Demoralization in essential tremor: prevalence, clinical correlates, and dissociation from tremor severity.

OBJECTIVE: Essential tremor (ET) is associated with psychological difficulties, including anxiety and depression. Demoralization (feelings of helplessness, hopelessness, inability to cope), another manifestation of psychological distress, has yet to be investigated in ET. Our objectives are to (1) estimate the prevalence of demoralization in ET, (2) assess its clinical correlates, and (3) determine whether demoralization correlates with tremor severity. METHODS: We administered the Kissane Demoralization Scale (KDS-II) and several psychosocial evaluations (ie, scales assessing subjective incompetence, resilience, and depression [eg, Geriatric Depression Scale]) to 60 ET subjects. Tremor was assessed with a disability score and total tremor score. KDS-II >8 indicated demoralization. RESULTS: Among 60 ET subjects (mean age = 70.2 ± 6.8 years), the prevalence of demoralization was 13.3%, 95% confidence interval = 6.9-24.2%. Although there was overlap between demoralization and depression (10% of the sample meeting criteria for both), 54% of depressed subjects were not demoralized, and 25% of demoralized subjects were not depressed. Demoralization correlated with psychological factors, but demoralized subjects did not have significantly higher total tremor scores, tremor disability scores, or years with tremor. CONCLUSIONS: Demoralization has a prevalence of 13.3% in ET, similar to that in other chronic or terminal illnesses (eg, cancer 13-18%, Parkinson's disease 18.1%, coronary heart disease 20%). Demoralization was not a function of increased tremor severity, suggesting that it is a separable construct, which could dictate how a patient copes with his/her disease. These data further our understanding of the psychological and psychosocial correlates of ET.

Profiles of Normal Cognition in Essential Tremor.

OBJECTIVES: Patients with essential tremor exhibit heterogeneous cognitive functioning. Although the majority of patients fall under the broad classification of cognitively "normal," essential tremor is associated with increased risk for mild cognitive impairment and dementia. It is possible that patterns of cognitive performance within the wide range of normal functioning have predictive utility for mild cognitive impairment or dementia. These cross-sectional analyses sought to determine whether cognitive patterns, or "clusters," could be identified among individuals with essential tremor diagnosed as cognitively normal. We also determined whether such clusters, if identified, were associated with demographic or clinical characteristics of patients. METHODS: Elderly subjects with essential tremor (age >55 years) underwent comprehensive neuropsychological testing. Domain means (memory, executive function, attention, visuospatial abilities, and language) from 148 individuals diagnosed as cognitively normal were partitioned using k-means cluster analysis. Individuals in each cluster were compared according to cognitive functioning (domain means and test scores), demographic factors, and clinical variables. RESULTS: There were three clusters. Cluster 1 (n = 64) was characterized by comparatively low memory scores (p < .001), Cluster 2 (n = 39) had relatively low attention and visuospatial scores (p < .001), and Cluster 3 (n = 45) exhibited consistently high performance across all domains. Cluster 1 had lower Montreal Cognitive Assessment scores and reported more prescription medication use and lower balance confidence. CONCLUSIONS: Three patterns of cognitive functioning within the normal range were evident and tracked with certain clinical features. Future work will examine the extent to which such patterns predict conversion to mild cognitive impairment and/or dementia.

The "Caring Giver": Emotional Caregiving in the Setting of Essential Tremor.

INTRODUCTION: Essential tremor (ET) is a common neurological disorder associated with functional impairment. Emerging evidence shows that some ET caregivers experience burden, but the unique interpersonal aspects of caregiving in the context of ET have not been fully examined. RESEARCH DESIGN: Open-ended questions were administered to 98 ET care-recipient-caregiver dyads. Responses were analyzed using conventional content analysis. RESULTS: The unique visibility of disability and feelings of embarrassment that occur with ET prompts caregivers to be highly attuned to care-recipient emotions. Providing companionship, promoting independence, and reducing embarrassment are three themes we found that describe the ET caregiving experience. DISCUSSION: Caregiving in ET often goes beyond aiding with activities of daily living; it has a significant emotional component especially in relation to independence and embarrassment. Future studies on caregiving in ET and conditions in which disability is visible should consider using a definition of caregiving that includes emotional caregiving.

