A study protocol for a double-blind randomised placebo-controlled trial evaluating the efficacy of carrageenan nasal and throat spray for COVID-19 prophylaxis-ICE-COVID.

INTRODUCTION: At present, vaccines form the only mode of prophylaxis against COVID-19. The time needed to achieve mass global vaccination and the emergence of new variants warrants continued research into other COVID-19 prevention strategies. The severity of COVID-19 infection is thought to be associated with the initial viral load, and for infection to occur, viruses including SARS-CoV-2 must first penetrate the respiratory mucus and attach to the host cell surface receptors. Carrageenan, a sulphated polysaccharide extracted from red edible seaweed, has shown efficacy against a wide range of viruses in clinical trials through the prevention of viral entry into respiratory host cells. Carrageenan has also demonstrated in vitro activity against SARS-CoV-2. METHODS AND ANALYSIS: A single-centre, randomised, double-blinded, placebo-controlled phase III trial was designed. Participants randomised in a 1:1 allocation to either the treatment arm, verum Coldamaris plus (1.2 mg iota-carrageenan (Carragelose®), 0.4 mg kappa-carrageenan, 0.5% sodium chloride and purified water), or placebo arm, Coldamaris sine (0.5% sodium chloride) spray applied daily to their nose and throat for 8 weeks, while completing a daily symptom tracker questionnaire for a total of 10 weeks. PRIMARY OUTCOME: Acquisition of COVID-19 infection as confirmed by a positive PCR swab taken at symptom onset or seroconversion during the study. Secondary outcomes include symptom type, severity and duration, subsequent familial/household COVID-19 infection and infection with non-COVID-19 upper respiratory tract infections. A within-trial economic evaluation will be undertaken, with effects expressed as quality-adjusted life years. DISCUSSION: This is a single-centre, phase III, double-blind, randomised placebo-controlled clinical trial to assess whether carrageenan nasal and throat spray reduces the risk of development and severity of COVID-19. If proven effective, the self-administered prophylactic spray would have wider utility for key workers and the general population. TRIAL REGISTRATION: NCT04590365; ClinicalTrials.gov NCT04590365. Registered on 19 October 2020.

Construct validity of the anglicised FACE-Q skin cancer module.

OBJECTIVES: The FACE-Q Skin Cancer module is a patient-reported outcome measure (PROM) for facial skin cancer. It has been anglicised for the UK population and undergone psychometric testing using classical test theory. In this study, further evaluation of construct validity using Rasch measurement theory and hypothesis testing was performed. METHODS: Patients were prospectively recruited to the Patient-Reported Outcome Measures In Skin Cancer Reconstruction (PROMISCR) study and asked to complete the anglicised FACE-Q Skin Cancer module. The scalability and unidimensionality of the data were assessed with a Mokken analysis prior to Rasch analysis. Response thresholds, targeting, fit statistics, local dependency, and internal consistency were examined for all items and subscales. Four a priori hypotheses were tested to evaluate the convergent and divergent validity. We additionally hypothesised that the median 'cancer worry' score would be lower in post-operative than pre-operative patients. RESULTS: 239 patients self-completed the questionnaire between August 2017 and May 2019. Of the ten subscales assessed, five showed relative fit to the Rasch model. Unidimensionality was present for all five subscales, with most demonstrating ordered item thresholds and appropriate fit statistics. Two items in the 'cancer worry' subscale had either disordered or very close response thresholds. Subscales of the FACE-Q Skin Cancer module demonstrated convergent and divergent validity with relevant Skin Cancer Index comparators (p < 0.001). Median 'cancer worry' was lower in post-operative patients (44 vs 39, p < 0.001). CONCLUSION: The anglicised FACE-Q Skin Cancer module shows psychometric validity through hypothesis testing, and both classical and modern test theory.

Mortality after surgery with SARS-CoV-2 infection in England: a population-wide epidemiological study.

