Management of acute cervical spinal cord injury in the non-specialist intensive care unit: a narrative review of current evidence.

Each year approximately one million people suffer spinal cord injury, which has significant physical, psychosocial and economic impacts on patients and their families. Spinal cord rehabilitation centres are a well-established part of the care pathway for patients with spinal cord injury and facilitate improvements in functional independence and reductions in healthcare costs. Within the UK, however, there are a limited number of spinal cord injury centres, which delays admission. Patients and their families often perceive that they are not receiving specialist care while being treated in non-specialist units. This review aimed to provide clinicians who work in non-specialist spinal injury centres with a summary of contemporary studies relevant to the critical care management of patients with cervical spinal cord injury. We undertook a targeted literature review including guidelines, systematic reviews, meta-analyses, clinical trials and randomised controlled trials published in English between 1 June 2017 and 1 June 2023. Studies involving key clinical management strategies published before this time, but which have not been updated or repeated, were also included. We then summarised the key management themes: acute critical care management approaches (including ventilation strategies, blood pressure management and tracheostomy insertion); respiratory weaning techniques; management of pain and autonomic dysreflexia; and rehabilitation.

Bi-national outbreak of Salmonella Newport infections linked to onions: the United States experience.

From 2016-2019, dry bulb onions were the suspected cause of three multistate outbreaks in the United States. We investigated a large multistate outbreak of Salmonella Newport infections that caused illnesses in both the United States and Canada in 2020. Epidemiologic, laboratory and traceback investigations were conducted to determine the source of the infections, and data were shared among U.S. and Canadian public health officials. We identified 1127 U.S. illnesses from 48 states with illness onset dates ranging from 19 June to 11 September 2020. Sixty-six per cent of ill people reported consuming red onions in the week before illness onset. Thirty-five illness sub-clusters were identified during the investigation and seventy-four per cent of sub-clusters served red onions to customers during the exposure period. Traceback for the source of onions in illness sub-clusters identified a common onion grower in Bakersfield, CA as the source of red onions, and onions were recalled at this time. Although other strains of Salmonella Newport were identified in environmental samples collected at the Bakersfield, CA grower, extensive environmental and product testing did not yield the outbreak strain. This was the third largest U.S. foodborne Salmonella outbreak in the last 30 years. It is the first U.S. multistate outbreak with a confirmed link to dry bulb onions, and it was nearly 10-fold larger than prior outbreaks with a suspected link to onions. This outbreak is notable for its size and scope, as well as the international data sharing that led to implication of red onions as the primary cause of the outbreak. Although an environmental assessment at the grower identified several factors that likely contributed to the outbreak, no main reason was identified. The expedient identification of the outbreak vehicle and response of multiple public health agencies allowed for recall and removal of product from the marketplace, and rapid messaging to both the public and industry on actions to protect consumers; these features contributed to a decrease in cases and expeditious conclusion of the outbreak.

Analysis of EEG Data Using Complex Geometric Structurization.

Electroencephalogram (EEG) is a common tool used to understand brain activities. The data are typically obtained by placing electrodes at the surface of the scalp and recording the oscillations of currents passing through the electrodes. These oscillations can sometimes lead to various interpretations, depending on, for example, the subject's health condition, the experiment carried out, the sensitivity of the tools used, or human manipulations. The data obtained over time can be considered a time series. There is evidence in the literature that epilepsy EEG data may be chaotic. Either way, the Embedding Theory in dynamical systems suggests that time series from a complex system could be used to reconstruct its phase space under proper conditions. In this letter, we propose an analysis of epilepsy EEG time series data based on a novel approach dubbed complex geometric structurization. Complex geometric structurization stems from the construction of strange attractors using Embedding Theory from dynamical systems. The complex geometric structures are themselves obtained using a geometry tool, the α-shapes from shape analysis. Initial analyses show a proof of concept in that these complex structures capture the expected changes brain in lobes under consideration. Further, a deeper analysis suggests that these complex structures can be used as biomarkers for seizure changes.

The effect of handedness on mental rotation of hands: a systematic review and meta-analysis.

