Preventing hospital falls: feasibility of care workforce redesign to optimise patient falls education.

OBJECTIVE: To examine the feasibility of using allied health assistants to deliver patient falls prevention education within 48 h after hospital admission. DESIGN AND SETTING: Feasibility study with hospital patients randomly allocated to usual care or usual care plus additional patient falls prevention education delivered by supervised allied health assistants using an evidence-based scripted conversation and educational pamphlet. PARTICIPANTS: (i) allied health assistants and (ii) patients admitted to participating hospital wards over a 20-week period. OUTCOMES: (i) feasibility of allied health assistant delivery of patient education; (ii) hospital falls per 1,000 bed days; (iii) injurious falls; (iv) number of falls requiring transfer to an acute medical facility. RESULTS: 541 patients participated (median age 81 years); 270 control group and 271 experimental group. Allied health assistants (n = 12) delivered scripted education sessions to 254 patients in the experimental group, 97% within 24 h after admission. There were 32 falls in the control group and 22 in the experimental group. The falls rate was 8.07 falls per 1,000 bed days in the control group and 5.69 falls per 1,000 bed days for the experimental group (incidence rate ratio = 0.66 (95% CI 0.32, 1.36; P = 0.26)). There were 2.02 injurious falls per 1,000 bed days for the control group and 1.03 for the experimental group. Nine falls (7 control, 2 experimental) required transfer to an acute facility. No adverse events were attributable to the experimental group intervention. CONCLUSIONS: It is feasible and of benefit to supplement usual care with patient education delivered by allied health assistants.

Public involvement in Australian clinical trials: A systematic review.

BACKGROUND: Public involvement enhances the relevance, quality, and impact of research. There is some evidence that public involvement in Australian research lags other countries, such as the United Kingdom. The purpose of the systematic review was to establish the rates and describe the characteristics of public involvement in Australian clinical trials. METHODS: We reviewed evidence of public involvement in all Australian randomised controlled trials published in the first 6 months of 2021. To determine the quality of public involvement, we used the five-item short-form version of the Guidance of Reporting Involvement Patients and the Public, version 2. RESULTS: In total, 325 randomised controlled trials were included, of which 17 (5%) reported any public involvement. Six trials reported public involvement in setting the research aim and seven in developing study methods. The authors of one study reflected on the overall role and influence of public involvement in the research. CONCLUSION: Rate of public involvement in Australian clinical trials is seemingly substantially lower than those reported in countries with similar advanced public health care systems, notably the United Kingdom. Our observations may be explained by a lack of researcher skills in how to involve the public and the failure by major funding agencies in Australia to mandate public involvement when deciding on how to award grant funding.

Integration of multiomics data shows down regulation of mismatch repair and tubulin pathways in triple-negative chemotherapy-resistant breast tumors.

BACKGROUND: Triple-negative breast cancer (TNBC) is the most aggressive breast cancer subtype. Patients with TNBC are primarily treated with neoadjuvant chemotherapy (NAC). The response to NAC is prognostic, with reductions in overall survival and disease-free survival rates in those patients who do not achieve a pathological complete response (pCR). Based on this premise, we hypothesized that paired analysis of primary and residual TNBC tumors following NAC could identify unique biomarkers associated with post-NAC recurrence. METHODS AND RESULTS: We investigated 24 samples from 12 non-LAR TNBC patients with paired pre- and post-NAC data, including four patients with recurrence shortly after surgery (< 24 months) and eight who remained recurrence-free (> 48 months). These tumors were collected from a prospective NAC breast cancer study (BEAUTY) conducted at the Mayo Clinic. Differential expression analysis of pre-NAC biopsies showed minimal gene expression differences between early recurrent and nonrecurrent TNBC tumors; however, post-NAC samples demonstrated significant alterations in expression patterns in response to intervention. Topological-level differences associated with early recurrence were implicated in 251 gene sets, and an independent assessment of microarray gene expression data from the 9 paired non-LAR samples available in the NAC I-SPY1 trial confirmed 56 gene sets. Within these 56 gene sets, 113 genes were observed to be differentially expressed in the I-SPY1 and BEAUTY post-NAC studies. An independent (n = 392) breast cancer dataset with relapse-free survival (RFS) data was used to refine our gene list to a 17-gene signature. A threefold cross-validation analysis of the gene signature with the combined BEAUTY and I-SPY1 data yielded an average AUC of 0.88 for six machine-learning models. Due to the limited number of studies with pre- and post-NAC TNBC tumor data, further validation of the signature is needed. CONCLUSION: Analysis of multiomics data from post-NAC TNBC chemoresistant tumors showed down regulation of mismatch repair and tubulin pathways. Additionally, we identified a 17-gene signature in TNBC associated with post-NAC recurrence enriched with down-regulated immune genes.

