Home-Monitoring Vision Tests to Detect Active Neovascular Age-Related Macular Degeneration.

Importance: Most neovascular age-related macular degeneration (nAMD) treatments involve long-term follow-up of disease activity. Home-monitoring would reduce the burden on patients and their caregivers and release clinic capacity. Objective: To evaluate 3 vision home-monitoring tests for patients to use to detect active nAMD compared with diagnosing active nAMD at hospital follow-up during the after-treatment monitoring phase. Design, Setting, and Participants: This was a diagnostic test accuracy study wherein the reference standard was detection of active nAMD by an ophthalmologist at hospital follow-up. The 3 home-monitoring tests evaluated included the following: (1) the KeepSight Journal (KSJ [International Macular and Retinal Foundation]), which contains paper-based near-vision tests presented as word puzzles, (2) the MyVisionTrack (mVT [Genentech]) vision-monitoring mobile app, viewed on an Apple mobile operating system-based device, and (3) the MultiBit (MBT [Visumetrics]) app, viewed on an Apple mobile operating system-based device. Participants were asked to test weekly; mVT and MBT scores were transmitted automatically, and KSJ scores were returned to the research office every 6 months. Raw scores between hospital follow-ups were summarized as averages. Patients were recruited from 6 UK hospital eye clinics and were 50 years and older with at least 1 eye first treated for active nAMD for at least 6 months or longer to a maximum of 42 months before approach. Participants were stratified by time since starting treatment. Study data were analyzed from May to September 2021. Exposures: The KSJ, mVT, and MBT were compared with the reference standard (in-hospital ophthalmologist examination). Main Outcomes and Measures: Estimated area under receiver operating characteristic curve (AUROC). The study had 90% power to detect a difference of 0.06, or 80% power to detect a difference of 0.05, if the AUROC for 2 tests was 0.75. Results: A total of 297 patients (mean [SD] age, 74.9 [6.6] years; 174 female [58.6%]) were included in the study. At least 1 hospital follow-up was available for 312 study eyes in 259 participants (1549 complete visits). Median (IQR) home-monitoring testing frequency was 3 (1-4) times per month. Estimated AUROC was less than 0.6 for all home-monitoring tests, and only the KSJ summary score was associated with lesion activity (odds ratio, 3.48; 95% CI, 1.09-11.13; P = .04). Conclusions and Relevance: Results suggest that no home-monitoring vision test evaluated provided satisfactory diagnostic accuracy to identify active nAMD diagnosed in hospital eye service follow-up clinics. Implementing any of these evaluated tests, with ophthalmologists only reviewing test positives, would mean most active lesions were missed, risking unnecessary sight loss.

Inequalities in Uptake and Use of Digital Applications for Home-Monitoring of Neovascular Age-Related Macular Degeneration in an Elderly Visually Impaired Population: The MONARCH Study.

Purpose: To describe inequalities in the Monitoring for Neovascular Age-related Macular Degeneration Reactivation at Home (MONARCH) diagnostic test accuracy study for: recruitment; participants' ability to self-test; and adherence to testing using digital applications during follow-up. Methods: Home-monitoring vision tests included two tests implemented as software applications (apps: MyVisionTrack and MultiBit) on an iPod Touch device. Patients were provided with all hardware required to participate (iPod and MIFI device) and trained to use the apps. Regression models estimated associations of age, sex, Index of Multiple Deprivation, strata of time since first diagnosis, and baseline visual acuity at study entry on outcomes of willingness to participate, ability to perform tests, and adherence to weekly testing. Results: A minority of patients who were approached were willing-in-principle to participate. Increasing age was associated with being unwilling-in-principle to participate. Patients from the most deprived areas had a 47% decrease in odds of being willing compared to those from the middle quintile deprived areas (odds ratio, 0.53; 95% confidence interval = 0.32, 0.88). Increasing age and worse deprivation were not consistently associated either with ability to self-monitor with the index tests, or adherence to weekly testing. Conclusions: Associations of increasing age and worse deprivation index were associated with unwillingness-in-principle to participate despite the provision of hardware' highlighting the potential for inequality with interventions of the kind evaluated. Translational Relevance: The clear evidence of inequalities in participation should prompt future research on ways to encourage adoption of mobile health technologies by underserved populations.

