Treatment of severe human mpox virus infection with tecovirimat: A case series.

Background: Tecovirimat (TCV, TPOXX®) is an orthopox-specific antiviral drug indicated for the treatment of smallpox. There is also a mechanistic basis for its use in mpox infection. However, its approval was based on animal studies, and its efficacy and side-effect profile in human patients with disease is unknown. Methods: During the 2022 international mpox epidemic, clinicians in Canada accessed TCV from the Public Health Agency of Canada's National Emergency Strategic Stockpile for severe cases of mpox disease. We describe the use of TCV in nine adults with severe mpox virus infection in Montréal, Canada. Results: Five patients were treated for severe and potentially life-threatening head and neck symptoms, while four were treated for genitourinary or anorectal disease. Two-thirds of patients were also treated for suspected bacterial superinfection. All patients recovered (median time to resolution of severe symptoms: nine days) without relapse or hospital readmission. No patients reported adverse events attributable to TCV and no patients stopped their treatment early. Conclusion: Our experience suggests that TCV is well tolerated and may accelerate recovery in severe cases. These preliminary, observational data may also be explained by concomitant treatment for superinfection and are limited by the absence of a control group. Controlled, clinical trials should be conducted to clarify the attributable benefit of TCV in severe mpox infection.

Parametric Design and Prototyping of a Low-Power Planar Biped Robot.

This study proposes a design approach and the development of a low-power planar biped robot named YU-Bibot. The kinematic structure of the robot consists of six independently driven axes, and it weighs approximately 20 kg. Based on biomimetics, the robot dimensions were selected as the average anthropomorphic dimensions of the human lower extremities. The optimization of the mechanical design and actuator selection of the robot was based on the results of parametric simulations. The natural human walking gait was mimicked as a walking pattern in these simulations. As a result of the optimization, a low power-to-weight ratio of 30 W/kg was obtained. The drive system of the robot joints consists of servo-controlled brushless DC motors with reduction gears and additional bevel gears at the knee and ankle joints. The robot features spring-supported knee and ankle joints that counteract the robot's weight and compensate for the backlash present in these joints. The robot is constrained to move only in the sagittal plane by using a lateral support structure. The robot's feet are equipped with low-cost, force-sensitive resistor (FSR)-type sensors for monitoring ground contact and zero-moment point (ZMP) criterion. The experimental results indicate that the proposed robot mechanism can follow the posture commands accurately and demonstrate locomotion at moderate stability. The proposed parametric natural gait simulation-based design approach and the resulting biped robot design with a low power/weight ratio are the main contributions of this study.

Comparative effectiveness of amphotericin B, azoles and echinocandins in the treatment of candidemia and invasive candidiasis: A systematic review and network meta-analysis.

BACKGROUND + OBJECTIVES: The echinocandins, amphotericin B preparations, voriconazole and fluconazole are approved for the treatment of invasive candidiasis, though it remains unclear which agent is most effective. In order to answer this question, we performed a systematic review and network meta-analysis of the randomised controlled trials (RCTs) which evaluated these agents in comparison. METHODS: Four electronic databases were searched from database inception to 8 October 2020. RCTs comparing triazoles, echinocandins or amphotericin B for the treatment of invasive candidiasis or candidemia were included. Random effect Bayesian network meta-analysis methods were used to compare treatment outcomes. RESULTS: Thirteen RCTs met inclusion criteria. Of the 3528 patients included from these trials, 1531 were randomised to receive an echinocandin, 944 to amphotericin B and 1053 to a triazole. For all forms of invasive candidiasis, echinocandins were associated with the highest rate of treatment success when compared to amphotericin B (OR 1.41, 95% CI 1.04-1.92) and the triazoles (OR 1.82, 95% CI 1.35-2.51). Rank probability analysis favoured echinocandins as the most effective choice 98% of the time. Overall survival did not significantly differ between groups. CONCLUSIONS: Among patients with invasive candidiasis, echinocandins had the best clinical outcomes and should remain the first-line agents in the treatment of invasive candidiasis.

Handheld infrared thermometer to evaluate cellulitis: the HI-TEC study.

OBJECTIVES: Differentiating cellulitis from pseudocellulitis is challenging, and misdiagnosis leads to unnecessary antimicrobial use and increased healthcare expenditure. Clinical diagnosis remains the criterion standard and may involve expert consultation. Our objective was to evaluate the usefulness of a handheld infrared thermometer to improve diagnostic certainty in cases of suspected cellulitis. METHODS: We conducted a cross-sectional study from August 2018 to January 2020 at a tertiary-care hospital in Montreal, Canada. We enrolled adult patients with suspected limb cellulitis. Using the infrared thermometer, we compared the average temperature of the affected area with that of the contralateral limb, and we used Youden's method to determine the optimal temperature difference which best differentiated cellulitis from pseudocellulitis as determined by an independent and blinded infectious diseases specialist. We used bootstrapping to estimate 95% confidence intervals for the sensitivity, specificity, and area under the receiver operating curve. RESULTS: Of 65 patients screened for enrolment, 52 patients were recruited (median age: 64 years, IQR 52-76); 39 of these were diagnosed with cellulitis and 13 were not. The mean temperature difference between affected and unaffected limbs was 2.6°C (95%CI 2.1-3.1°C) for patients with cellulitis and 0.4°C (95%CI -1.2°C to 2.1°C) for patients without (p < 0.001). An average temperature difference between limbs of 0.8°C or more was 95% sensitive (95%CI 74-100%) and 69% specific (95%CI 44-95%) for the diagnosis of cellulitis (c-statistic 0.82). CONCLUSIONS: In this proof-of-concept single-centre study, a handheld infrared thermometer was a useful aid to differentiate cellulitis from pseudocellulitis.

