Amyloid-PET imaging predicts functional decline in clinically normal individuals.

BACKGROUND: There is good evidence that elevated amyloid-ß (Aß) positron emission tomography (PET) signal is associated with cognitive decline in clinically normal (CN) individuals. However, it is less well established whether there is an association between the Aß burden and decline in daily living activities in this population. Moreover, Aß-PET Centiloids (CL) thresholds that can optimally predict functional decline have not yet been established. METHODS: Cross-sectional and longitudinal analyses over a mean three-year timeframe were performed on the European amyloid-PET imaging AMYPAD-PNHS dataset that phenotypes 1260 individuals, including 1032 CN individuals and 228 participants with questionable functional impairment. Amyloid-PET was assessed continuously on the Centiloid (CL) scale and using Aß groups (CL < 12 = Aß-, 12 ≤ CL ≤ 50 = Aß-intermediate/Aß± , CL > 50 = Aß+). Functional abilities were longitudinally assessed using the Clinical Dementia Rating (Global-CDR, CDR-SOB) and the Amsterdam Instrumental Activities of Daily Living Questionnaire (A-IADL-Q). The Global-CDR was available for the 1260 participants at baseline, while baseline CDR-SOB and A-IADL-Q scores and longitudinal functional data were available for different subsamples that had similar characteristics to those of the entire sample. RESULTS: Participants included 765 Aß- (61%, Mdnage = 66.0, IQRage = 61.0-71.0; 59% women), 301 Aß± (24%; Mdnage = 69.0, IQRage = 64.0-75.0; 53% women) and 194 Aß+ individuals (15%, Mdnage = 73.0, IQRage = 68.0-78.0; 53% women). Cross-sectionally, CL values were associated with CDR outcomes. Longitudinally, baseline CL values predicted prospective changes in the CDR-SOB (bCL*Time = 0.001/CL/year, 95% CI [0.0005,0.0024], p = .003) and A-IADL-Q (bCL*Time = -0.010/CL/year, 95% CI [-0.016,-0.004], p = .002) scores in initially CN participants. Increased clinical progression (Global-CDR > 0) was mainly observed in Aß+ CN individuals (HRAß+ vs Aß- = 2.55, 95% CI [1.16,5.60], p = .020). Optimal thresholds for predicting decline were found at 41 CL using the CDR-SOB (bAß+ vs Aß- = 0.137/year, 95% CI [0.069,0.206], p < .001) and 28 CL using the A-IADL-Q (bAß+ vs Aß- = -0.693/year, 95% CI [-1.179,-0.208], p = .005). CONCLUSIONS: Amyloid-PET quantification supports the identification of CN individuals at risk of functional decline. TRIAL REGISTRATION: The AMYPAD PNHS is registered at www.clinicaltrialsregister.eu with the EudraCT Number: 2018-002277-22.

Personalizing rehabilitation for individuals with musculoskeletal impairments: Feasibility of implementation of the Measures Associated to Prognostic (MAPS) tool.

INTRODUCTION: The Measures Associated to PrognoStic (MAPS) tool is a standardized questionnaire that integrates validated prognostic tools to detect the presence of biopsychosocial prognostic factors in patients consulting for musculoskeletal disorders. PURPOSE: The objectives were to assess the: 1) feasibility of implementation of the MAPS tool, 2) clinicians' acceptability of the dashboard, and 3) patients' acceptability of the MAPS tool. METHODS: Twenty physiotherapists and two occupational therapists from seven outpatient musculoskeletal clinics were recruited to implement the MAPS tool during a 3-month timeframe, where new patients completed the questionnaire upon initial assessment. The results were presented to the clinicians via a dashboard. Surveys and semi-structured interviews were conducted to measure feasibility and acceptability. RESULTS: Six out of 11 feasibility criteria (55%) and 21 out of 24 acceptability criteria (88%) reached the a priori threshold for success. The interviews allowed us to identify three main themes to facilitate implementation: 1) limiting the burden, 2) ensuring patients' understanding of the tool's purpose, and 3) integrating the dashboard as a clinical information tool. CONCLUSION: Our quantitative and qualitative results support the feasibility of implementation and acceptability of the MAPS tool pending minor adjustments. Depicting the patients' prognostic profile has the potential to help clinicians optimize their interventions for patients presenting with musculoskeletal disorders.

The spatial extent of tauopathy on [18F]MK-6240 tau PET shows stronger association with cognitive performances than the standard uptake value ratio in Alzheimer's disease.

