Neighborhood disadvantage, race, and clinical outcomes in neuromyelitis optica spectrum disorder.

BACKGROUND: Little is known about the relationship between neighborhood disadvantage and neuromyelitis optica spectrum disorder (NMOSD) outcomes. OBJECTIVE: The objective is to determine the impact of neighborhood disadvantage on time from symptom onset to diagnosis and annualized relapse rate (ARR). METHODS: Neighborhood disadvantage were captured with the Area Deprivation Index (ADI), a validated measure of neighborhood-level disadvantage. Negative binomial regression models assessed the impact of ADI on diagnostic delay (⩾3 months between symptom onset and diagnosis) and ARR. RESULTS: A total of 158 NMOSD patients were identified, a majority of whom were White (56.3%) and female (89.9%) with a mean age of 46 years at diagnosis. The ADI did not significantly affect odds of diagnostic delay (odds ratio (OR) = 0.99, p = 0.26). In univariable models, the ADI was not significantly associated with ARR (OR = 1.004, p = 0.29), but non-White race (OR = 1.541, p = 0.02) and time on immunosuppressive therapies (ISTs; OR = 0.994, p = 0.03) were. White patients used IST for an average of 81% of the follow-up period, compared to an average of 65% for non-White patients (p < 0.01). CONCLUSION: No significant relationship between neighborhood-level disadvantage and diagnostic delay or ARR in NMOSD patients was observed. Non-White patients had a higher ARR, which may be related to less IST use.

A stochastic model for topographically influenced cell migration.

Migrating cells traverse a range of topographic configurations presented by the native extracellular environment to conduct their physiologic functions. It is well documented cells can modulate their behaviour in response to different topographic features, finding promising applications in biomaterial and bioimplant design. It is useful, in these areas of research, to be able to predict which topographic arrangements could be used to promote certain patterns of migration prior to laboratory experimentation. Despite a profusion of study and interest shown in these fields by experimentalists, the related modelling literature is as yet relatively sparse and tend to focus more on either cell-matrix interaction or morphological responses of cells. We propose a mathematical model for individual cell migration based on an Ornstein-Uhlenbeck process, and set out to see if the model can be used to predict migration patterns on 2-d isotropic and anisotropic topographies, whose characteristics can be broadly described as either uniform flat, uniform linear with variable ridge density or non-uniform disordered with variable feature density. Results suggest the model is capable of producing realistic patterns of migration for flat and linear topographic patterns, with calibrated output closely approximating NIH3T3 fibroblast migration behaviour derived from an experimental dataset, in which migration linearity increased with ridge density and average speed was highest at intermediate ridge densities. Exploratory results for non-uniform disordered topographies suggest cell migration patterns may adopt disorderedness present in the topography and that 'distortion' introduced to linear topographic patterns may not impede linear guidance of migration, given its magnitude is bounded within certain limits. We conclude that an Ornstein-Uhlenbeck based model for topographically influenced migration may be useful to predict patterns of migration behaviour for certain isotropic (flat) and anisotropic (linear) topographies in the NIH3T3 fibroblast cell line, but additional investigation is required to predict with confidence migration patterns for non-uniform disordered topographic arrangements.

The accuracy of parent/carer proxy-reporting of caries experience in children and association with socioeconomic circumstances: a cross-sectional data linkage study.

