Evaluating the Dyadic Benefits of Early-Phase Behavioral Interventions: An Exemplar Using Data From Couples Living With Parkinson's Disease.

BACKGROUND AND OBJECTIVES: There are a growing number of early-phase (i.e., Stage I, NIH Stage Model) interventions targeted at family care dyads navigating chronic health conditions in older adults. Currently, the benefits of these interventions are often evaluated for older adults and their family care partners separately, even when controlling for interdependence. Without understanding the benefits (and potential harms) for dyads as a whole, understanding of program impact is incomplete. Moreover, few health behavior interventions involving dyads include relational measures to ensure no unintended consequences for the dyad or account for within-dyad pretest risk level. RESEARCH DESIGN AND METHODS: We used secondary data from a quasi-experimental trial involving 39 couples in which 1 member of the dyad was living with Parkinson's disease as an exemplar demonstration of 3 proposed approaches: an above-zero approach, a pretest risk status approach, and an expanded pattern analysis matrix approach. RESULTS: Approaches provided evidence for dyadic benefits of the intervention compared to the wait-list comparison condition, but carried different assumptions that did not always categorize dyads similarly. DISCUSSION AND IMPLICATIONS: Implications of using each approach and selecting different benchmarks for defining success are discussed. The descriptive approaches proposed, provide a rationale for more intentional evaluation of small-sample, early-phase dyadic interventions.

Benefits of a Self-Management Program for the Couple Living With Parkinson's Disease: A Pilot Study.

The goal of this pilot study was to explore health benefits for couples participating together in an existing community-based self-management workshop for Parkinson's disease (PD). A quasi-experimental two-wave design explored the effects of the Strive to Thrive program in comparison to a wait-list control condition. Preliminary data (n = 39 couples) showed that spouses in the intervention group had greater engagement in mental relaxation techniques at 7 weeks than those in the control condition (large effect size). Small effects were observed for increases in aerobic activity and mental relaxation for the adult with PD, increases in strength-based activities and self-efficacy for spouses, declines in depressive symptoms for spouses, and decreases in protective buffering for both adults with PD and spouses. The program showed potential for existing community-based programs to benefit couples living with chronic illness.

Does age make a difference in caregiver strain? Comparison of young versus older caregivers in early-stage Parkinson's disease.

Family care research has identified negative outcomes of providing care to a spouse with Parkinson's disease (PD), such as declining physical and mental health. Research has also identified protective variables that decrease negative outcomes such as high mutuality and rewards of meaning. It is important for clinicians to identify "at risk" family caregivers and provide earlier interventions. Despite the importance of age and developmental stage there is a paucity of research comparing young versus older spouse caregivers. This study compared the difference in negative aspects of strain and modulators of strain in young and older PD spouse caregivers. A series of hierarchical multiple regressions were used to examine the contribution of age on both positive and negative aspects of the care situation for 65 (37 young, 28 old) PD spouse caregivers. Negative variables included 3 dimensions of strain; strain from lack of personal resources, strain from worry, and global strain. Positive or protective variables included mutuality, preparedness, and rewards of meaning. Even in early stage disease before significant care is required, young spouses (40-55) were found to be at greater risk for negative consequences of the care situation reporting significantly more strain from lack of personal resources, and lower levels of mutuality and rewards of meaning than older (greater than 70) spouses. As expected, young spouses were more likely to be working, caring for children in the home, and in better physical health than older spouses. Clinicians are well-situated to identify the unique needs of young spouses and intervene early in the caregiving trajectory. These findings provide ideas for targeted interventions. Future larger studies that compare young and older spouses should include later stage disease to more fully understand the developmental differences raised by the present findings.

Do motor and nonmotor symptoms in PD patients predict caregiver strain and depression?

