Comprehensive Stroke Care and Outcomes: Time for a Paradigm Shift.

Worldwide, stroke is prevalent, costly, and disabling in >80 million survivors. The burden of stroke is increasing despite incredible progress and advancements in evidence-based acute care therapies and despite the substantial changes being made in acute care stroke systems, processes, and quality metrics. Although there has been increased global emphasis on the importance of postacute stroke care, stroke system changes have not expanded to include postacute care and outcome follow-up. Our objectives are to describe the gaps and challenges in postacute stroke care and suboptimal stroke outcomes; to report on stroke survivors' and caregivers' perceptions of current postacute stroke care and their call for improvements in follow-up services for recovery and secondary prevention; and, ultimately, to make the case that a paradigm shift is needed in the definition of comprehensive stroke care and the designation of Comprehensive Stroke Center. Three recommendations are made for a paradigm shift in comprehensive stroke care: (1) criteria should be established for designation of rehabilitation readiness for Comprehensive Stroke Centers, (2) The American Heart Association/American Stroke Association implement an expanded Get With The Guidelines-Stroke program and criteria for comprehensive stroke centers to be inclusive of rehabilitation readiness and measure outcomes at 90 days, and (3) a public health campaign should be launched to offer hopeful and actionable messaging for secondary prevention and recovery of function and health. Now is the time to honor the patients' and caregivers' strongest ask: better access and improved secondary prevention, stroke rehabilitation, and personalized care.

Recommendations for the Establishment of Stroke Systems of Care: A 2019 Update.

In 2005, the American Stroke Association published recommendations for the establishment of stroke systems of care and in 2013 expanded on them with a statement on interactions within stroke systems of care. The aim of this policy statement is to provide a comprehensive review of the scientific evidence evaluating stroke systems of care to date and to update the American Stroke Association recommendations on the basis of improvements in stroke systems of care. Over the past decade, stroke systems of care have seen vast improvements in endovascular therapy, neurocritical care, and stroke center certification, in addition to the advent of innovations, such as telestroke and mobile stroke units, in the context of significant changes in the organization of healthcare policy in the United States. This statement provides an update to prior publications to help guide policymakers and public healthcare agencies in continually updating their stroke systems of care in light of these changes. This statement and its recommendations span primordial and primary prevention, acute stroke recognition and activation of emergency medical services, triage to appropriate facilities, designation of and treatment at stroke centers, secondary prevention at hospital discharge, and rehabilitation and recovery.

Guidelines for Adult Stroke Rehabilitation and Recovery: A Guideline for Healthcare Professionals From the American Heart Association/American Stroke Association.

PURPOSE: The aim of this guideline is to provide a synopsis of best clinical practices in the rehabilitative care of adults recovering from stroke. METHODS: Writing group members were nominated by the committee chair on the basis of their previous work in relevant topic areas and were approved by the American Heart Association (AHA) Stroke Council's Scientific Statement Oversight Committee and the AHA's Manuscript Oversight Committee. The panel reviewed relevant articles on adults using computerized searches of the medical literature through 2014. The evidence is organized within the context of the AHA framework and is classified according to the joint AHA/American College of Cardiology and supplementary AHA methods of classifying the level of certainty and the class and level of evidence. The document underwent extensive AHA internal and external peer review, Stroke Council Leadership review, and Scientific Statements Oversight Committee review before consideration and approval by the AHA Science Advisory and Coordinating Committee. RESULTS: Stroke rehabilitation requires a sustained and coordinated effort from a large team, including the patient and his or her goals, family and friends, other caregivers (eg, personal care attendants), physicians, nurses, physical and occupational therapists, speech-language pathologists, recreation therapists, psychologists, nutritionists, social workers, and others. Communication and coordination among these team members are paramount in maximizing the effectiveness and efficiency of rehabilitation and underlie this entire guideline. Without communication and coordination, isolated efforts to rehabilitate the stroke survivor are unlikely to achieve their full potential. CONCLUSIONS: As systems of care evolve in response to healthcare reform efforts, postacute care and rehabilitation are often considered a costly area of care to be trimmed but without recognition of their clinical impact and ability to reduce the risk of downstream medical morbidity resulting from immobility, depression, loss of autonomy, and reduced functional independence. The provision of comprehensive rehabilitation programs with adequate resources, dose, and duration is an essential aspect of stroke care and should be a priority in these redesign efforts. (Stroke.2016;47:e98-e169. DOI: 10.1161/STR.0000000000000098.).

