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Franchi C, Rossio R, Mandelli S, Ardoino I, Nobili A, Peyvandi F, Mannucci PM. Statins, ACE/ARBs drug use, and risk of pneumonia in hospitalized older patients: a retrospective cohort study. Intern Emerg Med 2024; 19:689-696. [PMID: 38353881 DOI: 10.1007/s11739-023-03528-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/08/2023] [Accepted: 12/30/2023] [Indexed: 04/24/2024]
Abstract
The aims of this study is to evaluate the association between angiotensin-converting enzyme inhibitor (ACE-I), angiotensin II receptor blocker (ARBs) and/or statin use with the risk of pneumonia, as well as and with in-hospital and short-term outpatient mortality in hospitalized older patients with pneumonia. Patients aged 65 years or older hospitalized in internal medicine and/or geriatric wards throughout Italy and enrolled in the REPOSI (REgistro Politerapuie SIMI-Società Italiana di Medicina Interna) register from 2010 to 2019 were screened to assess the diagnosis of pneumonia and classified on whether or not they were prescribed with at least one drug among ACE-I, ARBs, and/or statins. Further study outcomes were mortality during hospital stay and at 3 months after hospital discharge. Among 5717 cases included (of whom 18.0% with pneumonia), 2915 (51.0%) were prescribed at least one drug among ACE-I, ARBs, and statins. An inverse association was found between treatment with ACE-I or ARBs and pneumonia (OR = 0.79, 95% CI 0.65-0.95). A higher effect was found among patients treated with ACE-I or ARBs in combination with statins (OR = 0.67, 95% CI 0.52-0.85). This study confirmed in the real-world setting that these largely used medications may reduce the risk of pneumonia in older people, who chronically take them for cardiovascular conditions.
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Affiliation(s)
- Carlotta Franchi
- Laboratory of Pharmacoepidemiology and Human Nutrition, Department of Health Policy, Istituto di Ricerche Farmacologiche Mario Negri IRCCS, Via Mario Negri, 2, 20156, Milan, Italy.
| | - Raffaella Rossio
- Department of Pathophysiology and Transplantation, Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico, Milan, Italy
| | - Sara Mandelli
- Laboratory of Pharmacoepidemiology and Human Nutrition, Department of Health Policy, Istituto di Ricerche Farmacologiche Mario Negri IRCCS, Via Mario Negri, 2, 20156, Milan, Italy
| | - Ilaria Ardoino
- Laboratory of Pharmacoepidemiology and Human Nutrition, Department of Health Policy, Istituto di Ricerche Farmacologiche Mario Negri IRCCS, Via Mario Negri, 2, 20156, Milan, Italy
| | - Alessandro Nobili
- Laboratory of Pharmacoepidemiology and Human Nutrition, Department of Health Policy, Istituto di Ricerche Farmacologiche Mario Negri IRCCS, Via Mario Negri, 2, 20156, Milan, Italy
| | - Flora Peyvandi
- Department of Pathophysiology and Transplantation, Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico, Milan, Italy
| | - Pier Mannuccio Mannucci
- Angelo Bianchi Bonomi Hemophilia and Thrombosis Center, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy
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Xun X, Yin Q, Fu Y, He X, Dong Z. Proton Pump Inhibitors and the Risk of Community-Acquired Pneumonia: An Updated Meta-analysis. Ann Pharmacother 2021; 56:524-532. [PMID: 34425689 DOI: 10.1177/10600280211039240] [Citation(s) in RCA: 16] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/21/2022] Open
Abstract
BACKGROUND Some studies suggested an increased risk of community-acquired pneumonia (CAP) among proton pump inhibitors (PPI) users. However, the published evidence is inadequate to define the association between PPI use and the risk of CAP. OBJECTIVE The aims of our meta-analysis were to systematically assess the association between the risk of CAP and PPI use in adults to reduce the adverse effects of PPI and ensure the safety of medication for patients. METHODS A comprehensive literature search was conducted, published between January 1, 2004, and February 1, 2021. The primary outcome was the incidence of CAP. This meta-analysis was performed using odds ratios (ORs) with 95% CIs as effective measures; 13 studies including 2 098 804 patients were enrolled in our meta-analysis. RESULTS Our study revealed that the incidence of CAP was higher in PPI users than non -PPI users [OR = 1.37 (95% CI = 1.22-1.53)], especially for PPI duration < 30 days [OR = 1.49 (95% CI = 1.34-1.66)]. Compared with non-PPI use, PPI use increased the incidence of CAP in the stroke disease population [OR = 1.52 (95% CI = 1.33-1.75)], but not in the liver disease population [OR = 1.13 (95% CI = 0.98-1.30)]. CONCLUSIONS AND RELEVANCE Using PPI could increase the risk of CAP when compared to not using PPI. PPI use increased the incidence of CAP in patients with stroke. Clinicians and clinical pharmacists should weigh the benefits before medication and strictly control the indication of the prescription, so as to reduce adverse reactions.
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Affiliation(s)
- Xuejiao Xun
- Hebei General Hospital, Shijiazhuang, Hebei Province, China
| | - Qifan Yin
- Hebei General Hospital, Shijiazhuang, Hebei Province, China.,Hebei Medical University First Affiliated Hospital, Shijiazhuang, Hebei Province, China
| | - Yuhao Fu
- Hebei General Hospital, Shijiazhuang, Hebei Province, China
| | - Xueru He
- Hebei General Hospital, Shijiazhuang, Hebei Province, China
| | - Zhanjun Dong
- Hebei General Hospital, Shijiazhuang, Hebei Province, China
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Sundaresh B, Xu S, Noonan B, Mansour MK, Leong JM, van Opijnen T. Host-informed therapies for the treatment of pneumococcal pneumonia. Trends Mol Med 2021; 27:971-989. [PMID: 34376327 DOI: 10.1016/j.molmed.2021.07.008] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/24/2021] [Revised: 07/06/2021] [Accepted: 07/12/2021] [Indexed: 12/11/2022]
Abstract
Over the past two decades, traditional antimicrobial strategies have lost efficacy due to a rapid rise in antibiotic resistance and limited success in developing new antibiotics. Rather than relying on therapeutics solely targeting the bacterial pathogen, therapies are emerging that simultaneously focus on host responses. Here, we describe the most promising 'host-informed therapies' (HITs) in two categories: those that aid patients with fully functional immune systems, and those that aid patients with perturbed immune processes. Using Streptococcus pneumoniae, the leading cause of bacterial pneumonia, as a case study, we show HITs as an attractive option for supplementing infection management. However, to broaden their applicability and design new strategies, targeted research and clinical trials will be essential.
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Affiliation(s)
| | - Shuying Xu
- Department of Molecular Biology and Microbiology, Tufts University School of Medicine, Boston, MA, USA; Graduate Program in Immunology, Tufts Graduate School of Biomedical Sciences, Boston, MA, USA
| | - Brian Noonan
- Stuart B. Levy Center for Integrated Management of Antimicrobial Resistance, Tufts Medical Center, Boston, MA, USA
| | - Michael K Mansour
- Division of Infectious Diseases, Massachusetts General Hospital, Boston, MA, USA; Harvard Medical School, Boston, MA, USA
| | - John M Leong
- Department of Molecular Biology and Microbiology, Tufts University School of Medicine, Boston, MA, USA; Stuart B. Levy Center for Integrated Management of Antimicrobial Resistance, Tufts Medical Center, Boston, MA, USA.
| | - Tim van Opijnen
- Department of Biology, Boston College, Chestnut Hill, MA, USA; Stuart B. Levy Center for Integrated Management of Antimicrobial Resistance, Tufts Medical Center, Boston, MA, USA.
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4
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Evers PD, Farkas DK, Khoury M, Olsen M, Madsen NL. Proton-pump inhibitor use and risk of community-acquired pneumonia in congenital heart disease patients. INTERNATIONAL JOURNAL OF CARDIOLOGY CONGENITAL HEART DISEASE 2021. [DOI: 10.1016/j.ijcchd.2021.100152] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/21/2022] Open
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5
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Chu C, Zeng S, Hasan AA, Hocher C, Krämer BK, Hocher B. Comparison of infection risks and clinical outcomes in patients with and without SARS-CoV-2 lung infection under renin-angiotensin-aldosterone system blockade: Systematic review and meta-analysis. Br J Clin Pharmacol 2021; 87:2475-2492. [PMID: 33217033 PMCID: PMC7753617 DOI: 10.1111/bcp.14660] [Citation(s) in RCA: 18] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/15/2020] [Revised: 10/28/2020] [Accepted: 11/10/2020] [Indexed: 02/06/2023] Open
Abstract
AIMS Angiotensin-converting enzyme-2 (ACE2) is the receptor for SARS-CoV-2. Animal studies suggest that renin-angiotensin-aldosterone system (RAAS) blockers might increase the expression of ACE2 and potentially increase the risk of SARS-CoV-2 infection. METHODS AND RESULTS The effect of ACE inhibitor (ACEI) treatment on the pneumonia incidence in non-COVID-19 patients (25 studies, 330 780 patients) was associated with a 26% reduction of pneumonia risk (odds ratio [OR]: 0.74, P < .001). Pneumonia-related death cases in ACEI-treated non-COVID-19 patients were reduced by 27% (OR: 0.73, P = .004). However, angiotensin II receptor blockers (ARB) treatment (10 studies, 275 621 non-COVID-19 patients) did not alter pneumonia risk in patients. Pneumonia-related death cases in ARB-treated non-COVID-19 patients was analysed only in 1 study and was significantly reduced (OR, 0.47; 95% confidence interval, 0.30 to 0.72). Results from 11 studies (8.4 million patients) showed that the risk of getting infected with the SARS-CoV-2 virus was reduced by 13% (OR: 0.87, P = .014) in patients treated with ACEI, whereas analysis from 10 studies (8.4 million patients) treated with ARBs showed no effect (OR, 0.92, P = .354). Results from 34 studies in 67 644 COVID-19 patients showed that RAAS blockade reduces all-cause mortality by 24% (OR = 0.76, P = .04). CONCLUSION ACEIs reduce the risk of getting infected with the SARS-CoV-2 virus. Blocking the RAAS may decrease all-cause mortality in COVID-19 patients. ACEIs also reduce the risk of non-COVID pneumonia. All-cause mortality due to non-COVID pneumonia is reduced by ACEI and potentially by ARBs.
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Affiliation(s)
- Chang Chu
- Fifth Department of Medicine (Nephrology/Endocrinology/Rheumatology)University Medical Centre Mannheim, University of HeidelbergGermany
- Department of NephrologyCharité‐Universitätsmedizin Berlin, Campus MitteBerlinGermany
| | - Shufei Zeng
- Fifth Department of Medicine (Nephrology/Endocrinology/Rheumatology)University Medical Centre Mannheim, University of HeidelbergGermany
- Department of NephrologyCharité‐Universitätsmedizin Berlin, Campus MitteBerlinGermany
| | - Ahmed A. Hasan
- Fifth Department of Medicine (Nephrology/Endocrinology/Rheumatology)University Medical Centre Mannheim, University of HeidelbergGermany
- Department of Nutritional Toxicology, Institute of Nutritional ScienceUniversity of PotsdamNuthetalGermany
- Department of Biochemistry, Faculty of PharmacyZagazig UniversityEgypt
| | - Carl‐Friedrich Hocher
- Fifth Department of Medicine (Nephrology/Endocrinology/Rheumatology)University Medical Centre Mannheim, University of HeidelbergGermany
| | - Bernhard K. Krämer
- Fifth Department of Medicine (Nephrology/Endocrinology/Rheumatology)University Medical Centre Mannheim, University of HeidelbergGermany
- European Center of Angioscience, Medical Faculty MannheimUniversity of HeidelbergGermany
| | - Berthold Hocher
- Fifth Department of Medicine (Nephrology/Endocrinology/Rheumatology)University Medical Centre Mannheim, University of HeidelbergGermany
- Key Laboratory of Study and Discovery of Small Targeted Molecules of Hunan Province, School of MedicineHunan Normal UniversityChangshaChina
- Reproductive and Genetic Hospital of CITIC‐XiangyaChangshaChina
- IMD Institut für Medizinische Diagnostik Berlin‐Potsdam GbRBerlinGermany
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Clinical characteristics and outcomes of community-acquired pneumonia in western Saudi Arabia: A four-year retrospective analysis of medical records. J Infect Public Health 2021; 14:960-966. [PMID: 34130120 DOI: 10.1016/j.jiph.2021.05.008] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/11/2021] [Revised: 05/07/2021] [Accepted: 05/12/2021] [Indexed: 10/21/2022] Open
Abstract
BACKGROUND Community-acquired pneumonia (CAP) is a significant cause of morbidity and mortality, especially for the elderly and people who suffer from chronic conditions. This study was conducted to assess the clinical and microbiological characteristics and disease outcomes associated with the occurrence of CAP. METHODS This retrospective chart review was conducted at King Abdulaziz Medical City, Jeddah, Saudi Arabia. Cases with documented clinical diagnosis of CAP during the period from 2016 to 2019 were included. Data were collected on demographic, clinical, and microbiological characteristics, used antimicrobials and patients' outcomes, including length of hospital stay, intensive care unit admission, and mortality. Multivariate regression analysis was performed to identify risk factors for increased length of hospital stay. RESULTS A total of two hundred and eighteen CAP episodes were identified. Patients had a median age of 64.5 years, and 54.1% were males. Microbiological diagnosis was established in 33 patients (15.1%). Admission to ICU and diagnosis of a neurological disease were significantly associated with longer hospital stay (>7 days). An average of 2.7 antimicrobials were used per patient, and the most common antibiotics used were Piperacillin/Tazobactam (46.3%), Doxycycline (44%), then Ceftriaxone (42.7%). Four patients (1.8%) died during hospital stay. CONCLUSIONS This retrospective analysis of CAP cases identified a lack of microbiological diagnosis and increased burden associated with disease severity and the need for hospitalization. The ability to identify CAP at an earlier stage will be a cornerstone to mitigate its impact on the healthcare system and ICU units.
