Neurologist prescribing versus psychiatry referral: Examining patient preferences for anxiety and depression management in a symptomatic epilepsy clinic sample.

OBJECTIVE: Anxiety and depression symptoms in epilepsy are common, impactful and under-recognized and undertreated. While prior survey data suggests equipoise among epileptologists for managing anxiety and/or depression via prescribing in the epilepsy clinic versus psychiatry referral, patient preferences are unknown and should potentially influence practice habits among epileptologists. Thus, the primary objective of this study was to determine patient preference for anxiety and/or depression prescribing by neurologists versus psychiatry referral among an adult epilepsy clinic sample of symptomatic patients. METHODS: Management preferences for anxiety and/or depression were surveyed in an adult tertiary care epilepsy clinic. Individuals who screened positive for anxiety and/or depression symptoms on validated instruments during a routine care-embedded learning health system study were recruited. Demographics, social variables, psychiatric treatment history, and treatment priorities and preferences were surveyed. Preference was defined as a slightly greater than 2:1 ratio in favor neurology prescribing or psychiatry referral. The study was powered to assess this primary objective using a two-sample binomial test. Multinomial logistic regression examined an a priori multivariable model of treatment preference (secondary objective). RESULTS: The study sample included N = 63 symptomatic adults, with 64% women and mean age 42.2 years. Most reported past or current treatment for anxiety and/or depression, and treatment for these symptoms was a high or moderate priority among 65.1% of the sample. Neurologist prescribing was preferred in 83.0% (nearly 5:1) over psychiatry referral among those who chose neurology or psychiatry (as opposed to neither of the two; p < 0.001, 95% CI 0.702-0.919). Overall, 69.8% of the total study sample preferred neurology prescribing. Multivariable modeling indicated preference for neither management option (compared with neurologist prescribing) was associated with low overall treatment prioritization and having never received neurologist medication management. None of the factors examined in the a priori multivariable model were associated with selecting psychiatry referral (compared to neurologist prescribing). CONCLUSION: In this sample, most patients indicated a preference for neurologists to prescribe for anxiety or depression symptoms in the epilepsy clinic. Care models involving neurologist prescribing for anxiety and depression symptoms merit further investigation and potential adoption in clinical practice.

Who is willing to participate in research? A screening model for an anxiety and depression trial in the epilepsy clinic.

OBJECTIVE: Anxiety and depression in epilepsy are prevalent, associated with poor outcomes, underrecognized, undertreated, and thus a key area of need for treatment research. The objective of this study was to assess factors associated with research participation among epilepsy clinic patients who screened positive for anxiety or depression. This was accomplished by characterizing clinical and psychiatric factors among patients seen in an epilepsy clinic and evaluating which factors were associated with consent for potential research participation, via a combined clinical and research screening model. METHODS: In a pragmatic trial of anxiety and depression treatment in epilepsy, individuals with a positive screen for anxiety and/or depression at a routine epilepsy clinic visit were invited to opt-in (via brief electronic consent) to further eligibility assessment for a randomized treatment study. Information on psychiatric symptoms and treatment characteristics were collected for dual clinical care and research screening purposes. Cross-sectional association of demographic, clinical, and psychiatric factors with opting-in to research was analyzed by multiple logistic regression. RESULTS: Among N = 199 unique adults with a first positive screen for anxiety and/or depression among 786 total screening events, 154 (77.4%) opted-in to further potential research assessment. Higher depression scores and current treatment with an antidepressant were independently associated with opting-in to research (depression odds ratio (OR) = 1.13 per 1-point increase in Neurological Disorders Depression Inventory-Epilepsy (NDDI-E) score, p = 0.028, 95% confidence interval (CI): 1.01-1.26; antidepressant OR = 2.37, p = 0.041, CI: 1.04-5.41). Nearly half of the 199 individuals (43.7%) with anxiety and/or depression symptoms were already being treated with an antidepressant, and 46.7% were receiving neither antidepressant therapy nor mental health specialty care. One-quarter (24.1%) reported a past psychiatric hospitalization, yet only half of these individuals were receiving mental health specialty care. SIGNIFICANCE: Our results demonstrate a high willingness to participate in research using a brief electronic consent approach at a routine clinic visit. Adults with persistent anxiety or depression symptoms despite antidepressant therapy and those with higher depression scores were more willing to consider a randomized treatment study. This has implications for future study design, as individuals already on treatment or those with more severe symptoms are often excluded from traditional research designs. We also found a high burden of psychiatric disease and high prevalence of persistent symptoms despite ongoing antidepressant treatment.