Acute Cardiac Injury in Coronavirus Disease 2019 and Other Viral Infections-A Systematic Review and Meta-Analysis.

OBJECTIVES: Severe acute respiratory syndrome-related coronavirus-2 binds and inhibits angiotensin-converting enzyme-2. The frequency of acute cardiac injury in patients with coronavirus disease 2019 is unknown. The objective was to compare the rates of cardiac injury by angiotensin-converting enzyme-2-binding viruses from viruses that do not bind to angiotensin-converting enzyme-2. DATA SOURCES: We performed a systematic review of coronavirus disease 2019 literature on PubMed and EMBASE. STUDY SELECTION: We included studies with ten or more hospitalized adults with confirmed coronavirus disease 2019 or other viral pathogens that described the occurrence of acute cardiac injury. This was defined by the original publication authors or by: 1) myocardial ischemia, 2) new cardiac arrhythmia on echocardiogram, or 3) new or worsening heart failure on echocardiogram. DATA EXTRACTION: We compared the rates of cardiac injury among patients with respiratory infections with viruses that down-regulate angiotensin-converting enzyme-2, including H1N1, H5N1, H7N9, and severe acute respiratory syndrome-related coronavirus-1, to those with respiratory infections from other influenza viruses that do not bind angiotensin-converting enzyme-2, including Influenza H3N2 and influenza B. DATA SYNTHESIS: Of 57 studies including 34,072 patients, acute cardiac injury occurred in 50% (95% CI, 44-57%) of critically ill patients with coronavirus disease 2019. The overall risk of acute cardiac injury was 21% (95% CI, 18-26%) among hospitalized patients with coronavirus disease 2019. In comparison, 37% (95% CI, 26-49%) of critically ill patients with other respiratory viruses that bind angiotensin-converting enzyme-2 (p = 0.061) and 12% (95% CI, 7-22%) of critically ill patients with other respiratory viruses that do not bind angiotensin-converting enzyme-2 (p < 0.001) experienced a cardiac injury. CONCLUSIONS: Acute cardiac injury may be associated with whether the virus binds angiotensin-converting enzyme-2. Acute cardiac injury occurs in half of critically ill coronavirus disease 2019 patients, but only 12% of patients infected by viruses that do not bind to angiotensin-converting enzyme-2.

Thrombotic Microangiopathy in a Pregnant Woman With Kidney Transplantation: A Case Report.

BACKGROUND: The differential diagnosis of thrombotic microangiopathy (TMA) in pregnancy includes common conditions, such as preeclampsia. In women with kidney transplantation, additional causes of TMA must be considered. CASE: A 22-year-old primigravid woman with a transplanted kidney presented with fetal growth restriction, hypertension, acute kidney injury, and hemolysis at 28 weeks gestation. While her clinical presentation was initially consistent with preeclampsia, hemolysis persisted beyond 1 week postpartum. Diagnoses of TMA associated with tacrolimus and antibody-mediated rejection were considered. An elevated tacrolimus level likely contributed to her TMA and a decrease in dosage improved her clinical picture and laboratory markers. CONCLUSION: We report the case of a pregnant kidney transplant recipient with TMA. A multidisciplinary approach is required to optimize the maternal health outcomes in this complex population.

Corrigendum to "Evaluating the Hemodynamical Response of a Cardiovascular System under Support of a Continuous Flow Left Ventricular Assist Device via Numerical Modeling and Simulations".

[This corrects the article DOI: 10.1155/2013/986430.].

Perceptions and intentions toward medical assistance in dying among Canadian medical students.

BACKGROUND: Medical assistance in dying (MAID) was legalized in Canada in 2016. As of July 2017, approximately 2149 patients have accessed MAID. There remains no national-level data on the perspectives of future physicians about MAID or its changing legal status. We provide evidence from a national survey of Canadian medical students about their opinions, intentions, and concerns about MAID. METHODS: From October 2016 to July 2017, we distributed an anonymous online survey to all students at 15 of Canada's 17 medical schools. The survey collected data on respondent socio-demographic characteristics, features of their medical education, intentions for medical practice, and perspectives on MAID. We analyzed responses using univariate descriptive and stepwise multivariate logistic regression. RESULTS: In 1210 completed surveys, 71% of respondents reported being willing to provide MAID under a legal framework that permits it. Non-religious respondents reported greater willingness to participate in MAID than respondents of any religious affiliation (p < 0.001). Frequency of religious attendance was inversely associated with willingness to provide MAID (p < 0.001). Medical students born in Québec were more willing to provide MAID than respondents from other provinces (OR 2.21; p < 0.001). Age, sex, socioeconomic status, year of medical study, previous academic major, and rural/urban city of birth were not associated with willingness to provide MAID. CONCLUSION: As the current class of medical students becomes the first cohort of new physicians to enter Canada's changing medical and legal landscape around MAID, our findings inform the public debate by examining attributes associated with support or opposition to the practice.

