Cardiogenic control of affective behavioural state.

Emotional states influence bodily physiology, as exemplified in the top-down process by which anxiety causes faster beating of the heart1-3. However, whether an increased heart rate might itself induce anxiety or fear responses is unclear3-8. Physiological theories of emotion, proposed over a century ago, have considered that in general, there could be an important and even dominant flow of information from the body to the brain9. Here, to formally test this idea, we developed a noninvasive optogenetic pacemaker for precise, cell-type-specific control of cardiac rhythms of up to 900 beats per minute in freely moving mice, enabled by a wearable micro-LED harness and the systemic viral delivery of a potent pump-like channelrhodopsin. We found that optically evoked tachycardia potently enhanced anxiety-like behaviour, but crucially only in risky contexts, indicating that both central (brain) and peripheral (body) processes may be involved in the development of emotional states. To identify potential mechanisms, we used whole-brain activity screening and electrophysiology to find brain regions that were activated by imposed cardiac rhythms. We identified the posterior insular cortex as a potential mediator of bottom-up cardiac interoceptive processing, and found that optogenetic inhibition of this brain region attenuated the anxiety-like behaviour that was induced by optical cardiac pacing. Together, these findings reveal that cells of both the body and the brain must be considered together to understand the origins of emotional or affective states. More broadly, our results define a generalizable approach for noninvasive, temporally precise functional investigations of joint organism-wide interactions among targeted cells during behaviour.

Back Pain According to Roland-Morris Low Back Pain Scale After Abdominoplasty With Plication: A Prospective Case Series.

INTRODUCTION: Chronic back pain is a physically debilitating condition that affects more than 80% of adults in the United States. A recent case series highlighted how abdominoplasty with plication can offer an alternative surgical approach for treating chronic back pain. These results have been corroborated by a large prospective series. However, this study excluded male and nulliparous subjects, who may also benefit from this surgery. Our group aims to investigate the effect of abdominoplasty on back pain in a more diverse patient population. METHODS: Subjects older than 18 years undergoing abdominoplasty with plication were recruited. An initial survey called the Roland-Morris Disability Questionnaire (RMQ) was administered at the preoperative visit. This questionnaire inquiries about and grades the patient's history of back pain and surgery. Demographic, medical, and social history was also obtained. A follow-up survey and RMQ was then given 6 months after surgery. RESULTS: Thirty subjects were enrolled. Subjects had a mean age of 43.4 ± 14.3 years. Twenty-eight subjects were female and 26 were postpartum. Twenty-one subjects reported initial back pain on the RMQ scale. Of these, 19 reported a decrease in RMQ score after surgery, including male and nulliparous subjects. A significant decrease in mean RMQ score was demonstrated 6 months after surgery (2.94-0.44, P < 0.001). Further subgroup analysis of female subjects demonstrated significantly decreased final RMQ score in parous women, vaginal or cesarean section delivery, and absence of twin gestation. CONCLUSIONS: Abdominoplasty with plication significantly decreases self-reported back pain 6 months after surgery. These results support that abdominoplasty is not purely a cosmetic procedure but can also be applied therapeutically to improve functional symptoms of back pain.

Examining impact forces during posterior spinal fusion to implement in a novel physics-driven virtual reality surgical simulator.

This study aims to understand the impact forces that surgeons apply to the human spine during a posterior spinal fusion procedure towards the development of a novel spine surgical simulator for training medical residents. The foci of this study are impact forces during graft placement and spinal interbody cage insertion. This study examined the lumbar intervertebral discs of two male cadaveric specimens. Impact forces were collected during graft and spinal cage insertion over multiple levels. An impulse hammer and a camera were used to collect impact forces and displacements, respectively. The results demonstrated a logarithmic relationship between impact forces and cumulative displacement during graft placement. This was also observed between cumulative displacement and number of impacts during spinal cage insertion. A linear relationship was observed for the impact forces and number of impacts during graft placement. Results suggest that surgeons rely on the feedback experienced from impact forces during graft insertion to gauge the amount of graft that was placed in a specific area of the disc. Impact forces during cage insertion provide information about any encountered obstacles. When developing surgical simulators, designing the force feedback system should require modelling these behaviors to effectively impart corresponding skills on a trainee.