Descriptive study of the challenges when implementing an app for patients with neovascular age-related macular degeneration to monitor their vision at home.

OBJECTIVES: Remote monitoring of health has the potential to reduce the burden to patients of face-to-face appointments and make healthcare more efficient. Apps are available for patients to self-monitor vision at home, for example, to detect reactivation of age-related macular degeneration (AMD). Describing the challenges when implementing apps for self-monitoring of vision at home was an objective of the MONARCH study to evaluate two vision-monitoring apps on an iPod Touch (Multibit and MyVisionTrack). DESIGN: Diagnostic Test Accuracy study. SETTING: Six UK hospitals. METHODS: The study provides an example of the real-world implementation of such apps across health sectors in an older population. Challenges described include the following: (1) frequency and reason for incoming calls made to a helpline and outgoing calls made to participants; (2) frequency and duration of events responsible for the tests being unavailable; and (3) other technical and logistical challenges. RESULTS: Patients (n=297) in the study were familiar with technology; 252/296 (85%) had internet at home and 197/296 (67%) had used a smartphone. Nevertheless, 141 (46%) called the study helpline, more often than anticipated. Of 435 reasons for calling, all but 42 (10%) related to testing with the apps or hardware, which contributed to reduced adherence. The team made at least one call to 133 patients (44%) to investigate why data had not been transmitted. Multibit and MyVisionTrack apps were unavailable for 15 and 30 of 1318 testing days for reasons which were the responsibility of the app providers. Researchers also experienced technical challenges with a multiple device management system. Logistical challenges included regulations for transporting lithium-ion batteries and malfunctioning chargers. CONCLUSIONS: Implementation of similar technologies should incorporate a well-resourced helpline and build in additional training time for participants and troubleshooting time for staff. There should also be robust evidence that chosen technologies are fit for the intended purpose. TRIAL REGISTRATION NUMBER: ISRCTN79058224.

Differences in Serum miRNA Profiles by Race, Ethnicity, and Socioeconomic Status: Implications for Developing an Equitable Ovarian Cancer Screening Test.

Serum miRNAs are promising biomarkers for several clinical conditions, including ovarian cancer. To inform equitable implementation of these tests, we investigated the effects of race, ethnicity, and socioeconomic status on serum miRNA profiles. Serum samples from a large institutional biobank were analyzed using a custom panel of 179 miRNA species highly expressed in human serum, measured using the Abcam Fireplex assay via flow cytometry. Data were log-transformed prior to analysis. Differences in miRNA by race and ethnicity were assessed using logistic regression. Pairwise t tests analyzed racial and ethnic differences among eight miRNAs previously associated with ovarian cancer risk. Pearson correlations determined the relationship between mean miRNA expression and the social deprivation index (SDI) for Massachusetts residents. Of 1,586 patients (76.9% white, non-Hispanic), compared with white, non-Hispanic patients, those from other racial and ethnic groups were younger (41.9 years ± 13.2 vs. 51.3 ± 15.1, P < 0.01) and had fewer comorbidities (3.5 comorbidities ± 2.7 vs. 4.6 ± 2.8, P < 0.01). On logistic regression, miRNAs predicted race and ethnicity at an AUC of 0.69 (95% confidence interval, 0.66-0.72), which remained consistent when stratified by most comorbidities. Among eight miRNAs previously associated with ovarian cancer risk, seven significantly varied by race and ethnicity (all P < 0.01). There were no significant differences in SDI for any of these eight miRNAs. miRNA expression is significantly influenced by race and ethnicity, which remained consistent after controlling for confounders. Understanding baseline differences in biomarker test characteristics prior to clinical implementation is essential to ensure instruments perform comparably across diverse populations. PREVENTION RELEVANCE: This study aimed to understand factors affecting miRNA expression, to ensure we create equitable screening tests for ovarian cancer that perform well in diverse populations. The goal is to ensure that we are detecting ovarian cancer cases earlier (secondary prevention) in women of all races, ethnic backgrounds, and socioeconomic means.

Robotic approach for retromuscular ventral hernia repair may be associated with improved wound morbidity in high-risk patients: a propensity score analysis.

