Regionalization of stroke systems of care in the stroke belt states: The IMPROVE stroke care quality improvement program.

BACKGROUND: Despite guidelines and strong evidence supporting intravenous thrombolysis and endovascular thrombectomy for acute stroke, access to these interventions remains a challenge. The objective of the IMPROVE stroke care program was to accelerate acute stroke care delivery by implementing best practices and improving the regional systems of care within comprehensive stroke networks. METHODS: The IMPROVE Stroke Care program was a prospective quality improvement program based on established models used in acute coronary care. Nine hub hospitals (comprehensive stroke centers), 52 regional/community referral hospitals (spokes), and over 100 emergency medical service agencies participated. Through 6 regional meetings, 49 best practices were chosen for improvement by the participating sites. Over 2 years, progress was tracked and discussed weekly and performance reviews were disseminated quarterly. RESULTS: Data were collected on 21,647 stroke code activations of which 8,502 (39.3%) activations had a final diagnosis of stroke. There were 7,226 (85.0%) ischemic strokes, and thrombolytic therapy was administered 2,814 times (38.9%). There was significant overall improvement in the proportion that received lytic therapy within 45 minutes (baseline of 44.6%-60.4%). The hubs were more frequently achieving this at baseline, but both site types improved. A total of 1,455 (17.1%) thrombectomies were included in the data of which 401 (27.6%) were transferred from a spoke. There was no clinically significant change in door-to-groin times for hub-presenting thrombectomy patients, however, significant improvement occurred for transferred cases, 46 minutes (interquartile range [IQR] 36, 115.5) at baseline to 27 minutes (IQR 10, 59). CONCLUSIONS: The IMPROVE program approach was successful at improving the delivery of thrombolytic intervention across the consortium at both spoke and hub sites through collaborative efforts to operationalize guideline-based care through iterative sharing of performance and best practices for implementation. Our approach allowed identification of both opportunities for improvement and operational best practices providing guidance on how best to create a regional stroke care network and operationalize the published acute stroke care guidelines.

Association of time-temperature curves with outcomes in temperature management for cardiac arrest.

Background/Purpose: Cardiac arrest is a common cause of death and neurological injury; therapeutic cooling for neuroprotection is standard of care. Despite numerous and ongoing trials targeting a specified cooling temperature for a target duration, the concept of temperature dose-the duration spent at a given depth of hypothermia-is not as well explored. Methods: In this retrospective study, we examined 66 patients 18 years of age or older undergoing therapeutic hypothermia for cardiac arrest between 2007 and 2010 to assess the relationship of temperature dose with outcomes. Demographic, clinical, outcome and temperature data were collected. Demographic and clinical data underwent bivariate regression analysis for association with outcome. Time-temperature curves were divided into pre-determined temperature thresholds and assessed by logistic regression analysis for association with outcome. A second, multivariate regression analysis was performed controlling for factors associated with poor outcomes. Results: Old age was significantly associated with poor outcome and a shockable arrest rhythm was significantly associated with positive outcome. Subjects spent an average of 2.82 hours below 35°C, 7.31 hours ≥35°C to ≤36.5°C, 24.75 hours >36.5 to <38.0°C and 7.06 hours ≥38°C. Logistic regression analysis revealed borderline significant positive association between good outcome and time at a cooling depth (35°C-36.5°C, p=0.05); adjusted for old age, the association became significant (p=0.04). Conclusion: Controlling for old age, longer durations between >35°C, ≤36.5°C during therapeutic hypothermia for cardiac arrest were significantly associated with good clinical outcomes. Time spent within a given temperature range may be useful for measuring the effect of temperature management.

Socioeconomic Influence on Emergency Medical Services Utilization for Acute Stroke: Think Nationally, Act Locally.

BACKGROUND AND PURPOSE: Rates of emergency medical services (EMS) utilization for acute stroke remain low nationwide, despite the time-sensitive nature of the disease. Prior research suggests several demographic and social factors are associated with EMS use. We sought to evaluate which demographic or socioeconomic factors are associated with EMS utilization in our region, thereby informing future education efforts. METHODS: We performed a retrospective analysis of patients for whom the stroke code system was activated at 2 hospitals in our region. Univariate and logistic regression analysis was performed to identify factors associated with use of EMS versus private vehicle. RESULTS: EMS use was lower in patients who were younger, had higher income, were married, more educated and in those who identified as Hispanic. Those arriving by EMS had significantly faster arrival to code, arrival to imaging, and arrival to thrombolytic treatment times. CONCLUSION: Analysis of regional data can identify specific populations underutilizing EMS services for acute stroke symptoms. Factors effecting EMS utilization varies by region and this information may be useful for targeted education programs promoting EMS use for acute stroke symptoms. EMS use results in more rapid evaluation and treatment of stroke patients.