Development of a screening tool to identify patients likely to benefit from clinical pharmacist review in a home-based primary care population.

OBJECTIVE: To create a novel screening tool that identified patients who were most likely to benefit from pharmacist in-home medication reviews. DESIGN: Single-center, retrospective study. SETTING AND PARTICIPANTS: A total of 25 homebound patients in Forsyth County, NC, aged 60 years or older with physical or cognitive impairments and enrolled in home-based primary care or transitional and supportive care programs participated in the study. Pharmacy resident-provider pairs conducted home visits for all patients in the study. Pharmacy residents assessed the subjective risk (high, medium, low) of medication nonadherence using information obtained from home visits (health literacy, support network, medications, and detection of something unexpected related to medications). An electronic medical record-based risk score was simultaneously calculated using screening tool components (i.e., electronic frailty index score, LACE+ index [length of stay in the hospital, acuity of admission, comorbidity, emergency department utilization in the 6 months before admission], and 2015 American Geriatric Society Beers Criteria). OUTCOME MEASURES: The electronic medical record-based screening tool numerical risk scores were compared with pharmacy resident subjective risk assessments using tree-based classification models to determine screening tool components that best predicted pharmacy residents' subjective assessment of patients' likelihood of benefit from in-home pharmacist medication review. Following the study, satisfaction surveys were given to providers and pharmacy residents. RESULTS: The best predictor of high-risk patients was an electronic frailty index score greater than 0.32 (indicating very frail) or LACE+ index greater than or equal to 59 (at high risk for hospital readmission). Pharmacy residents and providers agreed that homebound patients at high-risk for medication noncompliance benefited from pharmacist time and attention in home visits. CONCLUSION: In homebound older persons, this screening tool allowed for the identification of patients at high-risk for medication nonadherence through targeted in-home pharmacist medication reviews. Further studies are needed to validate the accuracy of this tool internally and externally.

Intern Boot Camp: Feasibility and impact of a 1-hour session to ensure graduating medical student competency in falls risk assessment.

The authors evaluated the feasibility of a 1-hour session to ensure competency in gait and falls risk assessment for medical students at their institution. The session included a history and exam with faculty and staff as standardized patients, gait recognition videos, and case evaluation for falls risk assessment and prevention. Student perceptions were evaluated using a retrospective pre-post survey, scored on a 5-point Likert-type scale. Wilcoxon signed-rank tests were used to assess change and Kruskal-Wallis tests were used to analyze differences by residency choice. A range of five to 11 faculty and staff certified 238 medical students during eight 1-hour sessions. Overall self-perception of competence in falls risk assessment and prevention improved (p ≤ .001), and did not differ by residency choice, both before and after the training program (p = .73 and p = .25). Feedback was positive. This session is a feasible way to teach and assess the competency for falls risk assessment with modest time commitment.

Serum calcium, albumin and tumor stage in cutaneous malignant melanoma.

AIM: Assess the relationship of serum calcium and serum albumin to tumor stage and other clinical characteristics in patients with cutaneous malignant melanoma (MM). PATIENTS & METHODS: A cross-sectional study to evaluate serum calcium as a marker of disease progression (n = 644) in MM. RESULTS: Serum albumin was significantly lower among men (p < 0.01) and among patients with stage 4 disease (p < 0.05). In a multivariable regression model adjusted for age, gender and site, albumin-corrected calcium was positively associated with disease stage (odds ratio: 1.46; 95% CI: 1.02-2.07; p = 0.04). The odds of higher stage increased 60% for each 1.0 mg/dl increase in albumin-corrected calcium. CONCLUSION: Higher albumin-corrected serum calcium may be a marker of disease progression in MM.

Standardized Rehabilitation and Hospital Length of Stay Among Patients With Acute Respiratory Failure: A Randomized Clinical Trial.