Identifying Predictors of Extubation on the day of Passing an SBT in Critically ill Adults.

INTRODUCTION: Many patients who pass a spontaneous awakening trial (SAT) and spontaneous breathing trial (SBT) do not undergo extubation that day. We aimed to identify predictors of extubation on the day of passing an SBT and to develop prediction models for extubation among mechanically ventilated patients. METHODS: In a cohort of mechanically ventilated patients who had passed an SBT in a single, academic medical intensive care unit (ICU) from 2018 to 2019, we developed a logistic regression model for identifying predictors of extubation. RESULTS: Of 745 patients in our study, 77% were extubated the day they passed a SBT. Independent predictors of extubation included higher Richmond Agitation Sedation Scale (RASS) (-2 compared to -4: odds ratio (OR) 1.83, 95% confidence interval (CI) 1.56 to 2.14), receipt of sedation on the day prior (OR 2.12, 95% CI 1.63 to 2.74), absence of diagnosis of sepsis or septic shock (OR 0.77, 95% CI 0.59 to 1), absence of neurological illness (OR 0.59, 95% CI 0.37 to 0.96), indication for intubation of altered mental status, seizure, or agitation (OR 1.67, 95% CI 1.05 to 2.65), and absence of hemodynamic instability or cardiac arrest (OR 0.67, 95% CI 0.47 to 0.95). CONCLUSION AND RELEVANCE: Patients on mechanical ventilation were more likely to be extubated on the day they passed an SBT if they had higher RASS scores, received sedation the day prior, or did not have diagnosis of sepsis, neurological illness, or hemodynamic instability. Future research should attempt to identify and address modifiable risk factors for failure to extubate after passing an SBT.

Evaluation of Peripheral Administration of 10% Calcium Chloride in a Retrospective, Single-Center Electronic Health Record Cohort.

BACKGROUND: Calcium chloride is commonly used in emergency departments in the treatment of a variety of emergencies. Historically, administration via central venous catheters has been preferred owing to its high osmolarity and vesicant properties. Although preferred, central access may not always be available in time-sensitive, emergent situations leading to many instances of peripheral administration. The objective of this analysis was to evaluate the charted safety of peripheral venous administration of 10% calcium chloride. METHODS: A single-center retrospective chart review was performed in patients who received 10% calcium chloride in the adult emergency department evaluating for the incidence of infusion-related adverse events. Patients were excluded if they were less than 18 years of age or had a lack of catheter documentation during 10% calcium chloride administration or if the 10% calcium chloride was documented as given through a central venous catheter. RESULTS: A total of 72 administrations were evaluated. Patients were predominantly male (67%), with a median age of 55 years and body mass index of 29.2. The primary outcome demonstrated that 4 infusion-related adverse events occurred (6%) with grade 1 (n = 1) and grade 0 (n = 3) documented incidence of infusion-related adverse events. None of the documented incidence of infusion-related adverse events resulted in permanent tissue injury, and all patients had conservative management. DISCUSSION: This study demonstrated that administration of 10% calcium chloride via peripheral venous catheters may be feasible and seemed to carry a low incidence of documented complications. Further prospective studies are needed to confirm study observations.

Correlation of Gastrointestinal Symptoms at Initial Presentation with Clinical Outcomes in Hospitalized COVID-19 Patients: Results from a Large Health System in the Southern USA.

