Phantom Limb Pain and Painful Neuroma After Dysvascular Lower-Extremity Amputation: A Systematic Review and Meta-Analysis.

BACKGROUND: Phantom limb pain (PLP) and symptomatic neuroma can be debilitating and significantly impact the quality of life of amputees. However, the prevalence of PLP and symptomatic neuromas in patients following dysvascular lower limb amputation (LLA) has not been reliably established. This systematic review and meta-analysis evaluates the prevalence and incidence of phantom limb pain and symptomatic neuroma after dysvascular LLA. METHODS: Four databases (Embase, MEDLINE, Cochrane Central, and Web of Science) were searched on October 5th, 2022. Prospective or retrospective observational cohort studies or cross-sectional studies reporting either the prevalence or incidence of phantom limb pain and/or symptomatic neuroma following dysvascular LLA were identified. Two reviewers independently conducted the screening, data extraction, and the risk of bias assessment according to the PRISMA guidelines. To estimate the prevalence of phantom limb pain, a meta-analysis using a random effects model was performed. RESULTS: Twelve articles were included in the quantitative analysis, including 1924 amputees. A meta-analysis demonstrated that 69% of patients after dysvascular LLA experience phantom limb pain (95% CI 53-86%). The reported pain intensity on a scale from 0-10 in LLA patients ranged between 2.3 ± 1.4 and 5.5 ± .7. A single study reported an incidence of symptomatic neuroma following dysvascular LLA of 5%. CONCLUSIONS: This meta-analysis demonstrates the high prevalence of phantom limb pain after dysvascular LLA. Given the often prolonged and disabling nature of neuropathic pain and the difficulties managing it, more consideration needs to be given to strategies to prevent it at the time of amputation.

Traumatic appendicitis is probably not real: an illustrative analysis of coincidental occurrences in nature.

There have been sporadic case reports describing 'traumatic appendicitis' (acute appendicitis occurring following injury) for almost a hundred years. Although this might seem to be an interesting and rare diagnosis for the journal reader, both appendicitis and trauma are very common, and their occurrence together may only give the illusion of causality. Indeed, such a diagnosis may not even exist. We provide an illustration of the statistical phenomenon of coincidental occurrences in nature using a computer simulation of traumatic appendicitis in the UK population. In our simulation, there are enough cases of traumatic appendicitis every 2 years to 3 years to account for the entire global literature on the topic. We suggest that unless there is a credible pathological process reported with demonstrable causality, further case reports of traumatic appendicitis need to have robust justification.

Prevalence of venous thromboembolism in patients undergoing diagnostic venous ultrasound during the first SARS-CoV-2 pandemic.

Background: Venous thromboembolism appears to be associated with severe COVID-19 infection than in those without it. However, this varies considerably depending on the cohort studied. The aims of this single-centre, multi-site retrospective cross-sectional study were to assess the number of all venous scans performed in the first month of pandemic in a large university teaching hospital, to evaluate the incidence of deep venous thrombosis (DVT), and assess the predictive ability of the clinical information available on the electronic patient record in planning work-up for DVT and prioritising ultrasound scans. Patients and methods: All consecutive patients undergoing venous ultrasound for suspected acute DVT between 1st of March and 30th of April 2020 were considered. Primary outcome was the proportion of scans positive for DVT; the secondary outcomes included association of a positive SARS-CoV-2 PCR test, demographic, clinical factors, and Wells scores. Results: 819 ultrasound scans were performed on 762 patients across the Trust in March and April 2020. This number was comparable to the corresponding pre-pandemic cohort from 2019. The overall prevalence of DVT in the studied cohort was 16.1% and was higher than before the pandemic (11.5%, p=.047). Clinical symptoms consistent with COVID-19, irrespective of the SARS-CoV-2 PCR test result (positive_COVID_PCR OR 4.97, 95%CI 2.31-10.62, p<.001; negative_COVID_PCR OR 1.97, 95%CI 1.12-3.39, p=.016), a history of AF (OR 0.20, 95%CI 0.03-0.73, p=.037), and personal history of venous thromboembolism (VTE) (OR 1.95, 95%CI 1.13-3.31, p=.014), were independently associated with the diagnosis of DVT on ultrasound scan. Wells score was not associated with the incidence of DVT. Conclusions: Amongst those referred for the DVT scan, SARS-CoV-2 PCR test was associated with an increased risk of VTE and should be taken into consideration when planning DVT work-up and prioritising diagnostic imaging. We postulate that the threshold for imaging should possibly be lower.