IMPORTANCE: Physical rehabilitation in the intensive care unit (ICU) may improve the outcomes of patients with acute respiratory failure. OBJECTIVE: To compare standardized rehabilitation therapy (SRT) to usual ICU care in acute respiratory failure. DESIGN, SETTING, AND PARTICIPANTS: Single-center, randomized clinical trial at Wake Forest Baptist Medical Center, North Carolina. Adult patients (mean age, 58 years; women, 55%) admitted to the ICU with acute respiratory failure requiring mechanical ventilation were randomized to SRT (n=150) or usual care (n=150) from October 2009 through May 2014 with 6-month follow-up. INTERVENTIONS: Patients in the SRT group received daily therapy until hospital discharge, consisting of passive range of motion, physical therapy, and progressive resistance exercise. The usual care group received weekday physical therapy when ordered by the clinical team. For the SRT group, the median (interquartile range [IQR]) days of delivery of therapy were 8.0 (5.0-14.0) for passive range of motion, 5.0 (3.0-8.0) for physical therapy, and 3.0 (1.0-5.0) for progressive resistance exercise. The median days of delivery of physical therapy for the usual care group was 1.0 (IQR, 0.0-8.0). MAIN OUTCOMES AND MEASURES: Both groups underwent assessor-blinded testing at ICU and hospital discharge and at 2, 4, and 6 months. The primary outcome was hospital length of stay (LOS). Secondary outcomes were ventilator days, ICU days, Short Physical Performance Battery (SPPB) score, 36-item Short-Form Health Surveys (SF-36) for physical and mental health and physical function scale score, Functional Performance Inventory (FPI) score, Mini-Mental State Examination (MMSE) score, and handgrip and handheld dynamometer strength. RESULTS: Among 300 randomized patients, the median hospital LOS was 10 days (IQR, 6 to 17) for the SRT group and 10 days (IQR, 7 to 16) for the usual care group (median difference, 0 [95% CI, -1.5 to 3], P = .41). There was no difference in duration of ventilation or ICU care. There was no effect at 6 months for handgrip (difference, 2.0 kg [95% CI, -1.3 to 5.4], P = .23) and handheld dynamometer strength (difference, 0.4 lb [95% CI, -2.9 to 3.7], P = .82), SF-36 physical health score (difference, 3.4 [95% CI, -0.02 to 7.0], P = .05), SF-36 mental health score (difference, 2.4 [95% CI, -1.2 to 6.0], P = .19), or MMSE score (difference, 0.6 [95% CI, -0.2 to 1.4], P = .17). There were higher scores at 6 months in the SRT group for the SPPB score (difference, 1.1 [95% CI, 0.04 to 2.1, P = .04), SF-36 physical function scale score (difference, 12.2 [95% CI, 3.8 to 20.7], P = .001), and the FPI score (difference, 0.2 [95% CI, 0.04 to 0.4], P = .02). CONCLUSIONS AND RELEVANCE: Among patients hospitalized with acute respiratory failure, SRT compared with usual care did not decrease hospital LOS. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00976833.

Effect of diabetes on brain structure: the action to control cardiovascular risk in diabetes MR imaging baseline data.

PURPOSE: To investigate the association of characteristics of type 2 diabetes mellitus (duration and biochemical severity of diabetes) to brain structure measured on magnetic resonance (MR) images, specifically testing whether more severity in metrics of diabetes is inversely correlated with brain volumes and positively correlated with ischemic lesion volumes. MATERIALS AND METHODS: This study protocol was approved by the institutional review board of each center and participants provided written informed consent. Baseline severity of diabetes was evaluated by testing fasting plasma glucose levels, hemoglobin A1c levels, and duration of diabetes. MR imaging was performed with fluid-attenuated inversion recovery, proton-density, T2-weighted, and T1-weighted sequences, which were postprocessed with an automated computer algorithm that classified brain tissue as gray or white matter and as normal or ischemic. Separate linear regression models adjusted for potential confounding factors were used to investigate the relationship of the diabetes measures to MR imaging outcomes in 614 participants (mean age, 62 years; mean duration of type 2 diabetes mellitus, 9.9 years). RESULTS: The mean volumes of total gray matter (463.9 cm(3)) and total white matter (463.6 cm(3)) were similar. The mean volume of abnormal tissue was 2.5 cm(3), mostly in the white matter (81% white matter, 5% gray matter, 14% deep gray and white matter). Longer duration of diabetes and higher fasting plasma glucose level were associated with lower normal (ß = -0.431 and -0.053, respectively; P < .01) and total gray matter volumes (ß = -0.428 and -0.053, respectively; P < .01). Fasting plasma glucose was also inversely correlated with ischemic lesion volume (ß = -0.006; P < .04). Hemoglobin A1c level was not associated with any MR imaging measure. CONCLUSION: Longer duration of diabetes is associated with brain volume loss, particularly in the gray matter, possibly reflecting direct neurologic insult; biochemical measures of glycemia were less consistently related to MR imaging changes. Contrary to common clinical belief, in this sample of patients with type 2 diabetes mellitus, there was no association of diabetes characteristics with small vessel ischemic disease in the brain.

