'Choosing shoes': a preliminary study into the challenges facing clinicians in assessing footwear for rheumatoid patients

Background: Footwear has been accepted as a therapeutic intervention for the foot affected by rheumatoid arthritis (RA). Evidence relating to the objective assessment of footwear in patients with RA is limited. The aims of this study were to identify current footwear styles, footwear characteristics, and factors that influence footwear choice experienced by patients with RA. Methods: Eighty patients with RA were recruited from rheumatology clinics during the summer months. Clinical characteristics, global function, and foot impairment and disability measures were recorded. Current footwear, footwear characteristics and the factors associated with choice of footwear were identified. Suitability of footwear was recorded using pre-determined criteria for assessing footwear type, based on a previous study of foot pain. Results: The patients had longstanding RA with moderate-to severe disability and impairment. The foot and ankle assessment demonstrated a low-arch profile with both forefoot and rearfoot structural deformities. Over 50% of shoes worn by patients were opentype footwear. More than 70% of patients’ footwear was defined as being poor. Poor footwear characteristics such as heel rigidity and sole hardness were observed. Patients reported comfort (17%) and fit (14%) as important factors in choosing their own footwear. Only five percent (5%) of patients wore therapeutic footwear. Conclusions: The majority of patients with RA wear footwear that has been previously described as poor. Future work needs to aim to define and justify the specific features of footwear that may be of benefit to foot health for people with RA

Measuring, monitoring, and improving sleep variables: its application to professional football players