Enfeeblement in Elders with Essential Tremor: Characterizing the Phenomenon and Its Role in Caregiver Burden.

Background: Individuals with essential tremor (ET), a common movement disorder, experience functional impairment, which contributes to burden experienced by their loved ones and caregivers. Some burdened caregivers report their loved ones as seeming debilitated or prematurely old, a concept that we have called enfeeblement. Using the Essential Tremor Enfeeblement Survey (ETES), we seek to characterize enfeeblement in elders with ET and assess its contribution to caregiver burden. Methods: We administered the ETES (range = 8-40, higher scores indicating more enfeeblement) and other scales to 98 caregivers of individuals with ET. Individuals with ET were also queried regarding tremors, cognitive abilities, and overall health. We then identified demographic and clinical correlates of ETES and modeled the contribution of ETES to caregiver burden (assessed using the Zarit 12-item Burden Interview [ZBI-12]). Results: Mean ETES score was 14.2 ± 6.2 (median = 12.0, range = 8.0-32.0); 26.5% of respondents endorsed at least one of the eight ETES items. Older age, greater tremor severity and disability, more functional and gait disability, more cognitive difficulty, and more depressive symptoms were associated with higher ETES scores. ETES was the strongest contributor to caregiver burden (ZBI-12) and substantially increased the variance explained in models of caregiver burden. Discussion: Enfeeblement seems to describe a previously unexplained component of caregiver burden in elders with ET. The presence of enfeeblement may contribute to greater burden and should be factored into assessments of patient and caregiver needs.

Enfeeblement in Essential Tremor: Development and Validation of a New Psychometric Measure.

INTRODUCTION: Despite a growing body of knowledge regarding essential tremor (ET), past studies have fallen short in capturing the full impact of ET on patients and caregivers. We propose enfeeblement (i.e., having the qualities of being prematurely old, helpless, or debilitated) as a novel clinical outcome measure in ET. Due to the lack of enfeeblement scales for ET in the literature, we developed and validated an enfeeblement scale for ET. METHODS: The Essential Tremor Enfeeblement Survey (ETES) consists of eight 5-point Likert-type scale questions and is designed to be a caregiver-reported outcome. RESULTS: Enfeeblement scores showed a floor effect of 15.3%, no ceiling effects, and demonstrated good overall test-retest reliability (intraclass correlation coefficient = 0.73), favorable internal consistency (Cronbach α coefficient = 0.92) and good convergent validity. CONCLUSION: The ETES has robust properties. Aside from future studies of enfeeblement in ET, enfeeblement should be explored more broadly as a psychometric measure across other neurological disorders.

What Predicts Mortality in Essential Tremor? A Prospective, Longitudinal Study of Elders.

Objective: Essential tremor (ET) is among the most common neurologic diseases. Although in the past it was considered a benign condition, recent research has demonstrated increased risk of mortality. To date, however, no studies have examined predictors of mortality in ET. Methods: In a longitudinal, prospective study of 141 elders with ET, we used Cox proportional-hazards models to estimate hazard ratios (HRs) for death. Results: The mean baseline age was 81.1 ± 8.8 years. During the follow-up interval, 27 (19.1%) died. Average time from baseline to death was 12.3 ± 8.7 months (range = 0.3-31.2). In univariate Cox regression models, older age (HR = 1.16, p < 0.001), lower Montreal Cognitive Assessment score (HR = 0.88, p = 0.004), higher Clinical Dementia Rating (CDR) score (HR = 4.53, p < 0.001), higher score on the Geriatric Depression scale (GDS) (HR = 1.07, p = 0.048), less balance confidence (HR = 0.98, p = 0.006), more falls (HR = 1.11, p = 0.003), and more tandem mis-steps (HR = 1.53, p = 0.004) were associated with increased risk of mortality. In the final multivariate Cox model, older age (HR = 1.14, p = 0.005), higher CDR score (HR = 3.80, p = 0.002) and higher GDS (HR = 1.11, p = 0.01) were independently associated with increased risk of mortality. Conclusions: This study highlights several independent predictors of mortality in elderly ET; clinicians should consider screening for depressive symptoms, assessing cognition and tracking CDR scores, and assessing balance while evaluating patients with ET.

