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R E S E A R C H A R T I C L E Open Access Burden of Clostridium difficile- associated disease among patients residing in nursing homes: a population-based cohort study Holly Yu 1*, Onur Baser 2,3 and Li Wang 4 Abstract Background: Clostridium difficile (C. difficile ) infection (CDI) is the leading cause of nosocomial diarrhea in the United States. This study aimed to examine the incidence of CDI and evaluate mortality and economic burden of CDI in an elderly population who reside in nursing homes (NHs).

Methods: This was a population-based retrospective cohort study focusing on US NHs by linking Medicare 5% sample, Medicaid, Minimum Data Set (MDS) (2008 –10). NH residents aged ≥65 years with continuous enrollment in Medicare and/or Medicaid Fee-for-Service plan for ≥12 months and ≥2 quarterly MDS assessments were eligible for the study. The incidence rate was calculated as the number of CDI episodes by 100,000 person-years. A 1:4 propensity score matched sample of cohorts with and without CDI was generated to assess mortality and health care costs following the first CDI.

Results: Among 32,807 NH residents, 941 residents had ≥1 episode of CDI in 2009, with an incidence of 3359.9 per 100,000 person-years. About 30% CDI episodes occurred in the hospital setting. NH residents with CDI (vs without CDI) were more likely to have congestive heart failure, renal disease, cerebrovascular disease, hospitalizations, and outpatient antibiotic use. During the follow-up period, the 30-day (14.7% vs 4.3%, P< 0.001), 60-day (22.7% vs 7.5%, P< 0.001), 6-month (36.3% vs 18.3%, P< 0.001), and 1-year mortality rates (48.2% vs 31.1%, P< 0.001) were significantly higher among the CDI residents vs non-CDI residents. Total health care costs within 2 months following the first CDI episode were also significantly higher for CDI residents ($28,621 vs $13,644, P< 0.001). Conclusions: CDI presents a serious public health issue in NHs. Mortality, health care utilization, and associated costs were significant following incident CDI episodes.

Keywords: Clostridium difficile (C. difficile ), CDI, Nursing homes, Medicare, Medicaid Background Clostridium difficile (C. difficile ) infection (CDI) is the leading cause of nosocomial diarrhea in the United States and has surpassed the infection rate of other health care-associated infections (HAI) such as methicillin-resistant Staphylococcus aureus [1, 2] .In a recent national prevalence survey, C. difficile was the most commonly-reported pathogen, accounting for 12% of HAIs and an estimated 80,400 hospital-onset infec- tions [3]. C. difficile was responsible for almost a half- million infections and approximately 28,000 deaths in 2011 [4]. The emergence of the epidemic BI/NAP1/027 strain has been associated with the increased incidence, severity, and mortality of CDI [5]. The increasing inci- dence of CDI also imposes a large financial burden on the health care system [6]. In 2008, the excess health care costs for CDI in acute care facilities alone were approximately $4.8 billion [7].

The elderly represent the population at greatest risk for CDI, accounting for the highest disease morbidity and mortality. Moreover, residents of nursing homes and other long-term care (LTC) facilities are more prone to CDI due to advanced age, frequent hospitalization, prevalent comorbid illnesses, extended stays, and fre- quent exposure to antibiotics [1]. In 2013, Garg et al. * Correspondence: [email protected] 1Pfizer Inc, Arcola Road, Collegeville, PA 19426, USAFull list of author information is available at the end of the article © The Author(s). 2016 Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link tothe Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver(http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. Yu et al. BMC Geriatrics (2016) 16:193 DOI 10.1186/s12877-016-0367-2 determined that there was a predominantly higher num- ber of patients diagnosed with LTC-acquired CDI (46.1%) compared to community-acquired (33.3%) or hospital-acquired (20.6%) CDI [8]. Additionally, state- wide surveillance in Ohio has found that there were more cases of CDI diagnosed in LTC facilities than in acute-care settings [9]. The increasing trends of CDI- incidence in LTC facilities such as nursing homes high- light the need for optimal C. difficile infection control measures [8].