The effects of medical management on the progression of diabetic retinopathy in persons with type 2 diabetes: the Action to Control Cardiovascular Risk in Diabetes (ACCORD) Eye Study.

PURPOSE: To report additional ocular outcomes of intensive treatment of hyperglycemia, blood pressure, and dyslipidemia in the Action to Control Cardiovascular Risk in Diabetes (ACCORD) study. DESIGN: Double 2×2 factorial, multicenter, randomized clinical trials in people with type 2 diabetes who had cardiovascular disease or cardiovascular risk factors. In the glycemia trial, targets of intensive and standard treatment were: hemoglobin A1c <6.0% and 7.0% to 7.9%, respectively, and in the blood pressure trial: systolic blood pressures of <120 and <140 mmHg, respectively. The dyslipidemia trial compared fenofibrate plus simvastatin with placebo plus simvastatin. PARTICIPANTS: Of the 3472 ACCORD Eye Study participants enrolled, 2856 had 4-year data (85% of survivors). METHODS: Eye examinations and fundus photographs were taken at baseline and year 4. Photographs were graded centrally for retinopathy severity and macular edema using the Early Treatment Diabetic Retinopathy Study (ETDRS) methods. MAIN OUTCOME MEASURES: Three or more steps of progression on the ETDRS person scale or treatment of retinopathy with photocoagulation or vitrectomy. RESULTS: As previously reported, there were significant reductions in the primary outcome in the glycemia and dyslipidemia trials, but no significant effect in the blood pressure trial. Results were similar for retinopathy progression by 1, 2, and 4 or more steps on the person scale and for ≥ 2 steps on the eye scale. In the subgroup of patients with mild retinopathy at baseline, effect estimates were large (odds ratios, ∼0.30; P < 0.001), but did not reach nominal significance for participants with no retinopathy or for those with moderate to severe retinopathy at baseline. CONCLUSIONS: Slowing of progression of retinopathy by intensive treatment of glycemia was observed in ACCORD participants, whose average age and diabetes duration were 62 and 10 years, respectively, and who had cardiovascular disease or cardiovascular risk factors. The effect seemed stronger in patients with mild retinopathy. Similar slowing of progression was observed in patients treated with fenofibrate, with no effect observed with intensive blood pressure treatment. This is the second study to confirm the benefits of fenofibrate in reducing diabetic retinopathy progression, and fenofibrate should be considered for treatment of diabetic retinopathy.

Local control and toxicity outcomes in brainstem metastases treated with single fraction radiosurgery: is there a volume threshold for toxicity?

Gamma Knife Radiosurgery (GKRS) has been reported in the treatment of brainstem metastases while dose volume toxicity thresholds remain mostly undefined. A retrospective review of 52 brainstem metastases in 44 patients treated with GKRS was completed. A median dose of 18 Gy (range 10-22 Gy) was prescribed to the tumor margin (median 50 % isodose). 25 patients had undergone previous whole brain radiation therapy. Toxicity was graded by the LENT-SOMA scale. Mean and median follow-up was 10 and 6 months. Only 3 of the 44 patients are living. Multiple brain metastases were treated in 75 % of patients. Median size of lesions was 0.134 cc, (range 0.013-6.600 cc). Overall survival rate at 1 year was 32 % (95 % CI 51.0-20.1 %) with a median survival time of 6 months (95 % CI 5.0-16.5). Local control rate at 6 months and 1 year was 88 % (95 % CI 70-95 %) and 74 % (95 % CI 52-87 %). Cause of death was neurologic in 17 patients, non-neurologic in 20 patients, and unknown in four. Four patients experienced treatment related toxicities. Univariate analysis of tumor volume revealed that volume greater than 1.0 cc predicted for toxicity. A strategy of using lower marginal doses with GKRS to brain stem metastases appears to lead to a lower local control rate than seen with lesions treated within the standard dose range in other locations. Tumor size greater than 1.0 cc predicted for treatment-related toxicity.

Single-institution retrospective series of gamma knife radiosurgery in the treatment of multiple sclerosis-related trigeminal neuralgia: factors that predict efficacy.

