Emerging Therapeutics, Technologies, and Drug Development Strategies to Address Patient Nonadherence and Improve Tuberculosis Treatment.

Imperfect medication adherence remains the biggest predictor of treatment failure for patients with tuberculosis. Missed doses during treatment lead to relapse, tuberculosis resistance, and further spread of disease. Understanding individual patient phenotypes, population pharmacokinetics, resistance development, drug distribution to tuberculosis lesions, and pharmacodynamics at the site of infection is necessary to fully measure the impact of adherence on patient outcomes. To decrease the impact of expected variabilityin drug intake on tuberculosis outcomes, an improvement in patient adherence and new forgiving regimens that protect against missed doses are needed. In this review, we summarize emerging technologies to improve medication adherence in clinical practice and provide suggestions on how digital adherence technologies can be incorporated in clinical trials and practice and the drug development pipeline that will lead to more forgiving regimens and benefit patients suffering from tuberculosis.

Inequities in the Training Environment and Health of Female Golfers Participating in the 2022 International Golf Federation World Amateur Team Championships.

OBJECTIVE: To assess health problems and training environment of female golfers participating in the 2022 World Amateur Team Championships (WATC) and to compare golfers (a) with and without health problems prior the WATC and (b) living and training in countries ranking in the upper versus lower 50% of the team results at the 2022 WATC. DESIGN: Cross-sectional cohort study using an anonymous questionnaire. SETTING: International Golf Federation WATC. PARTICIPANTS: One hundred sixty-two female golfers from 56 countries. INTERVENTIONS: N/A. MAIN OUTCOME MEASURES: Golfers' answers on the presence and characteristics of health problems, their training environment, and to the Oslo Sport Trauma Research Centre Questionnaire. RESULTS: Almost all golfers (n = 162; 96%) answered the questionnaire. In the 4 weeks before the WATC, 101 golfers (63.1%) experienced 186 musculoskeletal complaints, mainly at the lumbar spine/lower back, wrist, or shoulder. Just half of the golfers (50.6%) performed injury prevention exercises always or often. More than a third (37.4%) of the golfers reported illness complaints and 32.5% mental health problems in the 4 weeks preceding the WATC. General anxiety, performance anxiety, and low mood/depression were the most frequent mental health problems. Golfers with injury complaints rated their daily training environment poorer. Golfers ranking in the lower 50% at the WATC had significantly less support staff, rated their training environment poorer, and had a higher prevalence of illness complaints and mental health problems. CONCLUSIONS: Effective illness and injury prevention programs should be implemented and better access to education and health support in the daily training environment provided.

International consensus statement: methods for recording and reporting of epidemiological data on injuries and illnesses in golf.

Epidemiological studies of injury in elite and recreational golfers have lacked consistency in methods and definitions employed and this limits comparison of results across studies. In their sports-generic statement, the Consensus Group recruited by the IOC (2020) called for sport-specific consensus statements. On invitation by International Golf Federation, a group of international experts in sport and exercise medicine, golf research and sports injury/illness epidemiology was selected to prepare a golf-specific consensus statement. Methodological stages included literature review and initial drafting, online feedback from the consensus group, revision and second draft, virtual consensus meetings and completion of final version. This consensus statement provides golf-specific recommendations for data collection and research reporting including: (i) injury and illness definitions, and characteristics with golf-specific examples, (ii) definitions of golf-specific exposure measurements and recommendations for the calculation of prevalence and incidence, (iii) injury, illness and exposure report forms for medical staff and for golfers, and (iv) a baseline questionnaire. Implementation of the consensus methodology will enable comparison among golf studies and with other sports. It facilitates analysis of causative factors for injuries and illness in golf, and can also be used to evaluate the effects of prevention programmes to support the health of golfers.

Assessment of Bowel End Perfusion After Mesenteric Division: Eye Versus SPY.

