Research and Reports Clinical, Behavioral, and Treatment Differences in Nursing Facility Residents with Dementia, with and without Pseudobulbar Affect Symptomatology Barbara J. Zarowitz, Terrence O’Shea Objectives: Characterize the prevalence and impact of crying and tearfulness as symptoms that may be suggestive of pseudobulbar affect (PBA) in residents of nursing facilities, including those with Alzheimer’s disease (AD) and non-AD [non-AD-associated] associated dementia. Design: Data were extracted retrospectively from a large repository of de-identified and linked Minimum Data Set 2.0 (MDS) and prescription claims records for the period between October 1, 2009, and September 30, 2010. A score of 1 or 2 on MDS item E1m (“crying, tearfulness”) was used to identify potential PBA. Setting: 19,000 nursing facilities in 48 states. Patients/Participants: Prescription and MDS records of nursing facility residents. Main Outcome Measures: Comparison of concomitant diagnoses, MDS mood, and behavioral indicators, and psychopharmacologic medication use, in residents with crying/tearfulness to a control group matched for age, gender, diagnosis of AD or non-AD dementia, and diagnosis of depression. Results: A total of 137,829 residents underwent at least one MDS assessment during the study period. Of these, 12,595 (9.1%) had item E1m (“crying, tearfulness”) scored as a 1 or 2 on their MDS assessments. Ten thousand residents were then randomly selected from this group and matched to 10,000 controls without “crying, tearfulness” (MDS E1m = 0) for analysis. A total of 4,786 (47.9%) unique residents with “crying, tearfulness” had a diagnosis of AD (8.8%), non-AD dementia (31.5%), or both (7.6%). All of the MDS mood indicators were at least twice as prevalent in this group compared with those without “crying, tearfulness” Additionally, mood symptoms such as anger, worried/pained facial expressions, and repetitive verbalizations; and behavioral symptoms such as verbal/physical abuse and socially inappropriate/
disruptive behavior, were more than twice as frequent in the “crying, tearfulness” group. Antipsychotic medications were also used more often in this group (50% vs. 36.1%), as were antidepressants (59.1% vs. 49.8%). Conclusions: In the absence of an International Classification of Diseases 9th edition, Clinical Modification code, the presence of “crying, tearfulness” on MDS 2.0 item E1m was used as a proxy to identify potential PBA. Nursing facility residents with “crying, tearfulness” had a higher prevalence of all mood and behavior indicators as well as psychopharmacological medication use, compared with matched controls without “crying, tearfulness.” Similar results were seen in the subgroup of residents with an underlying diagnosis of AD and/or non-AD dementia. Further research should validate the actual prevalence of PBA in this population, and the corresponding impact on resident outcomes. Key Words: Alzheimer’s disease, Brain injury, Crying, Longterm care, Nursing facility, Omnicare, Pseudobulbar affect. Abbreviations: AD = Alzheimer’s disease, ADL = Activities of daily living, ALS = Amyotrophic lateral sclerosis, ICD-9-CM = International Classification of Diseases 9th edition, Clinical Modification, MDS = Minimum Data Set, MS = Multiple sclerosis, OSHO = Omnicare Senior Health Outcomes, PBA = Pseudobulbar affect, PD = Parkinson’s disease. Consult Pharm 2013;28:713-22.
Introduction Pseudobulbar affect (PBA) is a neurological condition characterized by sudden, frequent, and involuntary episodes of crying or laughing that are disproportionate to environmental stimuli or the individual’s prevailing mood .1-3 PBA occurs secondary to a variety of different central nervous system insults such as multiple sclerosis (MS; prevalence, 7%), amyotrophic lateral sclerosis (ALS; prevalence, 15%-49%), stroke (prevalence, 4.3%-52%), traumatic brain injury (prevalence, 5%-16%), and Alzheimer’s disease (AD; prevalence, 10%-39%).4-12 PBA is thought to result from interruption of pathways between the cerebral cortex and cerebellum that coordinate and modulate appropriate emotional responses.3
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Research and Reports The prevalence of moderate-to-severe PBA in the United States has been estimated at between 1.5 and 2 million people.4,13 PBA is often mistaken for depression (although the two conditions can be comorbid). PBA crying episodes are brief, paroxysmal, disruptive, and out of proportion to the eliciting circumstance.3,13 Episodes typically last seconds to minutes, followed by a return to baseline functioning. In contrast, there are surprisingly little available data on prevalence, frequency, and characteristics of crying episodes in persons with major depression. While available studies support an overall relationship between depression and self-reported crying, this relationship is complex and not necessarily linear. In one of the only controlled studies to specifically evaluate depression and self-rated crying proneness, increased crying propensity was reported only in response to negative emotions (sadness and not happiness), and was not directly related to depression severity.14 In another study, evaluating crying in response to a tear-provoking stimulus (sad movie clip), no significant differences in crying propensity or severity were seen between depressed patients and nondepressed controls.15 Crying is not a criterion symptom of depression in the Diagnostic and Statistical Manual of Mental Disorders, 4th edition.16 Patients with depression may also exhibit inability to cry, apathy, or lack of expression. PBA is an under-recognized and undertreated neurological disorder. Because of their socially or contextually inappropriate nature, PBA episodes are often embarrassing or upsetting to patients and others around them.4 Given that neurological conditions such as stroke, AD, among others are prevalent in nursing facility residents, evaluation of the prevalence of PBA in this environment is of interest. At the time of this research, there was no diagnostic code for PBA; an International Classification of Diseases 9th edition, Clinical Modification (ICD-9-CM) diagnostic code for PBA was released in November 2011. The Minimum Data Set (MDS) is a comprehensive, standardized resident assessment instrument that is utilized in nursing facilities to develop care delivery and planning; monitor clinical indicators such as falls, fractures, cognition, and behavior; and for payment from Medicare. MDS assessment is
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conducted for all residents of nursing facilities upon admission, quarterly, annually, and when the resident has a significant change in status. Although MDS does not have an item field specific to PBA, version 2.0 of MDS has an item specific to crying and tearfulness that could be used as a proxy for PBA to allow a preliminary estimate of PBA symptoms: Section E (“Mood and Behavior Patterns”), part 1 (“Indicators of Depression, Anxiety, Sad Mood”), item m (“crying, tearfulness”) is scored as “0” not present, “1” (exhibited up to 5 days a week), or 2 (exhibited daily or almost daily). The MDS data elements have been validated, and there is evidence for inter-rater reliability.17 More than 85% of MDS data elements have been found to be reliable, with adequate inter-rater reliability and overall good agreement.17,18 The strongest reliability was with elements related to activities of daily living (ADL), e.g., bathing, eating, dressing. ADL, pain, distressed mood, behavioral disturbances, and social engagement elements of the MDS have manifested discriminate validity.19 Validity problems have been reported with MDS data elements of visual acuity, pain frequency and intensity, and resident incontinence.19 The instrument has been criticized by some, noting that data discrepancies occur as a result of miscoding. Agreement rates for a number of data elements have been reportedly poor, but reliability adequate when calculated using a weighted kappa statistic.19 While there are limitations to this caregiver-rated assessment instrument, it is a standardized tool that provides the “best available evidence” of resident status and outcomes in the long-term care setting. The objective of this study was to approximate the prevalence and impact of potential PBA (using “crying, tearfulness” on MDS item E1m as a proxy) in nursing facilities and to develop a basic profile of these residents, including, but not limited to, pertinent demographic information, concurrent diagnoses, the use of antipsychotic and antidepressant medications, and numerous behavioral and functional parameters, compared with a matched cohort of residents without “crying, tearfulness” (MDS item E1m score = 0).