BACKGROUND: Gamma knife radiosurgery (GKRS) has been reported as a treatment option for multiple sclerosis (MS)-related trigeminal neuralgia. OBJECTIVE: To report the outcomes of a single-institution retrospective series of MS-related trigeminal neuralgia. METHODS: Between 2002 and 2010, 35 patients with MS-related trigeminal neuralgia were treated with GKRS. The median maximum dose was 90 Gy. Data were analyzed to determine the response to GKRS and factors that may predict for efficacy. RESULTS: Of the 35 patients, 88% experienced a Barrow Neurological Institute (BNI) pain score of I-III at 3 months after GKRS. Kaplan-Meier estimates of 1-, 2- and 5-year freedom from BNI IV-V pain relapse were 57, 57 and 52%, respectively. Numbness was experienced by 39% of patients after GKRS, though no patients reported bothersome numbness. Several differences were noted between how the MS-related variant responded to GKRS and what has previously been reported for idiopathic trigeminal neuralgia. These include the observations that development of post-GKRS numbness did not predict for treatment response (p = 0.62) and that dorsal root entry zone dose did not predict for freedom from pain relapse (odds ratio 1.01, p = 0.1). Active smoking predicted for freedom from pain relapse (odds ratio 67.4, p = 0.04). CONCLUSION: GKRS is a viable noninvasive treatment option for MS-related trigeminal neuralgia.

Effects of medical therapies on retinopathy progression in type 2 diabetes.

BACKGROUND: We investigated whether intensive glycemic control, combination therapy for dyslipidemia, and intensive blood-pressure control would limit the progression of diabetic retinopathy in persons with type 2 diabetes. Previous data suggest that these systemic factors may be important in the development and progression of diabetic retinopathy. METHODS: In a randomized trial, we enrolled 10,251 participants with type 2 diabetes who were at high risk for cardiovascular disease to receive either intensive or standard treatment for glycemia (target glycated hemoglobin level, <6.0% or 7.0 to 7.9%, respectively) and also for dyslipidemia (160 mg daily of fenofibrate plus simvastatin or placebo plus simvastatin) or for systolic blood-pressure control (target, <120 or <140 mm Hg). A subgroup of 2856 participants was evaluated for the effects of these interventions at 4 years on the progression of diabetic retinopathy by 3 or more steps on the Early Treatment Diabetic Retinopathy Study Severity Scale (as assessed from seven-field stereoscopic fundus photographs, with 17 possible steps and a higher number of steps indicating greater severity) or the development of diabetic retinopathy necessitating laser photocoagulation or vitrectomy. RESULTS: At 4 years, the rates of progression of diabetic retinopathy were 7.3% with intensive glycemia treatment, versus 10.4% with standard therapy (adjusted odds ratio, 0.67; 95% confidence interval [CI], 0.51 to 0.87; P=0.003); 6.5% with fenofibrate for intensive dyslipidemia therapy, versus 10.2% with placebo (adjusted odds ratio, 0.60; 95% CI, 0.42 to 0.87; P=0.006); and 10.4% with intensive blood-pressure therapy, versus 8.8% with standard therapy (adjusted odds ratio, 1.23; 95% CI, 0.84 to 1.79; P=0.29). CONCLUSIONS: Intensive glycemic control and intensive combination treatment of dyslipidemia, but not intensive blood-pressure control, reduced the rate of progression of diabetic retinopathy. (Funded by the National Heart, Lung, and Blood Institute and others; ClinicalTrials.gov numbers, NCT00000620 for the ACCORD study and NCT00542178 for the ACCORD Eye study.)

The use of a checklist in a pediatric oncology clinic.

BACKGROUND: Errors and near misses are common in medicine. Checklists and similar interventions are feasible and can reduce the incidence of errors and improve patient outcomes. This study assessed the feasibility and efficacy of a checklist in a pediatric oncology clinic. PROCEDURE: Errors and near misses of all types were systematically tracked for 1 month in a pediatric oncology clinic. Following the initial 1 month time period (baseline), a 10-item checklist was implemented for each patient encounter during a 4-month period. During month 5 of the study while the checklist was being used, errors and near misses were again systematically tracked for 1 month. RESULTS: The use of a checklist was associated with a significant reduction of errors in our clinic. The total number of errors (including documentation errors) decreased from 133 in month 1 to 39 in month 5 (P < 0.0001). In addition, checklist use decreased the rate of encounters with at least one error from 34% to 15% (P < 0.001). The reduction in errors occurred despite the checklist not being used for each encounter. The majority of practitioners were satisfied with the use of a checklist and think that the use of a checklist is a good way to reduce errors. CONCLUSIONS: A checklist is potentially a feasible, safe, inexpensive, and simple method to lower the rate of medical errors in a pediatric oncology clinic.

Comparison of standardized clinical classification with fundus photograph grading for the assessment of diabetic retinopathy and diabetic macular edema severity.

