Gait retraining to reduce falls: an experimental study toward scalable and personalised use in the home.

BACKGROUND: Age-related neurological conditions can result in poor mobility typified by gait abnormalities and falls, increasing risk of frailty and lowering quality of life. In the UK, the expense and inaccessibility of services to improve mobility through gait training (eg, auditory cueing) is a public health issue. Contemporary and scalable pervasive technologies for widespread public use could provide an affordable and accessible solution. We aimed to show the preliminary efficacy of a novel smartphone app that provides a personalised approach to mobility and gait assessment while facilitating gait training. METHODS: In this experimental study, we recruited participants aged 22-46 years with no physical functional impairments (ie, no age-related neurological condition and who could walk unaided) from Northumbria University staff (Newcastle upon Tyne, UK) between April 19, and May 26. Participants wore a smartphone on their lower back. Inertial data from the smartphone were recorded during two walks, one at a self-selected pace and the other with a personalised auditory cue via headphones (+10% pace on walk 1). Smartphone app functionality enabled the measurement of clinically relevant gait characteristics via a Python-based Cloud server. We compared smartphone-based mobility or gait characteristics with a gold-standard reference (Opal Mobility Lab, APDM). We used Pearson and intraclass correlation coefficients (ICC2,1) to examine agreement between the novel app and reference. The study ran from April 4 to July 21, 2023. This study received ethics approval from the Northumbria University Ethics committee, and all participants provided written informed consent. FINDINGS: Ten adults were recruited (six women and four men; mean age 27·4 years [SD 6·2], mean weight 79·6 kg [SD 12·7], mean height 174·7 cm [SD 7·9]). High levels of agreement were found between the smartphone app and reference, quantified by Pearson (≥0·858) and ICC values (≥0·911). The personalised cueing intervention increased the mean cadence by an average of 11%, which shows good participant adherence to cueing via an app. INTERPRETATION: Here, we propose a contemporary approach to increase the accessibility to a health-based intervention. Preliminary findings suggest the smartphone app is a suitable tool for personalised mobility or gait assessment while facilitating gait training. Use of a scalable app could be an accessible and affordable method for improving mobility to reduce falls in the home. Here, current limitations are the lack of investigation with the smartphone app for neurological gait assessment on older adults and the lack of information on participants app experience, but this will be included in future work. The pervasive use of smartphones enables a decentralised approach to overcoming issues such as frailty and logistical challenges of travelling to bespoke clinics. FUNDING: National Institute of Health and Care Research (NIHR) Applied Research Collaboration (ARC) North-East and North Cumbria (NENC); Faculty of Engineering and Environment at Northumbria University.

Better informing everyday fall risk assessment: experimental studies with contemporary technologies.

BACKGROUND: Age-related mobility issues and frailty are a major public health concern because of an increased risk of falls. Subjective assessment of fall risk in the clinic is limited, failing to account for an individual's habitual activities in the home or community. Equally, objective mobility trackers for use in the home and community lack extrinsic (ie, environmental) data capture to comprehensively inform fall risk. We propose a contemporary approach that combines artificial intelligence (AI) and video glasses to augment current methods of fall risk assessment. METHODS: Two case studies were performed to provide a framework to assess extrinsic factors within fall risk assessment via video glasses. The first was AI-based detection of environment and terrain type. We developed convolutional neural networks (CNN) via a bespoke dataset (>145 000 images) captured from different settings (eg, offices, high streets) via free-licenced video on social media. AI automated a textual description to uphold privacy while describing the scene (eg, indoor and carpet). In the second case study, we provided video glasses to participants within a university campus (two men, 17 women; aged 21-60 years) to capture data for automatically labelling environment and objects (eg, fall hazards) via a CNN object detection algorithm. The case studies ran from Dec 5, 2022, to March 24, 2023. FINDINGS: To date, results show promise for the efficient, and accurate AI-based approach to better inform fall risk. Each component of the framework achieved at least 75% accuracy across a range of walks (indoor and outdoor and multiple terrains) from a dataset of 6283 new images. The AI achieved a mean average precision score of 0·93 for the identification of fall risk hazards. INTERPRETATIONS: The AI-based approach provides a contemporary means to better inform fall risk while providing an ethical means to uphold privacy. The proposed approach could have significant implications for improving overall health and quality of life, enabling ageing in place through habitual data collection with contemporary wearables to decentralise fall risk assessment. A limitation was the lack of data collection on older adults within real world, unscripted settings. However, the next phase of this research is the deployment of the AI on real-world data from a cohort of more than 40 participants within UK-based homes. FUNDING: National Institute of Health and Care Research (NIHR) Applied Research Collaboration (ARC) North-East and North Cumbria (NENC), Faculty of Engineering and Environment at Northumbria University.

