Socio-economic and ethnic disparities in childhood cancer survival, Yorkshire, UK.

BACKGROUND: Establishing the existence of health inequalities remains a high research and policy agenda item in the United Kingdom. We describe ethnic and socio-economic differences in paediatric cancer survival, focusing specifically on the extent to which disparities have changed over a 20-year period. METHODS: Cancer registration data for 2674 children (0-14 years) in Yorkshire were analysed. Five-year survival estimates by ethnic group (south Asian/non-south Asian) and Townsend deprivation fifths (I-V) were compared over time (1997-2016) for leukaemia, lymphoma, central nervous system (CNS) and other solid tumours. Hazard ratios (HR: 95% CI) from adjusted Cox models quantified the joint effect of ethnicity and deprivation on mortality risk over time, framed through causal interpretation of the deprivation coefficient. RESULTS: Increasing deprivation was associated with significantly higher risk of death for children with leukaemia (1.11 (1.03-1.20)) and all cancers between 1997 and 2001. While we observed a trend towards reducing differences in survival over time in this group, a contrasting trend was observed for CNS tumours whereby sizeable variation in outcome remained for cases diagnosed until 2012. South Asian children with lymphoma had a 15% reduced chance of surviving at least 5 years compared to non-south Asian, across the study period. DISCUSSION: Even in the United Kingdom, with a universally accessible healthcare system, socio-economic and ethnic disparities in childhood cancer survival exist. Findings should inform where resources should be directed to provide all children with an equitable survival outcome following a cancer diagnosis.

Experiences of UK and Irish family carers of people with profound and multiple intellectual disabilities during the COVID-19 pandemic.

BACKGROUND: People with profound and multiple intellectual disabilities (PMID) have high and intensive support needs that ordinarily place significant strain on family carers. This was further heightened by the removal of many external supports during the COVID-19 pandemic. We sought to explore the experiences of family carers of people with PMID during the COVID-19 pandemic and understand what the longer-term impact might be on their lives. METHODS: Focus group interviews (n = 32) were conducted with family carers (n = 126) from the four countries of the UK and the Republic of Ireland. Participants were asked questions relating to their experiences of the COVID-19 pandemic, coping strategies, and challenges faced. All focus groups were conducted using the online platform, Zoom. These were audio recorded, transcribed verbatim and analysed employing inductive thematic analysis. FINDINGS: Three main themes were generated from the data including (1.0) COVID-19 as a double-edged sword (2.0), The struggle for support (3.0), Constant nature of caring. These included 11 subthemes. (1.1) 'COVID-19 as a catalyst for change', (1.2) 'Challenges during COVID-19: dealing with change', (1.3) 'Challenges during COVID-19: fear of COVID-19', (1.4); 'The online environment: the new normal' (2.1) 'Invisibility of male carers', (2.2) 'Carers supporting carers', (2.3) 'The only service you get is lip service: non-existent services', (2.4); 'Knowing your rights' (3.1) 'Emotional response to the caring role: Feeling devalued', (3.2) 'Emotional response to the caring role: Desperation of caring', (3.3) 'Multiple demands of the caring role.' CONCLUSIONS: The COVID-19 pandemic presented immense challenges to family carers of people with PMID but also provided some opportunities. Families had already struggled to receive many of the supports and services to which they were entitled to only to have these removed at the onset of the pandemic. The experiences of male carers have been largely absent from the literature with this research showing they want to be included in decision making and require tailored support services. Service providers should see the end of the COVID-19 pandemic as providing opportunity to re-examine current provision and design services with family carers. As the direct threat from COVID-19 diminishes and the experiences of those who lived through this period come to the fore, there is a need to re-examine current models and provision of support to family carers to better meet their needs.

Impact of the COVID-19 pandemic on family carers of those with profound and multiple intellectual disabilities: perspectives from UK and Irish Non-Governmental Organisations.