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Methods After obtaining an exemption from institutional review board review and waiver of authorization from the Sterling Institutional Review Board, de-identified information for this study was extracted from Omnicare Senior Health Outcomes (OSHO) Data Warehouse of resident records (demographic and admission tables), resident MDS records, prescription records, drug data and prescriber specialty records, facility records, and prescriber records. Most of the data in the OSHO Data Warehouse are refreshed on a daily basis, with the exception of resident MDS records and Drug Data records (data dictionary). The real-time data are collected from about 175 pharmacies serving more than 1.4 million residents in about 19,000 long-term care and other health care facilities in 48 states.The database stores more than 600 million prescription claims processed within the last six years. All de-identified datasets carry a unique resident identification key that allows longitudinal tracking at the prescription claims level. The prescription data can be analyzed by National Drug Code, brand name, strength, dosage form, individual ingredient, and drug therapeutic class. MDS records are available for approximately 10%-15% of residents in facilities within the Omnicare network that use the AccuMed electronic MDS system. Within the OSHO data warehouse are two data sets: pharmacy claims data for residents in Omnicare-serviced nursing facilities and MDS data for residents in nursing facilities that are clients of Accu-Med’s electronic MDS application. Omnicare is the owner of the pharmacy claims data and a processor of the MDS data. To perform the MDS/pharmacy claims data match, prescription claims and MDS data were obtained from the OSHO data warehouse for the time period of October 1, 2009, through September 30, 2010. Once the two data sets were extracted, they were matched using resident demographics, and the matched records were de-identified using a “safe harbor” method—all 18 identifiable data elements listed in section 164.514(b)(2) of the Health Insurance Portability and Accountability Act privacy rule were removed and replaced with internal identifiers. The internal identifier is a randomly generated number that is not derived from
nor related to the information about the individual, and it is not otherwise capable of being translated to identify the individual. In addition, all internal identifiers were encrypted using a 128-bit, one-way hashing algorithm to further ensure that identifiers cannot be traced to individuals. Figure 1 depicts the resident selection algorithm for this study. Initially, a count of unique residents for whom MDS data existed in the database was obtained. This count served as the denominator for approximating the potential prevalence of PBA. It is important to reiterate that PBA is not listed as one of the “Disease Diagnoses” in section I of the MDS, nor was it represented by an ICD-9-CM code during the study period. Thus, a score of 1 (exhibited up to five days a week) or 2 (exhibited daily or almost daily) on MDS section E (“Mood and Behavior Patterns”), part 1 (“Indicators of Depression, Anxiety, Sad Mood”), item m (“crying, tearfulness”) was used as a proxy for PBA. A score of 0 on item E1m (indicator not exhibited in the last 30 days) was used as a proxy for absence of PBA. Following identification of nursing facility residents with “crying, tearfulness,” a propensity age-, gender-, diagnosis of depression-, and diagnosis of AD or non-AD dementia-matched group without “crying, tearfulness” was selected for comparison. Propensity or frequency matching avoids the need for a direct one-to-one match of each unique resident, but rather matches residents by age range such that there are the same number of residents within a given age range in each group. AD and non-AD dementia were expected to be a significant component of the total number of nursing facility residents with PBA symptomatology. To further understand differences between residents with and without “crying, tearfulness,” the total groups were subdivided to evaluate residents with AD and non-AD dementia with and without “crying, tearfulness.” The number of residents who had “crying, tearfulness” and for whom we had prescription-claims records was used as the denominator to determine the prevalence of PBA symptomatology-related medication utilization. We evaluated the presence of antidepressant and antipsychotic claims, given that these medications may be used
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Figure 1. Resident Selection Algorithm
During the study period, many residents had more than one MDS assessment completed. To avoid counting MDS data elements multiple times, if a resident had more than one MDS assessment during the study period, and had different answers for the same MDS data element, then the answer representing the more severe condition was used. For example, if a resident had two MDS assessments during the study period, and in one of these assessments MDS item J1n (“Unsteady gait”) was not checked (which indicated that the resident did not have “unsteady gait” in the look-back period), and in the other MDS assessment item J1n was checked (indicating that the resident did have “unsteady gait” during the look-back period), then the resident was considered to have “unsteady gait.” Descriptive statistics were performed for all data fields.
Results “Crying, Tearfulness” Prevalence The total number of unique residents with at least one MDS assessment during the study period was 137,829. Of those, a total of 12,595 unique residents had item E1m (“crying, tearfulness”) noted on their MDS assessments, resulting in a prevalence of symptoms suggestive of PBA of 9.1%. For simplicity, the term “PBA proxy group” will be used hereinafter to describe the group of residents with “crying and tearfulness” on MDS item E1m.
Abbreviations: AD = Alzheimer’s disease, MDS = Minimum Data Set. PBA = Pseudobulbar affect. Note: HCR Manorcare and SAVA are both nursing facility chains.
in residents with PBA symptomatology. Not all residents with “crying, tearfulness” received antidepressants or antipsychotics, despite having other prescription claims in the OSHO data warehouse. Additionally, not all residents with “crying, tearfulness” received their medications from an Omnicare pharmacy. Therefore, to calculate the percent of treated residents, the denominator of residents for whom pharmacy records are available was used.
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PBA Proxy Group, Overall Ten thousand residents randomly selected from the PBA proxy group were matched to 10,000 controls without MDS item E1m “crying, tearfulness.” Characteristics of this PBA proxy group and matched controls are shown in Table 1. The PBA proxy group (and matched controls) was predominantly female (82.1%); two-thirds (65.3%) were 75 years of age or older; one-third (35.1%) were 85 years of age or older. A total of 47.9% of the PBA proxy group had a diagnosis of AD, non-AD dementia, or both; and 65.5% had a diagnosis of depression. The sample was not matched for race. Residents were predominantly white. However, there was some disparity in the proportions of black residents (PBA proxy group 8.3% vs. controls 12.2%).
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Table 1. Characteristics of Nursing Facility Residents with “Crying, Tearfulness” and Propensity Matched Controlsa (N = 10,000) Characteristic
Matched Control Residents without ”Crying, Tearfulness” n (%)
Nursing Facility Residents with “Crying, Tearfulness” n (%)
MATCHED CHARACTERISTICS Gender Female Male
8,213 (82.1) 1,787 (17.9)
8,213 (82.1) 1,787 (17.9)
Age Category, Years < 65 65-69 70-74 75-79 80-84 85-89 ≥ 90
1,812 (18.1) 762 (7.6) 898 (9.0) 1,329 (13.3) 1,686 (16.9) 1,887 (18.9) 1,626 (16.3)
1,812 (18.1) 762 (7.6) 898 (9.0) 1,329 (13.3) 1,686 (16.9) 1,887 (18.9) 1,626 (16.3)
Diagnoses AD Non-AD Dementia Both AD and non-AD Dementia Depression
881 (8.8) 3,148 (31.5) 757 (7.6) 6,547 (65.5)
861 (8.6) 3,213 (32.1) 712 (7.1) 6,547 (65.5)
8,153 (81.5) 829 (8.3) 721 (7.2) 297 (3.0)
7,613 (76.1) 1,223 (12.2) 737 (7.4) 427 (4.3)
663 (6.6)
498 (5.0)
462 (4.6)
416 (4.2)
741 (7.4) 460 (4.6) 4,499 (45.0)
306 (3.1) 180 (1.8) 3,628 (36.3)
3,881 (38.8) 5,968 (59.7)
2,723 (27.2) 5,050 (50.5)
UNMATCHED CHARACTERISTICS Race/Ethnicity White Black Hispanic Other/unknown Psychiatric Diagnoses Manic depression (bipolar disorder) Schizophrenia Health Conditions Delusions Hallucinations Fall during preceding 30 Days Medication Useb Antipsychotics Antidepressants
As documented in Minimum Data Set 2.0 records. At least one prescription during the analysis period. Abbreviation: AD = Alzheimer’s disease. a b
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Figure 2. Prevalence of Mood Indicator and Behavioral Symptoms in Nursing Figure 2. Prevalence of Mood Indicator and Behavioral Symptoms in Nursing Home Residents with vs. without “Crying/tearfulness” Prevalence of Mood Indicator and Behavioral Symptoms in Nursing HomeResidents Residents With vs.Without “Crying, Tearfulness” Home with vs. without “Crying/tearfulness” Mood Indicatorsa
Behavioral Symptomsb
a b
Score of 1 or 2 on specified item in Minimum Data Set 2.0, section E1. Score of 1, 2, or 3 on specified item in Minimum Data Set 2.0, section E4.