Anal Cancers in Previously Screened Versus Unscreened Patients: Tumor Stage and Treatment Outcomes.

BACKGROUND: Targeted screening programs for patients at high risk for anal squamous-cell carcinoma have been proposed; however, the evidence in support of screening remains unclear. OBJECTIVE: This study aimed to determine whether screening high-risk patients (predominantly those living with HIV) detected squamous-cell carcinoma at an earlier stage compared to the routine practice of not screening. DESIGN: This is a cohort study. SETTINGS: This study was conducted at a quaternary care center in Canada. PATIENTS: Included patients were at least 18 years old with a pathologic diagnosis of invasive anal squamous-cell carcinoma between 2002 and 2022. INTERVENTIONS: Patients diagnosed through a high-risk screening program were compared to those who did not undergo screening. MAIN OUTCOME MEASURES: The primary outcome was clinical stage at presentation, categorized as T1N0M0 vs other. Secondary outcomes included treatments received, treatment failure, and overall survival. RESULTS: A total of 612 patients with anal squamous-cell carcinoma were included, with 26 of those patients diagnosed through a screening program. Patients with screen-detected cancers had greater odds of presenting with T1N0M0 tumors compared to unscreened patients (18 [69.2%] vs 84 [14.3%]; adjusted OR 9.95; 95% CI, 3.95-25.08). A propensity score-matched sensitivity analysis found similar results (OR 11.13; 95% CI, 4.67-26.52). Screened patients had greater odds of treatment with wide local excision alone, as opposed to any combination of chemotherapy, radiation therapy, and surgery (3 [12.5%] vs 18 [3.2%]; OR 4.38; 95% CI, 1.20-16.04). There were no statistically significant differences in treatment failure or overall survival between groups. LIMITATIONS: The small number of screened patients limits the power of the analysis. CONCLUSIONS: Screening for anal squamous-cell carcinoma among high-risk populations detects cancers at an earlier stage. Patients with screen-detected cancers also had a greater likelihood of being candidates for wide local excision alone, which may have spared them the morbidity associated with chemoradiotherapy or abdominoperineal resection. See Video Abstract. CNCERES DE ANO EN PACIENTES PREVIAMENTE DETECTADOS POR CRIBADO VERSUS NO DETECTADOS ESTADIO DEL TUMOR Y RESULTADOS DEL TRATAMIENTO: ANTECEDENTES:Se han propuesto programas de cribado dirigidos a pacientes con alto riesgo de carcinoma anal de células escamosas; sin embargo, la evidencia a favor de la detección sigue sin estar clara.OBJETIVO:Este estudio tuvo como objetivo determinar si el cribado de pacientes de alto riesgo (predominantemente aquellos que viven con el VIH) detectó el carcinoma de células escamosas en una etapa más temprana en comparación con la práctica habitual de no cribado.DISEÑO:Este es un estudio de cohortes.CONFIGURACIÓN:Este estudio se realizó en un centro de atención cuaternaria en Canadá.PACIENTES:Los pacientes incluidos tenían al menos 18 años con un diagnóstico patológico de carcinoma de células escamosas anal invasivo entre 2002 y 2022.INTERVENCIONES:Los pacientes diagnosticados mediante un programa de cribado de alto riesgo se compararon con aquellos que no se sometieron a cribado.PRINCIPALES MEDIDAS DE RESULTADO:El resultado primario fue el estadio clínico en la presentación, categorizado como T1N0M0 versus otro. Los resultados secundarios incluyeron los tratamientos recibidos, el fracaso del tratamiento y la supervivencia general.RESULTADOS:Se incluyeron un total de 612 pacientes con carcinoma anal de células escamosas, con 26 de esos pacientes diagnosticados a través de un programa de cribado. Los pacientes con cánceres detectados mediante cribado tenían mayores probabilidades de presentar tumores T1N0M0 en comparación con los pacientes no cribados (18 [69.2%] frente a 84 [14.3%]; razón de probabilidad ajustada 9.95; intervalo de confianza del 95 % 3.95 -25.08). Un análisis de sensibilidad emparejado por puntaje de propensión encontró resultados similares (odds ratio 11.13; intervalo de confianza del 95% 4.67 -26.52; p < 0.001). Los pacientes examinados tenían mayores probabilidades de recibir tratamiento con escisión local amplia sola, en comparación con cualquier combinación de quimioterapia, radiación y cirugía (3 [12.5%] frente a 18 [3.2%]; razón de probabilidad 4.38; intervalo de confianza del 95 % 1.20 -16.04). No hubo diferencias estadísticamente significativas en el fracaso del tratamiento o la supervivencia global entre los grupos.LIMITACIONES:El pequeño número de pacientes evaluados limita el poder del análisis.CONCLUSIONES:La detección del carcinoma anal de células escamosas entre las poblaciones de alto riesgo detecta los cánceres en una etapa más temprana. Los pacientes con cánceres detectados mediante cribado también tenían una mayor probabilidad de ser candidatos para una escisión local amplia sola, lo que puede haberles evitado la morbilidad asociada con la quimiorradioterapia o la resección abdominoperineal. (Traducción --Dr. Aurian Garcia Gonzalez ).