PURPOSE: To compare evaluation by clinical examination with image grading at a reading center for the classification of diabetic retinopathy and diabetic macular edema. METHODS: Action to Control Cardiovascular Risk in Diabetes (ACCORD) and Family Investigations of Nephropathy in Diabetes (FIND) had similar methods of clinical and fundus photograph evaluation. For analysis purposes, the photographic grading scales were condensed to correspond to the clinical scales, and agreement between clinicians and reading center classification were compared. RESULTS: Six thousand nine hundred and two eyes of ACCORD participants and 3,638 eyes of FIND participants were analyzed for agreement (percent, kappa) on diabetic retinopathy on a 5-level scale. Exact agreement between clinicians and reading center on diabetic retinopathy severity category was 69% in ACCORD and 74% in FIND (kappa 0.42 and 0.65). Sensitivities of the clinical grading to identify the presence of mild nonproliferative retinopathy or worse were 0.53 in ACCORD and 0.84 in FIND. Specificities were 0.97 and 0.96, respectively. Diabetic macular edema agreement in 6,649 eyes of ACCORD participants and 3,366 eyes of FIND participants was similar (kappa 0.35 and 0.41). Sensitivities of the clinical grading to identify diabetic macular edema were 0.44 and 0.53 and specificities were 0.99 and 0.94, respectively. CONCLUSION: The results support the use of clinical information for defining broad severity categories but not for documenting small-to-moderate changes in diabetic retinopathy over time.

A longitudinal, experiential quality improvement curriculum meeting ACGME competencies for geriatrics fellows: lessons learned.

Quality improvement (QI) initiatives are critical in the care of older adults who are more vulnerable to substandard care. QI education meets aspects of core Accreditation Council of Graduate Medical Education competencies and prepares learners for the rising focus on performance measurement in health care. The authors developed, implemented, and evaluated a QI curriculum for geriatrics fellows. The evidence-based curriculum included didactics and a fellow-led QI intervention based on audit and feedback through the Practice Improvement Module in Care of the Vulnerable Elderly. QI knowledge, attitudes, and behaviors were assessed before and after the improvement project. Fellows' knowledge of QI improved (p = .0156), but behavior did not change significantly across a short-term improvement project. A structured focus group with fellows revealed themes of accountability and the importance of interprofessional teamwork in QI. QI education for geriatrics fellows can be feasible, well received, and prepare future physician leaders for patient-centered care, performance measurement, and effecting systems change.

Association of Type 2 Diabetes Subgroups With Cognitive Status Without Modification From Lifestyle Intervention.

CONTEXT: Type 2 diabetes is a risk factor for incident dementia but whether risk and treatment/prevention strategies differ by diabetes subgroup is unknown. OBJECTIVE: We assessed (1) whether specific type 2 diabetes (T2D) subgroups are associated with mild cognitive impairment (MCI) or probable dementia (PD), and (2) whether T2D subgroups modified the association of the Action for Health in Diabetes (Look AHEAD) multidomain intensive lifestyle intervention (ILI) with MCI/PD. METHODS: We included 3760 Look AHEAD participants with T2D and overweight or obesity randomly assigned to 10 years of ILI or diabetes support and education. We used k-means clustering techniques with data on age of diabetes diagnosis, body mass index, waist circumference, and glycated hemoglobin (HbA1c) to characterize diabetes subgroups at randomization. Prevalent MCI/PD were centrally adjudicated based on standardized cognitive tests and other health information 10 to 13 years after randomization. We estimated marginal probabilities for prevalent MCI/PD among T2D subgroups with adjustment for potential confounders and attrition and examined whether ILI modified any associations. RESULTS: Four distinct T2D subgroups were identified, characterized by older age at diabetes onset (43% of sample), high HbA1c (13%), severe obesity (23%), and younger age at onset (22%). Unadjusted prevalence of MCI/PD (314 cases, 8.4%) differed across T2D subgroup (older onset = 10.5%, severe obesity = 9.0%, high HbA1c = 7.9%, and younger onset = 4.0%). Adjusted probability for MCI/PD within T2D subgroup was highest for the severe obesity subgroup and lowest for the younger onset subgroup but did not differ by ILI arm (interaction P value = 0.84). CONCLUSIONS: Among individuals with T2D and overweight or obesity, probability of MCI/PD differed by T2D subgroup. Probability of MCI/PD was highest for a subgroup characterized by severe obesity. CLINICALTRIALS.GOV IDENTIFIER: NCT00017953.