All MDS mood indicators (section E1) and behavioral symptoms (section E4) showed greater prevalence in the PBA proxy group than in controls (Figure 2). The PBA proxy group was more likely than controls to be reported as having delusions (7.4% vs. 3.1%) or hallucinations (4.6% vs. 1.8%) and also more likely than controls to have prescription claims for antipsychotic medications (38.8% vs. 27.2%) or antidepressant (59.7% vs. 50.5%) medications. Notably, a greater proportion of the PBA proxy group had recorded falls during the preceding 30 days (45.0% vs. 36.3% of controls), and 16.9% had reported fractures (compared with 14.8% of controls).
PBA Proxy Group with Dementia Of the 10,000 residents in the PBA proxy group, 4,786 (47.9%) had a diagnosis of AD or non-AD dementia, or
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both. Like the overall sample, the PBA proxy group with dementia was predominantly female (83.4%) and had similar race distribution; however, these residents were older, with 81.5% 75 years of age or older, and 46.5% 85 years of age or older. A total of 3,362 (70.3%) of the PBA proxy group with dementia (and matched controls) had a diagnosis of depression (Table 2). In residents with dementia, as in the overall sample, all MDS mood indicators (section E1) showed greater prevalence in the PBA proxy group than in controls (Figure 3). The PBA proxy group with dementia was also more likely than matched controls to be reported as experiencing delusions (10.4% vs. 4.7%, respectively) or hallucinations (5.7% vs. 2.3%, respectively), and the overall prevalence of these symptoms was higher in residents with dementia (both PBA proxy and control groups) than for the full sample.
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Table 2. Characteristics of Nursing Facility Residents with Dementia, With vs. Without “Crying, Tearfulness”a (N = 4,786) Characteristic
Dementia Without “Crying/Tearfulness” n (%)
Dementia Plus “Crying/Tearfulness” n (%)
MATCHED CHARACTERISTICS Gender Female Male
3,992 (83.4) 794 (16.6)
3,992 (83.4) 794 (16.6)
Age Category, Years < 65 65-69 70-74 75-79 80-84 85-89 ≥ 90
302 (6.3) 212 (4.4) 371 (7.8) 664 (13.9) 1,011 (21.1) 1,151 (24.1) 1,075 (22.5)
302 (6.3) 212 (4.4) 371 (7.8) 664 (13.9) 1,011 (21.1) 1,151 (24.1) 1,075 (22.5)
Diagnoses AD Non-AD dementia Both AD and non-AD dementia Depression
881 (18.4) 3,148 (65.8) 757 (15.8) 3,362 (70.3)
861 (18.0) 3,213 (67.1) 712 (14.9) 3,362 (70.3)
3,898 (81.4) 382 (8.0) 393 (8.2) 113 (2.4)
3,594 (75.1) 619 (12.9) 385 (8.0) 188 (3.9)
280 (5.9)
225 (4.7)
205 (4.3)
202 (4.2)
496 (10.4) 273 (5.7) 2,391 (50.0)
224 (4.7) 109 (2.3) 1,922 (40.2)
2,393 (50.0) 2,830 (59.1)
1,729 (36.1) 2,382 (49.8)
UNMATCHED CHARACTERISTICS Race/Ethnicity White Black Hispanic Other/unknown Psychiatric Diagnoses Manic depression (bipolar disorder) Schizophrenia Health Conditions Delusions Hallucinations Fall during preceding 30 Days Medication Useb Antipsychotics Antidepressants
As documented in Minimum Data Set 2.0 records. At least one prescription during the analysis period. Abbreviation: AD = Alzheimer’s disease. a b
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Figure 2. Prevalence of Mood Indicator and Behavioral Symptoms in Nursing Figure 3. Prevalence of Mood Indicator and Behavioral Symptoms in Nursing Facility Home Residents with vs. without “Crying/tearfulness” Prevalence of Mood Indicator and Behavioral Symptoms in Nursing Residents with and/or non-AD Dementia, With vs. Without “Crying, Tearfulness” Home Residents withAD vs. without “Crying/tearfulness” Mood Indicatorsa
Behavioral Symptomsb
a b
Score of 1 or 2 on specified item in Minimum Data Set 2.0, section E1. Score of 1, 2, or 3 on specified item in Minimum Data Set 2.0, section E4.
Abbreviations: AD = Alzheimer’s disease, PBA = Pseudobulbar affect.
Sad, pained, or worried facial expression were noted in 73.9% of PBA proxy group residents with dementia compared with 30.6% of matched controls. As in the overall sample, but also with higher prevalence in both groups, a greater proportion of the PBA proxy group with dementia had recorded falls during the preceding 30 days (50.0% vs. 40.2% of controls). The percentage experiencing fractures was similar to the overall sample, with 16.5% of the PBA proxy group with dementia experiencing a recorded fracture compared with 13.0% of matched controls.