BACKGROUND: Family carers of people with profound and multiple intellectual disabilities (PMID) experienced a reduction in healthcare services due to the COVID-19 pandemic. Many subsequently turned to Non-Governmental Organisations who worked to support families. However, little research has sought to capture the experiences of family carers or identify effective interventions which might support them. To address these concerns we explored the views of Non-Governmental sector workers across the UK and Ireland who supported families people with PMID during the COVID-19 pandemic. We also sought to explore their views on the characteristics of online support programmes for family carers.  METHODS: This study employed a qualitative design using focus groups with participants (n = 24) from five Non-Governmental Organisations across the UK and Ireland. A focus group guide included questions on challenges, supports, coping and resources which helped during lockdown restrictions. Focus groups were held online, were audio recorded and transcribed verbatim. The resulting transcripts were pseudonymised and subjected to thematic analysis. FINDINGS: Four themes were identified (i) 'mental and emotional health', (ii) 'they who shout the loudest' (fighting for services), (iii) 'lack of trust in statutory services' and (iv) 'creating an online support programme'. Mental and emotional health emerged as the most prominent theme and included three subthemes named as 'isolation', 'fear of COVID-19' and 'the exhaustion of caring'. CONCLUSIONS: The COVID-19 pandemic has increased the vulnerability of family carers who were already experiencing difficulties in accessing services and supports for their families. While Non-Governmental Organisations have been a crucial lifeline there is urgent need to design services, including online support programmes, in partnership with family carers which adequately address their needs.

Identification of a unique anti-Ro60 subset with restricted serological and molecular profiles.

Anti-Ro60 is one of the most common and clinically important serum autoantibodies that has a number of diagnostic and predictive capabilities. Most diagnostic laboratories report this simply as a qualitative positive/negative result. The objective of this study was to examine the clinical and serological relevance of a novel subset of anti-Ro60 in patients who display low levels of anti-Ro60 (anti-Ro60low ). We retrospectively identified anti-Ro60 sera during a 12-month period at a major immunopathology diagnostic laboratory in Australia. These all were anti-Ro60-precipitin-positive on the diagnostic gold standard counter-immuno-electrophoresis (CIEP). Lineblot immunoassay was used to stratify patients into either anti-Ro60low or anti-Ro60high subsets. We compared the medical and laboratory parameters associated with each group. Enzyme-linked immunosorbent assay (ELISA) and mass spectrometry techniques were used to analyse the serological and molecular basis behind the two subsets. Anti-Ro60low patients displayed less serological activity than anti-Ro60high patients with less intermolecular spreading, hypergammaglobulinaemia and less tendency to undergo anti-Ro60 isotype-switching than anti-Ro60high patients. Mass spectrometric typing of the anti-Ro60low subset showed restricted variable heavy chain subfamily usage and amino acid point mutations. This subset also displayed clinical relevance, being present in a number of patients with systemic autoimmune rheumatic diseases (SARD). We identify a novel anti-Ro60low patient subset that is distinct from anti-Ro60high patients serologically and molecularly. It is not clear whether they arise from common or separate origins; however, they probably have different developmental pathways to account for the stark difference in immunological maturity. We hence demonstrate significance to anti-Ro60low and justify accurate detection in the diagnostic laboratory.

Synthesis of 2-Alkynoates by Palladium(II)-Catalyzed Oxidative Carbonylation of Terminal Alkynes and Alcohols.

A homogeneous Pd(II) catalyst, utilizing a simple and inexpensive amine ligand (TMEDA), allows 2-alkynoates to be prepared in high yields by an oxidative carbonylation of terminal alkynes and alcohols. The catalyst system overcomes many of the limitations of previous palladium carbonylation catalysts. It has an increased substrate scope, avoids large excesses of alcohol substrate and uses a desirable solvent. The catalyst employs oxygen as the terminal oxidant and can be operated under safer gas mixtures.

Kitchen knives and homicide: a systematic study of people charged with murder in the Lothian and Borders region of Scotland.