BACKGROUND: Retromuscular sublay (RMS) technique for repair of ventral hernias has gained popularity due to lower risk of recurrence and wound complications. Robotic approaches to RMS have been shown to decrease hospital stay; however, previous studies have failed to show a significant reduction in wound morbidity. Utilizing the Abdominal Core Health Quality Collaborative (ACHQC) database, this study sought to determine the effect of robotic approach on wound morbidity, while specifically focusing on a high-risk population. METHODS: A retrospective review of elective robotic and open RMS repairs in the ACHQC database was performed. Patients deemed to be high-risk for wound complications were included: adult patients with BMI greater than 35 and who were either current smokers or diabetics. A propensity score match was then done to balance covariates between the two groups. Main outcomes of concern were surgical site occurrences (SSO), surgical site infections (SSI), and surgical site occurrence requiring procedural intervention (SSOPI) at 30-day follow-up. RESULTS: A total of 917 patients met inclusion criteria. After propensity score matching, 211 patients matched for each approach. There was no difference in overall SSO (18% for Open vs 23% for Robotic, p = 0.23). Open repair was associated with higher rates of SSI (4% vs 1%, p = 0.032) and SSOPI (9% SSOPI vs 3%, p < 0. 015). As seen in previous studies, there was a higher rate of seroma associated with Robotic RMS repair (87% vs 48%, p < 0.001) in patients that developed an SSO. CONCLUSIONS: In this analysis, a robotic approach was associated with decreased rates of SSI and SSOPI in obese patients who were either current smokers or diabetics. In effort to reduce wound morbidity and the associated physical and economic costs, robotic approach for retromuscular ventral hernia repair should be considered in this patient population.

High-intensity sweet taste as a predictor of subjective alcohol responses to the ascending limb of an intravenous alcohol prime: an fMRI study.

High-intensity sweet-liking has been linked to alcohol use disorder (AUD) risk. However, the neural underpinning of this association is poorly understood. To find a biomarker predictive of AUD, 140 participants (social and heavy drinkers, ages 21-26) underwent functional magnetic resonance imaging (fMRI) during a monetary incentive delay (MID) task and stimulation with high (SucroseHigh)- and low-concentration sucrose, as well as viscosity-matched water. On another day after imaging, and just before free-access intravenous alcohol self-administration, participants experienced a 30 mg% alcohol prime (10 min ascent) using the Computerized Alcohol Infusion System. Principal component analysis (PCA) of subjective responses (SR) to the prime's ascending limb generated enjoyable (SRenjoy) and sedative (SRsed) intoxication components. Another PCA created one component reflective of self-administered alcohol exposure (AE) over 90 min. Component loadings were entered as regressors in a voxel-wise general linear fMRI model, with reward type as a fixed factor. By design, peak prime breath alcohol concentration was similar across participants (29 ± 3.4 mg%). SRenjoy on the prime's ascending limb correlated positively with [SucroseHigh > Water] in the supplementary motor area and right dorsal anterior insula, implicating the salience network. Neither SR component correlated with the brain's response to MID. AE was unrelated to brain reward activation. While these findings do not support a relationship between alcohol self-administration and (1) subjective liking of or (2) regional brain response to an intensely sweet taste, they show that alcohol's enjoyable intoxicating effects on the rising limb correspond with anterior insular and supplementary motor area responses to high-concentration sucrose taste. No such associations were observed with MID despite robust activation in those regions. Insula and supplementary motor area responses to intense sensations relate to a known risk factor for AUD in a way that is not apparent with a secondary (monetary) reward.

Learning curves of robotic extended totally extraperitoneal (eTEP) hernia repair among two surgeons at a high-volume community hospital: a cumulative sum analysis.