Amiodarone prevents wave front-tail interactions in patients with heart failure: an in silico study.

Amiodarone (AM) is an antiarrhythmic drug whose chronic use has proved effective in preventing ventricular arrhythmias in a variety of patient populations, including those with heart failure (HF). AM has both class III [i.e., it prolongs the action potential duration (APD) via blocking potassium channels) and class I (i.e., it affects the rapid sodium channel) properties; however, the specific mechanism(s) by which it prevents reentry formation in patients with HF remains unknown. We tested the hypothesis that AM prevents reentry induction in HF during programmed electrical stimulation (PES) via its ability to induce postrepolarization refractoriness (PRR) via its class I effects on sodium channels. Here we extend our previous human action potential model to represent the effects of both HF and AM separately by calibrating to human tissue and clinical PES data, respectively. We then combine these models (HF + AM) to test our hypothesis. Results from simulations in cells and cables suggest that AM acts to increase PRR and decrease the elevation of takeoff potential. The ability of AM to prevent reentry was studied in silico in two-dimensional sheets in which a variety of APD gradients (ΔAPD) were imposed. Reentrant activity was induced in all HF simulations but was prevented in 23 of 24 HF + AM models. Eliminating the AM-induced slowing of the recovery of inactivation of the sodium channel restored the ability to induce reentry. In conclusion, in silico testing suggests that chronic AM treatment prevents reentry induction in patients with HF during PES via its class I effect to induce PRR.NEW & NOTEWORTHY This work presents a new model of the action potential of the human, which reproduces the complex dynamics during premature stimulation in heart failure patients with and without amiodarone. A specific mechanism of the ability of amiodarone to prevent reentrant arrhythmias is presented.

Prison-based interventions are key to achieving HCV elimination among people who inject drugs in New South Wales, Australia: A modelling study.

BACKGROUND & AIMS: People who inject drugs (PWID) experience high incarceration rates which are associated with increased hepatitis C virus (HCV) transmission risk. We assess the importance of prison-based interventions for achieving HCV elimination among PWID in New South Wales (NSW), Australia. METHODS: A model of incarceration and HCV transmission among PWID was calibrated in a Bayesian framework to epidemiological and incarceration data from NSW, incorporating elevated HCV acquisition risk among recently released PWID. We projected the contribution of differences in transmission risk during/following incarceration to HCV transmission over 2020-2029. We estimated the past and potential future impact of prison-based opioid agonist therapy (OAT; ~33% coverage) and HCV treatment (1500 treatments in 2019 with 32.9%-83.3% among PWID) on HCV transmission. We estimated the time until HCV incidence reduces by 80% (WHO elimination target) compared to 2016 levels with or without prison-based interventions. RESULTS: Over 2020-2029, incarceration will contribute 23.0% (17.9-30.5) of new HCV infections. If prison-based interventions had not been implemented since 2010, HCV incidence in 2020 would have been 29.7% (95% credibility interval: 22.4-36.1) higher. If current prison and community HCV treatment rates continue, there is an 98.8% probability that elimination targets will be achieved by 2030, with this decreasing to 10.1% without current prison-based interventions. CONCLUSIONS: Existing prison-based interventions in NSW are critical components of strategies to reduce HCV incidence among PWID. Prison-based interventions are likely to be pivotal for achieving HCV elimination targets among PWID by 2030.

