DUAL ACTION ELECTROCHEMICAL BANDAGE OPERATED by a PROGRAMMABLE MULTIMODAL WEARABLE POTENTIOSTAT.

Electrochemical bandages (e-bandages) can be applied to biofilm-infected wounds to generate reactive oxygen species, such as hypochlorous acid (HOCl) or hydrogen peroxide (H 2 O 2 ). The e-bandage-generated HOCl or H 2 O 2 kills biofilms in vitro and in infected wounds on mice. The HOCl-generating e-bandage is more active against biofilms in vitro , although this distinction is less apparent in vivo . The H 2 O 2 -generating e-bandage, more than the HOCl-generating e-bandage, is associated with improved healing of infected wounds. A strategy in which H 2 O 2 and HOCl are generated alternately-for dual action-was explored. The goal was to develop a programmable multimodal wearable potentiostat (PMWP) that could be programmed to generate HOCl or H 2 O 2 , as needed. An ultralow-power microcontroller unit managed operation of the PMWP. The system was operated with a 260-mAh capacity coin battery and weighed 4.6 grams, making it suitable for small animal experiments or human use. The overall cost of a single wearable potentiostat was $6.50 (USD). The device was verified using established electrochemical systems and functioned comparably to a commercial potentiostat. To determine antimicrobial effectiveness, PMWP-controlled e-bandages were tested against clinical isolates of four prevalent chronic wound bacterial pathogens, methicillin-resistant Staphylococcus aureus (MRSA), Pseudomonas aeruginosa, Acinetobacter baumannii , and Enterococcus faecium , and one fungal pathogen of emerging concern, Candida auris . PMWP-controlled e-bandages exhibited broad-spectrum activity against biofilms of all study isolates tested when programmed to deliver HOCl followed by H 2 O 2 . These results show that the PMWP operates effectively and is suitable for animal testing.

Staff pooling in healthcare systems - results from a mixed-methods study.

This study examines how staff pooling can be used to create a higher service level at a predetermined total capacity in the healthcare sector. We develop new empirical knowledge through a systematic empirical study, using a mixed-methods approach, with a preliminary interview study followed by a principal quantitative survey study, with data from a multihospital system. The purpose was to explore practical barriers for a staff pooling strategy in healthcare systems. Three barriers were identified:recruitment difficulties, community view, and specialisation. Significant differences in perceived height among these barriers were found. The results from this study have important managerial implications for healthcare systems when implementing a staff pooling approach. This study contributes to the existing literature since, to the best of our knowledge, no previous research has been done where barriers to staff pools are systematically identified using a holistic approach that includes all healthcare professions in a multihospital system.

Hospital Staffing during the COVID-19 Pandemic in Sweden.

Staff management challenges in the healthcare system are inherently different during pandemic conditions than under normal circumstances. Surge capacity must be rapidly increased, particularly in the intensive care units (ICU), to handle the increased pressure, without depleting the rest of the system. In addition, sickness or fatigue among the staff can become a critical issue. This study explores the lessons learned by first- and second-line managers in Sweden with regard to staff management during the COVID-19 pandemic. A mixed-methods approach was used, with preliminary qualitative interview (n = 38) and principal quantitative questionnaire (n = 272) studies, based on principal component and multiple regression analyses. The results revealed that the pandemic created four types of challenges relating to staff management: staff movement within hospitals; addition of external staff; addition of hours for existing staff through overtime and new shift schedules; and avoidance of lost hours due to sickness or fatigue. Furthermore, the effects of these managerial challenges were different in the first wave than in later waves, and they significantly differed between the ICU and other units. Therefore, a greater proactive focus on staff management would be beneficial in future pandemic situations.

Creating Short-Term Volume Flexibility in Healthcare Capacity Management.

