachusetts Lowell, Lowell, Massachusetts, USA
| | - Jong Soo Lee
- Center for Population Health, University of Massachusetts Lowell, Lowell, Massachusetts, USA
- Department of Mathematical Sciences, University of Massachusetts Lowell, Lowell, Massachusetts, USA
| | - Tammy M Scott
- Center for Population Health, University of Massachusetts Lowell, Lowell, Massachusetts, USA
- Friedman School of Nutrition Science and Policy, Tufts University, Boston, Massachusetts, USA
- Department of Psychiatry, School of Medicine, Tufts University, Boston, Massachusetts, USA
| | - Katherine L Tucker
- Center for Population Health, University of Massachusetts Lowell, Lowell, Massachusetts, USA
- Department of Biomedical and Nutritional Sciences, University of Massachusetts Lowell, Lowell, Massachusetts, USA
| | - Natalia Palacios
- Center for Population Health, University of Massachusetts Lowell, Lowell, Massachusetts, USA
- Department of Public Health, University of Massachusetts Lowell, Lowell, Massachusetts, USA
- Department of Nutrition, Harvard University School of Public Health, Boston, Massachusetts, USA
- Geriatric Research Education Clinical Center, Department of Veterans Affairs, ENRM VA Hospital, Bedford, Massachusetts, USA
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29
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Shu C, Xu Z, He C, Xu X, Zhou Y, Cai B, Zhu Y. Application of biomaterials in the eradication of Helicobacter pylori: A bibliometric analysis and overview. Front Microbiol 2023; 14:1081271. [PMID: 37007524 PMCID: PMC10061102 DOI: 10.3389/fmicb.2023.1081271] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/27/2022] [Accepted: 03/06/2023] [Indexed: 03/18/2023] Open
Abstract
Helicobacter pylori is a prominent cause of gastritis, peptic ulcer, and gastric cancer. It is naturally colonized on the surface of the mucus layer and mucosal epithelial cells of the gastric sinus, surrounded not only by mucus layer with high viscosity that prevents the contact of drug molecules with bacteria but also by multitudinous gastric acid and pepsin, inactivating the antibacterial drug. With high-performance biocompatibility and biological specificity, biomaterials emerge as promising prospects closely associated with H. pylori eradication recently. Aiming to thoroughly summarize the progressing research in this field, we have screened 101 publications from the web of science database and then a bibliometric investigation was performed on the research trends of the application of biomaterials in eradicating H. pylori over the last decade utilizing VOSviewer and CiteSpace to establish the relationship between the publications, countries, institutions, authors, and most relevant topics. Keyword analysis illustrates biomaterials including nanoparticles (NPs), metallic materials, liposomes, and polymers are employed most frequently. Depending on their constituent materials and characterized structures, biomaterials exhibit diverse prospects in eradicating H. pylori regarding extending drug delivery time, avoiding drug inactivation, target response, and addressing drug resistance. Furthermore, we overviewed the challenges and forthcoming research perspective of high-performance biomaterials in H. pylori eradication based on recent studies.
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Affiliation(s)
- Chunxi Shu
- Department of Gastroenterology, Digestive Disease Hospital, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, China
| | - Zhou Xu
- The Second Clinical Medical College of Nanchang University, Nanchang, Jiangxi, China
| | - Cong He
- Department of Gastroenterology, Digestive Disease Hospital, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, China
| | - Xinbo Xu
- Department of Gastroenterology, Digestive Disease Hospital, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, China
| | - Yanan Zhou
- Department of Gastroenterology, Digestive Disease Hospital, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, China
| | - Baihui Cai
- The Second Clinical Medical College of Nanchang University, Nanchang, Jiangxi, China
| | - Yin Zhu
- Department of Gastroenterology, Digestive Disease Hospital, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, China
- *Correspondence: Yin Zhu,
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Simultaneous Pharmacokinetic Evaluation of Pantoprazole and Vitamin B Complex for Assessing Drug–Drug Interactions in Healthy Bangladeshi Adults by a Newly Developed and Validated HPLC Method. SEPARATIONS 2023. [DOI: 10.3390/separations10030170] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 03/06/2023] Open
Abstract
The present study has been designed to evaluate the impact of the co-administration of pantoprazole (PNT) with vitamin B (VTB) complex (VTB comprising VTB1, VTB6, and VTB12 in this study) on pharmacokinetic behavior. In this study, HPLC-based sensitive and efficient methods for simultaneous determination in human plasma were developed per US-FDA bioanalytical standards. The pharmacokinetic parameters of PNT, VTB1, VTB6, and VTB12 were also evaluated when the medicines were administered alone and co-administered. Following linearity, it was observed that the plasma PNT, VTB1, VTB6, and VTB12 retention times were 6.8 ± 0.2, 2.7 ± 0.1, 5.5 ± 0.2, and 3.8 ± 0.1 min, respectively, over the range of 1−100 μg/mL. For all analytes at the lower limit of quantification and all other values, intra-assay and inter-assay bias were within 15% and 13.5%, respectively. They barely interacted when PNT and VTB samples were evaluated in physical combinations through in vitro tests. Moreover, in the pharmacokinetics study, treatment with VTB did not significantly alter the pharmacokinetic characteristics of PNT. Therefore, the current work’s results might help assess drug–drug interactions that may be applied to bioequivalence studies and therapeutic drug monitoring.
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Impact of Vitamin B12 Insufficiency on the Incidence of Sarcopenia in Korean Community-Dwelling Older Adults: A Two-Year Longitudinal Study. Nutrients 2023; 15:nu15040936. [PMID: 36839293 PMCID: PMC9967932 DOI: 10.3390/nu15040936] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/18/2023] [Revised: 02/03/2023] [Accepted: 02/09/2023] [Indexed: 02/15/2023] Open
Abstract
The longitudinal effect of B12 insufficiency on sarcopenia has not yet been investigated in older adults. We aimed to study the impact of B12 levels on alterations in muscle mass, function and strength over two years. Non-sarcopenic older adults (n = 926) aged 70-84 were included. Using the Korean Frailty and Aging Cohort Study, this two-year longitudinal study used data across South Korea. The tools used for assessing muscle criteria were based on the Asian Working Group for Sarcopenia guidelines. Participants were divided into the insufficiency (initial serum B12 concentration < 350 pg/mL) and sufficiency groups (≥350 pg/mL). Logistic regression analyses were performed to evaluate the effect of initial B12 concentration on sarcopenia parameters over a two-year period. In women, multivariate analysis showed that the B12 insufficiency group had a significantly higher incidence of low SPPB scores (odds ratio [OR] = 3.28, 95% confidence interval [CI] = 1.59-6.76) and sarcopenia (OR = 3.72, 95% CI = 1.10-12.62). However, the B12 insufficiency group did not have a greater incidence of sarcopenia or other parameters in men. Our findings suggest B12 insufficiency negatively impacts physical performance and increases the incidence of sarcopenia only in women.