Evaluating Mild Cognitive Impairment in Essential Tremor: How Many and Which Neuropsychological Tests?

OBJECTIVES: Essential tremor (ET) confers an increased risk for developing both amnestic and non-amnestic mild cognitive impairment (MCI). Yet, the optimal measures for detecting mild cognitive changes in individuals with this movement disorder have not been established. We sought to identify the cognitive domains and specific motor-free neuropsychological tests that are most sensitive to mild deficits in cognition as defined by a Clinical Dementia Rating (CDR) of 0.5, which is generally associated with a clinical diagnosis of MCI. METHODS: A total of 196 ET subjects enrolled in a prospective, longitudinal, clinical-pathological study underwent an extensive motor-free neuropsychological test battery and were assigned a CDR score. Logistic regression analyses were performed to identify the neuropsychological tests which best identified individuals with CDR of 0.5 (mild deficits in cognition) versus 0 (normal cognition). RESULTS: In regression models, we identified five tests in the domains of Memory and Executive Function which best discriminated subjects with CDR of 0.5 versus 0 (86.9% model classification accuracy). These tests were the California Verbal Learning Test II Total Recall, Logical Memory II, Verbal-Paired Associates I, Category Switching Fluency, and Color-Word Inhibition. CONCLUSIONS: Mild cognitive difficulty among ET subjects is best predicted by combined performance on five measures of memory and executive function. These results inform the nature of cognitive dysfunction in ET and the creation of a brief cognitive battery to assess patients with ET for cognitively driven dysfunction in life that could indicate the presence of MCI. (JINS, 2018, 24, 1084-1098).

Perceived embarrassment and caregiver burden in essential tremor caregivers.

Essential tremor (ET) is a progressive neurological disease associated with functional disability, diminished quality of life and, in some individuals, poorer balance, cognitive impairment, depression and sleep dysregulation. Individuals with ET may rely on family members and friends to act as informal caregivers to assist with daily activities and provide emotional support. There is a high prevalence of embarrassment among individuals with ET, which may be a result of the outwardly visible nature of tremor. Studies in populations with outwardly visible disability have shown that perception by caregivers of a care-recipient's social distress can contribute to caregiver burden. We hypothesize that in ET, perception by caregivers of ET participant embarrassment is a predictor for caregiver burden. Data were collected from 57 ET participants and their caregivers. We measured ET participant embarrassment using the Essential Tremor Embarrassment Assessment (ETEA), and measured perception by caregivers of ET participant embarrassment using a modified version of the ETEA. The Zarit Burden Interview was used to measure caregiver burden. Perceived embarrassment was associated with ET participant embarrassment. In linear regression models, perceived embarrassment was a stronger predictor for caregiver burden than measures of ET participant cognitive and physical impairment. The results indicate that perception of ET participant embarrassment can be burdensome for caregivers. Clinicians may wish to address patient embarrassment and perceived embarrassment to better support caregivers and ET patients.

Psychological Suffering in Essential Tremor: A Study of Patients and Those Who Are Close to Them.

Background: Although the motor and non-motor features of essential tremor (ET) have been characterized in detail, it is not known whether ET patients suffer psychologically and whether those who are close to them consider them to be suffering in this way. Methods: Fifty ET patients and 50 "close others" (COs), identified by patients "as someone who knows you well and sees you often" and who can "provide a different perspective on your well-being", reported their own depressive symptoms, daily stress, and perceptions of patient psychological suffering and patient overall suffering with validated scales. ET patients' tremor severity, duration, disability, cognition, and number of medications were also assessed. Results: ET patients reported levels of psychological suffering within the range documented in arthritis and dementia patients from previous studies, and COs perceived significantly more psychological suffering in patients than patients reported themselves. Regression models, controlling for tremor severity, duration, and disability revealed that patients' greater psychological suffering was associated with greater patient depression. The greater perceptions of COs of patient psychological and overall suffering were associated with greater CO depression and daily stress. Sensitivity analysis showed that patients' cognitive status or number of medications did not affect the results. Discussion: Multidisciplinary teams caring for ET patients should look beyond simple clinical ET indicators. They should be aware of patient experiences and perceptions of COs of psychological and overall suffering. This will help guide the development of evidence-based, supportive interventions that improve communication about the needs of ET patients and those who are close to them.