BACKGROUND: Anastomotic complications related to tissue ischemia cause morbidity in gastrointestinal (GI) surgery. Surgeons' standard practice to predict bowel perfusion is inspection of mesenteric perfusion before anastomosing bowel ends. Augmenting this assessment with fluorescent imaging is under study. A standardized system to evaluate this imaging has not yet been developed. This study compared the surgeon's intraoperative assessment to a novel GI-specific imaging analysis method. MATERIALS AND METHODS: Forty-nine consecutive patients undergoing open or laparoscopic-assisted bowel resections were enrolled. After mesenteric division, the surgeon marked the site for bowel transection. Near-infrared fluorescence imaging was performed on the marked bowel ends. Imaging analysis identified theoretical transection sites based on the quantification of arterial and microvascular inflow (Perfusion) and venous outflow (Timing). The primary outcome was the measured disparity between the site marked by the surgeon using current standard of care parameters and the imaging-determined site. No clinical outcomes were assessed. RESULTS: Seventy-two bowel end segments from 46 patients were analyzed. Disparity was found in 11 of 72 (15%) bowel end segments. In five (7%), the disparity was due to either Perfusion or Timing (single), and in six (8%), due to both Perfusion and Timing (combined). In the single disparity group, the median disparity distance was 2.0 cm by Perfusion and 4.0 cm by Timing, and in the combined group, 3.8 cm by Perfusion and 3.5 cm by Timing. Disparity (either single or combined) was in 25% of colon and 11.5% of small bowel (P = NS). Combined and single disparity had equivalent lengths of disparity distance (P = NS). CONCLUSIONS: Imaging coupled with this GI-specific analysis provides objective, real-time, and interpretable data of intramural blood supply. A 15% disparity rate from current clinical practice was observed.

Digital health for the End TB Strategy: developing priority products and making them work.

In 2014, the World Health Organization (WHO) developed the End TB Strategy in response to a World Health Assembly Resolution requesting Member States to end the worldwide epidemic of tuberculosis (TB) by 2035. For the strategy's objectives to be realised, the next 20 years will need novel solutions to address the challenges posed by TB to health professionals, and to affected people and communities. Information and communication technology presents opportunities for innovative approaches to support TB efforts in patient care, surveillance, programme management and electronic learning. The effective application of digital health products at a large scale and their continued development need the engagement of TB patients and their caregivers, innovators, funders, policy-makers, advocacy groups, and affected communities.In April 2015, WHO established its Global Task Force on Digital Health for TB to advocate and support the development of digital health innovations in global efforts to improve TB care and prevention. We outline the group's approach to stewarding this process in alignment with the three pillars of the End TB Strategy. The supplementary material of this article includes target product profiles, as developed by early 2016, defining nine priority digital health concepts and products that are strategically positioned to enhance TB action at the country level.

Moment to moment variability in functional brain networks during cognitive activity in EEG data.

Functional brain networks (FBNs) are gaining increasing attention in computational neuroscience due to their ability to reveal dynamic interdependencies between brain regions. The dynamics of such networks during cognitive activity between stimulus and response using multi-channel electroencephalogram (EEG), recorded from 16 healthy human participants are explored in this research. Successive EEG segments of 500[Formula: see text]ms duration starting from the onset of cognitive stimulation have been used to analyze and understand the cognitive dynamics. The approach employs a combination of signal processing techniques, nonlinear statistical measures and graph-theoretical analysis. The efficacy of this approach in detecting and tracking cognitive load induced changes in EEG data is clearly demonstrated using graph metrics. It is revealed that most cognitive activity occurs within approximately 500[Formula: see text]ms of the stimulus presentation in addition to temporal variability in the FBNs. It is shown that mutual information (MI), a nonlinear measure, produces good correlations between the EEG channels thus enabling the construction of FBNs which are sensitive to cognitive load induced changes in EEG. Analyses of the dynamics of FBNs and the visualization approach reveal hard to detect subtle changes in cognitive function and hence may lead to a better understanding of cognitive processing in the brain. The techniques exploited have the potential to detect human cognitive dysfunction (impairments).