Factors Associated With Loss to Follow-Up in Surgical Trials: A Systematic Review and Meta-Analysis.

INTRODUCTION: Loss to follow-up (LTFU) distorts results of randomized controlled trials (RCTs). Understanding trial characteristics that contribute to LTFU may enable investigators to anticipate the extent of LTFU and plan retention strategies. The objective of this systematic review and meta-analysis was to investigate the extent of LTFU in surgical RCTs and evaluate associations between trial characteristics and LTFU. METHODS: MEDLINE, Embase, and PubMed Central were searched for surgical RCTs published between January 2002 and December 2021 in the 30 highest impact factor surgical journals. Two-hundred eligible RCTs were randomly selected. The pooled LTFU rate was estimated using random intercept Poisson regression. Associations between trial characteristics and LTFU were assessed using metaregression. RESULTS: The 200 RCTs included 37,914 participants and 1307 LTFU events. The pooled LTFU rate was 3.10 participants per 100 patient-years (95% confidence interval [CI] 1.85-5.17). Trial characteristics associated with reduced LTFU were standard-of-care outcome assessments (rate ratio [RR] 0.17; 95% CI 0.06-0.48), surgery for transplantation (RR 0.08; 95% CI 0.01-0.43), and surgery for cancer (RR 0.10; 95% CI 0.02-0.53). Increased LTFU was associated with patient-reported outcomes (RR 14.21; 95% CI 4.82-41.91) and follow-up duration ≥ three months (odds ratio 10.09; 95% CI 4.79-21.28). CONCLUSIONS: LTFU in surgical RCTs is uncommon. Participants may be at increased risk of LTFU in trials with outcomes assessed beyond the standard of care, surgical indications other than cancer or transplant, patient-reported outcomes, and longer follow-up. Investigators should consider the impact of design on LTFU and plan retention strategies accordingly.

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.

Hospital learning curves for robot-assisted surgeries: a population-based analysis.

BACKGROUND: Robot-assisted surgery has been rapidly adopted. It is important to define the learning curve to inform credentialling requirements, training programs, identify fast and slow learners, and protect patients. This study aimed to characterize the hospital learning curve for common robot-assisted procedures. STUDY DESIGN: This cohort study, using administrative health data for Ontario, Canada, included adult patients who underwent a robot-assisted radical prostatectomy (RARP), total robotic hysterectomy (TRH), robot-assisted partial nephrectomy (RAPN), or robotic portal lobectomy using four arms (RPL-4) between 2010 and 2021. The association between cumulative hospital volume of a robot-assisted procedure and major complications was evaluated using multivariable logistic models adjusted for patient characteristics and clustering at the hospital level. RESULTS: A total of 6814 patients were included, with 5230, 543, 465, and 576 patients in the RARP, TRH, RAPN, and RPL-4 cohorts, respectively. There was no association between cumulative hospital volume and major complications. Visual inspection of learning curves demonstrated a transient worsening of outcomes followed by subsequent improvements with experience. Operative time decreased for all procedures with increasing volume and reached plateaus after approximately 300 RARPs, 75 TRHs, and 150 RPL-4s. The odds of a prolonged length of stay decreased with increasing volume for patients undergoing a RARP (OR 0.87; 95% CI 0.82-0.92) or RPL-4 (OR 0.77; 95% CI 0.68-0.87). CONCLUSION: Hospitals may adopt robot-assisted surgery without significantly increasing the risk of major complications for patients early in the learning curve and with an expectation of increasing efficiency.

Hospital volume-outcome relationships for robot-assisted surgeries: a population-based analysis.