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Choi A, Noh Y, Jeong HE, Choi EY, Man KKC, Han JY, Kim HS, Yon DK, Shin JY. Association Between Proton Pump Inhibitor Use During Early Pregnancy and Risk of Congenital Malformations. JAMA Netw Open 2023; 6:e2250366. [PMID: 36626173 PMCID: PMC9856708 DOI: 10.1001/jamanetworkopen.2022.50366] [Citation(s) in RCA: 9] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/11/2023] Open
Abstract
IMPORTANCE Proton pump inhibitors (PPIs) are increasingly used during pregnancy; however, several observational studies have raised concerns about an increased risk of specific types of congenital malformations. OBJECTIVE To examine the association between PPI exposure during early pregnancy and the risk of congenital malformations. DESIGN, SETTING, AND PARTICIPANTS This population-based cohort study used data from the National Health Insurance Service-National Health Information Database of South Korea (2010-2020); sibling-controlled analyses were conducted to account for familial factors. A total of 2 696 216 pregnancies in women aged 19 to 44 years between June 1, 2011, and December 31, 2019, and their live-born infants were identified. Pregnant women who were exposed to known teratogens or who delivered infants with chromosomal abnormalities or genetic syndromes were excluded. Data on participant race and ethnicity were not collected because the National Health Information Database does not report this information. EXPOSURES Proton pump inhibitor use during the first trimester. MAIN OUTCOMES AND MEASURES Primary outcomes were major congenital malformations, congenital heart defects, cleft palate, hydrocephalus, and hypospadias. The subtypes of major congenital malformations and congenital heart defects were evaluated as exploratory outcomes. Propensity score fine stratification was used to control for potential confounders, and a weighted generalized linear model was used to estimate relative risks with 95% CIs. RESULTS Of 2 696 216 pregnancies (mean [SD] maternal age, 32.1 [4.2] years), 40 540 (1.5%; mean [SD] age, 32.4 [4.6] years) were exposed to PPIs during the first trimester. The absolute risk of major congenital malformations was 396.7 per 10 000 infants in PPI-exposed pregnancies and 323.4 per 10 000 infants in unexposed pregnancies. The propensity score-adjusted relative risks were 1.07 (95% CI, 1.02-1.13) for major congenital malformations, 1.09 (95% CI, 1.01-1.17) for congenital heart defects, 1.02 (95% CI, 0.72-1.43) for cleft palate, 0.94 (95% CI, 0.54-1.63) for hydrocephalus, and 0.77 (95% CI, 0.51-1.17) for hypospadias. In the sibling-controlled analyses, no associations were observed between PPI use and primary outcomes, including major congenital malformations (odds ratio, 1.05; 95% CI, 0.91-1.22) and congenital heart defects (odds ratio, 1.07; 95% CI, 0.88-1.30). A range of sensitivity analyses revealed results that were similar to the main findings. CONCLUSIONS AND RELEVANCE In this cohort study, the use of PPIs during early pregnancy was not associated with a substantial increase in the risk of congenital malformations, although small increased risks were observed for major congenital malformations and congenital heart defects; findings from sibling-controlled analyses revealed that PPIs were unlikely to be major teratogens. These findings may help guide clinicians and patients in decision-making about PPI use in the first trimester.
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Affiliation(s)
- Ahhyung Choi
- School of Pharmacy, Sungkyunkwan University, Suwon, South Korea
| | - Yunha Noh
- School of Pharmacy, Sungkyunkwan University, Suwon, South Korea
- Department of Biohealth Regulatory Science, Sungkyunkwan University, Suwon, South Korea
| | - Han Eol Jeong
- School of Pharmacy, Sungkyunkwan University, Suwon, South Korea
- Department of Biohealth Regulatory Science, Sungkyunkwan University, Suwon, South Korea
| | - Eun-Young Choi
- School of Pharmacy, Sungkyunkwan University, Suwon, South Korea
| | - Kenneth K. C. Man
- Research Department of Practice and Policy, University College London School of Pharmacy, London, United Kingdom
- Centre for Medicines Optimisation Research and Education, University College London Hospitals NHS Foundation Trust, London, United Kingdom
- Centre for Safe Medication Practice and Research, Department of Pharmacology and Pharmacy, Li Ka Shing Faculty of Medicine, University of Hong Kong, Hong Kong
| | - Jung Yeol Han
- Korean Mothersafe Counselling Center, Department of Obstetrics and Gynecology, Inje University Ilsan Paik Hospital, Goyang, South Korea
| | - Hyun-Soo Kim
- Division of Gastroenterology, Department of Internal Medicine, Yonsei University Wonju College of Medicine, Wonju, South Korea
| | - Dong Keon Yon
- Center for Digital Health, Medical Science Research Institute, Kyung Hee University Medical Center, Kyung Hee University College of Medicine, Seoul, South Korea
| | - Ju-Young Shin
- School of Pharmacy, Sungkyunkwan University, Suwon, South Korea
- Department of Biohealth Regulatory Science, Sungkyunkwan University, Suwon, South Korea
- Department of Clinical Research Design and Evaluation, Samsung Advanced Institute for Health Sciences and Technology, Sungkyunkwan University, Seoul, South Korea
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Kanbayashi Y, Ishikawa T, Kuriu Y, Otsuji E, Takayama K. Predictors for development of oxaliplatin-induced peripheral neuropathy in cancer patients as determined by ordered logistic regression analysis. PLoS One 2022; 17:e0275481. [PMID: 36174022 PMCID: PMC9521891 DOI: 10.1371/journal.pone.0275481] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/18/2022] [Accepted: 09/18/2022] [Indexed: 11/18/2022] Open
Abstract
Background Oxaliplatin causes acute cold-induced neurotoxicity and chronic cumulative neuropathy, which can require dose modification and impacts quality of life. However, effective strategies for managing oxaliplatin-induced peripheral neuropathy (OIPN) among affected patients remain elusive. Objective This retrospective study aimed to identify predictors for the development of OIPN. Methods Participants comprised 322 cancer patients at our hospital who were receiving oxaliplatin between January 2017 and March 2021. For the regression analysis of factors associated with OIPN, variables were manually extracted from medical charts. The severity of OIPN was evaluated using the National Cancer Institute’s Common Terminology Criteria for Adverse Events, version 5. Multivariate ordered logistic regression analysis was performed to identify predictors for the development of OIPN. Optimal cut-off thresholds were determined using receiver operating characteristic analysis. Values of P <0.05 (2-tailed) were considered significant. Results Significant risk factors identified included higher body mass index (BMI) (odds ratio [OR] = 1.06, 95% confidence interval [CI] = 1.00–1.12; P = 0.043), female sex (OR = 1.67, 95%CI = 1.06–2.61; P = 0.026) and higher total dosage (OR = 2.39, 95%CI = 1.67–3.42; P = < 0.0001). Conclusion High BMI, female sex and high total dosage were identified as significant predictors for the development of OIPN.