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Mitacchione G, Schiavone M, Curnis A, Arca M, Antinori S, Gasperetti A, Mascioli G, Severino P, Sabato F, Caracciolo MM, Arabia G, D'Erasmo L, Viecca M, Mancone M, Galli M, Forleo GB. Impact of prior statin use on clinical outcomes in COVID-19 patients: data from tertiary referral hospitals during COVID-19 pandemic in Italy. J Clin Lipidol 2021; 15:68-78. [PMID: 33390341 PMCID: PMC7833194 DOI: 10.1016/j.jacl.2020.12.008] [Citation(s) in RCA: 46] [Impact Index Per Article: 11.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/08/2020] [Revised: 12/04/2020] [Accepted: 12/15/2020] [Indexed: 01/08/2023]
Abstract
BACKGROUND Epidemiological evidence suggests that anti-inflammatory and immunomodulatory properties of statins may reduce the risk of infections and infection-related complications. OBJECTIVE We aimed to assess the impact of prior statin use on coronavirus disease (COVID-19) severity and mortality. METHODS In this observational multicenter study, consecutive patients hospitalized for COVID-19 were enrolled. In-hospital mortality and severity of COVID-19 assessed with National Early Warning Score (NEWS) were deemed primary and secondary outcomes, respectively. Propensity score (PS) matching was used to obtain balanced cohorts. RESULTS Among 842 patients enrolled, 179 (21%) were treated with statins before admission. Statin patients showed more comorbidities and more severe COVID-19 (NEWS 4 [IQR 2-6] vs 3 [IQR 2-5], p < 0.001). Despite having similar rates of intensive care unit admission, noninvasive ventilation, and mechanical ventilation, statin users appeared to show higher mortality rates. After balancing pre-existing relevant clinical conditions that could affect COVID-19 prognosis with PS matching, statin therapy confirmed its association with a more severe disease (NEWS ≥5 61% vs. 48%, p = 0.025) but not with in-hospital mortality (26% vs. 28%, p = 0.185). At univariate logistic regression analysis, statin use was confirmed not to be associated with mortality (OR 0.901; 95% CI: 0.537 to 1.51; p = 0.692) and to be associated with a more severe disease (NEWS≥5 OR 1.7; 95% CI 1.067-2.71; p = 0.026). CONCLUSIONS Our results did not confirm the supposed favorable effects of statin therapy on COVID-19 outcomes. Conversely, they suggest that statin use should be considered as a proxy of underlying comorbidities, which indeed expose to increased risks of more severe COVID-19.
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Affiliation(s)
| | - Marco Schiavone
- Department of Cardiology, Luigi Sacco - University Hospital, Milan, Italy
| | - Antonio Curnis
- Department of Cardiology, Spedali Civili Hospital, University of Brescia, Brescia, Italy
| | - Marcello Arca
- Department of Internal Medicine and Medical Specialties, Sapienza University of Rome, Rome, Italy
| | - Spinello Antinori
- Department of Infectious Diseases, ASST-Fatebenefratelli Sacco, Luigi Sacco Hospital, Milan, Italy
| | - Alessio Gasperetti
- Department of Cardiology, Luigi Sacco - University Hospital, Milan, Italy
| | - Giosuè Mascioli
- Department of Arrhythmology, Cliniche Humanitas Gavazzeni, Bergamo, Italy
| | - Paolo Severino
- Department of Clinical Internal, Anesthesiological and Cardiovascular Science, Sapienza University of Rome, Rome, Italy
| | - Federica Sabato
- Department of Cardiology, Luigi Sacco - University Hospital, Milan, Italy
| | - Maria M Caracciolo
- Department of Cardiology, Luigi Sacco - University Hospital, Milan, Italy
| | - Gianmarco Arabia
- Department of Cardiology, Spedali Civili Hospital, University of Brescia, Brescia, Italy
| | - Laura D'Erasmo
- Department of Internal Medicine and Medical Specialties, Sapienza University of Rome, Rome, Italy
| | - Maurizio Viecca
- Department of Cardiology, Luigi Sacco - University Hospital, Milan, Italy
| | - Massimo Mancone
- Department of Clinical Internal, Anesthesiological and Cardiovascular Science, Sapienza University of Rome, Rome, Italy
| | - Massimo Galli
- Department of Infectious Diseases, ASST-Fatebenefratelli Sacco, Luigi Sacco Hospital, Milan, Italy
| | - Giovanni B Forleo
- Department of Cardiology, Luigi Sacco - University Hospital, Milan, Italy
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8
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Lin SY, Ju SW, Lin CL, Lin CC, Hsu WH, Chou CH, Chi CY, Hsu CY, Kao CH. Risk of Viral Infection in Patients Using Either Angiotensin-converting Enzyme Inhibitors or Angiotensin Receptor Blockers: A Nationwide Population-based Propensity Score Matching Study. Clin Infect Dis 2020; 71:2695-2701. [PMID: 32504531 DOI: 10.1093/cid/ciaa734] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/24/2020] [Accepted: 06/04/2020] [Indexed: 11/13/2022] Open
Abstract
BACKGROUND We hypothesized that renin-angiotensin system (RAS) blockers have systemic protective effects beyond the respiratory tract and could reduce the risk of viral infections. METHODS We used the National Health Insurance Research Database and identified 2 study cohorts: the angiotensin receptor blocker (ARB) cohort and angiotensin-converting enzyme inhibitor (ACEI) cohort. Propensity score matching was applied at a 1:1 ratio by all associated variables to select 2 independent control cohorts for the ARB and ACEI cohorts. A Cox proportional hazards model was applied to assess the end outcome of viral infection. RESULTS The number of ARB and ACEI users was 20 207 and 18 029, respectively. The median age of ARB users and nonusers was 53.7 and 53.8 years, respectively. The median follow-up duration of ARB users and nonusers was 7.96 and 7.08 years; the median follow-up duration of ACEI users and nonusers was 8.70 and 8.98 years, respectively. The incidence rates of viral infections in ARB users and nonusers were 4.95 and 8.59 per 1000 person-years, respectively, and ARB users had a lower risk of viral infection than nonusers (adjusted hazard ratio [aHR], 0.53 [95% confidence interval {CI}, .48-.58]). The incidence rates of viral infections in ACEI users and nonusers were 6.10 per 1000 person-years and 7.72 per 1000 person-years, respectively, and ACEI users had a lower risk of viral infection than nonusers (aHR, 0.81 [95% CI, .74-.88]). CONCLUSIONS Hypertensive patients using either ARBs or ACEIs exhibit a lower risk of viral infection than nonusers.
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Affiliation(s)
- Shih-Yi Lin
- Graduate Institute of Biomedical Sciences, College of Medicine, China Medical University, Taichung, Taiwan.,Division of Nephrology and Kidney Institute, China Medical University Hospital, Taichung, Taiwan
| | - Shu-Woei Ju
- Graduate Institute of Biomedical Sciences, College of Medicine, China Medical University, Taichung, Taiwan.,Division of Nephrology and Kidney Institute, China Medical University Hospital, Taichung, Taiwan
| | - Cheng-Li Lin
- Management Office for Health Data, China Medical University Hospital, Taichung, Taiwan.,College of Medicine, China Medical University, Taichung, Taiwan
| | - Cheng-Chieh Lin
- Graduate Institute of Biomedical Sciences, College of Medicine, China Medical University, Taichung, Taiwan.,Department of Family Medicine, China Medical University Hospital, Taichung, Taiwan
| | - Wu-Huei Hsu
- Graduate Institute of Biomedical Sciences, College of Medicine, China Medical University, Taichung, Taiwan.,Department of Chest Medicine, China Medical University Hospital, Taichung, Taiwan
| | - Chia-Hui Chou
- Graduate Institute of Biomedical Sciences, College of Medicine, China Medical University, Taichung, Taiwan.,Department of Infection, China Medical University Hospital, Taichung, Taiwan
| | - Chih-Yu Chi
- Graduate Institute of Biomedical Sciences, College of Medicine, China Medical University, Taichung, Taiwan.,Department of Infection, China Medical University Hospital, Taichung, Taiwan
| | - Chung-Y Hsu
- Graduate Institute of Biomedical Sciences, College of Medicine, China Medical University, Taichung, Taiwan
| | - Chia-Hung Kao
- Graduate Institute of Biomedical Sciences, College of Medicine, China Medical University, Taichung, Taiwan.,Department of Nuclear Medicine and Positron Emission Tomography Center, China Medical University Hospital, Taichung, Taiwan.,Department of Bioinformatics and Medical Engineering, Asia University, Taichung, Taiwan.,Center of Augmented Intelligence in Healthcare, China Medical University Hospital, Taichung, Taiwan
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Choi YJ, Sim J, Jung YT, Shin S. Impact of a multidisciplinary quality improvement initiative to reduce inappropriate usage of stress ulcer prophylaxis in hospitalized patients. Br J Clin Pharmacol 2019; 86:903-912. [PMID: 31840265 DOI: 10.1111/bcp.14197] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/07/2019] [Revised: 11/27/2019] [Accepted: 11/28/2019] [Indexed: 12/21/2022] Open
Abstract
AIMS To promote effective methods to improve overutilization patterns of acid-suppressive therapy in hospitalized patients and to evaluate the impact of multidisciplinary team efforts to reduce inappropriate use of stress ulcer prophylaxis in low-risk patients. METHODS A multidisciplinary quality improvement initiative incorporating education, medication use reviews and reconciliation, and pharmaceutical intervention was implemented in June 2018 for surgical patients hospitalized via emergency department. For the pre-post analysis and time series analysis, patients admitted during April and May were classified into the pre-intervention cohort and those admitted during July and August into the post-intervention cohort. RESULTS Three hundred and seventeen patients were included in this study (153 and 164 in the pre- and post-intervention cohorts, respectively). The multidisciplinary program was effective in reducing overuse of stress ulcer prophylaxis and healthcare expenses associated with it. Biweekly education on risk factors warranting stress ulcer prophylaxis was provided for clinicians, and acid-suppressive therapy was removed from a preset list of admission orders. The incidence of inappropriate prophylaxis use declined substantially following intervention in overall patients (OR = 0.51, P = 0.01) and a significant decrease was primarily observed among non-ICU patients (OR = 0.50, P = 0.01). Interrupted time series analysis confirmed the significant decline in inappropriate use post intervention (coefficient = -0.63, P < 0.001). The total healthcare expenses associated with such overuse decreased by 58.5% from US$ 19.39 to US$ 8.04 per 100 patient-days. CONCLUSIONS Our multidisciplinary team efforts were associated with improvement in stress ulcer prophylaxis overuse patterns, resulting in a substantial decrease in the incidence of inappropriate use, especially in general wards, and associated healthcare costs.
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Affiliation(s)
- Yeo Jin Choi
- Clinical Trial Center, Hallym University Hospital, Anyang, Republic of Korea
| | - Joohyun Sim
- Department of Surgery, School of Medicine, Ajou University, Suwon, Republic of Korea
| | - Yun Tae Jung
- Department of Surgery, College of Medicine, Yonsei University, Seoul, Republic of Korea
| | - Sooyoung Shin
- Department of Clinical Pharmacy, College of Pharmacy, Ajou University, Suwon, Republic of Korea.,Research Institute of Pharmaceutical Science and Technology (RIPST), Ajou University, Suwon, Republic of Korea
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10
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Lin WL, Muo CS, Lin WC, Hsieh YW, Kao CH. Association of Increased Risk of Pneumonia and Using Proton Pump Inhibitors in Patients With Type II Diabetes Mellitus. Dose Response 2019; 17:1559325819843383. [PMID: 31080379 PMCID: PMC6498779 DOI: 10.1177/1559325819843383] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/15/2018] [Revised: 02/24/2019] [Accepted: 03/20/2019] [Indexed: 12/15/2022] Open
Abstract
Background: This study explored the possible association between the use of proton pump inhibitors (PPIs) and the increased incidence of pneumonia in patients with type 2 diabetes mellitus (T2DM). Methods: We selected 4940 patients with T2DM of whom 988 and 3952 were enrolled in PPI and propensity score-matched control cohorts, respectively. All patients were followed from the index date until admission with pneumonia, withdrawal from the National Health Insurance program or the end of 2013. The PPIs associated with risk of incident pneumonia were examined. Furthermore, we assessed the risk of pneumonia according to annual defined daily doses in the PPI cohort. Results: After a 14-year follow-up, the cumulative incidence of pneumonia in the PPI users was 11.4% higher than that in the controls (30.3% vs 18.9%). Compared to the controls, the PPI users had a 1.70-fold higher risk of pneumonia in the Cox proportional hazards model after adjustment for matched pairs. The risk of pneumonia increased with the annual PPI defined daily dose. Conclusion: The results of this population-based retrospective cohort study suggest that PPI use increased the risk of pneumonia in patients with T2DM. The effects were more prominent in patients administered higher doses of PPIs.