It is well-known that unpredictable variations in supply and demand of capacity in healthcare systems create the need for flexibility. The main tools used to create short-term volume flexibility in the healthcare system include overtime, temporary staff from internal calling lists, moving staff across units, internal staffing pools, external staffing agencies, queuing patients, and purchasing care from external providers. We study the creation of short-term volume flexibility in healthcare systems to manage short-term capacity losses and demand fluctuations. A questionnaire was developed and distributed among healthcare managers in the Region Västra Götaland healthcare system. Respondents were asked to what extent they used each tool to create short-term flexibility in capacity. Data were analyzed using multiple regression analysis. Several significant tendencies were found, including that acute units use overtime and internal staffing pools to a larger extent, and queuing patients and external providers to a lesser extent than planned units. The prerequisites and required managerial approaches used to efficiently manage aggregate capacity in the system differ substantially between different parts of the system. These differences must be addressed when, for example, capacity pools are considered. These results serve as a stepping stone towards a more thorough understanding of efficient capacity management in healthcare systems.

Thermodynamic Evidence of Structural Transformations in CO2-Loaded Metal-Organic Framework Zn(MeIm)2 from Heat Capacity Measurements.

Metal-organic frameworks are a class of porous compounds with potential applications in molecular sieving, gas sequestration, and catalysis. One family of MOFs, zeolitic imidizolate frameworks (ZIFs), is of particular interest for carbon dioxide sequestration. We have previously reported the heat capacity of the sodalite topology of the zinc 2-methylimidazolate framework (ZIF-8), and in this Article we present the first low-temperature heat capacity measurements of ZIF-8 with various amounts of sorbed CO2. Molar heat capacities from 1.8 to 300 K are presented for samples containing up to 0.99 mol of CO2 per mol of ZIF-8. Samples with at least 0.56 mol of CO2 per mol of ZIF-8 display a large, broad anomaly from 70 to 220 K with a shoulder on the low-temperature side, suggesting sorption-induced structural transitions. We attribute the broad anomaly partially to a gate-opening transition, with the remainder resulting from CO2 rearrangement and/or lattice expansion. The measurements also reveal a subtle anomaly from 0 to 70 K in all samples that does not exist in the sorbate-free material, which likely reflects new vibrational modes resulting from sorbate/ZIF-8 interactions. These results provide the first thermodynamic evidence of structural transitions induced by CO2 sorption in the ZIF-8 framework.

Is Emergency Medicine the Right Choice for Me?

One of the hardest decisions a medical student has to make is the choice of specialty. Many studies have explored what influences the choice of emergency medicine (EM) as a specialty. In this article, we elaborate on the most important incentives, including the diversity in patients' presentations, having a defined and flexible schedule, the plasticity in choosing and changing a practice location, and the acuity of care and trauma experience. Additionally, we tackle some of the challenges that emergency physicians face. For instance, having to follow a different thought process than most other physicians, as well as the patients' quality and expectations. We also address some of the concerns regarding the specialty, specifically burnout, stress, and the fear associated with maintaining a career in EM. Finally, we provide students interested in EM with some resources that can provide them with further guidance to decide whether EM is the right choice for them.

Phase I Study of the Investigational Aurora A Kinase Inhibitor Alisertib plus Rituximab or Rituximab/Vincristine in Relapsed/Refractory Aggressive B-cell Lymphoma.

PURPOSE: The aurora A kinase inhibitor alisertib demonstrated single-agent clinical activity and preclinical synergy with vincristine/rituximab in B-cell non-Hodgkin lymphoma (B-NHL). This phase I study aimed to determine the safety and recommended phase II dose (RP2D) of alisertib in combination with rituximab ± vincristine in patients with relapsed/refractory aggressive B-NHL. PATIENTS AND METHODS: Patients with relapsed/refractory, diffuse, large, or other aggressive B-NHL received oral alisertib 50 mg b.i.d. days 1 to 7, plus i.v. rituximab 375 mg/m2 on day 1, for up to eight 21-day cycles (MR). Patients in subsequent cohorts (3 + 3 design) received increasing doses of alisertib (30 mg starting dose; 10 mg increments) b.i.d. days 1 to 7 plus rituximab and vincristine [1.4 mg/m2 (maximum 2 mg) days 1, 8] for 8 cycles (MRV). Patients benefiting could continue single-agent alisertib beyond 8 cycles. Cell-of-origin and MYC/BCL2 IHC was performed on available archival tissue. RESULTS: Forty-five patients participated. The alisertib RP2D for MR was 50 mg b.i.d. For MRV (n = 32), the RP2D was determined as 40 mg b.i.d. [1 dose-limiting toxicity (DLT) at 40 mg; 2 DLTs at 50 mg]. Drug-related adverse events were reported in 89% of patients, the most common was neutropenia (47%). Seven patients had complete responses (CR), 7 had partial responses (PRs); 9 of 20 (45%) patients at the MRV RP2D responded (4 CRs, 5 PRs), all with non-germinal center B-cell (GCB) diffuse large B-cell lymphoma (DLBCL). CONCLUSIONS: The combination of alisertib 50 mg b.i.d. plus rituximab or alisertib 40 mg b.i.d. plus rituximab and vincristine was well tolerated and demonstrated activity in non-GCB DLBCL.