BACKGROUND: We aimed to understand the association of gastrointestinal (GI) symptoms at initial presentation with clinical outcomes during COVID-19 hospitalization. METHODS: This retrospective, multicenter cohort study included consecutive hospitalized COVID-19 patients from a single, large health system. The presence of GI symptoms was assessed at initial presentation and included one or more of the following: nausea, vomiting, diarrhea and abdominal pain. Patients were divided into three cohorts: Only GI symptoms, GI and non-GI symptoms and only non-GI symptoms. The primary outcome was association of GI symptoms with mortality. Secondary outcomes included prevalence of GI symptoms and survival analysis. RESULTS: A total of 1672 COVID-19 patients were hospitalized (mean age: 63 ± 15.8 years, females: 50.4%) in our system during the study period. 40.7% patients had at least one GI symptom (diarrhea in 28.3%, nausea/vomiting in 23%, and abdominal pain in 8.8% patients), and 2.6% patients had only GI symptoms at initial presentation. Patients presenting with GI symptoms (with or without non-GI symptoms) had a lower mortality rate compared to patients presenting with only non-GI symptoms (20% vs. 26%; p < 0.05). The time from hospitalization to being discharged was less for patients presenting with only GI symptoms (7.4 days vs. > 9 days, p < 0.0014). After adjusting for other factors, the presence of GI symptoms was not associated with mortality (p > 0.05). CONCLUSION: Among a hospitalized COVID-19 positive Southern US population, 41% patients presented with either diarrhea, nausea, vomiting or abdominal pain initially. The presence of GI symptoms has no association with in-hospital all-cause mortality.

Supporting the utilization of community-based primary health care implementation research in Ghana.

Ever since the 1990s, implementation research in Ghana has guided the development of policies and practices that are essential to establishing community-based primary health care. In response to evidence emerging from this research, the Community-based Health Planning and Services (CHPS) policy was promulgated in 1999 to scale-up results. However, during the first decade of CHPS operation, national monitoring showed that its pace of coverage expansion was unacceptably slow. In 2010, the Ghana Health Service launched a 5-year plausibility trial of CHPS reform for testing ways to accelerate scale-up. This initiative, known as the Ghana Essential Health Intervention Program (GEHIP), included a knowledge management component for establishing congruence of knowledge generation and flow with the operational system that GEHIP evidence was intended to reform. Four Upper East Region districts served as trial areas, while seven districts were comparison areas. Interventions tested means of developing the upward flow of information based on perspectives of district managers, sub-district supervisors and community-level workers. GEHIP also endeavoured to improve procedures for the downward flow and utilization of policy guidelines. Field exchanges were convened for providing national, regional and district leaders with opportunities for participatory learning about GEHIP implementation innovations. This systems approach facilitated the process of augmenting the communication of evidence with practical field experience. Scientific rigor associated with the production of evidence was thereby integrated into management decision-making processes in ways that institutionalized learning at all levels. The GEHIP knowledge management system functioned as a prototype for guiding the planning of a national knowledge management strategy. A follow-up project transferred its mechanisms from the Upper East Regional Health Administration to the Policy Planning Monitoring and Evaluation Division of the Ghana Health Service in Accra.

The Role of Early Subspeciality Consultation in the Timing of Hemophagocytic Lymphohistiocytosis Diagnosis and Management.

OBJECTIVE: The aim of this study was to investigate the relation between timing of subspeciality consult and hemophagocytic lymphohistiocytosis (HLH) consideration, immunosuppression initiation, and in-hospital mortality in patients with HLH. METHODS: We conducted a medical records review study of patients 18 years or older with definite or probable HLH at Montefiore Medical Center between 2006 and 2019. Earlier subspeciality consultation (rheumatology, hematology, and infectious disease) was defined as consultation in less than or equal to 18 hours from time of admission. Demographic, clinical characteristics, and outcomes were compared between patients with early and later subspecialty consultation. RESULTS: A total of 28 patients were included. The median age was 40 years, and 61% of patients were male. Infection was identified as a cause of HLH in 13 patients (46%). Fifteen patients (54%) were classified as having an earlier subspeciality consultation with a median time (interquartile range) to HLH consideration of 1.0 day (0.3-4.2 days) compared with 7.9 days (3.1-9.9 days) for the later consultation group (p = 0.002). The median time (interquartile range) to immunosuppression initiation was 4.6 days (1.7-7.8 days) versus 10.9 days (5.1-13.4 days) (p = 0.01), respectively. Five patients (33%) had in-hospital deaths in the early consultation group compared with 7 patients (54%) in later consultation group (p = 0.27). Among the subset of patients who survived to discharge, the 90-day readmission rate was higher in the later consultation group (83% vs 30%, p = 0.12). CONCLUSIONS: In patients with HLH, earlier subspeciality consultation may play a role in earlier HLH consideration and treatment initiation.

