2023 Undetectable = Untransmittable global policy roundtable report: a multistakeholder perspective on Undetectable = Untransmittable research and policy priorities.

Background Launched in 2016 by Prevention Access Campaign, the 'Undetectable=Untransmittable' (U=U) campaign empowers people living with HIV to live full social, sexual and reproductive lives, dismantle stigma, promote increased treatment access, and advocate for updated HIV guidelines. Methods Key priorities for promoting improvements to community-centred, evidence-informed U=U policy and research were the focus of a half-day global roundtable held in 2023 alongside the 12th International AIDS Society Conference in Brisbane, Australia. After a series of presentations, experts in U=U research, policymaking, advocacy and HIV clinical care participated in facilitated discussions, and detailed notes were taken on issues related to advancing U=U policy and research. Results Expert participants shared that knowledge and trust in U=U remains uneven, and is largely concentrated among people living with HIV, particularly those connected to gay and bisexual networks. It was agreed that there is a need to ensure all members of priority populations are explicitly included in U=U policies that promote U=U. Participants also identified a need for policymakers, healthcare professionals, advocates and researchers to work closely with community-based organisations to ensure the U=U message is relevant, useful, and utilised in the HIV response. Adopting language, such as 'zero risk', was identified as crucial when describing undetectable viral load as an effective HIV prevention strategy. Conclusion U=U can have significant benefits for the mental and physical wellbeing of people living with HIV. There is an urgent need to address the structural barriers to HIV care and treatment access to ensure the full benefits of U=U are realised.

Risk-Based Screening Tools to Optimise HIV Testing Services: a Systematic Review.

PURPOSE OF REVIEW: Effective ways to diagnose the remaining people living with HIV who do not know their status are a global priority. We reviewed the use of risk-based tools, a set of criteria to identify individuals who would not otherwise be tested (screen in) or excluded people from testing (screen out). RECENT FINDINGS: Recent studies suggest that there may be value in risk-based tools to improve testing efficiency (i.e. identifying those who need to be tested). However, there has not been any systematic reviews to synthesize these studies. We identified 18,238 citations, and 71 were included. The risk-based tools identified were most commonly from high-income (51%) and low HIV (<5%) prevalence countries (73%). The majority were for "screening in" (70%), with the highest performance tools related to identifying MSM with acute HIV. Screening in tools may be helpful in settings where it is not feasible or recommended to offer testing routinely. Caution is needed for screening out tools, where there is a trade-off between reducing costs of testing with missing cases of people living with HIV.

Does knowledge and attitude of healthcare professionals working in critical care areas affect their willingness to offer the option of organ donation? results of a tertiary hospital survey.

INTRODUCTION: Organ donation (OD) rates in Malaysia have remained suboptimal for decades. Healthcare professionals (HCPs) working in critical care areas are responsible for diagnosing brain death (BD) and initiating the OD process. Impact of their knowledge and attitudes on willingness to offer the option of OD to families of potential donors is unknown. METHODS: Knowledge and attitudes about BD, OD, and organ transplantation (OT) of critical care HCPs in a Malaysian transplant centre were studied using a validated questionnaire. Responses were analysed using multivariable analysis with willingness to offer the option of OD to families of potential donors as dependent variable. RESULTS: Age (p = 0.04), profession (doctors > nurses, p < 0.001), religion (Buddhists > others, p = 0.013) [but not ethnicity], higher knowledge scores for Brain Death Test, Brain Death Knowledge, Organ Donation and Transplantation, and overall knowledge score (p < 0.001) were associated with greater odds of offering OD to families. Belief in the reliable diagnosis of BD, confidence in explaining BD, and belief that OD will not affect religious services were significantly associated with willingness to offer OD, while HCPs who were willing to personally donate organs had greatest odds (p < 0.001). Other factors that significantly influenced HCPs' willingness to offer included their perception about families' willingness to donate, body disfigurement, and confidence in OT. CONCLUSIONS: Overall, HCPs had highly positive attitudes. However, potential barriers in offering OD to families were identified. Proven interventions from international experience could help address these issues and likely improve OD rates in Malaysia.

Foot care knowledge and self-care practices among diabetic patients in Penang: A primary care study.

