A cost-consequence analysis comparing three cardiac ablation strategies for the treatment of paroxysmal atrial fibrillation.

Background and aimsCardiac ablation is a well-established method for treating atrial fibrillation (AF). Pulsed field ablation (PFA) is a non-thermal therapeutic alternative to radiofrequency ablation (RFA) and cryoballoon ablation (CRYO). PFA uses high-voltage electric pulses to target cells. The present analysis aims to quantify the costs, outcomes, and resources associated with these three ablation strategies for paroxysmal AF.MethodsReal-world clinical data were prospectively collected during index hospitalization by three European medical centers (Belgium, Germany, the Netherlands) specialized in cardiac ablation. These data included procedure times (pre-procedural, skin-to-skin and post-procedural), resource use, and staff burden. Data regarding complications associated with each of the three treatment options and redo procedures were extracted from the literature. Costs were collected from hospital economic formularies and published cost databases. A cost-consequence model from the hospital perspective was built to estimate the impact of the three treatment options in terms of effectiveness and costs.ResultsAcross the three centers, N = 91 patients were included over a period of 12 months. A significant difference was seen in pre-procedural time (mean ± SD, PFA: 13.6 ± 3.7 min, CRYO: 18.8 ± 6.6 min, RFA: 20.4 ± 6.4 min; p < 0.001). Procedural time (skin-to-skin) was also different across alternatives (PFA: 50.9 ± 22.4 min, CRYO: 74.5 ± 24.5 min, RFA: 140.2 ± 82.4 min; p < 0.0001). The model reported an overall cost of €216,535 per 100 patients treated with PFA, €301,510 per 100 patients treated with CRYO and €346,594 per 100 patients treated with RFA. Overall, the cumulative savings associated with PFA (excluding kit costs) were €850 and €1,301 per patient compared to CRYO and RFA, respectively.ConclusionPFA demonstrated shorter procedure time compared to CRYO and RFA. Model estimates indicate that these time savings result in cost savings for hospitals and reduce outlay on redo procedures. Clinical practice in individual hospitals varies and may impact the ability to transfer results of this analysis to other settings.

Using artificial intelligence and deep learning to optimise the selection of adult congenital heart disease patients in S-ICD screening.

INTRODUCTION: The risk of complications associated with transvenous ICDs make the subcutaneous implantable cardiac defibrillator (S-ICD) a valuable alternative in patients with adult congenital heart disease (ACHD). However, higher S-ICD ineligibility and higher inappropriate shock rates-mostly caused by T wave oversensing (TWO)- are observed in this population. We report a novel application of deep learning methods to screen patients for S-ICD eligibility over a longer period than conventional screening. METHODS: Adult patients with ACHD and a control group of normal subjects were fitted with a 24-h Holters to record their S-ICD vectors. Their T:R ratio was analysed utilising phase space reconstruction matrices and a deep learning-based model to provide an in-depth description of the T: R variation plot for each vector. T: R variation was compared statistically using t-test. RESULTS: 13 patients (age 37.4 ± 7.89 years, 61.5 % male, 6 ACHD and 7 control subjects) were enrolled. A significant difference was observed in the mean and median T: R values between the two groups (p < 0.001). There was also a significant difference in the standard deviation of T: R between both groups (p = 0.04). CONCLUSIONS: T:R ratio, a main determinant for S-ICD eligibility, is significantly higher with more tendency to fluctuate in ACHD patients when compared to a population with normal hearts. We hypothesise that our novel model could be used to select S-ICD eligible patients by better characterisation of T:R ratio, reducing the risk of TWO and inappropriate shocks in the ACHD patient cohort.

Transurethral Resection of the Prostate in Younger Men: Effectiveness and Long-term Outcomes.

