Leveraging In Situ Simulation for Implementation of Teleobstetric Consultation Services in Rural and Community Hospitals.

Background: Our institution implemented acute-care obstetric (OB) telemedicine (TeleOB) to address rural disparities across our health system. We sought to determine whether in situ simulations with embedded TeleOB consultation increase participants' comfort managing OB emergencies and comfort with and likelihood of using TeleOB. Methods: Rural site care teams participated in multidisciplinary in situ OB emergency simulations. Physicians in OB and neonatology at the referral center assisted via telemedicine consultation. Participants were surveyed before and after the simulations and six months later regarding their experience during the simulations. Results: Participants reported increased comfort with TeleOB activation, indications, and workflow processes, as well as increased comfort managing OB emergencies. Participants also reported significantly increased likelihood of using TeleOB in the future. Conclusions: Consistent with previous work, in situ simulation with embedded telemedicine consultations is an effective approach to facilitate telemedicine implementation and promote use by rural clinicians.

A typology of HIV self-testing support systems: a scoping review.

To maximise the benefits of HIV self-testing (HIVST), it is critical to support self-testers in the testing process and ensure that they access appropriate prevention and care. To summarise systems and tools supporting HIVST (hereafter, 'support systems') and categorise them for future analysis, we synthesised the global data on HIVST support systems and proposed a typology. We searched five databases for articles reporting on one or more HIVST support systems and included 314 publications from 224 studies. Across 189 studies, there were 539 reports of systems supporting HIVST use; while across 115 studies, there were 171 reports of systems supporting result interpretation. Most commonly, these were pictorial instructions, followed by in-person demonstrations and in-person assistance while self-testing or reading self-test results. Less commonly, virtual interventions were also identified, including online video conferencing and smartphone apps. Smartphone-based automated result readers have been used in the USA, China, and South Africa. Across 173 studies, there were 987 reports of systems supporting post-test linkage to care; most commonly, these were in-person referrals/counselling, written referrals, and phone helplines. In the USA, Bluetooth beacons have been trialled to monitor self-test use and facilitate follow-up. We found that, globally, HIVST support systems use a range of methods, including static media, virtual tools, and in-person engagement. In-person and printed approaches were more common than virtual tools. Other considerations, such as linguistic and cultural appropriateness, may also be important in the development of effective HIVST programs.

International trends in daily disposable contact lens prescribing (2000-2023): An update.

PURPOSE: Daily disposable contact lenses offer numerous benefits in terms of ocular health and wearer convenience. The purpose of this work is to update earlier surveys by describing global trends in daily disposable lens fitting between 2000 and 2023. METHOD: An annual contact lens prescribing survey was sent to eye care practitioners in up to 71 countries between 2000 and 2023, inclusive. Data relating to 265,106 daily wear soft lens fits undertaken in 20 countries returning reliable longitudinal data were analysed in respect of daily disposable lens fitting. RESULTS: Overall, daily disposable lens prescribing increased over time, from 17.1 % of daily wear soft lens fits in 2000 to 46.7 % in 2023 (p < 0.0001). There were significant differences between countries in daily disposable lens prescribing (p < 0.0001), and between the percentage of males fitted with daily disposable lenses, as a proportion of all daily wear soft lenses (37.2 %), compared to females (35.2 %) (p < 0.0001). Daily disposable lens wearers are slightly younger at fitting than reusable soft lens wearers (31.0 vs 31.2 years, respectively) (p < 0.0001), although this difference is not clinically meaningful. Analysis of 50,240 daily wear soft lenses fitted recently (2019-2023) were found to be prescribed for the following replacement frequencies: daily - 47 %; monthly - 42 %; 1-2 weekly - 9 %; and ≥3 monthly - 2 %. CONCLUSION: There has been a substantial increase in daily disposable lens fitting throughout the first 24 years of this century. The gradual nature of this increase is commensurate with the staged introduction of daily disposable lens designs and expanded parameter ranges over the survey period.