INTRODUCTION: Robotic extended totally extraperitoneal hernia (eTEP) repair is a novel technique for minimally invasive ventral hernia repair with retromuscular placement of mesh. This study aimed to evaluate the learning curve for robotic eTEP hernia repair using risk-adjusted cumulative sum (RA-CUSUM) analysis for two general surgeons-one with dedicated fellowship training in robotic eTEP technique (surgeon 2) and another without robotic eTEP-specific training (surgeon 1). METHODS: We conducted a retrospective analysis of 98 patients undergoing robotic eTEP hernia repair from July 2020 to February 2022 for two surgeons. RA-CUSUM method was applied to the overall operative time (OT) in minutes, adjusting for transversus abdominis release (TAR). RESULTS: Figures 3 (surgeon 1) and 4 (surgeon 2) illustrate the three phases in the RA-CUSUM graphs of OT. For surgeon 1, the cases for each phase were determined: phase 1 (1 to 12), phase 2 (13 to 24), and phase 3 (25 to 51). For surgeon 2, the three phases were similarly determined as 1 to 8, 9 to 32, and 33 to 47, respectively. A significant (p = 0.017) difference existed for the OTs between phases 1 (262 ± 69) and 3 (192 ± 63.0) for surgeon 1. OT compared to the risk-adjusted value stabilized after case 12 and decreased after case 24 for surgeon 1; it began to decrease after case 8 for surgeon 2. CONCLUSIONS: The initial learning curve for surgeon 1 reached its plateau after 12 cases, shorter than comparable studies. This was likely due to the surgeon's intentional focus on learning this technique through courses, proctoring, and active mentorship. The flat learning curve seen in surgeon 2's series illustrates the value of experience gained during fellowship training. Our data support that, given the right resources and support, a short learning curve for eTEP is attainable for community surgeons without prior training in the technique.

Free-access intravenous alcohol self-administration in social drinkers and individuals with alcohol use disorder: Evaluation of relationships with phosphatidylethanol and self-reported alcohol consumption.

BACKGROUND: The free-access (FA) intravenous alcohol self-administration (IV-ASA) paradigm is an experimental approach that can identify modulators of alcohol consumption in humans. Moreover, the outcome measures of IV-ASA paradigms are associated with self-reported alcohol intake using the timeline follow-back method (TLFB). To evaluate how FA IV-ASA reflects drinking in real life, we examined the relationship between an objective marker of recent alcohol intake, phosphatidylethanol in blood (B-PEth), and TLFB and measures obtained during IV-ASA in individuals with alcohol use disorder (AUD) and social drinkers (SD). We also explored the associations between these measures and gut-brain peptides involved in AUD pathophysiology. METHODS: Thirty-eight participants completed a laboratory session in which they self-administered alcohol intravenously. The safety limit was 200 mg%, and main outcomes were mean and peak breath alcohol concentrations (BrAC). Blood samples were drawn prior to IV-ASA and subjective alcohol effects were rated during the experiment. RESULTS: The study sample comprised 24 SD and 14 participants with DSM-5 mild AUD. Although BrACs were not associated with B-PEth or TLFB in the full sample or AUD subgroup, there was an association with TLFB in SD. In both subgroups, BrACs were associated with alcohol craving but with differential timing. Total ghrelin levels were higher in AUD participants than in SD. CONCLUSIONS: No associations between B-PEth levels and achieved BrACs were observed in the mild AUD group, the SD group, or the full sample. The ability for FA IV-ASA to reflect recent drinking was confirmed only for TLFB in SD, whereas there were no associations within the smaller subsample of participants with mild AUD or in the full sample. Further studies that include a larger AUD sample are warranted. The association of BrACs with craving for alcohol suggests that the IV-ASA method may be useful for assessing interventions that target craving. This could be explored by using the FA IV-ASA model to evaluate the effects on craving of approved pharmacotherapies for AUD.

Psychological and psychosocial determinants of COVID Health Related Behaviours (COHeRe): An evidence and gap map.

