Grayson L. Baird

Multicenter Pilot Treatment Trial for Psychogenic Nonepileptic Seizures A Randomized Clinical Trial

IMPORTANCE There is a paucity of controlled treatment trials for the treatment of conversion disorder, seizures type, also known as psychogenic nonepileptic seizures (PNES). Psychogenic nonepileptic seizures, the most common conversion disorder, are as disabling as epilepsy and are not adequately addressed or treated by mental health clinicians. OBJECTIVE To evaluate different PNES treatments compared with standard medical care (treatment as usual). DESIGN, SETTING, AND PARTICIPANTS Pilot randomized clinical trial at 3 academic medical centers with mental health clinicians trained to administer psychotherapy or psychopharmacology to outpatients with PNES. Thirty-eight participants were randomized in a blocked schedule among 3 sites to 1 of 4 treatment arms and were followed up for 16 weeks between September 2008 and February 2012; 34 were included in the analysis. INTERVENTIONS Medication (flexible-dose sertraline hydrochloride) only, cognitive behavioral therapy informed psychotherapy (CBT-ip) only, CBT-ip with medication (sertraline), or treatment as usual. MAIN OUTCOMES AND MEASURES Seizure frequency was the primary outcome; psychosocial and functioning measures, including psychiatric symptoms, social interactions, quality of life, and global functioning, were secondary outcomes. Data were collected prospectively, weekly, and with baseline, week 2, midpoint (week 8), and exit (week 16) batteries. Within-group analyses for each arm were performed on primary (seizure frequency) and secondary outcomes from treatment-blinded raters using an intention-to-treat analysis. RESULTS The psychotherapy (CBT-ip) arm showed a 51.4% seizure reduction (P = .01) and significant improvement from baseline in secondary measures including depression, anxiety, quality of life, and global functioning (P < .001). The combined arm (CBT-ip with sertraline) showed 59.3% seizure reduction (P = .008) and significant improvements in some secondary measures, including global functioning (P = .007). The sertraline-only arm did not show a reduction in seizures (P = .08). The treatment as usual group showed no significant seizure reduction or improvement in secondary outcome measures (P = .19). CONCLUSIONS AND RELEVANCE This pilot randomized clinical trial for PNES revealed significant seizure reduction and improved comorbid symptoms and global functioning with CBT-ip for PNES without and with sertraline. There were no improvements in the sertraline-only or treatment-as-usual arms. This study supports the use of manualized psychotherapy for PNES and successful training of mental health clinicians in the treatment. Future studies could assess larger-scale intervention dissemination. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT00835627.

Changes in Recall Type and Patient Treatment Following Implementation of Screening Digital Breast Tomosynthesis

PURPOSE To compare recall rate, types of abnormalities recalled, additional imaging required, biopsy positive predictive value (PPV), and cancer detection rate before and after implementation of screening digital breast tomosynthesis (DBT). MATERIALS AND METHODS This retrospective analysis was approved by the institutional review board and complied with HIPAA. The requirement to obtain informed consent was waived. Results from all screening digital mammography (DM) examinations performed without tomosynthesis from March 1, 2011, through February 29, 2012, and DBT examinations performed from March 1, 2012, through February 28, 2013, were reviewed to identify all Breast Imaging Reporting and Data System (BI-RADS) category 0 examinations (needs additional imaging). Radiology and pathology reports were reviewed. The recall rate, biopsy PPV, and cancer detection rate were calculated. Statistical analysis was performed by using a two-proportions z test. RESULTS The recall rate was 9.3% (1175 of 12 577 examinations; 95% confidence interval [CI]: 8.8%, 9.9%) for DM and 6.4% (827 of 12 921 examinations; 95% CI: 6.0%, 6.8%) for DBT, an overall reduction of 31% (P < .00001). The recall rate was lower with DM than with DBT for masses (8.9% vs 26.8%, respectively), distortions (0.6% vs 5.3%), and calcifications (13.4% vs 20.3%) (P < .0001 for all). The recall rate was lower with DBT than with DM for asymmetries (13.3% vs 32.2%, respectively) and focal asymmetries (18.2% vs 32.2%) (P < .0001 for both). Diagnostic evaluation with ultrasonography (US) increased with DBT at the time of additional imaging (2.6% for DM vs 28.3% for DBT, P < .0001). There was no significant difference between DM and DBT with regard to biopsy PPV (30.2% vs 23.8%, P = .21) or cancer detection rate per 1000 patients (5.4 vs 4.6, P = .44). CONCLUSION With DBT, the recall rate decreased and the biopsy PPV and cancer detection rate did not decrease. The distribution of recalled abnormalities changed, and more patients were evaluated with US only.

