Study protocol: A cross-sectional survey of clinicians to identify barriers to clinical practice guideline implementation in the assessment and treatment of persistent tic disorders.

INTRODUCTION: Eight members of the International Parkinson's Disease and Movement Disorders Society Tic and Tourette Syndrome Study Group formed a subcommittee to discuss further barriers to practice guideline implementation. Based on expert opinion and literature review, the consensus was that practice variations continue to be quite broad and that many barriers in different clinical settings might negatively influence the adoption of the American Academy of Neurology and the European Society for the Study of Tourette Syndrome published guidelines. OBJECTIVES: 1) To identify how clinical practices diverge from the existing American Academy of Neurology and European Society for the Study of Tourette Syndrome guidelines, and 2) to identify categories of barriers leading to these clinical care gaps. METHODS AND ANALYSIS: This article presents the methodology of a planned cross-sectional survey amongst healthcare professionals routinely involved in the clinical care of patients with persistent tic disorders, aimed at 1) identifying how practices diverge from the published guidelines; and 2) identifying categories of barriers leading to these clinical care gaps. Purposeful sampling methods are used to identify and recruit critical persistent tic disorders stakeholders. The analysis will use descriptive statistics.

Comparative pharmacovigilance assessment of mortality with pimavanserin in Parkinson disease-related psychosis.

BACKGROUND: Pimavanserin is approved for treatment of Parkinson disease (PD)-related psychosis, but its use has been associated with an increased risk of death during clinical trials, as well as during postmarketing surveillance. Previous reports on the association between pimavanserin and mortality have not taken into account limitations of data sources nor included comparable populations or comparisons to relevant treatment alternatives. OBJECTIVE: To conduct a comparative pharmacovigilance assessment of pimavanserin vs treatment alternatives and by restricting surveillance data to more representative populations. METHODS: This was a retrospective analysis of adverse event case reports submitted to the FDA's Adverse Event Reporting System (FAERS) from 2016 through 2019 quarter 3 (Q3). FAERS data are collected from the full population, were further restricted to only those with PD, and were based on PD medication use. Reports were assessed for exposure to pimavanserin, clozapine, quetiapine, haloperidol, and other atypical antipsychotics. The outcome of interest was all-cause death. A proportional reporting ratio (PRR) and 95% confidence limits were calculated for each 2 by 2 contingency of outcome (death) and exposure (pimavanserin and others). For each outcome/exposure pair, the baseline population was altered to include the full FAERS sample, only reports with PD, reports with PD treated with levodopa, and reports with PD treated with multiple PD medications. The sample was also stratified by time period before April 2018 and after September 2018 to capture periods of public knowledge and federal response. A lower 95% CI (Lower95CI) ≥ 2 for the PRR was considered as the accepted threshold for a drug safety signal. RESULTS: As of 2019 Q3, there were 2,287 reports of death associated with pimavanserin. Compared within the full FAERS base population, pimavanserin yielded a PRR Lower95CI = 2.08 but was smaller when restricted to comparison among only a base population with PD (Lower95CI = 1.09), PD treated with levodopa (Lower95CI = 1.15), or PD treated with multiple PD medications (Lower95CI = 1.63). Metrics for quetiapine, clozapine, and other atypical antipsychotics were similar in magnitude. Stratification by time showed a possible reporting bias associated with pimavanserin, since no safety signal was detected before April 2018; however, a signal was present thereafter. CONCLUSIONS: Compared in context with treatment alternatives for patients with PD, pimavanserin was not associated with excess reports of death in the FAERS data. This information should be used in shared decision making between physicians and PD patients to balance the risks and benefits of pimavanserin and other treatments for PD psychosis. DISCLOSURES: No outside funding supported this study. The authors report no disclosures or conflicts of interest relevant to this study. Armstrong receives research support from the NIA (P30AG047266, R01AG068128) and the Florida Department of Health (grant 20A08). She is the local principal investigator of a Lewy Body Dementia Association Research Center of Excellence. She also receives compensation from the American Academy of Neurology for work as an evidence-based medicine methodology consultant. She is on the level of evidence editorial board for Neurology and related publications (uncompensated), receives publishing royalties for Parkinson's Disease: Improving Patient Care (Oxford University Press, 2014), and has received an honorarium for presenting for Medscape CME in 2018. Okun serves as a consultant for the Parkinson's Foundation and has received research grants from NIH, Parkinson's Foundation, the Michael J. Fox Foundation, the Parkinson Alliance, Smallwood Foundation, the Bachmann-Strauss Foundation, the Tourette Syndrome Association, and the UF Foundation. Okun has participated as a site principal investigator and/or co-investigator for several NIH-, foundation-, and industry-sponsored trials over the years but has not received honoraria. Malaty has participated in research funded by the Parkinson Foundation, Tourette Association, Dystonia Coalition, Abbvie, Boston Scientific, Eli Lilly, Neuroderm, Pfizer, Revance, and Teva. She has received travel compensation and/or honoraria from the Tourette Association of America, NeuroChallenge Foundation and NIH/Neurobiology of Disease in Children, Parkinson Foundation, Medscape, International Association of Parkinsonism and Related Disorders, and Cleveland Clinic, and royalties from Robert Rose publishers. The other authors have no disclosures.