Investigation of S-Nitrosoglutathione in stroke: A systematic review and meta-analysis of literature in pre-clinical and clinical research.

BACKGROUND: S-Nitrosoglutathione (GSNO) is a nitric oxide donor that has been investigated for neuroprotective and neuro-recovery effect. We aimed to conduct a systematic review on the published literatures using GSNO in both pre-clinical and clinical stroke studies. METHODS: We searched PubMed up to June 30, 2019, using the following keywords: S-Nitrosoglutathione, GSNO, stroke, cerebrovascular, carotid arteries, middle cerebral artery, and middle cerebral artery occlusion. Only studies published in the English language providing efficacy results of GSNO on ischemic stroke were included. Stroke Therapy Academic Industry Roundtable (STAIR) score was used to assess the quality of pre-clinical studies and PEDro score for clinical trials. A meta-analysis was conducted to compare the effect size. RESULTS: Of 39 articles identified, 10 (6 for pre-clinical and 4 for clinical studies) met the eligibility criteria and were included. The median STAIR score across the pre-clinical studies was 5.5 (range: 4-7), and the median PEDro score for the 4 clinical trials was 10 (ranged: 6 to 10). Among the 6 pre-clinical studies, GSNO reduced infarct size in 6 studies and improved neurological behavior scales in 5 studies compared to placebo. Inverse-variance weighted linear meta-analysis of standardized mean difference (Hedge's g) on 4 human studies revealed a big effect size (Hedge's g = -0.82, 95% CI: [-1.26, -0.38], P = .0003) favoring the GSNO group in term of reducing embolic signals. I2 value was 0 across the included clinical studies in the meta-analysis. CONCLUSIONS: Pre-clinical studies showed positive benefit of GSNO in animal stroke models. The meta-analysis of clinical studies demonstrated that GSNO is effective in reducing embolic signals in patients with symptomatic internal carotid artery stenosis undergoing carotid endarterectomy or stenting. Further investigation of this molecule is warranted.

Implementation of Best Practices-Developing and Optimizing Regional Systems of Stroke Care: Design and Methodology.

The AHA Guidelines recommend developing multi-tiered systems for the care of patients with acute stroke.1 An ideal stroke system of care should ensure that all patients receive the most efficient and timely care, regardless of how they first enter or access the medical care system. Coordination among the components of a stroke system is the most challenging but most essential aspect of any system of care. The Implementation of Best Practices For Acute Stroke Care-Developing and Optimizing Regional Systems of Stroke Care (IMPROVE Stroke Care) project, is designed to implement existing guidelines and systematically improve the acute stroke system of care in the Southeastern United States. Project participation includes 9 hub hospitals, approximately 80 spoke hospitals, numerous pre-hospital agencies (911, fire, and emergency medical services) and communities within the region. The goal of the IMPROVE Stroke program is to develop a regional integrated stroke care system that identifies, classifies, and treats acute ischemic stroke patients more rapidly and effectively with reperfusion therapy. The project will identify gaps and barriers to implementation of stroke systems of care, leverage existing resources within the regions, aid in designing strategies to improve care processes, bring regional representatives together to agree on and implement best practices, protocols, and plans based on guidelines, and establish methods to monitor quality of care. The impact of implementation of stroke systems of care on mortality and long-term functional outcomes will be measured.

A Phase 2 Randomized, Sham-Controlled Trial of Internal Carotid Artery Infusion of Autologous Bone Marrow-Derived ALD-401 Cells in Patients With Recent Stable Ischemic Stroke (RECOVER-Stroke).

