679814
letter2016
TAW0010.1177/2042098616679814Therapeutic Advances in Drug SafetyMA Pegoli, M Dedigama
Therapeutic Advances in Drug Safety
Letter to the Editor
Proton pump inhibitors and risk of readmission and mortality in older patients discharged from a tertiary hospital to residential aged care facilities
Ther Adv Drug Saf 2017, Vol. 8(4) 137–139 DOI: 10.1177/ 2042098616679814 © The Author(s), 2016. Reprints and permissions: http://www.sagepub.co.uk/ journalsPermissions.nav
Matthew A. Pegoli, Maneesha Dedigama, Arduino A. Mangoni, Patrick T. Russell, Luke E. Grzeskowiak and Tilenka Thynne Increasing evidence indicates that proton pump inhibitors (PPIs) are being overprescribed and are associated with numerous adverse effects [Forgacs and Loganayagam, 2008; McCarthy, 2010]. Studies over the past decade have linked PPI use to increased rates of Clostridium difficile infection, pneumonia, fractures, hypomagnesemia and both acute and chronic kidney disease [Schoenfeld and Grady, 2016]. Two studies, one involving institutionalized older patients, and another involving patients in acute geriatric wards and nursing homes, have demonstrated a link between PPI use and increased mortality [Bell et al. 2010; Teramura-Gronblad et al. 2012]. PPI use in older patients discharged from acute care hospitals was also associated with increased mortality [Maggio et al. 2013]. We sought to investigate whether the use of PPIs, specifically in older hospital patients discharged to residential aged care facilities (RACFs), had any impact on hospital readmission rates and mortality. Patients ⩾75 years, originally from home or a RACF, admitted to general medicine wards between 30 October 2014 and 1 May 2015 and discharged to a RACF, were recruited into the study. Palliative care patients were excluded. A comprehensive list of all preadmission medications, completed by a clinical pharmacist, was utilized as the list of medications on admission. A discharge medication chart for each RACF, completed by a medical officer and countersigned by a clinical pharmacist, was utilized as the list of medications on discharge. Only regular medications were included in data analysis. Readmission data was obtained via the electronic hospital clinical information system. Mortality data was collected via Births, Deaths and Marriages South Australia, who require mandatory reporting for all RACF deaths. Each patient was followed up
for six months in relation to readmission and mortality. Ethics approval was obtained via the Southern Adelaide Clinical Human Research Ethics Committee (457.14). The Charlson Comorbidity Index (CCI) scores were calculated via the electronic hospital clinical information system. Statistical analyses were performed using IBM® SPSS® Statistics Version 21. Cox proportional hazards regression (hazard ratios) and negative binomial regression with log link (incidence rate ratios) both with 95% confidence intervals were used to determine the association between PPIs and mortality and hospital readmissions, respectively. The possible indication for each PPI was identified based on the medical discharge summary, taking into account the patients’ concurrent medical conditions and medications.
Correspondence to: Matthew Alexander Pegoli, BPharm Department of Pharmacy, Flinders Medical Centre, Flinders Drive, Bedford Park, South Australia, 5042, Australia [email protected]. au
The mean (SD) age of participants (N = 102) was 87 (6) years, and 62 (60.8%) were female. Of the total population, 51 (50%) were taking a PPI on discharge. Of the population taking a PPI on discharge, 45 (88%) were already taking a PPI prior to their admission, 4 (8%) were initiated onto a PPI during their admission, and 2 (4%) had their PPI continued at a decreased dose. Of the 51 patients taking a PPI, 37 patients received pantoprazole; 9, esomeprazole; 4, omeprazole; and 1, rabeprazole. In adjusted analyses, PPI use was associated with an 82% increased rate of hospital readmission (Table 1), and 124% increased rate of mortality within six months from initial discharge from hospital (Table 2). The majority of patients (n = 30/51; 59%) had an identifiable indication for a PPI based on their medical discharge summary, the most common of which was gastroesophageal reflux disease (n = 16/30; 53%).
Patrick T. Russell, MD, FRACP Department of General Medicine, Royal Adelaide Hospital, South Australia, Australia
Maneesha Dedigama, MBBS, Arduino A. Mangoni, MD, PhD Tilenka Thynne, MBBS, FRACP Department of Clinical Pharmacology, Flinders Medical Centre, South Australia, Australia Luke E. Grzeskowiak, BPharm, GCertClinEpi, PhD Department of Pharmacy, Flinders Medical Centre, South Australia, Australia
PPI use in our patient population was associated with an increased rate of hospital readmission
journals.sagepub.com/home/taw 137
Therapeutic Advances in Drug Safety 8(4) Table 1. Relationship between use of PPIs and readmissions.