INTRODUCTION: In Malaysia, the prevalence of diabetes mellitus has been increasing annually, currently affecting 18.3% of the population. Diabetic foot ulcer, a common complication of diabetes, is associated with high morbidity and mortality, consequently increasing health care expenditure. A previous study showed that foot care knowledge and foot self-care practices help to reduce the development of ulcers.1,2 This study aims to identify the level of foot care knowledge and self-care practices among diabetic patients in the primary care setting. OBJECTIVE: This study was to determine the level of foot care knowledge and foot self-care practices among diabetic patients in the primary care setting in Penang Island and its determinants and the correlation between level of foot care knowledge and self-care practices among diabetic patients. MATERIAL AND METHODS: A cross sectional study was performed on 311 diabetic patients who were registered to two government health clinics in Penang. Information regarding respondents' demographic status, foot care knowledge, and foot self-care practices were gathered using a self-administered questionnaire. Data were analysed using the Statistical Package for the Social Sciences (SPSS) 22. The Mann-Whitney U test and Kruskal-Wallis test were applied to the analysis. Multiple linear regression was performed to identify the determinants. Correlation between knowledge and self-care practice was determined using the linear regression model. RESULTS: One hundred and sixty-five (53.1%) respondents achieved good knowledge scores and 196 respondents (63%) achieved good self-care practice scores. The median age of respondents was 61 years, who were mostly females (56.6%), Malays (41.2%), and unemployed (48.6%). Median HbA1c level was 7.5%, and 42.8% of respondents had diabetes for 5 to 10 years. Lowest scores for knowledge and self-care practices were observed in foot skin care questions. Formal foot care education was found to be a significant predictor of foot care knowledge (p<0.05, 95% CI -1.102, -0.098). Foot care knowledge was significantly and positively correlated with foot self-care practices (p<0.001, 95% CI 0.548, 0.727). CONCLUSION: Foot care knowledge has significant positive correlation with foot self-care practices. Empowering diabetic patients with foot care knowledge may lead to significantly better foot self-care practices.

Hyperglyceridaemia-induced acute pancreatitis in pregnancy: Experience from a tertiary hospital in Singapore.

Acute pancreatitis (AP) is a serious condition that can occur suddenly in pregnancy. We present a case of sudden onset of epigastric pain with severely deranged serum triglyceride levels in a 32-year-old Vietnamese primigravida with no significant past medical history in the Singapore General Hospital. The patient was managed in the intensive care unit, with plasmapheres and intravenous insulin and was eventually a healthy term foetus was delievered via ceasarian section. This case showcased multidisciplinary co operation between the obstetrics, anaesthetic, endocrinology and intensive care team and serves as a reminder to consider this rare condition for future similar presentations.

Does the gene matter? Genotype-phenotype and genotype-outcome associations in congenital melanocytic naevi.

BACKGROUND: Genotype-phenotype studies can identify subgroups of patients with specific clinical features or differing outcomes, which can help shape management. OBJECTIVES: To characterize the frequency of different causative genotypes in congenital melanocytic naevi (CMN), and to investigate genotype-phenotype and genotype-outcome associations. METHODS: We conducted a large cohort study in which we undertook MC1R genotyping from blood, and high-sensitivity genotyping of NRAS and BRAF hotspots in 156 naevus biopsies from 134 patients with CMN [male 40%; multiple CMN 76%; projected adult size (PAS) > 20 cm, 59%]. RESULTS: Mosaic NRAS mutations were detected in 68%, mutually exclusive with BRAF mutations in 7%, with double wild-type in 25%. Two separate naevi were sequenced in five of seven patients with BRAF mutations, confirming clonality. Five of seven patients with BRAF mutations had a dramatic multinodular phenotype, with characteristic histology distinct from classical proliferative nodules. NRAS mutation was the commonest in all sizes of CMN, but was particularly common in naevi with PAS > 60 cm, implying more tolerance to that mutation early in embryogenesis. Facial features were less common in double wild-type patients. Importantly, the incidence of congenital neurological disease, and apparently of melanoma, was not altered by genotype; no cases of melanoma were seen in BRAF-mutant multiple CMN, however, this genotype is rare. CONCLUSIONS: CMN of all sizes are most commonly caused by mutations in NRAS. BRAF is confirmed as a much rarer cause of multiple CMN, and appears to be commonly associated with a multinodular phenotype. Genotype in this cohort was not associated with differences in incidence of neurological disease in childhood. However, genotyping should be undertaken in suspected melanoma, for guidance of treatment. What's already known about this topic? Multiple congenital melanocytic naevi (CMN) have been shown to be caused by NRAS mosaic mutations in 70-80% of cases, by BRAF mosaicism in one case report and by inference in some previous cases. There has been debate about genotypic association with different sizes of CMN, and no data on genotype-outcome. What does this study add? NRAS mosaicism was found in 68%, BRAF in 7% and double wild-type in 25% of cases of CMN. NRAS was the commonest mutation in all sizes of CMN, but was nearly universal in projected adult size > 60 cm. BRAF is often associated with a distinct multinodular clinical/histological phenotype. Adverse outcomes did not differ between genotypes on current numbers.