Previous studies have focused on the costs related to CDI in acute-care facilities [10, 11]. However, to our knowledge, there are no recent studies assessing the costs of CDI in nursing homes. Therefore, the objectives of this study were to examine the incidence of CDI and evaluate the mortality and economic burden of CDI in an elderly population residing in nursing homes.

Methods Study design and data sources This population-based retrospective cohort study in- cluded adults aged ≥65 years enrolled in Medicare or with dual eligibility with the Medicaid fee-for-service (FFS) health plan during 2008 –2010. A Medicare 5% random sample was used, and all eligible enrollees were required to have both Part A (hospital insurance) and Part B (supplementary medical insurance) during the study period [12]. Because some Medicare enrollees, may also be covered by Medicaid due to socioeconomic factors, we linked the Medicare 5% sample with the 100% Medicaid claims data.

To identify Medicare enrollees residing in nursing homes, we linked the 5% Medicare sample and 100% Medicaid with the 100% Minimum Data Set (MDS) and required ≥2 consecutive MDS quarterly assessments in the 12 months prior to the CDI diagnosis. The MDS is a federally-mandated nursing home clinical assessment performed on all residents at admission, discharge, annually, and quarterly, regardless of the payer.

Identification of CDI episodes The primary outcome was the incidence of CDI, identi- fied as residents with ≥1 medical claim for CDI (International Classification of Diseases, 9th Revision, Clinical Modification [ICD-9-CM] code: 008.45) in Medicare or Medicaid data, or identified CDI (1 = yes) in MDS data from January 1, 2009 through December 31, 2009. An incident CDI episode was defined as a patient with no occurrences of CDI within 60 days prior to the first CDI claim. Among patients with multiple episodes of CDI, each episode was considered as incident if there was at least a 60-day gap between the 2 episodes. We also identified the setting (eg, inpatient, nursing home) of infection onset using the first CDI claim setting. Case-control analysis As a secondary objective, we examined mortality at 30, 60, and 180 days, and at 1 year following the onset of the index CDI episode. Since mortality information is derived from the Medicare enrollment file which is up- dated by the Social Security Administration, we were able to capture all deaths. We also analyzed all-cause health care costs and utilization stratified by health plan (eg, Medicare and Medicaid) within 2 months following the first incident episode among those with CDI (cases) and those without CDI (controls). For this analysis, in contrast to the incidence computation, residents were required to have no diagnosis of CDI within the 12 months prior to the first incident episode (index date) in 2009. The 12 months prior to this index date was used as an observation period to allow sufficient time to determine baseline demographic and clinical characteris- tics and health care utilization parameters. Residents with CDI episodes identified in the MDS typically lacked complete Medicare and Medicaid data; therefore, these residents were excluded from this portion of the ana- lysis. Eligible residents enrolled in Medicare or Medicaid without a CDI diagnosis between January 1, 2008 and December 31, 2010, served as the control group and were randomly assigned an index date in 2009.

Statistical analyses The incidence rates of CDI were calculated as the num- ber of residents with a CDI episode per 100,000 person- years and stratified by age, gender, race, and region. For the case-control analysis, each CDI case resident was matched to 4 non-CDI control residents using a ‘greedy ’ match method [13]; CDI cases were matched to non- CDI controls within 0.001 units of the propensity score [14]. The propensity score was calculated via a logistic regression model of factors associated with the risk of CDI, including the residents ’age, gender, race, US census region, comorbidities using the Charlson Comor- bidity Index (CCI) score, prior hospitalizations, nursing home stays, antibiotic exposure, gastric acid suppressant use within 90 days and 1 year prior to the incident CDI, individual comorbidities, and comorbid conditions included the MDS data.

Chi-square tests were used to evaluate differences in categorical variables. Student t-tests were used for evalu- ating differences in continuous variables. In addition to p-values, standardized differences were calculated for each variable. A standardized difference of >10% was used to assess significant practical differences in the case-control comparison [15].