BACKGROUND: Ischemic stroke has no approved treatments to enhance recovery. ALD-401 is an enriched population of aldehyde dehydrogenase-bright stem cells, capable of reducing neurological deficits in animal models. The primary objective of this trial was to determine the safety of internal carotid artery, intra-arterially delivered autologous bone marrow-derived ALD-401 in patients with disabling middle cerebral artery stroke in comparison with sham harvest with sham infusion. Secondary objectives were to determine feasibility and efficacy. METHODS: This was a prospective phase 2, industry-funded, randomized, sham-controlled, parallel-group, multicenter study with blinded assessments. One hundred subjects were planned, aged 30 to 83 years, with confirmed first-time middle cerebral artery ischemic stroke with modified Rankin scale ≥3. Study patients were randomly assigned 3:2 to bone marrow harvest at 11 to 17 days after stroke followed 2 days later by intracarotid infusion of ALD-401 versus sham harvest and then sham infusion in the same timeframe. The primary study outcome was safety based on the incidence of a 4-point National Institutes of Health Stroke Scale worsening and the proportion of serious adverse events. Efficacy was based on modified Rankin scale change at 90 days. Other secondary outcomes were the proportions of patients experiencing adverse events, disability by Barthel Index, quality of life using EQ-5D, rehabilitation utilization, disability at 1 year, and MRI evidence of complications. RESULTS: There were no infusional or allergic reactions and no difference in treatment emergent adverse events. Four patients had small areas of asymptomatic restricted diffusion on MRI in the treatment group. There was no significant difference between the ALD-401 and placebo groups on the modified Rankin scale for the intent-to-treat population at day 90 (mean difference, 0.3; 95% CI, -0.3 to 0.8; P=0.330). There were no significant differences between the groups on any of the secondary efficacy measures. CONCLUSIONS: Intracarotid infusion of ALD-401 does not lead to clinical adverse events in patients with subacute ischemic stroke, although there was a higher incidence of small lesions on MRI in the treatment group. There was no difference in the primary efficacy end point between the groups. The study provides a framework for the design and conduct of future intra-arterial cell therapy trials in stroke. CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov . Unique identifier: NCT01273337.

Assessment of healthcare personnel knowledge of stroke care at a large referral hospital in sub-Saharan Africa - A survey based approach.

There is no published literature regarding sub-Saharan health-care providers' understanding of stroke management patterns. Understanding current stroke management knowledge is important in formulating future education opportunities for providers to optimize patient outcomes. A cross-sectional survey of acute stroke diagnosis, hospital management, and secondary prevention questions was administered to health-care providers working in one large Kenyan acute referral hospital. Due to the prevalence of medical students (61.8%), an experienced-focused analysis contrasted students with more experienced providers. Providers (n=199) anonymously responded to the surveys. Among the acute diagnosis most respondents stated that stroke scales should always used (58.3% of respondents), 3h was the time period for alteplase (t-PA) (53.8% of respondents), and CT scan should be always be obtained prior to administration of anticoagulant therapy (61.3% of respondents). Neither VTE prophylaxis nor dysphagia/swallowing screening were considered to be done a majority of time. Secondary prevention results were variable. The respondent's level of clinical experience made the most difference in correctly answering the most appropriate IV Fluid to use in stroke patients (adjusted p=0.003) and the ideal initiation time for antithrombotic therapy (adjusted p=0.0017). Healthcare providers demonstrated a wide variability in their responses. Future efforts to improve stroke care in sub-Saharan Africa should include education and process improvement initiatives to focus on more specific aspects of stroke management based on the results from this survey.

Toward Solving the Sedation-Assessment Conundrum: Neurofunction Monitoring.

The sedation-assessment conundrum is the struggle to balance the need for sedation against the need to awaken the patient and perform a neurologic examination. This article discusses the nuances of the sedation-assessment conundrum as well as approaches to resolve this and reduce the negative impact of abruptly stopping sedative infusions. Both oversedation and undersedation affect critically ill patients. This article discusses methods of assessing sedation and interpreting individualized patient responses to sedation. The use of neurofunction monitors and periods of sedation interruption are discussed within the context of addressing the sedation-assessment conundrum.

Neurological complications of cardiac surgery.

As increasing numbers of elderly people undergo cardiac surgery, neurologists are frequently called upon to assess patients with neurological complications from the procedure. Some complications mandate acute intervention, whereas others need longer term observation and management. A large amount of published literature exists about these complications and guidance on best practice is constantly changing. Similarly, despite technological advances in surgical intervention and modifications in surgical technique to make cardiac procedures safer, these advances often create new avenues for neurological injury. Accordingly, rapid and precise neurological assessment and therapeutic intervention rests on a solid understanding of the evidence base and procedural variables.

