Assessment of resident and fellow knowledge of the organ donor referral process.

Maximizing deceased donation rates can decrease the organ shortage. Non-transplant physicians play a critical role in facilitating conversion of potential deceased donors to actual donors, but studies suggest that physicians lack knowledge about the organ donation process. As residency and fellowship are often the last opportunities for formal medical training, we hypothesized that deficiencies in knowledge might originate in residency and fellowship. We conducted a cross-sectional survey to assess knowledge about organ donation, experience in donor conversion, and opinions of the process among residents and fellows after their intensive care unit rotations at the Johns Hopkins Hospital. Of 40 participants, 50% had previously facilitated donor conversion, 25% were familiar with the guidelines of the organ procurement organization (OPO), and 10% had received formal instruction from the OPO. The median score on the knowledge assessment was five of 10; higher knowledge score was not associated with level of medical training, prior training in or experience with donor conversion, or with favorable opinions about the OPO. We identified a pervasive deficit in knowledge among residents and fellows at an academic medical center with an active transplant program that may help explain attending-level deficits in knowledge about the organ donation process.

The Potential of Twitter as a Data Source for Patient Safety.

BACKGROUND: Error-reporting systems are widely regarded as critical components to improving patient safety, yet current systems do not effectively engage patients. We sought to assess Twitter as a source to gather patient perspective on errors in this feasibility study. METHODS: We included publicly accessible tweets in English from any geography. To collect patient safety tweets, we consulted a patient safety expert and constructed a set of highly relevant phrases, such as "doctor screwed up." We used Twitter's search application program interface from January to August 2012 to identify tweets that matched the set of phrases. Two researchers used criteria to independently review tweets and choose those relevant to patient safety; a third reviewer resolved discrepancies. Variables included source and sex of tweeter, source and type of error, emotional response, and mention of litigation. RESULTS: Of 1006 tweets analyzed, 839 (83%) identified the type of error: 26% of which were procedural errors, 23% were medication errors, 23% were diagnostic errors, and 14% were surgical errors. A total of 850 (84%) identified a tweet source, 90% of which were by the patient and 9% by a family member. A total of 519 (52%) identified an emotional response, 47% of which expressed anger or frustration, 21% expressed humor or sarcasm, and 14% expressed sadness or grief. Of the tweets, 6.3% mentioned an intent to pursue malpractice litigation. CONCLUSIONS: Twitter is a relevant data source to obtain the patient perspective on medical errors. Twitter may provide an opportunity for health systems and providers to identify and communicate with patients who have experienced a medical error. Further research is needed to assess the reliability of the data.

Targeted nanoparticles that deliver a sustained, specific release of Paclitaxel to irradiated tumors.

To capitalize on the response of tumor cells to XRT, we developed a controlled-release nanoparticle drug delivery system using a targeting peptide that recognizes a radiation-induced cell surface receptor. Phage display biopanning identified Gly-Ile-Arg-Leu-Arg-Gly (GIRLRG) as a peptide that selectively recognizes tumors responding to XRT. Membrane protein extracts of irradiated glioma cells identified glucose-regulated protein GRP78 as the receptor target for GIRLRG. Antibodies to GRP78 blocked the binding of GIRLRG in vitro and in vivo. Conjugation of GIRLRG to a sustained-release nanoparticle drug delivery system yielded increased paclitaxel concentration and apoptosis in irradiated breast carcinomas for up to 3 weeks. Compared with controls, a single administration of the GIRLRG-targeted nanoparticle drug delivery system to irradiated tumors delayed the in vivo tumor tripling time by 55 days (P = 0.0001) in MDA-MB-231 and 12 days in GL261 (P < 0.005). This targeting agent combines a novel recombinant peptide with a paclitaxel-encapsulating nanoparticle that specifically targets irradiated tumors, increasing apoptosis and tumor growth delay in a manner superior to known chemotherapy approaches.

Recombinant peptides as biomarkers for tumor response to molecular targeted therapy.

PURPOSE: Phage display technology can be used to identify peptide sequences that bind rapidly and specifically to tumors responding to sunitinib therapy. These peptides may help to address problems with current methods of assessing tumor response to therapy that can be slow and have limited usage. EXPERIMENTAL DESIGN: The peptide of interest was isolated after four rounds of biopanning in MDA-MB-231 and MCF-7 xenografted tumors. The binding location of the peptide was investigated with immunohistochemistry. Its in vivo ability to bind to breast tumors responding to therapy was determined by treating nude mice, xenografted with various tumor cell lines, with sunitinib and using near IR imaging to assess the ability of the peptide conjugated to Alexafluor-750 to bind tumors. RESULTS: EGEVGLG was the dominant sequence isolated from biopanning. This peptide showed increased binding relative to control groups in two cancer cell lines (MDA-MB-435 and MCF-7 human breast) responding to sunitinib treatment, whereas no elevated binding occurred in vitro when samples were incubated with tumor cells that are unresponsive to sunitinib treatment (B16 melanoma and BxPC3 pancreatic). Mice xenografted with tumors that are responsive to sunitinib therapy showed increased peptide binding when compared with untreated control. Mice bearing tumors unresponsive to sunitinib therapy showed no increased peptide binding between treated and untreated groups. CONCLUSION: The use of recombinant peptides to assess the pharmacodynamic response of cancer holds promise in minimizing the duration of ineffective treatment regimens in patients, potentially providing a more rapid and less invasive assessment of cancer response to systemic therapy.

Determining glioma response to radiation therapy using recombinant peptides.

Presently, cancer response is measured by imaging assessment of tumor volumes or by repeated biopsy to analyze pharmacodynamics. These methods of monitoring cancer response are inefficient because volume changes typically require therapy for prolonged time intervals and neoplasms within the brain are less amenable to sequential biopsies. Peptide ligands selected from phage-displayed peptide libraries can rapidly differentiate responding from resistant gliomas. These peptides, in turn, can be labeled with internal emitters to provide a means of noninvasive assessment of glioma susceptibility to radiotherapy within 24 h of therapy. This is platform technology and could allow for ineffective therapy to be modified or switched so that patients are not subjected to a delayed reassessment (2 months) of response to therapy.