Diana Delgado

Caregiver Burden: A Clinical Review

IMPORTANCE Caregiver burden may result from providing care for patients with chronic illness. It can occur in any of the 43.5 million individuals providing support to midlife and older adults. Caregiver burden is frequently overlooked by clinicians. OBJECTIVES To outline the epidemiology of caregiver burden; to provide strategies to diagnose, assess, and intervene for caregiver burden in clinical practice; and to evaluate evidence on interventions intended to avert or mitigate caregiver burden and related caregiver distress. EVIDENCE Cohort studies examining the relation between demographic and social risk factors and adverse outcomes of caregiver burden were reviewed. Review of recent meta-analyses to summarize the effectiveness of caregiver burden interventions were identified by searching Ovid MEDLINE, AgeLine, and the Cochrane Library. RESULTS Risk factors for caregiver burden include female sex, low educational attainment, residence with the care recipient, higher number of hours spent caregiving, depression, social isolation, financial stress, and lack of choice in being a caregiver. Practical assessment strategies for caregiver burden exist to evaluate caregivers, their care recipients, and the care recipients overall caregiving needs. A variety of psychosocial and pharmacological interventions have shown mild to modest efficacy in mitigating caregiver burden and associated manifestations of caregiver distress in high-quality meta-analyses. Psychosocial interventions include support groups or psychoeducational interventions for caregivers of dementia patients (effect size, 0.09-0.23). Pharmacologic interventions include use of anticholinergics or antipsychotic medications for dementia or dementia-related behaviors in the care recipient (effect size, 0.18-0.27). Many studies showed improvements in caregiver burden-associated symptoms (eg, mood, coping, self-efficacy) even when caregiver burden itself was minimally improved. CONCLUSIONS AND RELEVANCE Physicians have a responsibility to recognize caregiver burden. Caregiver assessment and intervention should be tailored to the individual circumstances and contexts in which caregiver burden occurs.

Carotid Plaque MRI and Stroke Risk A Systematic Review and Meta-analysis

Background and Purpose— MRI characterization of carotid plaque has been studied recently as a potential tool to predict stroke caused by carotid atherosclerosis. We performed a systematic review and meta-analysis to summarize the association of MRI-determined intraplaque hemorrhage, lipid-rich necrotic core, and thinning/rupture of the fibrous cap with subsequent ischemic events. Methods— We performed a comprehensive literature search evaluating the association of carotid plaque composition on MRI with ischemic outcomes. We included cohort studies examining intraplaque hemorrhage, lipid-rich necrotic core, or thinning/rupture of the fibrous cap with mean follow-up of ≥1 month and an outcome measure of ipsilateral stroke or transient ischemic attack. A meta-analysis using a random-effects model with assessment of study heterogeneity and publication bias was performed. Results— Of the 3436 articles screened, 9 studies with a total of 779 subjects met eligibility for systematic review. The hazard ratios for intraplaque hemorrhage, lipid-rich necrotic core, and thinning/rupture of the fibrous cap as predictors of subsequent stroke/transient ischemic attack were 4.59 (95% confidence interval, 2.91–7.24), 3.00 (95% confidence interval, 1.51–5.95), and 5.93 (95% confidence interval, 2.65–13.20), respectively. No statistically significant heterogeneity or publication bias was present in the 3 main meta-analyses performed. Conclusions— The presence of intraplaque hemorrhage, lipid-rich necrotic core, and thinning/rupture of the fibrous cap on MRI of carotid plaque is associated with increased risk of future stroke or transient ischemic attack in patients with carotid atherosclerotic disease. Dedicated MRI of plaque composition offers stroke risk information beyond measurement of luminal stenosis in carotid atherosclerotic disease.

Cerebrovascular Reserve and Stroke Risk in Patients With Carotid Stenosis or Occlusion A Systematic Review and Meta-Analysis