BACKGROUND: Associations between procedure volumes and outcomes can inform minimum volume standards and the regionalization of health services. Robot-assisted surgery continues to expand globally; however, data are limited regarding which hospitals should be using the technology. STUDY DESIGN: Using administrative health data for all residents of Ontario, Canada, this retrospective cohort study included adult patients who underwent a robot-assisted radical prostatectomy (RARP), total robotic hysterectomy (TRH), robot-assisted partial nephrectomy (RAPN), or robotic portal lobectomy using 4 arms (RPL-4) between January 2010 and September 2021. Associations between yearly hospital volumes and 90-day major complications were evaluated using multivariable logistic regression models adjusted for patient characteristics and clustering at the level of the hospital. RESULTS: A total of 10,879 patients were included, with 7567, 1776, 724, and 812 undergoing a RARP, TRH, RAPN, and RPL-4, respectively. Yearly hospital volume was not associated with 90-day complications for any procedure. Doubling of yearly volume was associated with a 17-min decrease in operative time for RARP (95% confidence interval [CI] - 23 to - 10), 8-min decrease for RAPN (95% CI - 14 to - 2), 24-min decrease for RPL-4 (95% CI - 29 to - 19), and no significant change for TRH (- 7 min; 95% CI - 17 to 3). CONCLUSION: The risk of 90-day major complications does not appear to be higher in low volume hospitals; however, they may not be as efficient with operating room utilization. Careful case selection may have contributed to the lack of an observed association between volumes and complications.

Assessing frailty amongst older people admitted to hospital in a low-income setting: a multicentre study in northern Tanzania.

BACKGROUND: Populations are ageing globally and Low- and Middle-Income Countries (LMICs) are experiencing the fastest rates of demographic change. Few studies have explored the burden of frailty amongst older people in hospital in LMICs, where healthcare services are having to rapidly adapt to align with the needs of older people. This study aimed to measure the prevalence of frailty amongst older people admitted to hospital in Tanzania and to explore their demographic and clinical characteristics. METHODS: This study had a prospective observational design. Over a six-month period, all adults ≥ 60 years old admitted to medical wards in four hospitals in northern Tanzania were invited to participate. They were screened for frailty using the Clinical Frailty Scale (CFS) and the Frailty Phenotype (FP). Demographic and clinical characteristics of interest were recorded in a structured questionnaire. These included the Barthel Index, the Identification of Elderly Africans Instrumental Activities of Daily Living (IADEA-IADL) and Cognitive (IDEA-Cog) screens, the EURO-D depression scale and Confusion Assessment Method. RESULTS: 540 adults aged ≥ 60 were admitted, and 308 completed assessment. Frailty was present in 66.6% using the CFS and participants with frailty were significantly older, with lower levels of education and literacy, greater disability, greater comorbidity, poorer cognition and higher levels of delirium. Using the FP, 57.0% of participants were classed as frail though a majority of participants (n = 159, 51.6%) could not be classified due to a high proportion of missing data. CONCLUSIONS: This study indicates that the prevalence of frailty on medical wards in northern Tanzania is high according to the CFS. However, the challenges in operationalising the FP in this setting highlight the need for future work to adapt frailty screening tools for an African context. Future investigations should also seek to correlate frailty status with long-term clinical outcomes after admission in this setting.

Tungsten-182 evidence for an ancient kimberlite source.

Globally distributed kimberlites with broadly chondritic initial 143Nd-176Hf isotopic systematics may be derived from a chemically homogenous, relatively primitive mantle source that remained isolated from the convecting mantle for much of the Earth's history. To assess whether this putative reservoir may have preserved remnants of an early Earth process, we report 182W/184W and 142Nd/144Nd data for "primitive" kimberlites from 10 localities worldwide, ranging in age from 1,153 to 89 Ma. Most are characterized by homogeneous µ182W and µ142Nd values averaging -5.9 ± 3.6 ppm (2SD, n = 13) and +2.7 ± 2.9 ppm (2SD, n = 6), respectively. The remarkably uniform yet modestly negative µ182W values, coupled with chondritic to slightly suprachondritic initial 143Nd/144Nd and 176Hf/177Hf ratios over a span of nearly 1,000 Mya, provides permissive evidence that these kimberlites were derived from one or more long-lived, early formed mantle reservoirs. Possible causes for negative µ182W values among these kimberlites include the transfer of W with low µ182W from the core to the mantle source reservoir(s), creation of the source reservoir(s) as a result of early silicate fractionation, or an overabundance of late-accreted materials in the source reservoir(s). By contrast, two younger kimberlites emplaced at 72 and 52 Ma and characterized by distinctly subchondritic initial 176Hf/177Hf and 143Nd/144Nd have µ182W values consistent with the modern upper mantle. These isotopic compositions may reflect contamination of the ancient kimberlite source by recycled crustal components with µ182W ≥ 0.

SSR white paper: guidelines for utilization and performance of direct MR arthrography.