Effectiveness and Safety of Early Initiation of Poststernotomy Cardiac Rehabilitation Exercise Training: The SCAR Randomized Clinical Trial.

Importance: Guidelines recommend that cardiac rehabilitation (CR) exercise training should not start until 6 weeks after sternotomy, although this is not evidence based. Limited data suggest that starting earlier is not detrimental, but clinical trials are needed. Objective: To compare the effectiveness and safety of CR exercise training started either 2 weeks (early CR) or 6 weeks (usual-care CR) after sternotomy. Design, Setting, and Participants: This was an assessor-blind, noninferiority, parallel-group, randomized clinical trial that conducted participant recruitment from June 12, 2017, to March 17, 2020. Participants were consecutive cardiac surgery sternotomy patients recruited from 2 outpatient National Health Service rehabilitation centers: University Hospital, Coventry, UK, and Hospital of St Cross, Rugby, UK. Interventions: Participants were randomly assigned to 8 weeks of twice-weekly supervised CR exercise training starting either 2 weeks (early CR) or 6 weeks (usual-care CR) after sternotomy. Exercise training adhered to existing guidelines, including functional strength and cardiovascular components. Main Outcomes and Measures: Outcomes were assessed at baseline (inpatient after surgery), after CR (10 or 14 weeks after sternotomy), and 12 months after randomization. The primary outcome was the change in 6-minute walk test distance from baseline to after CR. Secondary outcomes included safety, functional fitness, and quality of life. Results: A total of 158 participants (mean [SD] age, 63 [11.5] years, 133 male patients [84.2%]) were randomly assigned to study groups; 118 patients (usual-care CR, 61 [51.7%]; early CR, 57 [48.3%]) were included in the primary analysis. Early CR was not inferior to usual-care CR (noninferiority margin, 35 m); the mean change in 6-minute walk distance from baseline to after CR was 28 m greater in the early CR group (95% CI, -11 to 66; P = .16). Mean differences for secondary outcomes were not statistically significant, indicating noninferiority of early CR. There were 46 vs 58 adverse events and 14 vs 18 serious adverse events in usual-care CR and early CR, respectively. There was no difference between the groups in the likelihood of participants having an adverse or serious adverse event. Conclusions and Relevance: Starting exercise training from 2 weeks after sternotomy was as effective as starting 6 weeks after sternotomy for improving 6-minute walk distance. With appropriate precautions, clinicians and CR professionals can consider starting exercise training as early as 2 weeks after sternotomy. Trial Registration: ClinicalTrials.gov Identifier: NCT03223558.

Genomic erosion in a demographically recovered bird species during conservation rescue.

The pink pigeon (Nesoenas mayeri) is an endemic species of Mauritius that has made a remarkable recovery after a severe population bottleneck in the 1970s to early 1990s. Prior to this bottleneck, an ex situ population was established from which captive-bred individuals were released into free-living subpopulations to increase population size and genetic variation. This conservation rescue led to rapid population recovery to 400-480 individuals, and the species was twice downlisted on the International Union for the Conservation of Nature (IUCN) Red List. We analyzed the impacts of the bottleneck and genetic rescue on neutral genetic variation during and after population recovery (1993-2008) with restriction site-associated sequencing, microsatellite analyses, and quantitative genetic analysis of studbook data of 1112 birds from zoos in Europe and the United States. We used computer simulations to study the predicted changes in genetic variation and population viability from the past into the future. Genetic variation declined rapidly, despite the population rebound, and the effective population size was approximately an order of magnitude smaller than census size. The species carried a high genetic load of circa 15 lethal equivalents for longevity. Our computer simulations predicted continued inbreeding will likely result in increased expression of deleterious mutations (i.e., a high realized load) and severe inbreeding depression. Without continued conservation actions, it is likely that the pink pigeon will go extinct in the wild within 100 years. Conservation rescue of the pink pigeon has been instrumental in the recovery of the free-living population. However, further genetic rescue with captive-bred birds from zoos is required to recover lost variation, reduce expression of harmful deleterious variation, and prevent extinction. The use of genomics and modeling data can inform IUCN assessments of the viability and extinction risk of species, and it helps in assessments of the conservation dependency of populations.