The potential for quality assurance systems to save costs and lives: the case of early infant diagnosis of HIV.

OBJECTIVES: Scaling up of point-of-care testing (POCT) for early infant diagnosis of HIV (EID) could reduce the large gap in infant testing. However, suboptimal POCT EID could have limited impact and potentially high avoidable costs. This study models the cost-effectiveness of a quality assurance system to address testing performance and screening interruptions, due to, for example, supply stockouts, in Kenya, Senegal, South Africa, Uganda and Zimbabwe, with varying HIV epidemics and different health systems. METHODS: We modelled a quality assurance system-raised EID quality from suboptimal levels: that is, from misdiagnosis rates of 5%, 10% and 20% and EID testing interruptions in months, to uninterrupted optimal performance (98.5% sensitivity, 99.9% specificity). For each country, we estimated the 1-year impact and cost-effectiveness (US$/DALY averted) of improved scenarios in averting missed HIV infections and unneeded HIV treatment costs for false-positive diagnoses. RESULTS: The modelled 1-year costs of a national POCT quality assurance system range from US$ 69 359 in South Africa to US$ 334 341 in Zimbabwe. At the country level, quality assurance systems could potentially avert between 36 and 711 missed infections (i.e. false negatives) per year and unneeded treatment costs between US$ 5808 and US$ 739 030. CONCLUSIONS: The model estimates adding effective quality assurance systems are cost-saving in four of the five countries within the first year. Starting EQA requires an initial investment but will provide a positive return on investment within five years by averting the costs of misdiagnoses and would be even more efficient if implemented across multiple applications of POCT.

OBJECTIFS: L'intensification du dépistage au point des soins (DPS) pour le diagnostic précoce du VIH chez le nourrisson (DPVN) pourrait réduire le grand écart dans le dépistage des nourrissons. Cependant, un DPVN DPS sous-optimal pourrait avoir un impact limité et des coûts évitables potentiellement élevés. Cette étude modélise la rentabilité d'un système d'assurance qualité pour traiter les performances des tests et les interruptions de dépistage, dues par exemple à des ruptures de stock, au Kenya, au Sénégal, en Afrique du Sud, en Ouganda et au Zimbabwe, avec des épidémies variables du VIH et des systèmes de santé différents. MÉTHODES: Nous avons modélisé une qualité de DPVN soulevée par le système d'assurance qualité à partir de niveaux sous-optimaux: c'est-à-dire des taux d'erreurs de diagnostic de 5%, 10% et 20% et des interruptions des tests de DPVN en mois, à des performances optimales ininterrompues (sensibilité de 98,5%, spécificité de 99,9%). Pour chaque pays, nous avons estimé l'impact sur un an et la rentabilité (en USD/DALY évitée) de scénarios améliorés pour éviter les infections à VIH manquées et les coûts inutiles de traitement du VIH pour les diagnostics faux positifs. RÉSULTATS: Les coûts modélisés sur un an d'un système national d'assurance qualité DPS vont de 69.359 USD en Afrique du Sud à 334.341 USD au Zimbabwe. Au niveau des pays, les systèmes d'assurance de la qualité pourraient potentiellement éviter entre 36 et 711 infections manquées (c'est-à-dire des faux négatifs) par an et des coûts de traitement inutiles entre 5.808 et 739.030 USD. CONCLUSIONS: Le modèle estime que l'ajout de systèmes d'assurance qualité efficaces permet de réaliser des économies dans quatre des cinq pays au cours de la première année. Le lancement de l'assurance qualité nécessite un investissement initial, mais fournira un retour sur investissement positif dans les cinq ans en évitant les coûts des diagnostics erronés et serait encore plus efficace s'il était mis en œuvre dans plusieurs applications de DPS.

Demographics of healthcare professionals' knowledge and attitude toward deceased organ donation: Survey of critical care areas in a tertiary hospital.