BACKGROUND: The COVID-19 pandemic has heavily impacted elective and emergency surgery around the world. We aimed to confirm the incidence of perioperative severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and associated mortality after surgery. METHODS: Analysis of routine electronic health record data from NHS hospitals in England. We extracted data from Hospital Episode Statistics in England describing adult patients undergoing surgery between January 1, 2020 and February 28, 2021. The exposure was SARS-CoV-2 infection defined by International Classification of Diseases (ICD)-10 codes. The primary outcome measure was 90 day in-hospital mortality. Data were analysed using multivariable logistic regression adjusted for age, sex, Charlson Comorbidity Index, Index of Multiple Deprivation, presence of cancer, surgical procedure type and admission acuity. Results are presented as n (%) and odds ratios (OR) with 95% confidence intervals (CI). RESULTS: We identified 2 666 978 patients undergoing surgery of whom 28 777 (1.1%) had SARS-CoV-2 infection. In total, 26 364 (1.0%) patients died in hospital. SARS-CoV-2 infection was associated with a much greater risk of death (SARS-CoV-2: 6153/28 777 [21.4%] vs no SARS-CoV-2: 20 211/2 638 201 [0.8%]; OR=5.7 [95% CI, 5.5-5.9]; P<0.001). Amongst patients undergoing elective surgery, 2412/1 857 586 (0.1%) had SARS-CoV-2, of whom 172/2412 (7.1%) died, compared with 1414/1 857 586 (0.1%) patients without SARS-CoV-2 (OR=25.8 [95% CI, 21.7-30.9]; P<0.001). Amongst patients undergoing emergency surgery, 22 918/582 292 (3.9%) patients had SARS-CoV-2, of whom 5752/22 918 (25.1%) died, compared with 18 060/559 374 (3.4%) patients without SARS-CoV-2 (OR=5.5 [95% CI, 5.3-5.7]; P<0.001). CONCLUSIONS: The low incidence of SARS-CoV-2 infection in NHS surgical pathways suggests current infection prevention and control policies are highly effective. However, the high mortality amongst patients with SARS-CoV-2 suggests these precautions cannot be safely relaxed.

Resource requirements for reintroducing elective surgery during the COVID-19 pandemic: modelling study.

BACKGROUND: The COVID-19 response required the cancellation of all but the most urgent surgical procedures. The number of cancelled surgical procedures owing to Covid-19, and the reintroduction of surgical acivirt, was modelled. METHODS: This was a modelling study using Hospital Episode Statistics data (2014-2019). Surgical procedures were grouped into four urgency classes. Expected numbers of surgical procedures performed between 1 March 2020 and 28 February 2021 were modelled. Procedure deficit was estimated using conservative assumptions and the gradual reintroduction of elective surgery from the 1 June 2020. Costs were calculated using NHS reference costs and are reported as millions or billions of euros. Estimates are reported with 95 per cent confidence intervals. RESULTS: A total of 4 547 534 (95 per cent c.i. 3 318 195 to 6 250 771) patients with a pooled mean age of 53.5 years were expected to undergo surgery between 1 March 2020 and 28 February 2021. By 31 May 2020, 749 247 (513 564 to 1 077 448) surgical procedures had been cancelled. Assuming that elective surgery is reintroduced gradually, 2 328 193 (1 483 834 - 3 450 043) patients will be awaiting surgery by 28 February 2021. The cost of delayed procedures is €5.3 (3.1 to 8.0) billion. Safe delivery of surgery during the pandemic will require substantial extra resources costing €526.8 (449.3 to 633.9) million. CONCLUSION: As a consequence of the Covid-19 pandemic, provision of elective surgery will be delayed and associated with increased healthcare costs.

Personal protective equipment for surgeons during COVID-19 pandemic: systematic review of availability, usage and rationing.

BACKGROUND: Surgeons need guidance regarding appropriate personal protective equipment (PPE) during the COVID-19 pandemic based on scientific evidence rather than availability. The aim of this article is to inform surgeons of appropriate PPE requirements, and to discuss usage, availability, rationing and future solutions. METHODS: A systematic review was undertaken in accordance with PRISMA guidelines using MEDLINE, Embase and WHO COVID-19 databases. Newspaper and internet article sources were identified using Nexis. The search was complemented by bibliographic secondary linkage. The findings were analysed alongside guidelines from the WHO, Public Health England, the Royal College of Surgeons and specialty associations. RESULTS: Of a total 1329 articles identified, 95 studies met the inclusion criteria. Recommendations made by the WHO regarding the use of PPE in the COVID-19 pandemic have evolved alongside emerging evidence. Medical resources including PPE have been rapidly overwhelmed. There has been a global effort to overcome this by combining the most effective use of existing PPE with innovative strategies to produce more. Practical advice on all aspects of PPE is detailed in this systematic review. CONCLUSION: Although there is a need to balance limited supplies with staff and patient safety, this should not leave surgeons treating patients with inadequate PPE.

The association of smoking and socioeconomic status on cutaneous melanoma: a population-based, data-linkage, case-control study.