After several papers reported that Whole Body Cryotherapy (WBC) can improve objective and subjective markers of sleep, supported by anecdotal reports of post-exposure sleepiness from players at Southampton FC (SFC; PhD sponsor), the original aim of this thesis was to elucidate the effect of WBC on sleep in professional football players. However, after the UK COVID-19 lockdowns, WBC was not considered covid safe and, therefore, sleep became the central theme. Sleep plays an important role in the maintenance of both physiological and psychological homeostasis. During sleep, the release of human growth hormone and other anabolic hormones peak, inflammatory processes are modulated, and memories and skills are consolidated. Therefore, sleep is considered integral to athletic recovery and player well-being. Despite this, professional football players regularly present with sub-optimal sleep duration and/or quality. However, the factors associated with sleep variability are not fully understood, and there is no consensus on what the optimal level of sleep for athletes is. Therefore, this thesis conceptualised the following research questions: (1) What is known about the quality and duration of sleep amongst professional footballers? (2) What factors affect sleep in professional football players, specifically at SFC? (3) What are suitable and effective ways of improving sleep in professional football players? These questions were addressed across 2 systematic reviews (Chapters 2 & 4), an interventional study (Chapter 3), an observational cohort study (Chapter 5), a method agreement study (Chapter 6), and finally a case study (Chapter 7). Chapter 3 presents a study that aimed to (1) investigate the effect of a WBC applied across an in-season microcycle on the objective and subjective sleep quality in under-18 (U18) professional footballers, and (2) determine the effect of WBC on game-day inflammation, testosterone, and cortisol. Unfortunately, this study was curtailed by the COVID lockdowns. Nevertheless, novel findings were reported. Specifically, whilst objective sleep data were not significantly different between groups, players who received WBC during the microcycle preceding a competitive fixture, reported a greater sense of alertness following wake, as determined by the Leeds Sleep Quality Index. Whilst these results are subjective, they could also be indicative of improved sleep architecture following WBC. However, considering objective sleep was determined from wrist-worn activity monitors without the capability to detect sleep stages, this cannot be known with certainty. In Chapter 4, a scoping review of observational studies was performed that suggested that professional football players’ mean sleep duration, sleep latency, and wake after sleep onset (WASO), were all within recommended guidelines (these same reference limits were also used for Chapter 4). This conclusion was made on the basis that over 63% of the included studies reported means that were above the lower reference boundary for sleep duration. Despite this, several papers reported error bars that exceeded the reference limits, suggesting that suboptimal sleep remains common among individual players. In Chapter 5, an observational study was performed on under-18 professional SFC players, and the results matched what was observed from the scoping review in Chapter 4. Specifically, whilst sleep duration on matchday+1 (the day proceeding matchday) presented with a beta estimate (derived from linear mixed models) of 400mins, the remaining day types presented with sleep durations of above 420mins, the lower end of the reference limits. Nevertheless, in this study, confidence intervals breached the reference limits, therefore, further suggesting that suboptimal sleep occurs in this population. In tandem, results from Chapter 4 and Chapter 5 potentially indicate that group-level interventions are unnecessary. Rather, practitioners may find it more efficient to target support to players who report sleep disturbances. The scoping review presented in Chapter 4 also suggested that professional football players' sleep was also more variable compared to age-matched controls and several factors (e.g. scheduling variables) were associated with disrupted sleep. Chapter 5 builds on these findings by demonstrating for the first time that scheduled start time (the time players were scheduled to arrive at training or for a fixture) was associated with the amount of sleep that U18 players attained. Specifically, for every hour increase in start time, player sleep duration increased by an estimated 19.1mins (CI:9.4–28.79; p<0.001). This occurred in tandem with an 18mins (CI:9.3–26.6; p<0.001) later wake time, per hour increase in scheduled start time. It is not clear to what magnitude start time would have to be extended to generate increases in player performance, secondary to increased sleep duration. However, considering the player's age from this study (age: 17.3 ± 0.7yrs), a later start time may befit their intrinsic chronotype and, therefore, support the players by reinforcing their natural sleep habits. Whilst data from Chapter 5 support the notion that scheduling variables are associated with sleep in U18 professional footballers, they also suggest that sleep is not meaningfully associated with external workload. Global positioning and accelerometry data were collected and collated across 1-day, 7-day, and 28-day periods. For every 100m increase in high-speed running (>5.5 m·s−1), sleep onset and wake time were extended by 4.68min (CI:2.78—6.58mins) and 3.38mins (CI: 1.27—5.5mins), respectively. However, considering that workload had no significant effect on total sleep duration, the changes to wake time and sleep onset time should not concern practitioners. In Chapters 3, 5, and 7, objective sleep monitoring was completed using ReadiBand wrist-worn activity monitors. Though, it was acknowledged that these devices cannot readily link objective sleep quality and performance, and players' data could be missing due to poor band adherence. Therefore, another approach was trialled where the effect that inadequate sleep has on cognitive variables that are sensitive to sleep loss was determined, rather than measuring sleep directly. Consequently, this thesis also assessed the use of a novel virtual reality eye-tracking device that could rapidly administer an oculomotor task which was reported to be sensitive to total sleep deprivation. However, to be efficacious in a footballing environment, the device would have to demonstrate sensitivity to the daily fluctuation of sleep. Target radial variation (a measure of spatial accuracy) was found to be significantly correlated with perceived daytime sleepiness (r=0.33, p=0.005), however, no further relationships were observed between oculomotor function, psychometric vigilance, daytime sleepiness, and sleep metrics. In a retrospective analysis on a second data set from military personnel (that was included to augment the original analysis), only psychomotor vigilance, and not oculomotor function, were associated with the total amount of sleep achieved. This suggested that this device would not be efficacious in a footballing environment as a replacement for sleep monitoring. Following the research presented in Chapters 4 and 5, it was surmised that a bespoke approach to sleep intervention would be more efficacious than team-based interventions. To this end, a framework was conceptualised in collaboration with a multidisciplinary team from SFC (Chapter 7). Next, a player was referred to the scheme after reporting excessive night time awakenings. After consultation, the player completed several subjective questionnaires to assess sleep quality (Pittsburgh Sleep Quality Index), insomnia severity (Insomnia Severity Index), and daytime sleepiness (Epworth Sleepiness Scale) followed by a period of objective sleep monitoring. The sleep monitoring confirmed excessive nighttime awakenings and based on the responses from the initial consultation, a sleep hygiene intervention was applied tailored to the players' responses during the initial consultation. Results revealed improved subjective sleep quality, insomnia severity, and nighttime awakenings. Whilst a case study cannot establish causality, it does provide a potential framework for practitioners looking to provide targeted sleep interventions. Conclusions: In general, professional football players' sleep quantity, latency, and WASO is within available population-based reference limits. Scheduling variables, and not workload variables, are associated with activity monitor-derived objective sleep metrics in professional football players. Scheduled start time is associated with the amount of sleep that professional U18 football players receive. An oculomotor task does not have the requisite sensitivity to detect acute sleep loss in professional football players. A bespoke sleep intervention strategy can be efficacious in an applied footballing environment for players reporting sleep disruption

Thermal conductivity measurement of liquids in a microfluidic device

A new microfluidic-based approach to measuring liquid thermal conductivity is developed to address the requirement in many practical applications for measurements using small (microlitre) sample size and integration into a compact device. The approach also gives the possibility of high-throughput testing. A resistance heater and temperature sensor are incorporated into a glass microfluidic chip to allow transmission and detection of a planar thermal wave crossing a thin layer of the sample. The device is designed so that heat transfer is locally one-dimensional during a short initial time period. This allows the detected temperature transient to be separated into two distinct components: a short-time, purely one-dimensional part from which sample thermal conductivity can be determined and a remaining long-time part containing the effects of three-dimensionality and of the finite size of surrounding thermal reservoirs. Identification of the one-dimensional component yields a steady temperature difference from which sample thermal conductivity can be determined. Calibration is required to give correct representation of changing heater resistance, system layer thicknesses and solid material thermal conductivities with temperature. In this preliminary study, methanol/water mixtures are measured at atmospheric pressure over the temperature range 30–50°C. The results show that the device has produced a measurement accuracy of within 2.5% over the range of thermal conductivity and temperature of the tests. A relation between measurement uncertainty and the geometric and thermal properties of the system is derived and this is used to identify ways that error could be further reduced

