- Email: [email protected]
NATIONAL ESTIMATES OF POTENTIALLY AVOIDABLE HOSPITALIZATIONS AMONG MEDICARE BENEFICIARIES WITH ALZHEIMER’S DISEASE AND RELATED DEMENTIAS
Podium Presentations: Monday, July 25, 2016 O2-10-06
A COMMON ALLELE IN SPI1 LOWERS RISK AND DELAYS AGE AT ONSET FOR ALZHEIMER’S DISEASE
Kuan-Lin Huang1, Sheng Chih Jin2, Oscar Harari1, Manav Kapoor3, Sarah Bertelsen3, Jake Czajkowski1, jean-Charles Lambert4, Vincent Chouraki5, Celine Bellenguez4, Benjamin Grenier-Boley4, Yuetiva Deming6, Andrew McKenzie3, Alan E. Renton3, John Budde6, Jorge L. Del-Aguila6, Maria Victoria Fernandez1, Laura Ibanez1, Denise Harold7, Paul Hollingworth7, Richard Mayeux8, Jonathan L. Haines9, Lindsay A. Farrer10, Margaret A. Pericak-Vance11, Sudha Seshadri5, Julie Williams12, Philippe Amouyel4, Gerard D. Schellenberg13, Bin Zhang3, Ingrid Borecki1, John Kauwe14, Eduardo Marcora3, Carlos Cruchaga1, Alison M. Goate3, The Alzheimer’s Disease Neuroimaging Initiative, 1Washington University in St. Louis, Saint Louis, MO, USA; 2Yale University, New Haven, CT, USA; 3Icahn School of Medicine at Mount Sinai, New York, NY, USA; 4Institut Pasteur de Lille, Lille, France; 5Boston University School of Medicine, Boston, MA, USA; 6 Washington University School of Medicine, Saint Louis, MO, USA; 7 Cardiff University, Cardiff, United Kingdom; 8Columbia University, New York, NY, USA; 9Case Western Reserve University, Cleveland, OH, USA; 10 Boston University, Boston, MA, USA; 11University of Miami, Miller School of Medicine, Miami, FL, USA; 12MRC Centre for Neuropsychiatric Genetics & Genomics, Institute of Psychological Medicine and Clinical Neurosciences, Cardiff University, Cardiff, United Kingdom; 13University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA; 14 Brigham Young University, Provo, UT, USA. Contact e-mail: kuan-lin. [email protected] Background: The age at onset of late-onset Alzheimer’s disease
(AD) spans at least 4 decades but its modifying genetic factors remain largely unknown. Methods: We conducted a genome-wide survival analysis on 39,855 samples of European ancestry from the International Genomics of Alzheimer’s Project (IGAP) Consortium to discover genetic variants associated with age at onset. We then validated the suggestive locus through CSF biomarker associations, and further investigated the underlying mechanisms with eQTL and gene expression analysis. Results: Rs1057233, located in a previously reported AD risk locus near CELF1/SPI1, was associated with lower age at onset (p¼8.3x10-6), higher cerebrospinal fluid Ab42 levels (p¼1.2x10-4), and lower expression of SPI1 in human monocytes (p¼6.39x10-102). SPI1, a transcription factor involved in myeloid and B-lymphoid cell differentiation and function, is co-expressed with multiple known AD microglial expressed genes including TYROBP, MS4A4A and CD33, and binds to the DNA at these loci. Conclusions: We nominate SPI1 as a new AD risk gene that affect CSF abeta and age at onset of AD. Therapeutics that lower SPI1 levels or modulate genes downstream of SPI1 may be effective in reducing risk for AD.