Deep brain stimulation may improve quality of life in people with Parkinson's disease without affecting caregiver burden.

OBJECTIVE: This study aims to investigate the influence of deep brain stimulation (DBS) on caregiver burden and quality of life in Parkinson's disease. METHODS: A cross-sectional retrospective study utilizing the National Parkinson Foundation Quality Improvement Initiative clinical study was conducted. A group of 275 patients who had undergone DBS for Parkinson's disease were extracted from 2916 subjects who were included in this data base. The data were compared to an age, sex, and disease severity matched control group. A secondary analysis was then performed on two more control groups that were matched to account for presence or absence of motor fluctuations. The multidimensional caregiver strain index and Parkinson's disease quality-of-life questionnaire 39 summary index were compared. RESULTS: The multidimensional caregiver strain index did not differ between the DBS group (16.9 ± 11.8) and a matched non-DBS group (16.1 ± 17.6, p = 0.618). The quality-of-life index was, however, significantly better in the DBS group (28.9 ± 15.6) than in the non-DBS group (32.3 ± 17.6, p = 0.034). A secondary analysis revealed that the total caregiver strain score was lower in the no motor fluctuation control group than the other two groups (p < 0.05). Regression analysis revealed significant relationships between the quality-of-life index and caregiver strain index total scores (p < 0.001), between caregiver strain index total score and age at surgery (p = 0.027), and also between the interval since surgery (p = 0.048). CONCLUSIONS: Although there were several limitations to this study, DBS seems to improve quality of life without significantly increasing caregiver burden.

High rates and the risk factors for emergency room visits and hospitalization in Parkinson's disease.

BACKGROUND: Parkinson's disease (PD) patients are hospitalized more frequently than their peers as a result of falls, psychosis, infections and other medical complications. However, patient-specific risk factors for hospitalization are unclear. OBJECTIVE: To identify rates and risk factors for hospital encounters (Emergency Room [ER] visits or hospitalization) among people with PD. METHODS: 3415 PD participants (mean age 67 ± 10 years, disease duration 9 ± 6 years, H&Y 2 47%, H&Y 3 26%) enrolled in the prospective international multicenter NPF-QII Study. One-year follow-up data was available for 1030 patients. Rates and risk factors for hospital encounters were determined at baseline and after one year follow-up. RESULTS: Of 3415 PD participants at study entry, 1120 (33%) reported at least one hospital encounter. Associations were: longer timed up-and-go test (OR: 1.33), increased comorbidities (OR: 1.25), motor fluctuations (OR: 1.32), and deep brain stimulation (DBS) (OR: 2.49). Of these 1120 persons, 311 had follow-up data and 158 (51%) had a repeat encounter one year later, associated with higher H&Y stage, fluctuations, and lower health-related quality-of-life. Of 2295 participants without a hospital encounter at baseline, 719 had follow-up data and 178 (25%) had a first hospital encounter one year later. Risk factors were female gender, comorbidities, lower cognition, fluctuations, and DBS. CONCLUSIONS: One-third of people with PD had a hospital encounter each year, and one-half of those had a repeat encounter. These high rates correlated with disease severity, comorbidities and DBS. There is an urgent need to develop programs to reduce PD hospital encounters.

What are the issues facing Parkinson's disease patients at ten years of disease and beyond? Data from the NPF-QII study.

BACKGROUND: Parkinson's disease (PD) is the second most common neurodegenerative syndrome, classically characterized by levodopa-responsive motor features accompanied by non-motor mood, cognitive, sensory and autonomic issues. Over time, disease burden slowly accumulates resulting in diminished health status. Many clinicians consider the 10 year disease duration mark as significant, however the clinical status and health-related quality of life of patients reaching this milestone have not been well documented. METHODS: A cross-sectional study was performed on PD patients with ≥ 10 years disease duration (PD-10) (n = 1835) included in the multicenter National Parkinson's Foundation Quality Improvement Initiative (NPF-QII). Demographic, clinical and health-related quality of life data was analyzed. RESULTS: PD-10 patients (62.2% male) had a mean age of 67.8 years (± 9.5) with a mean age of PD onset of 52.7 years (± 10.6), and median disease duration 14.3 years (interquartile range 11.5-18.1). Many were minimally disabled with Hoehn and Yahr stage 1 or 2 (44.0%) or experiencing postural instability (HY stage 3, 40.3%). Most (88.2%) were able to stand unaided, but falls were common (54.8%). Almost all were living at home (93.1%) with a family member as a regular caregiver (83.8%). PD-10 patients had an average of 1.9 (± 1.4) co-morbidities, with arthritis (48.9%) and heart problems (31.7%) most commonly encountered. The majority (86.7%) took at least 2 medications: levodopa (95.7%), dopamine agonists (45.6%) and antidepressants (37.3%) were most commonly recorded. Most PD-10 patients were not currently utilizing physical, occupational or speech therapy, although two-thirds reported engaging in physical activity. Deep brain stimulation was documented in 22.4%. Overall the mean health-related quality of life and caregiver burden was impaired in all domains. CONCLUSIONS: Our data on PD patients with at least 10 years disease duration confirmed the younger age of onset of PD, but not the higher proportion of females or rest tremor, or the lower proportion of Caucasians seen in other aged PD cohorts. PD-10 patients had increased disease burden, increased caregiver burden, and impaired health-related quality of life. Although subjects mostly remained independently mobile, balance could be impaired with frequent falls identified. The prevalence of PD-10 patients living at home (93%) was very high in our sample which was drawn from specialty clinics, compared to prior studies reporting up to 27% PD patients institutionalized at 10 years duration. Thus policies to improve in-home support and caregiver support will be crucial in efforts aimed at maintaining patients in a home setting.