The Experience of Essential Tremor Caregivers: Burden and Its Correlates.

BACKGROUND: Essential tremor (ET) is associated with physical and cognitive impairments, as well as embarrassment, avoidance of social settings, and related difficulties that negatively impact the lives of patients. In similar disease contexts, burden on friends and relatives acting as caregivers has been noted and has well-documented implications. There has been no study examining caregiver burden related to ET. METHODS: Data were gathered from 55 ET participants enrolled in a clinical study and their caregivers. The Zarit Burden Interview was used to assess caregiver burden. To assess clinical features that may be associated with burden, we collected several variables including the Montreal Cognitive Assessment, self-reported tremor disability, a videotaped neurological examination, questionnaires assessing ET participants' suffering, caregivers' perceptions of that suffering, and both caregiver and ET participant depressive symptoms. Spearman's correlations were performed between caregiver burden and clinical features, and we created a multivariate linear regression model predicting caregiver burden. RESULTS: Many ET caregivers provide little to no care and experience little to no burden. However, some caregivers (11%) provide over 25 h of care/week, and 13% experience high levels of burden. Caregivers most commonly provided assistance with writing and cooking. Increased burden was associated with the ET participants' decreased cognition, more caregiving tasks, more hours/week of caregiving activities, a longer duration of care, more ET participant falls/year, more medications taken by the ET participant, and more depressive symptoms in both the ET participant and the caregiver (all p < 0.05). ET participants' suffering and their caregivers' perceptions of suffering were both associated with increased burden. Neither tremor severity score nor self-reported tremor disability score was associated with increased caregiver burden. Using a multivariate linear regression model, we found that caregivers' increased perception of their partners' suffering was the best predictor of caregiver burden. CONCLUSION: While not all relatives and friends of ET patients provide extensive care or experience high burden, there is a group reporting high levels of caregiver burden that requires the attention and counseling of clinicians. This burden is associated with primarily non-tremor symptoms of ET and with caregivers' perception that their partners are suffering.

Cognitive Dysfunction Is Associated with Greater Imbalance and Falls in Essential Tremor.

BACKGROUND: Essential tremor (ET) is not exclusively a tremor disorder; it is also associated with cognitive and gait dysfunction. However, a gap in knowledge is that the relationship between cognitive and gait dysfunction has not been studied in detail in ET. We examined the relationship between cognition and balance and falls in ET and hypothesized that cognitive dysfunction in ET patients would be associated with greater problems with balance and more falls. METHODS: ET cases were recruited into the Clinical-pathological Study of Cognition in ET. A comprehensive cognitive assessment was performed. This included the Montreal Cognitive Assessment (MoCA) to measure global cognition, multiple motor-free tests comprehensively assessing performance in each cognitive domain, and an assignment of Clinical Dementia Rating (CDR) scores. We collected data on the number of reported falls in the past year, and balance confidence was assessed using the 6-item Activities of Balance Confidence Scale. These cross-sectional analyses utilized baseline data. RESULTS: There were 199 ET cases (mean age 78.6 years). In linear regression models that considered the effects of numerous confounding variables, lower global cognition (poorer cognition) was associated with greater number of falls and reduced balance confidence (p < 0.05). In similar adjusted linear regression models, higher CDR score (poorer functional cognition) was associated with greater number of falls and reduced balance confidence (p < 0.05). We also assessed whether number of falls and balance confidence was associated with performance in specific cognitive domains. Number of falls was most closely linked with performance on tests of executive function, and balance confidence, with executive function, attention, and memory. CONCLUSION: These data indicate that a correlate of poorer cognition in ET is greater number of falls and lower balance confidence. Cognition should enter the dialog with ET patients as an issue of clinical significance.