PRISM II: an open-label study to assess effectiveness of dextromethorphan/quinidine for pseudobulbar affect in patients with dementia, stroke or traumatic brain injury.

BACKGROUND: Phase 3 trials supporting dextromethorphan/quinidine (DM/Q) use as a treatment for pseudobulbar affect (PBA) were conducted in patients with amyotrophic lateral sclerosis (ALS) or multiple sclerosis (MS). The PRISM II study provides additional DM/Q experience with PBA secondary to dementia, stroke, or traumatic brain injury (TBI). METHODS: Participants in this open-label, multicenter, 90-day trial received DM/Q 20/10 mg twice daily. The primary outcome was the Center for Neurologic Study-Lability Scale (CNS-LS), assessing change in PBA episode frequency and severity. The CNS-LS final visit score was compared to baseline (primary analysis) and to the response in a previously conducted placebo-controlled trial with DM/Q in patients with ALS or MS. Secondary outcomes included change in PBA episode count and Clinical Global Impression of Change with respect to PBA as rated by a clinician (CGI-C) and by the patient or caregiver (PGI-C). RESULTS: The study enrolled 367 participants with PBA secondary to dementia, stroke, or TBI. Mean (standard deviation [SD]) CNS-LS score improved significantly from 20.4 (4.4) at baseline to 12.8 (5.0) at Day 90/Final Visit (change, -7.7 [6.1]; P < .001, 95 % CI: -8.4, -7.0). This magnitude of improvement was consistent with DM/Q improvement in the earlier phase-3, placebo-controlled trial (mean [95 % CI] change from baseline, -8.2 [-9.4, -7.0]) and numerically exceeds the improvement seen with placebo in that study (-5.7 [-6.8, -4.7]). Reduction in PBA episode count was 72.3 % at Day 90/Final Visit compared with baseline (P < .001). Scores on CGI-C and PGI-C showed that 76.6 and 72.4 % of participants, respectively, were "much" or "very much" improved with respect to PBA. The most frequently occurring adverse events (AEs) were diarrhea (5.4 %), headache (4.1 %), urinary tract infection (2.7 %), and dizziness (2.5 %); 9.8 % had AEs that led to discontinuation. Serious AEs were reported in 6.3 %; however, none were considered treatment related. CONCLUSIONS: DM/Q was shown to be an effective and well-tolerated treatment for PBA secondary to dementia, stroke, or TBI. The magnitude of PBA improvement was similar to that reported in patients with PBA secondary to ALS or MS, and the adverse event profile was consistent with the known safety profile of DM/Q. TRIAL REGISTRATION: Clinicaltrials.gov, NCT01799941, registered on 25 February 2013.

Palliative and end-of-life care in stroke: a statement for healthcare professionals from the American Heart Association/American Stroke Association.

BACKGROUND AND PURPOSE: The purpose of this statement is to delineate basic expectations regarding primary palliative care competencies and skills to be considered, learned, and practiced by providers and healthcare services across hospitals and community settings when caring for patients and families with stroke. METHODS: Members of the writing group were appointed by the American Heart Association Stroke Council's Scientific Statement Oversight Committee and the American Heart Association's Manuscript Oversight Committee. Members were chosen to reflect the diversity and expertise of professional roles in delivering optimal palliative care. Writing group members were assigned topics relevant to their areas of expertise, reviewed the appropriate literature, and drafted manuscript content and recommendations in accordance with the American Heart Association's framework for defining classes and level of evidence and recommendations. RESULTS: The palliative care needs of patients with serious or life-threatening stroke and their families are enormous: complex decision making, aligning treatment with goals, and symptom control. Primary palliative care should be available to all patients with serious or life-threatening stroke and their families throughout the entire course of illness. To optimally deliver primary palliative care, stroke systems of care and provider teams should (1) promote and practice patient- and family-centered care; (2) effectively estimate prognosis; (3) develop appropriate goals of care; (4) be familiar with the evidence for common stroke decisions with end-of-life implications; (5) assess and effectively manage emerging stroke symptoms; (6) possess experience with palliative treatments at the end of life; (7) assist with care coordination, including referral to a palliative care specialist or hospice if necessary; (8) provide the patient and family the opportunity for personal growth and make bereavement resources available if death is anticipated; and (9) actively participate in continuous quality improvement and research. CONCLUSIONS: Addressing the palliative care needs of patients and families throughout the course of illness can complement existing practices and improve the quality of life of stroke patients, their families, and their care providers. There is an urgent need for further research in this area.