Body-specific mental rotation is thought to rely upon internal representations of motor actions. Handedness is a source of distinctly different motor experience that shapes the development of such internal representations. Yet, the influence of handedness upon hand mental rotation has never been systematically evaluated. Five databases were searched for studies evaluating hand left/right judgement tasks in adults. Two independent reviewers performed screening, data extraction, and critical appraisal. Eighty-seven datasets were included, with 72 datasets pooled; all had unclear/high risk of bias. Meta-analyses showed that right-handers were faster, but not more accurate, than left-handers at hand mental rotation. A unique effect of handedness was found on performance facilitation for images corresponding to the dominant hand. Meta-analyses showed that right-handers were quicker at identifying images of right hands than left hands-a dominance advantage not evident in left-handers. Differing hand representations (more lateralised hand dominance in right-handers) likely underpin these findings. Given potential differences between hand preference and motor performance, future research exploring their distinct contributions to mental rotation is warranted.

Point-of-care lung ultrasound in the assessment of suspected COVID-19: a retrospective service evaluation with a severity score.

INTRODUCTION: Point-of-care lung ultrasound (POCUS) has been advocated as a tool to assess the severity of COVID19 and thereby aid risk stratification. METHODS: We conducted a retrospective service evaluation between the 3rd March and the 5th May 2020 to describe and characterise the use of POCUS within an acute care pathway designed specifically for the assessment of suspected or confirmed COVID-19. A novel POCUS severity scale was formulated by assessing pleural and interstitial abnormalities within six anatomical zones (three for each lung). An aggregated score was calculated for each patient and evaluated as a marker of disease severity using standard metrics of discriminatory performance. RESULTS: POCUS was performed in the assessment of 100 patients presenting with suspected COVID-19. POCUS was consistent with COVID-19 infection in 92% (n = 92) of the patients assessed. Severity, as assessed by POCUS, showed good discriminatory performance to predict all-cause inpatient mortality, death or critical care admission, and escalated oxygen requirements (AUC .80, .80, 82). The risk of all-cause mortality in patients with scores in lowest quartile was 2.5% (95%CI 0.12- 12.95) compared with 42.9% (95CI 15.8 - 75.0%) in the highest quartile. POCUS assessed severity correlated with length of stay and duration of supplemental oxygen therapy. CONCLUSION: A simple aggregated score formed by the summating the degree of pleural and interstitial change within six anatomical lung zones showed good discriminatory performance in predicting a range of adverse outcomes in patients with suspected COVID-19.

Mast Cells Exert Anti-Inflammatory Effects in an IL10-/- Model of Spontaneous Colitis.

Mast cells are well established as divergent modulators of inflammation and immunosuppression, but their role in inflammatory bowel disease (IBD) remains to be fully defined. While previous studies have demonstrated a proinflammatory role for mast cells in acute models of chemical colitis, more recent investigations have shown that mast cell deficiency can exacerbate inflammation in spontaneous colitis models, thus suggesting a potential anti-inflammatory role of mast cells in IBD. Here, we tested the hypothesis that in chronic, spontaneous colitis, mast cells are protective. We compared colitis and intestinal barrier function in IL10-/- mice to mast cell deficient/IL10-/- (double knockout (DKO): KitWsh/Wsh × IL10-/-) mice. Compared with IL10-/- mice, DKO mice exhibited more severe colitis as assessed by increased colitis scores, mucosal hypertrophy, intestinal permeability, and colonic cytokine production. PCR array analyses demonstrated enhanced expression of numerous cytokine and chemokine genes and downregulation of anti-inflammatory genes (e.g., Tgfb2, Bmp2, Bmp4, Bmp6, and Bmp7) in the colonic mucosa of DKO mice. Systemic reconstitution of DKO mice with bone marrow-derived mast cells resulted in significant amelioration of IL10-/--mediated colitis and intestinal barrier injury. Together, the results presented here demonstrate that mast cells exert anti-inflammatory properties in an established model of chronic, spontaneous IBD. Given the previously established proinflammatory role of mast cells in acute chemical colitis models, the present findings provide new insight into the divergent roles of mast cells in modulating inflammation during different stages of colitis. Further investigation of the mechanism of the anti-inflammatory role of the mast cells may elucidate novel therapies.