OBJECTIVES: This study aims to investigate the efficacy and outcomes of transurethral resection of the prostate (TURP) in the context of younger male patients. METHODS: Males aged ≤55 who underwent TURP at Rambam Health Care Campus from January 2011 to August 2023 were retrospectively reviewed. Clinicodemographic characteristics, indications for surgery, uroflowmetry, pressure-flow study, and early and late postoperative outcomes were collected. Patients with urethral or bladder abnormalities were excluded. Chi-square and Fisher's exact tests were employed for bivariate analysis. RESULTS: Inclusion criteria were met by 58 men who underwent TURP at a median age of 52 years (interquartile range [IQR] 49.5-54). Median prostate size was 35 mL (24.5-56), with median prostate-specific antigen of 1.4 ng/mL (0.65-3.1). A total of 60% of patients used α-blockers, and 19% used 5α-reductase inhibitors pre-surgery. Overall, 54 (93.1%) had severe lower urinary tract symptoms (LUTS), with 34 (59%) being predominantly emptying and 20 (35%) storage. Most surgeries were performed for refractory LUTS in 38 (66%), followed by urinary retention in 16 (28%). At 6 weeks, 57 (98%) patients were catheter-free. The maximum flow rate and residual volume showed significant improvement from a median of 6.85 mL/s to 17.9 mL/s (P<0.001), and from 120 mL to 10 mL (P=0.0142), respectively. Pathology revealed benign prostatic hyperplasia in 53 (91.4%), and inflammation in 5 (8.5%). A total of 13 auxiliary procedures were required in 12 patients (20.7%) during follow-up: 7 transurethral bladder neck incisions, 3 re-TURP, 1 meatus widening, and 1 patient required artificial urinary sphincter implantation followed by simple cystectomy for end-stage bladder. CONCLUSIONS: In young men, TURP showed short-term gains in flowmetry and catheter removal rates, but a sustained need for subsequent procedures in the long run. In this unique population, patients should be carefully selected, and alternative, less aggressive, interventions should be considered.

The use and misuse of the SCOFF screening measure over two decades: a systematic literature review.

PURPOSE: The SCOFF questionnaire was designed as a simple, memorable screening tool to raise suspicion that a person might have an eating disorder. It is over 20 years since the creation of the SCOFF, during which time it has been widely used. Considering this, we wish to review the use of the SCOFF in peer-reviewed scientific journals, and to assess whether it is being used appropriately in the manner in which it was originally devised and tested. METHODS: The Preferred Reporting Items for a Systematic Review and Meta-analysis (PRISMA) guidelines were followed, and all search strategies and methods were determined before the onset of the study. PubMed and Wiley Online Library were searched using the terms SCOFF and eating. Two reviewers were involved in the reviewing process. Criteria for appropriate use of the SCOFF were formalised with the tool's original authors. RESULTS: 180 articles were included in the final review. 48 articles had used the SCOFF appropriately, 117 articles inappropriately and 15 articles had been mixed in the appropriateness of their use. CONCLUSION: This systematic review highlights the inappropriate use of the SCOFF in diverse languages and settings. When used correctly the SCOFF has made a significant contribution to the understanding of eating disorders and its simplicity has been applauded and led to widespread use. However in over two-thirds of studies, the use of the SCOFF was inappropriate and the paper highlights how and in what way it was misused, Guidelines for the appropriate use of the SCOFF are stated. Future validation and avenues of research are suggested. LEVEL OF EVIDENCE: Level I.

How territoriality and sociality influence the habitat selection and movements of a large carnivore.

While territoriality is one of the key mechanisms influencing carnivore space use, most studies quantify resource selection and movement in the absence of conspecific influence or territorial structure. Our analysis incorporated social information in a resource selection framework to investigate mechanisms of territoriality and intra-specific competition on the habitat selection of a large, social carnivore. We fit integrated step selection functions to 3-h GPS data from 12 collared African wild dog packs in the Okavango Delta and estimated selection coefficients using a conditional Poisson likelihood with random effects. Packs selected for their neighbors' 30-day boundary (defined as their 95% kernel density estimate) and for their own 90-day core (defined as their 50% kernel density estimate). Neighbors' 30-day boundary had a greater influence on resource selection than any habitat feature. Habitat selection differed when they were within versus beyond their neighbors' 30-day boundary. Pack size, pack tenure, pup presence, and seasonality all mediated how packs responded to neighbors' space use, and seasonal dynamics altered the strength of residency. While newly-formed packs and packs with pups avoided their neighbors' boundary, older packs and those without pups selected for it. Packs also selected for the boundary of larger neighboring packs more strongly than that of smaller ones. Social structure within packs has implications for how they interact with conspecifics, and therefore how they are distributed across the landscape. Future research should continue to investigate how territorial processes are mediated by social dynamics and, in turn, how territorial structure mediates resource selection and movement. These results could inform the development of a human-wildlife conflict (HWC) mitigation tool by co-opting the mechanisms of conspecific interactions to manage space use of endangered carnivores.

