Defect-Induced Adsorption Switching (p- to n- Type) in Conducting Bare Carbon Nanotube Film for the Development of Highly Sensitive and Flexible Chemiresistive-Based Methanol and NO2 Sensor.

Lightweight and flexible gas sensors are essentially required for the fast detection of toxic gases to pass on the early warning to deter accident situations caused by gas leakage. In view of this, we have fabricated a thin paper-like free-standing, flexible, and sensitive carbon nanotube (CNT) aerogel gas sensor. The CNT aerogel film synthesized by the floating catalyst chemical vapor deposition method consists of a tiny network of long CNTs and ∼20% amorphous carbon. The pores and defect density of the CNT aerogel film were tuned by heating at 700 °C to obtain a sensor film, which showed excellent sensitivity for toxic NO2 and methanol gas in the concentration range of 1-100 ppm with a remarkable limit of detection ∼90 ppb. This sensor has consistently responded to toxic gas even after bending and crumpling the film. Moreover, the film heat-treated at 900 °C showed a lower response with opposite sensing characteristics due to switching of the semiconductor nature of the CNT aerogel film to n-type from p-type. The annealing temperature-based adsorption switching can be related to a type of carbon defect in the CNT aerogel film. Therefore, the developed free-standing, highly sensitive, and flexible CNT aerogel sensor paves the way for a reliable, robust, and switchable toxic gas sensor.

Clinical Considerations in the Selection of Preexposure Prophylaxis for HIV Prevention in Canada.

According to the Public Health Agency of Canada, approximately 62,050 people were living with HIV in Canada in 2018, and of those, 13% were undiagnosed. Currently, no single strategy provides complete protection or is universally effective across all demographic groups at risk for HIV. However, HIV preexposure prophylaxis (PrEP) is the newest HIV prevention strategy that shows promise. To date, two products have received an indication for PrEP by Health Canada: emtricitabine/tenofovir disoproxil fumarate (Truvada®; FTC/TDF) and emtricitabine/tenofovir alafenamide (Descovy®; FTC/TAF). Despite the high efficacy of these PrEP intervention methods, access to PrEP in Canada remains low. Identifying and addressing barriers to PrEP access, especially in high-risk groups, are necessary to reduce HIV transmission in Canada. While guidelines published by the Center for Disease Control and Prevention (CDC) include FTC/TAF information, the efficacy of FTC/TAF for PrEP has not yet been considered in Canada's clinical practice guidelines. Thus, the current paper reviews data regarding the use of FTC/TDF and FTC/TAF for PrEP, which may be useful for Canadian healthcare providers when counseling and implementing HIV prevention methods. The authors highlight these data in relation to various at-risk populations and review ongoing clinical trials investigating novel PrEP agents. Overall, FTC/TDF PrEP is effective for many populations, including men who have sex with men, transgender women, heterosexuals with partners living with HIV, and people who use drugs. While there is fewer data reported on the efficacy of FTC/TAF to date, recent clinical trials have demonstrated noninferiority of FTC/TAF in comparison to FTC/TDF. Notably, as studies have shown that FTC/TAF maintains renal function and bone mineral density to a greater extent than FTC/TDF, FTC/TAF may be a safer option for patients experiencing renal and/or bone dysfunction, for those at risk of renal and bone complications, and for those who develop FTC/TDF-related adverse events.

Review of intravitreal VEGF inhibitor toxicity and report of collapsing FSGS with TMA in a patient with age-related macular degeneration.