Exosomes induce and reverse monocrotaline-induced pulmonary hypertension in mice

AIMS Extracellular vesicles (EVs) from mice with monocrotaline (MCT)-induced pulmonary hypertension (PH) induce PH in healthy mice, and the exosomes (EXO) fraction of EVs from mesenchymal stem cells (MSCs) can blunt the development of hypoxic PH. We sought to determine whether the EXO fraction of EVs is responsible for modulating pulmonary vascular responses and whether differences in EXO-miR content explains the differential effects of EXOs from MSCs and mice with MCT-PH. METHODS AND RESULTS Plasma, lung EVs from MCT-PH, and control mice were divided into EXO (exosome), microvesicle (MV) fractions and injected into healthy mice. EVs from MSCs were divided into EXO, MV fractions and injected into MCT-treated mice. PH was assessed by right ventricle-to-left ventricle + septum (RV/LV + S) ratio and pulmonary arterial wall thickness-to-diameter (WT/D) ratio. miR microarray analyses were also performed on all EXO populations. EXOs but not MVs from MCT-injured mice increased RV/LV + S, WT/D ratios in healthy mice. MSC-EXOs prevented any increase in RV/LV + S, WT/D ratios when given at the time of MCT injection and reversed the increase in these ratios when given after MCT administration. EXOs from MCT-injured mice and patients with idiopathic pulmonary arterial hypertension (IPAH) contained increased levels of miRs-19b,-20a,-20b, and -145, whereas miRs isolated from MSC-EXOs had increased levels of anti-inflammatory, anti-proliferative miRs including miRs-34a,-122,-124, and -127. CONCLUSION These findings suggest that circulating or MSC-EXOs may modulate pulmonary hypertensive effects based on their miR cargo. The ability of MSC-EXOs to reverse MCT-PH offers a promising potential target for new PAH therapies.

Higher Estradiol and Lower Dehydroepiandrosterone-Sulfate Levels Are Associated with Pulmonary Arterial Hypertension in Men.

RATIONALE Recent studies have focused on the role of female sex and estradiol (E2) in pulmonary arterial hypertension (PAH), but it is not known whether sex hormones are risk factors for PAH in men. OBJECTIVES We performed a case-control study to determine whether hormone levels (E2, dehydroepiandrosterone-sulfate [DHEA-S], and testosterone) are associated with PAH in men. METHODS Plasma sex hormone levels in men with idiopathic, heritable, or connective tissue disease-associated PAH were compared with those from age- and body mass index-matched men without clinical cardiovascular disease. MEASUREMENTS AND MAIN RESULTS There were 23 cases with PAH (70% had idiopathic PAH, 65% were functional class III/IV) and 67 control subjects. Higher E2 and E2/testosterone levels were associated with the risk of PAH (odds ratio per 1 ln[E2:testosterone], 6.0; 95% confidence interval, 2.2-16.4; P = 0.001), whereas higher levels of DHEA-S were associated with a reduced risk (odds ratio per 1 ln[DHEA-S], 0.1; 95% confidence interval, 0.0-0.3; P = 0.001). E2 and DHEA-S levels were strong predictors of case status (C statistic for both, 0.82) but testosterone was not (C statistic, 0.53). Higher levels of E2 were associated with shorter 6-minute-walk distances (P = 0.03), whereas higher levels of DHEA-S were associated with lower right atrial pressure (P = 0.02) and pulmonary vascular resistance (P = 0.01) in men with PAH. CONCLUSIONS Higher levels of E2 and lower levels of DHEA-S were associated with PAH in men. Sex-based differences in sex hormone processing and signaling may contribute to unique phenotypes in pulmonary vascular disease.