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Affiliation(s)
- Wen-Ling Lin
- Graduate Institute of Pharmacy, China Medical University, Taichung.,Department of Pharmacy, China Medical University Hospital, Taichung
| | - Chin-Shin Muo
- Management Office for Health Data, China Medical University Hospital, Taichung.,College of Medicine, China Medical University, Taichung
| | - Wen-Chuan Lin
- Graduate Institute of Pharmacy, China Medical University, Taichung
| | - Yow-Wen Hsieh
- Graduate Institute of Pharmacy, China Medical University, Taichung.,Department of Pharmacy, China Medical University Hospital, Taichung
| | - Chia-Hung Kao
- Graduate Institute of Biomedical Sciences and School of Medicine, College of Medicine, China Medical University, Taichung.,Department of Nuclear Medicine and PET Center, China Medical University Hospital, Taichung.,Department of Bioinformatics and Medical Engineering, Asia University, Taichung
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11
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Wang CH, Li CH, Hsieh R, Fan CY, Hsu TC, Chang WC, Hsu WT, Lin YY, Lee CC. Proton pump inhibitors therapy and the risk of pneumonia: a systematic review and meta‐analysis of randomized controlled trials and observational studies. Expert Opin Drug Saf 2019; 18:163-172. [DOI: 10.1080/14740338.2019.1577820] [Citation(s) in RCA: 30] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Affiliation(s)
- Chih-Hung Wang
- Department of Emergency Medicine, National Taiwan University Hospital, Taipei, Taiwan
- Department of Emergency Medicine, College of Medicine, National Taiwan University, Taipei, Taiwan
| | - Cheng-Han Li
- College of Medicine, National Taiwan University, Taipei, Taiwan
| | - Ronan Hsieh
- Department of Medicine, Albert Einstein Medical Center, Philadelphia, PA, USA
| | - Cheng-Yi Fan
- College of Medicine, National Taiwan University, Taipei, Taiwan
| | - Tze-Chun Hsu
- Department of Emergency Medicine, National Taiwan University Hospital, Taipei, Taiwan
| | - Wei-Che Chang
- College of Medicine, National Taiwan University, Taipei, Taiwan
| | - Wan-Ting Hsu
- Department of Epidemiology, Harvard School of Public Health, Boston, MA, USA
| | - Yu-Ya Lin
- Department of Pharmacy, E-Da hospital, Kaohsiung, Taiwan
| | - Chien-Chang Lee
- Department of Emergency Medicine, National Taiwan University Hospital, Taipei, Taiwan
- Department of Emergency Medicine, College of Medicine, National Taiwan University, Taipei, Taiwan
- Department of Epidemiology, Harvard School of Public Health, Boston, MA, USA
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Liapikou A, Cilloniz C, Torres A. Drugs that increase the risk of community-acquired pneumonia: a narrative review. Expert Opin Drug Saf 2018; 17:991-1003. [PMID: 30196729 DOI: 10.1080/14740338.2018.1519545] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
INTRODUCTION Community-acquired pneumonia (CAP), a major cause of morbidity and mortality, is the leading infectious cause of death in the developed world. Population-based studies and systematic reviews have identified a large number of risk factors for the development of pneumonia in adults. In addition to age, lifestyle habits, and comorbidities, some forms of pharmacotherapy may also increase the risk for CAP. AREAS COVERED MEDLINE, CENTRAL, and Web of Science were used in 2017 to search for case-control, cohort studies, as well as randomized controlled trials and meta-analysis that involved outpatient proton pump inhibitors (PPIs), inhaled corticosteroids (ICSs), antipsychotics, oral antidiabetics, and CAP diagnosis in patients aged >18 years. EXPERT OPINION Our review confirmed that the use of ICSs, PPIs or antipsychotic drugs was independently associated with an increased risk for CAP. We also identified a positive association between specific oral antidiabetics and the development of pneumonia.
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Affiliation(s)
- Adamantia Liapikou
- a 6th Respiratory Department , Sotiria Chest Diseases Hospital , Athens , Greece
| | - Catia Cilloniz
- b Department of Pneumology, Institut Clinic del Tórax, Hospital Clinic of Barcelona - Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS) , University of Barcelona (UB) - SGR 911 - Ciber de Enfermedades Respiratorias (Ciberes) , Barcelona , Spain
| | - Antoni Torres
- b Department of Pneumology, Institut Clinic del Tórax, Hospital Clinic of Barcelona - Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS) , University of Barcelona (UB) - SGR 911 - Ciber de Enfermedades Respiratorias (Ciberes) , Barcelona , Spain
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13
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Kang JH, Kao LT, Lin HC, Wang TJ, Yang TY. Do outpatient statins and ACEIs/ARBs have synergistic effects in reducing the risk of pneumonia? A population-based case-control study. PLoS One 2018; 13:e0199981. [PMID: 29953536 PMCID: PMC6023201 DOI: 10.1371/journal.pone.0199981] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/25/2017] [Accepted: 05/11/2018] [Indexed: 01/05/2023] Open
Abstract
Whether statins and an angiotensin-converting enzyme inhibitors (ACEIs) / angiotensin receptor blockors (ARBs) are associated with reduced risks of infection events is still inconclusive. This study aimed to explore the risk of hospitalization for pneumonia among patients who had received treatment with ACEIs/ARBs and/or statins using a population-based dataset. This study included 19,281 patients as cases who were hospitalized for pneumonia and 19,281 controls. We used a logistic regression to compute the odds ratio (OR) and 95% confidence interval (CI) for having previously used statins or an ACEI/ ARB between patients who were hospitalized for pneumonia treatment and controls. We found there were significant associations between hospitalization for pneumonia and statin-only users (p<0.001), ACEI/ARB-only users (p<0.001), and statin and ACEI/ARB users (p<0.001). The logistic regression analysis suggested that statin-only users (adjusted OR = 0.38, 95% CI = 0.34~0.43), ACEI/ARB-only users (adjusted OR = 0.86, 95% CI = 0.82~0.91), and statin and ACEI/ARB users (adjusted OR = 0.47, 95% CI = 0.44~0.50) were all less likely to be hospitalized for pneumonia treatment than were non-users. Furthermore, we found that statin-only users (adjusted OR = 0.44, 95% CI = 0.40~0.50) and statin and ACEI/ARB users (adjusted OR = 0.55, 95% CI = 0.52~0.58) were less likely to be hospitalized for pneumonia treatment compared to ACEI-only users. However, combined statin and ACEI/ARB users (adjusted OR = 1.24, 95% CI = 1.10~1.40) were more likely to have been hospitalized for pneumonia treatment compared to statin-only users. Although we found use of both statins and ACEI/ARB were significantly associated with a lower risk of pneumonia, the combination of the two medications did not provide additional protection against pneumonia risk.
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Affiliation(s)
- Jiunn-Horng Kang
- Department of Physical Medicine and Rehabilitation, Taipei Medical University Hospital, Taipei, Taiwan
- Department of Physical Medicine and Rehabilitation, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan
| | - Li-Ting Kao
- Graduate Institute of Life Science, National Defense Medical Center, Taipei, Taiwan
- Department of Pharmacy Practice, Tri-Service General Hospital, Taipei, Taiwan
| | - Herng-Ching Lin
- School of Health Care Administration, Taipei Medical University, Taipei, Taiwan
- Sleep Research Center, Taipei Medical University Hospital, Taipei, Taiwan
- * E-mail:
| | - Ta-Jung Wang
- Division of Cardiology, Department of Internal Medicine, Shuang Ho Hospital, Taipei Medical University, Taipei, Taiwan
| | - Tsung-Yeh Yang
- Division of Cardiology, Department of Internal Medicine, Shuang Ho Hospital, Taipei Medical University, Taipei, Taiwan
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14
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Faust AC, Echevarria KL, Attridge RL, Sheperd L, Restrepo MI. Prophylactic Acid-Suppressive Therapy in Hospitalized Adults: Indications, Benefits, and Infectious Complications. Crit Care Nurse 2018; 37:18-29. [PMID: 28572098 DOI: 10.4037/ccn2017720] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/01/2022]
Abstract
Acid-suppressive therapy for prophylaxis of stress ulcer bleeding is commonly prescribed for hospitalized patients. Although its use in select, at-risk patients may reduce clinically significant gastrointestinal bleeding, the alteration in gastric pH and composition may place these patients at a higher risk of infection. Although any pharmacologic alteration of the gastric pH and composition is associated with an increased risk of infection, the risk appears to be highest with proton pump inhibitors, perhaps owing to the potency of this class of drugs in increasing the gastric pH. With the increased risk of infection, universal provision of pharmacologic acid suppression to all hospitalized patients, even all critically ill patients, is inappropriate and should be confined to patients meeting specific criteria. Nurses providing care in critical care areas may be instrumental in screening for appropriate use of acid-suppressive therapy and ensuring the drugs are discontinued upon transfer out of intensive care or when risk factors are no longer present.
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Affiliation(s)
- Andrew C Faust
- Andrew C. Faust is a critical care clinical pharmacist primarily working in the medical intensive care unit, Department of Pharmacy, Texas Health Presbyterian Hospital Dallas, Dallas, Texas. .,Kelly L. Echevarria is an infectious diseases and critical care clinical pharmacist, Department of Pharmacy, South Texas Veterans Health Care System, San Antonio, Texas. .,Rebecca L. Attridge is an associate professor, Department of Pharmacy Practice, University of the Incarnate Word Feik School of Pharmacy, and an adjunct assistant professor, Division of Pulmonary Diseases and Critical Care Medicine, Department of Medicine, UT Health San Antonio, San Antonio, Texas. .,Lyndsay Sheperd is a critical care clinical pharmacist primarily working in the surgical-trauma intensive care unit, Department of Pharmacy, Texas Health Presbyterian Hospital Dallas, Dallas, Texas. .,Marcos I. Restrepo is an associate professor in pulmonary and critical care medicine, Department of Medicine, Division of Pulmonary Diseases and Critical Care Medicine, University of Texas Health Science Center at San Antonio, and Veterans Evidence-Based Research Dissemination Implementation Center, South Texas Veterans Health Care System, San Antonio, Texas.
| | - Kelly L Echevarria
- Andrew C. Faust is a critical care clinical pharmacist primarily working in the medical intensive care unit, Department of Pharmacy, Texas Health Presbyterian Hospital Dallas, Dallas, Texas.,Kelly L. Echevarria is an infectious diseases and critical care clinical pharmacist, Department of Pharmacy, South Texas Veterans Health Care System, San Antonio, Texas.,Rebecca L. Attridge is an associate professor, Department of Pharmacy Practice, University of the Incarnate Word Feik School of Pharmacy, and an adjunct assistant professor, Division of Pulmonary Diseases and Critical Care Medicine, Department of Medicine, UT Health San Antonio, San Antonio, Texas.,Lyndsay Sheperd is a critical care clinical pharmacist primarily working in the surgical-trauma intensive care unit, Department of Pharmacy, Texas Health Presbyterian Hospital Dallas, Dallas, Texas.,Marcos I. Restrepo is an associate professor in pulmonary and critical care medicine, Department of Medicine, Division of Pulmonary Diseases and Critical Care Medicine, University of Texas Health Science Center at San Antonio, and Veterans Evidence-Based Research Dissemination Implementation Center, South Texas Veterans Health Care System, San Antonio, Texas
| | - Rebecca L Attridge
- Andrew C. Faust is a critical care clinical pharmacist primarily working in the medical intensive care unit, Department of Pharmacy, Texas Health Presbyterian Hospital Dallas, Dallas, Texas.,Kelly L. Echevarria is an infectious diseases and critical care clinical pharmacist, Department of Pharmacy, South Texas Veterans Health Care System, San Antonio, Texas.,Rebecca L. Attridge is an associate professor, Department of Pharmacy Practice, University of the Incarnate Word Feik School of Pharmacy, and an adjunct assistant professor, Division of Pulmonary Diseases and Critical Care Medicine, Department of Medicine, UT Health San Antonio, San Antonio, Texas.,Lyndsay Sheperd is a critical care clinical pharmacist primarily working in the surgical-trauma intensive care unit, Department of Pharmacy, Texas Health Presbyterian Hospital Dallas, Dallas, Texas.,Marcos I. Restrepo is an associate professor in pulmonary and critical care medicine, Department of Medicine, Division of Pulmonary Diseases and Critical Care Medicine, University of Texas Health Science Center at San Antonio, and Veterans Evidence-Based Research Dissemination Implementation Center, South Texas Veterans Health Care System, San Antonio, Texas
| | - Lyndsay Sheperd
- Andrew C. Faust is a critical care clinical pharmacist primarily working in the medical intensive care unit, Department of Pharmacy, Texas Health Presbyterian Hospital Dallas, Dallas, Texas.,Kelly L. Echevarria is an infectious diseases and critical care clinical pharmacist, Department of Pharmacy, South Texas Veterans Health Care System, San Antonio, Texas.,Rebecca L. Attridge is an associate professor, Department of Pharmacy Practice, University of the Incarnate Word Feik School of Pharmacy, and an adjunct assistant professor, Division of Pulmonary Diseases and Critical Care Medicine, Department of Medicine, UT Health San Antonio, San Antonio, Texas.,Lyndsay Sheperd is a critical care clinical pharmacist primarily working in the surgical-trauma intensive care unit, Department of Pharmacy, Texas Health Presbyterian Hospital Dallas, Dallas, Texas.,Marcos I. Restrepo is an associate professor in pulmonary and critical care medicine, Department of Medicine, Division of Pulmonary Diseases and Critical Care Medicine, University of Texas Health Science Center at San Antonio, and Veterans Evidence-Based Research Dissemination Implementation Center, South Texas Veterans Health Care System, San Antonio, Texas
| | - Marcos I Restrepo
- Andrew C. Faust is a critical care clinical pharmacist primarily working in the medical intensive care unit, Department of Pharmacy, Texas Health Presbyterian Hospital Dallas, Dallas, Texas.,Kelly L. Echevarria is an infectious diseases and critical care clinical pharmacist, Department of Pharmacy, South Texas Veterans Health Care System, San Antonio, Texas.,Rebecca L. Attridge is an associate professor, Department of Pharmacy Practice, University of the Incarnate Word Feik School of Pharmacy, and an adjunct assistant professor, Division of Pulmonary Diseases and Critical Care Medicine, Department of Medicine, UT Health San Antonio, San Antonio, Texas.,Lyndsay Sheperd is a critical care clinical pharmacist primarily working in the surgical-trauma intensive care unit, Department of Pharmacy, Texas Health Presbyterian Hospital Dallas, Dallas, Texas.,Marcos I. Restrepo is an associate professor in pulmonary and critical care medicine, Department of Medicine, Division of Pulmonary Diseases and Critical Care Medicine, University of Texas Health Science Center at San Antonio, and Veterans Evidence-Based Research Dissemination Implementation Center, South Texas Veterans Health Care System, San Antonio, Texas
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15
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Won HK, Yoon SJ, Song WJ. The double-sidedness of cough in the elderly. Respir Physiol Neurobiol 2018; 257:65-69. [PMID: 29337268 DOI: 10.1016/j.resp.2018.01.009] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/02/2017] [Revised: 01/07/2018] [Accepted: 01/11/2018] [Indexed: 12/11/2022]
Abstract
Cough is a physiological reflex to protect airways against aspiration, but also it is one of the most frequent problems that lead patients to seek medical care. Chronic cough is more prevalent in the elderly than younger subjects, and more challenging to manage due to frequent comorbidities and possible side effects from drug treatment. Meanwhile, cough reflex does not decrease with natural aging but is often impaired by pathologic conditions like stroke. The impairment in cough reflex may lead to fatal complication like aspiration pneumonia. In this paper, we reviewed epidemiology and clinical considerations for chronic cough in the elderly, and summarized aging-related changes in cough reflex and also possible ways to normalize cough reflex and prevent aspiration pneumonia.