PURPOSE: [18F]MK-6240, a second-generation tau PET tracer, is increasingly used for the detection and the quantification of in vivo cerebral tauopathy in Alzheimer's disease (AD). Given that neurological symptoms are better explained by the topography rather than by the nature of brain lesions, our study aimed to evaluate whether cognitive impairment would be more closely associated with the spatial extent than with the intensity of tau-PET signal, as measured by the standard uptake value ratio (SUVr). METHODS: [18F]MK6240 tau-PET data from 82 participants in the AD spectrum were quantified in three different brain regions (Braak ≤ 2, Braak ≤ 4, and Braak ≤ 6) using SUVr and the extent of tauopathy (EOT, percentage of voxels with SUVr ≥ 1.3). PET data were first compared between diagnostic categories, and ROC curves were computed to evaluate sensitivity and specificity. PET data were then correlated to cognitive performances and cerebrospinal fluid (CSF) tau values. RESULTS: The EOT in the Braak ≤ 2 region provided the highest diagnostic accuracies, distinguishing between amyloid-negative and positive clinically unimpaired individuals (threshold = 9%, sensitivity = 79%, specificity = 82%) as well as between prodromal AD and preclinical AD (threshold = 38%, sensitivity = 81%, specificity = 93%). The EOT better correlated with cognition than SUVr (∆R2 + 0.08-0.09) with the best correlation observed for EOT in the Braak ≤ 4 region (R2 = 0.64). Cognitive performances were more closely associated with PET metrics than with CSF values. CONCLUSIONS: Quantifying [18F]MK-6240 tau PET in terms of EOT rather than SUVr significantly increases the correlation with cognitive performances. Quantification in the mesiotemporal lobe is the most useful to diagnose preclinical AD or prodromal AD.

Definition of a Threshold for the Plasma Aß42/Aß40 Ratio Measured by Single-Molecule Array to Predict the Amyloid Status of Individuals without Dementia.

Alzheimer's disease (AD) is characterized by amyloid beta (Aß) plaques and hyperphosphorylated tau in the brain. Aß plaques precede cognitive impairments and can be detected through amyloid-positron emission tomography (PET) or in cerebrospinal fluid (CSF). Assessing the plasma Aß42/Aß40 ratio seems promising for non-invasive and cost-effective detection of brain Aß accumulation. This approach involves some challenges, including the accuracy of blood-based biomarker measurements and the establishment of clear, standardized thresholds to categorize the risk of developing brain amyloid pathology. Plasma Aß42/Aß40 ratio was measured in 277 volunteers without dementia, 70 AD patients and 18 non-AD patients using single-molecule array. Patients (n = 88) and some volunteers (n = 66) were subject to evaluation of amyloid status by CSF Aß quantification or PET analysis. Thresholds of plasma Aß42/Aß40 ratio were determined based on a Gaussian mixture model, a decision tree, and the Youden's index. The 0.0472 threshold, the one with the highest sensitivity, was retained for general population without dementia screening, and the 0.0450 threshold was retained for research and clinical trials recruitment, aiming to minimize the need for CSF or PET analyses to identify amyloid-positive individuals. These findings offer a promising step towards a cost-effective method for identifying individuals at risk of developing AD.

Establishing the prognostic profile of patients with work-related musculoskeletal disorders: Development and acceptability of the MAPS questionnaire.

PURPOSE: Work-related musculoskeletal disorders (WRMD) are the most common causes of disability worldwide and are associated with significant use of healthcare. One way to optimize the clinical outcomes of injured workers receiving rehabilitation is to identify and address individual prognostic factors (PF), which can facilitate the personalization of the treatment plan. As there is no pragmatic and systematic method to collect prognostic-related data, the purpose of the study was to develop and assess the acceptability of a set of questionnaires to establish the "prognostic profile" of workers with WRMD. METHODS: We utilized a multistep process to inform the acceptability of the Measures Associated to PrognoStic (MAPS) questionnaire. During STEP-1, a preliminary version of the was developed through a literature search followed by an expert consensus including a patient-advisor. During STEP-2, future users (rehabilitation professionals, healthcare administrators and compensation officers) were consulted through an online survey and were asked to rate the relevance of each content item; items that obtained ≥80% of "totally agree" answers were included. They were also asked to prioritize PF according to their usefulness for clinical decision-making, as well as perceived efficacy to enhance the treatment plan. RESULTS: The questionnaire was developed with three categories: the outcome predicted, the unique PF, and prognostic tools. Personal PF (i.e.: coping strategies, fear-avoidance beliefs), pain related PF (i.e.: pain intensity/severity, duration of pain), and work-related PF (i.e.: work physical demands, work accommodations) were identified to be totally relevant and included in the questionnaire. 84% of the respondents agreed that their patients could complete the MAPS questionnaire in their clinical setting, while 75% totally agreed that the questionnaire is useful to personalize rehabilitation interventions. CONCLUSION: The MAPS questionnaire was deemed acceptable to establish the "prognostic profile" of injured workers and help the clinicians in the treatment decision-making process.