INTRODUCTION: Organ donation rate in Malaysia is amongst the lowest in the World. Healthcare professionals (HCPs) working in critical care areas play an important role in the deceased organ donation (DOD) process. This study seeks to identify the demographics of HCPs working in the critical care areas and their knowledge and attitudes toward the DOD process. METHOD: A cross-sectional survey on the demographics, knowledge and attitudes of the doctors and nurses working in critical care areas was undertaken by the random sampling method, using a validated, structured questionnaire. HCP's knowledge and attitudes towards brain death (BD), DOD, organ transplantation (OT), and possession of organ donor card were compared against their demographics. RESULTS: Four hundred and twelve (72.9%) out of the total 565 HCPs in critical care areas responded of whom 163 (39.6%) were doctors and 249 (60.4%) were nurses. After adjusting for other factors, department of work and profession were highly correlated with the overall knowledge score (p<0.001 and p=0.003 respectively) and knowledge about BD (p<0.001 and p=0.013 respectively). HCPs from the neurosurgical intensive care unit (p<0.001) and doctors (p<0.001) had higher mean knowledge scores compared to their counterparts. Profession was most significantly correlated with having a positive attitude towards BD (p<0.001) and OT (p<0.001). CONCLUSION: Department, profession and ethnicity were the demographic characteristics that correlated with knowledge and attitudes of HCPs on organ donation. Efforts to improve DOD rates in Malaysia should include targeted interventions to address the knowledge and attitudes of HCPs working in critical care areas.

Chlamydia screening for pregnant women aged 16-25 years attending an antenatal service: a cost-effectiveness study.

OBJECTIVE: Determine the cost-effectiveness of screening all pregnant women aged 16-25 years for chlamydia compared with selective screening or no screening. DESIGN: Cost effectiveness based on a decision model. SETTING: Antenatal clinics in Australia. SAMPLE: Pregnant women, aged 16-25 years. METHODS: Using clinical data from a previous study, and outcomes data from the literature, we modelled the short-term perinatal (12-month time horizon) incremental direct costs and outcomes from a government (as the primary third-party funder) perspective for chlamydia screening. Costs were derived from the Medicare Benefits Schedule, Pharmaceutical Benefits Scheme, and average cost-weights reported for hospitalisations classified according to the Australian refined diagnosis-related groups. MAIN OUTCOME MEASURES: Direct costs of screening and managing chlamydia complications, number of chlamydia cases detected and treated, and the incremental cost-effectiveness ratios were estimated and subjected to sensitivity analyses. RESULTS: Assuming a chlamydia prevalence rate of 3%, screening all antenatal women aged 16-25 years at their first antenatal visit compared with no screening was $34,931 per quality-adjusted life-years gained. Screening all women could result in cost savings when chlamydia prevalence was higher than 11%. The incremental cost-effectiveness ratios were most sensitive to the assumed prevalence of chlamydia, the probability of pelvic inflammatory disease, the utility weight of a positive chlamydia test and the cost of the chlamydia test and doctor's appointment. CONCLUSION: From an Australian government perspective, chlamydia screening of all women aged 16-25 years old during one antenatal visit was likely to be cost-effective compared with no screening or selective screening, especially with increasing chlamydia prevalence. TWEETABLE ABSTRACT: Chlamydia screening for all pregnant women aged 16-25 years during an antenatal visit is cost effective.

A smoking cessation programme for current and recent ex-smokers following diagnosis of a potentially curable cancer.

BACKGROUND: Cancer patients who quit smoking have improved survival rates. The time of diagnosis provides a 'teachable moment' when healthcare providers can offer smoking-cessation treatment. AIMS: To assess the impact on quit rates of a tailored smoking-cessation intervention for patients diagnosed with a potentially curable cancer. METHODS: A prospective, one-arm cohort study of current smokers and recent quitters (<30 days) who had commenced treatment for a potentially curable cancer was performed. Intervention involved an initial motivational interview, regular follow up and pharmacotherapy when appropriate. Quit rates were measured at 1, 3, 6 and 12 months by self-reported abstinence and biochemical confirmation. The primary end point was prolonged abstinence at 12 months. Changes in quality of life parameters and distress were also assessed. RESULTS: Seventy-one patients were recruited, with a median age of 56 years. Forty-one patients (58%) had a smoking-related cancer. The prolonged abstinence rate at 12 months was 24% (95% confidence interval 14-36%). Factors associated with successful quitting included being in the preparation or action phase of readiness to change at study entry (P = 0.012) and having complications of treatment requiring hospitalisation (P = 0.024). Between baseline and 12 months, quitters reported improvement in self-control (P < 0.001) and reduced levels of distress (P = 0.03) compared to non-quitters. CONCLUSION: Patients who continue to smoke after being diagnosed with cancer require intensive support to quit. An individualised behavioural and pharmacological intervention can be successful in helping patients quit smoking, with quality of life improvements seen amongst successful quitters. Population measures to stop people starting smoking remain essential.

Triply resonant four-wave mixing in silicon-coupled resonator microring waveguides.

