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.

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.

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.

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.

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.

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.

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.

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.

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.

Co-designing a nature-based intervention to promote postnatal mental health for mothers and their infants: a complex intervention development study in England.

OBJECTIVES: There is burgeoning evidence for the potential of nature-based interventions to improve wellbeing. However, the role of nature in enhancing maternal mental health, child development and early relationships remains relatively unexplored. This study aimed to develop a co-designed nature-based intervention to improve postnatal mothers' and infants' wellbeing. DESIGN, SETTING AND PARTICIPANTS: Person-based and co-design approaches informed the planning and design of the postnatal nature-based intervention. In stage 1, a multidisciplinary team was formed to agree research questions and appropriate methodology, and a scoping review was conducted. Six qualitative focus groups were then held with 30 mothers and 15 professional stakeholders. In stage 2, intervention guiding principles and a logic model were developed, and a stakeholder consensus meeting was convened to finalise the prototype intervention. The research was conducted in Bristol, UK, across voluntary, educational and community-based healthcare settings. RESULTS: Stakeholder consultation indicated significant enthusiasm for a postnatal nature-based intervention. A scoping review identified little existing research in this area. Focus group data are reported according to four broad themes: (1) perceived benefits of a group postnatal nature-based intervention, (2) potential drawbacks and barriers to access, (3) supporting attendance and implementation, and (4) ideas for intervention content. The developed intervention was tailored for mothers experiencing, or at risk of, postnatal mental health difficulties. It was identified that the intervention should facilitate engagement with the natural world through the senses, while taking into account a broad range of postnatal-specific practical and psychological needs. CONCLUSIONS: To our knowledge, this is the first reported use of person-based and co-design approaches to develop a postnatal nature-based intervention. The resulting intervention was perceived by target users to address their needs and preferences. Further research is needed to determine the feasibility, clinical and cost-effectiveness of this approach.

How long does a shoulder replacement last? A systematic review and meta-analysis of case series and national registry reports with more than 10 years of follow-up.

BACKGROUND: Shoulder replacement is an increasingly common treatment for end-stage degenerative shoulder conditions. Some shoulder replacements are unsuccessful and additional operations might be required. It is important for patients and clinicians to know how long shoulder replacements last and how effectively they reduce pain and improve function. This study aims to determine the longevity and long-term efficacy of shoulder replacements. METHODS: In this systematic review and meta-analysis, we searched MEDLINE and Embase from their inception to Sept 24, 2019, for case series and registry data reporting 10-year or longer survival of total shoulder replacements, humeral hemiarthroplasties, and reverse total shoulder replacements of a specific brand of implant. Survival, implant, and patient-reported outcome measures data were extracted. The primary outcome was implant survival. We reviewed and analysed national joint replacement registries separately. We weighted each series by SE and calculated a pooled survival estimate at years 10, 15, and 20. For patient-reported outcome measures we pooled the standardised mean difference at 10 years. This study is registered with PROSPERO, CRD42019140221. FINDINGS: 927 non-duplicate articles were identified by our search, nine articles (reporting ten series) were eligible for analysis of survival and six articles were eligible for analysis of patient reported outcomes. The ten series reported all-cause survival of 529 total shoulder replacements and 364 humeral hemiarthroplasties; no series for reverse total shoulder replacement met the inclusion criteria. The estimated 10-year survival for total shoulder replacement was 94·6% (95% CI 93·6-97·6) and humeral hemiarthroplasties was 90·4% (87·0-94·0). A single registry contributed 7651 total shoulder replacements, 1395 humeral hemiarthroplasties, and 7953 reverse total shoulder replacements. The pooled registry 10-year survival was 92·0% (95% CI 91·0-93·0) for total shoulder replacement, 85·5% (83·3-87·7) for humeral hemiarthroplasties, and 94·4% (93·4-95·7) for patients with osteoarthritis who had reverse total shoulder replacement and 93·6% (91·1-95·8) for patients with rotator cuff arthropathy who had reverse total shoulder replacement. Pooled 10-year patient-reported outcome measures showed a substantial improvement from baseline scores, with a standardised mean difference of 2·13 (95% CI 1·93-2·34). INTERPRETATION: Our data show that approximately 90% of shoulder replacements last for longer than 10 years and patient-reported benefits are sustained. Our findings will be of use to surgeons and patients in the informed consent process and to health-care providers for resource planning. FUNDING: The National Institute for Health Research, the National Joint Registry for England, Wales, Northern Ireland, and Isle of Man, and the Royal College of Surgeons of England.