Statistical significance was set a priori at the alpha <0.05. All analyses were performed using Statistical Analysis System (SAS) version 9.3 (SAS Institute Inc., Cary, NC). Yu et al. BMC Geriatrics (2016) 16:193 Page 2 of 7 Results CDI incidence rates We identified 1,051 incident episodes of CDI among 941 residents with ≥1 CDI episode in a cohort of 32,807 resi- dents who met the eligibility criteria. The annual incidence density of CDI was 3,752.7 episodes per 100,000 person-years and 3,359.9 residents per 100,000 person-years (Table 1). Across the age strata, an inverse linear trend was observed: the incidence ranged from a low of 3,414.9 episodes per 100,000 person-years among residents aged ≥85 years to a high of 4,247.5 episodes/ per 100,000 person-years among those aged 65 –74 years. Incidence was slightly higher among men than women and lower among whites as compared to blacks or other race categories. Geographically, the incidence density of CDI was highest in the Northeast (4,641.1 per 100,000 person-years), and lowest in the Midwest (3,306.8 episodes per 100,000 person-years). The majority of CDI episodes occurred in a nursing home (71.7%), and 28.3% occurred in an inpatient hospital setting.

Case-control analysis After accounting for the inclusion and exclusion criteria, a sample of 789 residents with an incident CDI episode and 30,258 without were included for this analysis. The mean age of the residents with and without CDI was 83.1 years and 83.6 years, respectively. Geographically, a higher proportion of CDI residents resided in the Northeast region (36.1% vs 28.5%, P< 0.001), whereas a higher proportion of non-CDI residents resided in the Midwest (34.3% vs 27.8%, p< 0.001; Table 2). Approxi- mately two-thirds of residents had Medicaid coverage along with their Medicare insurance.

Residents with CDI were more often diagnosed with comorbidities than those without CDI (CCI scores: 4.6 ± 2.8 in CDI vs 3.2 ± 2.4 in non-CDI groups, P< 0.001; Additional file 1: Table S1). The hospitalization burden among those with CDI within the preceding 1 year (64.8% vs 32.4%, P< 0.001) or 90 days (43.2% vs 10.9%, P< 0.001) was significantly higher compared to residents without CDI. After propensity score matching (PSM), 653 residents with an incident CDI episode and 2,612 residents without a CDI episode were compared for the secondary objectives.

Mortality During the 12-month follow-up period, the 30-day (14.7% vs 4.3%, P< 0.001) mortality rate was significantly higher among the propensity score (PS)-matched CDI residents as compared to the PS-matched non-CDI resi- dents, so are mortality rates at 60-day, 6-month and 1- year follow up (Fig. 1).

Health care utilization Among Medicare-covered claims, during the 2-month follow-up period, the number of inpatient claims was significantly higher among PS-matched CDI residents compared to PS-matched non-CDI residents (0.66 vs 0.13, P< 0.001). Similarly, the number of skilled nursing facility (SNF) and carrier claims was significantly higher among PS-matched CDI residents. Among the Medicaid covered claims, the number of inpatient claims was sig- nificantly higher among PS-matched CDI residents as compared to PS-matched non-CDI residents (0.23 vs 0.08, P< 0.001); however, the number of pharmacy claims was significantly higher in the PS-matched non- CDI cohort as compared to the PS-matched CDI cohort (2.37 vs 1.74, p< 0.001; Table 3). Health care costs For Medicare covered expenses, inpatient costs ($9,678 vs $1,435, P< 0.001), SNF claims ($4,939 vs $1,452, P< 0.001), carrier claims ($2,463 vs $835, P< 0.001), and total costs ($18,993 vs $5,716, P< 0.001) during the 2- month follow-up period were significantly higher among CDI residents compared to non-CDI residents. For Medicaid-covered expenses, inpatient stay costs ($2,715 vs $316, P< 0.001) were significantly higher among those with CDI during the 2-month follow-up period (Table 3).