The Frequency of Nonmotor Symptoms among Advanced Parkinson Patients May Depend on Instrument Used for Assessment.

Background. Nonmotor symptoms (NMS) of Parkinson's disease (PD) may be more debilitating than motor symptoms. The purpose of this study was to determine the frequency and corecognition of NMS among our advanced PD cohort (patients considered for deep brain stimulation (DBS)) and caregivers. Methods. NMS-Questionnaire (NMS-Q), a self-administered screening questionnaire, and NMS Assessment-Scale (NMS-S), a clinician-administered scale, were administered to PD patients and caregivers. Results. We enrolled 33 PD patients (23 males, 10 females) and caregivers. The most frequent NMS among patients using NMS-Q were gastrointestinal (87.9%), sleep (84.9%), and urinary (72.7%), while the most frequent symptoms using NMS-S were sleep (90.9%), gastrointestinal (75.8%), and mood (75.8%). Patient/caregiver scoring correlations for NMS-Q and NMS-S were 0.670 (P < 0.0001) and 0.527 (P = 0.0016), respectively. Conclusion The frequency of NMS among advanced PD patients and correlation between patients and caregivers varied with the instrument used. The overall correlation between patient and caregiver was greater with NMS-Q than NMS-S.

Hospitalization in Parkinson disease: a survey of National Parkinson Foundation Centers.

OBJECTIVES: To explore current practices and opinions regarding hospital management of Parkinson disease (PD) patients in specialized PD Centers. METHODS: Fifty-one out of 54 National Parkinson Foundation (NPF) Centers worldwide completed an online survey regarding hospitalization of PD patients. RESULTS: Many Centers were concerned about the quality of PD-specific care provided to their patients when hospitalized. Primary concerns were adherence to the outpatient medication schedule and poor understanding by hospital staff of medications that worsen PD. Few Centers had a policy with their primary hospital that notified them when their patients were admitted. Rather, notification of hospitalization came often from the patient or a family member. Several Centers (29%) reported not finding out about a hospitalization until a routine clinic visit after discharge. Quick access to outpatient PD care following discharge was a problem in many Centers. Elective surgery, fall/fracture, infection, and mental status changes, were identified as common reasons for hospitalization. CONCLUSIONS: There is a perceived need for PD specialists to be involved during hospitalization of their patients. Improvement in communication between hospitals and PD Centers is necessary so that hospital clinicians can take advantage of PD specialists' expertise. Education of hospital staff and clinicians regarding management of PD, complications of PD, and medications to avoid in PD is critical. Most importantly, outpatient access to PD specialists needs to be improved, which may prevent unnecessary hospitalizations in these patients.

Management of the hospitalized patient with Parkinson's disease: current state of the field and need for guidelines.

OBJECTIVE: To review the literature and to identify practice gaps in the management of the hospitalized Parkinson's disease (PD) patient. BACKGROUND: Patients with PD are admitted to hospitals at higher rates, and frequently have longer hospital stays than the general population. Little is known about outpatient interventions that might reduce the need for hospitalization and also reduce hospital-related complications. METHODS: A literature review was performed on PubMed about hospitalization and PD between 1970 and 2010. In addition, in press peer-reviewed papers or published abstracts known to the authors were included. Information was reviewed by a National Parkinson Foundation workgroup and a narrative review article was generated. RESULTS: Motor disturbances in PD are believed to be a causal factor in the higher rates of admissions and complications. However, other conditions are commonly recorded as the primary reason for hospitalization including motor complications, reduced mobility, lack of compliance, inappropriate use of neuroleptics, falls, fractures, pneumonia, and other important medical problems. There are many relevant issues related to hospitalization in PD. Medications, dosages and specific dosage schedules are critical. Staff training regarding medications and medication management may help to avoid complications, particularly those related to reduced mobility, and aspiration pneumonia. Treatment of infections and a return to early mobility is also critical to management. CONCLUSIONS: Educational programs, recommendations, and guidelines are needed to better train interdisciplinary teams in the management of the PD patient. These initiatives have the potential for both cost savings and improved outcomes from a preventative and a hospital management standpoint.