OBJECTIVE: Direct magnetic resonance arthrography (dMRA) is often considered the most accurate imaging modality for the evaluation of intra-articular structures, but utilization and performance vary widely without consensus. The purpose of this white paper is to develop consensus recommendations on behalf of the Society of Skeletal Radiology (SSR) based on published literature and expert opinion. MATERIALS AND METHODS: The Standards and Guidelines Committee of the SSR identified guidelines for utilization and performance of dMRA as an important topic for study and invited all SSR members with expertise and interest to volunteer for the white paper panel. This panel was tasked with determining an outline, reviewing the relevant literature, preparing a written document summarizing the issues and controversies, and providing recommendations. RESULTS: Twelve SSR members with expertise in dMRA formed the ad hoc white paper authorship committee. The published literature on dMRA was reviewed and summarized, focusing on clinical indications, technical considerations, safety, imaging protocols, complications, controversies, and gaps in knowledge. Recommendations for the utilization and performance of dMRA in the shoulder, elbow, wrist, hip, knee, and ankle/foot regions were developed in group consensus. CONCLUSION: Although direct MR arthrography has been previously used for a wide variety of clinical indications, the authorship panel recommends more selective application of this minimally invasive procedure. At present, direct MR arthrography remains an important procedure in the armamentarium of the musculoskeletal radiologist and is especially valuable when conventional MRI is indeterminant or results are discrepant with clinical evaluation.

Enhancing fall risk assessment: instrumenting vision with deep learning during walks.

BACKGROUND: Falls are common in a range of clinical cohorts, where routine risk assessment often comprises subjective visual observation only. Typically, observational assessment involves evaluation of an individual's gait during scripted walking protocols within a lab to identify deficits that potentially increase fall risk, but subtle deficits may not be (readily) observable. Therefore, objective approaches (e.g., inertial measurement units, IMUs) are useful for quantifying high resolution gait characteristics, enabling more informed fall risk assessment by capturing subtle deficits. However, IMU-based gait instrumentation alone is limited, failing to consider participant behaviour and details within the environment (e.g., obstacles). Video-based eye-tracking glasses may provide additional insight to fall risk, clarifying how people traverse environments based on head and eye movements. Recording head and eye movements can provide insights into how the allocation of visual attention to environmental stimuli influences successful navigation around obstacles. Yet, manual review of video data to evaluate head and eye movements is time-consuming and subjective. An automated approach is needed but none currently exists. This paper proposes a deep learning-based object detection algorithm (VARFA) to instrument vision and video data during walks, complementing instrumented gait. METHOD: The approach automatically labels video data captured in a gait lab to assess visual attention and details of the environment. The proposed algorithm uses a YoloV8 model trained on with a novel lab-based dataset. RESULTS: VARFA achieved excellent evaluation metrics (0.93 mAP50), identifying, and localizing static objects (e.g., obstacles in the walking path) with an average accuracy of 93%. Similarly, a U-NET based track/path segmentation model achieved good metrics (IoU 0.82), suggesting that the predicted tracks (i.e., walking paths) align closely with the actual track, with an overlap of 82%. Notably, both models achieved these metrics while processing at real-time speeds, demonstrating efficiency and effectiveness for pragmatic applications. CONCLUSION: The instrumented approach improves the efficiency and accuracy of fall risk assessment by evaluating the visual allocation of attention (i.e., information about when and where a person is attending) during navigation, improving the breadth of instrumentation in this area. Use of VARFA to instrument vision could be used to better inform fall risk assessment by providing behaviour and context data to complement instrumented e.g., IMU data during gait tasks. That may have notable (e.g., personalized) rehabilitation implications across a wide range of clinical cohorts where poor gait and increased fall risk are common.

Bridging the gap: assessing the integration of robotic-assisted surgery into Canadian surgical training programs.

SummaryThe adoption of robotic surgery has surged globally across multiple surgical specialties, but uptake in Canada has unfolded at a slower pace. Surgical educators and trainees in Canada face potential challenges related to sufficient exposure, experience, and competence in robotic surgical procedures. We conducted a cross-sectional national survey to gain insight into the perspectives of program directors overseeing general surgery residency and fellowship programs on the integration of robotic surgery into Canadian surgical training programs. Despite the presence of robotic surgery platforms at most academic and academic-affiliated hospitals, few trainees have exposure to any robotic surgery. Furthermore, a gap exists between the training provided in robotic surgery and its anticipated relevance to trainees upon graduation. Increased focus on the integration of robotic surgery within general surgical training in Canada is required to equip trainees for their careers.

Controlled Human Infection Models To Accelerate Vaccine Development.