Squamate scavenging services: Heath goannas (Varanus rosenbergi) support carcass removal and may suppress agriculturally damaging blowflies.

Human-induced environmental change has caused widespread loss of species that support important functions for ecosystems and society. For example, vertebrate scavengers contribute to the functional health of ecosystems and provide services to agricultural landscapes by removing carcasses and associated pests. Widespread extirpation of native Australian mammals since the arrival of Europeans in Australia has removed many scavenging species from landscapes, while scavenging mammals such as European red foxes (Vulpes vulpes) have been introduced. In much of Australia, squamate reptiles are the largest native terrestrial scavengers remaining, where large native mammals are extinct and conservation management is being undertaken to remove invasive mammals. The contribution of reptiles to scavenging functions is not well understood. In this study, we investigated the ecosystem functions provided by large reptiles as scavengers to better understand how populations can be managed to support ecosystem services. We investigated the ecosystem services provided by vertebrate scavengers in Australian coastal mallee ecosystems, focusing on the heath goanna (Varanus rosenbergi), the only extant native terrestrial scavenger in the region. We carried out exclosure experiments, isolating the scavenging activity of different taxonomic groups to quantify the contribution of different taxa to scavenging services, specifically the removal of rat carcasses, and its impact on the occurrence of agriculturally damaging blowflies. We compared areas with different native and invasive scavenger communities to investigate the impact of invasive species removal and native species abundance on scavenging services. Our results indicated that vertebrate scavenging significantly contributes to carcass removal and limitation of necrophagous fly breeding in carcasses and that levels of removal are higher in areas associated with high densities of heath goannas and low densities of invasive mammals. Therefore, augmentation of heath goanna populations represents a promising management strategy to restore and maximize scavenging ecosystem services.

Standing versus supine pelvic incidence in adult spinal deformity patients.

PURPOSE: Pelvic incidence (PI) is commonly used to determine sagittal alignment. Historically, PI was believed to be a fixed anatomic parameter. However, recent studies have suggested that there is positionally-dependent motion that occurs through the sacroiliac joint (SIJ) resulting in changes in PI. METHODS: We reviewed 100 consecutive adult spinal deformity (ASD) patients seen at our academic tertiary referral center. Two reviewers measured pelvic incidence (PI), pelvic tilt (PT), sacral slope (SS), and lumbar lordosis (LL) on standing radiographs and scout computed tomography scans (CT). Unilateral, bilateral, or absent SIJ vacuum sign (VS) was determined using CTs. RESULTS: Eighty-six patients (42 M:44 F) were included with an average age of 64.1 years and BMI of 28.8 kg/m2. Standing PI was low (< 50°) in 35 patients (40.7%), average (50°-60°) in 22 (25.6%), and high (> 60°) in 29 (33.7%). Average and high PI patients had significant PI changes of 3.0° (p = 0.037) and 4.6° (p = 0.005), respectively. Bilateral SIJ VS was seen in 68 patients, unilateral VS in 9, and VS was absent in 9. The average change in PI between standing and supine was 2.1° in bilateral SIJ VS patients (p = 0.045), 2.2° in unilateral SIJ VS (p = 0.23), and - 0.1° in patients without SIJ VS (p = 0.93). The average absolute difference in PI between supine and standing was 5.5° ±5.5° (p < 0.001). CONCLUSION: There is a change in PI from supine to standing. In patients with high PI and bilateral VS on CT, the change from supine to standing is significant, perhaps representing instability of the SIJ.

Survival following liver transplantation: A population-based nested case-control study.