Background and Purpose— Impairments in cerebrovascular reserve (CVR) have been variably associated with increased risk of ischemic events and may stratify stroke risk in patients with high-grade internal carotid artery stenosis or occlusion. The purpose of this study is to perform a systematic review and meta-analysis to summarize the association of CVR impairment and stroke risk. Methods— We performed a literature search evaluating the association of impairments in CVR with future stroke or transient ischemic attack in patients with high-grade internal carotid artery stenosis or occlusion. We included studies with a minimum of 1-year patient follow-up with baseline CVR measures performed by any modality and primary outcome measures of stroke and/or transient ischemic attack. A meta-analysis with assessment of study heterogeneity and publication bias was performed. Results were presented in a forest plot and summarized using a random-effects model. Results— Thirteen studies met the inclusion criteria, representing a total of 1061 independent CVR tests in 991 unique patients with a mean follow-up of 32.7 months. We found a significant positive relationship between impairment of CVR and development of stroke with a pooled random effects OR of 3.86 (95% CI, 1.99–7.48). Subset analysis showed that this association between CVR impairment and future risk of stroke/transient ischemic attack remained significant regardless of ischemic outcome measure, symptomatic or asymptomatic disease, stenosis or occlusion, or CVR testing method. Conclusions— CVR impairment is strongly associated with increased risk of ischemic events in carotid stenosis or occlusion and may be useful for stroke risk stratification.

MR perfusion-weighted imaging in the evaluation of high-grade gliomas after treatment: a systematic review and meta-analysis

Background. Distinction between tumor and treatment related changes is crucial for clinical management of patients with high-grade gliomas. Our purpose was to evaluate whether dynamic susceptibility contrast-enhanced (DSC) and dynamic contrast enhanced (DCE) perfusion-weighted imaging (PWI) metrics can effectively differentiate between recurrent tumor and posttreatment changes within the enhancing signal abnormality on conventional MRI. Methods. A comprehensive literature search was performed for studies evaluating PWI-based differentiation of recurrent tumor and posttreatment changes in patients with high-grade gliomas (World Health Organization grades III and IV). Only studies published in the “temozolomide era” beginning in 2005 were included. Summary estimates of diagnostic accuracy were obtained by using a random-effects model. Results. Of 1581 abstracts screened, 28 articles were included. The pooled sensitivities and specificities of each studys best performing parameter were 90% and 88% (95% CI: 0.85–0.94; 0.83–0.92) and 89% and 85% (95% CI: 0.78–0.96; 0.77–0.91) for DSC and DCE, respectively. The pooled sensitivities and specificities for detecting tumor recurrence using the 2 most commonly evaluated parameters, mean relative cerebral blood volume (rCBV) (threshold range, 0.9–2.15) and maximum rCBV (threshold range, 1.49–3.1), were 88% and 88% (95% CI: 0.81–0.94; 0.78–0.95) and 93% and 76% (95% CI: 0.86–0.98; 0.66–0.85), respectively. Conclusions. PWI-derived thresholds separating viable tumor from treatment changes demonstrate relatively good accuracy in individual studies. However, because of significant variability in optimal reported thresholds and other limitations in the existing body of literature, further investigation and standardization is needed before implementing any particular quantitative PWI strategy across institutions.

Silent Brain Infarction and Risk of Future Stroke: A Systematic Review and Meta-Analysis

Background and Purpose— Silent brain infarction (SBI) on magnetic resonance imaging has been proposed as a subclinical risk marker for future symptomatic stroke. We performed a systematic review and meta-analysis to summarize the association between magnetic resonance imaging–defined SBI and future stroke risk. Methods— We searched the medical literature to identify cohort studies involving adults with SBI detected by magnetic resonance imaging who were subsequently followed up for incident clinically defined stroke. Study data and quality assessment were recorded in duplicate with disagreements in data extraction resolved by a third reader. Strength association between magnetic resonance imaging–detected SBI and future symptomatic stroke was measured by an hazard ratio. Results— The meta-analysis included 13 studies (14 764 subjects) with a mean follow-up ranging from 25.7 to 174 months. SBI predicted the occurrence of stroke with a random effects crude relative risk of 2.94 (95% confidence interval, 2.24–3.86, P<0.001; Q=39.65, P<0.001). In the 8 studies of 10 427 subjects providing hazard ratio adjusted for cardiovascular risk factors, SBI was an independent predictor of incident stroke (hazard ratio, 2.08 [95% confidence interval, 1.69–2.56; P<0.001]; Q=8.99; P=0.25). In a subgroup analysis pooling 9483 stroke-free individuals from large population-based studies, SBI was present in ≈18% of participants and remained a strong predictor of future stroke (hazard ratio, 2.06 [95% confidence interval, 1.64–2.59]; P<0.01). Conclusions— SBI is present in ≈1 in 5 stroke-free older adults and is associated with a 2-fold increased risk of future stroke. Future studies of in-depth stroke risk evaluations and intensive prevention measures are warranted in patients with clinically unrecognized radiologically evident brain infarctions.