MONDAY, JULY 25, 2016 ORAL SESSIONS O2-11 HEALTH ECONOMICS AND POLICY: UNDERSTANDING AND MODELING HEALTH ECONOMICS O2-11-01
NATIONAL ESTIMATES OF POTENTIALLY AVOIDABLE HOSPITALIZATIONS AMONG MEDICARE BENEFICIARIES WITH ALZHEIMER’S DISEASE AND RELATED DEMENTIAS
Pei-Jung Lin1, Pallavi B. Rane1, Howard M. Fillit2, Joshua T. Cohen1, Peter J. Neumann1, 1Tufts Medical Center, Boston, MA, USA; 2The Alzheimer’s Drug Discovery Foundation, New York, NY, USA. Contact e-mail: [email protected]
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Background: Alzheimer’s disease and related dementias (ADRD) can complicate management of some comorbidities, putting patients at high risk for hospitalizations that may be preventable with proactive ambulatory care. Methods: Using Medicare claims data, we identified 2,749,172 fee-for-service beneficiaries aged 65 who were continuously enrolled in Medicare Parts A and B during 2013 and had a coded diagnosis of ADRD. We measured ADRD patients’ potentially avoidable hospitalization (PAH) rates for Ambulatory Care Sensitive Conditions, as defined by the Agency for Healthcare Research and Quality, and the associated Medicare expenditures. We examined PAHs for acute (i.e., bacterial pneumonia, urinary tract infection and dehydration) and chronic conditions (i.e., diabetes, cardiovascular diseases and respiratory conditions), and overall composite PAH rates. Results: In 2013, one in ten ADRD patients had at least one PAH, and one in seven (14%) hospital admissions among ADRD patients was for a potentially avoidable condition. We identified 369,165 PAHs (13,428 hospitalizations per 100,000 population) in the ADRD population, totaling $2.58 billion in Medicare expenditures. Of these hospitalizations, 188,870 were for acute conditions, accounting for 47% of overall PAH costs; 180,307 hospitalizations were for chronic conditions, representing 53% of total PAH costs. Of the 280,547 ADRD patients with any PAHs, 50% were classified as having late-stage disease. Patients with advanced ADRD had a substantial number of PAHs (32,027 hospitalizations for acute conditions and 25,106 hospitalizations for chronic conditions, per 100,000 population). Late-stage ADRD patients accounted for 59% ($1.53 billion) of the total PAH costs in the ADRD population. Late-stage ADRD and multiple chronic comorbidities were significantly associated with PAHs, after adjusting for other patient characteristics. Conclusions: Our findings suggest that comorbidity management remains suboptimal among many ADRD patients, especially those with advanced ADRD. In 2013, as many as 369,165 hospital stays and $2.58 billion in Medicare Table 1 Rates of Potentially Avoidable Hospitalizations for Ambulatory Care Sensitive Conditions among Medicare ADRD Beneficiaries, 2013 PQI Measure Overall Composite Acute Conditions Infectious conditions Bacterial Pneumonia Urinary Tract Infection Other Dehydration Chronic Conditions Diabetes Diabetes Short term Diabetes Long term Diabetes Uncontrolled Lower Extremity Amputation Cardiovascular diseases Hypertension Heart failure Angina Respiratory conditions
Total # of discharges
Rates per 100,000 population
369,165 188,870 142,654 64,470 78,184
13,428 6,870 5,189 2,345 2,844
46,216 180,307 24,383 3,415 16,430 2,485 3,237 99,375 10,980 86,843 1,552 56,561
1,681 6,559 887 124 598 90 118 3,615 399 3,159 56 2,057
NOTE: Rates indicate admissions per 100,000 population. The numerator was number of discharges for the study population, which met the inclusion and exclusion rules for each measure. The denominator was total number of eligible ADRD beneficiaries (n¼2,749,172)* 100,000. This study population had a total of 2,696,129 discharges (including long stays, short stays, and SNF stays).