Equipping providers with principles, knowledge and skills to successfully integrate behaviour change counselling into practice: a primary healthcare framework.

OBJECTIVES: There is an urgent need for healthcare providers and healthcare systems to support productive interactions with patients that promote sustained health behaviour change in order to improve patient and population health outcomes. Behaviour change theories and interventions have been developed and evaluated in experimental contexts; however, most healthcare providers have little training, and therefore low confidence in, behaviour change counselling. Particularly important is how to integrate theory and method to support healthcare providers to engage in behaviour change counselling competently. In this article, we describe a general training model developed from theory, evidence, experience and stakeholder engagement. This model will set the stage for future evaluation research on training needed to achieve competency, sustainability of competency, as well as effectiveness/cost-effectiveness of training in supporting behaviour change. DESIGN AND METHODS: A framework to support competency based training in behaviour change counselling is described in this article. This framework is designed to be integrative, sustainable, scalable and capable of being evaluated in follow-up studies. RESULTS AND DISCUSSION: Effective training in behaviour change counselling is critical to meet the current and future healthcare needs of patients living with, or at risk of, chronic diseases. Increasing competency in establishing change-based relationships, assessing and promoting readiness to change, implementing behaviour modification and addressing psychosocial issues will be value added to the healthcare system.

OPTN/SRTR 2015 Annual Data Report: Lung.

In 2015, 2409 active candidates aged 12 years or older were added to the lung transplant waiting list; 2072 transplants were performed, the most of any year. The median waiting time for candidates listed in 2015 was 3.4 months; the shortest waiting time was for diagnosis group D. Despite the highest recorded transplant rate of 157 per 100 waitlist years, waitlist mortality continued a steady decade-long rise to a high of 16.5 deaths per 100 waitlist years. Measures of short- and long-term survival showed no trend toward improved overall survival in the past 5 years, except that 6-month death rates decreased from 9.4% in 2005 to 7.9% in 2014. At 5 years posttransplant, 55.5% of recipients remained alive. In 2015, 23 new child (ages 0-11 years) candidates were added to the list; 17 transplants were performed. Incidence of death was 6.1% at 6 months and 8.2% at 1 year for transplants in 2013-2014. Important policy changes will affect access to transplant. In February 2015, OPTN implemented a comprehensive revision of the lung allocation score to better reflect mortality risk. Broader geographic sharing of donor lungs for pediatric candidates and allowance for selected transplants across blood types for candidates aged younger than 2 years have been approved and are expected to improve pediatric access to transplant. The impact of these changes on lung transplant trends will be observed in the coming years.

OPTN/SRTR 2015 Annual Data Report: Heart.

The number of heart transplant candidates and transplants performed continued to rise each year. In 2015, 2819 heart transplants were performed. In addition, the number of new adult candidates on the waiting list increased 51% since 2004. The number of adult heart transplant survivors continued to increase, and in 2015, 29,172 recipients were living with heart transplants. Patient mortality following transplant has declined. The number of pediatric candidates and transplants performed also increased. New listings for pediatric heart transplants increased from 451 in 2004 to 644 in 2015. The number of pediatric heart transplants performed each year increased from 297 in 2004 to 460 in 2015. Among pediatric patients who underwent transplant in 2014, death occurred in 7.2% at 6 months and 9.6% at 1 year.

Retransplant and Medical Therapy for Cardiac Allograft Vasculopathy: International Society for Heart and Lung Transplantation Registry Analysis.

Cardiac retransplantation for heart transplant recipients with advanced cardiac allograft vasculopathy (CAV) remains controversial. The International Society for Heart and Lung Transplantation Registry was used to examine survival in adult heart recipients with CAV who were retransplanted (ReTx) or managed medically (MM). Recipients transplanted between 1995 and 2010 who developed CAV and were either retransplanted within 2 years of CAV diagnosis (ReTx) or alive at ≥2 years after CAV diagnosis, managed medically (MM), without retransplant, constituted the study groups. Donor, recipient, transplant characteristics and long-term survival were compared. The population included 65 patients in ReTx and 4530 in MM. During a median follow-up of 4 years, there were 24 deaths in ReTx, and 1466 in MM. Survival was comparable at 9 years (55% in ReTx and 51% in MM; p = 0.88). Subgroup comparison suggested survival benefit for retransplant versus MM in patients who developed systolic graft dysfunction. Adjusted predictors for 2-year mortality were diagnosis of CAV in the early era and longer time since CAV diagnosis following primary transplant. Retransplant was not an independent predictor in the model. Challenges associated with retransplantation as well as improved CAV treatment options support the current consensus recommendation limiting retransplant to highly selected patients with CAV.