Psoriatic Arthritis: The Influence of Co-morbidities on Drug Choice.

Psoriatic arthritis (PsA) is associated with a higher burden of co-morbidities such as obesity, cardiovascular disease, non-alcoholic fatty liver disease, inflammatory eye disease, inflammatory bowel disease, skin cancer and depression compared to the general population. In the last 20 years, the therapeutic options for PsA have increased exponentially with the availability of tumor necrosis factor-alpha (TNF) inhibitors, interleukin (IL)-17 inhibitors, IL-12/23 inhibitors and Janus kinases/signal transducer and activator of transcription proteins (JAK/STAT) inhibitors. The articular and extra-articular manifestations of PsA usually dictate the treatment choice but important consideration must be given to the corresponding co-morbidities while deciding the drug therapy due to associated safety profile, effect on disease activity, etc. This review provides a comprehensive review of common co-morbidities in PsA and how they can influence treatment choices.

Global genome analysis reveals a vast and dynamic anellovirus landscape within the human virome.

Anelloviruses are a ubiquitous component of healthy human viromes and remain highly prevalent after being acquired early in life. The full extent of "anellome" diversity and its evolutionary dynamics remain unexplored. We employed in-depth sequencing of blood-transfusion donor(s)-recipient pairs coupled with public genomic resources for a large-scale assembly of anellovirus genomes and used the data to characterize global and personal anellovirus diversity through time. The breadth of the anellome is much greater than previously appreciated, and individuals harbor unique anellomes and transmit lineages that can persist for several months within a diverse milieu of endemic host lineages. Anellovirus sequence diversity is shaped by extensive recombination at all levels of divergence, hindering traditional phylogenetic analyses. Our findings illuminate the transmission dynamics and vast diversity of anelloviruses and set the foundation for future studies to characterize their biology.

Midfacial Degloving Technique for Free Flap Reconstruction of Nasal and Anterior Skull Base Defects.

SUMMARY: Traditionally, surgical access for extirpation and reconstruction of midfacial tumors requires external incisions that can cause a myriad of complications, especially in irradiated patients. The modern midfacial degloving approach involves hidden, sublabial and intranasal incisions that provide reliable access for free flap reconstruction of nasal and maxillofacial tumors. Seven patients with a history of radiation therapy underwent free flap reconstruction of the midface. Five patients underwent the technique in a delayed manner, and the remaining two underwent reconstruction immediately at the time of resection. Five patients underwent free radial forearm fasciocutaneous free flaps and two underwent reconstruction with anterolateral thigh perforator flaps. Bone and/or rib cartilage grafting was used in all patients. All patients underwent successful free flap reconstruction of the midface without external incisions. The most common complication was postoperative infection requiring oral or intravenous antibiotics. No patients sustained loss of their grafts or hardware in the postoperative period. The midfacial degloving technique provides satisfactory exposure to the nasal cavity, midface, orbits, and skull base for free flap reconstruction, without disrupting the external soft tissue. The authors describe a novel use of the midfacial degloving technique to provide safe and reliable results with improved cosmetic outcome.

Multicenter observational study evaluating the impact of platelet transport bags on product wastage.