La paloma rosada (Nesoenas mayeri) es una especie endémica de Mauricio que se ha recuperado impresionantemente después de un grave cuello de botella poblacional a principios de la década de 1970 que duró hasta inicios de la década de 1990. Antes de este cuello de botella se había establecido una población ex situ de la cual se liberaban individuos reproducidos en cautiverio a las subpoblaciones en libertad para incrementar la variación genética y el tamaño poblacional. Este rescate de conservación derivó en una recuperación rápida de la población (400-480 individuos) y la especie cambió positivamente de categoría dos veces en la Lista Roja de la Unión Internacional para la Conservación de la Naturaleza (UICN). Analizamos los impactos del cuello de botella y el rescate genético sobre la variación genética neutral durante y después de la recuperación poblacional (de 1993 a 2008) mediante secuenciación RAD, análisis de microsatélites y análisis genéticos cuantitativos de los datos del libro genealógico de 1112 aves ubicadas en zoológicos de Europa y los Estados Unidos. Usamos simulaciones por computadora para estudiar los cambios pronosticados en la variación genética y en la viabilidad poblacional del pasado hacia el futuro. La variación genética declinó rápidamente, a pesar de la recuperación poblacional, y el tamaño efectivo de la población fue aproximadamente un orden de magnitud más pequeño que el tamaño del censo. La especie contó con una carga genética elevada de casi 15 equivalentes letales para la longevidad. Nuestras simulaciones pronostican que la endogamia continua probablemente resultará en un incremento en la expresión de mutaciones deletéreas (es decir, una carga realizada elevada) y en una depresión endogámica severa. Sin acciones continuas para la conservación, es probable que la paloma rosada esté extinta en vida libre dentro de cien años. El rescate de conservación de la paloma rosada ha sido fundamental en la recuperación de la población silvestre; sin embargo, se requiere de un rescate genético adicional con las aves de reproducción en cautiverio de los zoológicos para recuperar la variación perdida, reducir la expresión de la variación deletérea dañina y prevenir la extinción. El uso de la genómica y los datos modelados puede orientar las valoraciones de la UICN sobre la viabilidad y el riesgo de extinción de las especies, además de que ayuda en la evaluación de la dependencia que tienen las poblaciones de la conservación.

K.Vita: a feasibility study of a blend of medium chain triglycerides to manage drug-resistant epilepsy.

This prospective open-label feasibility study aimed to evaluate acceptability, tolerability and compliance with dietary intervention with K.Vita, a medical food containing a unique ratio of decanoic acid to octanoic acid, in individuals with drug-resistant epilepsy. Adults and children aged 3-18 years with drug-resistant epilepsy took K.Vita daily whilst limiting high-refined sugar food and beverages. K.Vita was introduced incrementally with the aim of achieving ≤35% energy requirements for children or 240 ml for adults. Primary outcome measures were assessed by study completion, participant diary, acceptability questionnaire and K.Vita intake. Reduction in seizures or paroxysmal events was a secondary outcome. 23/35 (66%) children and 18/26 (69%) adults completed the study; completion rates were higher when K.Vita was introduced more gradually. Gastrointestinal disturbances were the primary reason for discontinuation, but symptoms were similar to those reported from ketogenic diets and incidence decreased over time. At least three-quarters of participants/caregivers reported favourably on sensory attributes of K.Vita, such as taste, texture and appearance, and ease of use. Adults achieved a median intake of 240 ml K.Vita, and children 120 ml (19% daily energy). Three children and one adult had ß-hydroxybutyrate >1 mmol/l. There was 50% (95% CI 39-61%) reduction in mean frequency of seizures/events. Reduction in seizures or paroxysmal events correlated significantly with blood concentrations of medium chain fatty acids (C10 and C8) but not ß-hydroxybutyrate. K.Vita was well accepted and tolerated. Side effects were mild and resolved with dietetic support. Individuals who completed the study complied with K.Vita and additional dietary modifications. Dietary intervention had a beneficial effect on frequency of seizures or paroxysmal events, despite absent or very low levels of ketosis. We suggest that K.Vita may be valuable to those with drug-resistant epilepsy, particularly those who cannot tolerate or do not have access to ketogenic diets, and may allow for more liberal dietary intake compared to ketogenic diets, with mechanisms of action perhaps unrelated to ketosis. Further studies of effectiveness of K.Vita are warranted.