Background: The COVID-19 pandemic, caused by the SARS-CoV-2 virus, has resulted in illness, deaths and societal disruption on a global scale. Societies have implemented various control measures to reduce transmission of the virus and mitigate its impact. Individual behavioural changes are crucial to the successful implementation of these measures. Common recommended measures to limit risk of infection include frequent handwashing, reducing the frequency of social interactions and the use of face coverings. It is important to identify those factors that can predict the uptake and maintenance of these protective behaviours. Objectives: We aimed to identify and map the existing evidence (published and unpublished) on psychological and psychosocial factors that determine uptake and adherence to behaviours aimed at reducing the risk of infection or transmission of COVID-19. Search Methods: Our extensive search included electronic databases (n = 12), web searches, conference proceedings, government reports, other repositories including both published peer reviewed, pre-prints and grey literature. The search strategy was built around three concepts of interest including (1) context (terms relating to COVID-19), (2) behaviours of interest and (3) terms related to psychological and psychosocial determinants of COVID Health-Related Behaviours and adherence or compliance with recommended behaviours, to capture both malleable and non-malleable determinants (i.e. determinants that could be changed and those that could not). Selection Criteria: This Evidence and Gap Map (EGM) includes all types of studies examining determinants of common recommended behaviours aimed at mitigating human-to-human spread of COVID-19. All potential malleable and non-malleable determinants of one or more behaviours are included in the map. As part of the mapping process, categories are used to group determinants. The mapping categories were based on a previous rapid review by Hanratty 2021. These include: 'behaviour', 'cognition', 'demographics', 'disease', 'emotions', 'health status', 'information', 'intervention', and 'knowledge'. Those not suitable for categorisation in any of these groups are included in the map as 'other' determinants. Data Collection and Analysis: Results were imported to a bibliographic reference manager where duplications of identical studies gathered from multiple sources were removed. Data extraction procedures were managed in EPPI-Reviewer software. Information on study type, population, behaviours measured and determinants measured were extracted. We appraised the methodological quality of systematic reviews with AMSTAR-2. We did not appraise the quality of primary studies in this map. Main Results: As of 1 June 2022 the EGM includes 1034 records reporting on 860 cross-sectional, 68 longitudinal, 78 qualitative, 25 reviews, 62 interventional, and 39 other studies (e.g., mixed-methods approaches). The map includes studies that measured social distancing (n = 487), masks and face coverings (n = 382), handwashing (n = 308), physical distancing (n = 177), isolation/quarantine (n = 157), respiratory hygiene/etiquette (n = 75), cleaning surfaces (n = 59), and avoiding touching the T-zone (n = 48). There were 333 studies that assessed composite measures of two or more behaviours. The largest cluster of determinants was 'demographics' (n = 730 studies), followed by 'cognition' (n = 496 studies) and determinants categorised as 'other' (n = 447). These included factors such as 'beliefs', 'culture' and 'access to resources'. Less evidence is available for some determinants such as 'interventions' (n = 99 studies), 'information' (n = 101 studies), and 'behaviour' (149 studies). Authors' Conclusions: This EGM provides a valuable resource for researchers, policy-makers and the public to access the available evidence on the determinants of various COVID-19 health-related behaviours. The map can also be used to help guide research commissioning, by evidence synthesis teams and evidence intermediaries to inform policy during the ongoing pandemic and potential future outbreaks of COVID-19 or other respiratory infections. Evidence included in the map will be explored further through a series of systematic reviews examining the strength of the associations between malleable determinants and the uptake and maintenance of individual protective behaviours.

Spectral resolution enhancement for impulsive stimulated Brillouin spectroscopy by expanding pump beam geometry.

Brillouin microscopy has recently emerged as a powerful tool for mechanical property measurements in biomedical sensing and imaging applications. Impulsive stimulated Brillouin scattering (ISBS) microscopy has been proposed for faster and more accurate measurements, which do not rely on stable narrow-band lasers and thermally-drifting etalon-based spectrometers. However, the spectral resolution of ISBS-based signal has not been significantly explored. In this report, the ISBS spectral profile has been investigated as a function of the pump beam's spatial geometry, and novel methodologies have been developed for accurate spectral assessment. The ISBS linewidth was found to consistently decrease with increasing pump-beam diameter. These findings provide the means for improved spectral resolution measurements and pave the way to broader applications of ISBS microscopy.

Rapid and precise tracking of water influx and efflux across cell membranes induced by a pulsed electric field.

Quantitative measurements of water content within a single cell are notoriously difficult. In this work, we introduce a single-shot optical method for tracking the intracellular water content, by mass and volume, of a single cell at video rate. We utilize quantitative phase imaging and a priori knowledge of a spherical cellular geometry, leveraging a two-component mixture model to compute the intracellular water content. We apply this technique to study CHO-K1 cells responding to a pulsed electric field, which induces membrane permeabilization and rapid water influx or efflux depending upon the osmotic environment. The effects of mercury and gadolinium on water uptake in Jurkat cells following electropermeabilization are also examined.

Effects of acute alcohol exposure and chronic alcohol use on neurite orientation dispersion and density imaging (NODDI) parameters.

