Safety of MRI in patients with retained cardiac leads.

PURPOSE: To evaluate the safety of MRI in patients with fragmented retained leads (FRLs) through numerical simulation and phantom experiments. METHODS: Electromagnetic and thermal simulations were performed to determine the worst-case RF heating of 10 patient-derived FRL models during MRI at 1.5 T and 3 T and at imaging landmarks corresponding to head, chest, and abdomen. RF heating measurements were performed in phantoms implanted with reconstructed FRL models that produced highest heating in numerical simulations. The potential for unintended tissue stimulation was assessed through a conservative estimation of the electric field induced in the tissue due to gradient-induced voltages developed along the length of FRLs. RESULTS: In simulations under conservative approach, RF exposure at B1+ ≤ 2 µT generated cumulative equivalent minutes (CEM)43 < 40 at all imaging landmarks at both 1.5 T and 3 T, indicating no thermal damage for acquisition times (TAs) < 10 min. In experiments, the maximum temperature rise when FRLs were positioned at the location of maximum electric field exposure was measured to be 2.4°C at 3 T and 2.1°C at 1.5 T. Electric fields induced in the tissue due to gradient-induced voltages remained below the threshold for cardiac tissue stimulation in all cases. CONCLUSIONS: Simulation and experimental results indicate that patients with FRLs can be scanned safely at both 1.5 T and 3 T with most clinical pulse sequences.

Exploration and Development of a Simpler Respiratory Distress Observation Scale (modRDOS-4) as a Dyspnea Screening Tool: A Prospective Bedside Study.

Introduction: End-of-life patients face difficulties in reporting respiratory distress. The Respiratory Distress Observation Scale (RDOS) is a well-known tool; however, field implementation has been challenging from ground feedback. We sought to develop a simpler scale. Setting: Patients referred for palliative consult in a tertiary hospital in Singapore were recruited. Methods: A priori, we identified 18 dyspnea physical signs and documented their presence through bedside observation. Dyspnea severity was self-reported. The cohort was randomly split into training and test sets. Partial least square regression with leave-one-out cross-validation was used to develop a four-point model from the training set. Using the test set, data fit was compared using Akaike and Bayesian Information Criterion. Discrimination was assessed using receiver operating characteristics. Results: Of 122 patients, mean age was 67.9 years (range 23-93, standard deviation 12.9), 71.3% had a primary cancer diagnosis, and 58.1% were chair/bedbound with a Palliative Performance Scale of ≤50. Median reported dyspnea scale was 5 (interquartile range 3-7). Our model (modRDOS-4) consisted of four predictors (grunting, respiratory rate, accessory muscle use, paradoxical breathing). A modRDOS-4 of ≥6 identified moderate-to-severe dyspnea with a sensitivity of 0.78 and specificity of 0.90. Using the test set, with the modRDOS-4, the Akaike Information Criterion (AIC) is 149.8, Bayesian Information Criteria (BIC) is 154.1, and the receiver operating characteristics (ROC) is 0.74. With the original RDOS, the AIC is 145.2, BIC is 149.5, and ROC is 0.76. Conclusion: For a quick assessment of dyspnea, we developed a four-item tool with a pilot web-based nomogram. External validation is needed.

Vertical open-bore MRI scanners generate significantly less radiofrequency heating around implanted leads: A study of deep brain stimulation implants in 1.2T OASIS scanners versus 1.5T horizontal systems.

PURPOSE: Patients with active implants such as deep brain stimulation (DBS) devices are often denied access to MRI due to safety concerns associated with the radiofrequency (RF) heating of their electrodes. The majority of studies on RF heating of conductive implants have been performed in horizontal close-bore MRI scanners. Vertical MRI scanners which have a 90° rotated transmit coil generate fundamentally different electric and magnetic field distributions, yet very little is known about RF heating of implants in this class of scanners. We performed numerical simulations as well as phantom experiments to compare RF heating of DBS implants in a 1.2T vertical scanner (OASIS, Hitachi) compared to a 1.5T horizontal scanner (Aera, Siemens). METHODS: Simulations were performed on 90 lead models created from post-operative CT images of patients with DBS implants. Experiments were performed with wires and commercial DBS devices implanted in an anthropomorphic phantom. RESULTS: We found significant reduction of 0.1 g-averaged specific absorption rate (30-fold, P < 1 × 10-5 ) and RF heating (9-fold, P < .026) in the 1.2T vertical scanner compared to the 1.5T conventional scanner. CONCLUSION: Vertical MRI scanners appear to generate lower RF heating around DBS leads, providing potentially heightened safety or the flexibility to use sequences with higher power levels than on conventional systems.