BACKGROUND: Liver transplantation is the gold standard treatment for end-stage liver disease. This study evaluates post-transplantation survival compared with the general population by quantifying standardized mortality ratios in a nested case-control study. METHODS: Controls were noninstitutionalized United States inhabitants from the National Longitudinal Mortality Study. Cases underwent liver transplantation from 1990 to 2007 identified through the Organ Procurement and Transplantation Network database. Propensity matching (5:1, nearest neighbor, caliper 0.1) identified controls based on age, sex, race, and state. The primary endpoint was 10-year survival. RESULTS: 62,788 cases were matched to 313,381 controls. The overall standardized mortality ratio was 2.46 (95% CI â€‹= â€‹2.44-2.48). The standardized mortality ratio was higher for males (2.59 vs. 2.25) and Hispanic patients (4.80). Younger patients and those transplanted earlier (1990-1995) had higher standardized mortality ratios. CONCLUSIONS: Liver recipients have a standardized mortality ratio 2.46 times higher than the general population. Long-term mortality has declined over time.

Association of psychosocial risk factors and liver transplant evaluation outcomes in metabolic dysfunction-associated steatotic liver disease.

The Stanford Integrated Psychosocial Assessment for Transplantation (SIPAT) is a standardized psychosocial assessment tool used in liver transplantation (LT) evaluation and has been primarily studied in patients with alcohol-associated liver disease. We aimed to evaluate the relationship between SIPAT score and metabolic syndrome severity and LT waitlist outcomes in a large cohort of patients with metabolic dysfunction-associated steatotic liver disease (MASLD). We performed a single-center retrospective cohort study of patients with MASLD evaluated for LT from 2014-2021. The utility of the previously defined total SIPAT cut-off (<21 [excellent/good candidates] vs ≥21 [minimally acceptable/high risk candidates]) was studied. Multivariable logistic regression analyses examined associations between continuous SIPAT score and LT waitlisting outcomes. Youden's J statistic was used to identify the optimal SIPAT cut-off for MASLD patients. A total of 480 patients evaluated for transplant with MASLD were included. Only 9.4% of patients had SIPAT score ≥21. Patients with SIPAT score ≥21 had higher hemoglobin A1c compared to patients with lower psychosocial risk (median (IQR): 7.8 (6.0-9.7) vs 6.6 (5.8, 7.9); p=0.04). There were no other differences in metabolic comorbidities between SIPAT groups. Increasing SIPAT score was associated with decreased odds of listing (OR: 0.82 per five-point increase; p=0.003) in multivariable models. A SIPAT of ≥12 was identified as the optimal cut-off in this population, resulting in an adjusted OR for listing of 0.53 vs SIPAT <12 (p=0.001). In this large cohort of MASLD patients evaluated for LT, few patients met the previously defined high SIPAT cut-off for transplant suitability. Nevertheless, increasing SIPAT score was associated with waitlist outcome. Our suggested SIPAT cut-off of ≥12 for MASLD patients warrants further external validation using data from other centers.

Sacropelvic Fixation with Porous Fusion/Fixation Screws: A Technical Note and Retrospective Review.

OBJECTIVE: The goal of this study was to analyze our initial experience using a novel porous fusion/fixation screw (PFFS) for pelvic fixation, and to determine our rate of screw malposition requiring intraoperative repositioning. METHODS: We reviewed 83 consecutive patients who underwent sacropelvic fixation with PFFS at our institution from 6/1/2022-6/30/2023 using intraoperative CT-based computer-assisted navigation (CAN) via an open posterior approach. Following PFFS insertion, intraoperative CT scans were obtained to assess screw positioning. Demographic data was collected, and operative reports and patient images were reviewed to determine what implants were used and if any PFFS required repositioning. RESULTS: 74 patients (26M:48F) were included, and 57 (77.0%) had a prior sacroiliac joint or lumbar spine surgery. A stacked screw configuration was used in 62/74 cases (83.8%). A total of 235 PFFS were used and six (2.6%) were malpositioned. Of 88 cephalic screws placed in stacked configuration, 4 were malpositioned (4.5%); and 1/123 caudal screws were malpositioned (0.8%). One of 24 SAI screws placed in a stand-alone configuration was malpositioned (4.2%). Malpositions included four medial, one lateral, and one inferior; and all were revised intraoperatively without major sequela. CONCLUSIONS: Although PFFS are larger than traditional sacropelvic fixation screws, stacked SAI instrumentation can be done safely with CAN. We found a low malposition rate in our initial series of patients, the majority being the cephalad screw in a stacked configuration. This isn't surprising, as these are placed after the caudal screws which reduces the available corridor size and increases the placement difficulty.

