Working towards consensus on the assessment of mood after severe acquired brain injury: Focus groups with UK-based professionals.

OBJECTIVE: The assessment of mood after brain injury is more challenging when people have ongoing severe cognitive and receptive communication impairments. There is no gold standard on how these assessments should be undertaken. This study aimed to reach a consensus on this among specialists working with this population. DESIGN: Focus groups were completed using a structured nominal group technique. Groups were compared for overlapping themes and agreed processes. PARTICIPANTS: Five focus groups with a total of 14 participants who work with the population of interest were completed. Participants included 12 clinical psychologists, one psychiatrist and one consultant in rehabilitation medicine. RESULTS: Each of the five groups reached a consensus on a process for assessing mood in this population. Results overlapped and were combined into a proposed circular and iterative model of assessment that includes: (pre) information gathering, (peri) assessment processes, and (post) treatment; with formulation being seen as a vital part of the process. Standardised measures were not recommended for use with this population. Beyond the consensus processes, three implicit themes were identified: (1) depression is different after severe brain injury, (2) overlapping tasks and roles, and (3) looking at the bigger picture. CONCLUSIONS: A good level of consensus was achieved across the five groups on processes to follow when assessing mood when people have ongoing cognitive and receptive communication impairments after severe brain injury. We recommend that this formulation-based model be followed when assessing people in this clinical population.

The incidence of postoperative periprosthetic femoral fracture following total hip replacement: An analysis of UK National Joint Registry and Hospital Episodes statistics data.

BACKGROUND: Postoperative periprosthetic femoral fracture (POPFF) after total hip replacement (THR) requires complex surgery and is associated with a high morbidity, mortality, and cost. Although the United Kingdom based National Joint Registry (NJR) captures over 95% of THRs treated with revision, before June 2023 it did not capture POPFF treated with fixation. We aimed to estimate the incidence and epidemiology of POPFF treated with either surgery in England. METHODS AND FINDINGS: We performed a retrospective analysis of a mandatory, prospective database (NJR) linked to Hospital Episode Statistics (HES). All linkable primary THRs between 01/01/2004 and 31/12/2020 were included. Revision or fixation of POPFF were identified using a combination of procedural and diagnosis codes. We identified 809,832 THRs representing 5,542,332 prosthesis years at risk. A total of 5,100 POPFF were identified that had been surgically treated by revision, fixation, or both, and 2,831 of these fractures were treated with fixation alone, meaning 56% were not represented with revision data alone. The incidence of POPFF needing surgery was 0.92 (95% CI 0.90, 0.95) per 1,000 prostheses years. This incidence was higher in patients over the age of 70 at the time of primary THR (1.31 [95% CI 1.26, 1.35] per 1,000 prostheses years) and for patients who underwent THR for hip fracture (2.19 [95% CI 1.97, 2.42] per 1,000 prostheses years). This incidence appears to be increasing year on year. The cumulative probability of sustaining a POPFF within 10 years of THR was 1% and over 15% of patients died within 1 year of surgery for a POPFF. CONCLUSIONS: To date, the incidence of POPFF may have been underestimated with over 50% of cases missed if the case identification in this study is correct. After including these cases, we observed that POPFF is the largest reason for major reoperation following THR and patients sustaining these injuries have a high risk of death. The prevention and treatment of POPFF and requires further resource allocation and research.

Validation of a 5-Year Prognostic Model for Parkinson's Disease.

BACKGROUND: A simple prognostic model was previously developed to predict the probability of recently-diagnosed patients reaching negative outcomes (postural instability, dementia or death) in a 5-year period. OBJECTIVES: To validate this model in an independent cohort and establish utility at later time points. METHODS: Validation was performed using data collected in an incident cohort at baseline, 2 and 4 years. Predicted negative outcome probabilities were compared to actual 5-year outcomes. RESULTS: The model, based on age, MDS-UPDRS axial score and 60-second animal fluency, predicted poor 5-year outcome when applied at baseline, (area under the curve (AUC) 0.80), 2 years (AUC 0.82) and 4 years (AUC 0.71). Power calculations showed that selecting a subgroup with prognostic score >0.5 reduced the sample size required for a disease-modifying trial. CONCLUSIONS: This 5-year prognostic model has good accuracy when employed up to 4 years from diagnosis and may help stratification for disease-modifying trials.