Sutimlimab in Cold Agglutinin Disease.

BACKGROUND: Cold agglutinin disease is a rare autoimmune hemolytic anemia characterized by hemolysis that is caused by activation of the classic complement pathway. Sutimlimab, a humanized monoclonal antibody, selectively targets the C1s protein, a C1 complex serine protease responsible for activating this pathway. METHODS: We conducted a 26-week multicenter, open-label, single-group study to assess the efficacy and safety of intravenous sutimlimab in patients with cold agglutinin disease and a recent history of transfusion. The composite primary end point was a normalization of the hemoglobin level to 12 g or more per deciliter or an increase in the hemoglobin level of 2 g or more per deciliter from baseline, without red-cell transfusion or medications prohibited by the protocol. RESULTS: A total of 24 patients were enrolled and received at least one dose of sutimlimab; 13 patients (54%) met the criteria for the composite primary end point. The least-squares mean increase in hemoglobin level was 2.6 g per deciliter at the time of treatment assessment (weeks 23, 25, and 26). A mean hemoglobin level of more than 11 g per deciliter was maintained in patients from week 3 through the end of the study period. The mean bilirubin levels normalized by week 3. A total of 17 patients (71%) did not receive a transfusion from week 5 through week 26. Clinically meaningful reductions in fatigue were observed by week 1 and were maintained throughout the study. Activity in the classic complement pathway was rapidly inhibited, as assessed by a functional assay. Increased hemoglobin levels, reduced bilirubin levels, and reduced fatigue coincided with inhibition of the classic complement pathway. At least one adverse event occurred during the treatment period in 22 patients (92%). Seven patients (29%) had at least one serious adverse event, none of which were determined by the investigators to be related to sutimlimab. No meningococcal infections occurred. CONCLUSIONS: In patients with cold agglutinin disease who received sutimlimab, selective upstream inhibition of activity in the classic complement pathway rapidly halted hemolysis, increased hemoglobin levels, and reduced fatigue. (Funded by Sanofi; CARDINAL ClinicalTrials.gov number, NCT03347396.).

RF heating of deep brain stimulation implants during MRI in 1.2 T vertical scanners versus 1.5 T horizontal systems: A simulation study with realistic lead configurations.

Patients with deep brain stimulation (DBS) implants are often denied access to magnetic resonance imaging (MRI) due to safety concerns associated with RF heating of implants. Although MR-conditional DBS devices are available, complying with manufacturer guidelines has proved to be difficult as pulse sequences that optimally visualize DBS target structures tend to have much higher specific absorption rate (SAR) of radiofrequency energy than current guidelines allow. The MR-labeling of DBS devices, as well as the majority of studies on RF heating of conductive implants have been limited to horizontal close-bore MRI scanners. Vertical MRI scanners, originally introduced as open low-field MRI systems, are now available at 1.2 T field strength, capable of high-resolution structural and functional imaging. No literature exists on DBS SAR in this class of scanners which have a 90° rotated transmit coil and thus, generate a fundamentally different electric and magnetic field distributions. Here we present a simulation study of RF heating in a cohort of forty patient-derived DBS lead models during MRI in a commercially available vertical openbore MRI system (1.2 T OASIS, Hitachi) and a standard horizontal 1.5 T birdcage coil. Simulations were performed at two major imaging landmarks representing head and chest imaging. We calculated the maximum of 0.1g-averaged SAR (0.1g-SARMax) around DBS lead tips when a B1+ = 4 µT was generated on an axial plane passing through patients body. For head landmark, 0.1g-SARMax reached 220±188 W/kg in the 1.5 T birdcage coil, but only 14±11 W/kg in the OASIS coil. For chest landmark, 0.1g-SARMax was 24±17 W/kg in the 1.5 T birdcage coil and 3±2 W/kg in the OASIS coil. A paired two-tail t-test revealed a significant reduction in SAR with a large effect-size during head MRI (p < 1.5×10-8, Cohen's d = 1.5) as well as chest MRI (p < 6.5×10-10, Cohen's d = 1.7) in 1.2 T Hitachi OASIS coil compared to a standard 1.5 T birdcage transmitter. Our findings suggest that open-bore vertical scanners may offer an untapped opportunity for MRI of patients with DBS implants.

A phase 2 study of the bivalent VLP norovirus vaccine candidate in older adults; impact of MPL adjuvant or a second dose.

