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Brachial plexus injury: living with uncertainty.
No full textPURPOSE
A traumatic brachial plexus injury (BPI) has life-changing consequences for patients and their families. Despite advancements in treatments final outcome is unpredictable depending on factors including time to treatment, injury severity, neural regeneration, and available interventions. The final outcome may not be seen for up to four years. This study aimed to explore the impact of uncertainty on people with a traumatic BPI.
METHODS
Secondary qualitative analysis was conducted on data from a study exploring outcomes important to patients with a traumatic BPI. Data from semi-structured interviews with adult traumatic BPI patients ( = 13) were analyzed using reflexive thematic analysis.
RESULTS
Three major themes were identified in the qualitative data: (i) "I don't know what happened to me," focused on uncertainty in diagnosis. (ii) "I went to work one day… and then it all changed" centered around uncertainty in the future. (iii) Coping with uncertainty.
CONCLUSION
The results illustrate that people with a traumatic BPI face uncertainty regarding diagnosis, prognosis, and surrounding their roles in the future. Individuals respond to uncertainty in different ways and this needs to be understood by health care professionals. IMPLICATIONS FOR REHABILITATIONHealth professionals should consider uncertainty in all their contacts with people who have experienced a traumatic brachial plexus injury.People with a traumatic brachial plexus injury experience uncertainty in different ways therefore education and information given may be optimized if tailored to the individual rather than generic.Increasing awareness of the injury and its presentation in non-specialist acute care clinicians may accelerate diagnosis and reduce initial uncertainty.Acknowledging the presence of uncertainty is important during the shared decision-making in brachial plexus injuries
Increased Seroprevalence and Improved Antibody Responses Following Third Primary SARS-CoV-2 Immunisation: An Update From the COV-AD Study.
No full textBackground
Patients with primary and secondary antibody deficiency are vulnerable to COVID-19 and demonstrate diminished responses following two-dose SARS-CoV-2 vaccine schedules. Third primary vaccinations have been deployed to enhance their humoral and cellular immunity.
Objectives
To determine the immunogenicity of the third primary SARS-CoV-2 immunisation in a heterogeneous cohort of patients with antibody deficiency.
Methods
Participants enrolled in the COV-AD study were sampled before and after their third vaccine dose. Serological and cellular responses were determined using ELISA, live-virus neutralisation and ELISPOT assays.
Results
Following a two-dose schedule, 100% of healthy controls mounted a serological response to SARS-CoV-2 vaccination, however, 38.6% of individuals with antibody deficiency remained seronegative. A third primary SARS-CoV-2 vaccine significantly increased anti-spike glycoprotein antibody seroprevalence from 61.4% to 76.0%, the magnitude of the antibody response, its neutralising capacity and induced seroconversion in individuals who were seronegative after two vaccine doses. Vaccine-induced serological responses were broadly cross-reactive against the SARS-CoV-2 B.1.1.529 variant of concern, however, seroprevalence and antibody levels remained significantly lower than healthy controls. No differences in serological responses were observed between individuals who received AstraZeneca ChAdOx1 nCoV-19 and Pfizer BioNTech 162b2 during their initial two-dose vaccine schedule. SARS-CoV-2 infection-naive participants who had received a heterologous vaccine as a third dose were significantly more likely to have a detectable T cell response following their third vaccine dose (61.5% vs 11.1%).
Conclusion
These data support the widespread use of third primary immunisations to enhance humoral immunity against SARS-CoV-2 in individuals with antibody deficiency
Using root cause analysis as a tool to reduce central venous catheters in haemodialysis patients.
No full textBACKGROUND
Haemodialysis remains the most common modality of renal replacement therapy. National and international guidelines continue to promote arteriovenous fistulas or grafts as the preferred vascular access for haemodialysis, given the increased risks associated with use of central venous catheters (CVCs). Our renal centre pursues a 'fistula first' culture and uses root cause analysis and a patient safety incident based approach to meet the recommended standards of minimal CVC use in dialysis patients.
METHODS
We undertook a retrospective observational review looking at patterns of CVC use amongst our patients to identify themes and changes over time. Using data collected over a 5 year period, we examined 100 patient safety incidents involving CVC use in planned haemodialysis patients. We used a contributory factors framework to identify systemic contributors to each incident.
RESULTS
During the study period our centre achieved the national standard of at least 60% of incident dialysis patients commencing planned haemodialysis via arteriovenous access. About 26% of cases of CVC use in incident dialysis patients were deemed potentially avoidable. The most common contributory factor identified in these cases was poor communication.
CONCLUSIONS
Using a root cause analysis based methodology to examine CVC use in haemodialysis is a novel approach to quality improvement in this area. Our methodology can be used as a framework by other centres to optimise the provision of safe, effective, and timely vascular access for dialysis, with multiple benefits for both renal services and individual patients
Challenges in Comparative Meta-Analysis of the Accuracy of Multiple Diagnostic Tests.