Low Frequency Ventilation During Cardiopulmonary Bypass to Protect Postoperative Lung Function in Cardiac Valvular Surgery: The PROTECTION Phase II Randomized Trial.

BACKGROUND: Cardiac surgery with cardiopulmonary bypass (CPB) triggers pulmonary injury. In this trial we assessed the feasibility, safety, and efficacy of low frequency ventilation (LFV) during CPB in patients undergoing valvular surgery. METHODS AND RESULTS: Patients with severe mitral or aortic valve disease were randomized to either LFV or usual care. Primary outcomes included release of generic inflammatory and vascular biomarkers and the lung-specific biomarker sRAGE (soluble receptor for advance glycation end products) up to 24 hours postsurgery. Secondary outcomes included pulmonary function tests and 6-minute walking test up to 8 weeks postdischarge. Sixty-three patients were randomized (33 LFV versus 30 usual care). Mean age was 66.8 years and 30% were female. LFV was associated with changes of sRAGE (soluble receptor for advance glycation end products) levels (geometric mean ratio, 3.05; [95% CI, 1.13-8.24] 10 minutes post CPB, and 1.07 [95% CI, 0.64-1.79], 0.84 [95% CI, 0.55-1.27], 0.67 [95% CI, 0.42-1.07], and 0.62 [95% CI, 0.45-0.85] at 2, 6, 12, and 24 hours post CPB respectively). No changes were observed for any of the generic biomarkers. Respiratory index soon after surgery (mean difference, -0.61 [95% CI, -1.24 to 0.015] 10 minutes post end of CPB), forced expiratory volume after 1 second/forced vital capacity ratio (0.050 [95% CI, 0.007-0.093] at 6 to 8 weeks pos-surgery), Forced vital capacity alone (95% CI, -0.191 L [-0.394 to 0.012]) and 6-minute walking test score at discharge (63.2 m [95% CI, 12.9-113.6]) were better preserved in the LFV group. No other differences were noted. CONCLUSIONS: The use of LFV during CPB in patients undergoing valvular surgery was feasible and safe and was associated with changes in sRAGE levels along with better preserved lung function and walking performance. These observations warrant further investigation in larger future studies. REGISTRATION: URL: https://www.isrctn.com; Unique Identifier: ISRCTN75795633.

Prehabilitation for frail patients undergoing hip and knee replacement in the UK: Joint PREP feasibility study for a randomised controlled trial.

OBJECTIVE: To determine the feasibility of conducting a randomised controlled trial (RCT) to evaluate a prehabilitation programme for frail patients undergoing total hip replacement (THR) or total knee replacement (TKR). DESIGN: Randomised feasibility study with embedded qualitative work. SETTING: Three National Health Service hospitals. PARTICIPANTS: Adults aged ≥65 years, frail and scheduled for primary THR or TKR. INTERVENTION: Appointment with a physiotherapist to individualise a home-based exercise programme. Participants were encouraged to do the home exercises daily for 12 weeks pre-operative and were provided with a daily protein supplement. Participants were supported by six telephone calls over the 12-week intervention period. OUTCOME MEASURES: Eligibility and recruitment rates, intervention adherence, data completion rates of patient-reported outcome measures, retention rates and acceptability of the trial and intervention. Qualitative interviews were conducted with participants and non-participants and analysed using thematic analysis. RESULTS: Between December 2022 and August 2023, 411 patients were sent a screening pack. Of the 168 patients who returned a screening questionnaire, 79 were eligible and consented to participate, and 64 were randomised. Of the 33 participants randomised to the intervention, 26 attended the intervention appointment. Eighteen participants (69%) received all six intervention follow-up telephone calls. Nineteen participants (73%) completed an intervention adherence log; 13 (68%) adhered to the exercise programme and 11 (58%) adhered to the protein supplementation. The overall retention rate was 86% (55/64 overall) at 12 weeks. The 12-week follow-up questionnaire was returned by 46 of the 55 participants (84%) who were sent a questionnaire. Interviews with 19 patients found that the trial processes and intervention were generally acceptable, but areas of potential improvements were identified. CONCLUSIONS: This study demonstrated that a larger study is possible and has identified improvements to optimise the design of an RCT. TRIAL REGISTRATION NUMBER: ISRCTN11121506.