Immunotoxin Against a Donor MHC Class II Molecule Induces Indefinite Survival of Murine Kidney Allografts.

Rejection of donor organs depends on the trafficking of donor passenger leukocytes to the secondary lymphoid organs of the recipient to elicit an immune response via the direct antigen presentation pathway. Therefore, the depletion of passenger leukocytes may be clinically applicable as a strategy to improve graft survival. Because major histocompatibility complex (MHC) class II(+) cells are most efficient at inducing immune responses, selective depletion of this population from donor grafts may dampen the alloimmune response and prolong graft survival. In a fully MHC mismatched mouse kidney allograft model, we describe the synthesis of an immunotoxin, consisting of the F(ab')2 fragment of a monoclonal antibody against the donor MHC class II molecule I-A(k) conjugated with the plant-derived ribosomal inactivating protein gelonin. This anti-I-A(k) gelonin immunotoxin depletes I-A(k) expressing cells specifically in vitro and in vivo. When given to recipients of kidney allografts, it resulted in indefinite graft survival with normal graft function, presence of Foxp3(+) cells within donor grafts, diminished donor-specific antibody formation, and delayed rejection of subsequent donor-type skin grafts. Strategies aimed at the donor arm of the immune system using agents such as immunotoxins may be a useful adjuvant to existing recipient-orientated immunosuppression.

The OPTN Deceased Donor Potential Study: Implications for Policy and Practice.

The Organ Procurement and Transplantation Network (OPTN) Deceased Donor Potential Study, funded by the Health Resources and Services Administration, characterized the current pool of potential deceased donors and estimated changes through 2020. The goal was to inform policy development and suggest practice changes designed to increase the number of donors and organ transplants. Donor estimates used filtering methodologies applied to datasets from the OPTN, the National Center for Health Statistics, and the Agency for Healthcare Research and Quality and used these estimates with the number of actual donors to estimate the potential donor pool through 2020. Projected growth of the donor pool was 0.5% per year through 2020. Potential donor estimates suggested unrealized donor potential across all demographic groups, with the most significant unrealized potential (70%) in the 50-75-year-old age group and potential Donation after Circulatory Death (DCD) donors. Actual transplants that may be realized from potential donors in these categories are constrained by confounding medical comorbidities not identified in administrative databases and by limiting utilization practices for organs from DCD donors. Policy, regulatory, and practice changes encouraging organ procurement and transplantation of a broader population of potential donors may be required to increase transplant numbers in the United States.

Heart.

As the number of candidates listed for heart transplant continues to rise, it is encouraging that the number of heart transplants also continues to rise steadily each year. Evaluation of waitlist activity demonstrates a growing number of adult candidates removed from the list due to undergoing transplant, but also growing numbers of adult candidates added to the list over the past 3 years. In 2014, 2679 heart transplants were performed, an increase of 28.4% since 2003, and the number of people living with a transplanted heart continued to increase. The number of new pediatric candidates added to the heart transplant waiting list increased to 593 in 2014. The number of pediatric heart transplants performed each year increased from 293 in 2003 to 410 in 2014. Almost 60% of pediatric candidates waiting on December 31, 2014, had been waiting for less than 1 year, compared with 43.0% in 2004. Among pediatric patients who underwent transplant in 2008-2012, overall cumulative incidence of death at 1, 3, and 5 years was 9.2%, 14.7%, and 18.3%, respectively.

Lung.