Severely stigmatised skin neglected tropical diseases: a protocol for social science engagement.

More than one billion people are affected by neglected tropical diseases (NTDs) and many of these diseases are preventable. While the grouping of these conditions as NTDs has generated vast mapping, mass drug administration and surveillance programmes, there is growing evidence of gaps and weaknesses in purely biomedical approaches, and the need for responses that also recognise the social determinants of health. In order to unpack the social and political determinants of NTDs, it is important to view the problem from a social science perspective. Given this background, the Social Sciences for Severe Stigmatizing Skin Diseases (5S) Foundation has recently been established by the Centre for Global Health Research at Brighton and Sussex Medical School. The broad aim of the 5S Foundation is to incorporate social science perspectives in understanding and addressing the problems around three NTDs, namely, podoconiosis, mycetoma and scabies. This protocol paper sets out the aims and approaches of the 5S Foundation while activities such as research, public engagement, training and capacity building get underway.

Interests and concerns of the Army Medical Services as reflected by the publications in the Journal of the Royal Army Medical Corps 1903-2019.

INTRODUCTION: The Journal of the Royal Army Medical Corps (JRAMC) is published with the aim of propagating current knowledge and expertise while also acting as institutional memory for the practice of medicine within the military. This work aimed to examine how the interests of the JRAMC, and by inference the Army Medical Services, have changed over time as reflected by the articles published in the journal. METHODS: A text mining analysis of the titles of all published articles in the JRAMC between 1903 and 2019 was performed. The most commonly used terms were identified and their relative frequency over the decades analysed to identify trends. Article content and contemporary events were compared with the observed trends to identify explanatory events and themes of interest. RESULTS: Medical topics of interest centred around specific infectious diseases, particularly during the early/mid-20th century, and trauma and battle injury. The medical specialties of surgery, anaesthetics and mental health were all well represented in nearly all decades, while primary care only came to prominence as a named specialty from the 1960s onwards. India, France, Egypt and wider Africa were the most commonly cited geographical regions, although there were spikes of interest associated with specific conflicts in the Falklands, Bosnia, Afghanistan and Iraq. CONCLUSION: The interests of the JRAMC have changed considerably over the years primarily driven by the geopolitical interests of Britain-in particular its colonial interests and the conflicts it has been involved in, but also by medical advances seen in contemporary society.

Improving competing voices segregation for hearing impaired listeners using a low-latency deep neural network algorithm.

Hearing aid users are challenged in listening situations with noise and especially speech-on-speech situations with two or more competing voices. Specifically, the task of attending to and segregating two competing voices is particularly hard, unlike for normal-hearing listeners, as shown in a small sub-experiment. In the main experiment, the competing voices benefit of a deep neural network (DNN) based stream segregation enhancement algorithm was tested on hearing-impaired listeners. A mixture of two voices was separated using a DNN and presented to the two ears as individual streams and tested for word score. Compared to the unseparated mixture, there was a 13%-point benefit from the separation, while attending to both voices. If only one output was selected as in a traditional target-masker scenario, a larger benefit of 37%-points was found. The results agreed well with objective metrics and show that for hearing-impaired listeners, DNNs have a large potential for improving stream segregation and speech intelligibility in difficult scenarios with two equally important targets without any prior selection of a primary target stream. An even higher benefit can be obtained if the user can select the preferred target via remote control.

Risk of venous thromboembolism following surgical treatment of superficial venous incompetence.