Assessment of mood after severe acquired brain injury: Interviews with UK clinical psychologists and medical professionals.

OBJECTIVE: Mood assessment is challenging when people have cognitive and receptive communication impairments after severe brain injury. This study explored how UK-based medical and psychology professionals working with people with severe cognitive and communication impairments after brain injury assess mood in this population. DESIGN: Following their participation in an online survey, professionals were invited to participate in individual semi-structured interviews. Interviews were analysed using thematic analysis to label explicit data (semantic themes) and implicit data (latent themes). PARTICIPANTS: Twenty-three clinical psychologists and nine medical professionals participated in online or in-person interviews. RESULTS: Both groups explicitly reported using a combination of collateral information, history, observations, and patient interviews when assessing mood in this population. Medical professionals did not routinely use standardised measures and clinical psychologists often adjusted them when they used them. The respondents discussed difficulties conceptualising depression after brain injury, the experience needed by the assessor, and the need for an individualised approach for this population. Clinical psychologists discussed the pressures of working in healthcare systems and medical professionals discussed how symptoms may influence prescription choices. Seven latent themes were labelled which highlighted additional challenges and complexities experienced by those assessing mood, beyond the actual assessment process itself. CONCLUSIONS: No 'gold standard' approach to assessing mood in those with cognitive and communication difficulties after severe brain injury was identified. There was overlap in assessment approaches but no clear consensus. Interviewees felt that mood assessment must be approached differently in this population and that self-report measures are not useful.

Neuropsychological application of the International Test Commission Guidelines for Translation and Adapting of Tests.

OBJECTIVE: The number of test translations and adaptations has risen exponentially over the last two decades, and these processes are now becoming a common practice. The International Test Commission (ITC) Guidelines for Translating and Adapting Tests (Second Edition, 2017) offer principles and practices to ensure the quality of translated and adapted tests. However, they are not specific to the cognitive processes examined with clinical neuropsychological measures. The aim of this publication is to provide a specialized set of recommendations for guiding neuropsychological test translation and adaptation procedures. METHODS: The International Neuropsychological Society's Cultural Neuropsychology Special Interest Group established a working group tasked with extending the ITC guidelines to offer specialized recommendations for translating/adapting neuropsychological tests. The neuropsychological application of the ITC guidelines was formulated by authors representing over ten nations, drawing upon literature concerning neuropsychological test translation, adaptation, and development, as well as their own expertise and consulting colleagues experienced in this field. RESULTS: A summary of neuropsychological-specific commentary regarding the ITC test translation and adaptation guidelines is presented. Additionally, examples of applying these recommendations across a broad range of criteria are provided to aid test developers in attaining valid and reliable outcomes. CONCLUSIONS: Establishing specific neuropsychological test translation and adaptation guidelines is critical to ensure that such processes produce reliable and valid psychometric measures. Given the rapid global growth experienced in neuropsychology over the last two decades, the recommendations may assist researchers and practitioners in carrying out such endeavors.

Optimizing Oxford Shoulder Scores with computerized adaptive testing reduces redundancy while maintaining precision.

Aims: The Oxford Shoulder Score (OSS) is a 12-item measure commonly used for the assessment of shoulder surgeries. This study explores whether computerized adaptive testing (CAT) provides a shortened, individually tailored questionnaire while maintaining test accuracy. Methods: A total of 16,238 preoperative OSS were available in the National Joint Registry (NJR) for England, Wales, Northern Ireland, the Isle of Man, and the States of Guernsey dataset (April 2012 to April 2022). Prior to CAT, the foundational item response theory (IRT) assumptions of unidimensionality, monotonicity, and local independence were established. CAT compared sequential item selection with stopping criteria set at standard error (SE) < 0.32 and SE < 0.45 (equivalent to reliability coefficients of 0.90 and 0.80) to full-length patient-reported outcome measure (PROM) precision. Results: Confirmatory factor analysis (CFA) for unidimensionality exhibited satisfactory fit with root mean square standardized residual (RSMSR) of 0.06 (cut-off ≤ 0.08) but not with comparative fit index (CFI) of 0.85 or Tucker-Lewis index (TLI) of 0.82 (cut-off > 0.90). Monotonicity, measured by H value, yielded 0.482, signifying good monotonic trends. Local independence was generally met, with Yen's Q3 statistic > 0.2 for most items. The median item count for completing the CAT simulation with a SE of 0.32 was 3 (IQR 3 to 12), while for a SE of 0.45 it was 2 (IQR 2 to 6). This constituted only 25% and 16%, respectively, when compared to the 12-item full-length questionnaire. Conclusion: Calibrating IRT for the OSS has resulted in the development of an efficient and shortened CAT while maintaining accuracy and reliability. Through the reduction of redundant items and implementation of a standardized measurement scale, our study highlights a promising approach to alleviate time burden and potentially enhance compliance with these widely used outcome measures.