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Affiliation(s)
- Yuko Kanbayashi
- Department of Outpatient Oncology Unit, University Hospital, Kyoto Prefectural University of Medicine, Kyoto, Japan
- Department of Education and Research Center for Clinical Pharmacy, Faculty of Pharmacy, Osaka Medical and Pharmaceutical University, Takatsuki, Osaka, Japan
- * E-mail:
| | - Takeshi Ishikawa
- Department of Outpatient Oncology Unit, University Hospital, Kyoto Prefectural University of Medicine, Kyoto, Japan
- Department of Molecular Gastroenterology and Hepatology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan
| | - Yoshiaki Kuriu
- Division of Digestive Surgery, Department of Surgery, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan
| | - Eigo Otsuji
- Division of Digestive Surgery, Department of Surgery, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan
| | - Koichi Takayama
- Department of Pulmonary Medicine, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan
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Moffatt K, Rossi M, Park E, Svendsen JC, Wilson JM. Inhibition of gastric acid secretion with omeprazole affects fish specific dynamic action and growth rate: Implications for the development of phenotypic stomach loss. Front Physiol 2022; 13:966447. [PMID: 36237533 PMCID: PMC9552000 DOI: 10.3389/fphys.2022.966447] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/10/2022] [Accepted: 08/25/2022] [Indexed: 11/13/2022] Open
Abstract
An acid-secreting stomach provides many selective advantages to fish and other vertebrates; however, phenotypic stomach loss has occurred independently multiple times and is linked to loss of expression of both the gastric proton pump and the protease pepsin. Reasons underpinning stomach loss remain uncertain. Understanding the importance of gastric acid-secretion to the metabolic costs of digestion and growth will provide information about the metabolic expense of acid-production and performance. In this study, omeprazole, a well characterized gastric proton pump inhibitor, was used to simulate the agastric phenotype by significantly inhibiting gastric acidification in Nile tilapia. The effects on post-prandial metabolic rate and growth were assessed using intermittent flow respirometry and growth trials, respectively. Omeprazole reduced the duration (34.4%) and magnitude (34.5%) of the specific dynamic action and specific growth rate (21.3%) suggesting a decrease in digestion and assimilation of the meal. Gastric pH was measured in control and omeprazole treated fish to confirm that gastric acid secretion was inhibited for up to 12 h post-treatment (p < 0.05). Gastric evacuation measurements confirm a more rapid emptying of the stomach in omeprazole treated fish. These findings reinforce the importance of stomach acidification in digestion and growth and present a novel way of determining costs of gastric digestion.
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Affiliation(s)
| | - Mark Rossi
- Wilfrid Laurier University, Waterloo, Canada
| | - Edward Park
- Wilfrid Laurier University, Waterloo, Canada
| | - Jon Christian Svendsen
- Technical University of Denmark, National Institute of Aquatic Resources, Lyngby, Denmark
| | - Jonathan M. Wilson
- Wilfrid Laurier University, Waterloo, Canada
- CIIMAR University of Porto, Matosinhos, Portugal
- *Correspondence: Jonathan M. Wilson,
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Kugler TE, Malovichko IS, Gnilitskaya VB, Khristulenko AL, Yarovaya NF. Proton Pump Inhibitors in the COVID-19 Pandemic. THE RUSSIAN ARCHIVES OF INTERNAL MEDICINE 2022; 12:245-253. [DOI: 10.20514/2226-6704-2022-12-4-245-253] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/03/2025]
Abstract
The safety of proton pump inhibitors (PPIs) use in coronavirus infection (COVID-19) is not well understood. PPIs are potent suppressors of gastric secretion and become one of the ten most widely used drugs in the world. They are expected to influence virus susceptibility, severity, and outcomes in patients diagnosed with COVID-19. This concern is based on their mechanism of action — suppression of gastric acidity, which is considered the first line of defense against infections. Taken together, the results of most studies and meta-analyses support that PPIs use has been associated with increased risk of COVID-19 and severe outcomes. However, taking into account all potential risk factors for disease severity seems impossible in the real world in the context of COVID-19, so conclusions about causal relationships between PPI use and COVID-19 should be treated with great caution. An additional interesting point about the use of PPIs in the pandemic is that it reduced absorption of certain vitamins. On the other hand, several studies have appeared in the literature regarding the protective therapeutic effects of PPIs. There is growing evidence of an immunomodulatory and antifibrotic role of PPIs that could be used in the treatment of COVID-19. In addition, their ability to alkalize the contents of endosomes and lysosomes serves as an obstacle to the penetration of the virus into host cells. This review analyzes the possible effects of PPIs in patients with COVID-19.
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Affiliation(s)
- T. E. Kugler
- State Educational Organization of Higher Professional Education
«M. Gorky Donetsk National Medical University»
| | - I. S. Malovichko
- State Educational Organization of Higher Professional Education
«M. Gorky Donetsk National Medical University»
| | - V. B. Gnilitskaya
- State Educational Organization of Higher Professional Education
«M. Gorky Donetsk National Medical University»
| | - A. L. Khristulenko
- State Educational Organization of Higher Professional Education
«M. Gorky Donetsk National Medical University»
| | - N. F. Yarovaya
- State Educational Organization of Higher Professional Education
«M. Gorky Donetsk National Medical University»
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Abstract
Proton pump inhibitors (PPIs) are the most widely prescribed medications in the world. According to numerous studies, PPIs have been linked to hyperprolactinemia, which can lead to a variety of sexual and reproductive issues. This review summarizes the effects of numerous PPIs on the blood prolactin levels and associated sexual dysfunctions, which have an effect on the patient's life quality and fertility. The study is taken into account all the available resources till January 31, 2021. Out of total 364, only 27 relevant resources were involved in this review. In certain studies, short-term PPIs use has been shown to have little or no effect on the blood prolactin and other reproductive hormones levels. PPIs have been linked to the development of hyperprolactinemia in several case studies with varying degrees of the blood prolactin levels increase seen in individuals taking PPI alone or in combination with medications, like prokinetics. The relative risk of the sexual consequences development, such as gynecomastia, has been documented using lansoprazole and omeprazole in various cohort studies. On the other hand, other bits of data are insufficient to establish a definite relationship that can turn a possibility into certainty. The majority of the literature data is comprising of double-blind, randomized, crossover studies, case reports, and adverse drug reaction incidents reported to various pharmacovigilance centers. To investigate this link, high-quality studies in patients taking PPIs for a longer time period are needed. We conclude this article with a comprehensive discussion of the hyperprolactinemia clinical implications and the PPIs' function.