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Affiliation(s)
- Ha-Kyeong Won
- Division of Allergy and Clinical Immunology, Department of Internal Medicine, Seoul National University Hospital, Seoul, Republic of Korea
| | - Sol-Ji Yoon
- Division of Geriatrics, Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, Republic of Korea
| | - Woo-Jung Song
- Division of Allergy and Clinical Immunology, Department of Internal Medicine, Seoul National University Hospital, Seoul, Republic of Korea.
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16
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Batais MA, Khan AR, Bin Abdulhak AA. The Use of Statins and Risk of Community-Acquired Pneumonia. Curr Infect Dis Rep 2017; 19:26. [PMID: 28639080 DOI: 10.1007/s11908-017-0581-x] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/23/2022]
Abstract
PURPOSE OF THE REVIEW Community-acquired pneumonia (CAP) is still associated with a large burden and causes significant morbidity and mortality. Besides universal vaccination and antibiotic treatment, statins as adjunctive therapy may also have a beneficial role in the prevention and treatment of CAP. Our goal from this review is to discuss the epidemiology of CAP, and role of statins as adjunctive therapy in the development of CAP. RECENT FINDINGS Statins are lipid-lowering medications characterized by their ability to control hypercholesterolemia in addition to other pleiotropic effects that could explain their role in the pathogenesis of CAP. While most observational studies have shown that statins reduce risk of pneumonia in the general population, patients with diabetes, and recently in patients with myocardial infarction, no randomized controlled trial (RCT) to date has been conducted to assess the efficacy of statins to prevent development of CAP. Given the paucity of robust randomized evidence to assess statin use and the development of CAP, and considering conflicting results of the observational studies, we are not in favor of initiation of statins for either the prevention or treatment of CAP.
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Affiliation(s)
- Mohammed A Batais
- College of Medicine, King Saud University, Riyadh, 29391, Saudi Arabia.
| | - Abdur Rahman Khan
- Department of Medicine, Division of Cardiovascular Diseases, University of Louisville, Louisville, KY, USA
| | - Aref A Bin Abdulhak
- Department of Medicine, Division of Cardiovascular Diseases, University of Iowa Hospitals and Clinics, 200 Hawkins Dr., Int. Med. E315 GH, Iowa City, IA, 52242, USA
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17
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Othman F, Crooks CJ, Card TR. Community acquired pneumonia incidence before and after proton pump inhibitor prescription: population based study. BMJ 2016; 355:i5813. [PMID: 28715344 PMCID: PMC5110150 DOI: 10.1136/bmj.i5813] [Citation(s) in RCA: 49] [Impact Index Per Article: 5.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 10/18/2016] [Indexed: 01/01/2023]
Abstract
Objective To examine the risk of community acquired pneumonia before and after prescription of proton pump inhibitor (PPI) and assess whether unmeasured confounding explains this association.Design Cohort study and self controlled case series.Setting Clinical Practice Research Datalink (1990 to 2013) in UK.Participants Adult patients with a new prescription for a PPI individually matched with controls.Main outcome measures Association of community acquired pneumonia with PPI prescription estimated by three methods: a multivariable Cox model comparing risk in PPI exposed patients with controls, corrected for potential confounders; a self controlled case series; and a prior event rate ratio (PERR) analysis over the 12 month periods before and after the first PPI prescription.Results 160 000 new PPI users were examined. The adjusted Cox regression showed a risk of community acquired pneumonia 1.67 (95% confidence interval 1.55 to 1.79) times higher for patients exposed to PPI than for controls. In the self controlled case series, among 48 451 PPI exposed patients with a record of community acquired pneumonia, the incidence rate ratio was 1.19 (95% confidence interval 1.14 to 1.25) in the 30 days after PPI prescription but was higher in the 30 days before a PPI prescription (1.92, 1.84 to 2.00). The Cox regressions for prior event rate ratio similarly showed a greater increase in community acquired pneumonia in the year before than the year after PPI prescription, such that the analysis showed a reduced relative risk of pneumonia associated with PPI use (prior event rate ratio 0.91, 95% confidence interval 0.83 to 0.99).Conclusion The association between the use of PPIs and risk of community acquired pneumonia is likely to be due entirely to confounding factors.
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Affiliation(s)
- Fatmah Othman
- Department of Epidemiology and Public Health, University of Nottingham, Nottingham NG5 1PB, UK
- Department of Basic Medical Sciences, King Saud bin Abdulaziz University for Health Sciences, Saudi Arabia
| | - Colin J Crooks
- Department of Epidemiology and Public Health, University of Nottingham, Nottingham NG5 1PB, UK
| | - Timothy R Card
- Department of Epidemiology and Public Health, University of Nottingham, Nottingham NG5 1PB, UK
- NIHR Nottingham Digestive Diseases Biomedical Research Unit, Nottingham University Hospitals NHS Trust and University of Nottingham, Nottingham, UK
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18
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Zumla A, Rao M, Wallis RS, Kaufmann SHE, Rustomjee R, Mwaba P, Vilaplana C, Yeboah-Manu D, Chakaya J, Ippolito G, Azhar E, Hoelscher M, Maeurer M. Host-directed therapies for infectious diseases: current status, recent progress, and future prospects. THE LANCET. INFECTIOUS DISEASES 2016; 16:e47-63. [PMID: 27036359 PMCID: PMC7164794 DOI: 10.1016/s1473-3099(16)00078-5] [Citation(s) in RCA: 250] [Impact Index Per Article: 27.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 11/17/2015] [Revised: 01/16/2016] [Accepted: 02/02/2016] [Indexed: 12/13/2022]
Abstract
Despite extensive global efforts in the fight against killer infectious diseases, they still cause one in four deaths worldwide and are important causes of long-term functional disability arising from tissue damage. The continuing epidemics of tuberculosis, HIV, malaria, and influenza, and the emergence of novel zoonotic pathogens represent major clinical management challenges worldwide. Newer approaches to improving treatment outcomes are needed to reduce the high morbidity and mortality caused by infectious diseases. Recent insights into pathogen–host interactions, pathogenesis, inflammatory pathways, and the host's innate and acquired immune responses are leading to identification and development of a wide range of host-directed therapies with different mechanisms of action. Host-directed therapeutic strategies are now becoming viable adjuncts to standard antimicrobial treatment. Host-directed therapies include commonly used drugs for non-communicable diseases with good safety profiles, immunomodulatory agents, biologics (eg monoclonal antibodies), nutritional products, and cellular therapy using the patient's own immune or bone marrow mesenchymal stromal cells. We discuss clinically relevant examples of progress in identifying host-directed therapies as adjunct treatment options for bacterial, viral, and parasitic infectious diseases.
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Affiliation(s)
- Alimuddin Zumla
- Centre for Clinical Microbiology, Division of Infection and Immunity, University College London (UCL), London, UK; National Institute for Health Research Biomedical Research Centre, UCL Hospitals NHS Foundation Trust, London, UK
| | - Martin Rao
- Division of Therapeutic Immunology, Department of Laboratory Medicine, Karolinska Institutet, Stockholm, Sweden; Centre for Allogeneic Stem Cell Transplantation, Karolinska University Hospital Huddinge, Stockholm, Sweden
| | | | | | | | - Peter Mwaba
- University of Zambia-UCL Medical School (UNZA-UCLMS) Research and Training Project, University Teaching Hospital, Lusaka, Zambia; Ministry of Health, Lusaka, Zambia
| | - Cris Vilaplana
- Unitat de Tuberculosi Experimental Fundació Institut d'Investigació en Ciències de la Salut Germans Trias i Pujol CIBER Enfermedades Respiratorias, Can Ruti Campus, Edifici Laboratoris de Recerca, Barcelona, Spain
| | - Dorothy Yeboah-Manu
- Bacteriology Department, Noguchi Memorial Institute for Medical Research, University of Ghana, Legon, Ghana
| | | | - Giuseppe Ippolito
- National Institute for Infectious Diseases, Lazzaro Spallanzani, Rome, Italy
| | - Esam Azhar
- Special Infectious Agents Unit, King Fahd Medical Research Centre, and Medical Laboratory Technology Department, Faculty of Applied Medical Sciences, King Abdulaziz University, Jeddah, Saudi Arabia
| | - Michael Hoelscher
- Division of Infectious Diseases and Tropical Medicine, Medical Centre of the University of Munich, Munich, Germany; DZIF German Centre for Infection Research, Munich, Germany
| | - Markus Maeurer
- Division of Therapeutic Immunology, Department of Laboratory Medicine, Karolinska Institutet, Stockholm, Sweden; Centre for Allogeneic Stem Cell Transplantation, Karolinska University Hospital Huddinge, Stockholm, Sweden.
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Polverino E, Bothamley GH, Goletti D, Heyckendorf J, Sotgiu G, Aliberti S. The best of respiratory infections from the 2015 European Respiratory Society International Congress. ERJ Open Res 2016; 2:00049-2016. [PMID: 27730203 PMCID: PMC5034596 DOI: 10.1183/23120541.00049-2016] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/08/2016] [Accepted: 05/27/2016] [Indexed: 12/01/2022] Open
Abstract
The breadth and quality of scientific presentations on clinical and translational research into respiratory infections at the 2015 European Respiratory Society (ERS) International Congress in Amsterdam, the Netherlands, establishes this area as one of the leadings fields in pulmonology. The host-pathogen relationship in chronic obstructive pulmonary disease, and the impact of comorbidities and chronic treatment on clinical outcomes in patients with pneumonia were studied. Various communications were dedicated to bronchiectasis and, in particular, to different prognostic and clinical aspects of this disease, including chronic infection with Pseudomonas and inhaled antibiotic therapy. Recent data from the World Health Organization showed that Europe has the highest number of multidrug-resistant tuberculosis cases and the poorest countries have the least access to suitable treatments. Latent tuberculosis and different screening programmes were also discussed with particular attention to risk factors such as HIV infection and diabetes. Several biomarkers were proposed to distinguish between active tuberculosis and latent infection. Major treatment trials were discussed (REMOX, RIFQUIN and STREAM). The possibility of once-weekly treatment in the continuation phase (RIAQUIN) was especially exciting. The continuing rise of Mycobacterium abscessus as a significant pathogen was noted. This article reviews some of the best contributions from the Respiratory Infections Assembly to the 2015 ERS International Congress.
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Affiliation(s)
- Eva Polverino
- Fundació Clinic, Hospital Clinic of Barcelona – Institut d'Investigacions Biomèdiques August Pi i Sunyer, University of Barcelona, Ciber de Enfermedades Respiratorias, Barcelona, Spain
- These authors contributed equally
| | - Graham H. Bothamley
- Dept of Respiratory Medicine, Homerton University Hospital, London, UK
- These authors contributed equally
| | - Delia Goletti
- Translational Research Unit, Dept of Epidemiology and Preclinical Research, National Institute for Infectious Diseases, Rome, Italy
| | - Jan Heyckendorf
- Division of Clinical Infectious Diseases, German Center for Infection Research, Research Center, Borstel, Germany
| | - Giovanni Sotgiu
- Clinical Epidemiology and Medical Statistics Unit, Dept of Biomedical Sciences, University of Sassari, Medical Education and Professional Development Unit, Sassari, Italy
| | - Stefano Aliberti
- Dept of Pathophysiology and Transplantation, University of Milan, Cardio-Thoracic Unit and Cystic Fibrosis Adult Center, Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico, Milan, Italy
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20
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Dang TT, Majumdar SR, Marrie TJ, Eurich DT. Recurrent pneumonia: a review with focus on clinical epidemiology and modifiable risk factors in elderly patients. Drugs Aging 2016; 32:13-9. [PMID: 25491559 DOI: 10.1007/s40266-014-0229-6] [Citation(s) in RCA: 36] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
Abstract
Community-acquired pneumonia (CAP) is one of the most common reasons for physician visits and hospitalizations in North America. Rates of CAP increase with age and CAP is associated with significant morbidity and mortality, especially in the elderly. Though there is much written about the epidemiology and risk factors of incident (first episode) pneumonia, much less is known about recurrent pneumonia. Rates of recurrent pneumonia within 3-5-years of an episode of CAP are 9-12% with a median time to recurrence of 123-317 days and mortality ranging from 4 to 10%. Age ≥65-years-old and impaired functional status are the only patient characteristics that are independently associated with increased risk of recurrence. In terms of modifiable risk factors, only the use of proton-pump inhibitors and systemic and inhaled corticosteroids have consistently been associated with increased risk of recurrent pneumonia, while angiotensin-converting enzyme (ACE) inhibitors may exert a protective effect. Many chronic medical conditions typically associated with increased incident pneumonia-such as chronic obstructive pulmonary disease (COPD), neurological disease (resulting in dysphagia or silent aspiration), and heart failure-were not associated with increased risk of recurrent pneumonia. However, those who are immune-suppressed (e.g., immunoglobulin deficiencies) may be at increased risk of recurrent pneumonia. In summary, among those who survive an episode of pneumonia, recurrence is not uncommon, particularly in the elderly. Following recovery from an episode of pneumonia, patients should be evaluated for risk factors that would predispose to a second episode including seeking evidence of immunosuppression in younger patients and medication optimization, particularly in the elderly.