INTRODUCTION: Acute norovirus gastroenteritis causes significant morbidity and in uncommon cases fatality in older adults. We investigated the safety and immunogenicity of bivalent virus-like particle (VLP) vaccine candidate formulations with and without monophosphoryl lipid A (adjuvant MPL) in this population. METHODS: In this phase II, double-blind, controlled trial 294 healthy adults, ≥ 60 years of age, were randomized (1:1:1:1) to four groups to receive one or two intramuscular immunizations 28 days apart, with 26 18-49 year-old controls who received one MPL-free dose. One-dose groups received placebo on Day 1. Vaccine formulations contained 15 µg GI.1 and 50 µg GII.4c VLP antigens and 500 µg Al(OH)3, with or without 15 µg MPL. We measured histo-blood group antigen blocking (HBGA) antibodies and ELISA Ig at Days 1, 8, 29, 57, 211 and 393, and avidity indices and cell-mediated immunity (CMI). Solicited local and systemic adverse events (AE) were assessed for 7 days and unsolicited AEs for 28 days after each injection. RESULTS: After one dose HBGA antibodies to both VLP antigens increased with similar kinetics and magnitude in all groups; geometric mean titres (GMTs) persisted above baseline through Day 393. GMTs were similar across age strata (18-49, 60-74, 75-84 and ≥ 85 years of age) and unaffected by a second vaccination or MPL. Total Ig showed similar responses. No clinically relevant differences or changes in avidity or CMI were observed between formulations. Both formulations were well tolerated with no vaccine-related SAEs, the most frequent AEs being mild injection site pain and fatigue. CONCLUSIONS: Adults over 60 years of age displayed no safety concerns and had similar immune responses to the norovirus VLP vaccine candidate as younger adults, unaffected by increasing age, a second dose or inclusion of MPL. This data supports the further development of the MPL-free vaccine candidate for older adults.

Safety and immunogenicity of experimental stand-alone trivalent, inactivated Sabin-strain polio vaccine formulations in healthy infants: A randomized, observer-blind, controlled phase 1/2 trial.

BACKGROUND: To increase the global supply of affordable IPV vaccine, preferably using Sabin viruses to comply with GAPIII requirements, Takeda has assessed three dosages of a stand-alone sIPV. METHODS: In this phase I/II study two cohorts of 40 adults and 60 toddlers, respectively, were initially assessed for safety after receiving high-dosage sIPV compared with placebo (adults) or Salk IPV (toddlers). A cohort of 240 infants was then enrolled and randomized (1:1:1:1) to receive low-, medium- or high-dosage sIPV, or a reference Salk IPV in a three-dose primary schedule at 6, 10 and 14 weeks of age. Parents completed safety diaries for 4 weeks after each dose, and immunogenicity was measured as neutralization antibody titers at baseline and four weeks after vaccination. RESULTS: All vaccinations were generally well-tolerated and sIPV had a comparable safety profile to the control arm in adults or the reference Salk IPV vaccine in toddlers and infants. Infants displayed dosage-dependent immune responses to sIPV when assayed using Sabin strains, which were equivalent to the reference IPV in the high-dosage sIPV group for serotypes 1 and 2, but not for Sabin and Salk serotype 3. Seroconversion rates (SCR) of the low- and medium-dosage groups were significantly lower than the Salk IPV group for both Sabin and Salk serotypes 1 and type 2 (p < 0.05), with no significant differences for Salk or Sabin serotypes 3. Responses to sIPV, particularly to Sabin types 1 and 2, were higher in initially seronegative infants, indicating possible interference by maternally-derived antibodies. CONCLUSIONS: A novel stand-alone Sabin-based IPV vaccine was well tolerated with an acceptable safety profile, but less immunogenic than reference Salk IPV at 6, 10 and 14 weeks of age for Salk serotypes 1 and 2, with apparent interference by maternal antibodies. Additional preclinical assessments will be made before any further clinical development.

Intubation of the patient with a suspected or confirmed COVID-19 infection.

We propose a set of recommendations from our clinical practice for intubation of the patient with a suspected or confirmed COVID-19 infection, with a goal to safely securing the airway while optimizing infection prevention practices to reduce the risk to healthcare personnel.

Perspectives of cardiac rehabilitation staff on strategies used to assess, monitor and review - a descriptive qualitative study.

BACKGROUND: The mechanisms contributing to the success of cardiac rehabilitation (CR) are poorly understood and may include assessment, monitoring and review activities enabled by continuity of care and this is investigated in this study. OBJECTIVES: To identify active assessment components of CR. METHODS: A qualitative study using focus groups and individual interviews. CR staff (n = 39) were recruited via professional association email and network contacts and organised into major themes. RESULTS: CR staff assessment strategies and timely actions undertaken provided a sophisticated post-discharge safety net for patients. Continuity of care enabled detection of adverse health indicators, of which medication issues were prominent. Interventions were timely and personalised and therefore likely to impact outcomes, but seldom documented or reported and thus invisible to audit. CONCLUSION: CR staff assessment and intervention activities provide an unrecognised safety net of activities enabled by continuity of care, potentially contributing to the effectiveness of CR.