Factors Informing High-Risk Primary Care Patient Choice around Telehealth Use: a Framework.

BACKGROUND: While telehealth's presence in post-pandemic primary care appears assured, its exact role remains unknown. Value-based care's expansion has heightened interest in telehealth's potential to improve uptake of preventive and chronic disease care, especially among high-risk primary care populations. Despite this, the pandemic underscored patients' diverse preferences around using telehealth. Understanding the factors underlying this population's preferences can inform future telehealth strategies. OBJECTIVE: To describe the factors informing high-risk primary care patient choice of whether to pursue primary care via telehealth, in-office or to defer care altogether. DESIGN: Qualitative, cross-sectional study utilizing semi-structured telephone interviews of a convenience sample of 29 primary care patients between July 13 and September 30, 2020. PARTICIPANTS: Primary care patients at high risk of poor health outcomes and/or acute care utilization who were offered a follow-up primary care visit via audiovisual, audio-only or in-office modalities. APPROACH: Responses were analyzed via grounded theory, using a constant comparison method to refine emerging categories, distinguish codes, and synthesize evolving themes. KEY RESULTS: Of the 29 participants, 16 (55.2%) were female and 19 (65.5%) were Black; the mean age (SD) was 64.6 (11.1). Participants identified four themes influencing their choice of visit type: perceived utility (encapsulating clinical and non-clinical utility), underlying costs (in terms of time, money, effort, and safety), modifiers (e.g., participants' clinical situation, choice availability, decision phenotype), and drivers (inclusive of their background experiences and digital environment). The relationship of these themes is depicted in a novel framework of patient choice around telehealth use. CONCLUSIONS: While visit utility and cost considerations are foundational to participants' decisions around whether to pursue care via telehealth, underappreciated modifiers and drivers often magnify or mitigate these considerations. Policymakers, payers, and health systems can leverage these factors to anticipate and enhance equitable high-value telehealth use in primary care settings among high-risk individuals.

Evaluation of bidirectional gut-brain axis and anorectal function in Parkinson's disease with constipation.

BACKGROUND: Parkinson's disease (PD) is a neurodegenerative movement disorder with prodromal and highly prevalent gastrointestinal (GI) symptoms, especially constipation. Although PD models suggest gut-brain axis dysfunction, the mechanistic underpinnings and their correlation with GI symptoms are poorly understood. AIM: To examine the bidirectional gut-brain axis function in PD and correlate it with constipation severity, PD duration, and severity. METHODS: Rectal sensory thresholds and afferent cortical evoked potentials (CEP) were assessed using a 4-ring EMG electrode probe. Efferent anal and rectal motor evoked potentials (MEPs) were obtained following transcranial and lumbosacral magnetic stimulation. Bowel symptoms were assessed by prospective stool diary. The CEP and MEP latencies, rectal sensory thresholds, and anorectal sensorimotor data were compared between PD subjects and age-adjusted healthy subjects. KEY RESULTS: Twenty-five PD subjects with constipation (F/M = 6/19) and 20 healthy subjects (F/M = 14/6) were enrolled. The first and pain sensation thresholds were higher in PD subjects than healthy subjects (p < 0.002) but lost significance after adjustment for age. Age-adjusted rectal CEP and right-sided cortico-anal MEP latencies were prolonged in PD subjects compared to healthy subjects (p < 0.04). Also, half (4 of 8) age-adjusted spino-anal and rectal MEP latencies in PD subjects were significantly longer. In multivariate linear analysis, first rectal sensation and right-sided MEP latencies showed moderate correlation with constipation severity. CONCLUSIONS & INFERENCES: Parkinson's disease is associated with significant bidirectional gut-brain axis dysfunction as evidenced by prolonged afferent and efferent neuronal signaling. Constipation severity in PD is correlated to abnormal rectal sensation and lateralized disturbance of efferent brain-gut signaling.

Relative contribution of photodegradation to litter breakdown in Australian grasslands.