Thrombin generation, ProC(®)Global, prothrombin time and activated partial thromboplastin time in thawed plasma stored for seven days and after methylene blue/light pathogen inactivation.

BACKGROUND: Methylene blue pathogen inactivation and storage of thawed plasma both lead to changes in the activity of several clotting factors. We investigated how this translates into a global loss of thrombin generation potential and alterations in the protein C pathway. MATERIALS AND METHODS: Fifty apheresis plasma samples were thawed and each divided into three subunits. One subunit was stored for 7 days at 4 °C, one was stored for 7 days at 22 °C and one was stored at 4 °C after methylene blue/light treatment. Thrombin generation parameters, ProC(®)Global-NR, prothrombin time and activated partial thromboplastin time were assessed on days 0 and 7. RESULTS: The velocity of thrombin generation increased significantly after methylene blue treatment (increased thrombin generation rate; time to peak decreased) and decreased after storage (decreased thrombin generation rate and peak thrombin; increased lag time and time to peak). The endogenous thrombin generation potential remained stable after methylene blue treatment and storage at 4 °C. Methylene blue treatment and 7 days of storage at 4 °C activated the protein C pathway, whereas storage at room temperature and storage after methylene blue treatment decreased the functional capacity of the protein C pathway. Prothrombin time and activated partial thromboplastin time showed only modest alterations. DISCUSSION: The global clotting capacity of thawed plasma is maintained at 4 °C for 7 days and directly after methylene blue treatment of thawed plasma. Thrombin generation and ProC(®)Global are useful tools for investigating the impact of pathogen inactivation and storage on the clotting capacity of therapeutic plasma preparations.

A qualitative case study of child protection issues in the Indian construction industry: investigating the security, health, and interrelated rights of migrant families.

BACKGROUND: Many of India's estimated 40 million migrant workers in the construction industry migrate with their children. Though India is undergoing rapid economic growth, numerous child protection issues remain. Migrant workers and their children face serious threats to their health, safety, and well-being. We examined risk and protective factors influencing the basic rights and protections of children and families living and working at a construction site outside Delhi. METHODS: Using case study methods and a rights-based model of child protection, the SAFE model, we triangulated data from in-depth interviews with stakeholders on and near the site (including employees, middlemen, and managers); 14 participants, interviews with child protection and corporate policy experts in greater Delhi (8 participants), and focus group discussions (FGD) with workers (4 FGDs, 25 members) and their children (2 FGDs, 9 members). RESULTS: Analyses illuminated complex and interrelated stressors characterizing the health and well-being of migrant workers and their children in urban settings. These included limited access to healthcare, few educational opportunities, piecemeal wages, and unsafe or unsanitary living and working conditions. Analyses also identified both protective and potentially dangerous survival strategies, such as child labor, undertaken by migrant families in the face of these challenges. CONCLUSIONS: By exploring the risks faced by migrant workers and their children in the urban construction industry in India, we illustrate the alarming implications for their health, safety, livelihoods, and development. Our findings, illuminated through the SAFE model, call attention to the need for enhanced systems of corporate and government accountability as well as the implementation of holistic child-focused and child-friendly policies and programs in order to ensure the rights and protection of this hyper-mobile, and often invisible, population.

Interrelatedness of child health, protection and well-being: an application of the SAFE model in Rwanda.

This study examines the core components of children's basic security and well-being in order to examine issues central to improving child protection in Rwanda. Sources of data included 15 focus groups with adults, 7 focus groups with children ages 10-17, and 11 key informant interviews with child protection stakeholders, including representatives from international NGOs, community-based groups, and the Rwandan Government, all of which took place in April and May of 2010. Participants painted a complex picture of threats to children's basic security in Rwanda. Three key themes were pervasive across all interviews: (1) deterioration of social and community cohesion in post-genocide Rwanda; (2) the cascading effects of poverty; and (3) the impact of caregiver illness and death on the caregiving environment. Consistent with the SAFE (Safety/freedom from harm; Access to basic physiological needs and healthcare; Family and connection to others; Education and economic security) model of child protection, participants rarely elaborated on a child protection threat independent of other basic security needs and rights. Findings suggest a need for integrated approaches to child protection that recognize this interrelatedness and extend beyond issue-specific child protection responses. This study contributes to a growing body of work highlighting the interrelated nature of child protection threats and the implications of adaptive and dangerous survival strategies that children and families engage in to meet their basic security needs. Analysis of this interrelatedness provides a roadmap for improving policies and implementing integrated and robust child protection strategies in Rwanda and other settings.