OBJECTIVES: To compare parent/carer proxy-reported dental caries experience of their 5-year-old child with epidemiological survey clinician examination of caries experience in the same children. To determine any differences in the accuracy by area-based socioeconomic group. METHODS: A cross-sectional data linkage study linked data from the Growing Up in Scotland (GUS) study and the National Dental Inspection Programme (NDIP) school epidemiology survey. Parent/carer proxy-reported caries experience was compared with clinician-measured caries experience on n=3008 children, and data were stratified by home-residential area-based socioeconomic deprivation levels (Scottish Index of Multiple Deprivation (SIMD)). Sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) were calculated overall and stratified by SIMD. RESULTS: Overall, parent/carer proxy-reporting had low sensitivity (42.3% 95%CI: 39.0, 45.7) that decreased with decreasing deprivation (SIMD-1(most deprived): 49.4% to SIMD-5 (least deprived): 37.2%). Specificity remained consistently high overall and across area-based socioeconomic deprivation levels (overall=96.2%, 95%CI: 95.3, 97.0; SIMD-1: 94.4% SIMD-5: 97.8%). In children whose parents/carers reported them to have caries experience (GUS) a high percentage were found to have caries experience (NDIP) (PPV=81.8%, 95%CI: 78.2, 84.9). CONCLUSION: Parent/carer proxy-reporting of caries experience in 5-year-old children had very low sensitivity and was lowest in children from the least deprived areas. In contrast, parents/carers who reported their child had caries experience did so reasonably accurately. This study concludes that proxy reporting caries experience is not sufficiently sensitive to replace clinician examination in assessing dental caries experience in surveys of child populations and highlights the importance of data linkage to routine datasets.

Maternal serum fructosamine levels and stillbirth: a case-control study of the Stillbirth Collaborative Research Network.

OBJECTIVE: To evaluate the association between maternal fructosamine levels at the time of delivery and stillbirth. DESIGN: Secondary analysis of a case-control study. SETTING: Multicentre study of five geographic catchment areas in the USA. POPULATION: All singleton stillbirths with known diabetes status and fructosamine measurement, and representative live birth controls. MAIN OUTCOME MEASURES: Fructosamine levels in stillbirths and live births among groups were adjusted for potential confounding factors, including diabetes. Optimal thresholds of fructosamine to discriminate stillbirth and live birth. RESULTS: A total of 529 women with a stillbirth and 1499 women with a live birth were included in the analysis. Mean fructosamine levels were significantly higher in women with a stillbirth than in women with a live birth after adjustment (177 ± 3.05 versus 165 ± 2.89 µmol/L, P < 0.001). The difference in fructosamine levels between stillbirths and live births was greater among women with diabetes (194 ± 8.54 versus 162 ± 3.21 µmol/L), compared with women without diabetes (171 ± 2.50 versus 162 ± 2.56 µmol/L). The area under the curve (AUC) for fructosamine level and stillbirth was 0.634 (0.605-0.663) overall, 0.713 (0.624-0.802) with diabetes and 0.625 (0.595-0.656) with no diabetes. CONCLUSIONS: Maternal fructosamine levels at the time of delivery were higher in women with stillbirth compared with women with live birth. Differences were substantial in women with diabetes, suggesting a potential benefit of glycaemic control in women with diabetes during pregnancy. The small differences noted in women without diabetes are not likely to justify routine screening in all cases of stillbirth. TWEETABLE ABSTRACT: Maternal serum fructosamine levels are higher in women with stillbirth than in women with live birth, especially in women with diabetes.

A Health Inequalities Impact Assessment of the surveillance of COVID-19 in asymptomatic patients attending dental settings in Scotland.

INTRODUCTION: A key aspect of the public health response to COVID-19 in Scotland was enhanced community surveillance, including testing in dental settings. Across Scotland, dental settings offered patients over 5-years-old the opportunity to participate in community surveillance of COVID-19. METHODS: A Health Inequalities Impact Assessment (HIIA) was conducted to understand the differential impacts the programme would have on the population and to improve the accessibility of the programme. HIIA is a tool to allow the assessment, understanding, and mitigation of impacts on people of a proposed policy or practice. It fulfils an organisational duty to meet the requirements of the Equality Act and Fairer Scotland Duty. The HIIA was conducted rapidly in parallel with the programme development. An action research approach included an online workshop, consultation, review of population data and a literature search. RESULTS: Adjustments were required to improve the programme's accessibility. Stakeholders, including dental teams from across Scotland were involved in the consultation and brought their front-line experience in different settings. Common issues identified included digital literacy and access, language and cultural barriers to participation, and issues relating to the implications of a positive COVID-19 result. Literature indicated limited evidence on the acceptability, accessibility, and equity of asymptomatic COVID-19 surveillance. CONCLUSION: This HIIA was conducted during the COVID-19 pandemic. As an example of good practice in tackling inequalities in access to programmes it should represent the benchmark for other similar initiatives.