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Stretton B, Kovoor JG, Vanlint A, Maddern G, Thompson CH. Perioperative micronutrients, macroscopic benefits? J Perioper Pract 2022; 33:92-98. [PMID: 35445613 DOI: 10.1177/17504589221091058] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/15/2022]
Abstract
'Micronutrients' are vitamins and minerals vital for healthy metabolic function, wound healing and disease and infection prevention. Micronutrients may play a role in significantly improving postoperative recovery and indices of patient comfort; however, minimal research exists for surgical patients. Furthermore, current guidelines on perioperative nutrition have a macronutrient focus which may fail to guide detection and treatment of the subclinical micronutrient deficiency in a patient who is not obviously malnourished. Limited research into supplementation of some micronutrient deficiencies shows favourable results; however, given the financial implications of wound care, the prevalence of micronutrient deficiency and possible benefits from attention to micronutrition for postoperative recovery, further research into this area is urgently warranted. Interventions to guide optimal future clinical practice are suggested.
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Affiliation(s)
- Brandon Stretton
- Adelaide Medical School, Faculty of Health and Medical Sciences, The University of Adelaide, Adelaide, SA, Australia
| | - Joshua G Kovoor
- Discipline of Surgery, The Queen Elizabeth Hospital, The University of Adelaide, Adelaide, SA, Australia
| | - Andrew Vanlint
- Adelaide Medical School, Faculty of Health and Medical Sciences, The University of Adelaide, Adelaide, SA, Australia
| | - Guy Maddern
- Discipline of Surgery, The Queen Elizabeth Hospital, The University of Adelaide, Adelaide, SA, Australia
| | - Campbell H Thompson
- Adelaide Medical School, Faculty of Health and Medical Sciences, The University of Adelaide, Adelaide, SA, Australia
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Hewetson M, Tallon R. Equine Squamous Gastric Disease: Prevalence, Impact and Management. VETERINARY MEDICINE (AUCKLAND, N.Z.) 2021; 12:381-399. [PMID: 35004264 PMCID: PMC8725839 DOI: 10.2147/vmrr.s235258] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 07/29/2021] [Accepted: 12/07/2021] [Indexed: 12/12/2022]
Abstract
This narrative review explores the etiopathogenesis, clinical signs, diagnosis and treatment of ESGD (equine squamous gastric disease) and discusses the impact of this commonly encountered condition on the equine industry. ESGD refers specifically to peptic injury of the squamous mucosa of the stomach. Prevalence is highest in performance horses, but the disease has been documented across many breeds and ages, including in feral horses and foals. The pathogenesis of ESGD is well understood. Intensive management and exercise are important factors that contribute to a disruption of the normal stratification of gastric pH. This results in exposure of the vulnerable squamous mucosa to acid, leading to ulceration. Clinical signs are variable and there is little evidence to support a direct association between reported signs and the presence or absence of lesions seen on gastroscopy. Management is aimed at acid suppression and mitigation of known risk factors.
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Affiliation(s)
- Michael Hewetson
- Department of Clinical Science and Services, The Royal Veterinary College, North Mymms, Hertfordshire, UK
| | - Rose Tallon
- Department of Clinical Science and Services, The Royal Veterinary College, North Mymms, Hertfordshire, UK
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Phytic Acid and Whole Grains for Health Controversy. Nutrients 2021; 14:nu14010025. [PMID: 35010899 PMCID: PMC8746346 DOI: 10.3390/nu14010025] [Citation(s) in RCA: 23] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/30/2021] [Revised: 12/17/2021] [Accepted: 12/21/2021] [Indexed: 12/20/2022] Open
Abstract
Phytate (PA) serves as a phosphate storage molecule in cereals and other plant foods. In food and in the human body, PA has a high affinity to chelate Zn2+ and Fe2+, Mg2+, Ca2+, K+, Mn2+ and Cu2+. As a consequence, minerals chelated in PA are not bio-available, which is a concern for public health in conditions of poor food availability and low mineral intakes, ultimately leading to an impaired micronutrient status, growth, development and increased mortality. For low-income countries this has resulted in communications on how to reduce the content of PA in food, by appropriate at home food processing. However, claims that a reduction in PA in food by processing per definition leads to a measurable improvement in mineral status and that the consumption of grains rich in PA impairs mineral status requires nuance. Frequently observed decreases of PA and increases in soluble minerals in in vitro food digestion (increased bio-accessibility) are used to promote food benefits. However, these do not necessarily translate into an increased bioavailability and mineral status in vivo. In vitro essays have limitations, such as the absence of blood flow, hormonal responses, neural regulation, gut epithelium associated factors and the presence of microbiota, which mutually influence the in vivo effects and should be considered. In Western countries, increased consumption of whole grain foods is associated with improved health outcomes, which does not justify advice to refrain from grain-based foods because they contain PA. The present commentary aims to clarify these seemingly controversial aspects.
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Chae SA, Kim HS, Lee JH, Yun DH, Chon J, Yoo MC, Yun Y, Yoo SD, Kim DH, Lee SA, Chung SJ, Soh Y, Won CW. Impact of Vitamin B12 Insufficiency on Sarcopenia in Community-Dwelling Older Korean Adults. INTERNATIONAL JOURNAL OF ENVIRONMENTAL RESEARCH AND PUBLIC HEALTH 2021; 18:ijerph182312433. [PMID: 34886159 PMCID: PMC8656801 DOI: 10.3390/ijerph182312433] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 09/16/2021] [Revised: 11/21/2021] [Accepted: 11/23/2021] [Indexed: 10/31/2022]
Abstract
Vitamin B12 (B12) is involved as a cofactor in the synthesis of myelin. A lack of B12 impairs peripheral nerve production, which can contribute to sarcopenia. In this cross-sectional study, we aimed to investigate the relationship between B12 insufficiency and sarcopenia in community-dwelling older Korean adults. A total of 2325 (1112 men; 1213 women) adults aged 70-84 years were recruited. The tools used for sarcopenia were based on the Asian Working Group for Sarcopenia (AWGS) guidelines. Individuals with low appendicular skeletal muscle mass index (ASMI) (<7.0 kg/m2 for men; <5.4 kg/m2 for women) and low hand grip strength (HGS) (<28 kg for men; <18 kg for women) were defined as the sarcopenia group. Among this group, those who showed low physical performance (≤9 points on the Short Physical Performance Battery (SPPB)) were defined as the severe sarcopenia group. B12 concentrations were classified into insufficient (<350 pg/mL) and sufficient (≥350 pg/mL). Univariate and multivariate logistic regression analyses were used to evaluate the relationship between sarcopenia and B12 levels. Low ASMI showed a high incidence in the B12-insufficient group. However, HGS, SPPB, and the severity of sarcopenia showed no correlation with B12. Further, insufficient B12 may affect muscle quantity rather than muscle strength or physical performance.