Storage of thawed plasma for a liquid plasma bank: impact of temperature and methylene blue pathogen inactivation.

BACKGROUND: Rapid transfusion of fresh-frozen plasma (FFP) is desired for treating coagulopathies, but thawing and issuing of FFP takes more than 40 minutes. Liquid storage of plasma is a potential solution but uncertainties exist regarding clotting factor stability. We assessed different storage conditions of thawed FFP and plasma treated by methylene blue plus light (MB/light) for pathogen inactivation. STUDY DESIGN AND METHODS: Fifty thawed apheresis plasma samples (approx. 750 mL) were divided into three subunits and either stored for 7 days at 4°C, at room temperature (RT), and at 4°C after MB/light treatment. Clotting factor activities (Factor [F] II, FV, FVII through FXIII, fibrinogen, antithrombin, von Willebrand factor antigen, Protein C and S) were assessed after thawing and on Days 3, 5, and 7. Changes were classified as "minor" (activities within the reference range) and "major" (activities outside the reference range). RESULTS: FFP storage at 4°C revealed major changes for FVIII (median [range], 56% [33%-114%]) and Protein S (51% [20%-88%]). Changes were more pronounced when plasma was stored at RT (FVIII, 59% [37%-123%]; FVII, 69% [42%-125%]; Protein S, 20% [10%-35%]). MB/light treatment of thawed FFP resulted in minor changes. However, further storage for 7 days at 4°C revealed major decreases for FVIII (47% [12%-91%]) and Protein S (49% [18%-95%]) and increases for FVII (150% [48%-285%]) and FX (126% [62%-206%]). CONCLUSION: Storage of liquid plasma at 4°C for 7 days is feasible for FFP as is MB/light treatment of thawed plasma. In contrast, storage of thawed plasma for 7 days at RT or after MB/light treatment at 4°C affects clotting factor stability substantially and is not recommended.

Mechanical characterization of nacre as an ideal-model for innovative new endoprosthesis materials.

INTRODUCTION: To mimic the impressive mechanical behavior of natural ceramics for technical or biomedical applications, interest has been focused on nacre, a natural composite consisting of imbricated aragonite platelets embedded in a protein matrix. Nacre is an ideal model material for implants, since it possesses favorable strength and toughness properties compared to the component materials of which it is composed. The focus of the present study was to test standardized parameters which are good indicators of the material's suitability as an implant material. MATERIALS AND METHODS: A three-point bending test was performed on polished nacre samples according to international standards for Young's modulus, bending strength and fracture toughness. A total of 60 nacre samples were tested, with 5 samples each in 4 states of hydration (dry, distilled water, 0.9% NaCl and sea water). As a basis for comparison, 10 samples of a newly developed bioceramic material were tested for fracture toughness. RESULTS: The fracture toughness of nacre tended to be higher for specimens conditioned in 0.9% NaCl than for dry specimens (5.3 ± 0.6 vs. 4.3 ± 0.7 MPam(1/2), p = 0.061). The fracture toughness of the bioceramic investigated was observed to be somewhat higher than nacre (5.8 ± 0.4 vs. 4.3 ± 0.7 MPam(1/2), p ≤ 0.001). DISCUSSION AND CONCLUSION: The increase in fracture toughness of hydrated nacre was not as large as would be expected based on the difference in stiffness of the matrix material after hydration that has been reported. Modulus and toughness were similar to published values and the fracture toughness observed was somewhat higher than reported for alumina implant ceramics, which are in use in total hip arthroplasty. In a direct comparison, we found that a newly developed alumina bioceramic material can in fact match nature in terms of fracture toughness.