The current state of PEEK implant osseointegration and future perspectives: a systematic review.

Polyetheretherketone (PEEK) has been considered as an alternative to replace surgical metal implants. Several medical applications, including dental and orthopaedic implants, need confirmed osseointegration before functional loading. The present study aims at providing a comprehensive systematic review of the evidence on PEEK implants' osseointegration. A systematic search was conducted using Cochrane library, MEDLINE (PubMed), Ovid MEDLINE, Web of Science and EMBASE databases. Publications were identified in accordance with specific inclusion and exclusion criteria. Eligibility screening, data extraction and quality assessment were performed. The review protocol was registered in PROSPERO (CRD42018116061). A total of 55 articles were reviewed and 29 of the most relevant that met the inclusion criteria were selected. Heterogeneity was identified among the included studies. Several approaches have been applied to enhance PEEK osseointegration, with most in vivo studies conducted on small-scale animal models but no study evaluating the osseointegration of PEEK under cyclic loading. However, PEEK modifications are demonstrated to enhance osseointegration preclinically. Collectively, the present review shows a shortage of evidence, including a lack of comprehensive assessment of osseointegration, the need for large-animal-model tests, the need to assess the effect of loading on the implants and the lack of randomised controlled clinical trials.

Cognitive processing speed in multiple sclerosis clinical practice: association with patient-reported outcomes, employment and magnetic resonance imaging metrics.

BACKGROUND AND PURPOSE: To analyze the relationship between cognitive processing speed, patient-reported outcome measures (PROMs), employment and magnetic resonance imaging (MRI) metrics in a large multiple sclerosis cohort. METHODS: Cross-sectional clinical data, PROMs, employment and MRI studies within 90 days of completion of the Processing Speed Test (PST), a technology-enabled adaptation of the Symbol Digit Modalities Test, were collected. MRI was analyzed using semi-automated methods. Correlations of PST score with PROMs and MRI metrics were examined using Spearman's rho. Wilcoxon rank sum testing compared MRI metrics across PST score quartiles and linear regression models identified predictors of PST performance. Effects of employment and depression were also investigated. RESULTS: In 721 patients (mean age 47.6 ± 11.4 years), PST scores were significantly correlated with all MRI metrics, including cord atrophy and deep gray matter volumes. Linear regression demonstrated self-reported physical disability, cognitive function, fatigue and social domains (adjusted R2  = 0.44, P < 0.001) as the strongest clinical predictors of PST score, whereas that of MRI variables included T2 lesion volume, whole-brain fraction and cord atrophy (adjusted R2  = 0.42, P < 0.001). An inclusive model identified T2 lesion volume, whole-brain fraction, self-reported upper extremity function, cognition and social participation as the strongest predictors of PST score (adjusted R2  = 0.51, P < 0.001). There was significant effect modification by depression on the relationship between self-reported cognition and PST performance. Employment status was associated with PST scores independent of age and physical disability. CONCLUSION: The PST score correlates with PROMs, MRI measures of focal and diffuse brain injury, and employment. The PST score is a feasible and meaningful measure for routine multiple sclerosis care.

Guidelines for the safe provision of anaesthesia in magnetic resonance units 2019: Guidelines from the Association of Anaesthetists and the Neuro Anaesthesia and Critical Care Society of Great Britain and Ireland.