Credibility assessment of patient-specific computational modeling using patient-specific cardiac modeling as an exemplar.

Reliable and robust simulation of individual patients using patient-specific models (PSMs) is one of the next frontiers for modeling and simulation (M&S) in healthcare. PSMs, which form the basis of digital twins, can be employed as clinical tools to, for example, assess disease state, predict response to therapy, or optimize therapy. They may also be used to construct virtual cohorts of patients, for in silico evaluation of medical product safety and/or performance. Methods and frameworks have recently been proposed for evaluating the credibility of M&S in healthcare applications. However, such efforts have generally been motivated by models of medical devices or generic patient models; how best to evaluate the credibility of PSMs has largely been unexplored. The aim of this paper is to understand and demonstrate the credibility assessment process for PSMs using patient-specific cardiac electrophysiological (EP) modeling as an exemplar. We first review approaches used to generate cardiac PSMs and consider how verification, validation, and uncertainty quantification (VVUQ) apply to cardiac PSMs. Next, we execute two simulation studies using a publicly available virtual cohort of 24 patient-specific ventricular models, the first a multi-patient verification study, the second investigating the impact of uncertainty in personalized and non-personalized inputs in a virtual cohort. We then use the findings from our analyses to identify how important characteristics of PSMs can be considered when assessing credibility with the approach of the ASME V&V40 Standard, accounting for PSM concepts such as inter- and intra-user variability, multi-patient and "every-patient" error estimation, uncertainty quantification in personalized vs non-personalized inputs, clinical validation, and others. The results of this paper will be useful to developers of cardiac and other medical image based PSMs, when assessing PSM credibility.

Design and execution of a verification, validation, and uncertainty quantification plan for a numerical model of left ventricular flow after LVAD implantation.

BACKGROUND: Left ventricular assist devices (LVADs) are implantable pumps that act as a life support therapy for patients with severe heart failure. Despite improving the survival rate, LVAD therapy can carry major complications. Particularly, the flow distortion introduced by the LVAD in the left ventricle (LV) may induce thrombus formation. While previous works have used numerical models to study the impact of multiple variables in the intra-LV stagnation regions, a comprehensive validation analysis has never been executed. The main goal of this work is to present a model of the LV-LVAD system and to design and follow a verification, validation and uncertainty quantification (VVUQ) plan based on the ASME V&V40 and V&V20 standards to ensure credible predictions. METHODS: The experiment used to validate the simulation is the SDSU cardiac simulator, a bench mock-up of the cardiovascular system that allows mimicking multiple operation conditions for the heart-LVAD system. The numerical model is based on Alya, the BSC's in-house platform for numerical modelling. Alya solves the Navier-Stokes equation with an Arbitrary Lagrangian-Eulerian (ALE) formulation in a deformable ventricle and includes pressure-driven valves, a 0D Windkessel model for the arterial output and a LVAD boundary condition modeled through a dynamic pressure-flow performance curve. The designed VVUQ plan involves: (a) a risk analysis and the associated credibility goals; (b) a verification stage to ensure correctness in the numerical solution procedure; (c) a sensitivity analysis to quantify the impact of the inputs on the four quantities of interest (QoIs) (average aortic root flow [Formula: see text], maximum aortic root flow [Formula: see text], average LVAD flow [Formula: see text], and maximum LVAD flow [Formula: see text]); (d) an uncertainty quantification using six validation experiments that include extreme operating conditions. RESULTS: Numerical code verification tests ensured correctness of the solution procedure and numerical calculation verification showed a grid convergence index (GCI)95% <3.3%. The total Sobol indices obtained during the sensitivity analysis demonstrated that the ejection fraction, the heart rate, and the pump performance curve coefficients are the most impactful inputs for the analysed QoIs. The Minkowski norm is used as validation metric for the uncertainty quantification. It shows that the midpoint cases have more accurate results when compared to the extreme cases. The total computational cost of the simulations was above 100 [core-years] executed in around three weeks time span in Marenostrum IV supercomputer. CONCLUSIONS: This work details a novel numerical model for the LV-LVAD system, that is supported by the design and execution of a VVUQ plan created following recognised international standards. We present a methodology demonstrating that stringent VVUQ according to ASME standards is feasible but computationally expensive.