Grassy ecosystems cover ~40% of the global land surface and are an integral component of the global carbon (C) cycle. Grass litter decomposes via a combination of photodegradation (which returns C to the atmosphere rapidly) and biological decomposition (a slower C pathway). As such, decomposition and C storage in grasslands may vary with climate and exposure to solar radiation. We investigated rates of grass litter decomposition in Australian temperate grasslands along a climate gradient to uncouple the relative importance of photodegradation and climate on decomposition. Litterbags containing leaf litter from two common native grass species (Poa labillardierei, Themeda triandra) were deployed at six grassland sites across a precipitation gradient (380-890 mm) in south-eastern Australia. Bags were retrieved over 39 weeks to measure mass loss from decomposition. We used shade treatments on the litter of one species (T. triandra) to partition photodegradation from biological decomposition. The shade treatment reduced the rate of decomposition of T. triandra relative to the full-sun treatment at all sites, by an average of 38% at 39 weeks; the effect size of the shade treatment was not correlated with site productivity. The rate of decomposition in both species was positively correlated with rainfall midway through the experiment, but there were no significant differences in total decomposition among sites after 39 weeks. By week 39, total decomposition of T. triandra was significantly greater than for P. labillardierei. In general, we observed relatively linear decomposition rather than the strong negative exponential decay observed in many global litter decomposition studies. Synthesis: We found that solar radiation exposure was a strong contributor to litter decomposition in temperate Australian grasslands across a broad climate gradient, which may be related to a period of photopriming prior to further biotic decomposition. This study highlights the importance of litter composition and solar radiation exposure in our understanding of how decomposition patterns contribute to global C cycling.

Assessing the diet and seed dispersal ability of non-native sambar deer (Rusa unicolor) in native ecosystems of south-eastern Australia.

Understanding the influence of non-native herbivores on ecosystems by means of dietary foraging and seed dispersal is important for understanding how non-native species can alter an invaded landscape, yet requires multiple methodologies. In south-eastern Australia, introduced sambar deer (Rusa unicolor) are rapidly expanding in range and placing native ecosystems at risk through browsing and as vectors for seed dispersal. We simultaneously investigated sambar deer dietary composition and seed dispersal using DNA sequencing and germination trials, from faecal pellets collected in alpine and wet forest ecosystems. This allowed us to contrast the dietary impacts of introduced sambar deer in different environments, and to explore the potential for habitat-specific variation in diet. DNA sequencing of the trnL, ITS2 and rbcL gene regions revealed a diverse plant species dietary composition comprising 1003 operational taxonomic units (OTUs). Sambar deer exhibited intermediate feeder behaviours dominated by forbs in alpine and shrubs in wet forest ecosystems. A large proportion of plant OTUs were considered likely to be native, however, the proportion of exotic species in the diet in both ecosystems was greater than would be expected based on the proportion of exotic species in each of the two landscapes. Seed germination trials indicated that sambar deer can disperse a substantial number of native and exotic species in both alpine and wet forest ecosystems. In alpine ecosystems, an individual sambar deer was estimated to disperse on average 816 (±193) seeds per day during the study period, of which 652 (±176) were exotic. Synthesis and applications. Our results suggest that native plant species comprise the majority of sambar deer diets in Australian ecosystems and that the introduced species is dispersing both native and exotic plant species via endozoochory. However, exotic species seedling germination numbers were significantly higher in alpine ecosystems, and given the large daily movements of sambar deer, represents a significant vector for the spread of exotic plant species. Management of native plant species and vegetation communities of conservation significance, or at risk to sambar deer browsing is of high priority, through either the removal of sambar deer or implementation of exclusion-based methods.

Energy landscapes for proteins described by the UNRES coarse-grained potential.

The self-assembly of proteins is encoded in the underlying potential energy surface (PES), from which we can predict structure, dynamics, and thermodynamic properties. However, the corresponding analysis becomes increasingly challenging with larger protein sizes, due to the computational time required, which grows significantly with the number of atoms. Coarse-grained models offer an attractive approach to reduce the computational cost. In this Feature Article, we describe our implementation of the UNited RESidue (UNRES) coarse-grained potential in the Cambridge energy landscapes software. We have applied this framework to explore the energy landscapes of four proteins that exhibit native states involving different secondary structures. Here we have tested the ability of the UNRES potential to represent the global energy landscape of proteins containing up to 100 amino acid residues. The resulting potential energy landscapes exhibit good agreement with experiment, with low-lying minima close to the PDB geometries and to results obtained using the all-atom AMBER force field. The new program interfaces will allow us to investigate larger biomolecules in future work, using the UNRES potential in combination with all the methodology available in the computational energy landscapes framework.