Heat stress mediates toxicity of rutile titanium dioxide nanoparticles on fertilisation capacity in the broadcast spawning mussel Mytilus galloprovincialis.

Titanium dioxide nanoparticle (nTiO2) pollution of marine environments is rapidly increasing with potentially deleterious effects on wildlife. Yet, the impacts of nTiO2 on reproduction remain poorly understood. This is especially the case for broadcast spawners, who are likely to be more severely impacted by environmental disturbances because their gametes are directly exposed to the environment during fertilisation. In addition, it is unclear whether rising water temperatures will further exacerbate the impact of nTiO2 toxicity. Here, in a series of fertilisation trials, we systematically examine the main and interactive effects of nTiO2 exposure and seawater temperature on fertilisation success in the Mediterranean mussel Mytilus galloprovincialis. Specifically, our fertilisation trials explored whether nTiO2 exposure influences fertilisation rates when (i) eggs alone are exposed, (ii) both sperm and eggs are exposed simultaneously, and (iii) whether increases in seawater temperature interact with nTiO2 exposure to influence fertilisation rates. We also ask whether changes in nTiO2 concentrations influence key sperm motility traits using computer-assisted sperm analysis (CASA). In fertilisation trials for treatment groups (i) and (ii), we found no main effects of nTiO2 at environmentally relevant concentrations of 5, 10 and 50 µg L-1 on fertilisation capacity relative to the control. Consistent with these findings, we found no effect of nTiO2 exposure on sperm motility. However, in treatment group (iii), when fertilisation trials were conducted at higher temperatures (+6 °C), exposure of gametes from both sexes to 10 µg L-1 nTiO2 led to a reduction in fertilisation rates that was significantly greater than when gametes were exposed to elevated temperature alone. These interacting effects of nTiO2 exposure and seawater temperature demonstrate the toxic potential of nTiO2 for fertilisation processes in a system that is likely to be impacted heavily by predicted future increases in sea surface temperatures.

Could primary care records be used to identify women at risk of perinatal anxiety? A mixed-methods study.

BACKGROUND: Perinatal anxiety (PNA) occurs throughout the antenatal period or up to 1 year after childbirth, with a prevalence of 21%. AIM: To investigate if primary care records could be used to identify women at 'higher risk' of PNA. METHOD: Mixed-methods approach using quantitative and qualitative methods. Quantitative data analysis used Clinical Practice Research Datalink and IQVIA Medical Research Data to identify risk factors for PNA. Interviews explored the lived experiences of women with PNA about predisposing factors for PNA and acceptability of being informed of risk; and perspectives of primary healthcare professionals and Voluntary, Community, and Social Enterprise practitioners about risk communication. Interviews were conducted online, digitally recorded with consent, transcribed, and anonymised prior to analysis. Data were thematically analysed. Patient and clinical advisory groups informed each stage of the research. RESULTS: Women reflected on both positive and negative impacts of being identified at higher risk of PNA, a lack of understanding of how primary care records are used, and who has access to them. All interview participants suggested predisposing factors that would not be coded in primary care records. Quantitative analysis demonstrated that some predisposing factors for PNA can be identified in a woman's primary care records. Initial analysis suggests associations between PNA and infant health and healthcare use. CONCLUSION: While identification of higher risk of PNA may be acceptable, some factors that may contribute to PNA are not coded in primary care records. Identifying and managing PNA is needed to improve infant health.

Effects of fundamental frequency changes on spoken sound loudness.