Herpes simplex virus spreads rapidly in human foreskin, partly driven by chemokine-induced redistribution of Nectin-1 on keratinocytes.

HSV infects keratinocytes in the epidermis of skin via nectin-1. We established a human foreskin explant infection model to investigate HSV entry and spread. HSV1 entry could only be achieved by the topical application of virus via high density microarray projections (HD-MAPs) to the epidermis, which penetrated beyond one third of its thickness, simulating in vivo microtrauma. Rapid lateral spread of HSV1 to a mean of 13 keratinocytes wide occurred after 24 hours and free virus particles were observed between keratinocytes, consistent with an intercellular route of spread. Nectin-1 staining was markedly decreased in foci of infection in the epidermis and in the human keratinocyte HaCaT cell line. Nectin-1 was redistributed, at the protein level, in adjacent uninfected cells surrounding infection, inducible by CCL3, IL-8 (or CXCL8), and possibly CXCL10 and IL-6, thus facilitating spread. These findings provide the first insights into HSV1 entry and spread in human inner foreskin in situ.

Scoliosis Development in Spinal Muscular Atrophy: The Influences of Genetic Severity, Functional Level, and Disease-Modifying Treatments.

BACKGROUND: Spinal muscular atrophy (SMA) is caused by abnormalities of the survival motor neuron (SMN) 1 gene, leading to deficiency in SMN protein and loss of spinal cord alpha motor neurons. Newer disease-modifying agents (DMA) targeting the involved genes, including nusinersen and gene replacement therapies, have improved gross motor and respiratory function, but their impact on scoliosis development has not been established. This study aimed to determine risk factors for scoliosis development in SMA, specifically genetic severity and DMA use. METHODS: In this retrospective cohort study, children with SMA and minimum 2-year follow-up were included. The primary outcome was the prevalence of clinically relevant scoliosis. Secondary outcomes included SMA type, SMN2 copy number, Hammersmith Functional Motor Scale (HFMS), ambulatory status [functional mobility scale at 50m (FMS50)], DMA use, and hip displacement as risk factors. Univariate/multivariate logistic regression analyses were performed to identify dependent/independent risk factors. RESULTS: One hundred sixty-five patients (51% female) with SMA types I-III met the inclusion criteria, with total follow-up of 9.8 years. The prevalence of scoliosis was 79%; age of onset 7.9 years. The major curve angle for the entire cohort at first assessment and final follow-up was 37 degrees (SD: 27 degrees) and 62 degrees (SD: 31 degrees) (P<0.0001), respectively. Significant risk factors for scoliosis by univariate analysis were SMA type (I/II, P=0.02), HFMS (>23, P<0.001), nonambulatory status (FMS50=1, P<0.0001), DMA treatment (P=0.02), and hip displacement (P<0.0001). Multivariate analysis revealed that HFMS >23 (P=0.02) and DMA (P=0.05) treatment were independent (protective) risk factors. CONCLUSIONS: The development of scoliosis in SMA is high, with risk factors associated with proxy measures of disease severity, including SMA type, nonambulatory status, hip displacement, and most notably, gross motor function (by HFMS). DMA use and HFMS >23 were associated with a decreased risk of scoliosis development. Identified risk factors can be used in the development of surveillance programs for early detection of scoliosis in SMA. LEVEL OF EVIDENCE: Level III.

Comparative cost-effectiveness of termination of resuscitation rules for patients transported in cardiac arrest.

