Citations

Objective: Preliminary studies suggest that repetitive transcranial magnetic stimulation (rTMS) may be an effective and tolerable intervention for adolescents with treatment-resistant depression. There is limited rationale to inform coil placement for rTMS dosing in this population. We sought to examine and compare three localization techniques for coil placement in the context of an open-label trial of high-frequency rTMS for adolescents with treatment-resistant depression. Methods: Ten adolescents with treatment-resistant depression were enrolled in an open-label trial of high-frequency rTMS. Participants were offered 30 rTMS sessions (10 Hz, 120% motor threshold, left 3000 pulses applied to the dorsolateral prefrontal cortex) over 6–8 weeks. Coil placement for treatment was MRI guided. The scalp location for treatment was compared with the locations identified with standard 5 cm rule and Beam F3 methods. Results: Seven adolescents completed 30 rTMS sessions. No safety or tolerability concerns were identified. Depression severity as assessed with the Children's Depression Rating Scale Revised improved from baseline to treatment 10, treatment 20, and treatment 30. Gains in depressive symptom improvement were maintained at 6 month follow-up visits. An MRI-guided approach for coil localization was feasible and efficient. Our results suggest that the 5 cm rule, Beam F3, and the MRI-guided localization approaches provided variable scalp targets for rTMS treatment. Conclusions: Open-label, high-frequency rTMS was feasible, tolerable, and effective for adolescents with treatment-resistant depression. Larger, blinded, sham-controlled trials are needed for definitive safety and efficacy data. Further efforts to understand optimal delivery, dosing, and biomarker development for rTMS treatments of adolescent depression are warranted.

SummaryThis study revisited the Dohner prognostic hierarchy in a cohort of 1585 well‐documented patients with chronic lymphocytic leukaemia. The duration of both time to first treatment (TTFT) and overall survival (OS) were significantly longer than observed previously, and this is at least partly due to improved therapeutic options. Deletion 13q remains the most favourable prognostic group with median TTFT and OS from fluorescence in situ hybridization (FISH) testing of 72 months and >12 years, respectively. Deletion 11q had the poorest median TTFT (22 months) and 17p deletion the poorest median OS (5 years). The percentages of abnormal nuclei were significantly associated with differential TTFT for the trisomy 12, 13q and 17p deletion cohorts but not for the 11q deletion cohort. From the date of the first FISH study, patients with >85% 13q deletion nuclei had a notably shorter TTFT (24 months). Patients with ≤20% 17p deletion nuclei had longer median TTFT and OS from the date of the first FISH study (44 months and 11 years), and were more likely to be IGHV mutated.

ObjectivesPerformance measurement is used by health care providers, payers, and patients. Historically accomplished using administrative data, registries are used increasingly to track and improve care. We assess how measured diabetes care quality differs when calculated using claims versus registry.Data Sources/Study SettingCross‐sectional analysis of administrative claims and electronic health records (EHRs) of patients in a multispecialty integrated health system in 2012 (n = 368,883).Study DesignWe calculated percent of patients attaining glycohemoglobin <8.0 percent, LDL cholesterol <100 mg/dL, blood pressure <140/90 mmHg, and nonsmoking (D4) in cohorts, identified by Medicare Accountable Care Organization/Minnesota Community Measures (ACO‐MNCM; claims‐based), Healthcare Effectiveness Data and Information Set (HEDIS; claims‐based), and registry (EHR‐based).Data Collection/Extraction MethodsClaims were linked to EHR to create a dataset of performance‐eligible patients.Principal FindingsACO‐MNCM, HEDIS, and registry identified 6,475, 6,989, and 6,425 measurement‐eligible patients. Half were common among the methods; discrepancies were due to attribution, age restriction, and encounter requirements. D4 attainment was lower in ACO‐MNCM (36.09 percent) and HEDIS (37.51 percent) compared to registry (43.74 percent) cohorts.ConclusionsRegistry‐ and claims‐based performance measurement methods identify different patients, resulting in different rates of quality metric attainment with implications for innovative population health management.