A recent English study demonstrated high rates of kitchen knife use in homicides by mentally disordered offenders subject to independent inquiries. Everyone accused of homicide in Scotland undergoes psychiatric examination; all such evaluations in a Scottish region between 2006 and 2011 were systematically analysed to identify homicide characteristics. It was hypothesised that kitchen knives would be the commonest sharp instruments used, and would be associated with unplanned domestic homicide against known victims, with no independent association with mental disorder. Kitchen knives were used in 32 of 55 homicides: 94% of 34 sharp object homicides (p < 0.05). No independent association was found between kitchen knife use and planning, location, relationship, intoxication or mental disorder. Kitchen knife use in homicide appears to be a significant public health issue, and not only in the mentally disordered population. Research is recommended into kitchen knife use in non-fatal violence, and weapon control in populations at increased risk of knife violence.

Surgery under siege: A case study of leg amputation in 18th century Louisbourg, Nova Scotia, Canada.

OBJECTIVE: Paleopathological analysis of a below-knee amputation was conducted to explore the sociocultural reasons why the amputation took place. MATERIALS: Older adolescent male (18-21 years) from the New Englander mass burial at the 18th century Fortress of Louisbourg. METHODS: Macroscopic assessment and archival data. RESULTS: A surgical amputation of the right tibia and fibula, distal to the knee was identified. The cross-sectional diaphysis of the leg has kerf marks and a splinter (breakaway point) at the posterior-lateral border of the tibia suggesting the leg gave way from its own weight or was manually removed once most of the sawing was complete. CONCLUSIONS: Archival records suggest frostbite from prolonged exposure to freezing temperatures and trauma from unsafe working conditions at the Fortress were the main causes that led to amputation. SIGNIFICANCE: This case study highlights the importance of contextualizing cases of amputation to understand factors leading to the amputation procedure and techniques used in the past, and the social and living conditions of the individual. LIMITATIONS: Observations were restricted to skeletal material as soft tissue decomposed and there was no material evidence suggestive of amputation associated with this individual in their grave. SUGGESTIONS FOR FUTURE RESEARCH: Full trauma assessment of the Fortress of Louisbourg skeletal collection to provide additional insight into injury sustained at Louisbourg and 18th century surgical practices.

The first 100 thrombolysis cases in a novel Scottish mesh telestroke system.

Stroke thrombolysis has been a major driver for change within stroke services. However, until recently its widespread application has been limited to tertiary centres. Transfer to tertiary care can lead to significant delays in thrombolysis. We developed a novel mesh telestroke network, which allows stroke specialists to make videoconference-based thrombolysis decisions either from one of three stroke units or from home. We report data on the first 100 patients treated using this model and retrospectively review the first 100 strokes thrombolysed with tissue plasminogen activator across three stroke units. Prospectively collected data were extracted from the Stroke Audit In Lanarkshire database. Case notes were retrieved for clarification when necessary. Outcome measures were timings from symptom onset to infusion, post-thrombolysis symptomatic intracerebral haemorrhage and death. Fifty-one percent of cases were assessed by telestroke link. Median symptom onset to thrombolysis was 160 min (IQR 125-190). There were two symptomatic intracerebral haemorrhages, both in patients assessed face-to-face. Overall mortality was 14%. Our experience of tissue plasminogen activator is comparable to UK data extracted from SITS-MOST in overall timings and complication rates. This model of telemedicine could be replicated to provide safe thrombolysis to areas with challenging infrastructure, geography or insufficient stroke specialist cover.

Characterization of fennel germplasm for physiological persistence and drought recovery: Association with biochemical properties.