There has been an increase in the number of units providing anaesthesia for magnetic resonance imaging and the strength of magnetic resonance scanners, as well as the number of interventions and operations performed within the magnetic resonance environment. More devices and implants are now magnetic resonance imaging conditional, allowing scans to be undertaken in patients for whom this was previously not possible. There has also been a revision in terminology relating to magnetic resonance safety of devices. These guidelines have been put together by organisations who are involved in the pathways for patients needing magnetic resonance imaging. They reinforce the safety aspects of providing anaesthesia in the magnetic resonance environment, from the multidisciplinary decision making process, the seniority of anaesthetist accompanying the patient, to training in the recognition of hazards of anaesthesia in the magnetic resonance environment. For many anaesthetists this is an unfamiliar site to give anaesthesia, often in a remote site. Hospitals should develop and audit governance procedures to ensure that anaesthetists of all grades are competent to deliver anaesthesia safely in this area.

Presenting symptoms and long-term survival in head and neck cancer.

OBJECTIVES: To assess how type and number of symptoms are related to survival in patients with head and neck cancer. DESIGN: Patients were followed up for over 10 years from the Scottish Audit of Head and Neck Cancer (national cohort of head and neck cancer patients in Scotland 1999-2001). September 2013, cohort was linked to national mortality data. First, second and third presenting symptoms were recorded at diagnosis. SETTING: National prospective audit-Scotland. PARTICIPANTS: A subset of 1589 patients, from the original cohort of 1895, who had cancer arising from one of the four main subsites; larynx, oropharynx, oral cavity and hypopharynx. MAIN OUTCOME MEASURES: Median survival in relation to patients' presenting symptoms. RESULTS: A total of 1146 (72%) males and 443 (28%) females, mean age at diagnosis 64 years (13-95). There was a significant difference in survival in relation to the number of the patient's presenting symptoms; one symptom had a median survival of 5.3 years compared with 1.1 years for three symptoms. Patients who presented with weight loss had a median survival of 0.8 years, compared to 4.2 years if they did not (P < .001). Patients who presented with hoarseness had a median survival of 5.9 years compared to 2.6 years without (P < .001). There was no significant difference in long-term survival for patients who presented with an ulcer, compared to those that did not (P = .105). CONCLUSIONS: This study highlights the importance of patients' presenting symptoms, giving valuable information in highlighting appropriate "red flag" symptoms and subsequent treatment planning and prognosis.

A genetic risk score that includes common type 2 diabetes risk variants is associated with gestational diabetes.

OBJECTIVE: Gestational diabetes (GDM) is characterized by maternal glucose intolerance that manifests during pregnancy. Because GDM resembles type 2 diabetes (T2DM), shared genetic predisposition is likely but has not been established. We tested the hypothesis that a genetic risk score (GRS) that included variants known to be associated with T2DM is associated with GDM. STUDY DESIGN: We conducted a case-control study using the Vanderbilt Medical Center biobank (BioVU) and calculated a simple-count GRS using 34 variants previously associated with T2DM or fasting glucose in the general population, or with GDM or glucose intolerance in pregnancy. We assessed the association of the GRS with GDM adjusting for maternal age, parity, and body mass index (BMI) and calculated the area under the curve for the receiver-operating characteristic curve (c-statistic). STUDY POPULATION: Among Caucasian women, we identified 458 cases of GDM and 1538 pregnant controls with normal glucose tolerance. RESULTS: Cases of GDM had a higher number of risk alleles compared to controls (38.9±4.0 vs 37.4±4.0 risk alleles, P=1.6×10-11 ). The GRS was significantly associated with GDM; the adjusted odds ratio associated with each additional risk allele was 1.10 (95% CI: 1.07-1.13, P=6×10-11 ). Clinical variables predicted the risk of GDM (c-statistic 0.67, 95% CI: 0.64-0.70), and adding the GRS modestly improved prediction (0.70, 95% CI: 0.67-0.73). CONCLUSIONS: Among Caucasian women, a GRS that included common T2DM genetic risk variants was associated with increased risk of GDM but showed limited utility in the identification of GDM cases.

Impact of a peri-operative quality improvement programme on postoperative pulmonary complications.