Discussion Little is known about the prevalence of many conditions in residents of nursing facilities, as the population is infrequently studied in controlled investigations. Failure to include nursing facility residents in clinical studies occurs as a result of concern about confounders given the number of concurrent conditions often present and the potential
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for morbidity or mortality that can occur in randomized controlled trials of these vulnerable individuals. As a result, real-world analysis using available relational databases offer an attractive alternative to understand disease prevalence, characteristics, and treatment patterns in nursing facility residents. This retrospective database analysis of linked MDS and prescription data revealed that the prevalence of “crying, tearfulness” on MDS item E1m, a symptom suggestive of potential PBA, was 9.2% in nursing facility residents. This estimate is in general alignment with the overall 10% prevalence of PBA estimated among patients with AD, ALS, MS, Parkinson’s disease (PD), stroke, and traumatic brain injury in a large U.S. online survey.4 Further, when compared with a control population of residents matched for gender-, age-frequency, dementia diagnosis, and diagnosis of depression (a condition known to be comorbid with PBA, and a potential confounding
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diagnosis in patients with “crying, tearfulness”), residents with dementia and “crying, tearfulness” were more likely to exhibit MDS indicators of depression, anxiety, and sad mood, have delusions and hallucinations, and experience a fall. Consequently, it is not surprising that the use of antipsychotics and antidepressants was higher in nursing facility residents exhibiting “crying, tearfulness” than in the matched controls. Higher utilization of antipsychotics and antidepressants was also noted when residents with dementia (with and without “crying/tearfulness”) were evaluated as a subset of the overall nursing facility population. More than one-third of nursing facility residents with “crying, tearfulness” were treated with antipsychotics, and in those with dementia, 50% received antipsychotics. Comparatively, it has been reported previously that 21.4% of outpatients with PBA symptoms were treated with antipsychotics.4 The higher use of psychopharmacologic medications in nursing facility residents than outpatients may be reflective of more frequent or severe behavioral symptoms, which necessitated nursing facility admission, as well as more advanced underlying disease than is commonly managed in the outpatient environment. These findings have significant potential ramifications on resource utilization and cost of care for nursing facility residents with “crying, tearfulness.” Residents who exhibit alterations in mood and behavior are known to consume more caregiver time and resources.20 Depression is known to coexist in chronic conditions, such as AD, PD, and MS.21-23 The discussion is not complete without an understanding of the limitations associated with retrospective database analyses and use of MDS data. The approach we undertook was to use an MDS element as a proxy to obtain an initial approximation of PBA prevalence that could serve as a basis for future research. This approach is admittedly imprecise and may have led to under- or overidentification of the condition. Underidentification may have resulted from the inability to identify PBA symptoms of uncontrollable laughter; similarly, overidentification may occur because of the inability to rule out other unidentified causes of crying/tearfulness. There are potential inaccuracies in coding of MDS data as a result
of poor medical historical data and inter-rater variability. When reviewed by others, MDS data have been reported to have moderate to moderately high validity and reliability.24 Claims prescription data are accurate as they are adjudicated online and represent information six months or longer post-reconciliation. However, medication consumption may be over-represented using prescription claims data in nursing facility residents who may refuse doses, resulting in waste. Linking of these datasets allows investigators to ask questions that can be viewed as hypothesis-generating for future studies rather than conclusive or causative. Limitations notwithstanding, this study revealed that nursing facility residents with “crying, tearfulness” (MDS 2.0 item E1m), a marker suggestive of potential PBA, had a higher prevalence of all mood and behavioral indicators, as well as psychopharmacological medication use, compared with controls matched for age, gender, and depression/ dementia diagnoses, but without “crying, tearfulness.” Additionally, residents with “crying, tearfulness” and an underlying diagnosis of AD or non-AD dementia were similarly more likely to express other mood/behavioral indicators, and have a higher prevalence of antipsychotic and antidepressant use, than matched controls. Thus, a significant opportunity may exist to improve the care of nursing facility residents with “crying, tearfulness,” and potentially reduce the high utilization observed with antipsychotic and antidepressant medications, which may have contributed to a higher incidence of falls in affected residents. Further research should validate actual PBA prevalence and the corresponding impact on resident outcomes and resource utilization in this population as well as explore additional potential markers to identify PBA. In long-term care residents with neurologic disease or brain injury, there is the potential for disconnect between mood and expressed emotion.25,26 Unfortunately, many residents are not able to communicate their needs or psychological state. Crying in this resident population may not be “crying” as we commonly know it. Thus, we looked for other symptoms captured in the MDS that might be indicators for PBA versus a mood disorder or even psychosis. Symptoms of facial grimacing or repetitive
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Research and Reports vocal outbursts (especially if stereotypical versus random) could be distinct indicators of a neurological basis to the symptoms and potentially consistent with PBA, versus a behavior or mood disorder.3,14 Other causes of crying must also be considered, such as pain or discomfort. Additional work toward diagnostic guides or algorithms would be beneficial in discerning the potential etiology and classification of, and therapeutic approaches to, these distressing symptoms. Barbara J. Zarowitz, PharmD, BCPS, FCCP, CGP, FASCP, is chief clinical officer and vice president of clinical services, Omnicare, Inc., Livonia, Michigan, and adjunct associate professor of pharmacy practice, College of Pharmacy and Health Sciences, Wayne State University, Detroit, Michigan. Terrence O’Shea, PharmD, CGP, is senior director, consultant pharmacist performance and measurement, Omnicare, Inc. For correspondence: Barbara J. Zarowitz, PharmD, BCPS, FCCP, CGP, FASCP, Omnicare, Inc., 33510 Schoolcraft Road, Livonia, MI 48150; Phone: 734-525-3308; Fax: 734-525-3344; E-mail: barbara.zarowitz@ omnicare.com. Disclosure: This work was supported by Avanir Pharmaceuticals, Inc. Acknowledgement: We would like to acknowledge the support of Chuck Yonan and Andrea Formella of Avanir Pharmaceuticals, Inc., for assistance with protocol design, literature research, and manuscript editing. © 2013 American Society of Consultant Pharmacists, Inc. All rights reserved. Doi:10.4140/TCP.n.2013.713. References 1. Schiffer R, Pope LE. Review of pseudobulbar affect including a novel and potential therapy. J Neuropsychiatry Clin Neurosci 2005;17:447-54. 2. Anderson CA, Arciniegas DA, Oster TJ et al. Pathological laughing and crying: epidemiology, pathophysiology and treatment. CNS Drugs 2008;22:531-45. 3. Wilson SAK. Some problems in neurology, II: pathological laughing and crying. J Neurol Psychopath 1924;IV:299-333. 4. Work SS, Colimonico JA, Bradley WG et al. Pseudobulbar affect: an under recognized and under treated neurological disorder. Adv Ther 2011;28:586-601. 5. Starkstein SE, Migliorelli R, Teson A et al. Prevalence and clinical correlates of pathological affective display in Alzheimer’s disease. J Neurol Neurosurg Psychiatry 1995;59:55-60. 6. Kim JS. Post-stroke emotional incontinence after small lenticulocapsular stroke: correlation with lesion location. J Neurol 2002;249:805-10. 7. Kim JS, Choi-Kwon S. Post-stroke depression and emotional incontinence. Neurology 2000;54:1805-10.
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8. House A, Dennis M, Molyneux A et al. Emotionalism after stroke. BMJ 1989;298:991-4. 9. Tang WK, Chan SSM, Chiu HFK et al. Emotional incontinence in Chinese stroke patients: diagnosis, frequency and clinical and radiological correlates. J Neurol 2004;251:865-9. 10. Phuong L, Garg S, Duda JE et al. Involuntary emotional expression disorder (IEED) in Parkinson’s disease. Parkinsonism Relat Disord 2009;15:511-5. 11. Strowd RE, Cartwright MS, Okun MS et al. Pseudobulbar affect: prevalence and quality of life impact in movement disorders. J Neurol 2010;257:1382-7. 12. Petracca GM, Jorge RE, Acion L et al. Frequency and correlates of involuntary emotional expression in Parkinson’s disease. J Neuropsychiatry Clin Neurosci 2009;21:406-12. 13. Arciniegas DB, Lauterbach EC, Anderson KE et al. The differential diagnosis of pseudobulbar affect (PBA). Distinguishing PBA among disorders of mood and affect. Proceedings of a roundtable meeting. CNS Spectr 2005;10:1-16. 14. Rottenberg J, Cevaal A, Vingerhoets AJJM. Do mood disorders alter crying? A pilot investigation. Depression and Anxiety 2008;25:E9-15. 15. Rottenberg J, Gross JJ, Wilhelm FH et al. Crying intensity and threshold in patients with major depressive disorders. J Abnormal Psychol 2002;111:302-12. 16. Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV). Washington, D.C. American Psychiatric Association; 2000. Available at: http://www.psych.org/practice/dsm Accessed February 9, 2013. 17. Lawton MP, Casten R, Parmelee PA et al. Psychometric characteristics of the Minimum Data Set II: validity. J Am Geriatr Soc 1998;46:736-44. 18. Mor V, Angelelli J, Jones R et al. Inter-rater reliability of nursing facility quality indicators in the U.S. BMC Health Services Res 2003;3:20. Available at http://www.ncbi.nlm.nih.gov/pmc/articles/ PMC280691/?tool=pubmed. Accessed May 2, 2012. 19. Mor V. A comprehensive clinical assessment tool to inform policy and practice: applications of the Minimum Data Set. Med Care 2004;42 4 Suppl:50-9. 20. Tomaszewski Farias S, Cajm-Weiner DA, Harvey DJ et al. Longitudinal changes in memory and executive functioning are associated with longitudinal change in instrumental activities of daily living in older adults. Clin Neuropsychol 2009;23:446-61. 21. Barnes DE, Yaffe K, Byers AL et al. Midlife vs. late-life depressive symptoms and risk of dementia: differential effects for Alzheimer disease and vascular dementia. Arch Gen Psych 2012;69:493-8. 22. Riedel O, Dodel R, Deuschl G et al. Depression and care-dependency in Parkinson’s disease: results from a nationwide study of 1449 outpatients. Parkinsonism Rel Dis 2012;18:598-601. 23. Kirchner T, Lara S. Stress and depression symptoms in patients with multiple sclerosis: the mediating role of the loss of social functioning. Acta Neurol 2011;123:407-13. 24. Shin JH, Scherer Y. Advantages and disadvantages of using MDS data in nursing research. J Gerontol Nurs 2009;35:7-17. 25. Balakrisnan P, Rosen H. The causes and treatment of pseudobulbar affect in ischemic stroke. Curr Treat Opt Cardiovasc Med 2008;10: 216-22. 26. Lieberman A, Benson F. Control of emotional expression in pseudobulbar palsy: a personal experience. Arch Neurol 1977;34:717-9.