Intravitreal vascular endothelial growth factor (VEGF) receptor blockade is used for a variety of retinal pathologies. These include age-related macular degeneration (AMD), diabetic macular edema (DME) and central retinal vein obstruction. Reports of absorption of intravitreal agents into systemic circulation have increased in number and confirmation of depletion of VEGF has been confirmed. Increasingly there are studies and case reports showing worsening hypertension, proteinuria, renal dysfunction and glomerular disease. The pathognomonic findings of systemic VEGF blockade, thrombotic microangiopathies (TMAs), are also being increasingly reported. One lesion that occurs in conjunction with TMAs that has been described is collapsing focal segmental glomerulosclerosis (cFSGS). cFSGS has been postulated to occur due to TMA-induced chronic glomerular hypoxia. In this updated review we discuss the mechanistic, pharmacological, epidemiological and clinical evidence of intravitreal VEGF toxicity. We review cases of biopsy-proven toxicity presented by our group and other investigators. We also present the third reported case of cFSGS in the setting of intravitreal VEGF blockade with a chronic TMA component that was crucially found on biopsy. This patient is a 74-year-old nondiabetic male receiving aflibercept for AMD. Of the two prior cases of cFSGS in the setting of VEGF blockade, one had AMD and the other had DME. This case solidifies the finding of cFSGS and its association with chronic TMA as a lesion that may be frequently encountered in patients receiving intravitreal VEGF inhibitors.

Rare complication of ceftriaxone therapy: drug-induced thrombocytopenia (DITP).

A 62-year-old woman with a history of end-stage renal disease on haemodialysis, essential hypertension and type 2 diabetes mellitus was diagnosed with sepsis and placed on 600 mg oral linezolid every 12 hours and 1 g intravenous ceftriaxone every 24 hours. Blood cultures grew Streptococcus dysgalactiae, and she was switched to intravenous ceftriaxone 2 g daily. Platelet counts slowly trended down after starting ceftriaxone reaching 5 K/µL on day 12 of treatment. Ceftriaxone was discontinued and heparin-induced thrombocytopaenia was ruled out. She was switched to vancomycin and her platelet count improved. Given the temporal relationship between changing platelet counts and starting and discontinuing ceftriaxone, a diagnosis of drug-induced thrombocytopaenia was made.

Label-free rapid electrochemical detection of DNA hybridization using ultrasensitive standalone CNT aerogel biosensor.

We report the development of an ultrasensitive label-free DNA biosensor device with fully integrated standalone carbon nanotube (CNT) aerogel electrode. The multi-directional tenuous network of clustered CNT embedding into the CNT aerogel electrode demonstrates linear ohmic and near isotropic electrical properties, thereby providing high sensitivity for nucleic acid detection. Using this device, the target DNA hybridization is detected by a quantifiable change in the electrochemical impedance, with a distinct response to the single-stranded probe alone or double-stranded target-probe complex. The target DNA is specifically detected with limit of detection (LoD) of 1 pM with a turnaround time of less than 20 min, which is unprecedented for a miniaturized CNT aerogel sensor and impedance spectroscopy without an intermediate DNA amplification step. Moreover, this system is able to differentiate between the closely related target sequences by the distinct impedance response rendering it highly specific. To the best of our knowledge, this is the first report showing the use of standalone bare CNT aerogel electrode without any substrate support, coupled with electrochemical impedance spectroscopy, for the detection of DNA hybridization. Altogether, the results show that our system is fast, sensitive and specific for label-free rapid direct DNA detection, promising a novel avenue for bio-sensing.

Repurposing biomedical informaticians for COVID-19.

The COVID-19 pandemic is an unprecedented challenge to the biomedical research community at the intersection of great uncertainty due to the novelty of the virus and extremely high stakes due to the large global death count. The global quarantine shut-downs complicated scientific matters because many laboratories were closed down unless they were actively doing COVID-19 related research, making repurposing of activities difficult for many biomedical researchers. Biomedical informaticians, who have been primarily able to continue their research through remote work and video conferencing, have been able to maintain normal activities. In addition to continuing ongoing studies, there has been great grass roots interest in helping in the fight against COVID-19. In this commentary, we describe several projects that arose from this desire to help, and the lessons that the authors learned along the way. We then offer some insights into how these lessons might be applied to make scientific progress be more efficient in future crisis scenarios.