Postoperative pulmonary complications are common, with a reported incidence of 2-40%, and are associated with adverse outcomes that include death, longer hospital stay and reduced long-term survival. Enhanced recovery is now a standard of care for patients undergoing elective major surgery. Despite the high prevalence of pulmonary complications in this population, few elements of enhanced recovery specifically address reducing these complications. In 2013, a prevalence audit confirmed a postoperative pulmonary complication rate of 16/83 (19.3%) in patients undergoing elective major surgery who were admitted to critical care postoperatively. A quality improvement team developed and implemented ERAS+, an innovative model of peri-operative care combining elements of enhanced recovery with specific measures aimed at reducing pulmonary complications. ERAS+ was introduced in June 2014, with full implementation in September 2014. Patients were screened during full ERAS+ implementation and again one year following implementation. Following ERAS+ implementation, postoperative pulmonary complications reduced to 24/228 (10.5%). Sustained improvement was evident one year after implementation, with a pulmonary complication rate of 16/183 (8.7%). Median (IQR [range]) length of hospital stay one year after implementation of ERAS+ also improved from 12 (9-15 [4-101]) to 9 (5.5-10.5 [3-81]) days. The ERAS+ pathway is applicable to patients undergoing elective major surgery and appears effective in reducing postoperative pulmonary complications.

Linking routinely collected social work, education and health data to enable monitoring of the health and health care of school-aged children in state care ('looked after children') in Scotland: a national demonstration project.

BACKGROUND AND OBJECTIVES: Children in state care ('looked after children') have poorer health than children who are not looked after. Recent developments in Scotland and elsewhere have aimed to improve services and outcomes for looked after children. Routine monitoring of the health outcomes of looked after children compared to those of their non-looked after peers is currently lacking. Developing capacity for comparative monitoring of population-based outcomes based on linkage of routinely collected administrative data has been identified as a priority. To our knowledge there are no existing population-based data linkage studies providing data on the health of looked after and non-looked after children at national level. Smaller scale studies that are available generally provide very limited information on linkage methods and hence do not allow scrutiny of bias that may be introduced through the linkage process. STUDY DESIGN AND METHODS: National demonstration project testing the feasibility of linking routinely collected looked after children, education and health data. PARTICIPANTS: All children in publicly funded school in Scotland in 2011/12. RESULTS: Linkage between looked after children data and the national pupil census classified 10,009 (1.5%) and 1757 (0.3%) of 670,952 children as, respectively, currently and previously looked after. Recording of the unique pupil identifier (Scottish Candidate Number, SCN) on looked after children returns is incomplete, with 66% of looked after records for 2011/12 for children of possible school age containing a valid SCN. This will have resulted in some under-ascertainment of currently and, particularly, previously looked after children within the general pupil population. Further linkage of the pupil census to the National Health Service Scotland master patient index demonstrated that a safe link to the child's unique health service (Community Health Index) number could be obtained for a very high proportion of children in each group (94%, 95% and 95% of children classified as currently, previously, and non-looked after, respectively). In general, linkage rates were higher for older children and those living in more affluent areas. Within the looked after group, linkage rates were highest for children with the fewest placements and for those in permanent fostering. CONCLUSIONS: This novel data linkage demonstrates the feasibility of monitoring population-based health outcomes of school-aged looked after and non-looked after children using linked routine administrative data. Improved recording of the unique pupil identifier number on looked after data returns would be beneficial. Extending the range of personal identifiers on looked after children returns would enable linkage to health data for looked after children who are not in publicly funded schooling (i.e. those who are preschool or postschool, home schooled or in independent schooling).

Effect of testing experience and profession on provider acceptability of rapid HIV testing after implementation in public sexual health clinics in Sydney.

