Violet 405-nm light: a novel therapeutic agent against common pathogenic bacteria.

BACKGROUND: The increasing incidence of healthcare-associated infections (HAIs) and multidrug-resistant organisms demonstrate the need for innovative technological solutions. Staphylococcus aureus, Streptococcus pneumonia, Escherichia coli, and Pseudomonas aeruginosa in particular are common pathogens responsible for a large percentage of indwelling medical device-associated clinical infections. The bactericidal effects of visible light sterilization (VLS) using 405-nm is one potential therapeutic under investigation. MATERIALS AND METHODS: Light-emitting diodes of 405-nm were used to treat varying concentrations of S aureus, S pneumonia, E coli, and P aeruginosa. Irradiance levels between 2.71 ± 0.20 to 9.27 ± 0.36 mW/cm2 and radiant exposure levels up to 132.98 ± 6.68 J/cm2 were assessed. RESULTS: Dose-dependent effects were observed in all species. Statistically significant reductions were seen in both Gram-positive and Gram-negative bacteria. At the highest radiant exposure levels, bacterial log10 reductions were E coli-6.27 ± 0.54, S aureus-6.10 ± 0.60, P aeruginosa-5.20 ± 0.84, and S pneumoniae-6.01 ± 0.59. Statistically significant results (<0.001*) were found at each time point. CONCLUSIONS: We have successfully demonstrated high-efficacy bacterial reduction using 405-nm light sterilization. The VLS showed statistical significance against both Gram-positive and Gram-negative species with the given treatment times. The ß-lactam antibiotic-resistant E coli was the most sensitive to VLS, suggesting light therapy could a suitable option for sterilization in drug-resistant bacterial species. This research illustrates the potential of using VLS in treating clinically relevant bacterial infections.

Industry-academic partnerships: an approach to accelerate innovation.

BACKGROUND: Biotechnology companies are process-driven organizations and often struggle with their ability to innovate. Universities, on the other hand, thrive on discovery and variation as a source of innovation. As such, properly structured academic-industry partnerships in medical technology development may enhance and accelerate innovation. Through joint industry-academic efforts, our objective was to develop a technology aimed at global cervical cancer prevention. METHODS: Our Center for Medical Innovation assembled a multidisciplinary team of students, surgical residents, and clinical faculty to enter in the University of Utah's annual Bench-to-Bedside competition. Bench-to-Bedside is a university program centered on medical innovation. Teams are given access to university resources and are provided $500.00 for prototype development. Participation by team members are on a volunteer basis. Our industry partner presented the validated need and business mentorship. The team studied the therapeutic landscape, environmental constraints, and used simulation to understand human factors design and usage requirements. A physical device was manufactured by first creating a digital image (SOLIDWORKS 3D CAD). Then, using a 3-dimensional printer (Stratasys Objet30 Prime 3D printer), the image was translated into a physical object. Tissue burn depth analysis was performed on raw chicken breasts warmed to room temperature. Varying combinations of time and temperature were tested, and burn depth and diameter were measured 30 min after each trial. An arithmetic mean was calculated for each corresponding time and temperature combination. User comprehension of operation and sterilization was tested via a participant validation study. Clinical obstetricians and gynecologists were given explicit instructions on usage details and then asked to operate the device. Participant behaviors and questions were recorded. RESULTS: Our efforts resulted in a functional battery-powered hand-held thermocoagulation prototype in just 72 d. Total cost of development was <$500. Proof of concept trials at 100°C demonstrated an average ablated depth and diameter of 4.7 mm and 23.3 mm, respectively, corresponding to treatment efficacy of all grades of precancerous cervical lesions. User comprehension studies showed variable understanding with respect to operation and sterilization instructions. CONCLUSIONS: Our experience with using industry-academic partnerships as a means to create medical technologies resulted in the rapid production of a low-cost device that could potentially serve as an integral piece of the "screen-and-treat" approach to premalignant cervical lesions as outlined by World Health Organization. This case study highlights the impact of accelerating medical advances through industry-academic partnership that leverages their combined resources.

Implementation of national practice guidelines to reduce waste and optimize patient value.