The timelines for developing vaccines against infectious diseases are lengthy, and often vaccines that reach the stage of large phase 3 field trials fail to provide the desired level of protective efficacy. The application of controlled human challenge models of infection and disease at the appropriate stages of development could accelerate development of candidate vaccines and, in fact, has done so successfully in some limited cases. Human challenge models could potentially be used to gather critical information on pathogenesis, inform strain selection for vaccines, explore cross-protective immunity, identify immune correlates of protection and mechanisms of protection induced by infection or evoked by candidate vaccines, guide decisions on appropriate trial endpoints, and evaluate vaccine efficacy. We prepared this report to motivate fellow scientists to exploit the potential capacity of controlled human challenge experiments to advance vaccine development. In this review, we considered available challenge models for 17 infectious diseases in the context of the public health importance of each disease, the diversity and pathogenesis of the causative organisms, the vaccine candidates under development, and each model's capacity to evaluate them and identify correlates of protective immunity. Our broad assessment indicated that human challenge models have not yet reached their full potential to support the development of vaccines against infectious diseases. On the basis of our review, however, we believe that describing an ideal challenge model is possible, as is further developing existing and future challenge models.

The prevalence and outcomes of depression in older HIV-positive adults in Northern Tanzania: a longitudinal study.

Studies of depression and its outcomes in older people living with HIV (PLWH) are currently lacking in sub-Saharan Africa. This study aims to investigate the prevalence of psychiatric disorders in PLWH aged ≥ 50 years in Tanzania focussing on prevalence and 2-year outcomes of depression. PLWH aged ≥ 50 were systematically recruited from an outpatient clinic and assessed using the Mini-International Neuropsychiatric Interview (MINI). Neurological and functional impairment was assessed at year 2 follow-up. At baseline, 253 PLWH were recruited (72.3% female, median age 57, 95.5% on cART). DSM-IV depression was highly prevalent (20.9%), whereas other DSM-IV psychiatric disorders were uncommon. At follow-up (n = 162), incident cases of DSM-IV depression decreased from14.2 to 11.1% (χ2: 2.48, p = 0.29); this decline was not significant. Baseline depression was associated with increased functional and neurological impairment. At follow-up, depression was associated with negative life events (p = 0.001), neurological impairment (p < 0.001), and increased functional impairment (p = 0.018), but not with HIV and sociodemographic factors. In this setting, depression appears highly prevalent and associated with poorer neurological and functional outcomes and negative life events. Depression may be a future intervention target.

Dementia Prevalence and Risk Factors: Data From Rural Tanzania.

OBJECTIVES: The burden of dementia is increasing in sub-Saharan Africa (SSA), but there are limited epidemiological data on dementia in SSA. This study investigated the prevalence and associations of dementia in older adults (less than 60 y) attending the outpatient department of Mount Meru Hospital in Tanzania. METHODS: This one-phase cross-sectional study screened a sample using the Identification of Dementia in Elderly Africans (IDEA) cognitive screening tool. Those that screened as having possible and probable dementia were further assessed, and diagnosis of dementia was made according to the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV). Demographic and risk factor data were collected. RESULTS: Within those screened, 57/1141 (5.0%) (95% CI: 3.7-6.3) had dementia. Female sex [odds ratio (OR)=2.778, 95% CI: 1.074-7.189], having never attended school (OR=6.088, 95% CI: 1.360-27.256), alcohol (U/wk) (OR=1.080, 95% CI: 1.016-1.149), uncorrected visual impairment (OR=4.260, 95% CI: 1.623-11.180), body mass index <18.5 kg/m 2 (OR=6.588, 95% CI: 2.089-20.775), and stroke (OR=15.790, 95% CI: 3.48-74.475) were found to be significantly, independently associated with dementia. CONCLUSIONS: The prevalence of dementia in this population is similar to a recent community-based rate in Tanzania and lower than a hospital-based rate in Senegal. This is the first time the association between visual impairment and dementia has been reported in SSA. Other associations are in keeping with previous literature.

Ocular microtremor: a structured review.

Ocular microtremor (OMT) is the smallest of three involuntary fixational micro eye movements, which has led to it being under researched in comparison. The link between OMT and brain function generates a strong rationale for further study as there is potential for its use as a biomarker in populations with neurological injury and disease. This structured review focused on populations previously studied, instrumentation used for measurement, commonly reported OMT outcomes, and recommendations concerning protocol design and future studies. Current methods of quantifying OMT will be reviewed to analyze their efficacy and efficiency and guide potential development and understanding of novel techniques. Electronic databases were systematically searched and compared with predetermined inclusion criteria. 216 articles were identified in the search and screened by two reviewers. 16 articles were included for review. Findings showed that piezoelectric probe is the most common method of measuring OMT, with fewer studies involving non-invasive approaches, such as contact lenses and laser imaging. OMT frequency was seen to be reduced during general anesthesia at loss of consciousness and in neurologically impaired participants when compared to healthy adults. We identified the need for a non-invasive technique for measuring OMT and highlight its potential in clinical applications as an objective biomarker for neurological assessments. We highlight the need for further research on the clinical validation of OMT to establish its potential to identify or predict a meaningful clinical or functional state, specifically, regarding accuracy, precision, and reliability of OMT.