Cardiac Magnetic Resonance Imaging Versus Invasive-Based Strategies in Patients With Chest Pain and Detectable to Mildly Elevated Serum Troponin: A Randomized Clinical Trial.

BACKGROUND: The optimal diagnostic strategy for patients with chest pain and detectable to mildly elevated serum troponin is not known. The objective was to compare clinical outcomes among an early decision for a noninvasive versus an invasive-based care pathway. METHODS: The CMR-IMPACT trial (Cardiac Magnetic Resonance Imaging Strategy for the Management of Patients with Acute Chest Pain and Detectable to Elevated Troponin) was conducted at 4 United States tertiary care hospitals from September 2013 to July 2018. A convenience sample of 312 participants with acute chest pain symptoms and a contemporary troponin between detectable and 1.0 ng/mL were randomized early in their care to 1 of 2 care pathways: invasive-based (n=156) or cardiac magnetic resonance (CMR)-based (n=156) with modification allowed as the patient condition evolved. The primary outcome was a composite including death, myocardial infarction, and cardiac-related hospital readmission or emergency visits. RESULTS: Participants (N=312, mean age, 60.6 years, SD 11.3; 125 women [59.9%]), were followed over a median of 2.6 years (95% CI, 2.4-2.9). Early assigned testing was initiated in 102 out of 156 (65.3%) CMR-based and 110 out of 156 (70.5%) invasive-based participants. The primary outcome (CMR-based versus invasive-based) occurred in 59% versus 52% (hazard ratio, 1.17 [95% CI, 0.86-1.57]), acute coronary syndrome after discharge 23% versus 22% (hazard ratio, 1.07 [95% CI, 0.67-1.71]), and invasive angiography at any time 52% versus 74% (hazard ratio, 0.66 [95% CI, 0.49-0.87]). Among patients completing CMR imaging, 55 out of 95 (58%) were safely identified for discharge based on a negative CMR and did not have angiography or revascularization within 90 days. Therapeutic yield of angiography was higher in the CMR-based arm (52 interventions in 81 angiographies [64.2%] versus 46 interventions in 115 angiographies [40.0%] in the invasive-based arm [P=0.001]). CONCLUSIONS: Initial management with CMR or invasive-based care pathways resulted in no detectable difference in clinical and safety event rates. The CMR-based pathway facilitated safe discharge, enriched the therapeutic yield of angiography, and reduced invasive angiography utilization over long-term follow-up. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier: NCT01931852.

Reverse translation of phase I biomarker findings links the activity of angiotensin-(1-7) to repression of hypoxia inducible factor-1α in vascular sarcomas.

BACKGROUND: In a phase I study of angiotensin-(1-7) [Ang-(1-7)], clinical benefit was associated with reduction in plasma placental growth factor (PlGF) concentrations. The current study examines Ang-(1-7) induced changes in biomarkers according to cancer type and investigates mechanisms of action engaged in vitro. METHODS: Plasma biomarkers were measured prior to Ang-(1-7) administration as well as 1, 2, 3, 4, and 6 hours after treatment. Tests for interaction were performed to determine the impact of cancer type on angiogenic hormone levels. If a positive interaction was detected, treatment-induced biomarker changes for individual cancer types were assessed. To investigate mechanisms of action, in vitro growth assays were performed using a murine endothelioma cell line (EOMA). PCR arrays were performed to identify and statistically validate genes that were altered by Ang-(1-7) treatment in these cells. RESULTS: Tests for interaction controlled for dose cohort and clinical response indicated a significant impact of cancer type on post-treatment VEGF and PlGF levels. Following treatment, PlGF levels decreased over time in patients with sarcoma (P = .007). Treatment of EOMA cells with increasing doses of Ang-(1-7) led to significant growth suppression at doses as low as 100 nM. PCR arrays identified 18 genes that appeared to have altered expression after Ang-(1-7) treatment. Replicate analyses confirmed significant changes in 8 genes including reduction in PlGF (P = .04) and hypoxia inducible factor 1α (HIF-1α) expression (P < .001). CONCLUSIONS: Ang-(1-7) has clinical and pre-clinical activity for vascular sarcomas that is linked to reduced HIF-1α and PlGF expression.

Disparities in Adverse Event Reporting for Hospitalized Children.