Median number (range) of hospital readmissions within six months
PPI users (n = 51)
PPI nonusers (n = 51)
Adjusted IRR (95% CI)a
p value
1 (0–6)
0 (0–3)
1.82 (1.13–2.94)
0.014
PPI, proton pump inhibitors; CI, confidence interval; IRR, incidence rate ratio. aIndicates negative binomial regression with log link IRRs adjusted for age, gender, initial place of residence, CCI, number of days alive following discharge and number of regular medications taken on discharge.
Table 2. Relationship between use of PPIs and mortality.
Mortality (%) at six months
PPI users (n = 51)
PPI nonusers (n = 51)
Adjusted HR (95% CI)a
p value
19 (37.3%)
14 (27.5%)
2.24 (1.01–4.96)
0.047
PPI, proton pump inhibitors; CI, confidence interval; HR, hazard ratio. aIndicates Cox proportional hazards regression HRs adjusted for age, gender, initial place of residence, CCI, total number of days spent in hospital within six months and number of regular medications taken on discharge.
and mortality within six months. Our mortality data is consistent with previous studies. However, we also observed a significant increase in hospital readmission rates, as further evidence of potential PPI-related adverse events. These results may be explained by PPIs increasing the likelihood of infection, fractures and other adverse effects mentioned in literature. Increasing hospital readmissions places strain on the health care system, and a portion may be avoidable due to 41% of patients not having an identifiable indication for a PPI based on their medical discharge summary. A possibility of residual confounding cannot be excluded, the indication for each PPI was limited to that which was identifiable from medical discharge summaries, and we lacked data relating to how long each patient had already been on a PPI and for how long they remained on a PPI post-discharge. This frail patient population are already at a high risk of readmission and mortality, and PPIs may further increase this risk unnecessarily. Our study further highlights the need for physicians and pharmacists to continually review PPI use, especially in the older inpatient population. Acknowledgements Matthew A. Pegoli had full access to all the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis. Study concept and design, acquisition of data, analysis and interpretation of data, drafting of the manuscript, critical revision of the manuscript for
important intellectual content, statistical analysis: Pegoli, Dedigama, Mangoni, Grzeskowiak, Russell, Thynne. Gregory W Roberts (BPharm, FSHP, CRP) and Cameron Phillips (BPharm, MClinPharm) provided assistance with study guidance and concept. Justin P. Turner (PhD, BPharm, MClinPharm) and Sepehr Shakib (MBBS, FRACP, PhD) provided assistance with data management. No compensation was received for all of the above contributions. This study was approved by the Southern Adelaide Clinical Human Research Ethics Committee (457.14). Funding The author(s) received no financial support for the research, authorship, and/or publication of this article. Conflict of interest statement The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.
References Bell, J., Strandberg, T., Teramura-Gronblad, M., Laurila, J., Tilvis, R. and Pitkala, K. (2010) Use of proton pump inhibitors and mortality among institutionalized older people. Arch Intern Med 170: 1604–1605. Forgacs, I. and Loganayagam, A. (2008) Overprescribing proton pump inhibitors. BMJ 336: 2–3.
138 journals.sagepub.com/home/taw
MA Pegoli, M Dedigama et al. Maggio, M., Corsonello, A., Ceda, G., Cattabiani, C., Lauretani, F., Butto, V. et al. (2013) Proton pump inhibitors and risk of 1-year mortality and rehospitalization in older patients discharged from acute care hospitals. JAMA Intern Med 173: 518–523. McCarthy, D. (2010) Adverse effects of proton pump inhibitor drugs: clues and conclusions. Curr Opin Gastroenterol 26: 624–631.
Schoenfeld, A. and Grady, D. (2016) Adverse effects associated with proton pump inhibitors. JAMA Intern Med 176: 172–174. Teramura-Gronblad, M., Bell, J., Poysti, M., Strandberg, T., Laurila, J., Tilvis, R. et al. (2012) Risk of death associated with use of PPIs in three cohorts of institutionalized older people in Finland. J Am Med Dir Assoc 13: 488.