AIM: To compare the cost-effectiveness of termination-of-resuscitation (TOR) rules for patients transported in cardiac arrest. METHODS: The economic analyses evaluated cost-effectiveness of alternative TOR rules for OHCA from a National Health Service (NHS) and personal social services (PSS) perspective over a lifetime horizon. A systematic review was used to identify the different TOR rules included in the analyses. Data from the OHCAO outcomes registry, trial data and published literature were used to compare outcomes for the different rules identified. The economic analyses estimated discounted NHS and PSS costs and quality-adjusted life-years (QALYs) for each TOR rule, based on which incremental cost-effectiveness ratios (ICERs) were calculated. RESULTS: The systematic review identified 33 TOR rules and the economic analyses assessed the performance of 29 of these TOR rules plus current practice. The most cost-effective strategies were the European Resuscitation Council (ERC) termination of resuscitation rule (ICER of £8,111), the Korean Cardiac Arrest Research Consortium 2 (KOC 2) termination of resuscitation rule (ICER of £17,548), and the universal Basic Life Support (BLS) termination of resuscitation rule (ICER of £19,498,216). The KOC 2 TOR rule was cost-effective at the established cost-effectiveness threshold of £20,000-£30,000 per QALY. CONCLUSION: The KOC 2 rule is the most cost-effective at established cost-effectiveness thresholds used to inform health care decision-making in the UK. Further research on economic implications of TOR rules is warranted to support constructive discussion on implementing TOR rules.

Digital twin mathematical models suggest individualized hemorrhagic shock resuscitation strategies.

BACKGROUND: Optimizing resuscitation to reduce inflammation and organ dysfunction following human trauma-associated hemorrhagic shock is a major clinical hurdle. This is limited by the short duration of pre-clinical studies and the sparsity of early data in the clinical setting. METHODS: We sought to bridge this gap by linking preclinical data in a porcine model with clinical data from patients from the Prospective, Observational, Multicenter, Major Trauma Transfusion (PROMMTT) study via a three-compartment ordinary differential equation model of inflammation and coagulation. RESULTS: The mathematical model accurately predicts physiologic, inflammatory, and laboratory measures in both the porcine model and patients, as well as the outcome and time of death in the PROMMTT cohort. Model simulation suggests that resuscitation with plasma and red blood cells outperformed resuscitation with crystalloid or plasma alone, and that earlier plasma resuscitation reduced injury severity and increased survival time. CONCLUSIONS: This workflow may serve as a translational bridge from pre-clinical to clinical studies in trauma-associated hemorrhagic shock and other complex disease settings.

Research to improve survival in patients with severe bleeding after major trauma presents many challenges. Here, we created a computer model to simulate the effects of severe bleeding. We refined this model using data from existing animal studies to ensure our simulations were accurate. We also used patient data to further refine the simulations to accurately predict which patients would live and which would not. We studied the effects of different treatment protocols on these simulated patients and show that treatment with plasma (the fluid portion of blood that helps form blood clots) and red blood cells jointly, gave better results than treatment with intravenous fluid or plasma alone. Early treatment with plasma reduced injury severity and increased survival time. This modelling approach may improve our ability to evaluate new treatments for trauma-associated bleeding and other acute conditions.

Long-term survival follow-up for tebentafusp in previously treated metastatic uveal melanoma.

BACKGROUND: Tebentafusp, a bispecific (gp100×CD3) ImmTAC, significantly improved overall survival (OS) outcomes for HLA-A*02:01+ adult patients with untreated metastatic uveal melanoma (mUM) and showed promising survival in previously treated mUM with 1-year OS of 62% in the primary analysis of study IMCgp100-102. Here we report long-term outcomes from this phase 1/2 study in pretreated mUM. PATIENTS AND METHODS: Patients with previously treated mUM received tebentafusp weekly intravenous at 20 µg dose 1, 30 µg dose 2 and either 54, 64, 68, or 73 µg (phase 1) or 68 µg (phase 2) dose 3+. The primary objective was overall response rate. Secondary objectives included OS and safety. OS was estimated by Kaplan-Meier methods. Association between OS and baseline covariates, on-treatment Response Evaluation Criteria in Solid Tumors (RECIST) response, baseline tumor biopsy and circulating-tumor DNA (ctDNA) changes were assessed. RESULTS: 146 patients were treated with tebentafusp: 19 in phase 1 and 127 in phase 2. With a median follow-up duration of 48.5 months, the median OS was 17.4 months (95% CI, 13.1 to 22.8), and the 1-year, 2-year, 3-year and 4-year OS rates were 62%, 40%, 23% and 14%, respectively. Improved survival was associated with lower ctDNA baseline levels and greater ctDNA reductions by week 9 on-treatment, with 100% 1-year, 73% 2-year and 45% 3-year OS rates for patients with ctDNA clearance. Baseline gp100 expression was not associated with survival, despite more RECIST responses among patients with higher expression. No new safety signals were reported with long-term dosing. CONCLUSIONS: This study represents the longest follow-up of a Tcell receptor bispecific to date and confirms the durable survival benefits achieved with tebentafusp in previously treated mUM with good tolerability long-term. A role for ctDNA reduction as an early indicator of clinical benefit was again suggested for patients treated with tebentafusp.