Effects on decreasing upper-limb poststroke muscle tone using transcranial direct current stimulation: a randomized sham-controlled study.

OBJECTIVE: To assess the efficacy of transcranial direct current stimulation (tDCS) on decreasing upper-limb (UL) muscle tone after stroke. DESIGN: A prospective, sham-controlled, randomized controlled trial with 4-weeks follow-up. Randomization into the tDCS group or the control group. SETTING: Rehabilitation education and research hospital. PARTICIPANTS: Inpatients (N=90, 45 per group; age range, 15-70y; 69 men, 21 women; duration of stroke, 2-12mo) with poststroke UL spasticity. No participant withdrew because of adverse effects. INTERVENTION: The tDCS group received tDCS to the primary sensorimotor cortex of the affected side with cathodal stimulation, 20 minutes per day, 5 days per week, for 4 weeks and conventional physical therapy. The control group received sham stimulation (same area as the tDCS group) and conventional physical therapy. MAIN OUTCOME MEASURES: Modified Ashworth scale (MAS), Fugl-Meyer Assessment of motor recovery, and Barthel Index. All outcomes were measured at admission, after treatment, and after follow-up. A clinically important difference (CID) was defined as a reduction of ≥1 in the MAS score. RESULTS: Compared with the sham tDCS group, the active tDCS group had significantly more patients with a clinically important difference after treatment (80% and 78% vs 6% and 9%) and at 4-week follow-up (84% and 82% vs 7% and 4%), and UL motor function and activities of daily living (ADL) assessment improved more significantly in the active tDCS group (Fugl-Meyer Assessment of motor recovery from 12 [range, 4-26] to 22 [range, 7-50] to 32 [range, 28-41], Barthel Index from 55 [range, 0-85] to 85 [range, 5-100] to 90 [range, 10-100 vs Fugl-Meyer Assessment of motor recovery from 8 [range, 3-34] to 10 [range, 8-25] to 15 [range, 6-40], Barthel Index from 55 [range, 25-95] to 65 [range, 30-100] to 75 [range, 40-100], respectively, P<.01). CONCLUSIONS: UL muscle tone after stroke can be decreased using cathodal tDCS. Combined with conventional physical therapy, tDCS appears to improve motor function and ADL. Cathodal tDCS over ipsilesional primary sensorimotor cortex may inhibit primary sensorimotor cortex hyperactivation, resulting in significant reductions in muscle tone.

Anxiety and depression associated with caregiver burden in caregivers of stroke survivors with spasticity.

OBJECTIVE: To investigate the relationship between anxiety/depression and caregiver burden in informal caregivers of stroke survivors with spasticity. DESIGN: Data were collected via online surveys from informal caregivers 18 years or older who cared for stroke survivors. SETTING: Internet-based survey. PARTICIPANTS: 2007 through 2009 U.S. National Health and Wellness Survey database or Lightspeed Research general panel respondents (N=153). INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Anxiety and depression were self-reported by the caregiver as a physician diagnosis. Depression severity was measured by the Patient Health Questionnaire-9 (PHQ-9). Caregiver burden was measured by the Oberst Caregiving Burden Scale (OCBS) and the Bakas Caregiving Outcomes Scale (BCOS). Logistic regression analyses were conducted with anxiety, depression, and the PHQ-9 depression severity categories as a result of each caregiver burden scale. RESULTS: Data were analyzed for 153 informal caregivers; they were mostly women (70.6%) and white (78.4%), with a mean age of 51.6 years. For every 1-point increase in the OCBS Difficulty Scale, the odds of anxiety or depression were 2.57 times as great (P<.001) and 1.88 times as great (P=.007), respectively. The odds of PHQ-9 severe depression versus all other categories combined were 2.48 times as great (P<.001). For every 1-point decrease in the BCOS, the odds of anxiety or depression were 2.43 times as great (P<.001) and 2.27 times as great (P=.002), respectively. The odds of PHQ-9 severe depression versus all other categories combined were 4.55 times as great (P<.001). CONCLUSIONS: As caregiver burden increases, caregivers are more likely to have anxiety and depression. Depression severity also increases. Providing treatment to stroke survivors with spasticity that lessens the time and more importantly, the difficulty of caregiving may lead to a reduction in caregiver anxiety and depression.