Exploring the impact of augmenting sedation assessment with physiologic monitors.

BACKGROUND: Pharmacological sedation is a necessary tool in the management of critically ill, mechanically ventilated patients. The intensive care unit (ICU) sedation strategy is to use the least amount of medication to meet safety and comfort goals. Titration of pharmacological agents is currently guided by clinical assessment tools. The purpose of this study was to determine whether the addition of a neurophysiological monitor, bispectral index (BIS), aided the ICU nurse in reducing the amount of drug used, compared to a clinical tool alone, in a general critical care population. METHODS: In this prospective clinical trial, mechanically ventilated adults (N=300) were randomised to sedation assessment using only the observational assessment tool (RASS) or a combination of observational and physiologic measures (RASS+BIS). Subjects were enrolled from a medical ICU (N=154), a trauma ICU (N=72) and a general mixed-use ICU (N=74). RESULTS: BIS-augmented sedation was only associated with the reduction of drug use when patients were sedated with propofol or narcotic agents (propofol [1.61 mg/kg/h vs. 1.77 mg/kg/h; p<0.0001], fentanyl [54.73 mcg/h vs. 66.81 mcg/h; p<0.0001], and hydromorphone [0.97 mg/h vs. 4.00 mg/h: p<0.0001] compared to RASS alone. In contrast, patients sedated with dexmedetomidine or benzodiazepines were given higher doses under the BIS-augmented dexmedetomidine [0.46 mcg/kg/h vs. 0.33 mcg/kg/h; p<0.0001], lorazepam [4.13 mg/h vs. 3.29 mg/h p<0.0001], and midazolam [3.73 mg/h vs 2.86 mg/h; p<0.0001]) protocol compared to clinical assessment alone. CONCLUSION: The clinical evaluation of depth of sedation remains the most reliable method for the titration of pharmacological sedation in the critical care unit. However, BIS-augmented assessment is helpful in reducing the amount of propofol and narcotic medication used and may be considered an adjunct when these agents are utilised.

Hyperdense posterior cerebral artery sign in a setting of spontaneous vertebral artery dissection: a blessing in disguise?

OBJECTIVE: To report a case of a hyperdense posterior cerebral artery (PCA) sign in the setting of spontaneous vertebral artery dissection. CLINICAL PRESENTATION AND INTERVENTION: A 28-year-old, previously healthy female presented with rapidly progressive coma. A noncontrast computerized tomographic (CT) scan showed a hyperdense PCA sign, which prompted an urgent arteriogram. She was found to have spontaneous vertebral artery dissection with an occluding thrombus. She underwent intra-arterial thrombolysis with tissue plasminogen activator. Follow-up magnetic resonance imaging showed an area of acute infarction in the medial temporal and occipital regions corresponding to the area supplied by the left PCA. The patient was started on systemic anticoagulation therapy with intravenous heparin. She showed slow and continued recovery but was left with significant neurological deficits that required posthospital discharge to a long-term rehabilitation facility. CONCLUSION: This case showed that the hyperdense PCA sign on a noncontrast CT scan necessitated an emergent CT angiogram that showed vertebral artery dissection and a devastating vascular occlusion. Hence, we suggest an early intervention that may allow for potential revascularization therapy.

Clevidipine rapidly and safely reduces blood pressure in acute intracerebral hemorrhage: the ACCELERATE trial.

BACKGROUND: Intracerebral hemorrhage (ICH) causes 10-15% of primary strokes, with mortality related to hematoma volume. Blood pressure (BP) reduction may attenuate hematoma expansion. ACCELERATE (the Evaluation of Patients with Acute Hypertension and Intracerebral Hemorrhage with Intravenous Clevidipine Treatment) is a pilot study representing the first evaluation of safety and efficacy of intravenous clevidipine for the rapid treatment of hypertension in ICH patients. METHODS: ICH patients with a systolic BP (SBP) >160 mm Hg who present within 6 h (n = 27) or 12 h (n = 10) of symptoms were prospectively enrolled, treated with open-label clevidipine until SBP ≤160 mm Hg was achieved and then titrated to keep target SBP between 140-160 mm Hg. RESULTS: A total of 35 patients with baseline median Glasgow Coma Scale score of 12, median NIH Stroke Scale score of 14, mean SBP of 186 mm Hg and a mean time from onset of symptoms of 5.5 h received clevidipine. Median time to achieve SBP target range was 5.5 min. All patients achieved target SBP within 30 min; 96.9% achieved target SBP with clevidipine monotherapy. CT scans showed minimal hematoma volume change for the overall population (median change 0.01 ml, -2.9%). Mild/moderate hypotension was reported in 3 patients and resolved with dose reduction or drug discontinuation. CONCLUSION: Clevidipine monotherapy was effective and safe for rapid BP reduction in this cohort of critically ill ICH patients. Overall, patients showed minimal hematoma expansion with BP reduction, suggesting that rapid BP control with clevidipine may have a beneficial impact on hematoma expansion and warrants further investigation.