Systemic interindividual DNA methylation variants in cattle share major hallmarks with those in humans.

BACKGROUND: We recently identified ~ 10,000 correlated regions of systemic interindividual epigenetic variation (CoRSIVs) in the human genome. These methylation variants are amenable to population studies, as DNA methylation measurements in blood provide information on epigenetic regulation throughout the body. Moreover, establishment of DNA methylation at human CoRSIVs is labile to periconceptional influences such as nutrition. Here, we analyze publicly available whole-genome bisulfite sequencing data on multiple tissues of each of two Holstein cows to determine whether CoRSIVs exist in cattle. RESULTS: Focusing on genomic blocks with ≥ 5 CpGs and a systemic interindividual variation index of at least 20, our approach identifies 217 cattle CoRSIVs, a subset of which we independently validate by bisulfite pyrosequencing. Similar to human CoRSIVs, those in cattle are strongly associated with genetic variation. Also as in humans, we show that establishment of DNA methylation at cattle CoRSIVs is particularly sensitive to early embryonic environment, in the context of embryo culture during assisted reproduction. CONCLUSIONS: Our data indicate that CoRSIVs exist in cattle, as in humans, suggesting these systemic epigenetic variants may be common to mammals in general. To the extent that individual epigenetic variation at cattle CoRSIVs affects phenotypic outcomes, assessment of CoRSIV methylation at birth may become an important tool for optimizing agriculturally important traits. Moreover, adjusting embryo culture conditions during assisted reproduction may provide opportunities to tailor agricultural outcomes by engineering CoRSIV methylation profiles.

The Role of the Hand Surgery Consultant in the Care of the Amateur and Professional Golfer.

Golf is unique in this compendium of sports-related hand and wrist injury management. It is the only sport where the ball is stationary and there is no opponent against whom the player is defending. This distinctive sport dates to the 15th century in Scotland and is one of the oldest sports, but it is one where technology has changed many of the fundamental elements-from the "playing field (through advanced in agronomy) and the equipment (club and ball technology).

A method for evaluating population and infrastructure exposed to natural hazards: tests and results for two recent Tonga tsunamis.

Background: Coastal communities are highly exposed to ocean- and -related hazards but often lack an accurate population and infrastructure database. On January 15, 2022 and for many days thereafter, the Kingdom of Tonga was cut off from the rest of the world by a destructive tsunami associated with the Hunga Tonga Hunga Ha'apai volcanic eruption. This situation was made worse by COVID-19-related lockdowns and no precise idea of the magnitude and pattern of destruction incurred, confirming Tonga's position as second out of 172 countries ranked by the World Risk Index 2018. The occurrence of such events in remote island communities highlights the need for (1) precisely knowing the distribution of buildings, and (2) evaluating what proportion of those would be vulnerable to a tsunami. Methods and Results: A GIS-based dasymetric mapping method, previously tested in New Caledonia for assessing and calibrating population distribution at high resolution, is improved and implemented in less than a day to jointly map population clusters and critical elevation contours based on runup scenarios, and is tested against destruction patterns independently recorded in Tonga after the two recent tsunamis of 2009 and 2022. Results show that ~ 62% of the population of Tonga lives in well-defined clusters between sea level and the 15 m elevation contour. The patterns of vulnerability thus obtained for each island of the archipelago allow exposure and potential for cumulative damage to be ranked as a function of tsunami magnitude and source area. Conclusions: By relying on low-cost tools and incomplete datasets for rapid implementation in the context of natural disasters, this approach works for all types of natural hazards, is easily transferable to other insular settings, can assist in guiding emergency rescue targets, and can help to elaborate future land-use planning priorities for disaster risk reduction purposes. Supplementary Information: The online version contains supplementary material available at 10.1186/s40677-023-00235-8.

Multi-Level Precues for Guiding Tasks Within and Between Workspaces in Spatial Augmented Reality.