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Podium Presentations: Monday, July 25, 2016
Table 2 Medicare inpatient expenditures for potentially avoidable hospitalizations (PAHs) among ADRD beneficiaries, 2013 Mean Medicare expenditures per PAH (s.d.) # of PAHs Medicare expenditures % of the total Medicare PAH expenditures Overall composite $6,979 ($5,671) Acute conditions $6,431 ($4,899) Infectious conditions $6,558 ($5,136) Dehydration $6,042 ($4,058) Chronic conditions $7,554 ($6,331) Diabetes $10,048 ($10,142) Cardiovascular diseases $7,465 ($5,417) Respiratory conditions $6,639 ($5,336)
costs incurred by ADRD patients could have been prevented with better ambulatory care and effective treatment. Complex case management programs for ADRD patients should involve strategies to reduce PAHs in order to improve patient outcomes and lower costs. O2-11-02
COMPARISON OF ALL-CAUSE MORTALITY RATE AND ECONOMIC BURDEN BETWEEN NEWLY DIAGNOSED ALZHEIMER’S DISEASE PATIENTS WHO RECEIVED ANTI-DEMENTIA TREATMENT VERSUS NOT: A LONGITUDINAL RETROSPECTIVE STUDY
Christopher M. Black1, Xiaohan Hu1,2, Rezaul Karim Khandker1, Baishali M. Ambegaonkar1, Furaha Kariburyo3, Lin Xie3, Onur Baser3,4, Huseyin Yuce3,5, 1Merck&Co., Inc., Kenilworth, NJ, USA; 2Temple University, Philadelphia, PA, USA; 3STATinMED Research, Ann Arbor, MI, USA; 4Center for Innovation & Outcomes Research, Department of Surgery, New York, NY, USA; 5New York City College of Technology, Brooklyn, NY, USA. Contact e-mail: [email protected] Background: Few studies have evaluated all-cause mortality and
economic burden of treated versus untreated patients newly diagnosed with Alzheimer’s disease (AD) in the U.S. This study examined all-cause mortality rates and burden of illness among incident AD patients. Methods: Patients with 1 primary or 2 secondary AD diagnoses claims [International Classification of Disease, 9th Revision Clinical Modification (ICD-9-CM) code 331.0] were identified from Medicare fee-for-service claims from 01JAN2011–30JUN2013. Study sample included Medicare beneficiaries age 65-100 years with continuous medical and pharmacy
369,165 188,870 142,654 46,216 180,307 24,383 99,375 56,561
$2.58 B $1.22 B $0.93 B $0.27 B $1.36 B $0.24 B $0.74 B $0.37 B
100% 47% 36% 11% 53% 9% 29% 15%
benefits for 12 months pre-index (baseline period) and 6 months post-index date (first AD diagnosis date). Patients were followed until the earliest of death, disenrollment or 31DEC2013 (followup period). Patients were assigned to Treated and Non-treated cohorts based on anti-dementia treatment received post-index date. Mortality incidence rate (100 person-years), healthcare costs and utilizations were evaluated post-index date. One-to-one propensity score matching (PSM) used to adjust for baseline differences between the study cohorts. Time-to-death was assessed using Kaplan-Meir curve and Cox regression over PSM-matched population. Results: A total of 6,553 incident AD patients were identified, mostly female (74.22%) between 75-84 years (39.72%). Patients received anti-dementia medication (N¼2,322; 35%) on average 34 days post-AD diagnosis; mean follow-up days for treated and untreated patients was 611.18 vs. 592.40, p<0.0055. Treated patients received donepezil (66.86%), memantine (18.59%), rivastigmine (12.54%) and galantamine (2.02%) as their first treatment. Untreated patients were older (83.85 vs. 81.44 years, p<0.0001), with more severe baseline comorbidities (Mean Charlson comorbidity index: 3.54 vs. 3.20, p<0.0001) and high unadjusted incidence rate of death (17.36 vs. 10.00 ; in 100 personyears, p<0.0001). After 1:1 PSM, 694 patients with well-balanced baseline characteristics were matched from treated and untreated cohorts. Treated AD patients had better survival (Hazard ratio¼ 0.722, p¼ 0.0079), less monthly hospice visits (0.04 vs.0.09, p¼0.0001), and lower monthly all-cause cost ($2,207 vs. $2,349, p¼ 0.3037) compared to untreated patients. Conclusions: Newly diagnosed AD patients who did not receive anti-dementia treatment were older patients with more severe comorbidities. Even after adjusting for demographic and clinical differences, results suggested that treated AD patients had lower all-cause healthcare costs and lower mortality rates compared to untreated patients. O2-11-03