Continuous cerebral spinal fluid drainage associated with complications in patients admitted with subarachnoid hemorrhage.

OBJECT: Cerebral artery vasospasm is a major cause of death and disability in patients recovering from subarachnoid hemorrhage (SAH). Although the exact cause of vasospasm is unknown, one body of research suggests that clearing blood products by CSF drainage is associated with a lower frequency and severity of vasospasm. There are multiple approaches to facilitating CSF drainage, but there is inadequate evidence to determine the best practice. The purpose of this study was to explore whether continuous or intermittent CSF drainage was superior for reducing vasospasm. METHODS: The authors performed a randomized clinical trial. Within 72 hours of admission for SAH, patients with an external ventricular drain (EVD) were randomized to undergo continuous CSF drainage with intermittent intracranial pressure (ICP) monitoring (open-EVD group) or continuous ICP monitoring with intermittent CSF drainage (monitor-ICP group). RESULTS: After 60 patients completed the study, an interim analysis was performed. The complication rate of 52.9% for the open-EVD group was significantly higher than the 23.1% complication rate for the monitor-ICP group (OR 3.75, 95% CI 1.21-11.66, p = 0.022). These results were reported to the Data Safety and Monitoring Board and enrollment was terminated. The odds ratio of vasospasm for the open-EVD versus monitor-ICP group was not significant (OR 0.44, 95% CI 0.13-1.45, p = 0.177). CONCLUSIONS: Continuous CSF drainage with intermittent ICP monitoring is associated with a higher rate of complications than continuous ICP monitoring with intermittent CSF drainage, but there is no difference between the two types of monitoring in vasospasm. Clinical trial registration no.: NCT01169454 (clinicaltrials.gov).

Transitional care after hospitalization for acute stroke or myocardial infarction: a systematic review.

BACKGROUND: Transitional care is a time-limited service to prevent discontinuous care and adverse outcomes, including rehospitalization. PURPOSE: To describe transitional care interventions and evidence of benefit or harm in patients hospitalized for acute stroke or myocardial infarction (MI). DATA SOURCES: Cumulative Index to Nursing and Allied Health Literature, MEDLINE, Cochrane Database of Systematic Reviews, and EMBASE, supplemented with manual searches of reference lists of relevant studies and review articles (January 2000 to March 2012). STUDY SELECTION: 6 reviewers screened 5857 citations to identify English-language reports of trials or observational studies that compared transitional care with usual care among adults hospitalized for stroke or MI and that reported patient, caregiver, process, or systems outcomes within 1 year of hospital discharge. DATA EXTRACTION: Data on study design, quality, population, intervention characteristics, and patient- and system-level outcomes were extracted by 3 reviewers and confirmed by 1 additional reviewer. DATA SYNTHESIS: 62 articles representing 44 studies of transitional care for either acute stroke (27 studies) or MI (17 studies). Four intervention types were studied: hospital-initiated support (n = 14), patient and family education (n = 7), community-based support (n = 20), and chronic disease management (n = 3). Most studies (68%) were of fair quality. Overall, moderate-strength evidence showed that hospital-initiated support reduced length of stay for patients who had a stroke, and low-strength evidence showed that it reduced mortality for patients who had an MI. Evidence about benefits of other interventions and harms from transitional care services was insufficient. LIMITATIONS: Few studies had high-quality research designs. The usual care comparator was often poorly defined. Applicability to U.S. clinical practice was limited; only 6 studies were conducted in the United States. CONCLUSION: Available evidence shows that hospital-initiated transitional care can improve some outcomes in adults hospitalized for stroke or MI. Finding additional transitional care interventions that improve functional outcomes and prevent rehospitalizations and adverse events is a high priority for the growing population of patients who have an MI or a stroke. PRIMARY FUNDING SOURCE: Agency for Healthcare Research and Quality.