Our objective was to understand the impact of motor and nonmotor symptoms of patients with early and middle stage Parkinson's disease (PD) on their spouses' caregiver strain and depression. A sample of 219 spouse caregivers of PD patients participating in a clinical trial was evaluated for six dimensions of caregiver strain and depression using the Family Care Inventory. Motor and nonmotor (i.e., psychological) clinical symptoms collected from PD patients as part of the clinical trial protocol were used as predictors. Seven hierarchical regression analyses were used to determine the contribution of the motor and nonmotor clinical symptoms in explaining variation in each of the seven caregiver-dependent variables. Clinical symptoms explained 9-16% of the variance in caregiver strain and 10% of depression. Motor symptoms explained 0-6% of the variance and nonmotor psychological symptoms explained 7-13% of the variance in caregiver strain. Comparing our findings with literature that is deemed clinically relevant for patient symptoms that predict caregiver strain, we concluded that PD patient symptoms are important predictors of caregiver strain and depression. Patient nonmotor psychological symptoms have a much greater impact on caregiver strain and depression than patient motor symptoms.

Needs and experiences of caregivers for family members dying with Parkinson disease.

The caregiver burdens and unmet needs of patients with Parkinson disease (PD) in the final months of life are poorly documented. We surveyed 47 family caregivers of PD patients a median of 18 months after death. We measured caregiver preparedness for their role, assistance provided the patient, and types and settings of care received by the patient. Typical caregivers were older female spouses. Though 66% of patients resided in a care facility during the last month, over half received care from hospice, 36% from a home health agency, and 43% by privately paid aide in the months before death. Caregivers rated tasks involving physical effort as most difficult. While most caregivers felt prepared for their role, one-third or more were unprepared for the stress and physical strain encountered. These data suggest that increasing education and assistance with physical tasks may address unmet needs of PD caregivers.

Effects of methylphenidate on response to oral levodopa: a double-blind clinical trial.

OBJECTIVE: To determine if repeated dosing with methylphenidate hydrochloride (MPD) (Ritalin; Novartis Pharmaceuticals, East Hanover, NJ), an inhibitor of the dopamine transporter, would augment the effects of oral levodopa in patients with Parkinson disease. DESIGN: The study was a double-blind, randomized, placebo-controlled crossover trial. SETTING: The trial was conducted at the General Clinical Research Center (GCRC) as an inpatient study. Subjects Thirteen people with idiopathic Parkinson disease and a fluctuating motor response to levodopa were recruited from movement disorder clinics as a convenience sample. One subject was excluded because he did not have a 10% increase in tapping speed in response to levodopa. The remaining 12 subjects completed the protocol. INTERVENTIONS: A 0.4-mg/kg dose of MPD was administered orally at 8 am, noon, and 4 pm in conjunction with the subjects' normal oral antiparkinsonian medications. Oral levodopa dosage was decreased as clinically feasible during the first 4 days in the GCRC during open-label administration of MPD and hourly monitoring of parkinsonism and vital signs between 7 am and 8 pm. Subjects were discharged taking their usual antiparkinsonian medications without MPD. They returned 1 and 2 weeks later to the GCRC for 1 day of hourly monitoring of their response to the medication regimen derived during the 4 days in the GCRC, once with MPD and once with identical-appearing placebo, in a randomized sequence and double-blind conditions. MAIN OUTCOME MEASURES: The main outcome measure was the duration of "on" time between 9 am and 8 pm measured by an increase in tapping speed by 10% over the average of the 7 am to 8 am predosing tapping speed measurements. Secondary measures were estimates of "on" time obtained with the timed walking task, tremor scores, and dyskinesia scores. In addition, averages of hourly tapping speeds, walking speed, tremor scores, dyskinesia scores, vital signs, and analog scale scores for mood, anxiety, and fatigue between 9 am and 8 pm were examined. Adverse events on the double-blinded days were compared. RESULTS: Methylphenidate tended to increase the time "on" as measured by tapping (P = .09) but not by walking time or dyskinesia scores (P = .40 and .42, respectively). Methylphenidate tended to increase average tapping speed, decrease time to perform walking task, decrease tremor, and increase dyskinesia score but only the decrease in tremor reached significance. Neither the investigators nor the subjects could reliably identify active drug. Methylphenidate was well tolerated. CONCLUSIONS: The effects of 0.4 mg/kg of MPD 3 times per day on the motor response to levodopa were small and variable and judged to be clinically insignificant. Trial Registration clinicaltrials.gov Identifier: NCT00359723.

Palliative care and Parkinson's disease: Meeting summary and recommendations for clinical research.