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Affiliation(s)
- T T Dang
- Department of Medicine, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, AB, Canada
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21
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Pletz MW, Rohde GG, Welte T, Kolditz M, Ott S. Advances in the prevention, management, and treatment of community-acquired pneumonia. F1000Res 2016; 5. [PMID: 26998243 PMCID: PMC4786904 DOI: 10.12688/f1000research.7657.1] [Citation(s) in RCA: 19] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 03/03/2016] [Indexed: 01/06/2023] Open
Abstract
Community-acquired pneumonia (CAP) is the infectious disease with the highest number of deaths worldwide. Nevertheless, its importance is often underestimated. Large cohorts of patients with CAP have been established worldwide and improved our knowledge about CAP by far. Therefore, current guidelines are much more evidence-based than ever before. This article discusses recent major studies and concepts on CAP such as the role of biomarkers, appropriate risk stratification to identify patients in need of hospitalisation or intensive care, appropriate empiric antibiotic therapy (including the impact of macrolide combination therapy and antibiotic stewardship), and CAP prevention with novel influenza and pneumococcal vaccines.
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Affiliation(s)
- Mathias W Pletz
- Center for Infectious Diseases and Infection Control, Jena University Hospital, Jena, Germany
| | - Gernot G Rohde
- Department of Respiratory Medicine, Hannover Medical School, Hannover, Germany
| | - Tobias Welte
- Department of Respiratory Medicine, Maastricht University Medical Center, Maastricht, Netherlands
| | - Martin Kolditz
- Division of Pulmonology, University Hospital Carl Gustav Carus, Dresden, Germany
| | - Sebastian Ott
- Department of Pulmonary Medicine, Inselspital, University Hospital, Bern, Switzerland
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22
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Ticinesi A, Nouvenne A, Folesani G, Prati B, Morelli I, Guida L, Lauretani F, Maggio M, Meschi T. An investigation of multimorbidity measures as risk factors for pneumonia in elderly frail patients admitted to hospital. Eur J Intern Med 2016; 28:102-6. [PMID: 26686926 DOI: 10.1016/j.ejim.2015.11.021] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/08/2015] [Revised: 10/27/2015] [Accepted: 11/22/2015] [Indexed: 02/09/2023]
Abstract
OBJECTIVES To investigate the association of different chronic comorbidities, considered singularly and together in Cumulative Illness Rating Scale (CIRS) indexes, with pneumonia diagnosis in a group of elderly frail hospitalized patients. DESIGN AND METHODS With a retrospective cohort design, all clinical records of frail (Rockwood ≥ 5) nonterminal patients ≥ 65 years old acutely admitted over a 8-month span in an internal medicine ward were evaluated. Pneumonia status and its categorization (community-acquired, CAP, vs healthcare-associated, HCAP) were defined according to chest radiology findings and validated criteria. Chronic comorbidities, CIRS Comorbidity Score and CIRS Severity Index were collected for each participant through a standardized methodology. Multivariate logistic regression models were applied to assess the association of each comorbid condition or scores with pneumonia. RESULTS 1199 patients (546 M, median age 81.9, IQR 72.8-87.9 years), of whom 239 with pneumonia (180 CAP, 59 HCAP) were evaluated. CIRS Comorbidity Score was significantly associated with pneumonia, both at an age- and sex-adjusted model and at a multivariate model (OR for each unitary increase 1.03, 95% CI 1.001-1.062, p=0.04), together with provenience from nursing home (OR 1.96, 95% CI 1.41-2.73, p<0.001). Among single comorbidities, only COPD (OR 2.7, 95% CI 1.9-3.6, p<0.001) and dementia (OR 2.3, 95% CI 1.7-3.3, p<0.001) were associated with pneumonia, while stroke, cancer, cardiovascular, chronic liver and kidney disease were not. CONCLUSIONS In a small cohort of elderly frail hospitalized patients, measures of multimorbidity, like CIRS, are significantly associated with the risk of pneumonia. COPD and dementia are the main conditions concurring to define this risk.
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Affiliation(s)
- Andrea Ticinesi
- Department of Clinical and Experimental Medicine, University of Parma, Parma, Italy; Internal Medicine and Critical Subacute Care Unit, Geriatric-Rehabilitation Department, Parma University Hospital, Parma, Italy
| | - Antonio Nouvenne
- Department of Clinical and Experimental Medicine, University of Parma, Parma, Italy; Internal Medicine and Critical Subacute Care Unit, Geriatric-Rehabilitation Department, Parma University Hospital, Parma, Italy.
| | | | - Beatrice Prati
- Internal Medicine and Critical Subacute Care Unit, Geriatric-Rehabilitation Department, Parma University Hospital, Parma, Italy
| | - Ilaria Morelli
- Internal Medicine and Critical Subacute Care Unit, Geriatric-Rehabilitation Department, Parma University Hospital, Parma, Italy
| | - Loredana Guida
- Internal Medicine and Critical Subacute Care Unit, Geriatric-Rehabilitation Department, Parma University Hospital, Parma, Italy
| | - Fulvio Lauretani
- Department of Clinical and Experimental Medicine, University of Parma, Parma, Italy; Internal Medicine and Critical Subacute Care Unit, Geriatric-Rehabilitation Department, Parma University Hospital, Parma, Italy
| | - Marcello Maggio
- Department of Clinical and Experimental Medicine, University of Parma, Parma, Italy
| | - Tiziana Meschi
- Department of Clinical and Experimental Medicine, University of Parma, Parma, Italy; Internal Medicine and Critical Subacute Care Unit, Geriatric-Rehabilitation Department, Parma University Hospital, Parma, Italy
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Community-Acquired Pneumonia in Elderly Patients With Diabetes Mellitus. INFECTIOUS DISEASES IN CLINICAL PRACTICE 2015. [DOI: 10.1097/ipc.0000000000000302] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
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Risk of community-acquired pneumonia in patients with a diagnosis of pernicious anemia: a population-based retrospective cohort study. Eur J Gastroenterol Hepatol 2015; 27. [PMID: 26225868 PMCID: PMC4586398 DOI: 10.1097/meg.0000000000000444] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
OBJECTIVE Pernicious anemia (PA) is an autoimmune disease that causes achlorhydria or profound hypochlorhydria. We conducted a population-based study to determine whether individuals with PA are at an increased risk for community-acquired pneumonia (CAP). METHODS We performed a retrospective cohort study using The Health Improvement Network (THIN) from the UK (1993-2009). The eligible study cohort included individuals 18 years of age or older, with at least 1 year of THIN follow-up. The exposed group consisted of individuals with a diagnosis code for PA. The unexposed group consisted of individuals without a diagnosis of PA and was frequency matched with the exposed group with respect to age, sex, and practice site. Cox regression analysis was used to determine the hazard ratio with the 95% confidence interval for CAP associated with PA, accounting for a comprehensive list of potential confounders. RESULTS The study included 13,605 individuals with PA and 50,586 non-PA individuals. The crude incidence rate of CAP was 9.4/1000 person-years for those with PA, versus 6.4/1000 person-years for those without PA. The multivariable adjusted hazard ratio for CAP associated with PA was 1.18 (95% confidence interval 1.08-1.29). CONCLUSION In this large population-based cohort study, individuals with PA and presumed chronic achlorhydria were at an increased risk for CAP.
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Lima JJ, Franciosi JP. Pharmacogenomic testing: the case for CYP2C19 proton pump inhibitor gene-drug pairs. Pharmacogenomics 2015; 15:1405-16. [PMID: 25303292 DOI: 10.2217/pgs.14.103] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/23/2022] Open
Abstract
The use of proton pump inhibitors (PPIs) in the treatment of gastroesophageal reflux and related diseases is increasing, especially in the pediatric population. Prolonged use of PPIs has been associated with several adverse effects, including potentially life-threatening gastric and respiratory infections, which are related to dose or to the degree of gastric acid suppression. Genetic variation in the CYP2C19 gene gives rise to poor and extensive metabolizer phenotypes, which influence PPI clearance, efficacy and exposure. A recent paper linked lansoprazole-associated respiratory infections in children with the poor metabolizer phenotype. The case is made for implementing pharmacogenomic testing for the CYP2C19-PPI gene-drug pair and to dose accordingly in order to minimize PPI-associated infections.
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Affiliation(s)
- John J Lima
- Center for Pharmacogenomics & Translational Research, Nemours Children's Clinic, 807 Children's Way, Jacksonville, FL 32207, USA
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26
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Lambert AA, Lam JO, Paik JJ, Ugarte-Gil C, Drummond MB, Crowell TA. Risk of community-acquired pneumonia with outpatient proton-pump inhibitor therapy: a systematic review and meta-analysis. PLoS One 2015; 10:e0128004. [PMID: 26042842 PMCID: PMC4456166 DOI: 10.1371/journal.pone.0128004] [Citation(s) in RCA: 237] [Impact Index Per Article: 23.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/19/2015] [Accepted: 04/21/2015] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Proton-pump inhibitors (PPIs) are among the most frequently prescribed medications. Community-acquired pneumonia (CAP) is a common cause of morbidity, mortality and healthcare spending. Some studies suggest an increased risk of CAP among PPI users. We conducted a systematic review and meta-analysis to determine the association between outpatient PPI therapy and risk of CAP in adults. METHODS We conducted systematic searches of MEDLINE, EMBASE, CINAHL, Cochrane Central Register of Controlled Trials, Scopus and Web of Science on February 3, 2014. Case-control studies, case-crossover, cohort studies and randomized controlled trials reporting outpatient PPI exposure and CAP diagnosis for patients ≥18 years old were eligible. Our primary outcome was the association between CAP and PPI therapy. A secondary outcome examined the risk of hospitalization for CAP and subgroup analyses evaluated the association between PPI use and CAP among patients of different age groups, by different PPI doses, and by different durations of PPI therapy. RESULTS Systematic review of 33 studies was performed, of which 26 studies were included in the meta-analysis. These 26 studies included 226,769 cases of CAP among 6,351,656 participants. We observed a pooled risk of CAP with ambulatory PPI therapy of 1.49 (95% CI 1.16, 1.92; I2 99.2%). This risk was increased during the first month of therapy (OR 2.10; 95% CI 1.39, 3.16), regardless of PPI dose or patient age. PPI therapy also increased risk for hospitalization for CAP (OR 1.61; 95% CI: 1.12, 2.31). DISCUSSION Outpatient PPI use is associated with a 1.5-fold increased risk of CAP, with the highest risk within the first 30 days after initiation of therapy. Providers should be aware of this risk when considering PPI use, especially in cases where alternative regimens may be available or the benefits of PPI use are uncertain.
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Affiliation(s)
- Allison A. Lambert
- Department of Medicine, Division of Pulmonary and Critical Care, Johns Hopkins University, Baltimore, MD, United States of America
| | - Jennifer O. Lam
- Department of International Health, Johns Hopkins University, Baltimore, MD, United States of America
| | - Julie J. Paik
- Department of Medicine, Division of Rheumatology, Johns Hopkins University, Baltimore, MD, United States of America
| | - Cesar Ugarte-Gil
- Department of International Health, Johns Hopkins University, Baltimore, MD, United States of America
- Instituto de Medicina Tropical Alexander Von Humboldt, Universidad Peruana Cayetano Heredia, Lima, Perú
| | - M. Bradley Drummond
- Department of Medicine, Division of Pulmonary and Critical Care, Johns Hopkins University, Baltimore, MD, United States of America
| | - Trevor A. Crowell
- Department of Medicine, Division of Infectious Diseases, Johns Hopkins University, Baltimore, MD, United States of America
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Krishna RK, Issa O, Saha D, Macedo FYB, Correal B, Santana O. Pleiotropic effects of the 3-hydroxy-3-methylglutaryl-CoA reductase inhibitors in pulmonary diseases: A comprehensive review. Pulm Pharmacol Ther 2015; 30:134-40. [DOI: 10.1016/j.pupt.2014.08.006] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/17/2014] [Revised: 08/14/2014] [Accepted: 08/18/2014] [Indexed: 12/14/2022]
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Ansaldi F, Orsi A, Trucchi C, De Florentiis D, Ceravolo A, Coppelli M, Schiaffino S, Turello V, Rosselli R, Carloni R, Icardi G, Study Group LP, Canepa P, Sticchi L, Zanetti R, Cremonesi I, Brasesco P, Moscatelli P. Potential effect of PCV13 introduction on Emergency Department accesses for lower respiratory tract infections in elderly and at risk adults. Hum Vaccin Immunother 2014; 11:166-71. [PMID: 25483530 DOI: 10.4161/hv.34419] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022] Open
Abstract
Liguria, an administrative region in northern Italy characterized by a decade of high PCV coverage in paediatric age group, has issued new PCV13 recommendations for free active immunization in adults with risk factors and subjects aged ≥ 70 years old. Main aims of this study are: (1) a descriptive epidemiology of the clinical burden of lower respiratory tract infections (LRTI) in adults ≥18 years of age; and (2) a crossover evaluation of the effect of introduction of PCV13 vaccination in adults aged ≥70 years old, in terms of ED accesses for LRTI, obtained by a Syndrome Surveillance System (SSS). The ED access, chief complaint based SSS will allow an active surveillance of a population cohort of >430 000 individuals resident in Genoa metropolitan area, aged ≥18 years old, for a period of 60 months. During pre-PCV period, annual cumulative incidence of ED accesses for LRTI was equal to 7/1000 and 2% in ≥65 and ≥85 year adults, respectively. In ≥65 years adults, more than 70% of subjects identified by the SSS has at least one risk condition, with a peak of 87% in ≥85 year cohort. New Ligurian PCV13 recommendations can potentially reach more than 75% of ED accesses for LRTI. Data highlights the heavy impact of LRTI in terms of ED accesses, especially in the elderly and subjects with chronic conditions and the usefulness of SSS tool for monitoring PCV vaccination effect.