In the perennial medicinal plant fennel (Foeniculum vulgare), persistence over years, production stability, and successful post-drought recovery are as important as plant productivity. Characterization of productivity, post-drought recovery, persistency and their association with phytochemical properties has not yet been performed in fennel. In this study, 64 fennel genotypes (from 23 different countries) from four subspecies/varieties including F. vulgare ssp. piperitum, F. vulgare var. vulgare and F. vulgare var. dulce and F. vulgare var. azoricum were evaluated in the field over four years (2015-2018), then was assessed for post-drought recovery over the next two years (2019-2020). High genotypic variation was observed among genotypes and subspecies. Based on the GC-MS analysis, trans-anethole (22.4-90.6%), estragole (2.1-25.8%), fenchone (4.9-19.8%), and limonene (0.5-11.9%) are major components in the essential oils of the studied germplasm. The highest persistence and the lowest average post-drought recovery belonged to ssp. piperitum. This subspecies also had the highest amount of limonene, fenchone, and estragole and the lowest amount of trans-anethole compared to other subspecies. The highest essential oil content and stability was observed in var. dulce. Seed yield and persistence were found to be negatively associated, suggesting that selection for more productivity may indirectly promote less persistent genotypes. Post-drought recovery was negatively associated with two main phytochemical compounds of essential oil, fenchone and estragole, but positively associated with trans-anethole. Persistence had negative correlation with estragole content. Results indicated that indirect selection for post-drought recovery and persistence may be possible through selection for phytochemical properties. The negative correlation between some essential oil components may indicate that some are isomers, which can limit the ability to select for certain combinations. Superior genotypes identified in this study can be used to construct populations for future studies and as parents of crosses to develop new varieties.

Evaluating a novel approach to stimulate open science collaborations: a case series of "study-a-thon" events within the OHDSI and European IMI communities.

Objective: We introduce and review the concept of a study-a-thon as a catalyst for open science in medicine, utilizing harmonized real world, observation health data, tools, skills, and methods to conduct network studies, generating insights for those wishing to use study-a-thons for future research. Materials and Methods: A series of historical study-a-thons since 2017 to present were reviewed for thematic insights as to the opportunity to accelerate the research method to conduct studies across therapeutic areas. Review of publications and experience of the authors generated insights to illustrate the conduct of study-a-thons, key learning, and direction for those wishing to conduct future such study-a-thons. Results: A review of six study-a-thons have provided insights into their scientific impact, and 13 areas of insights for those wishing to conduct future study-a-thons. Defining aspects of the study-a-thon method for rapid, collaborative research through network studies reinforce the need to clear scientific rationale, tools, skills, and methods being collaboratively to conduct a focused study. Well-characterized preparatory, execution and postevent phases, coalescing skills, experience, data, clinical input (ensuring representative clinical context to the research query), and well-defined, logical steps in conducting research via the study-a-thon method are critical. Conclusions: A study-a-thon is a focused multiday research event generating reliable evidence on a specific medical topic across different countries and health systems. In a study-a-thon, a multidisciplinary team collaborate to create an accelerated contribution to scientific evidence and clinical practice. It critically accelerates the research process, without inhibiting the quality of the research output and evidence generation, through a reproducible process.

Randomized in situ clinical study comparing the ability of two new desensitizing toothpaste technologies to occlude patent dentin tubules.

OBJECTIVE: To compare the ability of two new desensitizing toothpaste technologies (one a 5% NovaMin-based toothpaste and the other an 8% arginine-based toothpaste) to occlude patent dentin tubules in a clinical environment relative to a negative control of water and a control toothpaste after four days of twice-daily brushing and dietary acidic challenges. METHODS: The study design was a single-center, single-blind, randomized, split-mouth, four-treatment, two-period, crossover, in situ clinical study. Healthy subjects wore two lower intra-oral appliances, retaining four dentin samples for four treatment days for each period of the clinical study. Samples were brushed twice daily with a test product (days 1-4), with an additional acidic challenge introduced on two selective days. Scanning electron microscopy (SEM) images were taken of the dentin surface, and dentinal tubule occlusion assessed using a categorical scale. RESULTS: The results demonstrated that the 5% NovaMin toothpaste was statistically superior at occluding patent dentin tubules compared to water (p = 0.009) and the control toothpaste (p = 0.02) at day 4. In contrast, the treatment effect resulting from the 8% arginine toothpaste did not demonstrate the same degree of occlusive propensity, showing no significant difference to the water and control toothpaste at the day 4 time point. CONCLUSION: Application of the 5% NovaMin toothpaste to dentin showed better dentin tubule occlusion and retention abilities in an oral environment under dietary acid challenge conditions, more so than the 8% arginine toothpaste technology. Given modern dietary habits and practices, these results highlight differences in the acid resistance properties of occlusion technologies, and a potential impact on clinical performance.