Prevalence and 1-year incidence of HIV-associated neurocognitive disorder (HAND) in adults aged ≥50 years attending standard HIV clinical care in Kilimanjaro, Tanzania.

OBJECTIVES: HIV-associated neurocognitive disorders (HANDs) are prevalent in older people living with HIV (PLWH) worldwide. HAND prevalence and incidence studies of the newly emergent population of combination antiretroviral therapy (cART)-treated older PLWH in sub-Saharan Africa are currently lacking. We aimed to estimate HAND prevalence and incidence using robust measures in stable, cART-treated older adults under long-term follow-up in Tanzania and report cognitive comorbidities. DESIGN: Longitudinal study. PARTICIPANTS: A systematic sample of consenting HIV-positive adults aged ≥50 years attending routine clinical care at an HIV Care and Treatment Centre during March-May 2016 and followed up March-May 2017. MEASUREMENTS: HAND by consensus panel Frascati criteria based on detailed locally normed low-literacy neuropsychological battery, structured neuropsychiatric clinical assessment, and collateral history. Demographic and etiological factors by self-report and clinical records. RESULTS: In this cohort (n = 253, 72.3% female, median age 57), HAND prevalence was 47.0% (95% CI 40.9-53.2, n = 119) despite well-managed HIV disease (Mn CD4 516 (98-1719), 95.5% on cART). Of these, 64 (25.3%) were asymptomatic neurocognitive impairment, 46 (18.2%) mild neurocognitive disorder, and 9 (3.6%) HIV-associated dementia. One-year incidence was high (37.2%, 95% CI 25.9 to 51.8), but some reversibility (17.6%, 95% CI 10.0-28.6 n = 16) was observed. CONCLUSIONS: HAND appear highly prevalent in older PLWH in this setting, where demographic profile differs markedly to high-income cohorts, and comorbidities are frequent. Incidence and reversibility also appear high. Future studies should focus on etiologies and potentially reversible factors in this setting.

Misjudging drinking water quality risk: Adopting a barrier approach for meaningful risk assessment to address latent risks.

The water quality risk assessment is the foundation for every drinking Water Safety Plan. The need to conform with a 'Corporate' risk assessment model commonly dominated by asset management frequency data can cause misjudgement of microbial risk. Well-performed risk assessments should identify potential risks. Risk assessments which place too much emphasis on historical evidence to demonstrate 'likelihood' of microbial contamination are unsuitable for drinking water quality because they fail to recognise 'latent' risks associated with absent or underperforming barriers to contamination. Most outbreaks occur when these 'latent' factors align to create a failure. Good risk assessments need to provide foresight. This is achieved if drinking water quality risk assessments are based on a 'barrier' approach. Where adequate and reliable multiple barriers to contamination are present the likelihood of a hazardous event should then be categorised as rare. Where barriers are absent, inadequate, or unreliable, then a higher likelihood is appropriate, depending on the nature and extent of the barrier shortfall. Practical examples show how the 'barrier' approach can be applied. The barrier risk assessment directly informs the operational monitoring programme, enabling regular confirmation that the challenge and barrier performance are consistent with the predictions of the risk assessment.

Is Enoxaparin Associated With a Higher Risk of Persistent Wound Drainage Than Aspirin? A Secondary Analysis of Data From the CRISTAL Randomized Trial.