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Affiliation(s)
- Filippo Ansaldi
- a Department of Health sciences (DiSSal); University of Genoa; Genoa, Italy
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de Groot MCH, Klungel OH, Leufkens HGM, van Dijk L, Grobbee DE, van de Garde EMW. Sources of heterogeneity in case-control studies on associations between statins, ACE-inhibitors, and proton pump inhibitors and risk of pneumonia. Eur J Epidemiol 2014; 29:767-75. [PMID: 25154551 DOI: 10.1007/s10654-014-9941-0] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/07/2014] [Accepted: 07/22/2014] [Indexed: 12/16/2022]
Abstract
The heterogeneity in case-control studies on the associations between community-acquired pneumonia (CAP) and ACE-inhibitors (ACEi), statins, and proton pump inhibitors (PPI) hampers translation to clinical practice. Our objective is to explore sources of this heterogeneity by applying a common protocol in different data settings. We conducted ten case-control studies using data from five different health care databases. Databases varied on type of patients (hospitalised vs. GP), level of case validity, and mode of exposure ascertainment (prescription or dispensing based). Identified CAP patients and controls were matched on age, gender, and calendar year. Conditional logistic regression was used to calculate odds ratios (OR) for the associations between the drugs of interest and CAP. Associations were adjusted by a common set of potential confounders. Data of 38,742 cases and 118,019 controls were studied. Comparable patterns of variation between case-control studies were observed for ACEi, statins and PPI use and pneumonia risk with adjusted ORs varying from 1.04 to 1.49, 0.82 to 1.50 and 1.16 to 2.71, respectively. Overall, higher ORs were found for hospitalised CAP patients matched to population controls versus GP CAP patients matched to population controls. Prevalence of drug exposure was higher in dispensing data versus prescription data. We show that case-control selection and methods of exposure ascertainment induce bias that cannot be adjusted for and to a considerable extent explain the heterogeneity in results obtained in case-control studies on statins, ACEi and PPIs and CAP. The common protocol approach helps to better understand sources of variation in observational studies.
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Affiliation(s)
- Mark C H de Groot
- Division of Pharmacoepidemiology and Clinical Pharmacology, Utrecht Institute for Pharmaceutical Sciences, Faculty of Science, Utrecht University, PO Box 80082, 3508 TB, Utrecht, The Netherlands,
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Xia J, Zhang D, Xu Y, Gong M, Zhou Y, Fang X. A retrospective analysis of carbapenem-resistant Acinetobacter baumannii-mediated nosocomial pneumonia and the in vitro therapeutic benefit of cefoperazone/sulbactam. Int J Infect Dis 2014; 23:90-3. [DOI: 10.1016/j.ijid.2014.01.017] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/29/2013] [Revised: 01/11/2014] [Accepted: 01/14/2014] [Indexed: 01/31/2023] Open
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Hsu WH, Kuo CH, Wang SSW, Lu CY, Liu CJ, Chuah SK, Kuo FC, Chen YH, Huang YB, Hou MF, Wu DC, Hu HM. Acid suppressive agents and risk of Mycobacterium tuberculosis: case-control study. BMC Gastroenterol 2014; 14:91. [PMID: 24884853 PMCID: PMC4030068 DOI: 10.1186/1471-230x-14-91] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/25/2013] [Accepted: 05/02/2014] [Indexed: 12/19/2022] Open
Abstract
Background The acid-suppressive agents have been linked with an increased risk of infectious disease. The relationship between these drugs and Mycobacterium Tuberculosis (TB) was not been reported. Methods We conducted a case–control study using data from National Health Insurance research database of Taiwan. From 1996 till 2008, and 6541 cases were defined as TB infection/activation (ICD-9 coding plus prescription two of four first-line anti-TB regimen for at least one month). Control subjects who were matched to the TB cases by age and sex were selected with 10:1 ratio. Medical records including acid-suppressive agent prescription and comorbidity, and socioeconomic status were analyzed. Results TB infection/activation was more frequent to comorbidity with chronic diseases, alcohol abuse, malignancy, immune deficient/suppression status and acid-related disease (peptic ulcer, reflux esophagitis). Among the TB cases, there was higher exposure record to acid-suppressive agents within 3 months before TB index date (OR 2.43(2.06-2.88) and 1.90 (1.68-2.14) for proton pump inhibitor (PPI) and histamine 2 receptor antagonist (H2RA) respectively). After adjusting confounding factors, PPIs prescription 3 months before TB index date had an association of TB infection/activation (adjusted OR 1.63(1.61-1.63)). Similar result was found in H2RA user (adjusted OR 1.51(1.50-1.52)). The association of acid-suppressive agents in TB infection/activation was fade gradually when the drug prescription period extended. Conclusions Recent prescription of acid-suppressive agent seems to associate the TB infection/activation. In the society where TB was prevalent, evaluation of pulmonary TB before prescription of PPI or H2RA is warranted.
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Affiliation(s)
| | | | | | | | | | | | | | | | | | | | | | - Huang-Ming Hu
- Division of Gastroenterology, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung City 807, Taiwan.
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32
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The effect of statin therapy on the incidence of infections: a retrospective cohort analysis. Am J Med Sci 2014; 347:211-6. [PMID: 23426088 DOI: 10.1097/maj.0b013e31828318e2] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/05/2023]
Abstract
BACKGROUND Statins have been postulated to prevent infection through immunomodulatory effects. OBJECTIVES To compare the incidence of infections in statin users to that in nonusers within the same health care system. METHODS This was a retrospective cohort study of patients enrolled as Tricare Prime or Plus in the San Antonio military multimarket. Statin users were patients who received a statin for at least 3 months between October 1, 2004 and September 30, 2005. Nonusers were patients who did not receive a statin within the study period (October 1, 2003-September 30, 2009). Inpatient and outpatient International Classification of Diseases, 9th Revision, Clinical Modification (ICD-9-CM) codes were used to determine the incidence of infections during the follow-up period (October 1, 2005-September 30, 2009) via multivariable regression analysis and time to infection via Cox regression analysis. RESULTS Of 45,247 patients who met the study criteria, 12,981 (29%) were statin users and 32,266 were nonusers. After adjustments for age, gender, Charlson Comorbidity Score, tobacco use, alcohol abuse/dependence, health care utilization and use of specific medication classes, statin use was associated with an increased incidence of common infections (odds ratio [OR]: 1.13; 95% confidence interval [CI]: 1.06-1.19) but not influenza or fungal infections (OR: 1.06, 95% CI: 0.80-1.39; OR: 0.97; 95% CI: 0.91-1.04, respectively). Time-to-first infection was similar in statin users and nonusers in all infection categories examined. CONCLUSIONS Statin use was associated with an increased incidence of common infections but not influenza or fungal infections. This study does not support a protective role of statins in infection prevention; however, the influence of potential confounders cannot be excluded.
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Filion KB, Chateau D, Targownik LE, Gershon A, Durand M, Tamim H, Teare GF, Ravani P, Ernst P, Dormuth CR, the CNODES Investigators. Proton pump inhibitors and the risk of hospitalisation for community-acquired pneumonia: replicated cohort studies with meta-analysis. Gut 2014; 63:552-8. [PMID: 23856153 PMCID: PMC3963530 DOI: 10.1136/gutjnl-2013-304738] [Citation(s) in RCA: 119] [Impact Index Per Article: 10.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/14/2023]
Abstract
OBJECTIVE Previous observational studies suggest that the use of proton pump inhibitors (PPIs) may increase the risk of hospitalisation for community-acquired pneumonia (HCAP). However, the potential presence of confounding and protopathic biases limits the conclusions that can be drawn from these studies. Our objective was, therefore, to examine the risk of HCAP with PPIs prescribed prophylactically in new users of non-steroidal anti-inflammatory drugs (NSAIDs). DESIGN We formed eight restricted cohorts of new users of NSAIDs, aged ≥40 years, using a common protocol in eight databases (Alberta, Saskatchewan, Manitoba, Ontario, Quebec, Nova Scotia, US MarketScan and the UK's General Practice Research Database (GPRD)). This specific patient population was studied to minimise bias due to unmeasured confounders. High-dimensional propensity scores were used to estimate site-specific adjusted ORs (aORs) for HCAP at 6 months in PPI patients compared with unexposed patients. Fixed-effects meta-analytic models were used to estimate overall effects across databases. RESULTS Of the 4,238,504 new users of NSAIDs, 2.3% also started a PPI. The cumulative 6-month incidence of HCAP was 0.17% among patients prescribed PPIs and 0.12% in unexposed patients. After adjustment, PPIs were not associated with an increased risk of HCAP (aOR=1.05; 95% CI 0.89 to 1.25). Histamine-2 receptor antagonists yielded similar results (aOR=0.95, 95% CI 0.75 to 1.21). CONCLUSIONS Our study does not support the proposition of a pharmacological effect of gastric acid suppressors on the risk of HCAP.
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Affiliation(s)
- Kristian B Filion
- Center for Clinical Epidemiology, Lady Davis Research Institute, Jewish General Hospital, McGill University, Montreal, Quebec, Canada
| | - Dan Chateau
- Manitoba Centre for Health Policy, Department of Community Health Sciences, University of Manitoba, Winnipeg, Manitoba, Canada
| | - Laura E Targownik
- Section of Gastroenterology, Division of Internal Medicine, University of Manitoba, Winnipeg, Manitoba, Canada
| | - Andrea Gershon
- Department of Medicine, Sunnybrook Health Sciences Centre and Institute for Clinical Evaluative Sciences, Toronto, Ontario, Canada
| | - Madeleine Durand
- Internal Medicine Service, Centre Hospitalier Universitaire de Montréal (CHUM) and Pharmacoepidemiology and Pharmacoeconomy Research Unit of the CHUM, Montreal, Quebec, Canada
| | - Hala Tamim
- School of Kinesiology and Health Science, York University, Toronto, Ontario, Canada
| | - Gary F Teare
- Health Quality Council, Saskatoon, Saskatchewan, Canada
| | - Pietro Ravani
- Department of Medicine, University of Calgary, Calgary, Alberta, Canada
| | - Pierre Ernst
- Center for Clinical Epidemiology, Lady Davis Research Institute, Jewish General Hospital, McGill University, Montreal, Quebec, Canada
| | - Colin R Dormuth
- Department of Anesthesiology, Pharmacology & Therapeutics, University of British Columbia, Vancouver, British Columbia, Canada
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Macedo AF, Taylor FC, Casas JP, Adler A, Prieto-Merino D, Ebrahim S. Unintended effects of statins from observational studies in the general population: systematic review and meta-analysis. BMC Med 2014; 12:51. [PMID: 24655568 PMCID: PMC3998050 DOI: 10.1186/1741-7015-12-51] [Citation(s) in RCA: 120] [Impact Index Per Article: 10.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/28/2013] [Accepted: 02/28/2014] [Indexed: 12/18/2022] Open
Abstract
BACKGROUND Efficacy of statins has been extensively studied, with much less information reported on their unintended effects. Evidence from randomized controlled trials (RCTs) on unintended effects is often insufficient to support hypotheses generated from observational studies. We aimed to systematically assess unintended effects of statins from observational studies in general populations with comparison of the findings where possible with those derived from randomized trials. METHODS Medline (1998 to January 2012, week 3) and Embase (1998 to 2012, week 6) were searched using the standard BMJ Cohort studies filter. The search was supplemented with reference lists of all identified studies and contact with experts in the field. We included prospective studies with a sample size larger than 1,000 participants, case control (of any size) and routine health service linkage studies of over at least one year duration. Studies in subgroups of patients or follow-up of patient case series were excluded, as well as hospital-based cohort studies. RESULTS Ninety studies were identified, reporting on 48 different unintended effects. Statins were associated with lower risks of dementia and cognitive impairment, venous thrombo-embolism, fractures and pneumonia, but these findings were attenuated in analyses restricted to higher quality studies (respectively: OR 0.74 (95% CI 0.62 to 0.87); OR 0.92 (95% CI 0.81 to 1.03); OR 0.97 (95% CI 0.88 to 1.05); OR 0.92 (95% CI 0.83 to 1.02)); and marked heterogeneity of effects across studies remained. Statin use was not related to any increased risk of depression, common eye diseases, renal disorders or arthritis. There was evidence of an increased risk of myopathy, raised liver enzymes and diabetes (respectively: OR 2.63 (95% CI 1.50 to 4.61); OR 1.54 (95% CI 1.47 to 1.62); OR 1.31 (95% CI 0.99 to 1.73)). CONCLUSIONS Our systematic review and meta-analyses indicate that high quality observational data can provide relevant evidence on unintended effects of statins to add to the evidence from RCTs. The absolute excess risk of the observed harmful unintended effects of statins is very small compared to the beneficial effects of statins on major cardiovascular events.
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Affiliation(s)
- Ana Filipa Macedo
- Cochrane Heart Group, London School of Hygiene and Tropical Medicine, London, UK
- Faculty of Health Sciences, University of Beira Interior, Covilhã, Portugal
| | - Fiona Claire Taylor
- Cochrane Heart Group, London School of Hygiene and Tropical Medicine, London, UK
- Department of Non-communicable Disease Epidemiology, London School of Hygiene and Tropical Medicine, London, UK
| | - Juan P Casas
- Cochrane Heart Group, London School of Hygiene and Tropical Medicine, London, UK
- Department of Non-communicable Disease Epidemiology, London School of Hygiene and Tropical Medicine, London, UK
- Institute of Cardiovascular Science, University College London, London, UK
| | - Alma Adler
- Cochrane Heart Group, London School of Hygiene and Tropical Medicine, London, UK
| | - David Prieto-Merino
- Department of Medical Statistics, London School of Hygiene and Tropical Medicine, London, UK
| | - Shah Ebrahim
- Cochrane Heart Group, London School of Hygiene and Tropical Medicine, London, UK
- Department of Non-communicable Disease Epidemiology, London School of Hygiene and Tropical Medicine, London, UK
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Cea Soriano L, Ruigómez A, Johansson S, García Rodríguez LA. Study of the Association Between Hip Fracture and Acid-Suppressive Drug Use in a UK Primary Care Setting. Pharmacotherapy 2014; 34:570-81. [DOI: 10.1002/phar.1410] [Citation(s) in RCA: 29] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/08/2022]
Affiliation(s)
- Lucia Cea Soriano
- Spanish Centre for Pharmacoepidemiologic Research (CEIFE); Madrid Spain
| | - Ana Ruigómez
- Spanish Centre for Pharmacoepidemiologic Research (CEIFE); Madrid Spain
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Abstract
BACKGROUND Some recent reports suggest an increased risk of fractures with use of proton pump inhibitors (PPIs) and histamine type 2 receptor antagonists (H2RAs), although results are inconsistent and a causal relationship has yet to be proven. As these acid-suppressive drugs may have uncommon adverse effects on the central nervous system (CNS), such as dizziness, we investigated whether their use is associated with falls as a possible mechanism for increasing fracture risk. METHODS A cohort study with nested case-control analysis and two validation strategies was performed using data from UK patients (aged 40-89 years) included in The Health Improvement Network database (2000-2008). Due to the large number of falls, a random sample of 20,000 cases was used for the analysis. RESULTS The overall incidence of falls per 1000 person-years was 13.0 (95% confidence interval [CI] = 12.9-13.1). After adjustment for potential confounders, there was no relationship between falls and current use of single PPIs (odds ratio [OR] = 0.95; 95% CI = 0.89-1.02) or H2RAs (OR = 1.01; 95% CI = 0.90-1.14); there was no relationship with dose or duration of treatment. Falls were associated with CNS disorders and treatment with various pharmacological agents including antiparkinson drugs (OR = 2.7; 95% CI = 2.2-3.3) and antiepileptics (OR = 2.1; 95% CI = 1.8-2.3). CONCLUSIONS There was no association between falls and use of PPIs or H2RAs. Any potential increase in the risk of fractures proposed to be associated with the use of acid-suppressive drugs is not via an increased risk of falls.