The need for a transparent, ethical, and successful relationship between academic scientists and the pharmaceutical industry: a view of the Group for the Respect of Ethics and Excellence in Science (GREES).

UNLABELLED: This paper provides recommendations for fair and unbiased relationship between academic scientists and the pharmaceutical industry. INTRODUCTION: Real or perceived problems in the relationship between academics and the industry have been the subject of much recent debate. It has been suggested that academic clinicians should sever all links with the industry-a view that is rarely challenged. METHODS: Academic experts and members of the pharmaceutical industry were invited to an expert consensus meeting to debate this topic. This meeting was organized by the Group for the Respect of Ethics and Excellence in Science. Conflict of interest, competing interest, right and duties of academic scientist, authorship, and staff and student education were discussed. RESULTS: Guidelines for a transparent, ethical, strong, and successful partnership between the academic scientist and the pharmaceutical industry have been provided. CONCLUSIONS: The Group support interactions between the industry and clinicians provided that it is transparent and ethical.

The composition of hydrogels for cartilage tissue engineering can influence glycosaminoglycan profile.

The injectable and hydrophilic nature of hydrogels makes them suitable candidates for cartilage tissue engineering. To date, a wide range of hydrogels have been proposed for articular cartilage regeneration but few studies have quantitatively compared chondrocyte behaviour and extracellular matrix (ECM) synthesis within the hydrogels. Herein we have examined the nature of ECM synthesis by chondrocytes seeded into four hydrogels formed by either temperature change, self-assembly or chemical cross-linking. Bovine articular cartilage chondrocytes were cultured for 14 days in Extracel, Pluronic F127 blended with Type II collagen, Puramatrix and Matrixhyal. The discriminatory and sensitive technique of fluorophore-assisted carbohydrate electrophoresis (FACE) was used to determine the fine detail of the glycosaminoglycans (GAG); hyaluronan and chondroitin sulphate. FACE analysis for chondroitin sulphate and hyaluronan profiles in Puramatrix closely matched that of native cartilage. For each hydrogel, DNA content, viability and morphology were assessed. Total collagen and total sulphated GAG production were measured and normalised to DNA content. Significant differences were found in total collagen synthesis. By day 14, Extracel and Puramatrix had significantly more total collagen than Matrixhyal (1.77+/-0.26 microg and 1.97+/-0.26 microg vs. 0.60+/-0.26 microg; p<0.05). sGAG synthesis occurred in all hydrogels but a significantly higher amount of sGAG was retained within Extracel at days 7 and 14 (p<0.05). In summary, we have shown that the biochemical and biophysical characteristics of each hydrogel directly or indirectly influenced ECM formation. A detailed understanding of the ECM in the development of engineered constructs is an important step in monitoring the success of cartilage regeneration strategies.

Mobile radiography at a music festival.

Limb injuries are common at music festival sites and traditionally patients seen by on-site medical services require referral to hospital emergency departments for radiographic exclusion of bony injury. This takes clinical personnel off site, increases demand on local emergency departments and is inconvenient for revellers. This is an audit of the use of a portable digital radiography system at the Virgin music festival in Staffordshire over a 3-year period.

Clinical in situ study investigating abrasive effects of two commercially available toothpastes.

The aim of this study was to determine if the abrasive effect on dentine of two commercially available toothpastes, known to vary in their in vitro abrasive levels, can be differentiated in an in situ model after 10 days, assessed by contact profilometry. This was a single centre, single blind, randomized, split mouth, two treatment, in situ study, in 34 healthy subjects, evaluating the abrasive effects of two marketed desensitizing toothpastes, (Colgate Sensitive Multi Protection toothpaste - C; Sensodyne Total Protection - S). Subjects wore bi-lateral, lower buccal appliances, each fitted with four dentine sections which were power brushed three times a day with the treatment regimen. Each subject received two toothpaste treatments for 10 days during the treatment period. Samples were measured at baseline and day 10 by contact and non-contact profilometry and day 5 by contact profilometry. Thirty-four subjects were included in the efficacy analysis. Results from contact profilometry showed statistically significant (P < 0.0001) dentine loss compared to baseline at day 5 and 10 for both pastes. At each time point, C showed statistically significantly greater dentine loss than S, P < 0.0001. After 10 days treatment, the difference in dentine loss between the pastes was 1.4 microm. The non-contact profilometry data showed similar trends. After 10 days of treatment, C showed statistically significantly greater dentine loss than S, with treatment difference of 0.9 microm, P = 0.0057. The methodology used has successfully differentiated between the abrasivity of the two pastes in respect of dentine surface loss over time in an in situ environment.