After summing all these costs from Medicare and Medicaid, inpatient stays represented the highest incre- mental cost increase ($10,642) followed by SNF costs. Table 1 Incidence Rate of CDI Stratified by Age, Sex, Race, and Region Incident CDI Cases per 100,000 Person-yearsof Observation #of CDI Residents per100,000 Person-yearsof Observation Overall 3752.7 3359.9 Incidence by Age Group 65–74 4247.5 3792.4 75–84 4048.1 3598.3 85 and older 3414.9 3075.5 Incidence by Sex Male 4339.3 3789.2 Female 3573.8 3229.0 Incidence by Race White 3614.2 3244.5 Black 4252.8 3750.9 Other 4583.6 4118.6 Incidence by Region Northeast 4641.1 4188.6 Midwest 3306.8 2941.6 South 3507.0 3170.4 West 3657.0 2904.1 CDI Clostridium difficile infection Yu et al. BMC Geriatrics (2016) 16:193 Page 3 of 7 The total CDI-attributable costs equaled $14,977, and most of these incremental costs were paid by Medicare.

Discussion This study estimated the burden of CDI among nursing home residents. To our knowledge, this is the first study to estimate the health care costs and utilization associ- ated with each CDI episode in this elderly population. We reported an incidence rate of 3,753 cases per 100,000 person-years (1.03 cases per 10,000 resident days), and 3,360 CDI patients per 100,000 person-years among nursing home residents. A study conducted by Kim et al. reported that the yearly incidence rate of LTC-associated CDI increased from 0.4 cases per 10,000 person-years in 2008 to 0.8 cases per 10,000 person- years in 2009 [1]. According to the results from another study conducted in 2010, the incidence rate of CDI in nursing homes was 2.3 cases per 10,000 resident days [16]. These results suggest a persistent increasing trend of CDI incidence among the nursing home residents in recent years. The emergence of new, severe, and hyper- virulent epidemic strains of C. difficile over the past years has particularly affected older adults and played a role in the increasing CDI rates [17].

Previous literature has noted the increased incidence of CDI; however, the majority of these studies focused on acute care settings [7, 10, 18]. Besides hospitalized patients, a trend of increased CDI incidence has been observed in nursing homes and communities [8, 19].