Lithiation Induced Phases in 1T'-MoTe2 Nanoflakes.

Multiple polytypes of MoTe2 with distinct structures and intriguing electronic properties can be accessed by various physical and chemical approaches. Here, we report electrochemical lithium (Li) intercalation into 1T'-MoTe2 nanoflakes, leading to the discovery of two previously unreported lithiated phases. Distinguished by their structural differences from the pristine 1T' phase, these distinct phases were characterized using in situ polarization Raman spectroscopy and in situ single-crystal X-ray diffraction. The lithiated phases exhibit increasing resistivity with decreasing temperature, and their carrier densities are two to 4 orders of magnitude smaller than the metallic 1T' phase, as probed through in situ Hall measurements. The discovery of these gapped phases in initially metallic 1T'-MoTe2 underscores electrochemical intercalation as a potent tool for tuning the phase stability and electron density in two-dimensional (2D) materials.

Cost-effectiveness of resistance-guided therapy for Mycoplasma genitalium in Australia.

The recommended first-line treatment for Mycoplasma genitalium infections is azithromycin. However, the prevalence of macrolide resistance for M. genitalium has increased to more than 50% worldwide. In 2013, Australia introduced a resistance-guided therapy (RGT) strategy to manage M. genitalium infections. This study assesses the cost-effectiveness of the RGT approach compared to no RGT (i.e., without macrolide resistance profile test) in women, men who have sex with men (MSM), and men who have sex with women (MSW) in Australia. We constructed dynamic transmission models of M. genitalium infections in women, MSM, and MSW in Australia, each with a population of 100,000. These models compared the costs and quality-adjusted life-years (QALYs) gained between RGT and no RGT scenarios from a healthcare perspective over ten years. All costs are reported in 2022 Australian dollars (Australian $). In our model, RGT is cost saving in women and MSM, with the incremental net monetary benefit of $1.3 million and $17.9 million, respectively. In MSW, the RGT approach is not cost-effective, with an incremental cost-effectiveness ratio of -$106.96 per QALY gained. RGT is cost saving compared to no RGT for M. genitalium infections in women and MSM, supporting its adoption as the national management strategy for these two population groups.

A Robust SARS-CoV-2-specific T and B Cell Response is Associated with Early Viral Clearance in SARS-CoV-2 Omicron-Infected Immunocompromised Individuals.