Safety and efficacy of pomalidomide, dexamethasone and pegylated liposomal doxorubicin for patients with relapsed or refractory multiple myeloma.

Immunomodulatory drugs including thalidomide, lenalidomide (LEN) and pomalidomide (POM), are effective for treating multiple myeloma (MM). POM has shown enhanced efficacy with dexamethasone (DEX). Pegylated liposomal doxorubicin (PLD) with bortezomib is US Food and Drug Administration-approved for treating MM. PLD with LEN or thalidomide has shown efficacy for MM patients. LEN with DEX, PLD and bortezomib achieves high response rates. We evaluated the combination of POM with DEX 40 mg and PLD 5 mg/m2 with the latter two drugs administered on days 1, 4, 8 and 11 on a 28-day cycle for the treatment of relapsed/refractory MM patients. During Phase 1, the maximum tolerated dose of POM was 4 mg, and was used in Phase 2, which also required patients to be refractory to LEN. However, neutropenia ≥ grade 3 was observed in 10/17 (59%) patients, and the dose was lowered to 3 mg. Median PFS was 5·4 months (range, 0·3-29·0 +  months). Overall response rates for patients in Phase 2 were 39% and 31% among subjects receiving POM at 3 mg and 4 mg, respectively, and clinical benefit rates were 51% and 44%, respectively. POM, PLD and DEX is a treatment option for relapsed/refractory MM patients including those who are refractory to LEN.

Measuring effective capacity in an emergency department.

PURPOSE: The purpose of this paper is to show how elements from queueing theory can be used to obtain objective measures of effective capacity in the triage function at Skaraborg Hospital in Sweden without direct observation of the function itself. DESIGN/METHODOLOGY/APPROACH: Approximately 30,000 patients arrived to the emergency department at Skaraborg Hospital in Sweden during 2011. The exact time of arrival and the exact time of triage were recorded for each patient on an individual level. Basic queueing theory uses arrival rates and system capacity measures to derive average queueing times. The authors use the theoretical relation between these three measures to derive system capacity measures based on observed arrival rates and observed average queueing times. FINDINGS: The effective capacity in the triage process is not a linear function of the number of nurses. However, the management of capacity seems well adapted to the actual demand, even though service levels vary substantially during the day and night. ORIGINALITY/VALUE: This paper uses elements from queueing theory in an innovative way to measure the effective capacity of a service process without direct observation, thereby also avoiding the potential risk of the Hawthorne effect.

Predicting Risk of Motor Vehicle Collisions in Patients with Glaucoma: A Longitudinal Study.