RATIONALE: Little is known about how acute and chronic alcohol exposure may alter the in vivo membrane properties of neurons. OBJECTIVES: We employed neurite orientation dispersion and density imaging (NODDI) to examine acute and chronic effects of alcohol exposure on neurite density. METHODS: Twenty-one healthy social drinkers (CON) and thirteen nontreatment-seeking individuals with alcohol use disorder (AUD) underwent a baseline multi-shell diffusion magnetic resonance imaging (dMRI) scan. A subset (10 CON, 5 AUD) received dMRI during intravenous infusions of saline and alcohol during dMRI. NODDI parametric images included orientation dispersion (OD), isotropic volume fraction (ISOVF), and corrected intracellular volume fraction (cICVF). Diffusion tensor imaging metrics of fractional anisotropy and mean, axial, and radial diffusivity (FA, MD, AD, RD) were also computed. Average parameter values were extracted from white matter (WM) tracts defined by the Johns Hopkins University atlas. RESULTS: There were group differences in FA, RD, MD, OD, and cICVF, primarily in the corpus callosum. Both saline and alcohol had effects on AD and cICVF in WM tracts proximal to the striatum, cingulate, and thalamus. This is the first work to indicate that acute fluid infusions may alter WM properties, which are conventionally believed to be insensitive to acute pharmacological challenges. It also suggests that the NODDI approach may be sensitive to transient changes in WM. The next steps should include determining if the effect on neurite density differs with solute or osmolality, or both, and translational studies to assess how alcohol and osmolality affect the efficiency of neurotransmission.

Dissemination of public health research to prevent non-communicable diseases: a scoping review.

BACKGROUND: Dissemination is a critical element of the knowledge translation pathway, and a necessary step to ensure research evidence is adopted and implemented by key end users in order to improve health outcomes. However, evidence-based guidance to inform dissemination activities in research is limited. This scoping review aimed to identify and describe the scientific literature examining strategies to disseminate public health evidence related to the prevention of non-communicable diseases. METHODS: Medline, PsycInfo and EBSCO Search Ultimate were searched in May 2021 for studies published between January 2000 and the search date that reported on the dissemination of evidence to end users of public health evidence, within the context of the prevention of non-communicable diseases. Studies were synthesised according to the four components of Brownson and colleagues' Model for Dissemination of Research (source, message, channel and audience), as well as by study design. RESULTS: Of the 107 included studies, only 14% (n = 15) directly tested dissemination strategies using experimental designs. The remainder primarily reported on dissemination preferences of different populations, or outcomes such as awareness, knowledge and intentions to adopt following evidence dissemination. Evidence related to diet, physical activity and/or obesity prevention was the most disseminated topic. Researchers were the source of disseminated evidence in over half the studies, and study findings/knowledge summaries were more frequently disseminated as the message compared to guidelines or an evidence-based program/intervention. A broad range of dissemination channels were utilised, although peer-reviewed publications/conferences and presentations/workshops predominated. Practitioners were the most commonly reported target audience. CONCLUSIONS: There is a significant gap in the peer reviewed literature, with few experimental studies published that analyse and evaluate the effect of different sources, messages and target audiences on the determinants of uptake of public health evidence for prevention. Such studies are important as they can help inform and improve the effectiveness of current and future dissemination practices in public health contexts.

Using naltrexone to validate a human laboratory test system to screen new medications for alcoholism (TESMA)- a randomized clinical trial.