No full textThe rapid increase in diagnostic and screening techniques has urged the need to choose among multiple diagnostic tests. For the majority of diseases, there is more than a single test available, and studies usually compare a subset of these tests. In such cases, a separate meta-analysis of each test cannot provide a reliable answer on the relative accuracy of the multiple available tests. Extensions of standard (hierarchical) meta-analysis to network meta-analysis (NMA) models for the comparison of at least three diagnostic tests have been the subject of methodological research in recent years. NMA can be used to jointly analyze the totality of evidence in order to provide estimates of relative accuracy (sensitivity and specificity ), to compare tests that have not been compared head-to-head, and to obtain a ranking of all competing tests in order to further facilitate the decision-making process.In this chapter, we illustrate current methodology for meta-analysis of multiple test comparisons, introduce NMA methods of diagnostic tests as an extension to the standard meta-analysis of diagnostic test accuracy (DTA) studies, and present existing approaches to rank tests according to their accuracy, specificity , and sensitivity . We also describe the basic concepts, underlying assumptions, and challenges in NMA of multiple diagnostic tests
The Impact of the COVID-19 Pandemic on Mobility Trends and the Associated Rise in Population-Level Physical Inactivity: Insights From International Mobile Phone and National Survey Data.
No full textIntroduction
The COVID-19 pandemic has reduced physical activity (PA) levels. This is important as physical inactivity is linked to poor COVID-19 outcomes. This study aimed to assess the impact of COVID-19 pandemic restrictions on greenspace and residence mobility, walking levels and in turn how these translated to trends in (UK) PA levels.
Methods
Google Mobility Reports, the Oxford COVID-19 Government Response Tracker and Apple Mobility geospatial datasets were interrogated for international data. Residence mobility represents home mobility, greenspace mobility includes parks, walking direction requests is proportion of walking directions; stringency index measures lockdown intensity. The Sports England Active Lives Survey dataset was assessed for complementary changes in English PA levels.
Results
Using mobility data of 10 countries we observed that during lockdown there were reductions in greenspace mobility and walking directions alongside increased residence mobility; more pronounced changes were seen in countries with higher stringency indices. From a UK perspective, complementary English PA survey data demonstrated the impact of these mobility changes on the proportion and demographic characteristics of PA levels. The most vulnerable in society, the elderly (ages 75+) and Black and Asian minority ethnicity (BAME) individuals were more likely to become physically inactive.
Conclusions
The COVID-19 pandemic reduced greenspace mobility and walking direction requests globally. Complementary assessment of English PA levels demonstrated a greater proportion of the population became inactive. Demographics (75+ and BAME) prone to worse COVID-19 outcomes became disproportionately inactive. UK Urban planning should prioritize greenspace development. This could improve city walkability and PA levels
Long-term functional outcomes following paediatric traumatic elbow dislocation, a clinical retrospective cohort study.
No full textBACKGROUND
Paediatric traumatic elbow dislocation occurs in 6 per 100,000 children per year and if not treated promptly can result in a poor outcome. Despite this, the long-term clinical and functional outcome of these injuries has not been well described using modern patient-reported outcome tools. The aim of our study was present the outcome of these injuries in the long term.
METHODS
Twenty children with an acute traumatic elbow dislocation who presented between February 2007 to February 2016 were included in our study. Patient demographics, management and complications were recorded from the clinical notes. Ten children had associated fractures and were managed surgically, while the remaining were managed with closed reduction and immobilisation. Functional outcomes were assessed with Kim's elbow performance score.
RESULTS
The mean age was 12 years (7 -15) and follow-up was 8 years (4 - 13). There was one (5%) re-dislocation requiring surgery and one (5%) ulna nerve neurapraxia that resolved within one month. The average Kim's scores were 87.5 (65 - 100) and 77.5 (60 - 100) in the closed reduction and open reduction groups, respectively (P=0.08). 80% (16/20) reported good or excellent outcome with a Kim's score of greater than 75 points with no cases of poor functional outcome reported in our series.
CONCLUSIONS
Traumatic elbow dislocations in children, with or without associated fracture, have a good long-term functional outcome with appropriate early management
Hypoxia Increases the Potential for Neutrophil-mediated Endothelial Damage in Chronic Obstructive Pulmonary Disease.