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disruptive behavior, were more than twice as frequent in the “crying, tearfulness” group. Antipsychotic medications were also used more often in this group (50% vs. 36.1%), as were antidepressants (59.1% vs. 49.8%). Conclusions: In the absence of an International Classification of Diseases 9th edition, Clinical Modification code, the presence of “crying, tearfulness” on MDS 2.0 item E1m was used as a proxy to identify potential PBA. Nursing facility residents with “crying, tearfulness” had a higher prevalence of all mood and behavior indicators as well as psychopharmacological medication use, compared with matched controls without “crying, tearfulness.” Similar results were seen in the subgroup of residents with an underlying diagnosis of AD and/or non-AD dementia. Further research should validate the actual prevalence of PBA in this population, and the corresponding impact on resident outcomes. Key Words: Alzheimer’s disease, Brain injury, Crying, Longterm care, Nursing facility, Omnicare, Pseudobulbar affect. Abbreviations: AD = Alzheimer’s disease, ADL = Activities of daily living, ALS = Amyotrophic lateral sclerosis, ICD-9-CM = International Classification of Diseases 9th edition, Clinical Modification, MDS = Minimum Data Set, MS = Multiple sclerosis, OSHO = Omnicare Senior Health Outcomes, PBA = Pseudobulbar affect, PD = Parkinson’s disease. Consult Pharm 2013;28:713-22.
Introduction Pseudobulbar affect (PBA) is a neurological condition characterized by sudden, frequent, and involuntary episodes of crying or laughing that are disproportionate to environmental stimuli or the individual’s prevailing mood .1-3 PBA occurs secondary to a variety of different central nervous system insults such as multiple sclerosis (MS; prevalence, 7%), amyotrophic lateral sclerosis (ALS; prevalence, 15%-49%), stroke (prevalence, 4.3%-52%), traumatic brain injury (prevalence, 5%-16%), and Alzheimer’s disease (AD; prevalence, 10%-39%).4-12 PBA is thought to result from interruption of pathways between the cerebral cortex and cerebellum that coordinate and modulate appropriate emotional responses.3
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Research and Reports The prevalence of moderate-to-severe PBA in the United States has been estimated at between 1.5 and 2 million people.4,13 PBA is often mistaken for depression (although the two conditions can be comorbid). PBA crying episodes are brief, paroxysmal, disruptive, and out of proportion to the eliciting circumstance.3,13 Episodes typically last seconds to minutes, followed by a return to baseline functioning. In contrast, there are surprisingly little available data on prevalence, frequency, and characteristics of crying episodes in persons with major depression. While available studies support an overall relationship between depression and self-reported crying, this relationship is complex and not necessarily linear. In one of the only controlled studies to specifically evaluate depression and self-rated crying proneness, increased crying propensity was reported only in response to negative emotions (sadness and not happiness), and was not directly related to depression severity.14 In another study, evaluating crying in response to a tear-provoking stimulus (sad movie clip), no significant differences in crying propensity or severity were seen between depressed patients and nondepressed controls.15 Crying is not a criterion symptom of depression in the Diagnostic and Statistical Manual of Mental Disorders, 4th edition.16 Patients with depression may also exhibit inability to cry, apathy, or lack of expression. PBA is an under-recognized and undertreated neurological disorder. Because of their socially or contextually inappropriate nature, PBA episodes are often embarrassing or upsetting to patients and others around them.4 Given that neurological conditions such as stroke, AD, among others are prevalent in nursing facility residents, evaluation of the prevalence of PBA in this environment is of interest. At the time of this research, there was no diagnostic code for PBA; an International Classification of Diseases 9th edition, Clinical Modification (ICD-9-CM) diagnostic code for PBA was released in November 2011. The Minimum Data Set (MDS) is a comprehensive, standardized resident assessment instrument that is utilized in nursing facilities to develop care delivery and planning; monitor clinical indicators such as falls, fractures, cognition, and behavior; and for payment from Medicare. MDS assessment is
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conducted for all residents of nursing facilities upon admission, quarterly, annually, and when the resident has a significant change in status. Although MDS does not have an item field specific to PBA, version 2.0 of MDS has an item specific to crying and tearfulness that could be used as a proxy for PBA to allow a preliminary estimate of PBA symptoms: Section E (“Mood and Behavior Patterns”), part 1 (“Indicators of Depression, Anxiety, Sad Mood”), item m (“crying, tearfulness”) is scored as “0” not present, “1” (exhibited up to 5 days a week), or 2 (exhibited daily or almost daily). The MDS data elements have been validated, and there is evidence for inter-rater reliability.17 More than 85% of MDS data elements have been found to be reliable, with adequate inter-rater reliability and overall good agreement.17,18 The strongest reliability was with elements related to activities of daily living (ADL), e.g., bathing, eating, dressing. ADL, pain, distressed mood, behavioral disturbances, and social engagement elements of the MDS have manifested discriminate validity.19 Validity problems have been reported with MDS data elements of visual acuity, pain frequency and intensity, and resident incontinence.19 The instrument has been criticized by some, noting that data discrepancies occur as a result of miscoding. Agreement rates for a number of data elements have been reportedly poor, but reliability adequate when calculated using a weighted kappa statistic.19 While there are limitations to this caregiver-rated assessment instrument, it is a standardized tool that provides the “best available evidence” of resident status and outcomes in the long-term care setting. The objective of this study was to approximate the prevalence and impact of potential PBA (using “crying, tearfulness” on MDS item E1m as a proxy) in nursing facilities and to develop a basic profile of these residents, including, but not limited to, pertinent demographic information, concurrent diagnoses, the use of antipsychotic and antidepressant medications, and numerous behavioral and functional parameters, compared with a matched cohort of residents without “crying, tearfulness” (MDS item E1m score = 0).