Removing hepatitis C antibody testing for Australian blood donations: A cost-effectiveness analysis.

BACKGROUND AND OBJECTIVES: The risk of transfusion-transmitted hepatitis C virus (HCV) infections is extremely low in Australia. This study aims to conduct a cost-effectiveness analysis of different testing strategies for HCV infection in blood donations. MATERIALS AND METHODS: The four testing strategies evaluated in this study were universal testing with both HCV antibody (anti-HCV) and nucleic acid testing (NAT); anti-HCV and NAT for first-time donations and NAT only for repeat donations; anti-HCV and NAT for transfusible component donations and NAT only for plasma for further manufacture; and universal testing with NAT only. A decision-analytical model was developed to assess the cost-effectiveness of alternative HCV testing strategies. Sensitivity analysis and threshold analysis were conducted to account for data uncertainty. RESULTS: The number of potential transfusion-transmitted cases of acute hepatitis C and chronic hepatitis C was approximately zero in all four strategies. Universal testing with NAT only was the most cost-effective strategy due to the lowest testing cost. The threshold analysis showed that for the current practice to be cost-effective, the residual risks of other testing strategies would have to be at least 1 HCV infection in 2424 donations, which is over 60,000 times the baseline residual risk (1 in 151 million donations). CONCLUSION: The screening strategy for HCV in blood donations currently implemented in Australia is not cost-effective compared with targeted testing or universal testing with NAT only. Partial or total removal of anti-HCV testing would bring significant cost savings without compromising blood recipient safety.

A HIV diagnosis and treatment cascade for Aboriginal and Torres Strait Islander peoples of Australia.

Aboriginal and Torres Strait Islander (hereafter Aboriginal) people are a priority population for HIV care in Australia; however, no HIV cascade exists for this population. We developed annual HIV cascades for 2010-2017 specific to Aboriginal peoples. By 2017, an estimated 595 Aboriginal people were living with HIV (PLWH); however, 14% remained undiagnosed. Cascade steps below global targets were: PLWH aware of their diagnosis (86%), and retention in care (81% of those who had received any care in previous two years in a sentinel network of clinics). For people retained in care, treatment outcomes surpassed global targets (92% receiving treatment, 93% viral suppression). Increases occurred across all HIV cascade steps over time; however, the least improvement was for retention in care, while the greatest improvement was achieving viral suppression. The HIV cascade for Aboriginal peoples highlights both gaps and strengths in the Australian HIV care system, and importantly highlights where potential interventions may be required to achieve the global UNAIDS targets.

Professional care workforce: a rapid review of evidence supporting methods of recruitment, retention, safety, and education.

BACKGROUND: Across the care economy there are major shortages in the health and care workforce, as well as high rates of attrition and ill-defined career pathways. The aim of this study was to evaluate current evidence regarding methods to improve care worker recruitment, retention, safety, and education, for the professional care workforce. METHODS: A rapid review of comparative interventions designed to recruit, retain, educate and care for the professional workforce in the following sectors: disability, aged care, health, mental health, family and youth services, and early childhood education and care was conducted. Embase and MEDLINE databases were searched, and studies published between January 2015 and November 2022 were included. We used the Quality Assessment tool for Quantitative Studies and the PEDro tools to evaluate study quality. RESULTS: 5594 articles were initially screened and after applying the inclusion and exclusion criteria, 30 studies were included in the rapid review. Studies most frequently reported on the professional nursing, medical and allied health workforces. Some studies focused on the single domain of care worker education (n = 11) while most focused on multiple domains that combined education with recruitment strategies, retention strategies or a focus on worker safety. Study quality was comparatively low with a median PEDro score of 5/10, and 77% received a weak rating on the Quality Assessment tool for Quantitative Studies. Four new workforce strategies emerged; early career rural recruitment supports rural retention; workload management is essential for workforce well-being; learning must be contextually relevant; and there is a need to differentiate recruitment, retention, and education strategies for different professional health and care workforce categories as needs vary. CONCLUSIONS: Given the critical importance of recruiting and retaining a strong health and care workforce, there is an immediate need to develop a cohesive strategy to address workforce shortfalls. This paper presents initial evidence on different interventions to address this need, and to inform care workforce recruitment and retention. Rapid Review registration PROSPERO 2022 CRD42022371721 Available from: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42022371721.