PURPOSE: To evaluate the ability of longitudinal Useful Field of View (UFOV) and simulated driving measurements to predict future occurrence of motor vehicle collision (MVC) in drivers with glaucoma. DESIGN: Prospective observational cohort study. PARTICIPANTS: 117 drivers with glaucoma followed for an average of 2.1 ± 0.5 years. METHODS: All subjects had standard automated perimetry (SAP), UFOV, driving simulator, and cognitive assessment obtained at baseline and every 6 months during follow-up. The driving simulator evaluated reaction times to high and low contrast peripheral divided attention stimuli presented while negotiating a winding country road, with central driving task performance assessed as "curve coherence". Drivers with MVC during follow-up were identified from Department of Motor Vehicle records. MAIN OUTCOME MEASURES: Survival models were used to evaluate the ability of driving simulator and UFOV to predict MVC over time, adjusting for potential confounding factors. RESULTS: Mean age at baseline was 64.5 ± 12.6 years. 11 of 117 (9.4%) drivers had a MVC during follow-up. In the multivariable models, low contrast reaction time was significantly predictive of MVC, with a hazard ratio (HR) of 2.19 per 1 SD slower reaction time (95% CI, 1.30 to 3.69; P = 0.003). UFOV divided attention was also significantly predictive of MVC with a HR of 1.98 per 1 SD worse (95% CI, 1.10 to 3.57; P = 0.022). Global SAP visual field indices in the better or worse eye were not predictive of MVC. The longitudinal model including driving simulator performance was a better predictor of MVC compared to UFOV (R2 = 0.41 vs R2 = 0.18). CONCLUSIONS: Longitudinal divided attention metrics on the UFOV test and during simulated driving were significantly predictive of risk of MVC in glaucoma patients. These findings may help improve the understanding of factors associated with driving impairment related to glaucoma.

A Portable Platform for Evaluation of Visual Performance in Glaucoma Patients.

PURPOSE: To propose a new tablet-enabled test for evaluation of visual performance in glaucoma, the PERformance CEntered Portable Test (PERCEPT), and to evaluate its ability to predict history of falls and motor vehicle crashes. DESIGN: Cross-sectional study. METHODS: The study involved 71 patients with glaucomatous visual field defects on standard automated perimetry (SAP) and 59 control subjects. The PERCEPT was based on the concept of increasing visual task difficulty to improve detection of central visual field losses in glaucoma patients. Subjects had to perform a foveal 8-alternative-forced-choice orientation discrimination task, while detecting a simultaneously presented peripheral stimulus within a limited presentation time. Subjects also underwent testing with the Useful Field of View (UFOV) divided attention test. The ability to predict history of motor vehicle crashes and falls was investigated by odds ratios and incident-rate ratios, respectively. RESULTS: When adjusted for age, only the PERCEPT processing speed parameter showed significantly larger values in glaucoma compared to controls (difference: 243ms; P<0.001). PERCEPT results had a stronger association with history of motor vehicle crashes and falls than UFOV. Each 1 standard deviation increase in PERCEPT processing speed was associated with an odds ratio of 2.69 (P = 0.003) for predicting history of motor vehicle crashes and with an incident-rate ratio of 1.95 (P = 0.003) for predicting history of falls. CONCLUSION: A portable platform for testing visual function was able to detect functional deficits in glaucoma, and its results were significantly associated with history of involvement in motor vehicle crashes and history of falls.

A first-in-human study of AMG 208, an oral MET inhibitor, in adult patients with advanced solid tumors.

BACKGROUND: This first-in-human study evaluated AMG 208, a small-molecule MET inhibitor, in patients with advanced solid tumors. METHODS: Three to nine patients were enrolled into one of seven AMG 208 dose cohorts (25, 50, 100, 150, 200, 300, and 400 mg). Patients received AMG 208 orally on days 1 and days 4-28 once daily. The primary objectives were to evaluate the safety, tolerability, pharmacokinetics, and maximum tolerated dose (MTD) of AMG 208. RESULTS: Fifty-four patients were enrolled. Six dose-limiting toxicities were observed: grade 3 increased aspartate aminotransferase (200 mg), grade 3 thrombocytopenia (200 mg), grade 4 acute myocardial infarction (300 mg), grade 3 prolonged QT (300 mg), and two cases of grade 3 hypertension (400 mg). The MTD was not reached. The most frequent grade ≥3 treatment-related adverse event was anemia (n = 3) followed by hypertension, prolonged QT, and thrombocytopenia (two patients each). AMG 208 exposure increased linearly with dose; mean plasma half-life estimates were 21.4-68.7 hours. One complete response (prostate cancer) and three partial responses (two in prostate cancer, one in kidney cancer) were observed. CONCLUSIONS: In this study, AMG 208 had manageable toxicities and showed evidence of antitumor activity, particularly in prostate cancer.