Predictive factors of Clostridioides difficile infection in hospitalized patients with new diarrhea: A retrospective cohort study.

INTRODUCTION AND OBJECTIVE: Diagnostic testing for Clostridioides difficile infection (CDI) by nucleic acid amplification test (NAAT) cannot distinguish between colonization and infection. A positive NAAT may therefore represent a false positive for infection, since diarrhea due to various aetiologies may occur in hospitalized patients. Our objective was to help answer the question: "does this medical inpatient with diarrhea have CDI?" DESIGN: We conducted a retrospective cohort study (n = 248) on the Clinical Teaching Units of the Royal Victoria Hospital (Montréal, Canada). Patients were included if they had a NAAT between January 2014 and September 2015 and their admission diagnosis was not CDI. CDI cases and non-CDI cases were compared, and independent predictors of CDI were determined by logistic regression. RESULTS: Several factors were independently associated with CDI, including: hemodialysis (OR: 13.5, 95% CI: 2.85-63.8), atrial fibrillation (OR: 3.70, 95% CI: 1.52-9.01), whether the patient received empiric treatment (OR: 3.01, 95% CI: 1.04-8.68), systemic antibiotic therapy prior to testing (OR: 4.23, 95% CI: 1.71-10.5), previous positive NAAT (OR: 3.70, 95% CI: 1.41-9.72), and a leukocyte count of 11x109/L or higher (OR: 3.43, 95% CI: 1.42-8.26). The area under the curve was 0.80. CONCLUSION: For patients presenting with hospital-onset diarrhea, various parameters can help differentiate between CDI and other causes. A clinical prediction calculator derived from our cohort (http://individual.utoronto.ca/leet/cdiff.html) might assist clinicians in estimating the risk of CDI for inpatients; those with low pre-test probability may not require immediate testing, treatment, nor prolonged isolation.

Hepatitis B Virus and Hepatitis D Virus Recurrence in Patients Undergoing Liver Transplantation for Hepatitis B Virus and Hepatitis B Virus Plus Hepatitis D Virus.

BACKGROUND: In this study, we retrospectively analyzed the recurrence of hepatitis B virus (HBV) and hepatitis D virus (HDV) infection after liver transplantation for HBV and HBV+HDV co-infection. METHODS: Data from patients infected with HBV and HBV+HDV who underwent liver transplantation between March 2003 and June 2013 at the Liver Transplantation Institute of Inonu University were analyzed retrospectively. A total of 255 patients were included in the study. Group 1 (n = 127) comprised patients who underwent liver transplantation because of HBV, and group 2 (n = 128) comprised patients who underwent liver transplantation because of HBV+HDV. A positive HDV antibody serologic test result was taken to indicate liver disease caused by HBV+HDV. RESULTS: Thirteen of 255 were positive for the HBs Ag (5.1%). Nine (7.1%) and 4 (3.1%) patients were positive for the HBs Ag in groups 1 and 2, respectively (7.1%); the difference was not significant (P = .150). No HDV recurrence was detected in either group. The average time to HBs Ag seroconversion in 13 patients was 7.8 months after surgery (6.34 months in group 1 and 11.1 months in group 2). CONCLUSIONS: In our study, recurrence rate of HBV after liver transplantation is not statistically different than the recurrence rate of HBV+HDV co-infection. A low recurrence rate was achieved by the prophylaxis protocol in use at our center. There is no standard protocol for prevention of HBV and HDV recurrence; therefore, we need new studies.

Evaluating the hemodynamical response of a cardiovascular system under support of a continuous flow left ventricular assist device via numerical modeling and simulations.

Dilated cardiomyopathy is the most common type of the heart failure which can be characterized by impaired ventricular contractility. Mechanical circulatory support devices were introduced into practice for the heart failure patients to bridge the time between the decision to transplant and the actual transplantation which is not sufficient due to the state of donor organ supply. In this study, the hemodynamic response of a cardiovascular system that includes a dilated cardiomyopathic heart under support of a newly developed continuous flow left ventricular assist device--Heart Turcica Axial--was evaluated employing computer simulations. For the evaluation, a numerical model which describes the pressure-flow rate relations of Heart Turcica Axial, a cardiovascular system model describing the healthy and pathological hemodynamics, and a baroreflex model regulating the heart rate were used. Heart Turcica Axial was operated between 8000 rpm and 11,000 rpm speeds with 1000 rpm increments for assessing the pump performance and response of the cardiovascular system. The results also give an insight about the range of the possible operating speeds of Heart Turcica Axial in a clinical application. Based on the findings, operating speed of Heart Turcica Axial should be between 10,000 rpm and 11,000 rpm.