This study aimed to investigate the perception of loudness in response to changes in fundamental frequency (F0) in spoken sounds, as well as the influence of linguistic background on this perceptual process. The results revealed that participants perceived changes in F0 to have accompanying changes in loudness, with a trend of lower F0 sounds being perceived as louder than higher F0 sounds. This finding contrasts with previous studies on pure tones, where increases in frequency typically led to increases in loudness. Furthermore, the study examined differences between two distinct groups of participants: Chinese-speaking and English-speaking individuals. It was observed that English-speaking participants exhibited a greater sensitivity to minor intensity changes compared to Chinese-speaking participants. This discrepancy in sensitivity suggests that linguistic background may play a significant role in shaping the perception of loudness in spoken sound. The study's findings contribute to our understanding of how F0 variations are perceived in terms of loudness, and highlight the potential impact of language experience on this perceptual process.

Population density effects on gamete traits and fertilisation dynamics under varying sperm environments in mussels.

Gamete traits can vary widely among species, populations and individuals, influencing fertilisation dynamics and overall reproductive fitness. Sexual selection can play an important role in determining the evolution of gamete traits with local environmental conditions determining the strength and direction of sexual selection. Here, we test for signatures of post-mating selection on gamete traits in relation to population density, and possible interactive effects of population density and sperm concentration on sperm motility and fertilisation rates among natural populations of mussels. Our study shows that males from high-density populations produce smaller sperm compared with males from low-density populations, but we detected no effect of population density on egg size. Our results also reveal that females from low-density populations tended to exhibit lower fertilisation rates across a range of sperm concentrations, although this became less important as sperm concentration increased. Variances in fertilisation success were higher for females than males and the effect of gamete compatibility between males and females increases as sperm concentrations increase. These results suggest that local population density can influence gamete traits and fertilisation dynamics but also highlight the importance of phenotypic plasticity in governing sperm-egg interactions in a highly dynamic selective environment.

The burden of periprosthetic femoral fractures in England and Wales: Insights from the first two years of data collection in the National Hip Fracture Database and regional variation in care.

INTRODUCTION: Periprosthetic femoral fractures (PPFFs) represent an important healthcare problem, with a rising incidence noted due to an increase in the number of arthroplasty surgeries being performed. There is a current lack of national consensus as to how these complex, often frail patients are managed. AIMS: Our primary aim was to present the epidemiology of PPFFs in England and Wales over the first two years of data collection by the National Hip Fracture Database (NHFD). Secondary aims included how well the NHFD Key Performance Indicators (KPIs) are met for PPFF patients, whether centres reporting a higher burden of PPFF patients are more likely to meet KPIs compared to lower volume centres, and to also identify if regional variation in care for these patients exist. METHODS: Patients aged 60 years or over, admitted to any acute hospital in England or Wales with a PPFF within the period 1st January 2020 to 31st December 2021 were included. Fractures were classified using the Vancouver system. The primary outcome of interest was the incidence of PPFF in England and Wales. Secondary outcomes included i) geographical distribution, ii) pattern of injury, iii) treatment received, iv) KPI performance nationally, v) KPI performance by top 5 highest volume hospitals vs the rest, vi) KPI performance by region and vii) KPI performance compared with native hip fracture patients. RESULTS: A total of 5,566 PPFFs were reported during our study period. A 31 % increase in cases was seen between 2020 and 2021 (2,405 to 3,161). The South-West of England reported the highest burden of PPFFs (14 % of all cases reported in 2021). Vancouver B subtypes were most common around hip replacements (62 %) and C subtype around knee replacements (55 %). A total of 4,598 patients (82.6 %) underwent operative management. There was regional variation in KPI attainment. When compared to KPI attainment for native hip fractures PPFF care under performed in most regions and domains. High volume PPFF centres were not associated with improved attainment of KPIs. CONCLUSION: We have described the incidence, nature, and management of PPFF at national and regional levels using routinely collected NHFD data. Both numerically and due to case complexity, PPFF are a considerable challenge to patients and health services alike. This epidemiology is not captured by other existing datasets and increased case contribution to the NHFD is encouraged to improve understanding and enable prioritisation and delivery of further care and research.

Neuropsychological tests associated with symptomatic HIV-associated neurocognitive disorder (HAND) in a cohort of older adults in Tanzania.