Management of Nodules with Initially Nondiagnostic Results of Thyroid Fine-Needle Aspiration: Can We Avoid Repeat Biopsy?

PURPOSE To identify demographic and ultrasonographic (US) features associated with malignancy after initially nondiagnostic results of fine-needle aspiration (FNA) to help clarify the role of repeat FNA, surgical excision, or serial US in these nodules. MATERIALS AND METHODS This study was HIPAA compliant and institutional review board approved; informed consent was waived. Thyroid nodules (n = 5349) that underwent US-guided FNA in 2004-2012 were identified; 393 were single nodules with nondiagnostic FNA results but adequate cytologic, surgical, or US follow-up. Demographic information and diameters and volume at US at first biopsy were modeled with malignancy as outcome through medical record review. Exact logistic regression was used to model malignancy outcomes, demographic comparisons with age were made (Student t test, Satterthwaite test), and proportion confidence intervals (CIs) were estimated (Clopper-Pearson method). RESULTS Of 393 nodules with initially nondiagnostic results, nine malignancies (2.3%) were subsequently diagnosed with repeat FNA (n = 2, 0.5%) or surgical pathologic examination (n = 7, 1.8%), 330 (84.0%) were benign, and 54 (13.7%) were stable or decreased in size at serial US (mean follow-up, 3.0 years; median, 2.5 years; range, 1.0-7.8 years). Patients with malignancies were significantly older (mean age, 62.7 years; median, 64 years; range, 47-77 years) than those without (mean age, 55.4 years; median, 57 years; range, 12-94 years; P = .0392). Odds of malignancy were 4.2 times higher for men versus women (P = .045) and increased significantly for each 1-cm increase in anteroposterior, minimum, and mean nodule diameter (1.78, 2.10, and 1.96, respectively). In 393 nodules, no malignancies were detected in cystic or spongiform nodules (both, n = 11, 2.8%; 95% CI: 1.4%, 5.0%), nodules with eggshell calcifications (n = 9, 2.3%; 95% CI: 1.1%, 4.3%), or indeterminate echogenic foci (n = 39, 9.9%; 95% CI: 7.2%, 13.3%). CONCLUSION Very few malignancies were diagnosed with repeat FNA following nondiagnostic FNA results (two of 336, 0.6%); therefore, clinical and US follow-up may be more appropriate than repeat FNA following nondiagnostic biopsy results.

Continuous aspiration prior to intracranial vascular embolectomy (CAPTIVE): a technique which improves outcomes

Background Modern stent retriever-based embolectomy for patients with emergent large vessel occlusion improves outcomes. Techniques aimed at achieving higher rates of complete recanalization would benefit patients. Objective To evaluate the clinical impact of an embolectomy technique focused on continuous aspiration prior to intracranial vascular embolectomy (CAPTIVE). Methods A retrospective review was performed of 95 consecutive patients with intracranial internal carotid artery or M1 segment middle cerebral artery occlusion treated with stent retriever-based thrombectomy over an 11-month period. Patients were divided into a conventional local aspiration group (traditional group) and those treated with a novel continuous aspiration technique (CAPTIVE group). We compared both early neurologic recovery (based on changes in National Institute of Health Stroke Scale (NIHSS) score), independence at 90 days (modified Rankin score 0–2), and angiographic results using the modified Thrombolysis in Cerebral Ischemia (TICI) scale including the TICI 2c category. Results There were 56 patients in the traditional group and 39 in the CAPTIVE group. Median age and admission NIHSS scores were 78 years and 19 in the traditional group and 77 years and 19 in the CAPTIVE group. Median times from groin puncture to recanalization in the traditional and CAPTIVE groups were 31 min and 14 min, respectively (p<0.0001). While rates of TICI 2b/2c/3 recanalization were similar (81% traditional vs 100% CAPTIVE), CAPTIVE offered higher rates of TICI 2c/3 recanalization (79.5% vs 40%, p<0.001). Median discharge NIHSS score was 10 in the traditional group and 3 in the CAPTIVE group; this difference was significant. There was also an increased independence at 90 days (25% traditional vs 49% CAPTIVE). Conclusions The CAPTIVE embolectomy technique may result in higher recanalization rates and better clinical outcomes.