BACKGROUND: Platelets are the most commonly discarded blood product in Canada, with the most common cause of in-date product loss being improper storage. Transport containers to maintain temperature and extend acceptable return time may represent a method to reduce wastage. The objective of this study was to evaluate the impact of a validated Platelet Transport Bag (PTB) on platelet wastage. STUDY DESIGN AND METHODS: Thirty-six hospitals with the highest platelet discards were invited to participate in a before-after observational study. Hospitals were instructed to utilize a validated 4-h PTB for clinical situations where immediate transfusion was not planned. Five hospitals audited in-date platelet discards from July 2018 to November 2019 to characterize wastage causes. In-date platelet discard data 12 months before and after the start date for each site were analyzed to determine changes in wastage. RESULTS: Of 36 hospital sites, 16 agreed to participate. Pre- and postdiscards were 277 and 301, respectively, for all sites combined. There were no significant before-after change in wastage rate (+0.05%, p = .51). Fifty discards were included in the detailed audit; the most common reasons were return to the blood bank after more than 60 min outside a PTB (n = 17, 34%) and return in a red cell cooler (n = 10, 20%). CONCLUSION: Implementation of PTB did not improve wastage. Common causes of in-date discards were return after 1 h outside of a PTB and placement in a red cell cooler in error. Further research is required to investigate potential strategies to mitigate in-date platelet wastage.

Rapid Implementation of a Multidisciplinary COVID-19 Cytokine Storm Syndrome Task Force.

OBJECTIVE: Patients with coronavirus disease 2019 (COVID-19) can progress to a state of unregulated inflammation called cytokine storm syndrome (CSS). We describe formation and operation of a COVID-19 multidisciplinary consultation service that was allowed to individualize treatment for critically ill patients with COVID-19 during the pandemic. METHODS: Institutional experts from different subspecialties formed a COVID-19 CSS task force at Montefiore Medical Center, Bronx, NY. They agreed on a set of four clinical and six laboratory parameters that can help early identify COVID-19 CSS. We describe the formation and implementation of the COVID-19 task force. The case series description of the COVID-19 CSS consultation cohort highlights consultation volume, baseline characteristics, clinical and laboratory parameters, and how biologic treatments were allocated to these patients. RESULTS: Between April 4,2020, and May 7,2020, the COVID-19 CSS task force was formed, consisting of adult and pediatric rheumatologists and allergy and immunology physicians. The task force evaluated a total of 288 patients, of whom 197 (68%) were male, the median (interquartile range [IQR]) age was 62 (51-70) years, 122 (42%) were Hispanic, and 88 (31%) were Black or African American. The common presenting symptoms in all referred patients were dyspnea (85%) and diarrhea (80%). Thirty-one patients who received biologic therapy were younger, with a median (IQR) age of 53 (32-63) years, as opposed to 62.5 (52-70) years in the nonbiologic group (P = 0.008). A higher proportion receiving biologics was in the critical care setting (26 [84%] vs 151 [59%]; P = 0.006). CONCLUSION: To the best of our knowledge, this is the first multidisciplinary collaborative effort to provide individualized patient recommendations for evaluation and treatment of patients with COVID-19 who may have CSS. This working model helped to devise an approach that may have identified patients who were most likely to benefit from biologic therapy in the absence of evidence-based guidelines.

Development and Validation of a Mixed Reality Configuration of a Simulator for a Minimally Invasive Spine Surgery Using the Workspace of a Haptic Device and Simulator Users.

Most surgical simulators leverage virtual or bench models to simulate reality. This study proposes and validates a method for workspace configuration of a surgical simulator which utilizes a haptic device for interaction with a virtual model and a bench model to provide additional tactile feedback based on planned surgical manoeuvers. Numerical analyses were completed to determine the workspace and position of a haptic device, relative to the bench model, used in the surgical simulator, and the determined configuration was validated using device limitations and user data from surgical and nonsurgical users. For the validation, surgeons performed an identical surgery on a cadaver prior to using the simulator, and their trajectories were then compared to the determined workspace for the haptic device. The configuration of the simulator was determined appropriate through workspace analysis and the collected user trajectories. Statistical analyses suggest differences in trajectories between the participating surgeons which were not affected by the imposed haptic workspace. This study, therefore, demonstrates a method to optimally position a haptic device with respect to a bench model while meeting the manoeuverability needs of a surgical procedure. The validation method identified workspace position and user trajectory towards ideal configuration of a mixed reality simulator.