Effects of health information technology on patient outcomes: a systematic review

OBJECTIVE To systematically review studies assessing the effects of health information technology (health IT) on patient safety outcomes. MATERIALS AND METHODS The authors employed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement methods. MEDLINE, Cumulative Index to Nursing Allied Health (CINAHL), EMBASE, and Cochrane Library databases, from 2001 to June 2012, were searched. Descriptive and comparative studies were included that involved use of health IT in a clinical setting and measured effects on patient safety outcomes. RESULTS Data on setting, subjects, information technology implemented, and type of patient safety outcomes were all abstracted. The quality of the studies was evaluated by 2 independent reviewers (scored from 0 to 10). A total of 69 studies met inclusion criteria. Quality scores ranged from 1 to 9. There were 25 (36%) studies that found benefit of health IT on direct patient safety outcomes for the primary outcome measured, 43 (62%) studies that either had non-significant or mixed findings, and 1 (1%) study for which health IT had a detrimental effect. Neither the quality of the studies nor the rate of randomized control trials performed changed over time. Most studies that demonstrated a positive benefit of health IT on direct patient safety outcomes were inpatient, single-center, and either cohort or observational trials studying clinical decision support or computerized provider order entry. DISCUSSION AND CONCLUSION Many areas of health IT application remain understudied and the majority of studies have non-significant or mixed findings. Our study suggests that larger, higher quality studies need to be conducted, particularly in the long-term care and ambulatory care settings.

Oxygen extraction fraction and stroke risk in patients with carotid stenosis or occlusion: a systematic review and meta-analysis.

BACKGROUND AND PURPOSE: Increased oxygen extraction fraction on PET has been considered a risk factor for stroke in patients with carotid stenosis or occlusion, though the strength of this association has recently been questioned. We performed a systematic review and meta-analysis to summarize the association between increased oxygen extraction fraction and ipsilateral stroke risk. MATERIALS AND METHODS: A comprehensive literature search was performed. We included studies with baseline PET oxygen extraction fraction testing, ipsilateral stroke as the primary outcome, and at least 1 year of follow-up. A meta-analysis was performed by use of a random-effects model. RESULTS: After screening 2158 studies, 7 studies with 430 total patients with mean 30-month follow-up met inclusion criteria. We found that 6 of 7 studies were amenable to meta-analysis. Although 4 of the 6 studies independently did not reach statistical significance, meta-analysis revealed a significant positive relationship between abnormal oxygen extraction fraction and future ipsilateral stroke, with a pooled OR of 6.04 (95% CI, 2.58–14.12). There was no statistically significant difference in OR in the subgroup analyses according to testing method or disease site. CONCLUSIONS: Abnormal oxygen extraction fraction remains a powerful predictor of stroke in carotid stenosis or occlusion and is a valuable reference standard to compare and validate MR imaging–based measures of brain oxygen metabolism. However, there is a need for further evaluation of oxygen extraction fraction testing in patients with high-grade but asymptomatic carotid disease.

Gadolinium Enhancement in Intracranial Atherosclerotic Plaque and Ischemic Stroke: A Systematic Review and Meta-Analysis

Background Gadolinium enhancement on high‐resolution magnetic resonance imaging (MRI) has been proposed as a marker of inflammation and instability in intracranial atherosclerotic plaque. We performed a systematic review and meta‐analysis to summarize the association between intracranial atherosclerotic plaque enhancement and acute ischemic stroke. Methods and Results We searched the medical literature to identify studies of patients undergoing intracranial vessel wall MRI for evaluation of intracranial atherosclerotic plaque. We recorded study data and assessed study quality, with disagreements in data extraction resolved by a third reader. A random‐effects odds ratio was used to assess whether, in any given patient, cerebral infarction was more likely in the vascular territory supplied by an artery with MRI‐detected plaque enhancement as compared to territory supplied by an artery without enhancement. We calculated between‐study heterogeneity using the Cochrane Q test and publication bias using the Begg‐Mazumdar test. Eight articles published between 2011 and 2015 met inclusion criteria. These studies provided information about plaque enhancement characteristics from 295 arteries in 330 patients. We found a significant positive relationship between MRI enhancement and cerebral infarction in the same vascular territory, with a random effects odds ratio of 10.8 (95% CI 4.1–28.1, P<0.001). No significant heterogeneity (Q=11.08, P=0.14) or publication bias (P=0.80) was present. Conclusions Intracranial plaque enhancement on high‐resolution vessel wall MRI is strongly associated with ischemic stroke. Evaluation for plaque enhancement on MRI may be a useful test to improve diagnostic yield in patients with ischemic strokes of undetermined etiology.