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Affiliation(s)
- Seon A Chae
- Department of Physical Medicine and Rehabilitation Medicine, Kyung Hee University Medical Center, Seoul 02447, Korea; (S.A.C.); (H.-S.K.); (J.H.L.); (D.H.Y.); (J.C.); (M.C.Y.); (Y.Y.)
| | - Hee-Sang Kim
- Department of Physical Medicine and Rehabilitation Medicine, Kyung Hee University Medical Center, Seoul 02447, Korea; (S.A.C.); (H.-S.K.); (J.H.L.); (D.H.Y.); (J.C.); (M.C.Y.); (Y.Y.)
| | - Jong Ha Lee
- Department of Physical Medicine and Rehabilitation Medicine, Kyung Hee University Medical Center, Seoul 02447, Korea; (S.A.C.); (H.-S.K.); (J.H.L.); (D.H.Y.); (J.C.); (M.C.Y.); (Y.Y.)
| | - Dong Hwan Yun
- Department of Physical Medicine and Rehabilitation Medicine, Kyung Hee University Medical Center, Seoul 02447, Korea; (S.A.C.); (H.-S.K.); (J.H.L.); (D.H.Y.); (J.C.); (M.C.Y.); (Y.Y.)
| | - Jinmann Chon
- Department of Physical Medicine and Rehabilitation Medicine, Kyung Hee University Medical Center, Seoul 02447, Korea; (S.A.C.); (H.-S.K.); (J.H.L.); (D.H.Y.); (J.C.); (M.C.Y.); (Y.Y.)
| | - Myung Chul Yoo
- Department of Physical Medicine and Rehabilitation Medicine, Kyung Hee University Medical Center, Seoul 02447, Korea; (S.A.C.); (H.-S.K.); (J.H.L.); (D.H.Y.); (J.C.); (M.C.Y.); (Y.Y.)
| | - Yeocheon Yun
- Department of Physical Medicine and Rehabilitation Medicine, Kyung Hee University Medical Center, Seoul 02447, Korea; (S.A.C.); (H.-S.K.); (J.H.L.); (D.H.Y.); (J.C.); (M.C.Y.); (Y.Y.)
| | - Seung Don Yoo
- Department of Physical Medicine and Rehabilitation, Kyung Hee University Hospital at Gangdong, Seoul 05278, Korea; (S.D.Y.); (D.H.K.); (S.A.L.); (S.J.C.)
| | - Dong Hwan Kim
- Department of Physical Medicine and Rehabilitation, Kyung Hee University Hospital at Gangdong, Seoul 05278, Korea; (S.D.Y.); (D.H.K.); (S.A.L.); (S.J.C.)
| | - Seung Ah Lee
- Department of Physical Medicine and Rehabilitation, Kyung Hee University Hospital at Gangdong, Seoul 05278, Korea; (S.D.Y.); (D.H.K.); (S.A.L.); (S.J.C.)
| | - Sung Joon Chung
- Department of Physical Medicine and Rehabilitation, Kyung Hee University Hospital at Gangdong, Seoul 05278, Korea; (S.D.Y.); (D.H.K.); (S.A.L.); (S.J.C.)
| | - Yunsoo Soh
- Department of Physical Medicine and Rehabilitation Medicine, Kyung Hee University Medical Center, Seoul 02447, Korea; (S.A.C.); (H.-S.K.); (J.H.L.); (D.H.Y.); (J.C.); (M.C.Y.); (Y.Y.)
- Correspondence: (Y.S.); (C.W.W.)
| | - Chang Won Won
- Department of Family Medicine, Kyung Hee University Medical Center, Seoul 02447, Korea
- Correspondence: (Y.S.); (C.W.W.)
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Amjad W, Qureshi W, Singh RR, Richter S. Nutritional deficiencies and predictors of mortality in diabetic and nondiabetic gastroparesis. Ann Gastroenterol 2021; 34:788-795. [PMID: 34815644 PMCID: PMC8596206 DOI: 10.20524/aog.2021.0660] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/17/2021] [Accepted: 06/16/2021] [Indexed: 11/11/2022] Open
Abstract
BACKGROUND Gastroparesis is a debilitating condition that may impact morbidity and mortality, but there is a lack of long-term studies examining this relation. The aim of this study was to determine the predictors of mortality in gastroparesis and to determine the nutritional deficiencies. METHODS Between September 30, 2009 and January 31, 2020, we identified 320 patients (mean age 47.5±5.3 years, 70% female, 71.3% Whites, 39.7% diabetic and 60.3% nondiabetic) with gastroparesis. 99mTc sulfur-labeled food was used to diagnose gastroparesis. Cox proportional-hazard regression was used to compute the association of mortality predictors. RESULTS Of the 320 patients, 46 (14.4%) died during the study period. Among diabetics, advanced age (hazard ratio [HR] 1.06, 95% confidence interval [CI] 1.03-1.10; P<0.001), chronic kidney disease (CKD) (HR 4.69, 95%CI 1.62-13.59; P=0.004), and malnutrition (HR 10.95, 95%CI 3.23-37.17; P<0.001) were associated with higher mortality, whereas in nondiabetics older age (HR 1.05, 95%CI 1.01-1.09; P=0.04), CKD (HR 10.2, 95%CI 2.48-41.99; P=0.001), chronic obstructive pulmonary disease (COPD) (HR 7.5, 95%CI 2.11-26.82; P=0.002), coronary artery disease (CAD) (HR 9.7, 95%CI 1.8-52.21; P=0.008), and malnutrition (HR 3.83, 95%CI 1.14-29.07; P=0.03) were associated with increased mortality. Overall, 48.8% had vitamin D, 18.2% had vitamin B12, and 50.8% had iron deficiencies. Only 19.4% of the whole cohort was evaluated by a nutritionist. CONCLUSIONS Advanced age, CAD, CKD, COPD and malnutrition were associated with higher mortality in gastroparesis. Despite the high prevalence of nutritional deficiencies, consultation of a specialist nutritionist was uncommon.
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Affiliation(s)
- Waseem Amjad
- Department of Internal Medicine, Albany Medical Center, Albany, NY (Waseem Amjad)
| | - Waqas Qureshi
- Department of Cardiovascular Medicine, University of Massachusetts, Worchester, MA (Waqas Qureshi)
| | - Ritu R. Singh
- Department of Medicine, Indiana University School of Medicine, Fort Wayne, Indiana, USA (Ritu R. Singh)
- Johns Hopkins Bloomberg School of Public Health (Ritu R. Singh)
| | - Seth Richter
- Department of Gastroenterology, Albany Medical Center, Albany NY (Seth Richter), USA
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Hussain MS, Mazumder T. Long-term use of proton pump inhibitors adversely affects minerals and vitamin metabolism, bone turnover, bone mass, and bone strength. J Basic Clin Physiol Pharmacol 2021; 33:567-579. [PMID: 34687598 DOI: 10.1515/jbcpp-2021-0203] [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: 07/02/2021] [Accepted: 10/01/2021] [Indexed: 11/15/2022]
Abstract
Notwithstanding, proton pump inhibitors (PPIs) are one of the most excellent options for different anti-secretory therapy in terms of improved symptomatic outcomes, numerous epidemiological and cohort studies provide evidence of an association between long-term proton PPIs use and increased fracture risk among users. The present attempt aimed to summarize the effect of long-term use of PPIs on musculoskeletal systems by considering the recent claims of different research groups to understand the risk of osteopenia and osteoporosis and to determine the risk factors associated with these complications. We extracted data from various systematic reviews and meta-analyses, cross-sectional studies, prospective studies, case-control studies, cohort studies, and in-vivo and in-vitro studies to observe the consequence of long-term PPIs uses over the patient's bone health. Recent findings suggested that long-term use of PPIs plays an introductory and cabalistic role in the development of osteoporosis mostly hip fractures by disturbing numerous biological pathways and thus able to set up a link between over-prescription of PPIs and bone loss. Frequent administration of PPIs is associated with a significantly worse outcome to bone mineral density (BMD) profile and produce a negative impression on bone health. Since, there are limited data to determine the association of PPIs use and change in BMD, recommending further studies to find out this dissertation.