Guidelines for Clinical Target Volume Definition for Perineural Spread of Major Salivary Gland Cancers.

AIMS: Postoperative radiotherapy is the standard of care for resected major salivary cancers that are at risk of locoregional recurrence. Of the various histological subtypes, perineural invasion is most common in adenoidcystic carcinomas of the three major salivary glands - parotid, submandibular and sublingual. The clinical target volume (CTV) for these cases must include the relevant cranial nerve pathways at risk. A contouring atlas was devised for delineation of the CTV of the nerves supplying the major salivary glands. MATERIALS AND METHODS: Using standard anatomy texts and e-anatomy sources the nerves supplying the major salivary glands were identified. Subsequently the pathways of the nerves were drawn on an archived patient's planning computed tomography scan. RESULTS: The innervation of the major salivary glands has been identified and studied. Both bone and soft tissue CTVs have been delineated. A full set of images and CTVs of all the relevant transverse computed tomography slices has been archived, a number of which are printed in this article. CONCLUSIONS: Variation in CTV delineation is a recognised problem in a variety of anatomic sites. Guidelines and atlases can standardise practice and may improve the safety and efficacy of therapy. An atlas has been generated to guide clinicians in delineating the CTVs for perineural spread in major salivary gland cancers.

Revisiting classic MRI findings of venous malformations: Changes in protocols may lead to potential misdiagnosis.

Introduction Magnetic resonance imaging (MRI) is most sensitive and specific for characterizing venous malformations (VMs). VMs typically demonstrate central enhancement on delayed-contrast imaging. Fluid-fluid levels (FFLs) are uncommon in VMs and common in lymphatic malformations (LMs). Technology has advanced since the initial description of these findings. Rates of detection of these MRI findings in VMs may have changed as MRI technology and techniques have evolved. Methods and methods A prospectively maintained database from a multidisciplinary vascular anomalies clinic was reviewed to identify patients with final diagnosis of VM or LM. Patients with reviewable contrast-enhanced MRIs were selected, reviewing the oldest MRI studies in the database against the newest MRI studies to identify equal numbers of patients from the temporal extremes. Imaging was reviewed to assess for presence of FFLs. Enhancement was quantified by measuring signal in the same location of the lesion both on pre- and postcontrast sequences Results Forty patients were identified for analysis. Twenty studies with sufficient archived imaging for review were performed between 1995 and 2006; 20 such studies were performed between 2011 and 2012. The new imaging cohort had higher rates of FFL visualization ( p = 0.001). Correlation was found between time to imaging following contrast and degree of enhancement ( p < 0.001). Inverse correlation was found between scan date and time to contrast ( p = 0.001) and scan date and enhancement ( p = 0.021). Conclusion FFLs should no longer be considered exclusionary for the diagnosis of VMs. Timing following contrast administration should be maximized to increase degree of enhancement to confirm the diagnosis of VMs.

Palladium(II)-Catalysed Aminocarbonylation of Terminal Alkynes for the Synthesis of 2-Ynamides: Addressing the Challenges of Solvents and Gas Mixtures.

2-Ynamides can be synthesised through PdII catalysed oxidative carbonylation, utilising low catalyst loadings. A variety of alkynes and amines can be used to afford 2-ynamides in high yields, whilst overcoming the drawbacks associated with previous oxidative methods, which rely on dangerous solvents and gas mixtures. The use of [NBu4 ]I allows the utilisation of the industrially recommended solvent ethyl acetate. O2 can be used as the terminal oxidant, and the catalyst can operate under safer conditions with low O2 concentrations.