Feasibility of removable balloon implant for simultaneous magnetic nanoparticle heating and HDR brachytherapy of brain tumor resection cavities.

AIM: Hyperthermia (HT) has been shown to improve clinical response to radiation therapy (RT) for cancer. Synergism is dramatically enhanced if HT and RT are combined simultaneously, but appropriate technology to apply treatments together does not exist. This study investigates the feasibility of delivering HT with RT to a 5-10mm annular rim of at-risk tissue around a tumor resection cavity using a temporary thermobrachytherapy (TBT) balloon implant. METHODS: A balloon catheter was designed to deliver radiation from High Dose Rate (HDR) brachytherapy concurrent with HT delivered by filling the balloon with magnetic nanoparticles (MNP) and immersing it in a radiofrequency magnetic field. Temperature distributions in brain around the TBT balloon were simulated with temperature dependent brain blood perfusion using numerical modeling. A magnetic induction system was constructed and used to produce rapid heating (>0.2°C/s) of MNP-filled balloons in brain tissue-equivalent phantoms by absorbing 0.5 W/ml from a 5.7 kA/m field at 133 kHz. RESULTS: Simulated treatment plans demonstrate the ability to heat at-risk tissue around a brain tumor resection cavity between 40-48°C for 2-5cm diameter balloons. Experimental thermal dosimetry verifies the expected rapid and spherically symmetric heating of brain phantom around the MNP-filled balloon at a magnetic field strength that has proven safe in previous clinical studies. CONCLUSIONS: These preclinical results demonstrate the feasibility of using a TBT balloon to deliver heat simultaneously with HDR brachytherapy to tumor bed around a brain tumor resection cavity, with significantly improved uniformity of heating over previous multi-catheter interstitial approaches. Considered along with results of previous clinical thermobrachytherapy trials, this new capability is expected to improve both survival and quality of life in patients with glioblastoma multiforme.

Prescribing of Opioids and Benzodiazepines Among Patients With History of Overdose.

OBJECTIVES: Addiction and overdose related to prescription drugs continues to be a leading cause of morbidity and mortality in the United States. We aimed to characterize the prescribing of opioids and benzodiazepines to patients who had previously presented with an opioid or benzodiazepine overdose. METHODS: This was a retrospective chart review of patients who were prescribed an opioid or benzodiazepine in a 1-month time-period in 2015 (May) and had a previous presentation for opioid or benzodiazepine overdose at a large healthcare system. RESULTS: We identified 60,129 prescribing encounters for opioids and/or benzodiazepines, 543 of which involved a patient with a previous opioid or benzodiazepine overdose. There were 404 unique patients in this cohort, with 97 having more than 1 visit including a prescription opioid and/or benzodiazepine. A majority of prescriptions (54.1%) were to patients with an overdose within the 2 years of the documented prescribing encounter. Prescribing in the outpatient clinical setting represented half (49.9%) of encounters, whereas emergency department prescribing was responsible for nearly a third (31.5%). CONCLUSIONS: In conclusion, prescribing of opioids and benzodiazepines occurs across multiple locations in a large health care system to patients with a previous overdose. Risk factors, such as previous overdose should be highlighted through clinical decision support tools in the medical record to help prescribers identify patients at higher risk and to mobilize resources for this patient population. Prescribers need further education on factors that place their patients at risk for opioid use disorder and on alternative therapies to opioids and benzodiazepines.

AVATS: Awake Video Assisted Thoracic Surgery--extended series report.

BACKGROUND: Traditionally, video-assisted thoracic surgery (VATS) is performed under general anesthesia with selective ventilation and endotracheal intubation. Although some sparse data exists on VATS under local anesthesia, most series reserve this technique for pleural-based surgery. Performing VATS under local anesthesia may extend the benefits of this procedure to those unable to tolerate general anesthesia and improve outcomes. METHOD: We have extended this technique to include more complex procedures, with results that surpass traditional open thoracotomies. We analyzed 293 patients who underwent awake video-assisted thoracic surgery (AVATS) from June 2010 to January 2014. RESULTS: Procedures such as pleural biopsies, wedge resections, decortications, and even lobectomies were able to be safely performed using AVATS technique with comparable or better results than VATS under general anesthesia. CONCLUSION: AVATS is a feasible technique with equal or improved outcomes without compromise in safety. Further study may help delineate the role of this technique in the care of the thoracic surgical patient.

Physiochemical drug properties associated with in vivo toxicological outcomes.

Relationships between physicochemical drug properties and toxicity were inferred from a data set consisting of animal in vivo toleration (IVT) studies on 245 preclinical Pfizer compounds; an increased likelihood of toxic events was found for less polar, more lipophilic compounds. This trend held across a wide range of types of toxicity and across a broad swath of chemical space.