OBJECTIVES: Rapid HIV testing (RHT) is well established in many countries, but it is new in Australia since a policy change in 2011. We assessed service provider acceptability of RHT before and after its implementation in four Sydney public sexual health clinics. METHODS: Service providers were surveyed immediately after training in RHT and again 6-12 months later. Differences in mean scores between survey rounds were assessed via t-tests, with stratification by profession and the number of tests performed. RESULTS: RHT was rated as highly acceptable among staff at baseline and acceptability scores improved between survey rounds. Belief in being sufficiently skilled and experienced to perform RHT (P = 0.004) and confidence in the delivery of nonreactive results increased (P = 0.007), while the belief that RHT was disruptive declined (P = 0.001). Acceptability was higher for staff who had performed a greater number of tests regarding comfort with their role in RHT (P = 0.004) and belief that patients were satisfied with RHT (P = 0.007). Compared with nurses, doctors had a stronger preference for a faster rapid test (P = 0.027) and were more likely to agree that RHT interfered with consultations (P = 0.014). CONCLUSIONS: Differences in responses between professions may reflect differences in staff roles, the type of patients seen by staff and the model of testing used, all of which may affect the number of tests performed by staff. These findings may inform planning for how best to implement RHT in clinical services.

Prominent intraspecific genetic divergence within Anopheles gambiae sibling species triggered by habitat discontinuities across a riverine landscape.

The Anopheles gambiae complex of mosquitoes includes malaria vectors at different stages of speciation, whose study enables a better understanding of how adaptation to divergent environmental conditions leads to evolution of reproductive isolation. We investigated the population genetic structure of closely related sympatric taxa that have recently been proposed as separate species (An. coluzzii and An. gambiae), sampled from diverse habitats along the Gambia river in West Africa. We characterized putatively neutral microsatellite loci as well as chromosomal inversion polymorphisms known to be associated with ecological adaptation. The results revealed strong ecologically associated population subdivisions within both species. Microsatellite loci on chromosome-3L revealed clear differentiation between coastal and inland populations, which in An. coluzzii is reinforced by a unusual inversion polymorphism pattern, supporting the hypothesis of genetic divergence driven by adaptation to the coastal habitat. A strong reduction of gene flow was observed between An. gambiae populations west and east of an extensively rice-cultivated region apparently colonized exclusively by An. coluzzii. Notably, this 'intraspecific' differentiation is higher than that observed between the two species and involves also the centromeric region of chromosome-X which has previously been considered a marker of speciation within this complex, possibly suggesting that the two populations may be at an advanced stage of differentiation triggered by human-made habitat fragmentation. These results confirm ongoing ecological speciation within these most important Afro-tropical malaria vectors and raise new questions on the possible effect of this process in malaria transmission.

Toothbrushing programme in Saudi Arabia 'TOPS': a study protocol for a cluster randomised controlled trial in kindergartens, Riyadh.

INTRODUCTION: Dental caries among children is a major global health problem and is a particular public health challenge in Saudi Arabia. Dental caries cause pain, infection and negatively impact quality of life. As part of population oral health improvement efforts in Saudi Arabia, this project aims to evaluate the effectiveness of a supervised toothbrushing programme in kindergartens. METHODS AND ANALYSIS: This study is a cluster randomised controlled trial. Enrolment began in September 2022, for two academic years (2022-2024) on 20 randomly selected kindergartens in Riyadh. The data collection phase will be completed in September 2024. Ten kindergartens are randomly allocated to supervised toothbrushing and 10 to treatment as usual, which is an annual oral health awareness visit. The primary endpoint will be the worsening of obvious decay experience as measured by decayed (into dentine), missing and filled teeth (d3mft) from baseline to the second year of follow-up. The secondary endpoint will be the increase in the number of teeth affected. A priori subgroups of the region of Riyadh, school type (public, private), child sex and presence/absence of prior decay at baseline, will be analysed. We require 244 evaluable endpoints using a power of 80% to meet the sample size requirement. In addition, questionnaires on behaviours, quality of life, process monitoring and cost analysis are being deployed. ETHICS AND DISSEMINATION: Ethics approval for this study was given by the King Fahad Medical City Institutional Review Board in the Saudi Ministry of Health (22-083E/March 2022). The data analysis has been approved by the University of Glasgow Medical Veterinary and Life Sciences Research Ethical Committee (200220194/March 2023). The results of this study will be disseminated through presentations at scientific conferences and in scientific journals. TRIAL REGISTRATION NUMBER: NCT05512156.