BACKGROUND: The financial health care crisis has provided the platform to drive operational improvements at US health care facilities. This has led to adoption of lean operation principles by many health care organizations as a means of eliminating waste and improving operational efficiencies and overall value to patients. We believe that standardized implementation of national practice guidelines can provide the framework to help to reduce financial waste. MATERIALS AND METHODS: We analyzed our institutional preoperative electrocardiogram (ECG) ordering practices for patients undergoing elective surgery at our institution from February-March, 2012 to identify utilization and review compliance with American Heart Association guidelines. We then implemented an ECG ordering algorithm based on these guidelines and studied changes in ordering patterns, associated cost savings and hospital billing for the same period in 2013. RESULTS: From February-March 2012, 677 noncardiac surgical procedures were performed at our institution, and 312 (46.1%) had a preoperative ECG. After implementation of our evidence-based ECG ordering algorithm for the same period in 2013, 707 noncardiac surgical cases were performed, and 120 (16.9%) had a preoperative ECG. Preoperative ECG utilization dropped 63% with an annual institutional cost savings of $72,906 and $291,618 in total annual health care savings. Based on our data, US-wide implementation of our evidence-based ECG ordering algorithm could save the US health care system >$1,868,800,000 per year. CONCLUSIONS: Here, we demonstrate that standardized application of a national practice guideline can be used to eliminate nearly $2 billion per year in waste from the US health care system.

A noncontact RF-based respiratory sensor: results of a clinical trial.

BACKGROUND: Respiratory rate (RR) is a critical vital signs monitored in health care setting. Current monitors suffer from sensor-contact failure, inaccurate data, and limited patient mobility. There is a critical need for an accurate and reliable and noncontact system to monitor RR. We developed a contact-free radio frequency (RF)-based system that measures movement using WiFi signal diffraction, which is converted into interpretable data using a Fourier transform. Here, we investigate the system's ability to measure fine movements associated with human respiration. MATERIALS AND METHODS: Testing was conducted on subjects using visual cue, fixed-tempo instruction to breath at standard RRs. Blinded instruction-based RRs were compared to RF-acquired data to determine measurement accuracy. The RF-based technology was studied on postoperative ventilator-dependent patients. Blinded ventilator capnographic RR data were collected for each patient and compared to RF-acquired data to determine measurement accuracy. RESULTS: Respiratory rate data collected from 10 subjects breathing at a fixed RR (14, 16, 18, or 20) demonstrated 95.5% measurement accuracy between the patient's actual rate and that measured by our RF technology. Ten patients were enrolled into the clinical trial. Blinded ventilator capnographic RR data were compared to RF-based acquired data. The RF-based data showed 88.8% measurement accuracy with ventilator capnography. CONCLUSIONS: Initial clinical pilot trials with our contact-free RF-based monitoring system demonstrate a high degree of RR measurement accuracy when compared to capnographic data. Based on these results, we believe RF-based systems present a promising noninvasive, inexpensive, and accurate tool for continuous RR monitoring.

Violet 405 nm light: A novel therapeutic agent against ß-lactam-resistant Escherichia coli.

BACKGROUND AND OBJECTIVE: Approximately 1.7 million patients are affected by hospital-acquired infections every year in the United States. The increasing prevalence of multidrug-resistant bacteria associated with these infections prompts the investigation of alternative sterilization and antibacterial therapies. One method currently under investigation is the antibacterial properties of visible light. This study examines the effect of a visible light therapy (VLT) on ß-lactam-resistant Escherichia coli, a common non-skin flora pathogen responsible for a large percentage of indwelling medical device-associated clinical infection. MATERIALS AND METHODS: 405 nm light-emitting diodes were used to treat varying concentrations of a common laboratory E. coli K-12 strain transformed with the pCIG mammalian expression vector. This conferred ampicillin resistance via expression of the ß-lactamase gene. Bacteria were grown on sterile polystyrene Petri dishes plated with Luria-Bertani broth. Images of bacterial growth colonies on plates were processed and analyzed using ImageJ. Irradiance levels between 2.89 ± 0.19 and 9.45 ± 0.63 mW cm(-2) and radiant exposure levels between 5.60 ± 0.39 and 136.91 ± 4.06 J cm(-2) were tested. RESULTS: VLT with variable irradiance and constant treatment time (120 minutes) demonstrated significant reduction (P < 0.001) in E. coli between an irradiance of 2.89 mW cm(-2) (81.70%) and 9.37 mW cm(-2) (100.00%). Similar results were found with variable treatment time with constant irradiance. Log10 reduction analysis produced between 1.98 ± 0.53 (60 minute treatment) and 6.27 ± 0.54 (250 minute treatment) log10 reduction in bacterial concentration (P < 0.001). CONCLUSIONS: We have successfully demonstrated a significant bacterial reduction using high intensity 405 nm light. Illustrating the efficacy of this technology against a ß-lactam-resistant E. coli is especially relevant to the need for novel methods of sterilization in healthcare settings. These results suggest that VLT using 405 nm light could be a suitable clinical option for eradication of ß-lactam-resistant E. coli. Visible light kills statistically significant concentrations of E. coli. Antibiotic-resistant Gram-negative bacteria exhibits sensitivity to 405 nm light. Greater than 6 log10 reduction in ß-lactam-resistant E. coli when treated with visible light therapy.