Hemispheric Differences in Leukoaraiosis in Patients with Carotid Artery Stenosis: A Systematic Review

PurposeDespite the prevalence of leukoaraiosis in neuroimaging and its link to dementia, stroke, and death, the exact pathogenesis is still unclear. While some have postulated a link between carotid artery disease and leukoaraiosis, the exact relationship between the two common clinical findings is unknown. To determine the link between carotid disease and leukoaraiosis, we performed a systematic review of interhemispheric differences in white matter disease in patients with carotid artery disease.MethodsWe performed a comprehensive literature search in multiple electronic databases evaluating the association of carotid artery and white matter disease using both subjective and volumetric assessment of white matter burden. The included studies examined patients with at least 30 % carotid artery stenosis for white matter burden both ipsilateral and contralateral to the site of carotid artery disease.ResultsOf the 2920 manuscripts screened, five were included in the systematic review. One study used a volumetric analysis of the white matter burden and the others used various subjective methods. Four studies found no statistically significant relationship between carotid artery disease and ipsilateral white matter burden and one study found a significantly higher amount of white matter disease ipsilateral to carotid artery stenosis.ConclusionsThe mixed results in degree of hemispheric leukoaraiosis in patients with carotid artery disease indicate that no definite relationship can be established based on the existing literature. Given the complex nature of carotid artery disease, including increased risk with certain plaque components, the exact relationship requires further investigation with more rigorous research design.

The Use of Noncontrast Quantitative MRI to Detect Gadolinium-Enhancing Multiple Sclerosis Brain Lesions: A Systematic Review and Meta-Analysis

The authors evaluated 37 journal articles that included 985 patients with MS who had MR imaging in which T1-weighted postcontrast sequences were compared with noncontrast sequences obtained during the same MR imaging examination by using ROI analysis of individual MS lesions. DTI-based fractional anisotropy values were significantly different between enhancing and nonenhancing lesions, with enhancing lesions showing decreased FA. None of the other most frequently studied MR imaging biomarkers (mean diffusivity, magnetization transfer ratio, or ADC) were significantly different between enhancing and nonenhancing lesions. They conclude that noncontrast MR imaging techniques, such as DTI-based FA, can assess MS lesion acuity without gadolinium. BACKGROUND: Concerns have arisen about the long-term health effects of repeat gadolinium injections in patients with multiple sclerosis and the incomplete characterization of MS lesion pathophysiology that results from relying on enhancement characteristics alone. PURPOSE: Our aim was to perform a systematic review and meta-analysis analyzing whether noncontrast MR imaging biomarkers can distinguish enhancing and nonenhancing brain MS lesions. DATA SOURCES: Our sources were Ovid MEDLINE, Ovid Embase, and the Cochrane data base from inception to August 2016. STUDY SELECTION: We included 37 journal articles on 985 patients with MS who had MR imaging in which T1-weighted postcontrast sequences were compared with noncontrast sequences obtained during the same MR imaging examination by using ROI analysis of individual MS lesions. DATA ANALYSIS: We performed random-effects meta-analyses comparing the standard mean difference of each MR imaging metric taken from enhancing-versus-nonenhancing lesions. DATA SYNTHESIS: DTI-based fractional anisotropy values are significantly different between enhancing and nonenhancing lesions (P = .02), with enhancing lesions showing decreased fractional anisotropy compared with nonenhancing lesions. Of the other most frequently studied MR imaging biomarkers (mean diffusivity, magnetization transfer ratio, or ADC), none were significantly different (P values of 0.30, 0.47, and 0.19. respectively) between enhancing and nonenhancing lesions. Of the limited studies providing diagnostic accuracy measures, gradient-echo-based quantitative susceptibility mapping had the best performance in discriminating enhancing and nonenhancing MS lesions. LIMITATIONS: MR imaging techniques and patient characteristics were variable across studies. Most studies did not provide diagnostic accuracy measures. All imaging metrics were not studied in all 37 studies. CONCLUSIONS: Noncontrast MR imaging techniques, such as DTI-based FA, can assess MS lesion acuity without gadolinium.