BACKGROUND: Owing to its association with prosthetic joint infection, persistent wound drainage has become an important clinical entity after THA or TKA. The association between venous thromboembolism (VTE) prophylaxis and persistent wound drainage has not been extensively reported before but has potentially important clinical implications. QUESTIONS/PURPOSES: (1) Is the type of VTE prophylaxis (enoxaparin or aspirin) used after hip arthroplasty or knee arthroplasty associated with a higher risk of persistent wound drainage? (2) In patients who experience persistent wound drainage, is the type of VTE prophylaxis associated with a longer time taken to achieve a dry wound? (3) Is type of VTE prophylaxis associated with a higher risk of joint-related reoperation within 6 months? METHODS: This was a secondary analysis of data from an earlier cluster-randomized trial conducted through the Australian Orthopaedic Association National Joint Replacement Registry; data were drawn from two participating hospitals from that study. According to the trial's allocation sequence, the two participating hospitals were randomized to administer aspirin (100 mg daily) or enoxaparin (40 mg daily) as VTE prophylaxis to all patients undergoing hip arthroplasty for 35 days after the procedure and for all patients undergoing knee arthroplasty for 14 days afterwards. Crossover to the alternate prophylaxis group occurred after the patient enrollment target had been met for the first arm. Between April 2019 and December 2020, 1339 of 1679 eligible patients were included in this study; 82% (707 of 861) of eligible patients were allocated to the enoxaparin group and 77% (632 of 818) of eligible patients we allocated to the aspirin group. The mean age in both groups was 67 ± 10 years and the mean BMI was 32 ± 7 kg/m 2 . There was a higher proportion of male patients (43% [302 of 707] versus 36% [227 of 632]; p = 0.01), hip arthroplasties (36% [254 of 707] versus 29% [182 of 632]; p = 0.006), and patients receiving subcuticular closure (62% [441 of 707] versus 33% [208 of 631]; p < 0.001) in the enoxaparin group than in the aspirin group. Patients were monitored for wound drainage on each postoperative day until discharge, and this was recorded in the medical record once per day. Assessors were not blinded to the type of prophylaxis each patient received. Persistent wound drainage was defined as any wound drainage beyond Postoperative Day 3. For patients who experienced persistent wound drainage, the time taken to achieve a dry wound was defined as the number of days beyond Postoperative Day 3 for the wound to become dry. Logistic regression was used to determine whether the prophylaxis type was associated with persistent wound drainage. For patients with persistent wound drainage, the median time of drainage was compared between groups using the Kruskal-Wallis test. The number of patients undergoing a joint-related reoperation within 6 months was identified through data linkage to the Australian Orthopaedic Association National Joint Replacement Registry and electronic record review, and was compared using a Fisher exact test. RESULTS: We found no difference between the enoxaparin and aspirin groups in terms of the percentage of patients who had persistent wound drainage (9% [65 of 707] versus 8% [49 of 632], odds ratio 1.2 [95% confidence interval 0.8 to 1.8]; p = 0.40). For patients receiving subcuticular closure, after controlling for other potentially confounding variables, including age, sex, BMI, preoperative anticoagulant use, and type of arthroplasty, enoxaparin was associated with a higher risk of persistent wound drainage than aspirin (OR 3.6 [95% CI 1.5 to 10.6]; p = 0.009). For patients receiving a skin staple closure, after controlling for the same variables above, we found enoxaparin was not associated with a higher risk of persistent wound drainage (OR 1.1 [95% CI 0.7 to 1.9]; p = 0.66). For patients who experienced persistent wound drainage patients (114: 65 in the enoxaparin group and 49 in the aspirin group), there was no difference in the median (interquartile range) time taken to achieve a dry wound (enoxaparin: 1 day [IQR 1 to 2 days], aspirin: 1 day [IQR 1 to 3 days]; p = 0.22). There was no difference in the risk of joint-related reoperation within 6 months between enoxaparin (2.4% [17 of 707]) and aspirin (2.2% [14 of 632], OR 1.1 [95% CI 0.5 to 2.4]; p = 0.86). CONCLUSION: Enoxaparin was not associated with an increased risk of persistent wound drainage compared with aspirin for all patients included in this study. Enoxaparin may be associated with a higher risk of drainage for patients receiving subcuticular closure. However, this finding should be interpreted cautiously, given the small sample size in this analysis. The duration of drainage was short regardless of the prophylaxis used, and enoxaparin was not associated with an increased risk of joint-related reoperation. These findings should not deter clinicians from using enoxaparin for VTE prophylaxis after hip or knee arthroplasty. LEVEL OF EVIDENCE: Level III, therapeutic study.

Sonification for Personalised Gait Intervention.

Mobility challenges threaten physical independence and good quality of life. Often, mobility can be improved through gait rehabilitation and specifically the use of cueing through prescribed auditory, visual, and/or tactile cues. Each has shown use to rectify abnormal gait patterns, improving mobility. Yet, a limitation remains, i.e., long-term engagement with cueing modalities. A paradigm shift towards personalised cueing approaches, considering an individual's unique physiological condition, may bring a contemporary approach to ensure longitudinal and continuous engagement. Sonification could be a useful auditory cueing technique when integrated within personalised approaches to gait rehabilitation systems. Previously, sonification demonstrated encouraging results, notably in reducing freezing-of-gait, mitigating spatial variability, and bolstering gait consistency in people with Parkinson's disease (PD). Specifically, sonification through the manipulation of acoustic features paired with the application of advanced audio processing techniques (e.g., time-stretching) enable auditory cueing interventions to be tailored and enhanced. These methods used in conjunction optimize gait characteristics and subsequently improve mobility, enhancing the effectiveness of the intervention. The aim of this narrative review is to further understand and unlock the potential of sonification as a pivotal tool in auditory cueing for gait rehabilitation, while highlighting that continued clinical research is needed to ensure comfort and desirability of use.