Factors predicting pain and early discontinuation of tumour necrosis factor-α-inhibitors in people with rheumatoid arthritis: Results from the British Society for Rheumatology Biologics Register

Background: We examined pain levels in 2 cohorts assembled from the British Society for Rheumatology Biologics Register (BSRBR), and investigated which factors predicted Bodily Pain scores and discontinuation of TNFα-inhibitors. Method: Data were retrieved from BSRBR-RA databases for up to 1 year after commencing TNFα-inhibitors (n=11995) or being treated with non-biologic therapies (n=3632). Bodily Pain scores were derived from the Short Form-36 (SF36) questionnaire and norm-transformed to allow comparison with UK population averages. Discontinuation data were from physician reports. Other data, including 28-joint disease activity score (DAS28) measurements, were from clinical examination, interview, medical records and self-report questionnaires. DAS28-P was derived as the proportion of DAS28 attributed to patient-reported factors (tender joint count and visual analogue score). Missing baseline variables from both cohorts were imputed into 20 replicate datasets. Odds ratios (OR) and adjusted OR were calculated for higher than median pain within each cohort. Results: Participants reported moderate to severe pain at baseline, and pain scores remained >1SD worse than normal population standards at 1 year, even when disease activity responded to treatment. Baseline pain was associated with DAS28-P, worse physical function, worse mental health, and DAS28. After logistic regression, independent predictors of higher than median pain at follow up were baseline Bodily Pain score, higher DAS28-P, worse physical function or mental health and co-morbidities. Higher age, male gender, and higher BMI were additional independent predictors of higher pain in participants who received TNFα-inhibitors. Baseline pain was also one of the predictors of discontinuation of the first TNFα-inhibitor within 1 year, as were female gender, current smoking, co-morbidities, extra-articular manifestations and worse function. Conclusion: Pain persists in people with treated RA, even in those for whom inflammation responds to treatment. Worse pain outcomes are predicted by factors different to those typically found to predict inflammatory disease activity in other studies. Worse pain at baseline also predicts discontinuation of TNFα-inhibitors. Improved pain management should complement inflammatory disease suppression in RA

A traditional Chinese medicine versus Western combination therapy in the treatment of rheumatoid arthritis: two-stage study protocol for a randomized controlled trial

<p>Abstract</p> <p>Background</p> <p>The common randomized controlled trial design has distinct limitations when applied to Chinese medicine, because Chinese medicine identifies and treats 'Chinese medicine patterns' rather than diagnosed diseases. Chinese medicine patterns are a group of associated symptoms, tongue appearances and pulse characteristics. These limitations could be overcome by developing new strategies to evaluate the effect of Chinese medicine. The idea behind pattern-based efficacy evaluations may optimize clinical trial design by identifying the responsiveness-related Chinese medicine patterns.</p> <p>Methods/Design</p> <p>This is a two-stage multi-center trial of Chinese herbal medicine for the management of rheumatoid arthritis. The stage one trial is an open-label trial and aims to explore what groups of Chinese medicine information (such as symptoms) correlates with better efficacy, and the stage two trial is a randomized, controlled, double-blind, double-dummy clinical trial that incorporates the efficacy-related information identified in the stage-one trial into the inclusion criteria.</p> <p>Discussion</p> <p>The indication of a Chinese herbal formula is a specific Chinese medicine pattern and not a single disease and stratifying a disease into several patterns with a group of symptoms is a feasible procedure in clinical trials. This study is the first to investigate whether this approach in the design of Chinese herbal medicine trials can improve responses.</p> <p>Trial registration</p> <p>ChiCTR-TRC-10000989</p

Clinical audit of foot problems in patients with rheumatoid arthritis treated at Counties Manukau District Health Board, Auckland, New Zealand