No full textPatients with chronic obstructive pulmonary disease (COPD) experience excess cardiovascular morbidity and mortality, and exacerbations further increase the risk of such events. COPD is associated with persistent blood and airway neutrophilia and systemic and tissue hypoxia. Hypoxia augments neutrophil elastase release, enhancing capacity for tissue injury. To determine whether hypoxia-driven neutrophil protein secretion contributes to endothelial damage in COPD. The healthy human neutrophil secretome generated under normoxic or hypoxic conditions was characterized by quantitative mass spectrometry, and the capacity for neutrophil-mediated endothelial damage was assessed. Histotoxic protein concentrations were measured in normoxic versus hypoxic neutrophil supernatants and plasma from patients experiencing COPD exacerbation and healthy control subjects. Hypoxia promoted PI3Kγ-dependent neutrophil elastase secretion, with greater release seen in neutrophils from patients with COPD. Supernatants from neutrophils incubated under hypoxia caused pulmonary endothelial cell damage, and identical supernatants from COPD neutrophils increased neutrophil adherence to endothelial cells. Proteomics revealed differential neutrophil protein secretion under hypoxia and normoxia, and hypoxia augmented secretion of a subset of histotoxic granule and cytosolic proteins, with significantly greater release seen in COPD neutrophils. The plasma of patients with COPD had higher content of hypoxia-upregulated neutrophil-derived proteins and protease activity, and vascular injury markers. Hypoxia drives a destructive "hypersecretory" neutrophil phenotype conferring enhanced capacity for endothelial injury, with a corresponding signature of neutrophil degranulation and vascular injury identified in plasma of patients with COPD. Thus, hypoxic enhancement of neutrophil degranulation may contribute to increased cardiovascular risk in COPD. These insights may identify new therapeutic opportunities for endothelial damage in COPD
Procedural and 12-month in-hospital costs of primary infra-popliteal bypass surgery, infrapopliteal best endovascular treatment, and major lower limb amputation for chronic limb threatening ischemia.
No full textOBJECTIVE
Chronic limb-threatening ischemia (CLTI) is a growing global problem due to the widespread use of tobacco and increasing prevalence of diabetes. Although the financial consequences are considerable, few studies have compared the relative cost-effectiveness of different CLTI management strategies. The Bypass vs Angioplasty in Severe Ischaemia of the Leg (BASIL)-2 trial is randomizing patients with CLTI to primary infrapopliteal (IP) vein bypass surgery (BS) or best endovascular treatment (BET) and includes a comprehensive within-trial cost-utility analysis. The aim of this study is to compare over a 12-month time horizon, the costs of primary IP BS, IP best endovascular treatment (BET), and major limb major amputation (MLLA) to inform the BASIL-2 cost-utility analysis.
METHODS
We compared procedural human resource (HR) costs and total in-hospital costs for the index admission, and over the following 12-months, in 60 consecutive patients undergoing primary IP BS (n = 20), IP BET (n = 20), or MLLA (10 transfemoral and 10 transtibial) for CLTI within the BASIL prospective cohort study.
RESULTS
Procedural HR costs were greatest for BS (BS £2551; 95% confidence interval [CI], £1934-£2807 vs MLLA £1130; 95% CI, £1046-£1297 vs BET £329; 95% CI, £242-£390; P < .001, Kruskal-Wallis) due to longer procedure duration and greater staff requirement. With regard to the index admission, MLLA was the most expensive due to longer hospital stay (MLLA £13,320; 95% CI, £8986-£18,616 vs BS £8714; 95% CI, £6097-£11,973 vs BET £4813; 95% CI, £3529-£6097; P < .001, Kruskal-Wallis). The total cost of the index admission and in-hospital care over the following 12 months remained least for BET (MLLA £26,327; 95% CI, £17,653-£30,458 vs BS £20,401; 95% CI, £12,071-£23,926 vs BET £12,298; 95% CI, £6961-£15,439; P < .001, Kruskal-Wallis).
CONCLUSIONS
Over a 12-month time horizon, MLLA and IP BS are more expensive than IP BET in terms of procedural HR costs and total in-hospital costs. These economic data, together with quality of life data from BASIL-2, will inform the calculation of incremental cost-effectiveness ratios for different CLTI management strategies within the BASIL-2 cost-utility analysis
Autoimmune disease and interconnections with vitamin D.
No full textVitamin D has well documented effects on calcium homeostasis and bone metabolism but recent studies suggest a much broader role for this secosteroid in human health. Key components of the vitamin D system, notably the vitamin D receptor (VDR) and the vitamin D activating enzyme (1α-hydroxylase), are present in a wide array of tissues, notably macrophages, dendritic cells and T lymphocytes (T cells) from the immune system. Thus, serum 25-hydroxyvitamin D (25D) can be converted to hormonal 1,25-dihydroxyvitamin D (1,25D) within immune cells, and then interact with VDR and promote transcriptional and epigenomic responses in the same or neighbouring cells. These intracrine and paracrine effects of 1,25D have been shown to drive antibacterial or antiviral innate responses, as well as attenuating inflammatory T cell adaptive immunity. Beyond these mechanistic observations, association studies have reported correlation between low serum 25D levels and the risk and severity of human immune disorders including autoimmune diseases such as inflammatory bowel disease, multiple sclerosis, type 1 diabetes and rheumatoid arthritis. The proposed explanation for this is that decreased availability of 25D compromises immune cell synthesis of 1,25D leading to impaired innate immunity and over-exuberant inflammatory adaptive immunity. The aim of the current review is to explore the mechanistic basis for immunomodulatory effects of 25D and 1,25D in greater detail with specific emphasis on how vitamin D-deficiency (low serum levels of 25D) may lead to dysregulation of macrophage, dendritic cell and T cell function, and increase risk of inflammatory autoimmune disease