Death and rehospitalization after transient ischemic attack or acute ischemic stroke: one-year outcomes from the adherence evaluation of acute ischemic stroke-longitudinal registry.

BACKGROUND: Longitudinal data directly comparing the rates of death and rehospitalization of patients discharged after transient ischemic attack (TIA) versus acute ischemic stroke (AIS) are lacking. METHODS: Data were analyzed from 2802 patients (TIA n = 552; AIS n = 2250) admitted to 100 U.S. hospitals participating in the Get With The Guidelines-Stroke and the Adherence Evaluation of Acute Ischemic Stroke-Longitudinal registry. The primary composite outcome was the adjusted rate of all-cause death and rehospitalization over 1 year after discharge. Four additional single or combined outcomes were explored. RESULTS: Compared with AIS, TIA patients were older (median 69 v 66 years; P = .007) and more likely female (53.3% v 44.2%; P < .0001). Secondary prevention medication use after hospital discharge was less intensive after TIA, with underuse for both conditions. All-cause death or rehospitalization at 1 year was similar for TIA and AIS patients (37.7% v 34.6%; P = .271); the frequency for TIA patients was higher after covariate adjustment (hazard ratio [HR] 1.19; 95% confidence interval [CI] 1.01-1.41). One-year all-cause mortality was similar among those with TIA compared to AIS patients (3.8% v 5.7%; P = .071; adjusted HR 0.86; 95% CI 0.52-1.42). All-cause rehospitalizations were higher for TIA compared to AIS patients (36.4% v 33.0%; P = .186; adjusted HR 1.20; 95% CI 1.02-1.42), but similar for stroke rehospitalizations (10.1% v 7.4%; P = .037; adjusted HR 1.38, 95% CI 0.997-1.92). CONCLUSIONS: Patients with TIA have similar or worse 12-month postdischarge risk of death or rehospitalization as compared with those with AIS. Outcomes after TIA and AIS might be improved with better adherence to secondary preventive guidelines.

Comparison of Functional Outcomes After Acute Inpatient Rehabilitation After Acquired Brain Injury Before and During the COVID-19 Pandemic.

OBJECTIVE: The objective of this study was to characterize and compare functional outcomes of acquired brain injury patients in an inpatient rehabilitation facility in the year before (April 2019-March 2020) and during the first year (April 2020-March 2021) of the COVID-19 pandemic, when the most drastic changes in the delivery of health care occurred. DESIGN: In this retrospective single-center chart review study, functional outcomes, based on the Center for Medicare and Medicaid Services Inpatient Rehabilitation Facility-Patient Assessment Instrument, were obtained and analyzed for patients in acute inpatient rehabilitation with acquired brain injury. RESULTS: Data from 1330 patients were included for analysis. Functional outcomes of average self-care, bed mobility, and transfer scores were statistically, but not clinically, different between groups. More patients in the pandemic group were discharged home (prepandemic n = 454 [65.4%]; pandemic n = 461 [72.6%]; P = 0.011), although they had significantly longer lengths of stay (prepandemic median = 14.0 [interquartile range = 9.0-23.0]; pandemic = 16.0 [10.0-23.0]; P = 0.037). CONCLUSIONS: Despite the impact of hospital policies due to the COVID-19 pandemic, similar functional outcomes were obtained for those with acquired brain injury after inpatient rehabilitation.

Clinical presentation of patients with lower limb spasticity undergoing routine treatment with botulinum toxin: baseline findings from an international observational study.