Ethical issues in using ambient intelligence in health-care settings.

Ambient intelligence is increasingly finding applications in health-care settings, such as helping to ensure clinician and patient safety by monitoring staff compliance with clinical best practices or relieving staff of burdensome documentation tasks. Ambient intelligence involves using contactless sensors and contact-based wearable devices embedded in health-care settings to collect data (eg, imaging data of physical spaces, audio data, or body temperature), coupled with machine learning algorithms to efficiently and effectively interpret these data. Despite the promise of ambient intelligence to improve quality of care, the continuous collection of large amounts of sensor data in health-care settings presents ethical challenges, particularly in terms of privacy, data management, bias and fairness, and informed consent. Navigating these ethical issues is crucial not only for the success of individual uses, but for acceptance of the field as a whole.

Osmotic Nephrosis and Acute Kidney Injury Associated With SGLT2 Inhibitor Use: A Case Report.

We report a case of a patient who developed dialysis-requiring acute kidney injury (AKI) after the use of canagliflozin. A 66-year-old man with type 2 diabetes who was recovering from left knee septic arthritis at a rehabilitation facility was admitted with oliguric AKI 5 days after starting treatment with canagliflozin, an inhibitor of sodium/glucose cotransporter 2 (SGLT2). The patient presented with hematuria, non-nephrotic-range proteinuria, and serum creatinine level of 6.8 (baseline, 1.1-1.3) mg/dL. There was no recent use of radiocontrast agents or exposure to other nephrotoxins. The patient subsequently required hemodialysis. Due to recent antibiotic use (ampicillin-sulbactam), acute interstitial nephritis was considered in the differential diagnosis. Kidney biopsy was performed, which showed the presence of osmotic nephropathy. The patient's kidney function returned to baseline after 2 weeks of hemodialysis. This case provides evidence of an association of osmotic nephropathy with the use of canagliflozin and discusses potential mechanisms. We recommend kidney biopsy for cases of severe AKI associated with SGLT2 inhibitors to better understand the relationship of this complication with the use of this class of medications.

Expanding Telehealth Competencies in Primary Care: A Longitudinal Interdisciplinary Simulation to Train Internal Medicine Residents in Complex Patient Care.

BACKGROUND: Despite increasing use of telehealth, there are limited published curricula training primary care providers in utilizing telehealth to deliver complex interdisciplinary care. OBJECTIVE: To describe and evaluate a telehealth curriculum with a longitudinal objective structured clinical examination (OSCE) to improve internal medicine residents' confidence and skills in coordinating complex interdisciplinary primary care via televisits, electronic consultation, and teleconferencing. METHODS: In 2019, 56 first- and third-year residents participated in a 3-part, 5-week OSCE training them to use telehealth to manage complex primary care. Learners conducted a standardized patient (SP) televisit in session 1, coordinated care via inter-visit e-messaging, and led a simulated interdisciplinary teleconference in session 2. Surveys measured confidence before session 1 (pre), post-session 1 (post-1), and post-session 2 (post-2). SP televisit checklists and investigators' assessment of e-messages evaluated residents' telehealth skills. RESULTS: Response rates were pre 100%, post-1 95% (53 of 56), and post-2 100%. Post-intervention, more residents were "confident/very confident" in adjusting their camera (33%, 95% CI 20-45 vs 85%, 95% CI 75-95, P < .0001), e-messaging (pre 36%, 95% CI 24-49 vs post-2 80%, 95% CI 70-91, P < .0001), and coordinating interdisciplinary care (pre 35%, 95% CI 22-47 vs post-2 84%, 95% CI 74-94, P < .0001). More residents were "likely/very likely" to use telemedicine in the future (pre 56%, 95% CI 43-69, vs post-2 79%, 95% CI 68-89, P = .001). CONCLUSIONS: A longitudinal, interdisciplinary telehealth simulation is feasible and can improve residents' confidence in using telemedicine to provide complex patient care.