Abstract Background: Several previous studies have found inverse associations between glioma susceptibility and a history of allergies or other atopic conditions. Some evidence indicates that respiratory allergies are likely to be particularly relevant with regard to glioma risk. Using data from the Glioma International Case-Control Study (GICC), we examined the effects of respiratory allergies and other atopic conditions on glioma risk. Methods: The GICC contains detailed information on history of atopic conditions for 4,533 cases and 4,171 controls, recruited from 14 study sites across five countries. Using two-stage random-effects restricted maximum likelihood modeling to calculate meta-analysis ORs, we examined the associations between glioma and allergy status, respiratory allergy status, asthma, and eczema. Results: Having a history of respiratory allergies was associated with an approximately 30% lower glioma risk, compared with not having respiratory allergies (mOR, 0.72; 95% confidence interval, 0.58–0.90). This association was similar when restricting to high-grade glioma cases. Asthma and eczema were also significantly protective against glioma. Conclusion: A substantial amount of data on the inverse association between atopic conditions and glioma has accumulated, and findings from the GICC study further strengthen the existing evidence that the relationship between atopy and glioma is unlikely to be coincidental. Impact: As the literature approaches a consensus on the impact of allergies in glioma risk, future research can begin to shift focus to what the underlying biologic mechanism behind this association may be, which could, in turn, yield new opportunities for immunotherapy or cancer prevention. Cancer Epidemiol Biomarkers Prev; 25(2); 282–90. ©2016 AACR.

Abstract Purpose: First-in-human phase I trial to determine the safety, pharmacokinetics, and antitumor activity of BIND-014, a novel, tumor prostate-specific membrane antigen (PSMA)–targeted nanoparticle, containing docetaxel. Experimental Design: Patients with advanced solid tumors received BIND-014 every three weeks (n = 28) or weekly (n = 27), with dose levels ranging from 3.5 to 75 mg/m2 and 15 to 45 mg/m2, respectively. Results: BIND-014 was generally well tolerated, with no unexpected toxicities. The most common drug-related toxicities (&gt;20% of patients) on either schedule included neutropenia, fatigue, anemia, alopecia, and diarrhea. BIND-014 demonstrated a dose-linear pharmacokinetic profile, distinct from docetaxel, with prolonged persistence of docetaxel-encapsulated circulating nanoparticles. Of the 52 patients evaluable for response, one had a complete response (cervical cancer on the every three week schedule) and five had partial responses (ampullary adenocarcinoma, non–small cell lung, and prostate cancers on the every-three-week schedule, and breast and gastroesophageal cancers on the weekly schedule). Responses were noted in both PSMA-detectable and -undetectable tumors. Conclusions: BIND-014 was generally well tolerated, with predictable and manageable toxicity and a unique pharmacokinetic profile compared with conventional docetaxel. Clinical activity was noted in multiple tumor types. The recommended phase II dose of BIND-014 is 60 mg/m2 every three weeks or 40 mg/m2 weekly. Clin Cancer Res; 22(13); 3157–63. ©2016 AACR.

The dual-layer Woven EndoBridge (WEB) device (WEB II) is designed to improve the performance of the first-generation WEB device. This study was performed to evaluate the acute and chronic performance of WEB II for aneurysm occlusion in an elastase-induced aneurysm model in rabbits. We implanted WEB II devices in 36 elastase-induced aneurysms and followed up for one, three, six, and 12 months. Degree of aneurysm occlusion at follow-up was graded on the Web Occlusion Scale (WOS): Grade A, complete aneurysm occlusion; Grade B, complete occlusion with recess filling; Grade C, residual neck filling; and Grade D, residual aneurysm filling. Hematoxylin and eosin staining was performed for histological assessment of aneurysm healing. Grades A, B, C, and D aneurysm occlusion at one-month follow-up were noted in three (17%), three (17%), eight (44%), and four (22%) of 18 cases, respectively. At the three-month time point Grades A, B, C, and D were shown in two (33%), two (33%), one (17%), and one (17%) aneurysms. Six months after treatment, one (17%), two (33%), two (33%), and one (17%) cases demonstrated Grades A, B, C, and D occlusion. At the 12-month time point, Grades B, C, and D were shown in three (50%), two (33%), and one (17%) aneurysms. Histologic evaluation showed progressive thrombus organization within aneurysm lumen from one to 12 months. These results indicated that the WEB II device can achieve high rates of aneurysm occlusion over time in experimental aneurysms.