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Affiliation(s)
- Md Saddam Hussain
- Department of Pharmacy, Faculty of Science, Noakhali Science and Technology University, Noakhali, Bangladesh
| | - Tanoy Mazumder
- Department of Pharmacy, Faculty of Science, Noakhali Science and Technology University, Noakhali, Bangladesh
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43
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George JS, Joseph R, Thomas ETA, John GP, Siby A, Nair MM. Active deprescribing program in chronic kidney disease patients undergoing haemodialysis. Nephrology (Carlton) 2021; 26:890-897. [PMID: 34240512 DOI: 10.1111/nep.13936] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/28/2021] [Revised: 06/20/2021] [Accepted: 07/04/2021] [Indexed: 12/22/2022]
Abstract
BACKGROUND Deprescribing is gaining attention of medical community to address polypharmacy. Existing deprescribing tools were not validated in haemodialysis population. We designed this study to assess the pill burden of patients undergoing haemodialysis and to measure the outcome after implementation of an active deprescribing program. METHODS An evidence based deprescription tool was formulated. All patients who were on dialysis for 3 months or more were eligible to participate. Medication reconciliation followed by medication list evaluation for appropriateness was done for all patients. All inappropriate medications were discontinued followed by monitoring for 6 months for complications. Primary outcome was the average number of medications and pills per patient before and 12 weeks after implementation of deprescribing program. RESULTS We enrolled 150 patients to the active deprescribing program. Mean age was 60.4 ± 10.9 years. After deprescription, there were significant reduction in the number of medications from 11 (Interquartile range 8-13.25) to 8 (IQR 6-9) (p < .001) and reduction in the number of pills from 16 (IQR 12.75-21.25) to 11 (IQR 8-14.25) (p < .001). Pill burden accessed using Living with Medication Questionnaire-Visual Analogue Scale score also had a significant reduction from 7 (IQR 5-8) to 4 (IQR 3-5) (p < .001). CONCLUSION Polypharmacy is a significant problem in haemodialysis patients, which can lead to poor quality of life and health hazards due to side effects of medications. Implementation of a proactive deprescribing program can cut down polypharmacy to a significant extent.
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Affiliation(s)
- Jyothi Susan George
- Department of Clinical Pharmacy, Believers Church Medical College Hospital, Thiruvalla, Kerala, India
| | - Rajesh Joseph
- Department of Nephrology, Believers Church Medical College Hospital, Thiruvalla, Kerala, India
| | - E T Arun Thomas
- Department of Nephrology, Believers Church Medical College Hospital, Thiruvalla, Kerala, India
| | - Geo Philip John
- Department of Nephrology, Believers Church Medical College Hospital, Thiruvalla, Kerala, India
| | - Anu Siby
- Department of Clinical Pharmacy, Believers Church Medical College Hospital, Thiruvalla, Kerala, India
| | - Midhun M Nair
- Department of Clinical Pharmacy, Believers Church Medical College Hospital, Thiruvalla, Kerala, India
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Sanajou S, Şahin G. Mechanistic Biomarkers in Toxicology. Turk J Pharm Sci 2021; 18:376-384. [PMID: 34157829 DOI: 10.4274/tjps.galenos.2020.10270] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/01/2022]
Abstract
Biomarkers are important parameters that are reliable, applicable, reproducible, and generally inexpensive. All biomarkers have a significant role in human health, especially mechanistic biomarkers, which are the most important for the prevention of toxic effects and diseases. They demonstrate the possibility of diagnosis, prognosis, recurrence, and spread of disease. Furthermore, they show the exposure levels to numerous chemical, biological, and physical agents. To date, the development and application of biomarkers require the knowledge of mechanisms underlying their production. Therefore, the present study focused on the possible mechanistic biomarkers.
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Affiliation(s)
- Sonia Sanajou
- Faculty of Pharmacy, Eastern Mediterranean University, 99628, Famagusta, North Cyprus, Via Mersin 10, Turkey
| | - Gönül Şahin
- Faculty of Pharmacy, Eastern Mediterranean University, 99628, Famagusta, North Cyprus, Via Mersin 10, Turkey
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Abstract
People with alcohol-associated liver disease often take medicines to manage complications of liver disease and comorbidities. However, patients may be at increased risk of drug-related harm Assessing the severity of liver disease is fundamental to management, as disease staging (steatosis, early fibrosis, cirrhosis) affects medication safety and guides treatment While clinically significant pharmacokinetic and pharmacodynamic changes predominantly occur in cirrhosis, people with early alcohol-associated liver disease may still experience adverse events with potentially inappropriate medicines such as proton pump inhibitors, opioids and benzodiazepines Regular medication review is essential to ensure ongoing appropriateness and safety Alcoholic hepatitis and cirrhosis require specialist gastroenterology or hepatology management. However, general practitioners will remain the cornerstone of day-to-day medication management
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Affiliation(s)
- Amy L Johnson
- Centre for Liver Disease Research, Faculty of Medicine, Translational Research Institute, The University of Queensland, Brisbane.,Department of Gastroenterology and Hepatology, Princess Alexandra Hospital, Brisbane
| | - Kelly L Hayward
- Centre for Liver Disease Research, Faculty of Medicine, Translational Research Institute, The University of Queensland, Brisbane.,Department of Gastroenterology and Hepatology, Princess Alexandra Hospital, Brisbane
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Systematic Review and Meta-analysis: The Effects of Prophylactic Proton Pump Inhibitor Treatment in Patients With Coronary Heart Disease Receiving Dual Antiplatelet Therapy. J Cardiovasc Pharmacol 2021; 77:835-861. [PMID: 34057160 DOI: 10.1097/fjc.0000000000001014] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/01/2020] [Accepted: 02/28/2021] [Indexed: 12/24/2022]
Abstract
Dual antiplatelet therapy (DAPT) and proton pump inhibitors (PPIs) are widely used in clinical treatment. However, the pharmacokinetic interaction between PPIs and DAPT is still unclear in patients with cardiovascular disease. This systematic review and meta-analysis aimed to evaluate the risks and benefits of the combination of PPI and DAPT in patients with coronary heart disease. The PubMed, EMBASE, Cochrane, and Web of Science databases were systematically searched from inception to April 1, 2020, for eligible studies. The outcomes investigated in this study included major adverse cardiovascular events, myocardial infarction, all-cause death, gastrointestinal complications, and platelet function testing. Studies were excluded from the review if other gastrointestinal medication or aspirin or P2Y12 receptor inhibitor monotherapy was administered. The review included 52 studies, and data from 40 studies were extracted for meta-analysis. No association was found between the risk of adverse clinical outcomes and the combination of PPI and DAPT based on the randomized controlled trial data (risk ratio: 0.98; 95% confidence interval: 0.87-1.09; P = 0.877; I2 = 0%). However, an increased risk of adverse clinical outcomes due to the use of PPIs was observed in patients treated with DAPT based on the data from observational studies (risk ratio: 1.259; 95% confidence interval: 1.079-1.468; P = 0.003; I2 = 67.8%), although the heterogeneity of these studies was high. In conclusion, this systematic review and meta-analysis demonstrated that pharmacokinetic interactions between PPI and DAPT do not lead to adverse clinical outcomes.