Beyond duty hours: leveraging large-scale paging data to monitor resident workload.

Monitoring and managing resident workload is a cornerstone of policy in graduate medical education, and the duty hours metric is the backbone of current regulations. While the duty hours metric measures hours worked, it does not capture differences in intensity of work completed during those hours, which may independently contribute to fatigue and burnout. Few such metrics exist. Digital data streams generated during the usual course of hospital operations can serve as a novel source of insight into workload intensity by providing high-resolution, minute-by-minute data at the individual level; however, study and use of these data streams for workload monitoring has been limited to date. Paging data is one such data stream. In this work, we analyze over 500,000 pages-two full years of pages in an academic internal medicine residency program-to characterize paging patterns among housestaff. We demonstrate technical feasibility, validity, and utility of paging burden as a metric to provide insight into resident workload beyond duty hours alone, and illustrate a general framework for evaluation and incorporation of novel digital data streams into resident workload monitoring.

An Integrated Kidney Care eConsult Practice Model: Results from the iKinect Project.

BACKGROUND: Collaborative management of kidney disease relies on coordinated and effective partnerships between multiple provider teams. Siloed care contributes to limited access between physicians, resulting in delays in the diagnosis and treatment of kidney disease and inappropriate use of healthcare resources. These gaps contribute to dissatisfied and disempowered providers and patients. Digital systems such as eConsult can support collaborative management and address these gaps, thereby streamlining the consultation and referral process between primary care physicians (PCPs) and nephrologists. In this study, we evaluated an established eConsult platform integrated with a central triage process for a network of PCPs and nephrologists. The study aimed to assess the acceptability, feasibility, and impact on access to nephrology when using eConsult integrated into the management of kidney disease between PCPs and nephrologists. METHODS: We conducted a 1-year pilot study and used mixed methods to measure the acceptability and feasibility of using eConsult for the management of kidney disease. We compared eConsult and traditional referrals with respect to types of consultation, referrals, and times to response to determine impact on access to kidney care. We conducted semi-structured interviews of PCPs and nephrologists to assess physician experience. RESULTS: From January 8, 2018, to January 11, 2019, 52 PCPs and 23 nephrologists participated in the study, with 250 traditional referrals and 106 eConsults submitted during that period. The median response time for eConsult was 15 (3-64) h, with 25% originating outside the central Toronto region. The median time to first clinic appointment from a traditional referral was 4 months (111 [61-163] days). PCP and nephrologist interviews revealed high user satisfaction, citing efficiency and timely response as key facilitators. CONCLUSION: The eConsult platform was acceptable, feasible, and facilitated access to nephrology care compared to traditional referrals. Physicians report improvements in physician care delivery, nephrology care gaps, patient experience, and healthcare utilization.

Twelve tips for designing curricula that support the development of adaptive expertise.

An essential component of expertise is a clinician's ability to adapt to uncertain, complex, or novel situations while maintaining their competence in routine situations. Adaptive expertise provides a framework for understanding and developing experts who have the skills to effectively balance and support these dimensions of work using both procedural and conceptual knowledge. It is important for educators to understand that often the training which fosters adaptive expertise does not require new tools or approaches, but rather a reconceptualization of training using many of the same instruction and assessment formats already available. The twelve tips discussed in this paper showcase ways in which education can be transformed to support the development of adaptive expertise including the significance of instruction that combines various forms for knowledge, the value of productive struggle, and shifting the design of assessments to support learning and performance beyond retention and direct application.

Vancomycin-Associated Acute Kidney Injury with a Steep Rise in Serum Creatinine.