An observational pilot study of CSF diversion in subarachnoid haemorrhage.

BACKGROUND: A primary focus of hospital treatment following admission for subarachnoid haemorrhage (SAH) is a prevention of cerebral artery vasospasm, which may result in ischaemic stroke. Intraventricular catheter (IVC) insertion to facilitate cerebral spinal fluid (CSF) drainage and intracranial pressure (ICP) monitoring may reduce the incidence or severity of vasospasm, but insufficient evidence exists from which clinicians may determine the best practice of CSF management. AIMS: The aim of this study was to provide the pilot data to explore the impact of different methods of CSF drainage on outcomes in patients with SAH. METHODS: In this non-randomized observational study, patients diagnosed with SAH who had ICP monitoring in situ were prospectively enrolled. Group assignment was determined by the method of external ventricular drainage (EVD) management prescribed by the attending physician prior to enrollment. RESULTS: The 37 subjects were disproportionately divided: open-EVD group (N = 24) and monitor-ICP group (N = 13). There were no statistically significant differences by group assignment with respect to vasospasm, length of stay (LOS), highest average ICP, total CSF drained and disability upon discharge between groups. CONCLUSIONS: Although not significant, our results show that the monitor-ICP group trended towards improved clinical outcomes. These results provide sufficient equipoise to support further research in ICP management in patients with SAH using a randomized clinical trial. RELEVANCE TO CLINICAL PRACTICE: This study provides a solid foundation for the development of a randomized trial exploring two different methods of ICP monitoring and CSF diversion during the acute phase of care following aneurysm rupture.

Transition of care for acute stroke and myocardial infarction patients: from hospitalization to rehabilitation, recovery, and secondary prevention.

OBJECTIVES: To review the available published literature to assess whether evidence supports a beneficial role for coordinated transition of care services for the postacute care of patients hospitalized with first or recurrent stroke or myocardial infarction (MI). This review was framed around five areas of investigation: (1) key components of transition of care services, (2) evidence for improvement in functional outcomes, morbidity, mortality, and quality of life, (3) associated risks or potential harms, (4) evidence for improvement in systems of care, and (5) evidence that benefits and harms vary by patient-based or system-based characteristics. DATA SOURCES: MEDLINE(®), CINAHL(®), Cochrane Database of Systematic Reviews, and Embase(®). REVIEW METHODS: We included studies published in English from 2000 to 2011 that specified postacute hospitalization transition of care services as well as prevention of recurrent stroke or MI. RESULTS: A total of 62 articles representing 44 studies were included for data abstraction. Transition of care interventions were grouped into four categories: (1) hospital -initiated support for discharge was the initial stage in the transition of care process, (2) patient and family education interventions were started during hospitalization but were continued at the community level, (3) community-based models of support followed hospital discharge, and (4) chronic disease management models of care assumed the responsibility for long-term care. Early supported discharge after stroke was associated with reduced total hospital length of stay without adverse effects on functional recovery, and specialty care after MI was associated with reduced mortality. Because of several methodological shortcomings, most studies did not consistently demonstrate that any specific intervention resulted in improved patient-or system -based outcomes. Some studies included more than one intervention, which made it difficult to determine the effect of individual components on clinical outcomes. There was inconsistency in the definition of what constituted a component of transition of care compared to "standard care." Standard care was poorly defined, and nearly all studies were underpowered to demonstrate a statistical benefit. The endpoints varied greatly from study to study. Nearly all the studies were single-site based, and most (26 of 44) were conducted in countries with national health care systems quite different from that of the U.S., therefore limiting their generalizability. CONCLUSIONS: Although a basis for the definition of transition of care exists, more consensus is needed on the definition of the interventions and the outcomes appropriate to those interventions. There was limited evidence that two components of hospital-initiated support for discharge (early supported discharge after stroke and specialty care followup after MI)were associated with beneficial effects. No other interventions had sufficient evidence of benefit based on the findings of this systematic review. The adoption of a standard set of definitions, a refinement in the methodology used to study transition of care, and appropriate selection of patient-centered and policy-relevant outcomes should be employed to draw valid conclusions pertaining to specific components of transition of care.