OBJECTIVE: Human immunodeficiency virus (HIV)-associated neurocognitive disorder (HAND) prevalence is expected to increase in East Africa as treatment coverage increases, survival improves, and this population ages. This study aimed to better understand the current cognitive phenotype of this newly emergent population of older combination antiretroviral therapy (cART)-treated people living with HIV (PLWH), in which current screening measures lack accuracy. This will facilitate the refinement of HAND cognitive screening tools for this setting. METHOD: This is a secondary analysis of 253 PLWH aged ≥50 years receiving standard government HIV clinic follow-up in Kilimanjaro, Tanzania. They were evaluated with a detailed locally normed low-literacy neuropsychological battery annually on three occasions and a consensus panel diagnosis of HAND by Frascati criteria based on clinical evaluation and collateral history. RESULTS: Tests of verbal learning and memory, categorical verbal fluency, visual memory, and visuoconstruction had an area under the receiver operating characteristic curve >0.7 for symptomatic HAND (s-HAND) (0.70-0.72; p < 0.001 for all tests). Tests of visual memory, verbal learning with delayed recall and recognition memory, psychomotor speed, language comprehension, and categorical verbal fluency were independently associated with s-HAND in a logistic mixed effects model (p < 0.01 for all). Neuropsychological impairments varied by educational background. CONCLUSIONS: A broad range of cognitive domains are affected in older, well-controlled, East African PLWH, including those not captured in widely used screening measures. It is possible that educational background affects the observed cognitive impairments in this setting. Future screening measures for similar populations should consider assessment of visual memory, verbal learning, language comprehension, and executive and motor function.

Defining tennis elbow characteristics - The assessment of magnetic resonance imaging defined tendon pathology in an asymptomatic population.

Background: This radiological study aims to assess the prevalence of lateral elbow pathology in an asymptomatic population using 3.0T magnetic resonance imaging (MRI). Methods: Bilateral elbow MRI was undertaken in 30 asymptomatic volunteers. Exclusion criteria included elbow pain within 3 months, elbow trauma or previous diagnosis of lateral epicondylar tendinopathy. Baseline patient-reported outcome measures were recorded along with age and body mass index (BMI). Two musculoskeletal radiologists independently graded the degree of abnormality at the common extensor tendon. Results: Thirty volunteers were categorised according to age; 35-44 (n = 10), 45-54 (n = 11), and 55-65 (n = 9) with a 1:1 male-to-female ratio. Radiological evidence of tendon abnormality was found in 37% of volunteers. The proportion with abnormal findings increased with age; 35-44 (10%), 45-54 (36%), 55-65 (67%) and BMI; 18-24.9 (23%), 25-29.9 (43%), > 30 (67%). Changes were generally 'mild' or 'moderate', with a single volunteer showing 'severe' pathology. Kappa for the radiographic agreement was 0.91 (0.83-0.98). Discussion: This study has demonstrated MRI findings suggestive of pathology at the common extensor tendon to be prevalent in an asymptomatic population, increasing with age and BMI. This draws into question the diagnostic and prognostic value of MRI imaging in lateral epicondylar tendinopathy, especially in older patients.

Does the presence of chronic pain affect scores on cognitive screening tests/brief cognitive measures for dementia? A systematic review and meta-analysis.

OBJECTIVE: Cognitive screening tests can identify potential dementia by indicating a concerning level of cognitive impairment. The older populations for whom this is most relevant are more likely to experience chronic pain, which also impairs cognitive function, but pain's impact on cognitive screening tests specifically remains unknown. METHOD: We conducted a systematic review and meta-analysis (SR/MA) following PRISMA guidelines evaluating cognitive screening scores in studies involving participants with chronic pain compared with a pain-free control group. Our question was whether the presence of chronic pain (self-reported or based on diagnosis) was associated with poorer performance on these screens, and to identify the heterogeneity across groups and screens. RESULTS: The 51 studies identified yielded 62 effect size estimates. The pooled g was 0.76 (95% confidence interval 0.57 to 0.95). Heterogeneity was high for the full model (= 93.16%) with some reductions in sub-analyses. Around half of the studies were identified as being at a low risk of bias. There was no evidence of publication bias. CONCLUSIONS: As a whole, this analysis suggests medium to large effect sizes on cognitive screen performance when people are living with chronic pain. We suggest that clinicians should consider the effect of chronic pain when cognitive screens are employed to investigate dementia. Further research could clarify the effect pain has on different screen sub-domains to aid their effective use with these populations.