This registered clinical trial sought to validate a laboratory test system devised to screen medications for alcoholism treatment (TESMA) under different contingencies of alcohol reinforcement. Forty-six nondependent, but at least medium-risk drinkers were given the opportunity to earn intravenous infusions of ethanol, or saline, as rewards for work in a progressive-ratio paradigm. Work demand pattern and alcohol exposure dynamics were devised to achieve a gradual shift from low-demand work for alcohol (WFA) permitting quickly increasing breath alcohol concentrations (BrAC) to high-demand WFA, which could only decelerate an inevitable decrease of the previously earned BrAC. Thereby, the reward contingency changed, modeling different drinking motivations. The experiment was repeated after at least 7 days of randomized, double-blinded treatment with naltrexone, escalated to 50 mg/d, or placebo. Subjects treated with naltrexone reduced their cumulative WFA (cWFA) slightly more than participants receiving placebo. This difference was not statistically significant in the preplanned analysis of the entire 150 min of self-administration, i.e., our primary endpoint (p = 0.471, Cohen's d = 0.215). Naltrexone serum levels correlated with change in cWFA (r = -0.53; p = 0.014). Separate exploratory analyses revealed that naltrexone significantly reduced WFA during the first, but not the second half of the experiment (Cohen's d = 0.643 and 0.14, respectively). Phase-dependent associations of WFA with changes in subjective stimulation, wellbeing and desire for alcohol suggested that the predominant reinforcement of WFA was positive during the first phase only, and might have been negative during the second. We conclude that the TESMA is a safe and practical method. It bears the potential to quickly and efficiently screen new drugs for their efficacy to attenuate positively reinforced alcohol consumption. It possibly also provides a condition of negative reinforcement, and for the first time provides experimental evidence suggesting that naltrexone's effect might depend on reward contingency.

Fat-free mass accounts for most of the variance in alcohol elimination rate in women.

BACKGROUND: Understanding how blood alcohol concentrations (BAC) achieved after drinking are determined is critical to predicting alcohol exposure to the brain and other organs and alcohol's effects. However, predicting end-organ exposures is challenging, as there is wide variation in BAC achieved after drinking a specified volume of alcohol. This variation is partly due to differences in body composition and alcohol elimination rates (AER), but there are limited data on how obesity affects AER. Here, we assess associations between obesity, fat-free mass (FFM), and AER in women and examine whether bariatric surgeries, which are linked to an increased risk of alcohol misuse, affect these associations. METHODS: We analyzed data from three studies that used similar intravenous alcohol clamping procedures to estimate AER in 143 women (21 to 64 years old) with a wide range of body mass index (BMI; 18.5 to 48.4 kg/m2 ). Body composition was measured in a subgroup using dual-energy X-ray absorptiometry (n = 42) or Bioimpedance (n = 60), and 19 of the women underwent bariatric surgery 2.1 ± 0.3 years before participation. We analyzed data using multiple linear regression analyses. RESULTS: Obesity and older age were associated with a faster AER (BMI: rs  = 0.70 and age: rs  = 0.61, both p < 0.001). Compared to women with normal weight, AER was 52% faster (95% Confidence Interval: 42% to 61%) in women with obesity. However, BMI lost predictive value when adding fat-free mass (FFM) to the regression model. Age, FFM, and its interaction explained 72% of individual variance in AER (F (4, 97) = 64.3, p < 0.001). AER was faster in women with higher FFM, particularly women in the top tertile of age. After controlling for FFM and age, bariatric surgery was not associated with differences in AER (p = 0.74). CONCLUSIONS: Obesity is associated with a faster AER, but this association is mediated by an obesity-related increase in FFM, particularly in older women. Previous findings of a reduced alcohol clearance following bariatric surgery compared with prior to surgery are likely explained by a reduction in FFM post-surgery.

Physical Demands of Tennis Across the Different Court Surfaces, Performance Levels and Sexes: A Systematic Review with Meta-analysis.