BACKGROUND: The immunological determinants of delayed viral clearance and intra-host viral evolution that drive the development of new pathogenic virus strains in immunocompromised individuals are unknown. Therefore, we longitudinally studied SARS-CoV-2-specific immune responses in relation to viral-clearance and evolution in immunocompromised individuals. METHODS: Among Omicron-infected immunocompromised individuals, we determined SARS-CoV-2-specific T- and B-cell responses, anti-spike IgG(3) titers, neutralization titers, and monoclonal antibody (mAb)-resistance-associated mutations. The 28-day post-enrollment nasopharyngeal specimen defined early (RT-PCR negative ≤28 days) or late (RT-PCR- positive >28 days) viral-clearance. RESULTS: Of 30 patients included (median age 61.9 years [IQR 47.4-72.3], 50% females), 20 (66.7%) received mAb-therapy. Thirteen (43.3%) demonstrated early and 17 (56.7%) late viral-clearance. Early viral-clearance patients and patients without resistance-associated mutations had significantly higher baseline IFN-γ release and early viral-clearance patients had a higher frequency of SARS-CoV-2-specific B-cells at baseline. In non-mAb-treated patients, day 7 IgG and neutralization titers were significantly higher in those with early versus late viral-clearance. CONCLUSION: An early robust adaptive immune response is vital for efficient viral-clearance and associated with less emergence of mAb-resistance-associated mutations in Omicron-infected immunocompromised patients. This emphasizes the importance of early SARS-CoV-2-specific T- and B-cell responses and thereby provides a rationale for development of novel therapeutic approaches.

Economic evaluation alongside a clinical trial of near-to-patient testing for sexually transmitted infections.

BACKGROUND: Current clinical care for common bacterial STIs (Chlamydia trachomatis (CT), Neisseria gonorrhoeae (NG) and Mycoplasma genitalium (MG)) involves empiric antimicrobial therapy when clients are symptomatic, or if asymptomatic, waiting for laboratory testing and recall if indicated. Near-to-patient testing (NPT) can improve pathogen-specific prescribing and reduce unnecessary or inappropriate antibiotic use in treating sexually transmitted infections (STI) by providing same-day delivery of results and treatment. METHODS: We compared the economic cost of NPT to current clinic practice for managing clients with suspected proctitis, non-gonococcal urethritis (NGU), or as an STI contact, from a health provider's perspective. With a microsimulation of 1000 clients, we calculated the cost per client tested and per STI- and pathogen- detected for each testing strategy. Sensitivity analyses were conducted to assess the robustness of the main outcomes. Costs are reported as Australian dollars (2023). RESULTS: In the standard care arm, cost per client tested for proctitis, NGU in men who have sex with men (MSM) and heterosexual men were the highest at $247.96 (95% Prediction Interval (PI): 246.77-249.15), $204.23 (95% PI: 202.70-205.75) and $195.01 (95% PI: 193.81-196.21) respectively. Comparatively, in the NPT arm, it costs $162.36 (95% PI: 161.43-163.28), $158.39 (95% PI: 157.62-159.15) and $149.17 (95% PI: 148.62-149.73), respectively. Using NPT resulted in cost savings of 34.52%, 22.45% and 23.51%, respectively. Among all the testing strategies, substantial difference in cost per client tested between the standard care arm and the NPT arm was observed for contacts of CT or NG, varying from 27.37% to 35.28%. CONCLUSION: We found that NPT is cost-saving compared with standard clinical care for individuals with STI symptoms and sexual contacts of CT, NG, and MG.

The neuron as a direct data-driven controller.

In the quest to model neuronal function amid gaps in physiological data, a promising strategy is to develop a normative theory that interprets neuronal physiology as optimizing a computational objective. This study extends current normative models, which primarily optimize prediction, by conceptualizing neurons as optimal feedback controllers. We posit that neurons, especially those beyond early sensory areas, steer their environment toward a specific desired state through their output. This environment comprises both synaptically interlinked neurons and external motor sensory feedback loops, enabling neurons to evaluate the effectiveness of their control via synaptic feedback. To model neurons as biologically feasible controllers which implicitly identify loop dynamics, infer latent states, and optimize control we utilize the contemporary direct data-driven control (DD-DC) framework. Our DD-DC neuron model explains various neurophysiological phenomena: the shift from potentiation to depression in spike-timing-dependent plasticity with its asymmetry, the duration and adaptive nature of feedforward and feedback neuronal filters, the imprecision in spike generation under constant stimulation, and the characteristic operational variability and noise in the brain. Our model presents a significant departure from the traditional, feedforward, instant-response McCulloch-Pitts-Rosenblatt neuron, offering a modern, biologically informed fundamental unit for constructing neural networks.

International trends in rigid contact lens prescribing (2000-2023): An update.