Surgical tracheostomy in a patient with a stuck tracheal tube in situ.

The inability to extubate a patient's trachea due to a mechanical complication is rarely encountered in clinical practice. The risks of attempting to remove a stuck tracheal tube include laryngeal trauma, vocal cord injury and arytenoid dislocation, all of which have significant implications. Here, we report the case of a patient who was admitted to the intensive care unit for mechanical ventilation following liver transplant surgery. Her trachea was initially extubated on the second postoperative day, but she required further mechanical ventilation the following day and her trachea was re-intubated. Five days later, she was deemed suitable for tracheal extubation, but the formation of granulation tissue around the tracheal tube prevented its removal. A multi-disciplinary decision-making approach was taken when deciding to site a surgical tracheostomy. A flexible bronchoscope was used as an aid for safe placement. This facilitated safe extrication of the tracheal tube, which was freed by gentle manipulation both proximally and distally. We suspect that tracheal tube size may have been a factor in the development of the granulation tissue in this case. It is important to consider tracheal tube size in all patients, particularly if they require tracheal re-intubation or are likely to require mechanical ventilation for a prolonged period.

Use of symptom-guided physical activity and exercise rehabilitation for COVID-19 and other postviral conditions.

There are many similarities in symptoms between postviral conditions, including clinical features such as fatigue, reduced daily activity and postexertional symptom exacerbation. Unfavourable responses to exercise have influenced the wider debate on how to reintegrate physical activity (PA) and exercise while simultaneously managing symptoms during recovery from post-COVID-19 syndrome (or Long COVID). This has resulted in inconsistent advice from the scientific and clinical rehabilitation community on how and when to resume PA and exercise following COVID-19 illness. This article provides commentary on the following topics: (1) controversies surrounding graded exercise therapy as a treatment modality for post-COVID-19 rehabilitation; (2) evidence supporting PA promotion, resistance exercise and cardiorespiratory fitness for population health, and the consequences of physical inactivity in patients with complex rehabilitation needs; (3) population-based challenges for UK Defence Rehabilitation practitioners for the management of postviral conditions; and (4) 'symptom guided PA and exercise rehabilitation' as an appropriate treatment option for managing individuals with multifaceted medical needs.

Economic Evaluation of the Protecting Teeth @ 3 Randomized Controlled Trial.

INTRODUCTION: An economic evaluation (EE) was conducted alongside a randomized controlled trial (the Protecting Teeth @ 3 Study [PT@3]), exploring the additional preventive value of fluoride varnish (FV) application at 6-monthly intervals in nursery schools compared to treatment as usual (TAU) in the same nurseries. TAU represented a multicomponent national child oral health improvement intervention, the Childsmile program, apart from nursery FV. METHODS: The EE was a within-trial cost-utility analysis (CUA) comparing the FV and TAU groups. The CUA was conducted from a National Health Service perspective and followed relevant methods guidance. Within-trial costs included intervention costs and health care resource use costs. Health outcomes were expressed in quality-adjusted life years (QALYs) accrued over the 2-y follow-up period. The Child Health Utility 9 Dimensions questionnaire was used to obtain utility scores. National reference costs were used, a discount rate of 1.5% for public health interventions was adopted, multiple imputation methods for missing data were employed, sensitivity analyses were conducted, and incremental cost-utility ratios were calculated. RESULTS: Data from 534 participants from the 2014-2015 PT@3 intake were used in the EE analyses, n = 265 (50%) in the FV arm and n = 269 (50%) in the TAU arm. Mean incremental cost per child in the FV arm was £68.37 (P = 0.382; 95% confidence interval [CI], -£18.04 to £143.82). Mean incremental QALY was -0.004 (P = 0.636; 95% CI, -0.016 to 0.007). The probability that the FV intervention was cost-effective at the UK £20,000 threshold was 11.3%. CONCLUSION: The results indicate that applying FV in nurseries in addition to TAU (all other components of Childsmile, apart from nursery FV) would not be deemed cost-effective given current UK thresholds. In view of previously proven clinical effectiveness and economic worthiness of the universal nursery toothbrushing component of Childsmile, continuation of the additional, targeted nursery FV component in its pre-COVID-19 form should be reviewed given its low probability of cost-effectiveness. KNOWLEDGE TRANSFER STATEMENT: The results of this study can be used by child oral health policy makers and dental public health professionals. They can form part of the evidence to inform the Scottish, UK, and international guidance on community-based child oral health promotion programs.