We explore Spatial Augmented Reality (SAR) precues (predictive cues) for procedural tasks within and between workspaces and for visualizing multiple upcoming steps in advance. We designed precues based on several factors: cue type, color transparency, and multi-level (number of precues). Precues were evaluated in a procedural task requiring the user to press buttons in three surrounding workspaces. Participants performed fastest in conditions where tasks were linked with line cues with different levels of color transparency. Precue performance was also affected by whether the next task was in the same workspace or a different one.

Event Related Brain Responses Reveal the Impact of Spatial Augmented Reality Predictive Cues on Mental Effort.

This article presents the results from a Spatial Augmented Reality (SAR) study which evaluated the cognitive cost of several predictive cues. Participants performed a validated procedural button pressing task, where the predictive cue annotations guided them to the upcoming task. While existing research has evaluated predictive cues based on their performance and self-rated mental effort, actual cognitive cost has yet to be investigated. To measure the user's brain activity, this study utilized electroencephalogram (EEG) recordings. Cognitive load was evaluated by measuring brain responses for a secondary auditory oddball task, with reduced brain responses to oddball tones expected when cognitive load in the primary task is highest. A simple monitor n-back task and procedural task comparing monitor versus SAR were conducted, followed by a version of the procedural task comparing the SAR predictive cues. Results from the brain responses were able to distinguish between performance enhancing cues with a high and low cognitive load. Electrical brain responses also revealed that having an arc or arrow guide towards the upcoming task required the least amount of mental effort.

Adaptive Reset Techniques for Haptic Retargeted Interaction.

This article presents a set of adaptive reset techniques for use with haptic retargeting systems focusing on interaction with hybrid virtual reality interfaces that align with a physical interface. Haptic retargeting between changing physical and virtual targets requires a reset where the physical and virtual hand positions are re-aligned. We present a modified Point technique to guide the user in the direction of their next interaction such that the remaining distance to the target is minimized upon completion of the reset. This, along with techniques drawn from existing work are further modified to consider the angular and translational gain of each redirection and identify the optimal position for the reset to take place. When the angular and translational gain is within an acceptable range, the reset can be entirely omitted. This enables continuous retargeting between targets removing interruptions from a sequence of retargeted interactions. These techniques were evaluated in a user study which showed that adaptive reset techniques can provide a significant decrease in task completion time, travel distance, and the number of user errors.

Digital adherence technologies to improve tuberculosis treatment outcomes in China: a cluster-randomised superiority trial.

BACKGROUND: Drug-sensitive tuberculosis treatment requires 6 months of therapy, so adherence problems are common. Digital adherence technologies might improve tuberculosis treatment outcomes. We aimed to evaluate the effect of a daily reminder medication monitor, monthly review of adherence data by the health-care provider, and differentiated care for patients with adherence issues, on tuberculosis treatment adherence and outcomes. METHODS: We did a cluster-randomised superiority trial across four prefectures in China. 24 counties or districts (clusters) were randomly assigned (1:1) to intervention or control groups. We enrolled patients aged 18 years or older with GeneXpert-positive, rifampicin-sensitive pulmonary tuberculosis, who were receiving daily fixed-dose combination treatment. Patients in the intervention group received a medication monitor for daily drug-dosing reminders, monthly review of adherence data by health-care provider, and management of poor adherence; and patients in the control group received routine care (silent-mode monitor-measured adherence). Only the independent endpoints review committee who assessed endpoint data for some participants were masked to study group assignment. Patients were followed up (with sputum solid culture) at 12 and 18 months. The primary outcome was a composite of death, loss to follow-up, treatment failure, switch to multidrug-resistant tuberculosis treatment, or tuberculosis recurrence by 18 months from treatment start, analysed in the intention-to-treat population. Analysis accounted for study design with multiple imputation for the primary outcome. This trial is now complete and is registered with ISRCTN, 35812455. FINDINGS: Between Jan 26, 2017, and April 3, 2019, 15 257 patients were assessed for eligibility and 3074 were enrolled, 2686 (87%) of whom were included in the intention-to-treat population. 1909 (71%) of 2686 patients were male, 777 (29%) were female, and the median age was 44 years (IQR 29-58). By 18 months from treatment start, using multiple imputation for missing outcomes, 239 (16% [geometric mean of cluster-level proportion]) of 1388 patients in the control group and 224 (16%) of 1298 in the intervention group had a primary composite outcome event (289 [62%] of 463 events were loss to follow-up during treatment and 42 [9%] were tuberculosis recurrence). The intervention had no effect on risk of the primary composite outcome (adjusted risk ratio 1·01, 95% CI 0·73-1·40). INTERPRETATION: Our digital medication monitor intervention had no effect on unfavourable outcomes, which included loss to follow-up during treatment, tuberculosis recurrence, death, and treatment failure. There was a failure to change patient management following identification of treatment non-adherence at monthly reviews. A better understanding of adherence patterns and how they relate to poor outcomes, coupled with a more timely review of adherence data and improved implementation of differentiated care, may be required. FUNDING: Bill & Melinda Gates Foundation.