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Dubourg S, Huck O, Jung S. Implant-based oral rehabilitation in systemic sclerosis patients: a systematic review. J ORAL IMPLANTOL 2021; 48:251-260. [PMID: 33945625 DOI: 10.1563/aaid-joi-d-20-00384] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/22/2022]
Abstract
Systemic sclerosis is a rare multisystem autoimmune disorder that significantly impacts the orofacial region. Several oral features including microstomia and increased tooth loss contribute to the mouth-related disability. Prosthetic rehabilitation is very challenging in these patients. As the spectrum of dental implants indications has been recently extended to patients with various systemic disorders, the aim of this systematic review was to evaluate the outcome of dental implants in patients with systemic sclerosis. A literature search was conducted in Medline/PubMed database to identify eligible case-reports. 10 publications were included in qualitative synthesis. A total of 71 implants have been reported in 10 patients with systemic sclerosis with a mean of 7.1 +/- 3.8 implants per patient. Pre-implant surgeries have been described for 3 patients. Implant survival rates were higher than 98% but the mean follow-up time was only 28.3 +/- 18.6 months. Complications have been observed in 3 patients with 1 implant failure and peri-implant bone resorption in 2 patients. Although implant survival rates were high, an individualized assessment of risk-benefit balance is mandatory before indicating implant-based rehabilitation in patients suffering from systemic sclerosis and a scrupulous maintenance program has to be implemented. Further studies are strongly required to establish clinical guidelines.
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Affiliation(s)
- Sarah Dubourg
- Hôpitaux Universitaires de Strasbourg, Centre de Référence Maladies Rares Orales et Dentaires (O-Rares), Pôle de Médecine et de Chirurgie Bucco-Dentaires - Strasbourg, France
| | - Olivier Huck
- Université de Strasbourg, Faculté de Chirurgie Dentaire - Hôpitaux Universitaires de Strasbourg, Service de Parodontologie et Centre de Référence Maladies Rares Orales et Dentaires - INSERM UMR 1260 - Strasbourg, France
| | - Sophie Jung
- Universite de Strasbourg 1: Universite de Strasbourg Faculté de Chirurgie Dentaire 8 rue Sainte Elisabeth FRANCE STRASBOURG Alsace 67000 Université de Strasbourg, Faculté de Chirurgie Dentaire - Hôpitaux Universitaires de Strasbourg, Centre de Référence Maladies Rares Orales et Dentaires - INSERM UMR_S 1109 - Strasbourg, France
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Chande S, Dijk F, Fetene J, Yannicelli S, Carpenter TO, van Helvoort A, Bergwitz C. Phosphorus bioaccessibility measured in four amino acid-based formulas using in-vitro batch digestion translates well into phosphorus bioavailability in mice. Nutrition 2021; 89:111291. [PMID: 34111672 DOI: 10.1016/j.nut.2021.111291] [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: 10/18/2020] [Revised: 04/07/2021] [Accepted: 04/18/2021] [Indexed: 10/21/2022]
Abstract
OBJECTIVE The aim of this study was to quantify the bioaccessibility of phosphorus from amino acid-based formulas (AAFs) under different digestive conditions. METHODS We developed in-vitro batch digestion models with stomach digestion at different pH mimicking the normal digestive condition and conditions representing use of acid-suppressive medication. To validate bioaccessibility findings, we devised a low phosphorus murine model to test phosphorus bioavailability under compromised digestive conditions using proton pump inhibitors (PPIs) to neutralize stomach pH. RESULTS In vitro phosphorus bioaccessibility of AAFs Neocate® Infant and Neocate Junior ranged between 57% and 65% under normal digestive conditions for infants (stomach pH 3.5) and between 38% and 46% under conditions that simulated bypass of stomach acidification, which is comparable to control diet and two EleCare® AAFs. In vivo bioavailability analysis showed that both Neocate formulas were able to normalize plasma phosphorus levels when administered to low phosphorus mice along with PPIs (control diet + PPI 8 ± 0.4; Neocate Infant 10.1 ± 0.9; Neocate Junior 9.2 ± 0.6; EleCare Infant 8.6 ± 0.4; EleCare Junior 8.7 ± 0.5; n = 8-10; P < 0.0001 versus baseline 3.4 ± 0.2 mg/dL). In comparison, plasma phosphorus levels remained lower on the low phosphorus diet (5.7 ± 0.2 mg/dL). Furthermore, urinary phosphorus/creatinine and intact fibroblast growth factor 23 were significantly lowered by low phosphorus diet. In contrast, intact parathyroid hormone and 1,25-dihydroxy vitamin D decreased and increased, respectively, and these parameters likewise normalized in mice administered AAFs. CONCLUSION The present findings indicated that phosphorus bioaccessibility in the in-vitro batch digestion model translates well into phosphorus bioavailability in mice even under compromised digestive conditions that bypass gastric acidification.
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Affiliation(s)
- Sampada Chande
- Yale University School of Medicine, Section of Endocrinology and Metabolism, New Haven, Connecticut, USA
| | | | - Jonathan Fetene
- Yale University School of Medicine, Section of Endocrinology and Metabolism, New Haven, Connecticut, USA
| | | | - Thomas O Carpenter
- Yale University School of Medicine, Department of Pediatrics, New Haven, Connecticut, USA
| | - Ardy van Helvoort
- Danone Nutricia Research, Utrecht, The Netherlands; School of Nutrition and Translational Research in Metabolism, Maastricht University, Maastricht, The Netherlands
| | - Clemens Bergwitz
- Yale University School of Medicine, Section of Endocrinology and Metabolism, New Haven, Connecticut, USA.