OBJECTIVE: Describe how people with lower limb spasticity present for treatment in routine clinical practice. METHODS: Prospective, observational study (Clinicaltrials.gov: NCT04050527) of ambulatory adult patients (≥ 18 years) with unilateral lower limb spasticity (able to take ≥ 5 steps with or without assistance) presenting for routine spasticity management, including treatment with abobotulinumtoxinA. RESULTS: The study population included 430 adults with lower limb spasticity. Despite their relatively young age (mean ± standard deviation 53.7 ± 13.9 years), only 20% of patients were employed. Most patients had an acquired brain injury due to cerebrovascular disease; 84.1% reported having concomitant upper limb spasticity. Using the Leg Activity Measure, most patients reported no or only mild difficulties in performing hygiene/positioning tasks, while 80.7% had at least mild difficulty with indoor ambulation and 90.5% had at least mild difficulty with walking outdoors. Sensory, communication and/or cognitive impairments were also common. At the first treatment cycle, 50.7% of patients set active function primary goals, including locomotion transferring or standing. CONCLUSION: These observations highlight the complexity of presentation that must be considered when setting treatment goals for lower limb spasticity and emphasize the types of impairment and activity (functional) limitations that treating teams may expect to encounter in their patients and should cover in their initial and follow-up assessments.

Telehealth in PM&R: Past, present, and future in clinical practice and opportunities for translational research.

Telehealth refers to the use of telecommunication devices and other forms of technology to provide services outside of the traditional in-person health care delivery system. Growth in the use of telehealth creates new challenges and opportunities for implementation in clinical practice. The American Academy of Physical Medicine and Rehabilitation (AAPM&R) assembled an expert group to develop a white paper to examine telehealth innovation in Physical Medicine and Rehabilitation (PM&R). The resultant white paper summarizes how telehealth is best used in the field of PM&R while highlighting current knowledge deficits and technological limitations. The report identifies new and transformative opportunities for PM&R to advance translational research related to telehealth and enhance patient care.

Advances in brain recovery and rehabilitation 2010.

Discoveries in the past year have impacted the understanding of brain recovery and there is more of a need than ever for a foothold in recovery and rehabilitation This review reports on translational efforts, new (and old) potential drugs, various approaches to neurorehabilitation, and brain imaging that demonstrate reorganization in the human brain during stroke rehabilitation.

Metrics for measuring quality of care in comprehensive stroke centers: detailed follow-up to Brain Attack Coalition comprehensive stroke center recommendations: a statement for healthcare professionals from the American Heart Association/American Stroke Association.

BACKGROUND: Stroke is a major cause of disability and death. The Brain Attack Coalition has proposed establishment of primary and comprehensive stroke centers to provide appropriate care to stroke patients who require basic and more advanced interventions, respectively. Primary stroke centers have been designated by The Joint Commission since 2003, as well as by various states. The designation of comprehensive stroke centers (CSCs) is now being considered. To assist in this process, we propose a set of metrics and related data that CSCs should track to monitor the quality of care that they provide and to facilitate quality improvement. METHODS AND RESULTS: We analyzed available guideline statements, reviews, and other literature to identify the major features that distinguish CSCs from primary stroke centers, drafted a set of metrics and related data elements to measure the key components of these aspects of stroke care, and then revised these through an iterative process to reach a consensus. We propose a set of metrics and related data elements that cover the major aspects of specialized care for patients with ischemic cerebrovascular disease and nontraumatic subarachnoid and intracerebral hemorrhages at CSCs. CONCLUSIONS: The metrics that we propose are intended to provide a framework for standardized data collection at CSCs to facilitate local quality improvement efforts and to allow for analysis of pooled data from different CSCs that may lead to development of national performance standards for CSCs in the future.

Stroke rehabilitation quality indicators: raising the bar in the inpatient rehabilitation facility.

Even though quality indicators are becoming more common in clinical medicine, there are very few of them in the area of stroke rehabilitation. This article proposes quality indicators for stroke rehabilitation based upon the Donabedian triad of structure, process, and outcomes. The quality indicators are in 3 categories: service delivery; system care coordination; and stroke prevention, health promotion, and medical management. Specific areas of focus include organized care, intensity of service, transitions of care, secondary stroke prevention, hypertension, diabetes mellitus, coronary artery disease, hyperlipidemia, deep venous thrombosis prophylaxis, pneumonia and influenza vaccines, and patient and professional education. By highlighting both the presence and absence of evidence in various aspects of stroke rehabilitation, clinicians and researchers can focus on quality improvement in areas that already are known while providing opportunities for research into areas that evidence does not yet support.

Costs and rehabilitation use of stroke survivors: a retrospective study of Medicare beneficiaries.