Blood and organ donation patterns of trauma surgeons.

Allogenic blood product transfusion and organ donation are critical components of modern medicine. However, only 5 per cent of the eligible population donate blood and only 53 per cent declare themselves organ donors. Trauma surgeons have an intimate exposure to these needs and their personal donation patterns may reflect this knowledge. A 14 question survey about personal blood and organ donation was sent to 635 members of the American Association for the Surgery of Trauma by e-mail. Seventy-eight per cent of respondents have donated blood and 86 per cent of those donors have done so repeatedly. However, 83 per cent of respondents have not given blood in the past year. Medical reasons were the most common reason cited for inability to donate (45%). With regard to organ donation, 90 per cent of respondents have filled out the organ donation section on their driver's license and 89 per cent have discussed organ donation with their family. The rates of blood and organ donation are higher than the rates of the general population. Trauma surgeons are likely to be blood and organ donors. Their intimate knowledge of the importance of donation plays a role. Personal medical conditions that restrict donation were, among respondents, a more common cause of failure to donate than were time constraints.

There Is No Spoon: Evaluating Performance, Space Use, and Presence with Expert Domain Users in Immersive Analytics.

Immersive analytics turns the very space surrounding the user into a canvas for data analysis, supporting human cognitive abilities in myriad ways. We present the results of a design study, contextual inquiry, and longitudinal evaluation involving professional economists using a Virtual Reality (VR) system for multidimensional visualization to explore actual economic data. Results from our preregistered evaluation highlight the varied use of space depending on context (exploration vs. presentation), the organization of space to support work, and the impact of immersion on navigation and orientation in the 3D analysis space.

Patterns of management of atrial fibrillation complicating coronary artery bypass grafting: Results from the PRoject of Ex-vivo Vein graft ENgineering via Transfection IV (PREVENT-IV) Trial.

BACKGROUND: Current practice related to the management of atrial fibrillation (AF) complicating coronary artery bypass grafting (CABG) is uncertain. METHODS: We examined management of post-CABG AF in the PREVENT-IV trial, and we explored patterns of use of postoperative rhythm versus rate control and anticoagulation for AF by geographic region and type of site. We also compared outcomes of patients who developed post-CABG AF (663) with those who did not (2,131). RESULTS: The incidence of AF was 24%. Post-CABG AF was treated with a rhythm control strategy in 81% of patients and with warfarin in 23% of patients. Although there were significant variations across sites in the management of post-CABG AF, patterns of use of postoperative rhythm versus rate control and anticoagulation did not differ by geographic region or by whether or not the enrolling site was an academic institution. Mortality was higher in patients with post-CABG AF than patients without AF at 30 days (1.5% vs 0.7%, P = .01) but not at 3 years (6.9% vs 4.9%, P = .41). There was a trend toward a higher risk of mortality or stroke at 30 days in patients with AF (2.4% vs 1.9%, P = .08). CONCLUSION: Although a rhythm control strategy was used in most of the patients in this trial and the overall rate of use of warfarin was low, the significance of these findings is uncertain because of the lack of data from randomized clinical trials. The substantial variations in the management of post-CABG AF across sites are likely because of definitive data on the most effective therapies, highlighting the need for clinical trials on rate versus rhythm control and on anticoagulation for AF in this setting.