Lungs are allocated to adult and adolescent transplant candidates (aged ≥ 12 years) on the basis of age, geography, blood type compatibility, and the lung allocation score (LAS), which reflects risk of waitlist mortality and probability of posttransplant survival. In 2014, 2458 active candidates aged 12 years or older, the most of any year, were added to the list; 1949 transplants were performed. Overall median waiting time to transplant for candidates listed in 2014 was 3.7 months. Candidates undergoing lung transplant in 2014 were sicker than ever before with median LAS 44.4. Measures of short-term survival continue to improve; however, long-term survival has plateaued since the implementation of the LAS in 2005; at 5 years posttransplant, 42.4% of recipients had died. In 2014, 30 new active child (ages 0-11) candidates were added to the list; 19 transplants were performed. Incidence of patient death was 7.1% at 6 months and 10.8% at 1 year for transplants in 2013, 29.7% at 3 years for transplants in 2009-2010, and 42.7% at 5 years for transplants in 2007-2008. By age, 5-year patient survival was poorest for recipients aged younger than 1 year.

Serological, genomic and structural analyses of the major mite allergen Der p 23.

BACKGROUND: Der p 23 was recently identified in a European population as a major allergen and potentially a chitin binding protein. OBJECTIVE: This study sought to assess the importance of Der p 23 among other Dermatophagoides allergens in a North American population and to determine the structure for functional characterization. METHODS: IgE binding to Der p 23, Der p 1, Der p 2, Der p 5, Der p 7 and Der p 8 was measured by ELISA. RNA-seq data from D. pteronyssinus were compared as estimates of allergen expression levels. The structure was analysed by X-ray crystallography and NMR. RESULTS: Despite a high prevalence of Der p 23, (75% vs. 87% and 79% for Der p 1 and Der p 2, respectively), the anti-Der p 23 IgE levels were relatively low. The patient response to the 6 allergens tested was variable (n = 47), but on average anti-Der p 1 and anti-Der p 2 together accounted for 85% of the specific IgE. In terms of abundance, the RNA expression level of Der p 23 is the lowest of the major allergens, thirty fold less than Der p 1 and sevenfold less than Der p 2. The structure of Der p 23 is a small, globular protein stabilized by two disulphide bonds, which is structurally related to allergens such as Blo t 12 that contain carbohydrate binding domains that bind chitin. Functional assays failed to confirm chitin binding by Der p 23. CONCLUSIONS AND CLINICAL RELEVANCE: Der p 23 accounts for a small percentage of the IgE response to mite allergens, which is dominated by Der p 1 and Der p 2. The prevalence and amount of specific IgE to Der p 23 and Der p 2 are disproportionately high compared to the expression of other Dermatophagoides allergens.

Impact of concomitant medication use on belimumab efficacy and safety in patients with systemic lupus erythematosus.

Practicing physicians have requested efficacy and safety data for belimumab, when used with specific systemic lupus erythematosus (SLE) medications. This was a post hoc analysis of pooled efficacy and safety data from patients who received belimumab 10 mg/kg plus standard of care (SoC) or placebo (SoC) in two Phase III, randomized trials, BLISS-52 and BLISS-76. Patients were categorized into four groups based on baseline concomitant medication usage: steroids only; antimalarials (AM) only; steroids + AM; or steroids + AM + immunosuppressants (IS). The primary endpoint was the SLE Responder Index (SRI) at Week 52. SRI over time and individual SRI components were secondary endpoints. Time to first flare and changes in concomitant medications were exploratory endpoints. Safety was assessed using adverse event (AE) reporting. Across 834 patients, steroids + AM was the largest group (n = 346, 41.5%) and AM only was the smallest (n = 77, 9.2%). Disease duration was shortest in the steroids + AM group (5.7 years vs 6.4-7.1 years); SELENA-SLEDAI scores were similar across groups. At Week 52, the percentage of SRI responders was greatest in the steroids + AM group for belimumab 10 mg/kg (59%) compared with placebo (44%); treatment response and SRI component improvements were also observed across other groups. The probability of experiencing an SLE flare was reduced in the steroids-only group for patients who received belimumab 10 mg/kg compared with placebo (64.3% vs 78.1%; hazard ratio 0.64; 95% confidence interval: 0.42-0.96). There was little or no change in daily AM or IS dose in any group. For all groups, there was a general decrease in steroid dose over time; a quarter to a third of patients experienced decreased steroid doses at Week 52. The overall safety profile was similar across treatment arms and concomitant medication groups, with the exception of serious AEs in the steroids + AM group (belimumab 10 mg/kg 16%, placebo 8%). The efficacy and safety of belimumab in combination with SoC was demonstrated for various groupings of steroids, AM and IS. These findings may improve the understanding of the safety and efficacy of adding belimumab to different treatments.