Relationship Between Motor Vehicle Collisions and Results of Perimetry, Useful Field of View, and Driving Simulation in Drivers With Glaucoma.

PURPOSE: To examine the relationship between Motor Vehicle Collisions (MVCs) in drivers with glaucoma and standard automated perimetry (SAP), Useful Field of View (UFOV), and driving simulator assessment of divided attention. METHODS: A cross-sectional study of 153 drivers from the Diagnostic Innovations in Glaucoma Study. All subjects had SAP and divided attention was assessed using UFOV and driving simulation using low-, medium-, and high-contrast peripheral stimuli presented during curve negotiation and car following tasks. Self-reported history of MVCs and average mileage driven were recorded. RESULTS: Eighteen of 153 subjects (11.8%) reported a MVC. There was no difference in visual acuity but the MVC group was older, drove fewer miles, and had worse binocular SAP sensitivity, contrast sensitivity, and ability to divide attention (UFOV and driving simulation). Low contrast driving simulator tasks were the best discriminators of MVC (AUC 0.80 for curve negotiation versus 0.69 for binocular SAP and 0.59 for UFOV). Adjusting for confounding factors, longer reaction times to driving simulator divided attention tasks provided additional value compared with SAP and UFOV, with a 1 standard deviation (SD) increase in reaction time (approximately 0.75 s) associated with almost two-fold increased odds of MVC. CONCLUSIONS: Reaction times to low contrast divided attention tasks during driving simulation were significantly associated with history of MVC, performing better than conventional perimetric tests and UFOV. TRANSLATIONAL RELEVANCE: The association between conventional tests of visual function and MVCs in drivers with glaucoma is weak, however, tests of divided attention, particularly using driving simulation, may improve risk assessment.

Association between progressive retinal nerve fiber layer loss and longitudinal change in quality of life in glaucoma.

IMPORTANCE: Evaluation of structural optic nerve damage is a fundamental part of diagnosis and management of glaucoma. However, the relationship between structural measurements and disability associated with the disease is not well characterized. Quantification of this relationship may help validate structural measurements as markers directly relevant to quality of life. OBJECTIVE: To evaluate the relationship between rates of retinal nerve fiber layer (RNFL) loss and longitudinal changes in quality of life in glaucoma. DESIGN, SETTING, AND PARTICIPANTS: Observational cohort study including 260 eyes of 130 patients with glaucoma followed up for a mean (SD) of 3.5 (0.7) years. All patients had repeatable visual field defects on standard automated perimetry (SAP) at baseline. The 25-item National Eye Institute Visual Function Questionnaire (NEI VFQ-25) was performed annually, and spectral-domain optical coherence tomography and SAP were performed at 6-month intervals. A joint model was used to investigate the association between change in NEI VFQ-25 Rasch-calibrated scores and change in RNFL thickness, adjusting for confounding socioeconomic and clinical variables. MAIN OUTCOMES AND MEASURES: Association between change in binocular RNFL thickness (RNFL thickness in the better eye at each point) and change in NEI VFQ-25 scores. RESULTS: Progressive binocular RNFL thickness loss was associated with worsening of NEI VFQ-25 scores over time. In a multivariable model adjusting for baseline disease severity and the rate of change in binocular SAP sensitivity, each 1-µm-per-year loss of RNFL thickness was associated with a decrease of 1.3 units (95% CI, 1.02-1.56) per year in NEI VFQ-25 scores (P < .001). After adjusting for the contribution from SAP, 26% (95% CI, 12%-39%) of the variability of change in NEI VFQ-25 scores was associated uniquely with change in binocular RNFL thickness. The P value remained less than .001 after adjusting for potential confounding factors. CONCLUSIONS AND RELEVANCE: Progressive binocular RNFL thickness loss was associated with longitudinal loss in quality of life, even after adjustment for progressive visual field loss. These findings suggest that rates of binocular RNFL change are valid markers for the degree of neural loss in glaucoma with significant relationship to glaucoma-associated disability.