OBJECTIVES: Hospitals rely on voluntary event reporting (VER) for adverse event (AE) identification, although it captures fewer events than a trigger tool, such as Global Assessment of Pediatric Patient Safety (GAPPS). Medical providers exhibit bias based on patient weight status, race, and English proficiency. We compared the AE rate identified by VER with that identified using the GAPPS between hospitalized children by weight category, race, and English proficiency. METHODS: We identified a cohort of patients 2 years to younger than 18 years consecutively discharged from an academic children's hospital between June and October 2018. We collected data on patient weight status from age, sex, height, and weight, race/ethnicity by self-report, and limited English proficiency by record of interpreter use. We reviewed each chart with the GAPPS to identify AEs and reviewed VER entries for each encounter. We calculated an AE rate per 1000 patient-days using each method and compared these using analysis of variance. RESULTS: We reviewed 834 encounters in 680 subjects; 262 (38.5%) had overweight or obesity, 144 (21.2%) identified as Black, and 112 (16.5%) identified as Hispanic; 82 (9.8%) of encounters involved an interpreter. We identified 288 total AEs, 270 (93.8%) by the GAPPS and 18 (6.3%) by VER. A disparity in AE reporting was found for children with limited English proficiency, with fewer AEs by VER ( P = 0.03) compared with no difference in AEs by GAPPS. No disparities were found by weight category or race. CONCLUSIONS: Voluntary event reporting may systematically underreport AEs in hospitalized children with limited English proficiency.

Body Mass Index Category and Adverse Events in Hospitalized Children.

OBJECTIVE: To identify associations between patient body mass index (BMI) category and adverse event (AE) rate, severity, and preventability in a cohort of children discharged from an academic children's hospital. METHODS: We identified patients 2 to 17 years old consecutively discharged between June and October 2018. Patient age, sex, height, and weight were used to categorize patients as having underweight, normal weight, overweight, or obesity. We used the Global Assessment of Pediatrics Patient Safety trigger tool to identify AEs, which were scored for harm and preventability. The primary outcome was the rate of AEs; these were compared with Poisson regression. We used multivariable logistic regression to model event preventability. RESULTS: We reviewed 834 encounters in 680 subjects; 51 (7.5%) had underweight, 367 (54.0%) had normal weight, 112 (16.5%) had overweight, and 150 (22.1%) had obesity. Our cohort experienced 270 AEs, with an overall rate of 69.7 (61.8-78.5) AEs per 1000 patient-days: 67.7 (46.4-98.7) in underweight, 70.0 (59.4-82.4) in normal weight, 58.6 (42.5-79.7) in overweight, and 80.4 (62.5-103.6) in obesity, P = .46. No associations were seen between BMI category and AE severity. Children with obesity had an increased rate of preventable AEs (P < .01), but this association did not persist in the multivariable model. CONCLUSIONS: In this single-center study, we did not find associations between BMI category and rate, severity, or preventability of AEs.

Visual acuity outcomes after cataract surgery in type 2 diabetes: the Action to Control Cardiovascular Risk in Diabetes (ACCORD) study.

AIMS: To evaluate visual acuity (VA) outcomes of cataract surgery, and factors associated with good visual outcomes, among a population with diabetes. METHODS: Participants with type 2 diabetes enrolled in The Action to Control Cardiovascular Risk in Diabetes (ACCORD) study and ACCORD-eye substudy. 1136 eyes of 784 ACCORD participants receiving cataract surgery during follow-up (2001-2014) were included. Of these, 362 eyes had fundus photographs gradable for diabetic retinopathy. The main outcome measure was the achievement of postoperative VA of 20/40 or better. RESULTS: In the sample of 1136 eyes, 762 eyes (67.1%) achieved good visual outcome of 20/40 or better. Factors predictive of good visual outcome were higher level of educational attainment (college vs some high school, OR 2.35 (95% CI 1.44 to 3.82)), bilateral cataract surgery (OR 1.55 (1.14 to 2.10)) and preoperative VA (20/20 or better vs worse than 20/200, OR 10.59 (4.07 to 27.54)). Factors not significantly associated (p>0.05) included age, sex, race, smoking, diabetes duration, blood pressure, lipid levels and haemoglobin A1C (HbA1C). In the subsample of 362 eyes, absence of diabetic retinopathy was associated with good visual outcome (OR 1.73 (1.02 to 2.94)). CONCLUSION: Among individuals with diabetes, two-thirds of eyes achieved good visual outcome after cataract surgery. Notable factors associated with visual outcome included preoperative VA and diabetic retinopathy, but not HbA1C, underscoring that while certain ocular measures may help evaluate visual potential, systemic parameters may not be as valuable. Sociodemographic factors might also be important considerations. Although the current visual prognosis after cataract surgery is usually favourable, certain factors still limit the visual potential in those with diabetes.