BACKGROUND: The invasive management of varicose veins has a known risk of post-operative deep venous thrombosis and subsequent pulmonary embolism. The aim of this study was to evaluate absolute and relative risk of venous thromboembolism (VTE) following commonly used varicose vein procedures. PATIENTS AND METHODS: A retrospective analysis of secondary data using Hospital Episode Statistics database was performed for all varicose vein procedures performed between 2003 and 2013 and all readmissions for VTE in the same patients within 30 days, 90 days, and one year. Comparison of the incidence of VTEs between procedures was performed using a Pearson's Chi-squared test. RESULTS: In total, 261,169 varicose vein procedures were performed during the period studied. There were 686 VTEs recorded at 30 days (0.26 % incidence), 884 at 90 days (0.34 % incidence), and 1,246 at one year (0.48 % incidence). The VTE incidence for different procedures was between 0.15-0.35 % at 30 days, 0.26-0.50 % at 90 days, and 0.46-0.58 % at one year. At 30 days there was a significantly lower incidence of VTEs for foam sclerotherapy compared to other procedures (p = 0.01). There was no difference in VTE incidence between procedures at 90 days (p = 0.13) or one year (p = 0.16). CONCLUSIONS: Patients undergoing varicose vein procedures have a small but appreciable increased risk of VTE compared to the general population, with the effect persisting at one year. Foam sclerotherapy had a lower incidence of VTE compared to other procedures at 30 days, but this effect did not persist at 90 days or at one year. There was no other significant difference in the incidence of VTE between open, endovenous, and foam sclerotherapy treatments.

An improved assembly and annotation of the allohexaploid wheat genome identifies complete families of agronomic genes and provides genomic evidence for chromosomal translocations.

Advances in genome sequencing and assembly technologies are generating many high-quality genome sequences, but assemblies of large, repeat-rich polyploid genomes, such as that of bread wheat, remain fragmented and incomplete. We have generated a new wheat whole-genome shotgun sequence assembly using a combination of optimized data types and an assembly algorithm designed to deal with large and complex genomes. The new assembly represents >78% of the genome with a scaffold N50 of 88.8 kb that has a high fidelity to the input data. Our new annotation combines strand-specific Illumina RNA-seq and Pacific Biosciences (PacBio) full-length cDNAs to identify 104,091 high-confidence protein-coding genes and 10,156 noncoding RNA genes. We confirmed three known and identified one novel genome rearrangements. Our approach enables the rapid and scalable assembly of wheat genomes, the identification of structural variants, and the definition of complete gene models, all powerful resources for trait analysis and breeding of this key global crop.

An evaluation of the normal range of StO2measurements at rest and following a mixed exercise protocol.

BACKGROUND: Assessment of local tissue oxygenation (StO2) using near infrared spectroscopy is an emerging technique in medical practice with applications in trauma/sepsis management, diagnosis of acute compartment syndrome and assessment of tissue viability. Despite this, there have been little published data on the range of StO2values in normal subjects. METHODS: StO2measurements were recorded in 105 infantry soldiers using an INVOS System Monitor (Somanetics) from both deltoids, the anterior compartment of the leg and the frontal lobe of the brain. Measurements were taken at rest and following completion of a mixed exercise protocol, consisting of overarm pull-ups, sit-ups and a 3-mile run. RESULTS: StO2values at rest were found to have a wide normal range with a skew left distribution. Mean StO2was similar between the deltoids (left deltoid 80%, right deltoid 79%), but significantly different between other anatomical sites (leg 68%, brain 73%). However, all sites demonstrated a similar lower range cut-off at approximately 40%. Following exercise, there was a significant increase in StO2values at all sites (left deltoid by 3.1 ± 2.0%, right deltoid by 2.6 ± 2.3%, leg by 8.0 ± 2.3% and brain by 8.6 ± 1.9%), which persisted for at least 10 min. CONCLUSIONS: There were statistically significant differences in mean StO2values recorded at different anatomical sites, although the reference ranges were wide and substantially overlapped. StO2increased at all sites after exercise with the effect persisting for at least 10 min. The interaction between exercise and pathological phenomena remains unknown and is an area for further study.