Benchtop Models of Patient-Specific Intraventricular Flow During Heart Failure and LVAD Support.

The characterization of intraventricular flow is critical to evaluate the efficiency of fluid transport and potential thromboembolic risk but challenging to measure directly in advanced heart failure (HF) patients with left ventricular assist device (LVAD) support. The study aims to validate an in-house mock loop (ML) by simulating specific conditions of HF patients with normal and prosthetic mitral valves (MV) and LVAD patients with small and dilated left ventricle volumes, then comparing the flow-related indices result of vortex parameters, residence time (RT), and shear-activation potential (SAP). Patient-specific inputs for the ML studies included heart rate, end-diastolic and end-systolic volumes, ejection fraction, aortic pressure, E/A ratio, and LVAD speed. The ML effectively replicated vortex development and circulation patterns, as well as RT, particularly for HF patient cases. The LVAD velocity fields reflected altered flow paths, in which all or most incoming blood formed a dominant stream directing flow straight from the mitral valve to the apex. RT estimation of patient and ML compared well for all conditions, but SAP was substantially higher in the LVAD cases of the ML. The benchtop system generated comparable and reproducible hemodynamics and fluid dynamics for patient-specific conditions, validating its reliability and clinical relevance. This study demonstrated that ML is a suitable platform to investigate the fluid dynamics of HF and LVAD patients and can be utilized to investigate heart-implant interactions.

Impact of increased antiretroviral therapy use during the treatment as prevention era in Australia.

BACKGROUND: We analysed the impact of increased antiretroviral therapy (ART) on HIV epidemiology and healthcare costs in Australia during the 'Treatment-as-prevention' and 'Undetectable equals Untransmissible (U=U)' eras. METHODS: We conducted a retrospective modelling analysis between 2009 and 2019 to calculate the potential impact of early initiation of ART and treatment-as-prevention on HIV among gay and bisexual men (GBM). The model incorporates the change in the proportion diagnosed, treated, and virally suppressed, as well as the scale-up of oral HIV pre-exposure prophylaxis (PrEP) and the change in sexual behaviour during this period. We simulated a baseline and a no ART increase scenario and conducted a costing analysis from a national health provider perspective with cost estimates in 2019 AUD. RESULTS: Increasing ART use between 2009 and 2019 averted an additional 1624 [95% percentile interval (PI): 1220-2099] new HIV infections. Without the increase in ART, the number of GBM with HIV would have increased from 21 907 (95% PI: 20 753-23 019) to 23 219 (95% PI: 22 008-24 404) by 2019. HIV care and treatment costs for people with HIV increased by $296 (95% PI: $235-367) million AUD (assuming no change in annual healthcare costs). This was offset by a decrease in the lifetime HIV costs (with 3.5% discounting) for those newly infected of $458 (95% PI: $344-592) million AUD, giving a net cost saving of $162 (95%: $68-273) million AUD (and a benefits-to-cost ratio of 1.54). CONCLUSIONS: Increasing the proportion of Australian GBM on effective ART between 2009 and 2019 likely resulted in substantial reductions in new HIV infections and cost savings.

A scoping review of nurse-led randomised controlled trials.