Early-melting snowpatch plant communities are transitioning into novel states.

Snowpatch plant community distribution and composition are strongly tied to the duration of long-lasting snow cover in alpine areas; they are vulnerable to global climatic changes that result in warmer temperatures and longer growing seasons. We used a revisitation study to quantify early-melting snowpatch floristic and functional diversity change in southern Australia, and document shrub size-class distributions over time to detect evidence for their encroachment into snowpatches, a key prediction with climatic change. Early-melting snowpatch vegetation has declined in areal extent, changed in species composition, and shrub and tussock grass cover has increased, but changes in functional trait diversity were less clear. Species gains, particularly by non-clonal species, accounted for most of the floristic change observed. Shrub recruitment was ongoing by most shrub species. Biotic differentiation is occurring; many early-melting snowpatches are transitioning to a novel state with changed composition and taller vegetation structure, but there is little evidence for species loss having occurred. Given enough time, however, the long-term loss of species is likely (i.e. biotic homogenisation) if taller shrubs outcompete short-statured snowpatch species. Our results provide evidence that this alpine ecosystem is forming a novel community with an uncertain future.

Multidimensional responses of grassland stability to eutrophication.

Eutrophication usually impacts grassland biodiversity, community composition, and biomass production, but its impact on the stability of these community aspects is unclear. One challenge is that stability has many facets that can be tightly correlated (low dimensionality) or highly disparate (high dimensionality). Using standardized experiments in 55 grassland sites from a globally distributed experiment (NutNet), we quantify the effects of nutrient addition on five facets of stability (temporal invariability, resistance during dry and wet growing seasons, recovery after dry and wet growing seasons), measured on three community aspects (aboveground biomass, community composition, and species richness). Nutrient addition reduces the temporal invariability and resistance of species richness and community composition during dry and wet growing seasons, but does not affect those of biomass. Different stability measures are largely uncorrelated under both ambient and eutrophic conditions, indicating consistently high dimensionality. Harnessing the dimensionality of ecological stability provides insights for predicting grassland responses to global environmental change.

Rural Zambian Oral Health Transition: A Long-Term Retrospective Examination of an Outreach Program's Progress and Impact.

Objective: This study aimed to (a) describe an annual prevention-focused, community-based oral health outreach program in rural Zambia, (b) assess its oral health outcomes using demographic and oral health variables, and c) identify milestones resulting from program activities. Methods: A retrospective analysis of demographic and oral health data from a single site between 2007-2014 and 2018-2019 was conducted. Demographic variables included sex and age, while clinical outcomes encompassed pain, untreated caries, and treatment urgency. Bivariate and multivariable analyses were performed, adjusting for sex and age categories. Information on community development was obtained from the Ministry of Health and local community representatives. Results: Data from 5,791 subjects were analyzed. The prevalence of pain, untreated caries, and highest treatment urgency category decreased consistently across year categories. Both bivariate and multivariable analyses showed statistically significant differences in clinical outcomes between year categories (p < 0.001). In addition, the percentage of male participants and younger age categories increased during the study period. Key program milestones included the installation of two boreholes for clean water, the development of a local community oral health volunteer program, the establishment of an educational pipeline by the Dental Training School for residents, and the construction of a maternal/oral health center with district and ministry oversight. Conclusion: The observed decrease in treatment urgency scores, presence of pain, and untreated caries are consistent with the prevention-seeking behavior of program participants. The increasing participation and changing demographic patterns over time suggest a growing demand for oral health services among males and younger individuals. The positive oral health outcomes and development of a maternal child/oral health facility exemplify a program design aligned with community needs and appropriate care delivery.

Utility of Weekly Laboratory Monitoring in the Expectant Management of Hypertensive Disorders of Pregnancy.