Role of medical history and medication use in the aetiology of upper aerodigestive tract cancers in Europe: the ARCAGE study.

BACKGROUND: The study aimed to investigate the role of medical history (skin warts, Candida albicans, herpetic lesions, heartburn, regurgitation) and medication use (for heartburn; for regurgitation; aspirin) in the aetiology of upper aerodigestive tract (UADT) cancer. METHODS: A multicentre (10 European countries) case-control study [Alcohol-Related CAncers and GEnetic susceptibility (ARCAGE) project]. RESULTS: There were 1779 cases of UADT cancer and 1993 controls. History of warts or C. albicans infection was associated with a reduced risk [odds ratio (OR) 0.80, 95% confidence interval (CI) 0.68-0.94 and OR 0.73, 95% CI 0.60-0.89, respectively] but there was no association with herpetic lesions, heartburn, regurgitation or medication for related symptoms. Regurgitation was associated with an increased risk for cancer of the oesophagus (OR 1.47, 95% CI 0.98-2.21). Regular aspirin use was not associated with risk of UADT cancer overall but was associated with a reduced risk for cancer of oesophagus (OR 0.51, 95% CI 0.28-0.96), hypopharynx (OR 0.53, 95% CI 0.28-1.02) and larynx (OR 0.74, 95% CI 0.54-1.01). CONCLUSIONS: A history of some infections appears to be a marker for decreased risk of UADT cancer. The role of medical history and medication use varied by UADT subsites with aspirin use associated with a decreased risk of oesophageal cancer and suggestive of a decreased risk of hypopharyngeal and laryngeal cancers.

Killer-cell immunoglobulin-like receptors and malaria caused by Plasmodium falciparum in The Gambia.

The relevance of innate immune responses to Plasmodium falciparum infection, in particular the central role of natural killer (NK) cell-derived interferon gamma (IFN-γ), is becoming increasingly recognised. Recently, it has been shown that IFN-γ production in response to P. falciparum antigens is in part regulated by killer-cell immunoglobulin-like receptor (KIR) genes, and a study from malaria-exposed Melanesians suggested an association between KIR genotypes and susceptibility to infection. This prompted us to determine and compare the frequencies of 15 KIR genes in Gambian children presenting with either severe malaria (n = 133) or uncomplicated malaria (n = 188) and in cord-blood population control samples (n = 314) collected from the same area. While no significant differences were observed between severe and uncomplicated cases, proportions of individuals with KIR2DS2+C1 and KIR2DL2+C1 were significantly higher among malaria cases overall than in population control samples. In an exploratory analysis, activating KIR genes KIR2DS2, KIR3DS1 and KIR2DS5 were slightly higher in children in disease subgroups associated with the highest mortality. In addition, our data suggest that homozygosity for KIR genotype A might be associated with different malaria outcomes including protection from infection and higher blood parasitaemia levels in those that do get infected. These findings are consistent with a probable role of KIR genes in determining susceptibility to malaria, and further studies are warranted in different populations.