BACKGROUND: Nurses comprise the largest portion of the healthcare workforce worldwide. However, nurse representation in the leadership of clinical research and research funding is largely unknown. The Australasian Nursing and Midwifery Clinical Trials Network was established to provide a coordinated network, focussed on building research capacity in nursing and midwifery. To support this work, this scoping review of nurse-led randomised controlled trials was conducted to summarise research activity, as well as highlight future research directions, gaps and resources. Midwife-led trials will be reported elsewhere. AIM: To quantify number, type and quality of nurse-led randomised controlled trials registered between 2000-2021. DESIGN: A scoping review of RCTs. DATA SOURCES: Medline, Emcare and Scopus were searched from 2000 to August 2021. ANZCTR, NHMRC, MRFF and HRC (NZ) registries were searched from inception to July 2021. REVIEW METHODS: This review was informed by the JBI scoping review framework using the PRISMA-ScR. RESULTS: Our search yielded 188 nurse-led publications and 279 registered randomised controlled trials. Multiple trials had the same nurse leaders. There were more registrations than publications. Publications were predominantly of high methodological quality; however, there was a reliance on active controls and blinding was low. Trial registrations indicate that universities and hospital/healthcare organisations were the major sources of funding, while publications indicate that Governments and the National Health and Medical Research Council were the main funding bodies. CONCLUSION: A small number of high-quality, large-scale, nationally funded randomised controlled trials were identified, with a larger number of locally funded small trials. There was a disparity between the number of registered trials and those published. Additional infrastructure, funding and career frameworks are needed to enable nurses to design, conduct and publish clinical trials that inform the health system and improve health outcomes. RELEVANCE TO CLINICAL PRACTICE: Research initiated and led by nurses has the potential to improve the health and well-being of individuals and communities, and current nurse-led research is of high methodological quality; however, there were very few nurse-led RCTs, conducted by a small pool of nurse researchers. This gap highlights the need for support in the design, conduct and publishing of nurse-led RCTs. PATIENT OR PUBLIC CONTRIBUTION: This is a scoping review; therefore, patient or public contribution is not applicable.

Co-designing a peer-led model of delivering behavioural activation for people living with depression or low mood in Australian farming communities.

INTRODUCTION: Farmers face a range of factors that negatively influence their mental health and suicide risk, yet have limited access to appropriate support. Behavioural activation (BA) is an evidence-based therapy that can be effectively delivered by nonclinical workers. Working with members of farming communities to deliver BA to their peers has the potential to overcome many well-established barriers to mental health help-seeking and improve outcomes for this at-risk group. OBJECTIVE: This paper describes the findings of a co-design phase informing the development of a peer (farmer)-led approach for delivering BA for farmers living with depression or low mood. DESIGN: This qualitative study used a co-design approach involving members of the target community. Focus groups were transcribed and analysed using Thematic Analysis and the Framework approach. FINDINGS: Ten online focus groups with 22 participants were held over 3 months. Four overarching, interlinked themes were identified: (i) filling the gap in rural mental health support; (ii) alignment with the farming context-tailoring how, where and when we engage about mental health; (iii) the 'messenger' is as important as the message; and (iv) sustainability, governance and support. DISCUSSION: Findings suggest BA could be a contextually appropriate model of support for the farming community-given its practical and solution-focused approach-and could help improve access to support. Having peer workers deliver the intervention was viewed as appropriate. Ensuring governance structures are developed to support peers to deliver the intervention will be essential to facilitate effectiveness, safety and sustainability. CONCLUSION: Insights gained through co-design have been critical to the success of developing this new model of support for members of farming communities experiencing depression or low mood.

A Gonococcal Vaccine Has the Potential to Rapidly Reduce the Incidence of Neisseria gonorrhoeae Infection Among Urban Men Who Have Sex With Men.

BACKGROUND: A gonococcal vaccine is urgently needed due to increasing gonorrhea incidence and emerging multidrug-resistant gonococcal strains worldwide. Men who have sex with men (MSM) have among the highest incidences of gonorrhea and may be a key target population for vaccination when available. METHODS: An individual-based, anatomical site-specific mathematical model was used to simulate Neisseria gonorrhoeae transmission in a population of 10 000 MSM. The impact of vaccination on gonorrhea prevalence was assessed. RESULTS: With a gonococcal vaccine of 100% or 50% protective efficacy, gonorrhea prevalence could be reduced by 94% or 62%, respectively, within 2 years if 30% of MSM are vaccinated on presentation for sexually transmitted infection (STI) testing. Elimination of gonorrhea is possible within 8 years with vaccines of ≥ 50% efficacy lasting 2 years, providing a booster vaccination is available every 3 years on average. A vaccine's impact may be reduced if it is not effective at all anatomical sites. CONCLUSIONS: Our study indicates that with a vaccine of modest efficacy and an immunization strategy that targets MSM presenting for STI screening, the prevalence of gonorrhea in this population could be rapidly and substantially reduced.