Suspecting Non-Alzheimer's Pathologies and Mixed Pathologies: A Comparative Study Between Brain Metabolism and Tau Images.

BACKGROUND: Alzheimer's disease (AD) pathology can be disclosed in vivo using amyloid and tau imaging, unlike non-AD neuropathologies for which no specific markers exist. OBJECTIVE: We aimed to compare brain hypometabolism and tauopathy to unveil non-AD pathologies. METHODS: Sixty-one patients presenting cognitive complaints (age 48-90), including 32 with positive AD biomarkers (52%), performed [18F]-Fluorodeoxyglucose (FDG)-PET (brain metabolism) and [18F]-MK-6240-PET (tau). We normalized these images using data from clinically normal individuals (n = 30), resulting in comparable FDG and tau z-scores. We computed between-patients correlations to evaluate regional associations. For each patient, a predominant biomarker (i.e., Hypometabolism > Tauopathy or Hypometabolism≤Tauopathy) was determined in the temporal and frontoparietal lobes. We computed within-patient correlations between tau and metabolism and investigated their associations with demographics, cognition, cardiovascular risk factors (CVRF), CSF biomarkers, and white matter hypointensities (WMH). RESULTS: We observed negative associations between tau and FDG in 37 of the 68 cortical regions-of-interest (average Pearson's r = -0.25), mainly in the temporal lobe. Thirteen patients (21%) had Hypometabolism > Tauopathy whereas twenty-five patients (41%) had Hypometabolism≤Tauopathy. Tau-predominant patients were more frequently females and had greater amyloid burden. Twenty-three patients (38%) had Hypometabolism≤Tauopathy in the temporal lobe, but Hypometabolism > Tauopathy in the frontoparietal lobe. This group was older and had higher CVRF than Tau-predominant patients. Patients with more negative associations between tau and metabolism were younger, had worse cognition, and greater amyloid and WMH burdens. CONCLUSIONS: Tau-FDG comparison can help suspect non-AD pathologies in patients presenting cognitive complaints. Stronger Tau-FDG correlations are associated with younger age, worse cognition, and greater amyloid and WMH burdens.

Prognostic factors specific to work-related musculoskeletal disorders: An overview of recent systematic reviews.

PURPOSE: Work-related injuries affect a considerable number of people each year and represent a significant burden for society. To reduce this burden, optimizing rehabilitation care by integrating prognostic factors (PF) into the clinical decision-making process is a promising way to improve clinical outcomes. The aim of this study was to identify PF specific to work-related musculoskeletal disorders. METHODS: We performed an overview of systematic reviews reporting on PF that had the following outcomes of interest: Return to work, pain, disability, functional status, or poor outcomes. Each extracted PF was categorized according to its level of evidence (grade A or B) and whether it was modifiable or not. The risk of bias of each study was assessed with the ROBIS tool. RESULTS: We retrieved 757 citations from 3 databases. After removing 307 duplicates, 450 records were screened, and 20 studies were retained. We extracted a total of 20 PF with a Grade A recommendation, where 7 were deemed modifiable, 11 non-modifiable and 2 were index test. For example, return to work expectations, previous sick leave, delay in referral and pain intensity were found to be predictors of return-to-work outcomes. We also identified 17 PF with a Grade B recommendation, where 11 were deemed modifiable. For example, poor general health, negative recovery expectations, coping and fear-avoidance beliefs, pain severity, and particularly physical work were found to predict return to work outcomes. CONCLUSION: We found numerous modifiable PFs that can help clinicians personalize their treatment plan beyond diagnostic-related information for work-related musculoskeletal disorders.

A perspective on the use of the cervical flexion rotation test in the physical therapy management of cervicogenic headaches.