INTRODUCTION: Palliative care is an approach to caring for patients and families affected by serious illnesses that focuses on the relief of suffering through the management of medical symptoms, psychosocial issues, advance care planning and spiritual wellbeing. Over the past decade there has been an emerging clinical and research interest in the application of palliative care approaches to Parkinson's disease (PD) and outpatient palliative care services are now offered by several movement disorders centers. METHODS: An International Working Group Meeting on PD and Palliative Care supported by the Parkinson's Disease Foundation was held in October 2015 to review the current state of the evidence and to make recommendations for clinical research and practice. RESULTS: Topics included: 1) Defining palliative care for PD; 2) Lessons from palliative care for heart failure and other chronic illnesses; 3) Patient and caregiver Needs; 4) Needs assessment tools; 5) Intervention strategies; 6) Predicting prognosis and hospice referrals; 7) Choice of appropriate outcome measures; 8) Implementation, dissemination and education research; and 9) Need for research collaborations. We provide an overview of these discussions, summarize current evidence and practices, highlight gaps in our knowledge and make recommendations for future research. CONCLUSIONS: Palliative Care for PD is a rapidly growing area which holds great promise for improving outcomes for PD patients and their caregivers. While clinical research in this area can build from lessons learned in other diseases, there is a need for observational, methodological and interventional research to address the unique needs of PD patients and caregivers.

Interprofessional education increases knowledge, promotes team building, and changes practice in the care of Parkinson's disease.

OBJECTIVE: Examine outcomes for the National Parkinson Foundation (NPF) Allied Team Training for Parkinson (ATTP), an interprofessional education (IPE) program in Parkinson's disease (PD) and team-based care for medicine, nursing, occupational, physical and music therapies, physician assistant, social work and speech-language pathology disciplines. BACKGROUND: Healthcare professionals need education in evidence-based PD practices and working effectively in teams. Few evidence-based models of IPE in PD exist. METHODS: Knowledge about PD, team-based care, the role of other disciplines and attitudes towards healthcare teams were measured before and after a protocol-driven training program. Knowledge, attitudes and practice changes were again measured at 6-month post-training. Trainee results were compared to results of controls. RESULTS: Twenty-six NPF-ATTP trainings were held across the U.S. (2003-2013). Compared to control participants (n = 100), trainees (n = 1468) showed statistically significant posttest improvement in all major outcomes, including self-perceived (p < 0.001) and objective knowledge (p < 0.001), Understanding Role of Other Disciplines (p < 0.001), Attitudes Toward Health Care Teams Scale (p < 0.001), and the Attitudes Toward Value of Teams (p < 0.001) subscale. Despite some decline, significant improvements were largely sustained at six-month post-training. Qualitative analyses confirmed post-training practice changes. CONCLUSIONS: The NPF-ATTP model IPE program showed sustained positive gains in knowledge of PD, team strategies and role of other disciplines, team attitudes, and important practice improvements. Further research should examine longer-term outcomes, objectively measure practice changes and mediators, and determine impact on patient outcomes.

Melatonin for sleep disturbances in Parkinson's disease.

BACKGROUND AND PURPOSE: Many patients with Parkinson's disease (PD) experience sleep-related symptoms. Studies in other populations indicate that melatonin can increase sleep efficiency, decrease nighttime activity, and shorten sleep latency, but there has been little research on the use of melatonin in PD. The purpose of this study was to compare the effects of two doses of melatonin to placebo on sleep, daytime sleepiness, and level of function in patients with PD who complained of sleep disturbances. PATIENTS AND METHODS: A multi-site double-blind placebo-controlled cross-over trial was employed; 40 subjects completed the 10-week protocol. There was a 2-week screening period, 2-week treatment periods, and 1-week washouts between treatments. Nocturnal sleep was assessed by actigraphy and diaries, whereas daytime sleepiness and function were assessed by the Epworth Sleepiness Scale (ESS), Stanford Sleepiness Scale (SSS), and General Sleep Disturbance Scale (GSDS). RESULTS: Repeated measures analysis of variance revealed a significant improvement in total nighttime sleep time during the 50 mg melatonin treatment compared to placebo. There was significant improvement in subjective sleep disturbance, sleep quantity, and daytime sleepiness during the 5 mg melatonin treatment compared to placebo as assessed by the GSDS. CONCLUSIONS: Although we found a statistically significant improvement in actigraphically measured total sleep time on 50 mg melatonin compared to 5 mg or placebo, this small improvement (10 min) may not be clinically significant. However, the significant improvement found in subjective sleep disturbance suggests that these modest effects may be clinically relevant in this patient population.