SIMULATION STUDY ON THE EFFECT OF EARLY TREATMENT WITH A HYPOTHETICAL DISEASE MODIFYING THERAPY (DMT) ON TIME IN INSTITUTIONAL CARE FOR PATIENTS WITH ALZHEIMER’S DISEASE
Ali Tafazzoli1, Rodrigo DosSantos1, K Jack Ishak2, Stanimira Krotneva2, Anuraag R. Kansal1, 1Evidera, Bethesda, MD, USA; 2Evidera, Montreal, QC, Canada. Contact e-mail: [email protected] Background: A key potential benefit of DMT for AD is the delay or
Figure 1. Kaplan-Meier Curve for Time-to-Death based on PSM-Matched Population
avoidance of the need for institutional care. This outcome, however, is difficult to assess in a trial setting, particularly for early treatment, but can be investigated using a simulation that can follow patients over their remaining lifetimes. We sought to evaluate the potential impact of early treatment on the need for institutional
A COMMON ALLELE IN SPI1 LOWERS RISK AND DELAYS AGE AT ONSET FOR ALZHEIMER’S DISEASE
Kuan-Lin Huang1, Sheng Chih Jin2, Oscar Harari1, Manav Kapoor3, Sarah Bertelsen3, Jake Czajkowski1, jean-Charles Lambert4, Vincent Chouraki5, Celine Bellenguez4, Benjamin Grenier-Boley4, Yuetiva Deming6, Andrew McKenzie3, Alan E. Renton3, John Budde6, Jorge L. Del-Aguila6, Maria Victoria Fernandez1, Laura Ibanez1, Denise Harold7, Paul Hollingworth7, Richard Mayeux8, Jonathan L. Haines9, Lindsay A. Farrer10, Margaret A. Pericak-Vance11, Sudha Seshadri5, Julie Williams12, Philippe Amouyel4, Gerard D. Schellenberg13, Bin Zhang3, Ingrid Borecki1, John Kauwe14, Eduardo Marcora3, Carlos Cruchaga1, Alison M. Goate3, The Alzheimer’s Disease Neuroimaging Initiative, 1Washington University in St. Louis, Saint Louis, MO, USA; 2Yale University, New Haven, CT, USA; 3Icahn School of Medicine at Mount Sinai, New York, NY, USA; 4Institut Pasteur de Lille, Lille, France; 5Boston University School of Medicine, Boston, MA, USA; 6 Washington University School of Medicine, Saint Louis, MO, USA; 7 Cardiff University, Cardiff, United Kingdom; 8Columbia University, New York, NY, USA; 9Case Western Reserve University, Cleveland, OH, USA; 10 Boston University, Boston, MA, USA; 11University of Miami, Miller School of Medicine, Miami, FL, USA; 12MRC Centre for Neuropsychiatric Genetics & Genomics, Institute of Psychological Medicine and Clinical Neurosciences, Cardiff University, Cardiff, United Kingdom; 13University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA; 14 Brigham Young University, Provo, UT, USA. Contact e-mail: kuan-lin. [email protected] Background: The age at onset of late-onset Alzheimer’s disease
(AD) spans at least 4 decades but its modifying genetic factors remain largely unknown. Methods: We conducted a genome-wide survival analysis on 39,855 samples of European ancestry from the International Genomics of Alzheimer’s Project (IGAP) Consortium to discover genetic variants associated with age at onset. We then validated the suggestive locus through CSF biomarker associations, and further investigated the underlying mechanisms with eQTL and gene expression analysis. Results: Rs1057233, located in a previously reported AD risk locus near CELF1/SPI1, was associated with lower age at onset (p¼8.3x10-6), higher cerebrospinal fluid Ab42 levels (p¼1.2x10-4), and lower expression of SPI1 in human monocytes (p¼6.39x10-102). SPI1, a transcription factor involved in myeloid and B-lymphoid cell differentiation and function, is co-expressed with multiple known AD microglial expressed genes including TYROBP, MS4A4A and CD33, and binds to the DNA at these loci. Conclusions: We nominate SPI1 as a new AD risk gene that affect CSF abeta and age at onset of AD. Therapeutics that lower SPI1 levels or modulate genes downstream of SPI1 may be effective in reducing risk for AD.