OBJECTIVE: To examine mortality, costs, and rehabilitation use in patients with stroke and stroke-related hemiparesis during a 4-year period following stroke onset. METHOD: This study was a retrospective, longitudinal claims analysis. Patients newly diagnosed with stroke and discharged from the hospital were identified from a 5% random sample of Medicare beneficiaries. Mortality, total Medicare costs, use of rehabilitation, and associated costs in stroke survivors with or without hemiparesis were the main outcome measures. RESULTS: Out of 4,604 newly diagnosed stroke patients, 1,166 developed hemiparesis. The 4-year mortality rate was significantly higher in the hemiparesis cohort than the nonhemiparesis cohort (55.2% vs. 47.5%; p < .01). The average Medicare cost per patient over the 4-year period was $77,143 for the hemiparesis cohort and $53,319 for the nonhemiparesis cohort (p < .01). A significantly higher proportion of patients in the hemiparesis cohort received rehabilitation than in the nonhemiparesis cohort (84% vs. 36% in Year 1, 30% vs. 10% in Year 2, 21% vs. 9% in Year 3, 16% vs. 7% in Year 4). Among patients who received rehabilitation, costs were significantly higher for the hemiparesis cohort ($17,680) than for the nonhemiparesis cohort ($7,841) in the fi rst year. While most rehabilitation costs for the hemiparesis cohort were incurred in the hospital inpatient setting in the fi rst year, the cost burden shifted to skilled nursing facilities and home health agencies in the following 3 years. CONCLUSIONS: Hemiparesis following stroke onset contributes to a higher mortality rate and higher Medicare costs in both the short and long term.

Acute Spinal Epidural Hematoma as a Complication of Dry Needling: A Case Report.

Dry needling is a procedure commonly performed for the relief of myofascial pain disorders. The procedure is generally well tolerated. Adverse events often are mild, but severe complications have been reported. This case report describes an acute spinal epidural hematoma as a complication of dry needling. It is a reminder to the performing physician or therapist to take specific precautions when placing a needle near the spine. Sudden onset of neuropathic pain after needling therapy in and around the spine should prompt emergency assessment with possibly advanced spine imaging to evaluate the integrity of the spinal cord. LEVEL OF EVIDENCE: V.

Dextromethorphan/Quinidine for Pseudobulbar Affect Following Stroke: Safety and Effectiveness in the PRISM II Trial.

BACKGROUND: Dextromethorphan (DM) / quinidine (Q) was approved for pseudobulbar affect (PBA) treatment based on efficacy and safety trials in patients with PBA caused by amyotrophic lateral sclerosis or multiple sclerosis. The PRISM II trial evaluated DM/Q as PBA treatment in patients with stroke, dementia, or traumatic brain injury. OBJECTIVE: To report results from the stroke cohort of PRISM II, including the Stroke Impact Scale (SIS). DESIGN: Open-label trial evaluating twice-daily DM/Q over 90 days. STUDY PARTICIPANTS: Adults (n = 113) with a clinical diagnosis of PBA secondary to stroke; stable psychiatric medications were allowed. METHODS: PRISM II was an open-label, 12-week trial enrolling adults with PBA caused by dementia, stroke (reported here), or TBI. All study participants received DM/Q 20/10 mg twice daily. Study visits occurred at baseline and at days 30 and 90. SETTING: 150 U.S. centers. MAIN OUTCOME MEASUREMENTS: Primary efficacy measure was changed from baseline to day 90 in Center for Neurologic Study-Lability Scale (CNS-LS) scores. Secondary outcomes included PBA episodes (estimated over 7 days), Clinical and Patient/Caregiver Global Impression of Change (CGI-C and PGI-C), Quality of Life-Visual Analog Scale (QOL-VAS), SIS, Patient Health Questionnaire (PHQ-9), and Mini-Mental State Examination (MMSE). RESULTS: Compared with baseline, CNS-LS scores (SD) improved by -6.2 (6.1, P < .001) at day 30 and -7.6 (6.7, P < .001) at day 90. PBA episodes were reduced by 65% and 75% at day 30 and 90, respectively. Seventy-five percent of clinicians and 67% of patients/caregivers rated PBA as "much" or "very much improved." All SIS items significantly improved from baseline (P < .05, all). Adverse events included diarrhea (4.4%), headache (3.5%), constipation (2.7%), and dizziness (2.7%); 5.3% had adverse events leading to study discontinuation. CONCLUSIONS: DM/Q effectively treated PBA and was associated with global and functional improvement; adverse events were consistent with the known safety profile of DM/Q.