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Methods After obtaining an exemption from institutional review board review and waiver of authorization from the Sterling Institutional Review Board, de-identified information for this study was extracted from Omnicare Senior Health Outcomes (OSHO) Data Warehouse of resident records (demographic and admission tables), resident MDS records, prescription records, drug data and prescriber specialty records, facility records, and prescriber records. Most of the data in the OSHO Data Warehouse are refreshed on a daily basis, with the exception of resident MDS records and Drug Data records (data dictionary). The real-time data are collected from about 175 pharmacies serving more than 1.4 million residents in about 19,000 long-term care and other health care facilities in 48 states.The database stores more than 600 million prescription claims processed within the last six years. All de-identified datasets carry a unique resident identification key that allows longitudinal tracking at the prescription claims level. The prescription data can be analyzed by National Drug Code, brand name, strength, dosage form, individual ingredient, and drug therapeutic class. MDS records are available for approximately 10%-15% of residents in facilities within the Omnicare network that use the AccuMed electronic MDS system. Within the OSHO data warehouse are two data sets: pharmacy claims data for residents in Omnicare-serviced nursing facilities and MDS data for residents in nursing facilities that are clients of Accu-Med’s electronic MDS application. Omnicare is the owner of the pharmacy claims data and a processor of the MDS data. To perform the MDS/pharmacy claims data match, prescription claims and MDS data were obtained from the OSHO data warehouse for the time period of October 1, 2009, through September 30, 2010. Once the two data sets were extracted, they were matched using resident demographics, and the matched records were de-identified using a “safe harbor” method—all 18 identifiable data elements listed in section 164.514(b)(2) of the Health Insurance Portability and Accountability Act privacy rule were removed and replaced with internal identifiers. The internal identifier is a randomly generated number that is not derived from
nor related to the information about the individual, and it is not otherwise capable of being translated to identify the individual. In addition, all internal identifiers were encrypted using a 128-bit, one-way hashing algorithm to further ensure that identifiers cannot be traced to individuals. Figure 1 depicts the resident selection algorithm for this study. Initially, a count of unique residents for whom MDS data existed in the database was obtained. This count served as the denominator for approximating the potential prevalence of PBA. It is important to reiterate that PBA is not listed as one of the “Disease Diagnoses” in section I of the MDS, nor was it represented by an ICD-9-CM code during the study period. Thus, a score of 1 (exhibited up to five days a week) or 2 (exhibited daily or almost daily) on MDS section E (“Mood and Behavior Patterns”), part 1 (“Indicators of Depression, Anxiety, Sad Mood”), item m (“crying, tearfulness”) was used as a proxy for PBA. A score of 0 on item E1m (indicator not exhibited in the last 30 days) was used as a proxy for absence of PBA. Following identification of nursing facility residents with “crying, tearfulness,” a propensity age-, gender-, diagnosis of depression-, and diagnosis of AD or non-AD dementia-matched group without “crying, tearfulness” was selected for comparison. Propensity or frequency matching avoids the need for a direct one-to-one match of each unique resident, but rather matches residents by age range such that there are the same number of residents within a given age range in each group. AD and non-AD dementia were expected to be a significant component of the total number of nursing facility residents with PBA symptomatology. To further understand differences between residents with and without “crying, tearfulness,” the total groups were subdivided to evaluate residents with AD and non-AD dementia with and without “crying, tearfulness.” The number of residents who had “crying, tearfulness” and for whom we had prescription-claims records was used as the denominator to determine the prevalence of PBA symptomatology-related medication utilization. We evaluated the presence of antidepressant and antipsychotic claims, given that these medications may be used
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Figure 1. Resident Selection Algorithm
During the study period, many residents had more than one MDS assessment completed. To avoid counting MDS data elements multiple times, if a resident had more than one MDS assessment during the study period, and had different answers for the same MDS data element, then the answer representing the more severe condition was used. For example, if a resident had two MDS assessments during the study period, and in one of these assessments MDS item J1n (“Unsteady gait”) was not checked (which indicated that the resident did not have “unsteady gait” in the look-back period), and in the other MDS assessment item J1n was checked (indicating that the resident did have “unsteady gait” during the look-back period), then the resident was considered to have “unsteady gait.” Descriptive statistics were performed for all data fields.
Results “Crying, Tearfulness” Prevalence The total number of unique residents with at least one MDS assessment during the study period was 137,829. Of those, a total of 12,595 unique residents had item E1m (“crying, tearfulness”) noted on their MDS assessments, resulting in a prevalence of symptoms suggestive of PBA of 9.1%. For simplicity, the term “PBA proxy group” will be used hereinafter to describe the group of residents with “crying and tearfulness” on MDS item E1m.
Abbreviations: AD = Alzheimer’s disease, MDS = Minimum Data Set. PBA = Pseudobulbar affect. Note: HCR Manorcare and SAVA are both nursing facility chains.
in residents with PBA symptomatology. Not all residents with “crying, tearfulness” received antidepressants or antipsychotics, despite having other prescription claims in the OSHO data warehouse. Additionally, not all residents with “crying, tearfulness” received their medications from an Omnicare pharmacy. Therefore, to calculate the percent of treated residents, the denominator of residents for whom pharmacy records are available was used.
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PBA Proxy Group, Overall Ten thousand residents randomly selected from the PBA proxy group were matched to 10,000 controls without MDS item E1m “crying, tearfulness.” Characteristics of this PBA proxy group and matched controls are shown in Table 1. The PBA proxy group (and matched controls) was predominantly female (82.1%); two-thirds (65.3%) were 75 years of age or older; one-third (35.1%) were 85 years of age or older. A total of 47.9% of the PBA proxy group had a diagnosis of AD, non-AD dementia, or both; and 65.5% had a diagnosis of depression. The sample was not matched for race. Residents were predominantly white. However, there was some disparity in the proportions of black residents (PBA proxy group 8.3% vs. controls 12.2%).
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Table 1. Characteristics of Nursing Facility Residents with “Crying, Tearfulness” and Propensity Matched Controlsa (N = 10,000) Characteristic
Matched Control Residents without ”Crying, Tearfulness” n (%)
Nursing Facility Residents with “Crying, Tearfulness” n (%)
MATCHED CHARACTERISTICS Gender Female Male
8,213 (82.1) 1,787 (17.9)
8,213 (82.1) 1,787 (17.9)
Age Category, Years < 65 65-69 70-74 75-79 80-84 85-89 ≥ 90
1,812 (18.1) 762 (7.6) 898 (9.0) 1,329 (13.3) 1,686 (16.9) 1,887 (18.9) 1,626 (16.3)
1,812 (18.1) 762 (7.6) 898 (9.0) 1,329 (13.3) 1,686 (16.9) 1,887 (18.9) 1,626 (16.3)
Diagnoses AD Non-AD Dementia Both AD and non-AD Dementia Depression
881 (8.8) 3,148 (31.5) 757 (7.6) 6,547 (65.5)
861 (8.6) 3,213 (32.1) 712 (7.1) 6,547 (65.5)
8,153 (81.5) 829 (8.3) 721 (7.2) 297 (3.0)
7,613 (76.1) 1,223 (12.2) 737 (7.4) 427 (4.3)
663 (6.6)
498 (5.0)
462 (4.6)
416 (4.2)
741 (7.4) 460 (4.6) 4,499 (45.0)
306 (3.1) 180 (1.8) 3,628 (36.3)
3,881 (38.8) 5,968 (59.7)
2,723 (27.2) 5,050 (50.5)
UNMATCHED CHARACTERISTICS Race/Ethnicity White Black Hispanic Other/unknown Psychiatric Diagnoses Manic depression (bipolar disorder) Schizophrenia Health Conditions Delusions Hallucinations Fall during preceding 30 Days Medication Useb Antipsychotics Antidepressants
As documented in Minimum Data Set 2.0 records. At least one prescription during the analysis period. Abbreviation: AD = Alzheimer’s disease. a b
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Figure 2. Prevalence of Mood Indicator and Behavioral Symptoms in Nursing Figure 2. Prevalence of Mood Indicator and Behavioral Symptoms in Nursing Home Residents with vs. without “Crying/tearfulness” Prevalence of Mood Indicator and Behavioral Symptoms in Nursing HomeResidents Residents With vs.Without “Crying, Tearfulness” Home with vs. without “Crying/tearfulness” Mood Indicatorsa
Behavioral Symptomsb
a b
Score of 1 or 2 on specified item in Minimum Data Set 2.0, section E1. Score of 1, 2, or 3 on specified item in Minimum Data Set 2.0, section E4.