PURPOSE: Rigid contact lenses have an important role in contact lens practice. The purpose of this work is to update earlier surveys by describing global trends in rigid lens fitting between 2000-2023. METHOD: An annual contact lens prescribing survey was sent to eye care practitioners in up to 71 countries between 2000 and 2023. Data relating to 342,500 fits undertaken in 20 countries returning reliable longitudinal data were analysed in respect of rigid lens fitting, defined as the fitting of any design of a contact lens manufactured in a rigid material. RESULTS: Overall, rigid lens prescribing increased slightly over time, from 14.2 % of lens fits in 2000 to 15.2 % in 2023 (p < 0.0001). However, post-hoc analysis shows that the change over time is best described as a decline between 2000 and 2012, followed by a steady increase subsequently. There were significant differences in rigid lens prescribing between countries (p < 0.0001). The difference between the percentage of males fitted with rigid lenses, as a proportion of all contact lenses (12.7 %), and females (12.0 %) is significant (p < 0.0001), although not clinically meaningful. Rigid lens wearers are older at fitting than soft lens wearers (38.7 vs 31.3 years, respectively) (p < 0.0001). Analysis of 5,994 rigid lens fits prescribed currently (2019-2023) were categorised as: corneal sphere - 30 %; scleral and corneo-scleral - 28 %; corneal myopia control/orthokeratology - 21 %; and corneal complex (including toric, multifocal and monovision) - 16 %. CONCLUSION: There has been a slight increase in rigid lens fitting during the second decade of this century. This increase is apparently due to a 'repurposing' of rigid lenses, with the growth of scleral/corneo-scleral and myopia control/orthokeratology lens fits essentially replacing conventional spherical corneal lens fits.

Safety of pembrolizumab as adjuvant therapy in a pooled analysis of phase 3 clinical trials of melanoma, non-small cell lung cancer, and renal cell carcinoma.

BACKGROUND: The safety profile of adjuvant pembrolizumab was evaluated in a pooled analysis of 4 phase 3 clinical trials. METHODS: Patients had completely resected stage IIIA, IIIB, or IIIC melanoma per American Joint Committee on Cancer, 7th edition, criteria (AJCC-7; KEYNOTE-054); stage IIB or IIC melanoma per AJCC-8 (KEYNOTE-716); stage IB, II, or IIIA non-small cell lung cancer per AJCC-7 (PEARLS/KEYNOTE-091); or postnephrectomy/metastasectomy clear cell renal cell carcinoma at increased risk of recurrence (KEYNOTE-564). Patients received adjuvant pembrolizumab 200 mg (2 mg/kg up to 200 mg for pediatric patients) or placebo every 3 weeks for approximately 1 year. Adverse events (AEs) were summarized for patients who received ≥ 1 dose of treatment. RESULTS: Data were pooled from 4125 patients treated with pembrolizumab (n = 2060) or placebo (n = 2065). Median (range) duration of treatment was 11.1 months (0.0-18.9) with pembrolizumab and 11.2 months (0.0-18.1) with placebo. Treatment-related AEs occurred in 78.6 % (1620/2060) of patients in the pembrolizumab group (grade 3-5, 16.3 % [336/2060]) and 58.7 % (1212/2065) in the placebo group (grade 3-5, 3.5 % [72/2065]). Immune-mediated AEs (e.g. adrenal insufficiency, hypophysitis, and thyroiditis) occurred in 36.2 % (746/2060) of patients in the pembrolizumab group (grade 3-5, 8.6 % [177/2060]) and 8.4 % (174/2065) in the placebo group (grade 3-5, 1.1 % [23/2065]). Of patients with ≥ 1 immune-mediated AE or infusion reaction, systemic corticosteroids were required for 35.2 % (268/761) and 20.2 % (39/193) of patients in the pembrolizumab and placebo groups, respectively. CONCLUSIONS: Adjuvant pembrolizumab demonstrated a manageable safety profile that was comparable to prior reports in advanced disease.