The impact of the introduction of fidaxomicin on the management of Clostridium difficile infection in seven NHS secondary care hospitals in England: a series of local service evaluations.

Clostridium difficile infection (CDI) is associated with high mortality. Reducing incidence is a priority for patients, clinicians, the National Health Service (NHS) and Public Health England alike. In June 2012, fidaxomicin (FDX) was launched for the treatment of adults with CDI. The objective of this evaluation was to collect robust real-world data to understand the effectiveness of FDX in routine practice. In seven hospitals introducing FDX between July 2012 and July 2013, data were collected retrospectively from medical records on CDI episodes occurring 12 months before/after the introduction of FDX. All hospitalised patients aged ≥18 years with primary CDI (diarrhoea with presence of toxin A/B without a previous CDI in the previous 3 months) were included. Recurrence was defined as in-patient diarrhoea re-emergence requiring treatment any time within 3 months after the first episode. Each hospital had a different protocol for the use of FDX. In hospitals A and B, where FDX was used first line for all primary and recurrent episodes, the recurrence rate reduced from 10.6 % to 3.1 % and from 16.3 % to 3.1 %, with a significant difference in 28-day mortality from 18.2 % to 3.1 % (p < 0.05) and 17.3 % to 6.3 % (p < 0.05) for hospitals A and B, respectively. In hospitals using FDX in selected patients only, the changes in recurrence rates and mortality were less marked. The pattern of adoption of FDX appears to affect its impact on CDI outcome, with maximum reduction in recurrence and all-cause mortality where it is used as first-line treatment.

Brief Assessment of Parental Perception (BAPP): Development and validation of a new measure for assessing paediatric outcomes after bilateral cochlear implantation.

OBJECTIVE: In contrast to previous clinical practice, current guidelines recommend bilateral cochlear implantation in children, resulting in a cohort of children who initially received one implant, but have subsequently had a second, contralateral implant. This study aimed to explore satisfaction and quality of life in children implanted simultaneously or sequentially. DESIGN: A novel measure of satisfaction and quality of life following paediatric bilateral cochlear implantation (the Brief Assessment of Parental Perception; BAPP) was developed and preliminary validation undertaken as part of a large, national project of bilateral implantation. Children's parents completed the measure yearly for up to three years following implantation. STUDY SAMPLE: Children from 14 UK implant centres were recruited into the study; data were available for 410 children one year post-implantation. RESULTS: The BAPP was found to have good face and convergent validity, and internal consistency. Results indicated very high levels of satisfaction with the devices, and improvements in quality of life. However there was evidence that children implanted sequentially were less willing to wear their second implant in the first two years than those children receiving simultaneous implants. CONCLUSION: Simultaneous and sequential cochlear implants have a positive impact on the quality of life of deaf children.

An Extraperitoneal Technique for Murine Heterotopic Cardiac Transplantation.

The mouse heterotopic cardiac transplantation model has been used extensively by investigators in the field of organ transplantation to study the rejection process, test new antirejection treatments, tolerance induction protocols or to understand basic immunological principles. Due to its extensive use, any small refinement of the technique would have a major impact on replacement, reduction and refinement (commonly known as the 3Rs). Here, we describe a novel approach to refine this model. The donor aorta and pulmonary artery are anastomosed peripherally to the femoral artery and vein of the recipient, respectively. The technical success rate is comparable to the conventional abdominal site, but it avoids a laparotomy and handling of the bowels making it less invasive method. As a result, recipients recover faster and require less postoperative analgesia. It is a major refinement under one of the 3Rs and would represent an advance in animal welfare in scientific research.