BACKGROUND: Previous studies have identified an inverse association between melanoma and smoking; however, data from population-based studies are scarce. OBJECTIVES: To determine the association between smoking and socioeconomic (SES) on the risk of development of melanoma. Furthermore, we sought to determine the implications of smoking and SES on survival. METHODS: We conducted a population-based case-control study. Cases were identified from the Welsh Cancer Intelligence and Surveillance Unit (WCISU) during 2000-2015 and controls from the general population. Smoking and SES were obtained from data linkage with other national databases. The association of smoking status and SES on the incidence of melanoma were assessed using binary logistic regression. Multivariate survival analysis was performed on a melanoma cohort using a Cox proportional hazard model using survival as the outcome. RESULTS: During 2000-2015, 9636 patients developed melanoma. Smoking data were obtained for 7124 (73·9%) of these patients. There were 26 408 controls identified from the general population. Smoking was inversely associated with melanoma incidence [odds ratio (OR) 0·70, 95% confidence interval (CI) 0·65-0·76]. Smoking was associated with an increased overall mortality [hazard ratio (HR) 1·30, 95% CI 1·09-1·55], but not associated with melanoma-specific mortality. Patients with higher SES had an increased association with melanoma incidence (OR 1·58, 95% CI 1·44-1·73). Higher SES was associated with an increased chance of both overall (HR 0·67, 95% CI 0·56-0·81) and disease-specific survival (HR 0·69, 95% CI 0·53-0·90). CONCLUSIONS: Our study has demonstrated that smoking appeared to be associated with reduced incidence of melanoma. Although smoking increases overall mortality, no association was observed with melanoma-specific mortality. Further work is required to determine if there is a biological mechanism underlying this relationship or an alternative explanation, such as survival bias. What's already known about this topic? Previous studies have been contradictory with both negative and positive associations between smoking and the incidence of melanoma reported. Previous studies have either been limited by publication bias because of selective reporting or underpowered. What does this study add? Our large study identified an inverse association between smoking status and melanoma incidence. Although smoking status was negatively associated with overall disease survival, no significant association was noted in melanoma-specific survival. Socioeconomic status remains closely associated with melanoma. Although higher socioeconomic populations are more likely to develop the disease, patients with lower socioeconomic status continue to have a worse prognosis.

The effect of the acute inflammatory response of burns and its treatment on clot characteristics and quality: A prospective case controlled study.

INTRODUCTION: Burns are known to have an effect on coagulation in the early period after burn. Current coagulation tests have been criticised in acute burns due to their inherent limitations. This study aims to investigate the potential for a new quantitative functional biomarker of clot quality, fractal dimension, to identify changes in clot microstructure as a result of the burn inflammatory response and its treatment. METHODS: A total of fifty-eight burn patients were included in this prospective case-controlled study. The control group (29 patients mean TBSA 1%), and case group (29 patients mean TBSA 30%) were compared at baseline and the case group investigated further over four time points (baseline, 12h, 24h and 5-7 days). Fractal analysis was performed, as well as current markers of coagulation, inflammatory markers and point-of-care tests, Thromboelastography and Multiplate analysis. RESULTS: Fractal dimension did not differ between groups at admission (1.73±0.06 and 1.72±0.1), and fell within the healthy index normal range (1.74±0.7), suggesting a normal clot microstructure in the early period after burn. Fractal dimension significantly reduced from baseline over the first 24h following injury (1.59±0.03 p<0.005), indicating a significant reduction in mechanical clot strength and functionality consistent with a hypocoagulable state, not identified with other markers. CONCLUSIONS: This is the first study to quantify the changes in clot microstructure following burn injury. This study confirms clot microstructure is significantly altered during the first 24h after burn, with the production of a weaker, more porous fibrin clot, consistent with a hypocoagulable state.

An 18-year Study of Malignant Melanoma in Childhood and Adolescence.

Malignant melanoma is rare in childhood and adolescence. Diagnostic uncertainty and misdiagnosis often lead to delayed treatment. METHODS: We evaluated children and adolescents under 20 years of age presenting with malignant melanoma at our institution over an 18-year period. Data were collected, analyzed, and interpreted, following which findings were compared with the existing literature. RESULTS: Twenty-four patients were included in the study with mean follow-up of 61.8 months. Males comprised 54% of cases. On presentation, 33% of children had melanoma of s thickness 2-4 mm and 34% had stage III disease. Younger children presented with thicker melanomas, differing subtypes, and more advanced stage disease compared with older children. Extremities were the most common sites affected (42%). Dissection of the draining lymph node basins was undertaken in 38% of cases. Overall survival was 92%. CONCLUSIONS: Tumor subtype, biology, hormonal influence, and lymph node status are all important prognostic factors in malignant melanoma in childhood and adolescence. Compared with adults, children presenting with thicker melanomas and more advanced stage disease generally have more favorable outcomes and a better survival. Plastic surgeons, commonly encountering skin lesion in children, must maintain a high index of suspicion so that early excision and sentinel lymph node biopsy may be promptly offered to patients with melanoma.