All MDS mood indicators (section E1) and behavioral symptoms (section E4) showed greater prevalence in the PBA proxy group than in controls (Figure 2). The PBA proxy group was more likely than controls to be reported as having delusions (7.4% vs. 3.1%) or hallucinations (4.6% vs. 1.8%) and also more likely than controls to have prescription claims for antipsychotic medications (38.8% vs. 27.2%) or antidepressant (59.7% vs. 50.5%) medications. Notably, a greater proportion of the PBA proxy group had recorded falls during the preceding 30 days (45.0% vs. 36.3% of controls), and 16.9% had reported fractures (compared with 14.8% of controls).
PBA Proxy Group with Dementia Of the 10,000 residents in the PBA proxy group, 4,786 (47.9%) had a diagnosis of AD or non-AD dementia, or
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both. Like the overall sample, the PBA proxy group with dementia was predominantly female (83.4%) and had similar race distribution; however, these residents were older, with 81.5% 75 years of age or older, and 46.5% 85 years of age or older. A total of 3,362 (70.3%) of the PBA proxy group with dementia (and matched controls) had a diagnosis of depression (Table 2). In residents with dementia, as in the overall sample, all MDS mood indicators (section E1) showed greater prevalence in the PBA proxy group than in controls (Figure 3). The PBA proxy group with dementia was also more likely than matched controls to be reported as experiencing delusions (10.4% vs. 4.7%, respectively) or hallucinations (5.7% vs. 2.3%, respectively), and the overall prevalence of these symptoms was higher in residents with dementia (both PBA proxy and control groups) than for the full sample.
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Table 2. Characteristics of Nursing Facility Residents with Dementia, With vs. Without “Crying, Tearfulness”a (N = 4,786) Characteristic
Dementia Without “Crying/Tearfulness” n (%)
Dementia Plus “Crying/Tearfulness” n (%)
MATCHED CHARACTERISTICS Gender Female Male
3,992 (83.4) 794 (16.6)
3,992 (83.4) 794 (16.6)
Age Category, Years < 65 65-69 70-74 75-79 80-84 85-89 ≥ 90
302 (6.3) 212 (4.4) 371 (7.8) 664 (13.9) 1,011 (21.1) 1,151 (24.1) 1,075 (22.5)
302 (6.3) 212 (4.4) 371 (7.8) 664 (13.9) 1,011 (21.1) 1,151 (24.1) 1,075 (22.5)
Diagnoses AD Non-AD dementia Both AD and non-AD dementia Depression
881 (18.4) 3,148 (65.8) 757 (15.8) 3,362 (70.3)
861 (18.0) 3,213 (67.1) 712 (14.9) 3,362 (70.3)
3,898 (81.4) 382 (8.0) 393 (8.2) 113 (2.4)
3,594 (75.1) 619 (12.9) 385 (8.0) 188 (3.9)
280 (5.9)
225 (4.7)
205 (4.3)
202 (4.2)
496 (10.4) 273 (5.7) 2,391 (50.0)
224 (4.7) 109 (2.3) 1,922 (40.2)
2,393 (50.0) 2,830 (59.1)
1,729 (36.1) 2,382 (49.8)
UNMATCHED CHARACTERISTICS Race/Ethnicity White Black Hispanic Other/unknown Psychiatric Diagnoses Manic depression (bipolar disorder) Schizophrenia Health Conditions Delusions Hallucinations Fall during preceding 30 Days Medication Useb Antipsychotics Antidepressants
As documented in Minimum Data Set 2.0 records. At least one prescription during the analysis period. Abbreviation: AD = Alzheimer’s disease. a b
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Figure 2. Prevalence of Mood Indicator and Behavioral Symptoms in Nursing Figure 3. Prevalence of Mood Indicator and Behavioral Symptoms in Nursing Facility Home Residents with vs. without “Crying/tearfulness” Prevalence of Mood Indicator and Behavioral Symptoms in Nursing Residents with and/or non-AD Dementia, With vs. Without “Crying, Tearfulness” Home Residents withAD vs. without “Crying/tearfulness” Mood Indicatorsa
Behavioral Symptomsb
a b
Score of 1 or 2 on specified item in Minimum Data Set 2.0, section E1. Score of 1, 2, or 3 on specified item in Minimum Data Set 2.0, section E4.
Abbreviations: AD = Alzheimer’s disease, PBA = Pseudobulbar affect.
Sad, pained, or worried facial expression were noted in 73.9% of PBA proxy group residents with dementia compared with 30.6% of matched controls. As in the overall sample, but also with higher prevalence in both groups, a greater proportion of the PBA proxy group with dementia had recorded falls during the preceding 30 days (50.0% vs. 40.2% of controls). The percentage experiencing fractures was similar to the overall sample, with 16.5% of the PBA proxy group with dementia experiencing a recorded fracture compared with 13.0% of matched controls.
Discussion Little is known about the prevalence of many conditions in residents of nursing facilities, as the population is infrequently studied in controlled investigations. Failure to include nursing facility residents in clinical studies occurs as a result of concern about confounders given the number of concurrent conditions often present and the potential
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for morbidity or mortality that can occur in randomized controlled trials of these vulnerable individuals. As a result, real-world analysis using available relational databases offer an attractive alternative to understand disease prevalence, characteristics, and treatment patterns in nursing facility residents. This retrospective database analysis of linked MDS and prescription data revealed that the prevalence of “crying, tearfulness” on MDS item E1m, a symptom suggestive of potential PBA, was 9.2% in nursing facility residents. This estimate is in general alignment with the overall 10% prevalence of PBA estimated among patients with AD, ALS, MS, Parkinson’s disease (PD), stroke, and traumatic brain injury in a large U.S. online survey.4 Further, when compared with a control population of residents matched for gender-, age-frequency, dementia diagnosis, and diagnosis of depression (a condition known to be comorbid with PBA, and a potential confounding
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diagnosis in patients with “crying, tearfulness”), residents with dementia and “crying, tearfulness” were more likely to exhibit MDS indicators of depression, anxiety, and sad mood, have delusions and hallucinations, and experience a fall. Consequently, it is not surprising that the use of antipsychotics and antidepressants was higher in nursing facility residents exhibiting “crying, tearfulness” than in the matched controls. Higher utilization of antipsychotics and antidepressants was also noted when residents with dementia (with and without “crying/tearfulness”) were evaluated as a subset of the overall nursing facility population. More than one-third of nursing facility residents with “crying, tearfulness” were treated with antipsychotics, and in those with dementia, 50% received antipsychotics. Comparatively, it has been reported previously that 21.4% of outpatients with PBA symptoms were treated with antipsychotics.4 The higher use of psychopharmacologic medications in nursing facility residents than outpatients may be reflective of more frequent or severe behavioral symptoms, which necessitated nursing facility admission, as well as more advanced underlying disease than is commonly managed in the outpatient environment. These findings have significant potential ramifications on resource utilization and cost of care for nursing facility residents with “crying, tearfulness.” Residents who exhibit alterations in mood and behavior are known to consume more caregiver time and resources.20 Depression is known to coexist in chronic conditions, such as AD, PD, and MS.21-23 The discussion is not complete without an understanding of the limitations associated with retrospective database analyses and use of MDS data. The approach we undertook was to use an MDS element as a proxy to obtain an initial approximation of PBA prevalence that could serve as a basis for future research. This approach is admittedly imprecise and may have led to under- or overidentification of the condition. Underidentification may have resulted from the inability to identify PBA symptoms of uncontrollable laughter; similarly, overidentification may occur because of the inability to rule out other unidentified causes of crying/tearfulness. There are potential inaccuracies in coding of MDS data as a result