MONDAY, JULY 25, 2016 ORAL SESSIONS O2-11 HEALTH ECONOMICS AND POLICY: UNDERSTANDING AND MODELING HEALTH ECONOMICS O2-11-01
NATIONAL ESTIMATES OF POTENTIALLY AVOIDABLE HOSPITALIZATIONS AMONG MEDICARE BENEFICIARIES WITH ALZHEIMER’S DISEASE AND RELATED DEMENTIAS
Pei-Jung Lin1, Pallavi B. Rane1, Howard M. Fillit2, Joshua T. Cohen1, Peter J. Neumann1, 1Tufts Medical Center, Boston, MA, USA; 2The Alzheimer’s Drug Discovery Foundation, New York, NY, USA. Contact e-mail: [email protected]
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Background: Alzheimer’s disease and related dementias (ADRD) can complicate management of some comorbidities, putting patients at high risk for hospitalizations that may be preventable with proactive ambulatory care. Methods: Using Medicare claims data, we identified 2,749,172 fee-for-service beneficiaries aged 65 who were continuously enrolled in Medicare Parts A and B during 2013 and had a coded diagnosis of ADRD. We measured ADRD patients’ potentially avoidable hospitalization (PAH) rates for Ambulatory Care Sensitive Conditions, as defined by the Agency for Healthcare Research and Quality, and the associated Medicare expenditures. We examined PAHs for acute (i.e., bacterial pneumonia, urinary tract infection and dehydration) and chronic conditions (i.e., diabetes, cardiovascular diseases and respiratory conditions), and overall composite PAH rates. Results: In 2013, one in ten ADRD patients had at least one PAH, and one in seven (14%) hospital admissions among ADRD patients was for a potentially avoidable condition. We identified 369,165 PAHs (13,428 hospitalizations per 100,000 population) in the ADRD population, totaling $2.58 billion in Medicare expenditures. Of these hospitalizations, 188,870 were for acute conditions, accounting for 47% of overall PAH costs; 180,307 hospitalizations were for chronic conditions, representing 53% of total PAH costs. Of the 280,547 ADRD patients with any PAHs, 50% were classified as having late-stage disease. Patients with advanced ADRD had a substantial number of PAHs (32,027 hospitalizations for acute conditions and 25,106 hospitalizations for chronic conditions, per 100,000 population). Late-stage ADRD patients accounted for 59% ($1.53 billion) of the total PAH costs in the ADRD population. Late-stage ADRD and multiple chronic comorbidities were significantly associated with PAHs, after adjusting for other patient characteristics. Conclusions: Our findings suggest that comorbidity management remains suboptimal among many ADRD patients, especially those with advanced ADRD. In 2013, as many as 369,165 hospital stays and $2.58 billion in Medicare Table 1 Rates of Potentially Avoidable Hospitalizations for Ambulatory Care Sensitive Conditions among Medicare ADRD Beneficiaries, 2013 PQI Measure Overall Composite Acute Conditions Infectious conditions Bacterial Pneumonia Urinary Tract Infection Other Dehydration Chronic Conditions Diabetes Diabetes Short term Diabetes Long term Diabetes Uncontrolled Lower Extremity Amputation Cardiovascular diseases Hypertension Heart failure Angina Respiratory conditions
Total # of discharges
Rates per 100,000 population
369,165 188,870 142,654 64,470 78,184
13,428 6,870 5,189 2,345 2,844
46,216 180,307 24,383 3,415 16,430 2,485 3,237 99,375 10,980 86,843 1,552 56,561
1,681 6,559 887 124 598 90 118 3,615 399 3,159 56 2,057
NOTE: Rates indicate admissions per 100,000 population. The numerator was number of discharges for the study population, which met the inclusion and exclusion rules for each measure. The denominator was total number of eligible ADRD beneficiaries (n¼2,749,172)* 100,000. This study population had a total of 2,696,129 discharges (including long stays, short stays, and SNF stays).