Rethinking Thrombolysis in Cerebral Infarction 2b: Which Thrombolysis in Cerebral Infarction Scales Best Define Near Complete Recanalization in the Modern Thrombectomy Era

Background and Purpose— Within the thrombolysis in cerebral infarction (TICI) classification, TICI 2b has been historically considered successful recanalization. Recent studies have suggested that TICI 3 and a proposed TICI 2c should be separately reported from TICI 2b, in both the original (>66% reperfusion) and modified (>50% reperfusion) definitions, because of differences in clinical outcomes with greater reperfusion. The purpose of this study was to evaluate differences in early neurological improvement and independence at 90 days using the original TICI, modified TICI, and modified TICI with 2c scales. Methods— A retrospective review of 129 consecutive patients with middle cerebral artery, M1 segment or intracranial internal carotid artery occlusions. Patient angiograms were graded by 2 experienced readers by percentage recanalization. This was then categorized into original TICI, modified TICI (mTICI), and mTICI with TICI 2c (mTICI 2c) grading scales. Comparison of baseline demographics, early neurological improvement, and independence at 90 days was performed. Results— A significant difference in early neurological improvement was observed between 2b and 3 (P=0.032), as well as between 2b and 2c (P=0.028) under the mTICI 2c grading scale. Similarly, a significant difference in functional independence was observed between 2b and 3 (P=0.037), as well as between 2b and 2c (P=0.047) under the mTICI 2c scale. The difference in early neurological improvement or functional independence between 2b and 3 for the original TICI and mTICI scales was not significant. When combining the 2c and 3 groups under the mTICI 2c scale, there were significant differences between 2b and 2c/3 in regards to both early neurological improvement (P=0.011) and independence (P=0.018). Conclusions— Using a TICI grading system that includes an additional category beyond TICI 2b allows for refined prediction of early neurological improvement and functional independence.

Association of a Primary Stroke Center Protocol for Suspected Stroke by Large-Vessel Occlusion With Efficiency of Care and Patient Outcomes.

Importance While prehospital triage to the closest comprehensive stroke center (CSC) may improve the delivery of care for patients with suspected emergent large-vessel occlusion (ELVO), efficient systems of care must also exist for patients with ELVO who first present to a primary stroke center (PSC). Objective To describe the association of a PSC protocol focused on 3 key steps (early CSC notification based on clinical severity, vessel imaging at the PSC, and cloud-based image sharing) with the efficiency of care and the outcomes of patients with suspected ELVO who first present to a PSC. Design, Setting, and Participants In this retrospective cohort study, 14 regional PSCs unfamiliar with the management of patients with ELVO were instructed on the use of the following protocol for patients presenting with a Los Angeles Motor Scale score 4 or higher: (1) notify the CSC on arrival, (2) perform computed tomographic angiography concurrently with noncontract computed tomography of the brain and within 30 minutes of arrival, and (3) share imaging data with the CSC using a cloud-based platform. A total of 101 patients were transferred from regional PSCs to the CSC between July 1, 2015, and May 31, 2016, and received mechanical thrombectomy for acute ischemic stroke. The CSC serves approximately 1.7 million people and partners with 14 PSCs located between 6.4 and 73.6 km away. All consecutive patients with internal carotid artery or middle cerebral artery occlusions transferred over an 11-month period were reviewed, and they were divided into 2 groups based on whether the PSC protocol was partially or fully executed. Main Outcomes and Measures The primary outcomes were efficiency measures including time from PSC door in to PSC door out, time from PSC door to CSC groin puncture, and 90-day modified Rankin Scale score (range, 0-6; scores of 0-2 indicate a good outcome). Results Although 101 patients were transferred, only 70 patients met the inclusion criteria during the study period. The protocol was partially executed for 48 patients (68.6%) (mean age, 77 years [interquartile range, 65-84 years]; 22 of the 48 patients [45.0%] were women) and fully executed for 22 patients (31.4%) (mean age, 76 years [interquartile range, 59-86 years]; 13 of the 22 patients [59.1%] were women). When fully executed, the protocol was associated with a reduction in the median time for PSC arrival to CSC groin puncture (from 151 minutes [95% CI, 141-166 minutes] to 111 minutes [95% CI, 88-130 minutes]; P < .001). This was primarily related to an improvement in the time from PSC door in to door out that reduced from a median time of 104 minutes (95% CI, 82-112 minutes) to a median time of 64 minutes (95% CI, 51-71.0 minutes) (P < .001). When the protocol was fully executed, patients were twice as likely to have a favorable outcome (50% vs 25%, P < .04). Conclusions and Relevance When fully implemented, a standardized protocol at PSCs for patients with suspected ELVO consisting of early CSC notification, computed tomographic angiography on arrival to the PSC, and cloud-based image sharing is associated with a reduction in time to groin puncture and improved outcomes.