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Zippi M, Fiorino S, Budriesi R, Micucci M, Corazza I, Pica R, de Biase D, Gallo CG, Hong W. Paradoxical relationship between proton pump inhibitors and COVID-19: A systematic review and meta-analysis. World J Clin Cases 2021; 9:2763-2777. [PMID: 33969059 PMCID: PMC8058681 DOI: 10.12998/wjcc.v9.i12.2763] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/08/2020] [Revised: 01/01/2021] [Accepted: 02/12/2021] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND The proton pump inhibitors (PPIs), used to reduce gastric acid secretion, represent one of the most widely used pharmaceutical classes in the world. Their consumption as a risk factor for the evolution of severe forms of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has been investigated as well as the mortality of these patients. These risks also appear to be linked to the duration and the dosage. On the other hand, several studies have emerged with regard to the protective or therapeutic effects of these drugs. More and more evidence underlines the immunomodulatory and anti-fibrotic role of PPIs. In addition, their ability to alkalize the contents of endosomes and lysosomes serves as an obstacle to the entry of the virus into the host cells. AIM To identify studies on the relationship between the intake of PPIs and coronavirus disease 2019 (COVID-19) in patients affected by SARS-CoV-2 infection, with the main objective of evaluating the outcomes related to severity and mortality. METHODS A literature review was performed in November 2020. The MEDLINE/PubMed, Cochrane Library, EMBASE and Google Scholar databases were searched for all relevant articles published in English on this topic. The search terms were identified by means of controlled vocabularies, such as the National Library of Medicine's MESH (Medical Subject Headings) and keywords. The MESH terms and keywords used were as follows: "COVID-19", "proton pump inhibitors", "PPIs", "SARS-CoV-2", "outcomes", "severity" and "mortality". The inclusion criteria regarding the studies considered in our analysis were: meta-analysis, case-control, hospital-based case-control, population-based case-control, retrospective studies, online survey, as well as cohort-studies, while articles not published as full reports, such as conference abstracts, case reports and editorials were excluded. We tried to summarize and pool all the data if available. RESULTS A total of 9 studies were found that described the use of PPIs, of which only 5 clearly reported the severity and mortality data in SARS-CoV-2 patients. Our pooled incidence analysis of severe events did not differ between patients with and without PPIs (odds ratio 1.65, 95% confidence interval: 0.62-4.35) (P = 0.314), or for mortality (odds ratio 1.77, 95% confidence interval: 0.62-5.03) (P = 0.286). CONCLUSION Detailed and larger case studies are needed to accurately understand the role of PPIs in this viral infection.
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Affiliation(s)
- Maddalena Zippi
- Unit of Gastroenterology and Digestive Endoscopy, Sandro Pertini Hospital, Rome 00157, Italy
| | - Sirio Fiorino
- Unit of Internal Medicine, Maggiore Hospital, Local Health Unit of Bologna, Bologna 40133, Italy
| | - Roberta Budriesi
- Food Chemistry and Nutraceuticals Laboratory, Department of Pharmacy and Biotechnology (FaBiT), Alma Mater Studiorum, University of Bologna, Bologna 40133, Italy
| | - Matteo Micucci
- Food Chemistry and Nutraceuticals Laboratory, Department of Pharmacy and Biotechnology (FaBiT), Alma Mater Studiorum, University of Bologna, Bologna 40133, Italy
| | - Ivan Corazza
- Experimental, Diagnostic and Speciality Medicine Department, University of Bologna, Bologna 40138, Italy
| | - Roberta Pica
- Unit of Gastroenterology and Digestive Endoscopy, Sandro Pertini Hospital, Rome 00157, Italy
| | - Dario de Biase
- Department of Pharmacy and Biotechnology, University of Bologna, Bologna 40138, Italy
| | | | - Wandong Hong
- Department of Gastroenterology and Hepatology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000, Zhejiang Province, China
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50
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Wu Y, Song Z, Deng G, Jiang K, Wang H, Zhang X, Han H. Gastric Acid Powered Nanomotors Release Antibiotics for In Vivo Treatment of Helicobacter pylori Infection. SMALL (WEINHEIM AN DER BERGSTRASSE, GERMANY) 2021; 17:e2006877. [PMID: 33619851 DOI: 10.1002/smll.202006877] [Citation(s) in RCA: 34] [Impact Index Per Article: 8.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 11/03/2020] [Revised: 01/04/2021] [Indexed: 05/18/2023]
Abstract
Helicobacter pylori (H. pylori) infection has ≈75% probability of causing gastric cancer, so it is considered to be the strongest single risk factor for gastric malignancies. However, the harsh gastric acid environment has created obstacles to medical treatment. This work reports a nanomotor with a bottle-shaped container that can be loaded with small molecules of clarithromycin, nano calcium peroxide (CaO2 ), and Pt nanoparticles (Pt NPs) by ultrasound. Nanomotors can quickly consume gastric acid through the chemical reaction of CaO2 to temporarily neutralize gastric acid. The product hydrogen peroxide (H2 O2 ) is catalytically decomposed into a large amount of oxygen (O2 ) by Pt NPs. The local concentration gradient of O2 bubbles causes it to be expelled from the nanobottles through a narrow opening, and then push the nanobottles forward to provide maximum release and prodrug efficacy. Experiments in animal models show that 15 mg nanomotors can safely and quickly neutralize gastric acid in the stomach and simultaneously release prodrugs to achieve good therapeutic effects without causing acute toxicity. H. pylori burden in mice was 2.6 orders of magnitude lower than that in the control group. The stomach returns to normal pH within 1 d after administration.
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Affiliation(s)
- Yang Wu
- State Key Laboratory of Agriculture Microbiology, College of Life Science and Technology, Huazhong Agricultural University, Wuhan, 430070, China
| | - Zhiyong Song
- State Key Laboratory of Agriculture Microbiology, College of Science, Huazhong Agricultural University, Wuhan, 430070, China
| | - Guiyun Deng
- State Key Laboratory of Agriculture Microbiology, College of Science, Huazhong Agricultural University, Wuhan, 430070, China
| | - Kai Jiang
- State Key Laboratory of Agriculture Microbiology, College of Science, Huazhong Agricultural University, Wuhan, 430070, China
| | - Huajuan Wang
- State Key Laboratory of Agriculture Microbiology, College of Food Science and Technology, Huazhong Agricultural University, Wuhan, 430070, China
| | - Xueji Zhang
- School of Biomedical Engineering, Shenzhen University, Shenzhen, Guangdong, 518060, China
| | - Heyou Han
- State Key Laboratory of Agriculture Microbiology, College of Life Science and Technology, Huazhong Agricultural University, Wuhan, 430070, China
- State Key Laboratory of Agriculture Microbiology, College of Science, Huazhong Agricultural University, Wuhan, 430070, China
- State Key Laboratory of Agriculture Microbiology, College of Food Science and Technology, Huazhong Agricultural University, Wuhan, 430070, China
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