Inosine to increase serum and cerebrospinal fluid urate in Parkinson disease: a randomized clinical trial.

IMPORTANCE: Convergent biological, epidemiological, and clinical data identified urate elevation as a candidate strategy for slowing disability progression in Parkinson disease (PD). OBJECTIVE: To determine the safety, tolerability, and urate-elevating capability of the urate precursor inosine in early PD and to assess its suitability and potential design features for a disease-modification trial. DESIGN, SETTING, AND PARTICIPANTS: The Safety of Urate Elevation in PD (SURE-PD) study, a randomized, double-blind, placebo-controlled, dose-ranging trial of inosine, enrolled participants from 2009 to 2011 and followed them for up to 25 months at outpatient visits to 17 credentialed clinical study sites of the Parkinson Study Group across the United States. Seventy-five consenting adults (mean age, 62 years; 55% women) with early PD not yet requiring symptomatic treatment and a serum urate concentration less than 6 mg/dL (the approximate population median) were enrolled. INTERVENTIONS: Participants were randomized to 1 of 3 treatment arms: placebo or inosine titrated to produce mild (6.1-7.0 mg/dL) or moderate (7.1-8.0 mg/dL) serum urate elevation using 500-mg capsules taken orally up to 2 capsules 3 times per day. They were followed for up to 24 months (median, 18 months) while receiving the study drug plus 1 washout month. MAIN OUTCOMES AND MEASURES: The prespecified primary outcomes were absence of unacceptable serious adverse events (safety), continued treatment without adverse event requiring dose reduction (tolerability), and elevation of urate assessed serially in serum and once (at 3 months) in cerebrospinal fluid. RESULTS Serious adverse events (17), including infrequent cardiovascular events, occurred at the same or lower rates in the inosine groups relative to placebo. No participant developed gout and 3 receiving inosine developed symptomatic urolithiasis. Treatment was tolerated by 95% of participants at 6 months, and no participant withdrew because of an adverse event. Serum urate rose by 2.3 and 3.0 mg/dL in the 2 inosine groups (P < .001 for each) vs placebo, and cerebrospinal fluid urate level was greater in both inosine groups (P = .006 and <.001, respectively). Secondary analyses demonstrated nonfutility of inosine treatment for slowing disability. CONCLUSIONS AND RELEVANCE: Inosine was generally safe, tolerable, and effective in raising serum and cerebrospinal fluid urate levels in early PD. The findings support advancing to more definitive development of inosine as a potential disease-modifying therapy for PD. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00833690.

Optimism, pessimism, mutuality, and gender: predicting 10-year role strain in Parkinson's disease spouses.

PURPOSE: There is wide variability in how spouses providing care respond to their care situations. Few studies focus on the roles of both intra- and interpersonal factors in long-term spousal care, particularly in the context of Parkinson's disease (PD). The current study uses longitudinal data over a 10-year period to examine the roles of optimism, pessimism, mutuality, and spouse gender in predicting role strain in PD spouses. DESIGN AND METHODS: A longitudinal design was used to study 255 spouses of persons with PD over a 10-year period, with data points at baseline (Year 0), Year 2, and Year 10. A series of multilevel models were used to examine four role strain variables -- global strain, strain from worry, strain from feelings of being manipulated, and strain from increased tension. RESULTS: Female spouse gender predicted both higher Year 10 role strain and faster increases in role strain over the 10-year period. In addition, high mutuality and optimism and low pessimism at baseline played important protective roles against increased role strain at Year 10. IMPLICATIONS: This study focused on early-stage spousal care in a primarily physical disability context. Findings suggest that gender differences place wives at greater risk for negative outcomes, even in the absence of dementia. Additionally, clinicians have opportunities to target interventions early in the care trajectory based on intra- and interpersonal risk factors.

The dopamine transporter: importance in Parkinson's disease.