Examining the Reading Level of Internet Medical Information for Common Internal Medicine Diagnoses

BACKGROUND The National Institutes of Health (NIH) recommend that health materials be written at a grade 6-7 reading level, which has generally not been achieved in online reading materials. Up to the present time, there have not been any assessments focused on the reading level of online educational materials across the most popular consumer Web sites for common internal medicine diagnoses. In this study, we examined the readability of open-access online health information for 9 common internal medicine diagnoses. METHODS Nine of the most frequently encountered inpatient and ambulatory internal medicine diagnoses were selected for analysis. In November and December 2014, these diagnoses were used as search terms in Google, and the top 5 Web sites across all diagnoses and a diagnosis-specific site were analyzed across 5 validated reading indices. RESULTS On average, the lowest reading grade-level content was provided by the NIH (10.7), followed by WebMD (10.9), Mayo Clinic (11.3), and diagnosis-specific Web sites (11.5). Conversely, Wikipedia provided content that required the highest grade-level readability (14.6). The diagnoses with the lowest reading grade levels were chronic obstructive pulmonary disease (10.8), followed by diabetes (10.9), congestive heart failure (11.7), osteoporosis (11.7) and hypertension (11.7). Depression had the highest grade-level readability (13.8). DISCUSSION Despite recommendations for patient health information to be written at a grade 6-7 reading level, our examination of online educational materials pertaining to 9 common internal medicine diagnoses revealed reading levels significantly above the NIH recommendation. This was seen across both diagnosis-specific and general Web sites. There is a need to improve the readability of online educational materials made available to patients. These improvements have the potential to greatly enhance patient awareness, engagement, and physician-patient communication.

Clinical and Radiologic Follow-up Study for Biopsy Diagnosis of Radial Scar/Radial Sclerosing Lesion without Other Atypia.

To determine the incidence of malignancy for radial scars (RS)/radial sclerosing lesions (RSL) without associated atypia or malignancy identified at needle biopsy. Retrospective review of the pathology data base from January 2004 to July 2013 yielded 100 needle biopsies diagnosed as RS/RSL without associated atypia/malignancy. The RS/RSL was considered “incidental” if the target was calcifications and “targeted” if imaging revealed a mass, architectural distortion, or suspicious magnetic resonance imaging enhancement. The electronic medical record was used to identify surgical pathology, follow‐up imaging, and clinical course; all pathology slides and imaging were reviewed by a board‐certified pathologist and radiologist, respectively. Patient age, laterality, RS/RSL size, microcalcifications, and associated benign lesions were recorded. Among 100 cases, 54 were “incidental” and 46 were “targeted.” In the incidental group, 14 underwent excision, 30 had imaging follow‐up, and 10 were lost to follow‐up. In the targeted group, 27 underwent excision, 11 had imaging follow‐up, and 8 were lost to follow‐up. Atypia was identified in four excisions: three from the incidental group and one from the targeted group. Among these, three had negative imaging follow‐up (mean 45 months; range 15–60 months); the fourth patient (one of the incidental group) underwent excision alone. One of the 27 “targeted” patients who underwent excision developed ductal carcinoma in situ of the contralateral breast at 96 months. There have been no ipsilateral malignancies. We found no evidence of associated malignancy at excision for either incidental or targeted biopsies of RS/RSL without atypia. Our study suggests that close imaging follow‐up is adequate for patients with RS/RSL without associated atypia/malignancy on needle biopsy.