Silicon photonic four-wave mixing (FWM) devices intended for telecommunications applications must satisfy three requirements: achieve conversion efficiencies close to the detection threshold of typical receivers, while keeping pump power requirements modest and providing enough bandwidth for typical signal formats. Here, we report a continuous-wave FWM efficiency of -21.3 dB at 100 mW pump power and demonstrate wavelength conversion at 10 Gbps in a coupled-resonator optical-waveguide device.

Impact of a national audit on child and adolescent psychiatrists' prescribing practices.

BACKGROUND: A look back review of South Kerry Child and Adolescent Mental Health Services (CAMHS) in Ireland, known as the 'Maskey report' (MR), highlighted substandard prescribing practices. The aim of this 'Maskey Impact Study' (MIS) was to explore changes to child and adolescent psychiatrists' prescribing practices following the MR. METHOD: The study was cross-sectional and mixed method. A study specific questionnaire was distributed electronically to psychiatrists working in CAMHS (n = 160). RESULTS: 102 psychiatrists participated in the study (response rate 63.8%). Perceived improvement in prescribing practices included improved medical record keeping (63.7%), consent documentation (53.9%), medication information provision (41.2%) and physical health monitoring (60.8%). However, 43.1% of psychiatrists reported a reluctance to prescribe medication even when clinically indicated and 50% were more likely to avoid off-label use. Most respondents reported increased stress levels (80.4%) with higher stress being significantly associated with reticence in prescribing (χ2 = 11.746, p < .001) and avoiding off-label use (χ2 = 15.392, p < 0.001). Thematic analysis highlighted increased medication hesitancy, enforced 'meaningless' bureaucracy and medication mistrust among families. DISCUSSION: Although improvements reported are welcomed, the increased hesitancy of medication use, avoidance of prescribing more than one medication, and avoidance of off-label use, is of concern with potential unintended adverse consequences. Reluctance in prescribing may deprive youth of access to evidence-based treatments and limit exposure of NCHDs to the safe practice of consultant-initiated psychopharmacology. Further research will be important to determine if this impacts clinical care. Continued education in psychopharmacology is essential along with increased public awareness of the evidence for medication, to help restore public confidence and trust in psychopharmacology.

Non-linear QED approach for betatron radiation in a laser wakefield accelerator.

Laser plasma-based accelerators provide an excellent source of collimated, bright, and adequately coherent betatron-type x-ray pulses with potential applications in science and industry. So far the laser plasma-based betatron radiation has been described within the concept of classical Liénard-Wiechert potentials incorporated in particle-in-cell simulations, a computing power-demanding approach, especially for the case of multi-petawatt lasers. In this work, we describe the laser plasma-based generation of betatron radiation at the most fundamental level of quantum mechanics. In our approach, photon emission from the relativistic electrons in the plasma bubble is described within a nonlinear quantum electrodynamics (QED) framework. The reported QED-based betatron radiation results are in excellent agreement with similar results using Liénard-Wiechert potentials, as well as in very good agreement with betatron radiation measurements, obtained with multi-10-TW lasers interacting with He and multielectron N[Formula: see text] gas targets. Furthermore, our QED approach results in a dramatic reduction of the computational runtime demands, making it a favorable tool for designing betatron radiation experiments, especially in multi-petawatt laser facilities.

Nanowire implosion under laser amplified spontaneous emission pedestal irradiation.

Nanowire array targets exhibit high optical absorption when interacting with short, intense laser pulses. This leads to an increased yield in the production of accelerated particles for a variety of applications. However, these interactions are sensitive to the laser prepulse and could be significantly affected. Here, we show that an array of aligned nanowires is imploded when irradiated by an Amplified Spontaneous Emission pedestal of a [Formula: see text] laser with an intensity on the order of [Formula: see text]. Using radiation hydrodynamics simulations, we demonstrate that the electron density profile is radially compressed at the tip by the rocket-like propulsion of the ablated plasma. The mass density compression increases up to [Formula: see text] when a more dense nanowire array is used. This is due to the ablation pressure from the neighboring nanowires. These findings offer valuable information for selecting an appropriate target design for experiments aimed at enhancing production of accelerated particles.

Ultra-high-pressure generation in the relativistic transparency regime in laser-irradiated nanowire arrays.

We show that an ultra-high-pressure plasma can be generated when an aligned nanowire is irradiated by a laser with relativistic transparent intensity. Using a particle-in-cell simulation, we demonstrate that the expanded plasma following the z pinch becomes relativistically transparent and compressed longitudinally by the oscillating component of the ponderomotive force. The compressed structure persists throughout the pulse duration with a maximum pressure of 40Tbar when irradiated with a laser at an intensity of 10^{23}Wcm^{-2}, 5× higher than the z-pinch pressure. These results suggest an alternative approach to extending the current attainable pressure in the laboratory.