The impact of socio-economic deprivation on burn injury: A nine-year retrospective study of 6441 patients.

INTRODUCTION: Low socio-economic status is thought to be associated with increased burn risk, however the significance and generalisability across different populations and cultures has been questioned. METHODS: A nine-year retrospective study of burn presentations to a large teaching hospital (2005-2014) was performed to investigate the association between socio-economic status and burns. Demographic and injury data was collected via the trust 'Information portal'. The Welsh Index of Multiple: Deprivation 2011 was used to score for socio-economic status. Chi-squared test and Odds Ratios were calculated and statistical significance defined as p<0.05 throughout. RESULTS: 6441 burns were identified, with 755 (11.7%) admitted. Overall incidence rates were the highest published in the UK (0.35/1000/year) with sub group analysis showing the highest rates in under fives and males. Significant relationships between both age and burn mechanism and gender and burn mechanism (p=0.0005) were identified. Scald (67.1%) was the most common mechanism with the upper limb (48%) most commonly burned. Chi square analysis demonstrated a significant relationship between socio-economic deprivation, age and burn incidence (p≤0.0005), with a disproportionately high number of burns in patients under the age of 16 in the most deprived quintile (OR 1.23; 95% CI 1.06-1.44). CONCLUSION: This study specifically highlights patients under the age of 16 living in poorer socio-economic areas as the most at risk of suffering burns receiving hospital attention. This study demonstrates burns as a significant public health issue, and the results should aid in designing specific burn prevention strategies to target high-risk groups.

Nanotechnology for Stimulating Osteoprogenitor Differentiation.

BACKGROUND: Bone is the second most transplanted tissue and due to its complex structure, metabolic demands and various functions, current reconstructive options such as foreign body implants and autologous tissue transfer are limited in their ability to restore defects. Most tissue engineering approaches target osteoinduction of osteoprogenitor cells by modifying the extracellular environment, using scaffolds or targeting intracellular signaling mechanisms or commonly a combination of all of these. Whilst there is no consensus as to what is the optimal cell type or approach, nanotechnology has been proposed as a powerful tool to manipulate the biomolecular and physical environment to direct osteoprogenitor cells to induce bone formation. METHODS: Review of the published literature was undertaken to provide an overview of the use of nanotechnology to control osteoprogenitor differentiation and discuss the most recent developments, limitations and future directions. RESULTS: Nanotechnology can be used to stimulate osteoprogenitor differentiation in a variety of way. We have principally classified research into nanotechnology for bone tissue engineering as generating biomimetic scaffolds, a vector to deliver genes or growth factors to cells or to alter the biophysical environment. A number of studies have shown promising results with regards to directing ostroprogenitor cell differentiation although limitations include a lack of in vivo data and incomplete characterization of engineered bone. CONCLUSION: There is increasing evidence that nanotechnology can be used to direct the fate of osteoprogenitor and promote bone formation. Further analysis of the functional properties and long term survival in animal models is required to assess the maturity and clinical potential of this.

Pilot project in rural western Madhya Pradesh, India, to assess the feasibility of using LED and solar-powered lanterns to remove kerosene lamps and related hazards from homes.

BACKGROUND: Globally, 300,000 deaths are estimated to occur annually and the incidence is far greater as a large majority of burns are small and go unreported. Ninety-five percent of the global burden of burns is found in low- and middle-income countries; however, there is relatively little in the literature regarding effective primary prevention in these areas. Flame is the most common cause of burn in Madhya Pradesh, the central state of India. The most common demographic among the burn unit inpatient of Choithram hospital Indore, is young women from 21 to 40 years of age, whose burns are primarily caused by kerosene lamps. A non electrical source of illumination is essential for every household in rural areas due to the infrequent and poor power supply. At the baseline, 23 kerosene lamp burns were reported by villagers in the past 5 years among the study population of this pilot project. METHOD: A pilot project to investigate the strategies for reducing the incidence of domestic burns in rural villages around the city of Indore was performed, by replacing kerosene lamps with safer and more sustainable alternatives, including solar-powered and light-emitting diode (LED) lamps. A total of 1042 households were randomly chosen from 18 villages within the Malwa region of Madhya Pradesh (population of 28,825) to receive the alternative light source (670 LED and 372 solar lamps). We investigated the efficacy of this strategy of reducing the incidence of burns, measured the social acceptance by villagers, and quantified the cost implications and availability of LED lamps in rural communities with a high incidence of burns. RESULTS: Replacing kerosene lamps with LED and solar alternatives was deemed socially acceptable by 99.34% of the participants and reduced the cost of lighting for impoverished rural villagers by 85% over 1 year. We successfully demonstrated a significant decrease in the use of kerosene lamps (p<0.01). More evidence is required to investigate the efficacy of this strategy in reducing burns. CONCLUSION: This pilot study highlights the viability of the approach of replacing kerosene lamps as an effective primary prevention strategy for reducing burns in rural areas. However, barriers remain to the wider adoption of these lamps, including accessibility and availability for the populations of rural India.