Deep brain optogenetics without intracranial surgery.

Achieving temporally precise, noninvasive control over specific neural cell types in the deep brain would advance the study of nervous system function. Here we use the potent channelrhodopsin ChRmine to achieve transcranial photoactivation of defined neural circuits, including midbrain and brainstem structures, at unprecedented depths of up to 7 mm with millisecond precision. Using systemic viral delivery of ChRmine, we demonstrate behavioral modulation without surgery, enabling implant-free deep brain optogenetics.

The pharmacist's role in implementation of the ABCDEF bundle into clinical practice.

PURPOSE: To summarize published data regarding implementation of the ABCDEF bundle, a multicomponent process for avoidance of oversedation and prolonged ventilation in intensive care unit (ICU) patients; discuss pertinent literature to support each bundle element; and discuss the role of the pharmacist in coordinating bundle elements and implementation of the ABCDEF bundle into clinical practice. SUMMARY: Neuromuscular weakness and ICU-acquired weakness are common among critically ill patients and associated with significant cost and societal burdens. Recent literature supporting early liberation from mechanical ventilation and early mobilization has demonstrated improved short- and long-term outcomes. With expanded use of pharmacy services in the ICU setting, pharmacists are well positioned to advocate for best care practices in ICUs. A dedicated, interprofessional team is necessary for the implementation of the ABCDEF bundle in inpatient clinical practice settings. As evidenced by a number of studies, successful implementation of the ABCDEF bundle derives from involvement by motivated and highly trained individuals, timely completion of individual patient care tasks, and effective leadership to ensure proper implementation and ongoing support. Factors commonly identified by clinicians as barriers to bundle implementation in clinical practice include patient instability and safety concerns, lack of knowledge, staff concerns, unclear protocol criteria, and lack of interprofessional team care coordination. This narrative review discusses research on bundle elements and recommendations for application by pharmacists in clinical practice. CONCLUSIONS: Despite the benefits associated with implementation of the ABCDEF bundle, evidence suggests that the recommended interventions may not be routinely used within the ICU. The pharmacist provides the expertise and knowledge for adoption of the bundle into everyday clinical practice.

Development of the Indian scale of the fear of COVID-19.

BACKGROUND: The first human case of COVID-19, the disease caused by the novel coronavirus causing COVID-19, subsequently named SARS-CoV-2 was reported by the officials in Wuhan City, China, in December 2019. In India, on January 31, 2020, the first case of COVID-19 was reported. MATERIALS AND METHODS: The Indian scale of fear related to COVID-19 (ISF-C19) Scale was developed in Hindi and was rated by two raters. Then, it was applied on twenty individuals (ten males and ten females) as a pilot study. The study had been conducted in Eastern India, in the state of Jharkhand. ISF-C19 was completed by 118 participants (females - 75; males - 43), aged 18 years or older from the community, and the subjective well-being was assessed. The psychometric properties of this instrument were investigated. Safety measures (i.e., mask, maintaining distance, gloves, and sanitizers) were taken throughout the data collection period. RESULTS: Findings suggested that this scale has adequate sampling, adequate interitem reliability coefficient, and higher overall scores on the ISF-C19 indicated more severe fear related to COVID-19. CONCLUSION: In light of the current scenario of the emerging cases in India, there is an urgent need to develop a scale related to COVID-19 as there is no published Indian standardized scale before this recent outbreak of pandemic. Considering the current scenario, this scale is useful to assess the fear related to COVID-19.