Unresectable Pancreatic Adenocarcinoma: Eight Years Later.

Pancreatic cancer is the fourth leading cause of cancer deaths in the United States, and is considered uniformly fatal when patients present with unresectable, advanced-stage disease at the time of diagnosis. Long-term survival of patients with advanced-stage pancreatic adenocarcinoma remains rare, despite advances in adjuvant chemoradiation protocols. A 73-year-old male presented to our emergency department with abdominal pain and a history of biopsy-proven, stage III pancreatic adenocarcinoma. His initial staging CT scan and trans-duodenal ultrasound had demonstrated a stage IIa (T3, N0, Mx) lesion. On surgical exploration, he was up-staged to stage III (T4, N0, Mx), noting encasement of the superior mesenteric vessels and involvement of the portal vein. He underwent palliative choledochojejunostomy and was treated with 4 months of oxaliplatin and capecitabine, with concurrent radiation therapy (50.4 Gy), followed by 4 months of gemcitabine. After 7 months, the patient withdrew from therapy due to treatment intolerance. He then turned to self-medication with non-traditional herbal therapies. After 3 years of surveillance, he was lost to follow-up until presenting to our facility with abdominal pain 8 years after his initial diagnosis. On diagnostic CT scan during his current presentation for abdominal pain, he was found to have no evidence of pancreatic cancer. Based on our review of the literature, we present the longest known survival of a patient with surgically unresectable pancreatic adenocarcinoma. Further study of this patient's phenotypic or genotypic characteristics may provide insight into better therapeutic agents, or a predictive subset of patients who will benefit from specific chemotherapeutic options.

Addressing challenges of training a new generation of clinician-innovators through an interdisciplinary medical technology design program: Bench-to-Bedside.

Graduate medical education has traditionally focused on training future physicians to be outstanding clinicians with basic and clinical science research skills. This focus has resulted in substantial knowledge gains, but a modest return on investment based on direct improvements in clinical care. In today's shifting healthcare landscape, a number of important challenges must be overcome to not only improve the delivery of healthcare, but to prepare future physicians to think outside the box, focus on and create healthcare innovations, and navigate the complex legal, business and regulatory hurdles of bringing innovation to the bedside. We created an interdisciplinary and experiential medical technology design competition to address these challenges and train medical students interested in moving new and innovative clinical solutions to the forefront of medicine. Medical students were partnered with business, law, design and engineering students to form interdisciplinary teams focused on developing solutions to unmet clinical needs. Over the course of six months teams were provided access to clinical and industry mentors, $500 prototyping funds, development facilities, and non-mandatory didactic lectures in ideation, design, intellectual property, FDA regulatory requirements, prototyping, market analysis, business plan development and capital acquisition. After four years of implementation, the program has supported 396 participants, seen the development of 91 novel medical devices, and launched the formation of 24 new companies. From our perspective, medical education programs that develop innovation training programs and shift incentives from purely traditional basic and clinical science research to also include high-risk innovation will see increased student engagement in improving healthcare delivery and an increase in the quality and quantity of innovative solutions to medical problems being brought to market.

Gastrointestinal perforation and the acute abdomen.

The acute abdomen accounts for up to 40% of all emergency-surgical hospital admissions and is considered in the differential in the more than 7 million visits to the emergency department annually for abdominal pain in the United States. A large percentage of these cases are secondary to perforation or impending gastrointestinal perforation. Gastrointestinal perforation causes considerable mortality and usually requires emergency surgery.Rapid diagnosis and treatment of these conditions is essential to reduce the high morbidity and mortality of late-stage presentation. Successful treatment requires a thorough understanding of the anatomy, microbiology, and pathophysiology of this disease process and in-depth knowledge of the therapy, including resuscitation,antibiotics, source control, and physiologic support.