Hyperglycaemia is a causal risk factor for upper limb pathologies.

BACKGROUND: Diabetes (regardless of type) and obesity are associated with a range of musculoskeletal disorders. The causal mechanisms driving these associations are unknown for many upper limb pathologies. We used genetic techniques to test the causal link between glycemia, obesity and musculoskeletal conditions. METHODS: In the UK Biobank's unrelated European cohort (N = 379 708) we performed mendelian randomisation (MR) analyses to test for a causal effect of long-term high glycaemia and adiposity on four musculoskeletal pathologies: frozen shoulder, Dupuytren's disease, carpal tunnel syndrome and trigger finger. We also performed single-gene MR using rare variants in the GCK gene. RESULTS: Using MR, we found evidence that long-term high glycaemia has a causal role in the aetiology of upper limb conditions. A 10-mmol/mol increase in genetically predicted haemoglobin A1C (HbA1c) was associated with frozen shoulder: odds ratio (OR) = 1.50 [95% confidence interval (CI), 1.20-1.88], Dupuytren's disease: OR = 1.17 (95% CI, 1.01-1.35), trigger finger: OR = 1.30 (95% CI, 1.09-1.55) and carpal tunnel syndrome: OR = 1.20 (95% CI, 1.09-1.33). Carriers of GCK mutations have increased odds of frozen shoulder: OR = 7.16 (95% CI, 2.93-17.51) and carpal tunnel syndrome: OR = 2.86 (95% CI, 1.50-5.44) but not Dupuytren's disease or trigger finger. We found evidence that an increase in genetically predicted body mass index (BMI) of 5 kg/m2 was associated with carpal tunnel syndrome: OR = 1.13 (95% CI, 1.10-1.16) and associated negatively with Dupuytren's disease: OR = 0.94 (95% CI, 0.90-0.98), but no evidence of association with frozen shoulder or trigger finger. Trigger finger (OR 1.96 (95% CI, 1.42-2.69) P = 3.6e-05) and carpal tunnel syndrome [OR 1.63 (95% CI, 1.36-1.95) P = 8.5e-08] are associated with genetically predicted unfavourable adiposity increase of one standard deviation of body fat. CONCLUSIONS: Our study consistently demonstrates a causal role of long-term high glycaemia in the aetiology of upper limb musculoskeletal conditions. Clinicians treating diabetes patients should be aware of these complications in clinic, specifically those managing the care of GCK mutation carriers. Upper limb musculoskeletal conditions should be considered diabetes complications.

Clinical characteristics and treatment outcomes of angiosarcoma of the head and neck: A 17-year single-centre experience.

INTRODUCTION: Angiosarcomas in the head and neck region are aggressive tumours associated with high local recurrence and metastatic rates. We present our 17-year experience at the North of England Bone and Soft Tissue Tumour Service. METHODS: A retrospective review of our prospectively maintained database was undertaken, looking for patients diagnosed with angiosarcomas affecting the head and neck. Data were gathered using a pre-defined proforma to include demographics, histological characteristics, treatment modalities, adjuvant therapies, local recurrence, distant spread, and disease-specific survival. RESULTS: A total of 23 patients (17 males, 6 females) were identified, with a mean age of 76 years at presentation. Fourteen presented with scalp lesions, whereas the remainder arose on the face. Eighteen patients underwent resection with curative intent, whereas three received palliative radiotherapy and two received comfort-based care only. Of the patients undergoing surgery, 12 had local flap reconstruction and 6 underwent free tissue transfer. Clear resection margins were obtained in nine cases (50%). Fourteen patients (78%) presented with local recurrence after surgery, and 11 (61%) developed distant metastases. The median disease-specific survival time for patients treated with curative intent was 38 months. Eight patients had mapping biopsies ahead of their resection; however, complete resection was achieved in only two cases. DISCUSSION: Angiosarcomas of the head and neck are associated with a poor prognosis, with most patients rapidly developing local recurrence, resulting in adverse clinical outcomes. Mapping biopsies do not demonstrate a clear advantage for achieving complete surgical resection. A radical surgical approach is warranted, given the aggressiveness of the pathology. However, there remains no consensus on optimal surgical management; we recommend further synthesising studies to determine the most appropriate treatment pathway.