Our retrospective cohort study evaluates the diagnostic yield of weekly laboratory surveillance in outpatient management of hypertensive disorders of pregnancy (HDP) based on patient clinical status at the time of laboratory testing. The study included 459 patients and 1,082 laboratory episodes: 356 (32.9%) episodes were performed in the setting of concerning clinical findings and 726 (67.1%) when the patient was asymptomatic. Overall, the diagnostic yield for abnormal laboratory values (n=11) was 1.0% (95% CI 0.4-1.6%) of all assessments performed and 2.4% (95% CI 1.0-3.8%) among all patients in the cohort. The prevalence of abnormal test results was higher in patients with clinical findings (2.8%, 95% CI 1.1-4.5%) compared with those who were asymptomatic (0.1%, 95% CI 0-0.2%) ( P <.01). Clinical findings suggestive of worsening disease had a 91% sensitivity (95% CI 59-100%) and a 99% (95% CI 99-100%) negative predictive value for abnormal laboratory values. Directed screening based on signs and symptoms, rather than universal weekly screening, may be a potential strategy to lower costs and reduce multiple blood draws for patients with HDP, because there is a low diagnostic yield for this practice.

Global analysis of energy landscapes for materials modeling: A test case for C60.

In this contribution, we employ computational tools from the energy landscape approach to test Gaussian Approximation Potentials (GAPs) for C60. In particular, we apply basin-hopping global optimization and explore the landscape starting from the low-lying minima using discrete path sampling. We exploit existing databases of minima and transition states harvested from previous work using tight-binding potentials. We explore the energy landscape for the full range of structures and pathways spanning from the buckminsterfullerene global minimum up to buckybowls. In the initial GAP model, the fullerene part of the landscape is reproduced quite well. However, there are extensive families of C1@C59 and C2@C58 structures that lie lower in energy. We succeeded in refining the potential to remove these artifacts by simply including two minima from the C2@C58 families found by global landscape exploration. We suggest that the energy landscape approach could be used systematically to test and improve machine learning interatomic potentials.

Understanding neuropsychiatric symptoms in Alzheimer's disease: challenges and advances in diagnosis and treatment.

Neuropsychiatric symptoms (NPS) in Alzheimer's disease (AD) affect up to 97% of AD patients, with an estimated 80% of current AD patients experiencing these symptoms. Common AD-associated NPS include depression, anxiety, agitation, aggression, and apathy. The severity of NPS in AD is typically linked to the disease's progression and the extent of cognitive decline. Additionally, these symptoms are responsible for a significant increase in morbidity, mortality, caregiver burden, earlier nursing home placement, and greater healthcare expenditure. Despite their high prevalence and significant impact, there is a notable lack of clinical research on NPS in AD. In this article, we explore and analyze the prevalence, symptom manifestations, challenges in diagnosis, and treatment options of NPS associated with AD. Our literature review reveals that distinguishing and accurately diagnosing the NPS associated with AD remains a challenging task in clinical settings. It is often difficult to discern whether NPS are secondary to pathophysiological changes from AD or are comorbid psychiatric conditions. Furthermore, the availability of effective pharmaceutical interventions, as well as non-pharmacotherapies for NPS in AD, remains limited. By highlighting the advance and challenges in diagnosis and treatment of AD-associated NPS, we aspire to offer new insights into the complexity of identifying and treating these symptoms within the context of AD, and contribute to a deeper understanding of the multifaceted nature of NPS in AD.

Exploring energy landscapes for solid-state systems with variable cells at the extended tight-binding level.

The design of novel materials requires a theoretical understanding of dynamical processes in the solid state, including polymorphic transitions and associated pathways. The organization of the potential energy landscape plays a crucial role in such processes, which may involve changes in the periodic boundaries. This study reports the implementation of a general framework for periodic condensed matter systems in our energy landscape analysis software, allowing for variation in both the unit cell and atomic positions. This implementation provides access to basin-hopping global optimization, the doubly nudged elastic band procedure for identifying transition state candidates, the missing connection approach for multi-step pathways, and general tools for the construction and analysis of kinetic transition networks. The computational efficacy of the procedures is explored using the state-of-the-art semiempirical method GFN1-xTB for the first time in this solid-state context. We investigate the effectiveness of this level of theory by characterizing the potential energy and enthalpy landscapes of several systems, including silicon, CdSe, ZnS, and NaCl, and discuss further technical challenges, such as translational permutation of the cell. Despite the expected limitations of the semiempirical method, we find that the resulting energy landscapes provide useful insight into solid-state simulations, which will facilitate detailed analysis of processes such as defect and ion migration, including refinement at higher levels of theory.