<p>Abstract</p> <p>Background</p> <p>At diagnosis, 16% of rheumatoid arthritis (RA) patients may have foot joint involvement, increasing to 90% as disease duration increases. This can lead to joint instability, difficulties in walking and limitation in functional ability that restricts activities of daily living. The podiatrist plays an important role in the multidisciplinary team approach to the management of foot problems. The aim of this study was to undertake a clinical audit of foot problems in patients with RA treated at Counties Manukau District Health Board.</p> <p>Methods</p> <p>Patients with RA were identified through rheumatological clinics run within CMDHB. 100 patients were eligible for inclusion. Specific foot outcome tools were used to evaluate pain, disability and function. Observation on foot lesions were noted and previous history of foot assessment, footwear/insoles and foot surgery were evaluated.</p> <p>Results</p> <p>The median age of the cohort was 60 (IQR: 51–64) years old with median disease duration of 15 (IQR: 7.3–25) years. Over 85% presented with foot lesions that included corns and callus over the forefoot region and lesser toe deformities. Moderate to high disability was noted. High levels of forefoot structural damage were observed. 76% had not seen a podiatrist and 77% reported no previous formal foot assessment. 40% had been seen at the orthotic centre for specialised footwear and insoles. 27% of RA patients reported previous foot surgery. A large proportion of patients wore inappropriate footwear.</p> <p>Conclusion</p> <p>This clinical audit suggests that the majority of RA patients suffer from foot problems. Future recommendations include the provision of a podiatrist within the current CMDHB multidisciplinary rheumatology team to ensure better services for RA patients with foot problems.</p

Atoh8, a bHLH Transcription Factor, Is Required for the Development of Retina and Skeletal Muscle in Zebrafish

Math6/atoh8, a bHLH transcription factor, is thought to be indispensable for early embryonic development and likely has important roles in vertebrate tissue-specific differentiation. However, the function of Atoh8 during early development is not clear because homozygous knockout causes embryonic lethality in mice. We have examined the effects of the atoh8 gene on the differentiation of retina and skeletal muscle during early development in zebrafish.We isolated a Math6 homologue in zebrafish, designated as zebrafish atoh8. Whole -mount in situ hybridization analysis showed that zebrafish atoh8 is dynamically expressed mainly in developing retina and skeletal muscle. Atoh8-MO knock-down resulted in reduced eye size with disorganization of retinal lamination. The reduction of atoh8 function also affected the arrangement of paraxial cells and differentiated muscle fibers during somite morphogenesis.Our results show that Atoh8 is an important regulator for the development of both the retina and skeletal muscles necessary for neural retinal cell and myogenic differentiation during zebrafish embryogenesis

Insect Brains Use Image Interpolation Mechanisms to Recognise Rotated Objects

Recognising complex three-dimensional objects presents significant challenges to visual systems when these objects are rotated in depth. The image processing requirements for reliable individual recognition under these circumstances are computationally intensive since local features and their spatial relationships may significantly change as an object is rotated in the horizontal plane. Visual experience is known to be important in primate brains learning to recognise rotated objects, but currently it is unknown how animals with comparatively simple brains deal with the problem of reliably recognising objects when seen from different viewpoints. We show that the miniature brain of honeybees initially demonstrate a low tolerance for novel views of complex shapes (e.g. human faces), but can learn to recognise novel views of stimuli by interpolating between or ‘averaging’ views they have experienced. The finding that visual experience is also important for bees has important implications for understanding how three dimensional biologically relevant objects like flowers are recognised in complex environments, and for how machine vision might be taught to solve related visual problems

Social Class Differences in Secular Trends in Established Coronary Risk Factors over 20 Years: A Cohort Study of British Men from 1978–80 to 1998–2000

Background: Coronary heart disease (CHD) mortality in the UK since the late 1970s has declined more markedly among higher socioeconomic groups. However, little is known about changes in coronary risk factors in different socioeconomic groups. This study examined whether changes in established coronary risk factors in Britain over 20 years between 1978-80 and 1998-2000 differed between socioeconomic groups.Methods and Findings: A socioeconomically representative cohort of 7735 British men aged 40-59 years was followed-up from 1978-80 to 1998-2000; data on blood pressure (BP), cholesterol, body mass index (BMI) and cigarette smoking were collected at both points in 4252 survivors. Social class was based on longest-held occupation in middle-age. Compared with men in non-manual occupations, men in manual occupations experienced a greater increase in BMI (mean difference=0.33 kg/m(2); 95%CI 0.14-0.53; p for interaction=0.001), a smaller decline in non-HDL cholesterol (difference in mean change=0.18 mmol/l; 95%CI 0.11-0.25, p for interaction <= 0.0001) and a smaller increase in HDL cholesterol (difference in mean change=0.04 mmol/l; 95%CI 0.02-0.06, p for interaction <= 0.0001). However, mean systolic BP declined more in manual than non-manual groups (difference in mean change=3.6; 95%CI 2.1-5.1, p for interaction <= 0.0001). The odds of being a current smoker in 1978-80 and 1998-2000 did not differ between non-manual and manual social classes (p for interaction = 0.51).Conclusion: Several key risk factors for CHD and type 2 diabetes showed less favourable changes in men in manual occupations. Continuing priority is needed to improve adverse cardiovascular risk profiles in socially disadvantaged groups in the UK