BACKGROUND: The Cervical Flexion-Rotation Test (CFRT) is widely used in the assessment of upper cervical spine mobility impairments and in the diagnosis of cervicogenic headache (CGH) by physiotherapist. Many studies investigated its different properties, and the results show that the CFRT has good construct validity in the measurement of C1-C2 rotation as well as good to excellent reliability. PURPOSE: In this theoretical paper, we explore the value and point out two methodological issues associated to the CFRT, one related to the procedures and another related to its diagnostic accuracy. RESULTS: Our analysis indicate that there are many confounding factors that could affect the CFRT cut-off's accuracy, which are likely to overestimate the diagnosis properties of CFRT. Potential solutions are discussed. Moreover, the gold standard (manual examination) used to examine the validity of the CFRT for the diagnosis of CGH appears to be far from perfect - we could argue that the diagnostic properties of the CFRT for CGH might be biased and the likelihood ratios are likely to be overestimated. However, it could be relevant to explore if results of the CFRT could be considered as a treatment-effect modifier. Maybe the CFRT could be more valuable as a prognostic factor? CONCLUSION: The quality of evidence supporting the validity of the CFRT is most likely biased. In the absence of a better gold standard, maybe the CFRT could be a more valuable test to establish the patient's prognosis and help the clinician to choose the most appropriate treatment options.

Fat Infiltration of Multifidus Muscle Is Correlated with Neck Disability in Patients with Non-Specific Chronic Neck Pain.

Background: Chronic non-specific neck pain (CINP) is common, but the etiology remains unclear. This study aimed to examine the relationship between cervical muscle composition (cervical multifidus and longus capitis/longus colli), morphometry, range of movement, muscle function, and disability severity (Neck Disability Index) in patients with CINP. Methods: From September 2020 to July 2021, subjects underwent cervical MRI and clinical tests (cervical range of motion, cranio-cervical flexion test, neck flexor, and extensor muscle endurance). MRI analysis comprised muscle cross-sectional area, volume, and fat infiltration of multifidus and longus colli between C4 and C7 levels. Results: Twenty-five participants were included. Multiple linear regression analysis indicated that NDI was positively correlated with the volume percentage of fat infiltration of the multifidus (B = 0.496), negatively correlated with fat-free muscle volume of the multifidus normalized by subject height (B = −0.230), and accounted for 32% of the variance. There was no relationship between neck disability and longus capitis/longus colli morphology. We also found no relationship between neck disability scores, neck flexor or extensor muscle endurance, or the outcome motor control test of craniocervical flexion (p > 0.05). Conclusions: Neck disability was moderately correlated with the percentage of fat volume in the multifidus muscle and fat-free volume of the multifidus. There was no relationship between NDI scores and muscle function test outcomes or any fat or volume measures pertaining to the longus colli muscle.

Integrating artificial intelligence into haematology training and practice: Opportunities, threats and proposed solutions.

There remains a limited emphasis on the use beyond the research domain of artificial intelligence (AI) in haematology and it does not feature significantly in postgraduate medical education and training. This perspective article considers recent developments in the field of AI research in haematology and anticipates the potential benefits and risks associated with its deeper integration into the specialty. Anxiety towards the greater use of AI in healthcare stems from legitimate concerns surrounding data protection, lack of transparency in clinical decision-making, and erosion of the doctor-patient relationship. The specialty of haematology has successfully embraced multiple disruptive innovations. We are at the cusp of a new era of closer integration of AI into routine haematology practice that will ultimately benefit patient care but to harness its benefits the next generation of haematologists will need access to bespoke learning opportunities with input from data scientists.

Disclosing tau tangles using PET imaging: a pharmacological review of the radiotracers available in 2021.

Neurological symptoms depend on the topography of the lesions in the nervous system, hence the importance of brain imaging for neurologists. Neurological treatment, however, depends on the biological nature of the lesions. The development of radiotracers specific for the proteinopathies observed in neurodegenerative disorders is, therefore, crucially important for better understanding the relationships between the pathology and the clinical symptoms, as well as the efficacy of therapeutical interventions. The tau protein is involved in several neurodegenerative disorders, that can be distinguished both biologically and clinically as the type of tau isoforms and filaments observed in brain aggregates, and the brain regions affected differ between tauopathies. Over the past few years, several tracers have been developed for imaging tauopathies with positron emission tomography. The present review aims to compare the binding properties of these tracers, with a specific focus on how these properties might be relevant for neurologists using these biomarkers to characterize the pathology of patients presenting with clinical symptoms suspect of a neurodegenerative disorder.