CDI outbreaks have been reported in nursing facilities since 1986 [5]. An influx of CDI in nursing homes from Table 2 Baseline Demographic Characteristics Between CDI and Non-CDI Residents Before and After PSM Unmatched Groups 1:4 PSM-Matched Groups Non-CDI Residents CDI Residents Non-CDI Residents CDI Residents (N= 30258) ( N= 789) (N= 2612) ( N= 653) N/Mean % N/Mean % P-value Std. Diff. N/Mean % N/Mean % P-value Std. Diff. Age (mean ± SD) 83.6 ± 9.3 83.1 ± 8.8 0.1103 5.6 83.5 ± 9.1 83.6 ± 8.7 0.9206 0.4 65–74 5979 19.8% 156 19.8% 0.9934 0.0 501 19.2% 116 17.8% 0.4082 3.6 75–84 8541 28.2% 237 30.0% 0.2648 4.0 770 29.5% 200 30.6% 0.5657 2.5 85 or older 15738 52.0% 396 50.2% 0.3117 3.6 1341 51.3% 337 51.6% 0.9025 0.5 Gender Female 23020 76.1% 585 74.1% 0.2089 4.5 1946 74.5% 498 76.3% 0.3535 4.1 Region Northeast 8610 28.5% 285 36.1% <0.001 16.4 895 34.3% 230 35.2% 0.6453 2.0 Midwest 10375 34.3% 219 27.8% 0.0001 14.2 739 28.3% 185 28.3% 0.9845 0.1 South 10239 33.8% 261 33.1% 0.6563 1.6 905 34.6% 224 34.3% 0.8685 0.7 West 1033 3.4% 23 2.9% 0.4453 2.8 73 2.8% 14 2.1% 0.3557 4.2 Race/Ethnicity White 24337 80.4% 612 77.6% 0.0455 7.0 2065 79.1% 527 80.7% 0.3523 4.1 Black 4198 13.9% 128 16.2%% 0.06 6.6 392 15.0% 92 14.1%% 0.5545 2.6 Other 1723 5.7% 49 6.2% 0.5373 2.2 155 5.9% 34 5.2% 0.4765 3.2 Insurance Type Medicare only 5812 19.2% 151 19.1% 0.9607 0.2 460 17.6% 129 19.8% 0.2025 5.5 Medicaid only 5221 17.3% 112 14.2% 0.0245 8.4 366 14.0% 84 12.9% 0.4463 3.4 Medicare and Medicaid dual 19225 63.5% 526 66.7% 0.0712 6.6 1786 68.4% 440 67.4% 0.6252 2.1 CDI Clostridium difficile infection, SDstandard deviation; Std. Diff standardized difference, PSM propensity score matching Fig. 1 Adjusted 12-month Follow-up Mortality After the Index date Between Non-CDI and CDI Residents. CDI: C. difficile infection Yu et al. BMC Geriatrics (2016) 16:193 Page 4 of 7 acute care may lead to subsequent transmission within the facility, leading to an overall increase in nursing home CDI rates. Residents may also acquire CDI during their stay at the nursing home, adding to the increased incidence rate [1]. Several factors may have contributed to the shift from primarily a hospital-acquired infection to a nursing home-acquired infection, such as an increase in the elderly population admitted to nursing home facilities, an increase in use of multiple medica- tions (especially antibiotics and proton pump inhibitors [PPIs]), and multiple comorbidities among the elderly population [8]. Because nursing home residents are one Table 3 Adjusted Utilization and Costs After the Initial CDI Diagnosis Between Non-CDI and CDI Residents Non-CDI Residents CDI Residents (N= 2,612) (N= 653) N/Mean %/SD N/Mean %/SD P-value Std diff 2- months Follow-up All-cause Health Care Utilization Medicare: Number of Claims # inpatient claims 0.13 0.41 0.66 0.88 <0.001 77.03 # outpatient claims 1.39 2.27 1.57 2.62 0.1039 7.42 # SNF claims 0.33 0.80 0.85 1.31 <0.001 47.96 # HSP claims 0.15 0.57 0.20 0.58 0.06 8.29 # HHA claims 0.01 0.10 0.00 0.06 0.181 4.90 # DME claims 0.26 0.87 0.34 1.00 0.0633 8.48 # carrier claims 5.33 5.60 10.17 9.57 <0.001 61.71 # pharmacy visits among those with ≥1 pharmacy visit 7.62 7.02 5.50 6.91 <0.001 30.37 Medicaid: Number of Claims # inpatient claims 0.08 0.40 0.23 0.56 <0.001 31.27 # long term care claims 3.01 4.28 2.50 4.53 0.0092 11.62 # Other therapy claims 3.82 7.88 6.10 9.57 <0.001 25.95 # pharmacy visits among those with ≥1 pharmacy visit 2.37 4.67 1.74 4.23 0.0009 14.17 2- months Follow-up All-cause Health Care Costs Medicare:

Overall Costs Inpatient stay costs $1435 $5664 $9678 $21206 <0.001 53.1 Outpatient costs $550 $1480 $527 $1292 0.6931 1.7 SNF costs $1452 $5049 $4939 $9091 <0.001 47.4 HSP costs $551 $2140 $610 $2202 0.5343 2.7 HHA costs $22 $474 $20 $391 0.918 0.4 DME costs $92 $412 $126 $457 0.0877 7.7 Carrier claims costs $835 $1882 $2463 $3677 <0.001 55.7 Pharmacy visit costs among those with ≥1 pharmacy visit $777 $914 $629 $963 0.0004 15.8 Total costs $5716 $10120 $18993 $27290 <0.001 64.5 Medicaid:

Overall Costs Inpatient stay costs $316 $2807 $2715 $14083 <0.001 23.6 Long term care costs $6738 $5526 $5141 $5740 <0.001 28.4 Other therapy costs $696 $2337 $1590 $17513 0.1935 7.2 Pharmacy visit costs among those with ≥1 pharmacy visit $178 $650 $183 $809 0.8855 0.7 Total costs $7928 $7088 $9628 $24163 0.0757 9.5 Combined Medicare/Medicaid costs $13644 $11362 $28621 $33532 <0.001 59.8 CDI Clostridium difficile infection, DME Durable Medical Equipment, HHA Home Health Agency, HSP , Hospital Specific Portion, SDstandard deviation, Std. Diff standardized difference, SNF Skilled Nursing Facility Yu et al. BMC Geriatrics (2016) 16:193 Page 5 of 7 of the groups most vulnerable to CDI, preventative mea- sures are crucial to effectively prevent the disease. These include additional nursing care, meticulous hand hygiene, contact precautions, appropriate use of antimicrobials and future interventions, such as vaccines. Accompanied by a high increase in the incidence rate, high mortality associ- ated with CDI was also observed. Although there is limited data on long-term mortality, a few studies have assessed 30-day mortality [4, 19] and our 30-day mortality result (10.4%) is similar to these studies.

As the incidence of CDI continues to rise, health care costs and utilization related to CDI will have a tremen- dous impact on the health care system. Previous studies reported costs attributable to CDI ranging from $8,000 –$30,000 that vary with coexisting conditions [20]. However to our knowledge, no study has systemat- ically assessed healthcare costs and utilization associated with CDI in nursing homes where incidence of CDI is quickly growing. Our study is unique since it used a large data sample by linking Medicare, Medicaid, and MDS; examined total health care costs including in- patient, outpatient, SNF, and pharmacy costs; and pro- vided an overall picture of the costs among residents in a nursing home facility. Our study included both Medi- care and Medicaid covered claims and expenses. Medi- care covers relatively few LTC services, such as SNF and home health care [21, 22]. Over 60% of nursing home resident care, and an even higher percentage of long- term resident care, is paid for by state Medicaid pro- grams [23]. Thus, providing costs using both claims data offers more generalizable results, helps to better under- stand the true overall resource utilization, and indicates that CDI is associated with high health care costs, espe- cially among patients residing in nursing home facilities.

A few limitations should be noted for this study. We included both Medicare and Medicaid claims data, but a certain proportion of residents may have supplemental long-term care insurance such as Medigap plans to fill the ‘gaps ’that are not covered by Medicare plans. These direct medical costs were not captured in this study. The indirect costs, such as those associated with additional nursing care, cleaning, isolation, and possible transmis- sion to other patients, were also not accounted for in this study. Therefore, this study underestimates the true total burden of CDI among nursing home residents.

Given that Medicare and Medicaid data contain admin- istrative information from multiple inpatient and out- patient sources, under-reporting or misclassification of health outcomes of interest may occur. Since we required patients to have at least 2 MDS quarterly assessments, the sample consisted entirely of long-term stay residents. Patients who were in the nursing home for a short amount of time and were discharged were excluded from the study. Although the Medicare, Medicaid, and MDS datasets contain uniquely integrated data, its beneficiaries are considered a vulnerable population since they are older and have a higher disease burden. Our results demon- strated an inverse distribution of CDI incidence as the residents grew older. Few previous studies have also demonstrated such an inverse trend among nursing home residents; however, no explanations have been provided [24, 25]. To verify our findings, we did a sensi- tivity analysis to analyze the baseline CCI score and medical costs across the age strata. We found a similar inverse trend in which residents ≥85 years residing in nursing homes had a lower comorbidity score, health care utilization, and costs prior to the incident CDI compared to patients aged 65 –74 years and 75 –84 years. An explanation may be that older adults ( ≥85 years) are more likely to reside in a nursing home facility due to comorbid conditions and frailty, and younger seniors (65 –74) are more likely to reside in a nursing home fa- cility due to poor health and may experience increased health care exposures, putting them at a higher risk for CDI.