The dopamine transporter (DAT) may be the single most important determinant of extracellular dopamine concentrations. The importance of DAT in Parkinson's disease (PD) in which DAT may be reduced by 50 to 70% is unclear. We have examined the effects of methylphenidate (MPD), an inhibitor of DAT, administered alone or with levodopa, on parkinsonism measured with tapping and walking speeds, dyskinesia, subjective effects, and vital signs. MPD in oral doses of up to 0.4 mg/kg was well tolerated. Administered alone, MPD produced no objective improvement of parkinsonism. MPD, 0.4 mg/kg orally, coadministered with 2-hour levodopa infusions at 0.5 or 1.0mg/kg/hr increased the percentage of patients responding to the 0.5mg/kg/hr dose and prolonged the response to levodopa infusions as measured by tapping and walking speeds. Dyskinesia was prolonged in proportion to the increase in antiparkinson actions but severity was not increased. MPD decreased the hypotensive response to levodopa. In conclusion, MPD appeared to have no effect given alone but potentiated the effects of levodopa, particularly doses at threshold for clinical effects. These observations indicate that the residual DAT is functional in PD and is a potential target for symptomatic therapy of PD.

Evolution of the response to levodopa during the first 4 years of therapy.

The short-duration response, long-duration response, and dyskinetic response to levodopa change during long-term levodopa therapy. How these responses evolve, and which changes contribute to the emergence of motor fluctuations, remain unclear. We studied 18 subjects with Parkinson's disease before they began levodopa therapy and after 6, 12, 24, and 48 months of long-term levodopa therapy. The responses to 2-hour levodopa infusions after overnight and after 3 days of levodopa withdrawal were studied from 6 months onward. The mean magnitude of the short-duration response and the long-duration response measured after overnight without antiparkinsonian medications did not change during the 4 years. However, after 3 days without levodopa, it was apparent that the short-duration-response magnitude was progressively increasing (p < 0.0001) and that the long-duration response was decaying more rapidly (p = 0.0004). The short-duration-response magnitude at 4 years was inversely related to the long-duration-response magnitude (p = 0.022), suggesting that the long-duration response was one determinant of the short-duration-response magnitude. Dyskinesia increased progressively in severity during the study (p = 0.013). The duration of the short-duration response and dyskinesia did not change during the 4 years. Subject reports of motor fluctuations tended to be associated with a large short-duration response (p = 0.054). We suggest that a larger long-duration response, rather than a shortened one, is more important to the development of fluctuations. Improving the baseline or practical-off motor function to reduce the magnitude of the short-duration response may be a strategy to treat fluctuations.

Locating and retaining research participants for follow-up studies.

Two common pitfalls of longitudinal research are loss of participants over time and inability to locate participants whose contact information has changed. This article is based on our experiences in locating and retaining a sample of caregivers of persons with Parkinson's disease 8-10 years after we last contacted them. The strategies we used resulted in locating 86% of our sample and retaining 80% of those who were eligible. These strategies included asking participants for a backup contact, asking participants if they would be willing to be contacted again for a future study, making the most of existing search engines, keeping in touch, and being flexible, patient, and professional.

Pessimism and optimism as early warning signs for compromised health for caregivers of patients with Parkinson's disease.

BACKGROUND: Although pessimism and optimism are associated with health-related outcomes, the long-term effects of pessimism and optimism in the caregiving process are understudied, and little is known about their role in health changes over time. OBJECTIVE: To determine whether pessimism and optimism can be used as early warning signs for negative changes in caregiver depressive symptoms and physical health over a 10-year period. METHODS: Multilevel modeling was used to examine longitudinal data from 311 spouse caregivers of individuals with Parkinson's disease, with data points at baseline, Year 2, and Year 10. Measures included the Life Orientation Test, the Center for Epidemiological Studies-Depression Scale, and the SF-36 Health Survey physical functioning scale. RESULTS: Caregiver pessimism early in the caregiver role was found to be a warning sign for poor current and future caregiver health. High baseline pessimism signaled high levels of baseline depressive symptoms and poor physical health, as well as a faster decline in health over the 10-year study. Optimism played a role in predicting baseline depressive symptoms, although the magnitude of its beneficial contribution was not as great as the deleterious effects of pessimism. CONCLUSIONS: Nurses and clinicians have a unique opportunity to detect and intervene with caregivers who show high levels of pessimism early in the caregiving trajectory.