Educational Preparation, Roles, and Competencies to Guide Career Development for Cardiac Rehabilitation Nurses.

BACKGROUND: Cardiac rehabilitation is one of the most widely recommended strategies to reduce the burden of cardiovascular disease. The multicomponent nature of cardiac rehabilitation programs requires a multidisciplinary team of healthcare professionals including nurses who are equipped with extensive knowledge and skills. However, there is a lack of a comprehensive, explicit career pathway that contains academic and clinical development to prepare nurses to become cardiac rehabilitation specialists. OBJECTIVE: The aim of this study is to identify the 3 essential components for cardiac rehabilitation professionals: (1) educational preparation, (2) role/responsibility, and (3) competency to inform the framework of career development for cardiac rehabilitation nurses. METHODS: Through scoping review, 4 stages from the methodological framework of scoping review by Arksey and O'Malley (Int J Soc Methodol. 2005;8:19-32) were used. RESULTS: Some attempts have been made in developing frameworks of career development for cardiac rehabilitation professionals with these 3 components through guidelines/standards and core curriculum development worldwide, among which the United States is the only country with a well-established system including guidelines for cardiac rehabilitation/secondary prevention programs, a position statement in terms of competencies, and certification examination for cardiac rehabilitation professionals. Nevertheless, further development and integration of these efforts, specifically for cardiac rehabilitation nurses, are required. CONCLUSIONS: It is vital to raise the awareness of the significant contribution that appropriately educated and trained nurses make in reducing the global burden of cardiovascular disease through cardiac rehabilitation. Therefore, action on establishing a system of comprehensive, clearly defined career development pathway for cardiac rehabilitation nurses worldwide is of immediate priority.

What does the Development of the European Core Curriculum for Cardiovascular Nurses Mean for Australia?

A core curriculum for the continuing professional development of nurses has recently been published by the Council on Cardiovascular Nursing and Allied Professions of the European Society of Cardiology. This core curriculum was envisaged to bridge the educational gap between qualification as a nurse and an advance practice role. In addition, the shared elements and international consensus on core themes creates a strong pathway for nursing career development that is directly relevant to Australia. Education programs for nurses in Australia must meet the mandatory standards of the Australian Nursing and Midwifery Accreditation Council (ANMAC), but without a national core curriculum, there can be considerable variation in the content of such courses. The core curriculum is developed to be adapted locally, allowing the addition of nationally relevant competencies, for example, culturally appropriate care of Aboriginal and Torres Strait Islander individuals. Two existing specialist resources could be utilised to deliver a tailored cardiovascular core curriculum; the Heart Education Assessment and Rehabilitation Toolkit (HEART) online (www.heartonline.org.au) and HeartOne (www.heartone.com.au). Both resources could be further enhanced by incorporating the core curriculum. The release of the European core curriculum should be viewed as a call to action for Australia to develop a core curriculum for cardiovascular nurses.

Hypoxic damage to the periventricular white matter in neonatal brain: role of vascular endothelial growth factor, nitric oxide and excitotoxicity.

The present study examined factors that may be involved in the development of hypoxic periventricular white matter damage in the neonatal brain. Wistar rats (1-day old) were subjected to hypoxia and the periventricular white matter (corpus callosum) was examined for the mRNA and protein expression of hypoxia-inducible factor-1alpha (HIF-1alpha), endothelial, neuronal and inducible nitric oxide synthase (eNOS, nNOS and iNOS), vascular endothelial growth factor (VEGF) and N-methyl-D-aspartate receptor subunit 1 (NMDAR1) between 3 h and 14 days after hypoxic exposure by real-time RT-PCR, western blotting and immunohistochemistry. Up-regulated mRNA and protein expression of HIF-1alpha, VEGF, NMDAR1, eNOS, nNOS and iNOS in corpus callosum was observed in response to hypoxia. NMDAR1 and iNOS expression was found in the activated microglial cells, whereas VEGF was localized to astrocytes. An enzyme immunoassay showed that the VEGF concentration in corpus callosum was significantly higher up to 7 days after hypoxic exposure. NO levels, measured by colorimetric assay, were also significantly higher in hypoxic rats up to 14 days after hypoxic exposure as compared with the controls. A large number of axons undergoing degeneration were observed between 3 h and 7 days after the hypoxic exposure at electron-microscopic level. Our findings point towards the involvement of excitotoxicity, VEGF and NO in periventricular white matter damage in response to hypoxia.