Assessing the Impact of HIV Preexposure Prophylaxis Scale-Up on Gonorrhea Incidence Among Gay and Bisexual Men in Sydney: A Mathematical Modeling Study.

BACKGROUND: The rollout of preexposure prophylaxis (PrEP) for HIV prevention among gay and bisexual men (GBM) is associated with increases in condomless anal intercourse, potentially increasing the incidence of other sexually transmissible infections (STIs). METHODS: We developed an individual-based mathematical model to simulate the transmission of Neisseria gonorrhoeae among GBM in Sydney, accounting for changes in sexual practices, STI testing, and PrEP use. We calibrated and validated the model using reported incidence rates for HIV-positive and HIV-negative GBM from 2010 to 2019. Scenarios were run with varying PrEP uptake, PrEP-related STI testing, and PrEP-related sexual behavior and testing intervals up to 2030 to assess the impact of PrEP use on gonorrhea incidence. RESULTS: Preexposure prophylaxis uptake and associated 3-monthly STI testing from 2015 onward resulted in a predicted increase from 20 to 37 N. gonorrhoeae infections per 100 person-years among HIV-negative GBM by the end of 2020. This is lower than the counterfactual predictions of 45 per 100 person-years if PrEP were not scaled up and 48 per 100 person-years with nonadherence to 3-monthly STI testing. Increasing the time between STI tests for PrEP users by 1 month from 2018 results in the incidence rate among HIV-negative GBM increasing by 8% by 2030. If PrEP coverage doubles from 24% to 53%, incidence among HIV-negative GBM declines by ~25% by 2030. CONCLUSIONS: Behavior change due to widespread PrEP use may lead to significant increases in gonorrhea incidence in GBM, but the recommended quarterly STI testing recommended for PrEP users should reduce incidence by 18% by 2030.

A Mental Health Chatbot with Cognitive Skills for Personalised Behavioural Activation and Remote Health Monitoring.

Mental health issues are at the forefront of healthcare challenges facing contemporary human society. These issues are most prevalent among working-age people, impacting negatively on the individual, his/her family, workplace, community, and the economy. Conventional mental healthcare services, although highly effective, cannot be scaled up to address the increasing demand from affected individuals, as evidenced in the first two years of the COVID-19 pandemic. Conversational agents, or chatbots, are a recent technological innovation that has been successfully adapted for mental healthcare as a scalable platform of cross-platform smartphone applications that provides first-level support for such individuals. Despite this disposition, mental health chatbots in the extant literature and practice are limited in terms of the therapy provided and the level of personalisation. For instance, most chatbots extend Cognitive Behavioural Therapy (CBT) into predefined conversational pathways that are generic and ineffective in recurrent use. In this paper, we postulate that Behavioural Activation (BA) therapy and Artificial Intelligence (AI) are more effectively materialised in a chatbot setting to provide recurrent emotional support, personalised assistance, and remote mental health monitoring. We present the design and development of our BA-based AI chatbot, followed by its participatory evaluation in a pilot study setting that confirmed its effectiveness in providing support for individuals with mental health issues.

Stakeholders' perceptions of how nurse-physician communication may impact patient care: protocol for a concept mapping study.

Effective nurse-physician interprofessional communication is important to ensure that patients receive evidence-based care and treatment. There is a gap in knowledge about how nurse-physician communication impacts patient care. We propose using concept mapping to develop an in-depth understanding of patients, nurses, and physicians' perspectives on how physician-nurse communication affects patient care. There are six phases to concept mapping: determining the focus, generating statements, structuring statements, producing the map, interpretating the map, and map utilization. We will use 'Ariadne', a concept mapping software package for data collection and analysis. The study outcome will be a two-dimensional concept map providing a visual representation of how nurse-physician communication influences patient care. We will report similarity and differences among three stakeholder groups. Our research will inform the development of testable hypotheses about nurse-physician communication and patient care.