Conclusions Results from our study showed 3,753 cases per 100,000 person-years, 10.4% 30-day mortality, and $15,000 in expenditures per case. With 1.4 million people residing in nursing homes in the United States, [26, 27] we esti- mated that approximately 53,000 annual CDI cases were associated with 5,500 deaths and $800 million in costs among this population. These numbers suggest that C. difficile is endemic in nursing home facilities, and more effective disease prevention and infection control measures are warranted to prevent CDI and thus im- prove patient outcomes and reduce overall health care costs.

Additional file Additional file 1: Table S1. Clinical Characteristics and Health Care Utilizations Between Non-CDI and CDI Residents Before and After PSM. Table S1. includes the baseline clinical characteristics such as hospitalization, antibiotic use, and heart, musculoskeletal, neurological, and psychiatric conditions between the CDI and non-CDI residents beforeand after propensity score matching. CDI: Clostridium difficile infection; CCI: Charlson Comorbidity Index; CDS: Chronic Disease Score; MDS: MinimumData Set; SD: standard deviation; Std. Diff: standardized difference; PSM:Propensity score matching. (DOCX 34 kb) AbbreviationsCCI: Charlson Comorbidity Index; CDI: Clostridium difficile (C. difficile ) infection; FFS: Fee-for-service; ICD-9-CM: International Classification of Diseases, 9 th Revision, Clinical Modification; LTC: Long-term care; MDS: Minimum Data Set; NH: Nursing home; PPIs: Proton pump inhibitors; PS: Propensity score; PSM: Propensity score matching; SAS: Statistical Analysis System; SNF: Skillednursing facility Yu et al. BMC Geriatrics (2016) 16:193 Page 6 of 7 Acknowledgements The authors would like to thank Sulena Shrestha and Chris Haddlesey of STATinMED Research and Scott Vuocolo of Pfizer, Inc. for assistance with thewriting and editing of this manuscript. The editorial support was funded byPfizer, Inc.

Funding This study was funded by Pfizer, Inc. Pfizer, Inc. participated in the design of the study, the interpretation of data, and in writing the manuscript.

Availability of data and material The dataset supporting the conclusions this article is available from The Centers for Medicare and Medicaid Services (CMS); however, restrictionsapply to the availability of these data, which were used under license for thecurrent study, and so are not publicly available.

Authors ’contributions All authors (HY, LW and OB) conceived of the study design. All authors (LW, HY and OB) analyzed and interpreted the data. All authors (HY, LW and OB) contributed to the writing of this manuscript. All authors (HY, LWand OB) read and approved the final manuscript.

Competing interests HY is an employee of Pfizer Inc., the study sponsor. LW and OB areemployees of STATinMED Research, which is a paid consultant to Pfizer Inc.

Consent for publication Not applicable.

Ethics approval and consent to participate Since the core study proposed herein did not involve the collection, use ortransmittal of individual identifiable data, Institutional Review Board (IRB) approval to conduct this study was not required. The security of the data meets the requirements of the Health Insurance Portability andAccountability Act (HIPAA) of 1996. The study protocol was reviewed anddetermined to be exempt from the Office for Human Research Protections (OHRP ’s) Regulations for the Protection of Human Subjects (45 CFR 46) under the following category: Exemption 4: Research involving the collection or study of existing data, documents, records, pathological specimens, ordiagnostic specimens, if these sources are publicly available or if the information is recorded by the investigator in such a manner that subjects cannot be identified, directly or through identifiers linked to the subjects.

Author details1Pfizer Inc, Arcola Road, Collegeville, PA 19426, USA. 2Center for Innovation & Outcomes Research, Department of Surgery, Columbia University, New York, NY, USA. 3STATinMED Research, New York, NY, USA. 4STATinMED Research, Plano, TX, USA.

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