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Podium Presentations: Monday, July 25, 2016
Table 2 Medicare inpatient expenditures for potentially avoidable hospitalizations (PAHs) among ADRD beneficiaries, 2013 Mean Medicare expenditures per PAH (s.d.) # of PAHs Medicare expenditures % of the total Medicare PAH expenditures Overall composite $6,979 ($5,671) Acute conditions $6,431 ($4,899) Infectious conditions $6,558 ($5,136) Dehydration $6,042 ($4,058) Chronic conditions $7,554 ($6,331) Diabetes $10,048 ($10,142) Cardiovascular diseases $7,465 ($5,417) Respiratory conditions $6,639 ($5,336)
costs incurred by ADRD patients could have been prevented with better ambulatory care and effective treatment. Complex case management programs for ADRD patients should involve strategies to reduce PAHs in order to improve patient outcomes and lower costs. O2-11-02
COMPARISON OF ALL-CAUSE MORTALITY RATE AND ECONOMIC BURDEN BETWEEN NEWLY DIAGNOSED ALZHEIMER’S DISEASE PATIENTS WHO RECEIVED ANTI-DEMENTIA TREATMENT VERSUS NOT: A LONGITUDINAL RETROSPECTIVE STUDY
Christopher M. Black1, Xiaohan Hu1,2, Rezaul Karim Khandker1, Baishali M. Ambegaonkar1, Furaha Kariburyo3, Lin Xie3, Onur Baser3,4, Huseyin Yuce3,5, 1Merck&Co., Inc., Kenilworth, NJ, USA; 2Temple University, Philadelphia, PA, USA; 3STATinMED Research, Ann Arbor, MI, USA; 4Center for Innovation & Outcomes Research, Department of Surgery, New York, NY, USA; 5New York City College of Technology, Brooklyn, NY, USA. Contact e-mail: [email protected] Background: Few studies have evaluated all-cause mortality and
economic burden of treated versus untreated patients newly diagnosed with Alzheimer’s disease (AD) in the U.S. This study examined all-cause mortality rates and burden of illness among incident AD patients. Methods: Patients with 1 primary or 2 secondary AD diagnoses claims [International Classification of Disease, 9th Revision Clinical Modification (ICD-9-CM) code 331.0] were identified from Medicare fee-for-service claims from 01JAN2011–30JUN2013. Study sample included Medicare beneficiaries age 65-100 years with continuous medical and pharmacy
369,165 188,870 142,654 46,216 180,307 24,383 99,375 56,561
$2.58 B $1.22 B $0.93 B $0.27 B $1.36 B $0.24 B $0.74 B $0.37 B
100% 47% 36% 11% 53% 9% 29% 15%
benefits for 12 months pre-index (baseline period) and 6 months post-index date (first AD diagnosis date). Patients were followed until the earliest of death, disenrollment or 31DEC2013 (followup period). Patients were assigned to Treated and Non-treated cohorts based on anti-dementia treatment received post-index date. Mortality incidence rate (100 person-years), healthcare costs and utilizations were evaluated post-index date. One-to-one propensity score matching (PSM) used to adjust for baseline differences between the study cohorts. Time-to-death was assessed using Kaplan-Meir curve and Cox regression over PSM-matched population. Results: A total of 6,553 incident AD patients were identified, mostly female (74.22%) between 75-84 years (39.72%). Patients received anti-dementia medication (N¼2,322; 35%) on average 34 days post-AD diagnosis; mean follow-up days for treated and untreated patients was 611.18 vs. 592.40, p<0.0055. Treated patients received donepezil (66.86%), memantine (18.59%), rivastigmine (12.54%) and galantamine (2.02%) as their first treatment. Untreated patients were older (83.85 vs. 81.44 years, p<0.0001), with more severe baseline comorbidities (Mean Charlson comorbidity index: 3.54 vs. 3.20, p<0.0001) and high unadjusted incidence rate of death (17.36 vs. 10.00 ; in 100 personyears, p<0.0001). After 1:1 PSM, 694 patients with well-balanced baseline characteristics were matched from treated and untreated cohorts. Treated AD patients had better survival (Hazard ratio¼ 0.722, p¼ 0.0079), less monthly hospice visits (0.04 vs.0.09, p¼0.0001), and lower monthly all-cause cost ($2,207 vs. $2,349, p¼ 0.3037) compared to untreated patients. Conclusions: Newly diagnosed AD patients who did not receive anti-dementia treatment were older patients with more severe comorbidities. Even after adjusting for demographic and clinical differences, results suggested that treated AD patients had lower all-cause healthcare costs and lower mortality rates compared to untreated patients. O2-11-03
SIMULATION STUDY ON THE EFFECT OF EARLY TREATMENT WITH A HYPOTHETICAL DISEASE MODIFYING THERAPY (DMT) ON TIME IN INSTITUTIONAL CARE FOR PATIENTS WITH ALZHEIMER’S DISEASE
Ali Tafazzoli1, Rodrigo DosSantos1, K Jack Ishak2, Stanimira Krotneva2, Anuraag R. Kansal1, 1Evidera, Bethesda, MD, USA; 2Evidera, Montreal, QC, Canada. Contact e-mail: [email protected] Background: A key potential benefit of DMT for AD is the delay or
Figure 1. Kaplan-Meier Curve for Time-to-Death based on PSM-Matched Population
avoidance of the need for institutional care. This outcome, however, is difficult to assess in a trial setting, particularly for early treatment, but can be investigated using a simulation that can follow patients over their remaining lifetimes. We sought to evaluate the potential impact of early treatment on the need for institutional