Sodium sensitivity of KNa channels in mouse CA1 neurons.

Potassium channels play an important role regulating transmembrane electrical activity in essentially all cell types. We were especially interested in those that determine the intrinsic electrical properties of mammalian central neurons. Over 30 different potassium channels have been molecularly identified in brain neurons, but there often is not a clear distinction between molecular structure and the function of a particular channel in the cell. Using patch-clamp methods to search for single potassium channels in excised inside-out (ISO) somatic patches with symmetrical potassium, we found that nearly all patches contained non-voltage-inactivating channels with a single-channel conductance of 100-200 pS. This conductance range is consistent with the family of sodium-activated potassium channels (Slo2.1, Slo2.2, or collectively, KNa). The activity of these channels was positively correlated with a low cytoplasmic Na+ concentration (2-20 mM). Cell-attached recordings from intact neurons, however, showed little or no activity of this K+ channel. Attempts to increase channel activity by increasing intracellular sodium concentration ([Na+]i) with bursts of action potentials or direct perfusion of Na+ through a whole cell pipette had little effect on KNa channel activity. Furthermore, excised outside-out (OSO) patches across a range of intracellular [Na+] showed less channel activity than we had seen with excised ISO patches. Blocking the Na+/K+ pump with ouabain increased the activity of the KNa channels in excised OSO patches to levels comparable with ISO-excised patches. Our results suggest that despite their apparent high levels of expression, the activity of somatic KNa channels is tightly regulated by the activity of the Na+/K+ pump.NEW & NOTEWORTHY We studied KNa channels in mouse hippocampal CA1 neurons. Excised inside-out patches showed the channels to be prevalent and active in most patches in the presence of Na+. Cell-attached recordings from intact neurons, however, showed little channel activity. Increasing cytoplasmic sodium in intact cells showed a small effect on channel activity compared with that seen in inside-out excised patches. Blockade of the Na+/K+ pump with ouabain, however, restored the activity of the channels to that seen in inside-out patches.

A Predictive Model for Nodal Metastases in Patients With Appendiceal Cancers.

BACKGROUND: Histologic subtypes of appendiceal cancer vary in their propensity for metastases to regional lymph nodes (LN). A predictive model would help direct subsequent surgical therapy. METHODS: The National Cancer Database was queried for patients with appendiceal cancer undergoing surgery between 1998 and 2012. Multivariable logistic regression was used to develop a predictive model of LN metastases which was internally validated using Brier score and Area under the Curve (AUC). RESULTS: A total of 21,647 patients were identified, of whom 9079 (41.9%) had node negative disease, 4575 (21.1%) node positive disease, and 7993 (36.9%) unknown LN status. The strongest predictors of LN positivity were histology (carcinoid tumors OR 12.78, 95% CI 9.01-18.12), increasing T Stage (T3 OR 3.36, 95% CI 2.52-4.50, T4 OR 6.30, 95% CI 4.71-8.42), and tumor grade (G3 OR 5.55, 95% CI 4.78-6.45, G4 OR 5.98, 95% CI 4.30-8.31). The coefficients from the regression analysis were used to construct a calculator that generated predicted probabilities of LN metastases given certain inputs. Internal validation of the overall model showed an AUC of 0.75 (95% CI 0.74-0.76) and Brier score of 0.188. Histology-specific predictive models were also constructed with an AUC that varied from 0.669 for signet cell to 0.75 for goblet cell tumors. CONCLUSIONS: The risk for nodal metastases in patients with appendiceal cancers can be quantified with reasonable accuracy using a predictive model incorporating patient age, sex, tumor histology, T-stage, and grade. This can help inform clinical decision making regarding the need for a right hemicolectomy following appendectomy.