BACKGROUND: Vancomycin-associated (VA) acute kidney injury (AKI) is being increasingly recognized. A distinct pattern of rapid rise in serum creatinine (sCr) during VA-AKI has occasionally been observed. However, such scenarios remain underreported. METHODS: We conducted an online survey at the American Society of Nephrology Communities forum and reviewed publications of VA-AKI via PubMed or Google searching for cases of precipitous AKI (those with rise in sCr ≥1.5 mg/dL/day) attributable to vancomycin. RESULTS: We identified 12 original cases compiled from 6 different hospitals and 4 published cases (n = 16; 38% women, age 43.5 ± 16 years, weight 108 ± 23 kg, body mass index 35 ± 7 kg/m2) of precipitous AKI observed shortly after large cumulative doses of VA (8.8 ± 5 g). The median steepest 24-h rise in sCr was 2.6 mg/dL (range 1.5-3.5 mg/dL) and the slope of the initial 48-h sCr rise was greater than that of a control AKI (non-VA, n = 48) group (2.03 ± 0.1 vs. 0.62 ± 0.0 mg/dL/day; p < 0.0001). The steep rise in sCr in the VA-AKI was not accompanied by anuria. Overt rhabdomyolysis was absent in all cases. Further, in 3 precipitous VA-AKI cases, simultaneous serum cystatin C values did not rise precipitously, suggesting that the reductions in glomerular filtration rate were overestimated by the sCr increase. CONCLUSIONS: VA-AKI can manifest with a precipitous rise in sCr shortly after a high cumulative dose of vancomycin. True toxic tubular injury overrepresented by the sCr rise is postulated.

Urinary, Plasma, and Serum Biomarkers' Utility for Predicting Acute Kidney Injury Associated With Cardiac Surgery in Adults: A Meta-analysis.

BACKGROUND: Early accurate detection of acute kidney injury (AKI) occurring after cardiac surgery may improve morbidity and mortality. Although several novel biomarkers have been developed for the early detection of AKI, their clinical utility in the critical intraoperative and immediate postoperative period remains unclear. STUDY DESIGN: Systematic review and meta-analysis. SETTING & POPULATION: Adult patients having cardiac surgery. SELECTION CRITERIA FOR STUDIES: EMBASE, CINAHL, Cochrane Library, Scopus, and PubMed from January 1990 until January 2015 were systematically searched for cohort studies reporting the utility of novel biomarkers for the early diagnosis of AKI after adult cardiac surgery. Reviewers extracted data for study design, population, timing of biomarker measurement and AKI occurrence, biomarker performance (area under the receiver operating characteristic curve [AUROC]), and risk of bias. INDEX TESTS: Novel urine, plasma, and serum AKI biomarkers, measured intraoperatively and in the early postoperative period (<24 hours). REFERENCE TESTS: AKI was defined according to the RIFLE, AKIN, or 2012 KDIGO criteria. RESULTS: We found 28 studies reporting intraoperative and/or early postoperative measurement of urine (n=23 studies) or plasma or serum (n=12 studies) biomarkers. Only 4 of these studies measured biomarkers intraoperatively. Overall, intraoperative discrimination by the urine biomarkers neutrophil gelatinase-associated lipocalin (NGAL) and kidney injury marker 1 (KIM-1) demonstrated AUROCs<0.70, whereas N-acetyl-ß-d-glucosaminidase (NAG) and cystatin C had AUROCs<0.75. In the immediate 24-hour postoperative period, the urine biomarkers NGAL (16 studies), KIM-1 (6 studies), and liver-type fatty acid binding protein (6 studies) exhibited composite AUROCs of 0.69 to 0.72. The composite AUROCs for postoperative urine cystatin C, NAG, and interleukin 18 were ≤0.70. Similarly, the composite AUROCs for postoperative plasma NGAL (6 studies) and cystatin-C (5 studies) were <0.70. LIMITATIONS: Heterogeneous AKI definitions. CONCLUSIONS: In adults, known urinary, plasma, and serum biomarkers of AKI possess modest discrimination at best when measured within 24 hours of cardiac surgery.