Conveying spatial awareness cues in xR collaborations.

Spatial Augmented Reality (SAR) systems can be suitably combined with other existing Extended Reality (xR) technologies to support collaboration. In existing strategies, users unencumbered by a viewing technology, such as a tablet interface or a head-mounted display, must rely on the transmission of their collaborators' positioning through interpreting a first-person camera view. This design creates a seam between a user's experience of the augmented physical environment in SAR, and their collaborators' experience inside the virtual environment. To assist in development and evaluation of spatial cues to support spatial awareness in SAR environments, an egocentric spatial-communication taxonomy is presented given two determining dimensions, a cue's attachment (physical/virtual) and animation (local/world). We developed four egocentric cues which characterize the four independent dimensions of the matrix: arrow, path, glow, and radial, and a single exocentric world in miniature visualization. Our study shows that virtual attachment cues are preferred, providing the highest accuracy, highest performance when collaborators are occluded, and produce the least mental effort when used with a single virtual collaborator. For multiple collaborators however, the virtual attached, world animated radial cue produces significant increases in mental load and reductions in preference, demonstrating the impact of visual augmentation clutter. The single exocentric visualization produced higher levels of head movement, and poorer accuracy, however the novelty of the visualization produced positive qualitative results.

Outcomes of tube thoracostomies performed by advanced practice providers vs trauma surgeons.

BACKGROUND: The role of advanced registered nurse practitioners and physician assistants in emergency departments, trauma centers, and critical care is becoming more widely accepted. These personnel, collectively known as advanced practice providers, expand physicians' capabilities and are being increasingly recruited to provide care and perform invasive procedures that were previously performed exclusively by physicians. OBJECTIVES: To determine whether the quality of tube thoracostomies performed by advanced practice providers is comparable to that performed by trauma surgeons and to ascertain whether the complication rates attributable to tube thoracostomies differ on the basis of who performed the procedure. METHODS: Retrospective blinded reviews of patients' charts and radiographs were conducted to determine differences in quality indicators, complications, and outcomes of tube thoracostomies by practitioner type: trauma surgeons vs advanced practice providers. RESULTS: Differences between practitioner type in insertion complications, complications requiring additional interventions, hospital length of stay, and morbidity were not significant. The only significant difference was a complication related to placement of the tube: when the tube extended caudad, toward the feet, from the insertion site. Interrater reliability ranged from good to very good. CONCLUSIONS: Use of advanced practice providers provides consistent and quality tube thoracostomies. Employment of these practitioners may be a safe and reasonable solution for staffing trauma centers.

Superman vs Giant: A Study on Spatial Perception for a Multi-Scale Mixed Reality Flying Telepresence Interface.

The advancements in Mixed Reality (MR), Unmanned Aerial Vehicle, and multi-scale collaborative virtual environments have led to new interface opportunities for remote collaboration. This paper explores a novel concept of flying telepresence for multi-scale mixed reality remote collaboration. This work could enable remote collaboration at a larger scale such as building construction. We conducted a user study with three experiments. The first experiment compared two interfaces, static and dynamic IPD, on simulator sickness and body size perception. The second experiment tested the user perception of a virtual object size under three levels of IPD and movement gain manipulation with a fixed eye height in a virtual environment having reduced or rich visual cues. Our last experiment investigated the participant's body size perception for two levels of manipulation of the IPDs and heights using stereo video footage to simulate a flying telepresence experience. The studies found that manipulating IPDs and eye height influenced the user's size perception. We present our findings and share the recommendations for designing a multi-scale MR flying telepresence interface.