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journals.sagepub.com/home/taw 139
letter2016
TAW0010.1177/2042098616679814Therapeutic Advances in Drug SafetyMA Pegoli, M Dedigama
Therapeutic Advances in Drug Safety
Letter to the Editor
Proton pump inhibitors and risk of readmission and mortality in older patients discharged from a tertiary hospital to residential aged care facilities
Ther Adv Drug Saf 2017, Vol. 8(4) 137–139 DOI: 10.1177/ 2042098616679814 © The Author(s), 2016. Reprints and permissions: http://www.sagepub.co.uk/ journalsPermissions.nav
Matthew A. Pegoli, Maneesha Dedigama, Arduino A. Mangoni, Patrick T. Russell, Luke E. Grzeskowiak and Tilenka Thynne Increasing evidence indicates that proton pump inhibitors (PPIs) are being overprescribed and are associated with numerous adverse effects [Forgacs and Loganayagam, 2008; McCarthy, 2010]. Studies over the past decade have linked PPI use to increased rates of Clostridium difficile infection, pneumonia, fractures, hypomagnesemia and both acute and chronic kidney disease [Schoenfeld and Grady, 2016]. Two studies, one involving institutionalized older patients, and another involving patients in acute geriatric wards and nursing homes, have demonstrated a link between PPI use and increased mortality [Bell et al. 2010; Teramura-Gronblad et al. 2012]. PPI use in older patients discharged from acute care hospitals was also associated with increased mortality [Maggio et al. 2013]. We sought to investigate whether the use of PPIs, specifically in older hospital patients discharged to residential aged care facilities (RACFs), had any impact on hospital readmission rates and mortality. Patients ⩾75 years, originally from home or a RACF, admitted to general medicine wards between 30 October 2014 and 1 May 2015 and discharged to a RACF, were recruited into the study. Palliative care patients were excluded. A comprehensive list of all preadmission medications, completed by a clinical pharmacist, was utilized as the list of medications on admission. A discharge medication chart for each RACF, completed by a medical officer and countersigned by a clinical pharmacist, was utilized as the list of medications on discharge. Only regular medications were included in data analysis. Readmission data was obtained via the electronic hospital clinical information system. Mortality data was collected via Births, Deaths and Marriages South Australia, who require mandatory reporting for all RACF deaths. Each patient was followed up
for six months in relation to readmission and mortality. Ethics approval was obtained via the Southern Adelaide Clinical Human Research Ethics Committee (457.14). The Charlson Comorbidity Index (CCI) scores were calculated via the electronic hospital clinical information system. Statistical analyses were performed using IBM® SPSS® Statistics Version 21. Cox proportional hazards regression (hazard ratios) and negative binomial regression with log link (incidence rate ratios) both with 95% confidence intervals were used to determine the association between PPIs and mortality and hospital readmissions, respectively. The possible indication for each PPI was identified based on the medical discharge summary, taking into account the patients’ concurrent medical conditions and medications.
Correspondence to: Matthew Alexander Pegoli, BPharm Department of Pharmacy, Flinders Medical Centre, Flinders Drive, Bedford Park, South Australia, 5042, Australia [email protected]. au
The mean (SD) age of participants (N = 102) was 87 (6) years, and 62 (60.8%) were female. Of the total population, 51 (50%) were taking a PPI on discharge. Of the population taking a PPI on discharge, 45 (88%) were already taking a PPI prior to their admission, 4 (8%) were initiated onto a PPI during their admission, and 2 (4%) had their PPI continued at a decreased dose. Of the 51 patients taking a PPI, 37 patients received pantoprazole; 9, esomeprazole; 4, omeprazole; and 1, rabeprazole. In adjusted analyses, PPI use was associated with an 82% increased rate of hospital readmission (Table 1), and 124% increased rate of mortality within six months from initial discharge from hospital (Table 2). The majority of patients (n = 30/51; 59%) had an identifiable indication for a PPI based on their medical discharge summary, the most common of which was gastroesophageal reflux disease (n = 16/30; 53%).
Patrick T. Russell, MD, FRACP Department of General Medicine, Royal Adelaide Hospital, South Australia, Australia
Maneesha Dedigama, MBBS, Arduino A. Mangoni, MD, PhD Tilenka Thynne, MBBS, FRACP Department of Clinical Pharmacology, Flinders Medical Centre, South Australia, Australia Luke E. Grzeskowiak, BPharm, GCertClinEpi, PhD Department of Pharmacy, Flinders Medical Centre, South Australia, Australia
PPI use in our patient population was associated with an increased rate of hospital readmission
journals.sagepub.com/home/taw 137
Therapeutic Advances in Drug Safety 8(4) Table 1. Relationship between use of PPIs and readmissions.