The oldest reported mirror hand? The curse of the coal-house frog!

Despite being one of the rarest congenital upper limb abnormalities, a wide spectrum of the typical mirror hand has been described in the literature. We report a very interesting case of a new variant of mirror hand presenting in a 78-year-old man. The unique features of the case include the age at diagnosis, the anatomical features present and the acquired function despite no form of reconstructive surgery.

Change in operative workload for rheumatoid disease of the hand: 1,109 procedures over 13 years.

Orthopaedic literature regarding lower limb joints reports a decline in operative management of rheumatoid arthritis since the 1980s. We investigated whether the demand for hand surgery for rheumatoid disease had changed over the last 13 years in our unit. Data for all patients undergoing operative treatment for rheumatoid arthritis of the hand and wrist over a 13-year period were analysed. Between 1996 and 2009, 1,069 patients with rheumatoid disease (182 men, 887 women) underwent a total of 1,109 hand surgery procedures. The operations were synovectomy (430, 39%), arthroplasty (252, 23%), arthrodesis (194, 18%) and tendon surgery (233, 21.0%). Linear regression analysis showed a statistically significant decrease in the number of synovectomies, arthroplasties and arthrodeses between 1996 and 2009, but no decrease in tendon surgery. We explore possible factors responsible for this change in operative workload.

Sting-ray injuries to the hand: case report, literature review and a suggested algorithm for management.

Sting-ray injuries have recently had high profile media coverage following a rare fatality. However, minor injuries to the hands and feet are common. We present a case of a sting-ray injury to the hand. This was washed out under local anaesthetic at the local emergency department and was a delayed presentation to a specialist hand surgeon, 1 month post injury with severe pain. Ultrasound scan showed synovitis of the palm, confirmed at synovectomy the following day, along with frankly necrotic lumbrical muscles. Histology showed extensive low grade chronic inflammation. At 1 month follow up the patient was pain free and making good progress with a full and functional range of movement. We review the available literature and discuss the circumstances and pathophysiology of the sting-ray sting, the most appropriate first aid management, need for prompt surgical exploration and wound debridement and the possible complications. We would also like to suggest an algorithm for the management of sting-ray injuries to the hand.

Post operative monitoring of microvascular breast reconstructions using the implantable Cook-Swartz doppler system: a study of 145 probes & technical discussion.

INTRODUCTION: Accurate post operative assessment of free tissue transfers is challenging despite all the subjective and objective techniques available today. In our continual search to optimise patient outcomes, we introduced the Cook-Swartz probe into our clinical practice in May 2006. METHODS: We present our single centre experience in 103 patients undergoing 121 microvascular breast reconstructions and monitored using implantable Cook-Swartz venous dopplers between May 2006 and January 2008. RESULTS: In total, we used 145 probes on 121 microvascular breast reconstructions (DIEP=102, SIEP=15, SGAP=4) in 103 female patients. The mean operative time was 4h and 55 min (mu=295; range 117-630; ó+/-101 min) and we suffered 2 complete flap losses. A problem with the audible signal was noted in 15 patients (4 intra-operatively). We revised 14 of the 15. All fourteen had compromised anastomoses. In the remaining case, the patient was not returned to theatre as the primary surgeon was confident there were no other signs of vascular compromise. Overall, when using the venous doppler probe we found a false positive rate of 6.7% and 0% false negatives. DISCUSSION: We advocate the use of a Cook-Swartz probe which has been well received by both surgeons, nursing staff and patients, as an adjunct to traditional clinical monitoring techniques. We also include a comprehensive experience based technical discussion concerning its application, attachment, use and post-operative removal.