Comparison of 68Ga-Prostate Specific Membrane Antigen (PSMA) Positron Emission Tomography Computed Tomography (PET-CT) and Whole-Body Magnetic Resonance Imaging (WB-MRI) with Diffusion Sequences (DWI) in the Staging of Advanced Prostate Cancer.

BACKGROUND: Prostate specific membrane antigen (PSMA) positron emission tomography computed tomography (PET-CT) and whole-body magnetic resonance imaging (WB-MRI) outperform standard imaging technology for the detection of metastasis in prostate cancer (PCa). There are few direct comparisons between both modalities. This paper compares the diagnostic accuracy of PSMA PET-CT and WB-MRI for the detection of metastasis in PCa. One hundred thirty-four patients with newly diagnosed PCa (n = 81) or biochemical recurrence after curative treatment (n = 53) with high-risk features prospectively underwent PSMA PET-CT and WB-MRI. The diagnostic accuracy of both techniques for lymph node, skeletal and visceral metastases was compared against a best valuable comparator (BVC). Overall, no significant difference was detected between PSMA PET-CT and WB-MRI to identify metastatic patients when considering lymph nodes, skeletal and visceral metastases together (AUC = 0.96 (0.92-0.99) vs. 0.90 (0.85-0.95); p = 0.09). PSMA PET-CT, however, outperformed WB-MRI in the subgroup of patients with newly diagnosed PCa for the detection of lymph node metastases (AUC = 0.96 (0.92-0.99) vs. 0.86 (0.79-0.92); p = 0.0096). In conclusion, PSMA PET-CT outperforms WB-MRI for the detection of nodal metastases in primary staging of PCa.

2048-QAM transmission at 15 GBd over 100 km using geometric constellation shaping.

We experimentally investigated a pilot-aided digital signal processing (DSP) chain in combination with high-order geometric constellation shaping to increase the achievable information rates (AIRs) in standard intradyne coherent transmission systems. We show that the AIR of our system at 15 GBd was maximised using geometrically-shaped (GS) 2048 quadrature amplitude modulation (QAM), reaching 18.0 b/4D-symbol in back-to-back transmission and 16.9 b/4D-symbol after transmission through 100 km of a single-mode fibre after subtracting the pilot overhead (OH). This represents the highest-order GS format demonstrated to date, supporting the highest AIR of any standard intradyne system using conventional optics and 8-bit electronics. Detailed characterisation of the DSP, transceiver performance, and transmission modelling has also been carried out to provide insight into sources of impairments and directions for further improvement.

AI-optimised tuneable sources for bandwidth-scalable, sub-nanosecond wavelength switching.

Wavelength routed optical switching promises low power and latency networking for data centres, but requires a wideband wavelength tuneable source (WTS) capable of sub-nanosecond switching at every node. We propose a hybrid WTS that uses time-interleaved tuneable lasers, each gated by a semiconductor optical amplifier, where the performance of each device is optimised using artificial intelligence. Through simulation and experiment we demonstrate record wavelength switch times below 900 ps across 6.05 THz (122×50 GHz) of continuously tuneable optical bandwidth. A method for further bandwidth scaling is evaluated and compared to alternative designs.

Sun, sea and sex: a review of the sex tourism literature.

BACKGROUND: Sex tourism is defined as travel planned specifically for the purpose of sex, generally to a country where prostitution is legal. While much of the literature on sex tourism relates to the commercial sex worker industry, sex tourism also finds expression in non-transactional sexual encounters. This narrative review explores current concepts related to travel and sex, with a focus on trans-national sex tourism. METHODS: The PubMed database was accessed to source relevant literature, using combinations of pertinent search terms. Only articles published in the English language were selected. Reference lists of published articles were also examined for relevant articles. RESULTS: With regard to preferred destinations, South/Central America and the Caribbean were more likely to receive tourists looking for casual sex. Longer duration of travel, travelling alone or with friends, alcohol or drug use, being younger and being single were factors associated with higher levels of casual sex overseas. The majority of literature retrieved on sex workers focused on risk behaviours, sexually transmitted infections (STI), mobility of sex workers and how these factors affected their lives. Sex tourists require better access to effective methods of preventing HIV, such as pre-exposure prophylaxis, and better education on HIV prevention. Drugs and alcohol play a major role as risk factors for and cofactors in casual sexual behaviour while abroad. CONCLUSIONS: Travellers need to be informed of the increased risks of STI before travel. They should be aware of the local prevalence of STIs and the risks associated with their sexual practices when they travel, including engaging with commercial sex workers, having unprotected sexual intercourse and becoming victims of sexual violence.