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Torres A, Peetermans WE, Viegi G, Blasi F. Risk factors for community-acquired pneumonia in adults in Europe: a literature review. Thorax 2013; 68:1057-65. [PMID: 24130229 PMCID: PMC3812874 DOI: 10.1136/thoraxjnl-2013-204282] [Citation(s) in RCA: 424] [Impact Index Per Article: 35.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
Background Community-acquired pneumonia (CAP) causes considerable morbidity and mortality in adults, particularly in the elderly. Methods Structured searches of PubMed were conducted to identify up-to-date information on the incidence of CAP in adults in Europe, as well as data on lifestyle and medical risk factors for CAP. Results The overall annual incidence of CAP in adults ranged between 1.07 to 1.2 per 1000 person-years and 1.54 to 1.7 per 1000 population and increased with age (14 per 1000 person-years in adults aged ≥65 years). Incidence was also higher in men than in women and in patients with chronic respiratory disease or HIV infection. Lifestyle factors associated with an increased risk of CAP included smoking, alcohol abuse, being underweight, having regular contact with children and poor dental hygiene. The presence of comorbid conditions, including chronic respiratory and cardiovascular diseases, cerebrovascular disease, Parkinson's disease, epilepsy, dementia, dysphagia, HIV or chronic renal or liver disease all increased the risk of CAP by twofold to fourfold. Conclusion A range of lifestyle factors and underlying medical conditions are associated with an increased risk of CAP in European adults. Understanding of the types of individual at greatest risk of CAP can help to ensure that interventions to reduce the risk of infection and burden of disease are targeted appropriately.
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Affiliation(s)
- Antoni Torres
- Servei de Pneumologia, Hospital Clínic de Barcelona, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), CIBER de Enfermedades Respiratorias (CIBERes), University of Barcelona, Barcelona, Spain
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Lima JJ, Lang JE, Mougey EB, Blake KB, Gong Y, Holbrook JT, Wise RA, Teague WG. Association of CYP2C19 polymorphisms and lansoprazole-associated respiratory adverse effects in children. J Pediatr 2013; 163:686-91. [PMID: 23623526 PMCID: PMC7274090 DOI: 10.1016/j.jpeds.2013.03.017] [Citation(s) in RCA: 38] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/23/2012] [Revised: 01/28/2013] [Accepted: 03/12/2013] [Indexed: 12/12/2022]
Abstract
OBJECTIVE To determine whether cytochrome P450 (CYP)2C19 haplotype associates with lansoprazole-associated adverse event frequency. STUDY DESIGN Respiratory adverse events from a clinical trial of lansoprazole in children with asthma were analyzed for associations with extensive or poor metabolizer (PM) phenotype based on CYP2C19 haplotypes. Carriers of CYP2C19*2, *3, *8, or *9 alleles were PMs; carriers of 2 wild-type alleles were extensive metabolizers (EMs). Plasma concentrations of lansoprazole were determined in PM and EM phenotypes. RESULTS The frequency of upper respiratory infection among PMs (n = 45) was higher than that among EMs (n = 91), which in turn was higher than that in placebo subjects (n = 135; P = .0039). The frequency of sore throat (ST) was similarly distributed among EMs and PMs (P = .0015). The OR (95% CI) for upper respiratory infections in PMs was 2.46 (1.02-5.96) (P = .046); for EMs, the OR (95% CI) was 1.55 (0.86-2.79). The OR (95% CI) for ST in EMs and PMs was 2.94 (1.23-7.05, P = .016) vs 1.97 (1.09-3.55, P = .024), respectively. Mean ± SD plasma concentrations of lansoprazole were higher in PMs than in EMs: 207 ± 179 ng/mL vs 132 ± 141 ng/mL (P = .04). CONCLUSIONS Lansoprazole-associated upper respiratory infections and ST in children are related in part to CYP2C19 haplotype. Our data suggest that lansoprazole-associated adverse events in children may be mitigated by adjusting the conventional dose in PMs. Additional studies are required to replicate our findings.
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Affiliation(s)
- John J Lima
- Center for Pharmacogenomics and Translational Research, Nemours Children's Clinic, Jacksonville, FL, USA.
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Liu CL, Shau WY, Chang CH, Wu CS, Lai MS. Pneumonia risk and use of angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers. J Epidemiol 2013; 23:344-50. [PMID: 23912052 PMCID: PMC3775528 DOI: 10.2188/jea.je20120112] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022] Open
Abstract
Background Recent studies have shown that use of angiotensin-converting enzyme (ACE) inhibitors may decrease pneumonia risk in various populations. We investigated the effect of ACE inhibitors and angiotensin II receptor blockers (ARBs) on pneumonia hospitalization in the general population of Taiwan. Methods We conducted a case-crossover study using the Taiwan Longitudinal Health Insurance Database for the year 2005. Data from patients hospitalized for the first time for pneumonia during 1997–2007 were analyzed. The case period was defined as the 30 days before admission; the periods 90 to 120 days and 180 to 210 days before admission were used as control periods. Prescribing status of ACE inhibitors and ARBs during the 3 periods was assessed for each patient. Conditional logistic regression was used to estimate the odds ratio (OR) for pneumonia associated with use of ACE inhibitors and ARBs. Results We identified 10 990 cases of hospitalization for new pneumonia. After adjustment for time-variant confounding factors, pneumonia was not associated with use of ACEI or ARBS: the ORs were 0.99 (95% CI, 0.81–1.21) and 0.96 (0.72–1.28), respectively. No association was seen for cumulative defined daily doses (DDDs), as compared with nonusers, for 0 to 30, 31 to 60, or more than 60 DDDs. The results were found to be robust in sensitivity analysis. Conclusions Neither the use nor cumulative dose of ACE inhibitors or ARBs was associated with pneumonia among the Taiwanese general population.
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Affiliation(s)
- Chia-Lin Liu
- Department of Family Medicine, En Chu Kong Hospital, New Taipei City, Taiwan
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Juthani-Mehta M, De Rekeneire N, Allore H, Chen S, O'Leary JR, Bauer DC, Harris TB, Newman AB, Yende S, Weyant RJ, Kritchevsky S, Quagliarello V. Modifiable risk factors for pneumonia requiring hospitalization of community-dwelling older adults: the Health, Aging, and Body Composition Study. J Am Geriatr Soc 2013; 61:1111-8. [PMID: 23772872 DOI: 10.1111/jgs.12325] [Citation(s) in RCA: 50] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/01/2023]
Abstract
OBJECTIVES To identify novel modifiable risk factors, focusing on oral hygiene, for pneumonia requiring hospitalization of community-dwelling older adults. DESIGN Prospective observational cohort study. SETTING Memphis, Tennessee, and Pittsburgh, Pennsylvania. PARTICIPANTS Of 3,075 well-functioning community-dwelling adults aged 70 to 79 enrolled in the Health, Aging, and Body Composition Study from 1997 to 1998, 1,441 had complete data in the data set of all variables used, a dental examination within 6 months of baseline, and were eligible for this study. MEASUREMENTS The primary outcome was pneumonia requiring hospitalization through 2008. RESULTS Of 1,441 participants, 193 were hospitalized for pneumonia. In a multivariable model, male sex (hazard ratio (HR) = 2.07, 95% confidence interval (CI) = 1.51-2.83), white race (HR = 1.44, 95% CI = 1.03-2.01), history of pneumonia (HR = 3.09, 95% CI = 1.86-5.14), pack-years of smoking (HR = 1.006, 95% CI = 1.001-1.011), and percentage of predicted forced expiratory volume in 1 minute (moderate vs mild lung disease or normal lung function, HR = 1.78, 95% CI = 1.28-2.48; severe lung disease vs mild lung disease or normal lung function, HR = 2.90, 95% CI = 1.51-5.57) were nonmodifiable risk factors for pneumonia. Incident mobility limitation (HR = 1.77, 95% CI = 1.32-2.38) and higher mean oral plaque score (HR = 1.29, 95% CI = 1.02-1.64) were modifiable risk factors for pneumonia. Average attributable fractions revealed that 11.5% of cases of pneumonia were attributed to incident mobility limitation and 10.3% to a mean oral plaque score of 1 or greater. CONCLUSION Incident mobility limitation and higher mean oral plaque score were two modifiable risk factors that 22% of pneumonia requiring hospitalization could be attributed to. These data suggest innovative opportunities for pneumonia prevention among community-dwelling older adults.
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Affiliation(s)
- Manisha Juthani-Mehta
- Section of Infectious Diseases, Department of Internal Medicine, School of Medicine, Yale University, New Haven, Connecticut 06520, USA.
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The immunomodulatory effects of statins in community-acquired pneumonia: a systematic review. J Infect 2013; 67:93-101. [PMID: 23665030 DOI: 10.1016/j.jinf.2013.04.015] [Citation(s) in RCA: 19] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/22/2013] [Revised: 04/14/2013] [Accepted: 04/20/2013] [Indexed: 12/11/2022]
Abstract
OBJECTIVE To evaluate the potential immunomodulatory effects of statins in community-acquired pneumonia. METHODS We performed a systematic review of available literature on experimental and clinical studies. We used a PubMed/MEDLINE and EMBASE search to identify potential articles. RESULTS We identified 34 original studies, 17 experimental and 17 clinical studies, published up to March 2013. CONCLUSIONS Statins attenuated pulmonary inflammation by modulating neutrophil function, by reducing cytokine expression and release, and by protecting against disruption of pulmonary integrity. However, additional experimental studies are needed to fully elucidate the exact mechanisms. Several clinical studies suggested a decreased risk of CAP or a reduction in mortality due to CAP for current statin users, but the mostly observational design of these studies hampers the interpretation of their results. Therefore, appropriately designed studies, such as randomised controlled trials, are required to demonstrate the usefulness of statins in the prevention and treatment of CAP.
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Frandah W, Colmer-Hamood J, Mojazi Amiri H, Raj R, Nugent K. Oropharyngeal flora in patients admitted to the medical intensive care unit: clinical factors and acid suppressive therapy. J Med Microbiol 2013; 62:778-784. [PMID: 23378561 DOI: 10.1099/jmm.0.053066-0] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022] Open
Abstract
Acid suppression therapy in critically ill patients significantly reduces the incidence of stress ulceration and gastrointestinal (GI) bleeding; however, recent studies suggest that proton pump inhibitors (PPIs) increase the risk of pneumonia. We wanted to test the hypothesis that acid suppressive therapy promotes alteration in the bacterial flora in the GI tract and leads to colonization of the upper airway tract with pathogenic species, potentially forming the biological basis for the observed increased incidence of pneumonia in these patients. This was a prospective observational study on patients (adults 18 years or older) admitted to the medical intensive care unit (MICU) at a tertiary care centre. Exclusion criteria included all patients with a diagnosis of pneumonia at admission, with infection in the upper airway, or with a history of significant dysphagia. Oropharyngeal cultures were obtained on day 1 and days 3 or 4 of admission. We collected data on demographics, clinical information, and severity of the underlying disease using APACHE II scores. There were 110 patients enrolled in the study. The mean age was 49±16 years, 50 were women, and the mean APACHE II score was 9.8 ± 6.5. Twenty per cent of the patients had used a PPI in the month preceding admission. The first oropharyngeal specimen was available in 110 cases; a second specimen at 72-96 h was available in 68 cases. Seventy-five per cent of the patients admitted to the MICU had abnormal flora. In multivariate logistic regression, diabetes mellitus and PPI use were associated with abnormal oral flora on admission. Chronic renal failure and a higher body mass index reduced the frequency of abnormal oral flora on admission. Most critically ill patients admitted to our MICU have abnormal oral flora. Patients with diabetes and a history of recent PPI use are more likely to have abnormal oral flora on admission.