BACKGROUND: Tennis is a multidirectional high-intensity intermittent sport for male and female individuals played across multiple surfaces. Although several studies have attempted to characterise the physical demands of tennis, a meta-analysis is still lacking. OBJECTIVE: We aimed to describe and synthesise the physical demands of tennis across the different court surfaces, performance levels and sexes. METHODS: PubMed, Embase, CINAHL and SPORTDiscus were searched from inception to 19 April, 2022. A backward citation search was conducted for included articles using Scopus. The PECOS framework was used to formulate eligibility criteria. POPULATION: tennis players of regional, national or international playing levels (juniors and adults). EXPOSURE: singles match play. Comparison: sex (male/female), court surface (hard, clay, grass). OUTCOME: duration of play, on-court movement and stroke performance. STUDY DESIGN: cross-sectional, longitudinal. Pooled means or mean differences with 95% confidence intervals were calculated. A random-effects meta-analysis with robust variance estimation was performed. The measures of heterogeneity were Cochrane Q and 95% prediction intervals. Subgroup analysis was used for different court surfaces. RESULTS: The literature search generated 7736 references; 64 articles were included for qualitative and 42 for quantitative review. Mean [95% confidence interval] rally duration, strokes per rally and effective playing time on all surfaces were 5.5 s [4.9, 6.3], 4.1 [3.4, 5.0] and 18.6% [15.8, 21.7] for international male players and 6.4 s [5.4, 7.6], 3.9 [2.4, 6.2] and 20% [17.3, 23.3] for international female players. Mean running distances per point, set and match were 9.6 m [7.6, 12.2], 607 m [443, 832] and 2292 m [1767, 2973] (best-of-5) for international male players and 8.2 m [4.4, 15.2], 574 m [373, 883] and 1249 m [767, 2035] for international female players. Mean first- and second-serve speeds were 182 km·h-1 [178, 187] and 149 km·h-1 [135, 164] for international male players and 156 km·h-1 95% confidence interval [151, 161] and 134 km·h-1 [107, 168] for international female players. CONCLUSIONS: The findings from this study provide a comprehensive summary of the physical demands of tennis. These results may guide tennis-specific training programmes. We recommend more consistent measuring and reporting of data to enable future meta-analysts to pool meaningful data. CLINICAL TRIAL REGISTRATION: The protocol for this systematic review was registered a priori at the Open Science Framework (Registration DOI https://doi.org/10.17605/OSF.IO/MDWFY ).

Intraoperative plasma proteomic changes in cardiac surgery: In search of biomarkers of post-operative delirium.

PURPOSE: Delirium presents a significant healthcare burden. It complicates post-operative care in up to 50% of cardiac surgical patients with worse outcomes, longer hospital stays and higher cost of care. Moreover, the nature of delirium following cardiac surgery with cardiopulmonary bypass (CPB) remains unclear, the underlying pathobiology is poorly understood, status quo diagnostic methods are subjective, and diagnostic biomarkers are currently lacking. OBJECTIVE: To identify diagnostic biomarkers of delirium and for insights into possible neuronal pathomechanisms. EXPERIMENTAL DESIGN: Comparative proteomic analyses were performed on plasma samples from a nested matched cohort of patients who underwent cardiac surgery. Validation by targeted proteomics was performed in an independent set of samples. Biomarkers were assessed for biological functions and diagnostic accuracy. RESULTS: Forty-seven percent of subjects demonstrated delirium. Of 3803 proteins identified from patient samples by multiplexed quantitative proteomics, 16 were identified as signatures of exposure to CPB, and 11 biomarkers distinguished delirium cases from non-cases (AuROC = 93%). Notable among these biomarkers are C-reactive protein, serum amyloid A-1 and cathepsin-B. CONCLUSIONS AND CLINICAL RELEVANCE: The interplay of systemic and central inflammatory markers sheds new light on delirium pathogenesis. This work suggests that accurate identification of cases may be achievable using panels of biomarkers.

Echocardiographic Evidence of Cardiac Atrophy in the Critically Ill.

The purpose of this explorative study is to determine if critically ill patients experience cardiac atrophy that can be quantified as a loss of left ventricular mass (LVM) and thus detected by echocardiography. DESIGN: Retrospective single-center cohort study. SETTING: Patients admitted to a tertiary medical center in Boston, MA. PATIENTS: Adult critically ill patients with ICU length of stay greater than or equal to 5 days. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: We conducted a retrospective cohort study of 68 patients, of which 42 were included in the final analysis (mean age 60.9 ± 19.2 yr; 47.6% male). The median length of ICU stay was 11.3 days (interquartile range, 6.8-20.1 d). A decrease in mean LVM over the course of admission for critical illness was observed (median 189.11 g [162.82-240.20 g] vs 176.69 g [142.37-226.26 g]; p = 0.01). After adjusting for sex, age, fluid balance, ICU type, dietary orders, time between echocardiograms, and vasopressor use, this decrease in LVM remained consistent (mean difference, -21.30 g; 95% CI, -41.85 to -0.74; p = 0.04). Relative wall thickness (RWT) did not change during admission. CONCLUSIONS: These data reveal that a loss of LVM is present in patients over their ICU stay without a corresponding change in RWT, consistent with cardiac atrophy. Future prospective studies are needed to confirm these findings and identify possible sequelae of this finding.