Median number (range) of hospital readmissions within six months
PPI users (n = 51)
PPI nonusers (n = 51)
Adjusted IRR (95% CI)a
p value
1 (0–6)
0 (0–3)
1.82 (1.13–2.94)
0.014
PPI, proton pump inhibitors; CI, confidence interval; IRR, incidence rate ratio. aIndicates negative binomial regression with log link IRRs adjusted for age, gender, initial place of residence, CCI, number of days alive following discharge and number of regular medications taken on discharge.
Table 2. Relationship between use of PPIs and mortality.
Mortality (%) at six months
PPI users (n = 51)
PPI nonusers (n = 51)
Adjusted HR (95% CI)a
p value
19 (37.3%)
14 (27.5%)
2.24 (1.01–4.96)
0.047
PPI, proton pump inhibitors; CI, confidence interval; HR, hazard ratio. aIndicates Cox proportional hazards regression HRs adjusted for age, gender, initial place of residence, CCI, total number of days spent in hospital within six months and number of regular medications taken on discharge.
and mortality within six months. Our mortality data is consistent with previous studies. However, we also observed a significant increase in hospital readmission rates, as further evidence of potential PPI-related adverse events. These results may be explained by PPIs increasing the likelihood of infection, fractures and other adverse effects mentioned in literature. Increasing hospital readmissions places strain on the health care system, and a portion may be avoidable due to 41% of patients not having an identifiable indication for a PPI based on their medical discharge summary. A possibility of residual confounding cannot be excluded, the indication for each PPI was limited to that which was identifiable from medical discharge summaries, and we lacked data relating to how long each patient had already been on a PPI and for how long they remained on a PPI post-discharge. This frail patient population are already at a high risk of readmission and mortality, and PPIs may further increase this risk unnecessarily. Our study further highlights the need for physicians and pharmacists to continually review PPI use, especially in the older inpatient population. Acknowledgements Matthew A. Pegoli had full access to all the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis. Study concept and design, acquisition of data, analysis and interpretation of data, drafting of the manuscript, critical revision of the manuscript for
important intellectual content, statistical analysis: Pegoli, Dedigama, Mangoni, Grzeskowiak, Russell, Thynne. Gregory W Roberts (BPharm, FSHP, CRP) and Cameron Phillips (BPharm, MClinPharm) provided assistance with study guidance and concept. Justin P. Turner (PhD, BPharm, MClinPharm) and Sepehr Shakib (MBBS, FRACP, PhD) provided assistance with data management. No compensation was received for all of the above contributions. This study was approved by the Southern Adelaide Clinical Human Research Ethics Committee (457.14). Funding The author(s) received no financial support for the research, authorship, and/or publication of this article. Conflict of interest statement The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.
References Bell, J., Strandberg, T., Teramura-Gronblad, M., Laurila, J., Tilvis, R. and Pitkala, K. (2010) Use of proton pump inhibitors and mortality among institutionalized older people. Arch Intern Med 170: 1604–1605. Forgacs, I. and Loganayagam, A. (2008) Overprescribing proton pump inhibitors. BMJ 336: 2–3.
138 journals.sagepub.com/home/taw
MA Pegoli, M Dedigama et al. Maggio, M., Corsonello, A., Ceda, G., Cattabiani, C., Lauretani, F., Butto, V. et al. (2013) Proton pump inhibitors and risk of 1-year mortality and rehospitalization in older patients discharged from acute care hospitals. JAMA Intern Med 173: 518–523. McCarthy, D. (2010) Adverse effects of proton pump inhibitor drugs: clues and conclusions. Curr Opin Gastroenterol 26: 624–631.
Schoenfeld, A. and Grady, D. (2016) Adverse effects associated with proton pump inhibitors. JAMA Intern Med 176: 172–174. Teramura-Gronblad, M., Bell, J., Poysti, M., Strandberg, T., Laurila, J., Tilvis, R. et al. (2012) Risk of death associated with use of PPIs in three cohorts of institutionalized older people in Finland. J Am Med Dir Assoc 13: 488.
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SAGE journals
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