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Affiliation(s)
- Wesam Frandah
- Department of Internal Medicine, Texas Tech University Health Sciences Center, Lubbock, TX, USA
| | - Jane Colmer-Hamood
- Department of Microbiology, Texas Tech University Health Sciences Center, Lubbock, TX, USA
| | - Hoda Mojazi Amiri
- Department of Internal Medicine, Texas Tech University Health Sciences Center, Lubbock, TX, USA
| | - Rishi Raj
- Department of Internal Medicine, Texas Tech University Health Sciences Center, Lubbock, TX, USA
| | - Kenneth Nugent
- Department of Internal Medicine, Texas Tech University Health Sciences Center, Lubbock, TX, USA
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Bourne C, Charpiat B, Charhon N, Bertin C, Gouraud A, Mouchoux C, Skalli S, Janoly-Dumenil A. Effets indésirables émergents des inhibiteurs de la pompe à protons. Presse Med 2013; 42:e53-62. [DOI: 10.1016/j.lpm.2012.09.016] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/13/2012] [Revised: 08/08/2012] [Accepted: 09/04/2012] [Indexed: 12/12/2022] Open
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Khan AR, Riaz M, Bin Abdulhak AA, Al-Tannir MA, Garbati MA, Erwin PJ, Baddour LM, Tleyjeh IM. The role of statins in prevention and treatment of community acquired pneumonia: a systematic review and meta-analysis. PLoS One 2013; 8:e52929. [PMID: 23349694 PMCID: PMC3538683 DOI: 10.1371/journal.pone.0052929] [Citation(s) in RCA: 54] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/11/2012] [Accepted: 11/22/2012] [Indexed: 12/27/2022] Open
Abstract
BACKGROUND Emerging epidemiological evidence suggests that statins may reduce the risk of community-acquired pneumonia (CAP) and its complications. PURPOSE Performed a systematic review to address the role of statins in the prevention or treatment of CAP. DATA SOURCE Ovid MEDLINE, Cochrane, EMBASE, ISI Web of Science, and Scopus from inception through December 2011 were searched for randomized clinical trials, cohort and case-control studies. STUDY SELECTION Two authors independently reviewed studies that examined the role of statins in CAP. DATA EXTRACTION Data about study characteristics, adjusted effect-estimates and quality characteristics was extracted. DATA SYNTHESIS Eighteen studies corresponding to 21 effect-estimates (eight and 13 of which addressed the preventive and therapeutic roles of statins, respectively) were included. All studies were of good methodological quality. Random-effects meta-analyses of adjusted effect-estimates were used. Statins were associated with a lower risk of CAP, 0.84 (95% CI, 0.74-0.95), I(2) = 90.5% and a lower short-term mortality in patients with CAP, 0.68 (95% CI, 0.59-0.78), I(2) = 75.7%. Meta-regression did not identify sources of heterogeneity. A funnel plot suggested publication bias in the treatment group, which was adjusted by a novel regression method with a resultant effect-estimate of 0.85 (95% CI, 0.77-0.93). Sensitivity analyses using the rule-out approach showed that it is unlikely that the results were due to an unmeasured confounder. CONCLUSIONS Our meta-analysis reveals a beneficial role of statins for the risk of development and mortality associated with CAP. However, the results constitute very low quality evidence as per the GRADE framework due to observational study design, heterogeneity and publication bias.
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Affiliation(s)
- Abdur Rahman Khan
- Department of Internal Medicine, University of Toledo Medical Center, Toledo, Ohio, United States of America
| | - Muhammad Riaz
- Research and Scientific Publication Center, King Fahad Medical City, Riyadh, Saudi Arabia
| | - Aref A. Bin Abdulhak
- Department of Internal Medicine, University of Missouri – Kansas City, Kansas City, Missouri, United States of America
| | - Mohamad A. Al-Tannir
- Research and Scientific Publication Center, King Fahad Medical City, Riyadh, Saudi Arabia
| | - Musa A. Garbati
- Department of Internal Medicine, King Fahad Medical City, Riyadh, Saudi Arabia
| | - Patricia J. Erwin
- Mayo Medical Library, Mayo Clinic, Rochester, Minnesota, United States of America
| | - Larry M. Baddour
- Division of Infectious Diseases, Mayo Clinic, Rochester, Minnesota, United States of America
| | - Imad M. Tleyjeh
- Department of Internal Medicine, King Fahad Medical City, Riyadh, Saudi Arabia
- Division of Infectious Diseases, Mayo Clinic, Rochester, Minnesota, United States of America
- Division of Epidemiology, Mayo Clinic, Rochester, Minnesota, United States of America
- College of Medicine, Alfaisal University, Riyadh, Saudi Arabia
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Chung EY, Yardley J. Are there risks associated with empiric acid suppression treatment of infants and children suspected of having gastroesophageal reflux disease? Hosp Pediatr 2013; 3:16-23. [PMID: 24319831 DOI: 10.1542/hpeds.2012-0077] [Citation(s) in RCA: 37] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 06/03/2023]
Abstract
BACKGROUND It has become common practice to empirically treat infants and children who have suspected gastroesophageal reflux disease by using acid-suppressive medications. However, evidence to support the effectiveness of these medications in the pediatric population is limited. With multiple studies in adult patients indicating increased risk of infection, we reviewed the literature to determine the association between acid-suppressive medications and serious adverse effects in infants and children. METHODS We conducted a PubMed search on the adverse effects of H2 antagonists and proton pump inhibitors in pediatric patients. The studies selected were original research and systematic reviews with control groups and study objectives evaluating the relationship between acid-suppressive medications and serious adverse effects (namely, infections). RESULTS Fourteen studies met our inclusion criteria. The majority of studies found a significant association between acid-suppressive medications and the risk of necrotizing enterocolitis, sepsis/bacteremia, pneumonia, and gastrointestinal infections in infants and children. CONCLUSIONS Given the questionable efficacy of H2 antagonists and proton pump inhibitors and the growing evidence of increased risk of serious infections, acid-suppressive medications should be used cautiously in infants and children suspected of having gastroesophageal reflux disease.
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Affiliation(s)
- Erica Y Chung
- The Warren Alpert Medical School of Brown University, Rhode Island Hospital/Hasbro Children's Hospital, Providence, Rhode Island, USA.
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Angiotensin-converting enzyme inhibitor/angiotensin II receptor blockers and pneumonia risk among stroke patients. J Hypertens 2012; 30:2223-9. [DOI: 10.1097/hjh.0b013e328357a87a] [Citation(s) in RCA: 23] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/31/2023]
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Giuliano C, Wilhelm SM, Kale-Pradhan PB. Are proton pump inhibitors associated with the development of community-acquired pneumonia? A meta-analysis. Expert Rev Clin Pharmacol 2012; 5:337-44. [PMID: 22697595 DOI: 10.1586/ecp.12.20] [Citation(s) in RCA: 82] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
This study was presented at the American College of Chest Physicians meeting in Pittsburgh (PA, USA) in October 2011. The study objective was to evaluate the association of proton pump inhibitors (PPIs) and community-acquired pneumonia (CAP). The design was a meta-analysis of nine case-controlled and cohort studies. 120,863 pneumonia cases from 1987 to 2006 were included in the meta-analysis. PubMed and Ovid Medline were searched from inception through May 2011 by two investigators independently using keywords: PPI, pneumonia, CAP, anti-ulcer, antacid, omeprazole, esomeprazole, lansoprazole, pantoprazole and rabeprazole. This meta-analysis only included case-controlled and cohort studies that were published in full in English and evaluated PPI use and CAP incidence. Studies were excluded if they included the following patients: pediatric, Helicobacter pylori treatment and critically ill. Bibliographies of recent review articles and systematic reviews were hand-searched. Quality of studies was assessed using the Newcastle-Ottawa Quality Assessment Scale. Two investigators independently extracted data into standardized data collection forms that were confirmed by a third investigator. Data were analyzed based on current use of PPIs, duration of PPI use (<30 days or >180 days) and PPI dose (high vs low). Overall association of PPI and CAP was analyzed using the random effects model (Comprehensive Meta analysis(®) Version 2.0). Nine studies met all criteria for the primary outcome. Newcastle-Ottawa Quality Assessment Scale scores ranged from 4 to 8 out of 9. Current use of PPIs (odds ratio [OR]: 1.39; 95% CI: 1.09-1.76), PPI use <30 days (OR: 1.65; 95% CI: 1.25-2.19), PPI high dose (OR: 1.50; 95% CI: 1.33-1.68) and PPI low dose (OR: 1.17; 95% CI: 1.11-1.24) were significantly associated with CAP. There was no association between CAP and PPI use >180 days (OR: 1.10; 95% CI: 1.00-1.21). In conclusion, patients currently receiving PPIs, particularly <30 days or high dose, showed an association with CAP. Practitioners need to be vigilant about adverse effects of PPIs and consider alternative therapies.
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Affiliation(s)
- Christopher Giuliano
- Department of Pharmacy Practice, Eugene Applebaum College of Pharmacy and Health Science, Wayne State University, St John Hospital and Medical Center, Detroit, MI 48201, USA
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Kayani WT, Bandeali SJ, Lee VV, Elayda M, Khan A, Nambi V, Jneid H, Alam M, Wilson JM, Huang HD, Birnbaum Y, Ballantyne CM, Virani SS. Association between statins and infections after coronary artery bypass grafting. Int J Cardiol 2012; 168:117-20. [PMID: 23046597 DOI: 10.1016/j.ijcard.2012.09.060] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/23/2012] [Revised: 06/22/2012] [Accepted: 09/14/2012] [Indexed: 12/14/2022]
Abstract
BACKGROUND We determined whether pre-operative statin therapy is associated with a decrease in the incidence of infections after coronary artery bypass grafting (CABG). METHODS A retrospective cohort study of 6253 patients undergoing isolated CABG, from the Texas Heart Institute Database from January 1, 2000 to December 31, 2010 (3869 receiving statins and 2384 not receiving statins) was conducted. Primary outcome was the development of any postoperative infection (composite of deep-sternal wound infection, leg harvest-site infection, pneumonia, or sepsis) after CABG. Secondary outcome was the association between pre-operative statin use and individual incidence of each aforementioned infection. Logistic regression analyses were performed. RESULTS Incidence of any postoperative infection in patients who received statins pre-operatively was 6.5% compared to 8.3% in patients who did not receive statins. Pre-operative statin therapy was associated with a significant reduction in the primary outcome (odds ratio (OR) 0.74, 95% confidence interval (CI) 0.60-0.90) in adjusted models. Among individual secondary outcomes, pre-operative statin therapy was associated with a reduced incidence of sternal wound infections (2.5% vs. 3.2%, OR 0.6, 95% CI 0.5-0.8) and leg harvest site infections (0.6% vs. 1.3%, OR 0.46, 95% CI 0.2-0.8). Pre-operative statin therapy was not associated with a reduced incidence of pneumonia or sepsis. CONCLUSION Pre-operative statin use is associated with a decrease in overall incidence of post-operative infections after CABG. We propose immunomodulatory effects of statins leading to a dampening of inflammatory cascade as the cause of our findings.
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Affiliation(s)
- Waleed T Kayani
- Department of Medicine, Baylor College of Medicine, Houston, TX, United States.
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Dublin S, Walker RL, Jackson ML, Nelson JC, Weiss NS, Jackson LA. Angiotensin-converting enzyme inhibitor use and pneumonia risk in community-dwelling older adults: results from a population-based case-control study. Pharmacoepidemiol Drug Saf 2012; 21:1173-82. [PMID: 22949094 DOI: 10.1002/pds.3340] [Citation(s) in RCA: 12] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/09/2012] [Revised: 05/21/2012] [Accepted: 07/30/2012] [Indexed: 11/06/2022]
Abstract
PURPOSE To test whether angiotensin-converting enzyme (ACE) inhibitor use is associated with decreased risk of community-acquired pneumonia in older adults. METHODS We analyzed data from a nested case-control study of community-dwelling, immunocompetent adults aged 65-94 within an integrated healthcare delivery system. Cases of ambulatory and hospitalized pneumonia from 2000 to 2003 were identified from International Classification of Disease, version 9, codes and validated using medical record review. Controls were matched to cases by age, sex, and calendar year. Using health plan pharmacy data, we defined current use as filling ≥2 prescriptions during the 180 days prior to the case's diagnosis date. We calculated standardized doses per day using World Health Organization defined daily doses. Multivariable conditional logistic regression estimated adjusted odds ratios (ORs) for pneumonia in relation to ACE inhibitor use, adjusting for comorbidity, functional and cognitive status, and other covariates from medical record review and pharmacy data. RESULTS Current use of ACE inhibitors was seen in 23% (242/1039) of cases and 21% (433/2022) of controls. Lisinopril accounted for 95% of prescriptions. The OR for pneumonia comparing current use to no current use was 0.99 (95% confidence interval [CI] 0.83-1.19). The OR for use of more than two standardized daily doses per day was 1.39 (95% CI 0.93-2.06) compared to no current use. CONCLUSIONS ACE inhibitor use is not associated with reduced pneumonia risk in community-dwelling older adults.
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Affiliation(s)
- Sascha Dublin
- Group Health Research Institute, Seattle, WA 98101-1448, USA.
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Nielsen AG, Nielsen RB, Riis AH, Johnsen SP, Sørensen HT, Thomsen RW. The impact of statin use on pneumonia risk and outcome: a combined population-based case-control and cohort study. CRITICAL CARE : THE OFFICIAL JOURNAL OF THE CRITICAL CARE FORUM 2012; 16:R122. [PMID: 22789037 PMCID: PMC3580701 DOI: 10.1186/cc11418] [Citation(s) in RCA: 45] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 05/02/2012] [Accepted: 07/12/2012] [Indexed: 01/03/2023]
Abstract
Introduction The impact of statin use on pneumonia risk and outcome remains unclear. We therefore examined this risk in a population-based case-control study and did a 5-year update of our previous 30-day mortality analyses. Methods We identified 70,953 adults with a first-time hospitalization for pneumonia between 1997 and 2009 in Northern Denmark. Ten age- and sex-matched population controls were selected for each pneumonia patient. To control for potential confounders, we retrieved individual-level data on other medications, comorbidities, recent surgery, socioeconomic indicators, influenza vaccination, and other markers of frailty or health awareness from medical databases. We followed all pneumonia patients for 30 days after hospital admission. Results A total of 7,223 pneumonia cases (10.2%) and 64 523 controls (9.1%) were statin users before admission, corresponding to an age- and sex-matched odds ratio (OR) of 1.17 (95% confidence interval [CI]: 1.14-1.21). After controlling for higher comorbidity and a wide range of other potential confounders, the adjusted OR for pneumonia associated with current statin use dropped to 0.80 (95% CI: 0.77-0.83). Previous statin use was not associated with decreased pneumonia risk (adjusted OR = 0.97, 95% CI: 0.91-1.02). Decreased risk remained significant after further adjustment for frailty and health awareness markers. The prevalence of statin use among Danish pneumonia patients increased from 1% in 1997 to 24% in 2009. Thirty-day mortality following pneumonia hospitalization was 11.3% among statin users versus 15.1% among nonusers. This corresponded to a 27% reduced mortality rate (adjusted hazard ratio = 0.73, 95% CI: 0.67-0.79), corroborating our earlier findings. Conclusions Current statin use was associated with both a decreased risk of hospitalization for pneumonia and lower 30-day mortality following pneumonia.
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