of poor medical historical data and inter-rater variability. When reviewed by others, MDS data have been reported to have moderate to moderately high validity and reliability.24 Claims prescription data are accurate as they are adjudicated online and represent information six months or longer post-reconciliation. However, medication consumption may be over-represented using prescription claims data in nursing facility residents who may refuse doses, resulting in waste. Linking of these datasets allows investigators to ask questions that can be viewed as hypothesis-generating for future studies rather than conclusive or causative. Limitations notwithstanding, this study revealed that nursing facility residents with “crying, tearfulness” (MDS 2.0 item E1m), a marker suggestive of potential PBA, had a higher prevalence of all mood and behavioral indicators, as well as psychopharmacological medication use, compared with controls matched for age, gender, and depression/ dementia diagnoses, but without “crying, tearfulness.” Additionally, residents with “crying, tearfulness” and an underlying diagnosis of AD or non-AD dementia were similarly more likely to express other mood/behavioral indicators, and have a higher prevalence of antipsychotic and antidepressant use, than matched controls. Thus, a significant opportunity may exist to improve the care of nursing facility residents with “crying, tearfulness,” and potentially reduce the high utilization observed with antipsychotic and antidepressant medications, which may have contributed to a higher incidence of falls in affected residents. Further research should validate actual PBA prevalence and the corresponding impact on resident outcomes and resource utilization in this population as well as explore additional potential markers to identify PBA. In long-term care residents with neurologic disease or brain injury, there is the potential for disconnect between mood and expressed emotion.25,26 Unfortunately, many residents are not able to communicate their needs or psychological state. Crying in this resident population may not be “crying” as we commonly know it. Thus, we looked for other symptoms captured in the MDS that might be indicators for PBA versus a mood disorder or even psychosis. Symptoms of facial grimacing or repetitive
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Research and Reports vocal outbursts (especially if stereotypical versus random) could be distinct indicators of a neurological basis to the symptoms and potentially consistent with PBA, versus a behavior or mood disorder.3,14 Other causes of crying must also be considered, such as pain or discomfort. Additional work toward diagnostic guides or algorithms would be beneficial in discerning the potential etiology and classification of, and therapeutic approaches to, these distressing symptoms. Barbara J. Zarowitz, PharmD, BCPS, FCCP, CGP, FASCP, is chief clinical officer and vice president of clinical services, Omnicare, Inc., Livonia, Michigan, and adjunct associate professor of pharmacy practice, College of Pharmacy and Health Sciences, Wayne State University, Detroit, Michigan. Terrence O’Shea, PharmD, CGP, is senior director, consultant pharmacist performance and measurement, Omnicare, Inc. For correspondence: Barbara J. Zarowitz, PharmD, BCPS, FCCP, CGP, FASCP, Omnicare, Inc., 33510 Schoolcraft Road, Livonia, MI 48150; Phone: 734-525-3308; Fax: 734-525-3344; E-mail: barbara.zarowitz@ omnicare.com. Disclosure: This work was supported by Avanir Pharmaceuticals, Inc. Acknowledgement: We would like to acknowledge the support of Chuck Yonan and Andrea Formella of Avanir Pharmaceuticals, Inc., for assistance with protocol design, literature research, and manuscript editing. © 2013 American Society of Consultant Pharmacists, Inc. All rights reserved. Doi:10.4140/TCP.n.2013.713. References 1. Schiffer R, Pope LE. Review of pseudobulbar affect including a novel and potential therapy. J Neuropsychiatry Clin Neurosci 2005;17:447-54. 2. Anderson CA, Arciniegas DA, Oster TJ et al. Pathological laughing and crying: epidemiology, pathophysiology and treatment. CNS Drugs 2008;22:531-45. 3. Wilson SAK. Some problems in neurology, II: pathological laughing and crying. J Neurol Psychopath 1924;IV:299-333. 4. Work SS, Colimonico JA, Bradley WG et al. Pseudobulbar affect: an under recognized and under treated neurological disorder. Adv Ther 2011;28:586-601. 5. Starkstein SE, Migliorelli R, Teson A et al. Prevalence and clinical correlates of pathological affective display in Alzheimer’s disease. J Neurol Neurosurg Psychiatry 1995;59:55-60. 6. Kim JS. Post-stroke emotional incontinence after small lenticulocapsular stroke: correlation with lesion location. J Neurol 2002;249:805-10. 7. Kim JS, Choi-Kwon S. Post-stroke depression and emotional incontinence. Neurology 2000;54:1805-10.
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8. House A, Dennis M, Molyneux A et al. Emotionalism after stroke. BMJ 1989;298:991-4. 9. Tang WK, Chan SSM, Chiu HFK et al. Emotional incontinence in Chinese stroke patients: diagnosis, frequency and clinical and radiological correlates. J Neurol 2004;251:865-9. 10. Phuong L, Garg S, Duda JE et al. Involuntary emotional expression disorder (IEED) in Parkinson’s disease. Parkinsonism Relat Disord 2009;15:511-5. 11. Strowd RE, Cartwright MS, Okun MS et al. Pseudobulbar affect: prevalence and quality of life impact in movement disorders. J Neurol 2010;257:1382-7. 12. Petracca GM, Jorge RE, Acion L et al. Frequency and correlates of involuntary emotional expression in Parkinson’s disease. J Neuropsychiatry Clin Neurosci 2009;21:406-12. 13. Arciniegas DB, Lauterbach EC, Anderson KE et al. The differential diagnosis of pseudobulbar affect (PBA). Distinguishing PBA among disorders of mood and affect. Proceedings of a roundtable meeting. CNS Spectr 2005;10:1-16. 14. Rottenberg J, Cevaal A, Vingerhoets AJJM. Do mood disorders alter crying? A pilot investigation. Depression and Anxiety 2008;25:E9-15. 15. Rottenberg J, Gross JJ, Wilhelm FH et al. Crying intensity and threshold in patients with major depressive disorders. J Abnormal Psychol 2002;111:302-12. 16. Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV). Washington, D.C. American Psychiatric Association; 2000. Available at: http://www.psych.org/practice/dsm Accessed February 9, 2013. 17. Lawton MP, Casten R, Parmelee PA et al. Psychometric characteristics of the Minimum Data Set II: validity. J Am Geriatr Soc 1998;46:736-44. 18. Mor V, Angelelli J, Jones R et al. Inter-rater reliability of nursing facility quality indicators in the U.S. BMC Health Services Res 2003;3:20. Available at http://www.ncbi.nlm.nih.gov/pmc/articles/ PMC280691/?tool=pubmed. Accessed May 2, 2012. 19. Mor V. A comprehensive clinical assessment tool to inform policy and practice: applications of the Minimum Data Set. Med Care 2004;42 4 Suppl:50-9. 20. Tomaszewski Farias S, Cajm-Weiner DA, Harvey DJ et al. Longitudinal changes in memory and executive functioning are associated with longitudinal change in instrumental activities of daily living in older adults. Clin Neuropsychol 2009;23:446-61. 21. Barnes DE, Yaffe K, Byers AL et al. Midlife vs. late-life depressive symptoms and risk of dementia: differential effects for Alzheimer disease and vascular dementia. Arch Gen Psych 2012;69:493-8. 22. Riedel O, Dodel R, Deuschl G et al. Depression and care-dependency in Parkinson’s disease: results from a nationwide study of 1449 outpatients. Parkinsonism Rel Dis 2012;18:598-601. 23. Kirchner T, Lara S. Stress and depression symptoms in patients with multiple sclerosis: the mediating role of the loss of social functioning. Acta Neurol 2011;123:407-13. 24. Shin JH, Scherer Y. Advantages and disadvantages of using MDS data in nursing research. J Gerontol Nurs 2009;35:7-17. 25. Balakrisnan P, Rosen H. The causes and treatment of pseudobulbar affect in ischemic stroke. Curr Treat Opt Cardiovasc Med 2008;10: 216-22. 26. Lieberman A, Benson F. Control of emotional expression in pseudobulbar palsy: a personal experience. Arch Neurol 1977;34:717-9.
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