Large language models: a new frontier in paediatric cataract patient education.

BACKGROUND/AIMS: This was a cross-sectional comparative study. We evaluated the ability of three large language models (LLMs) (ChatGPT-3.5, ChatGPT-4, and Google Bard) to generate novel patient education materials (PEMs) and improve the readability of existing PEMs on paediatric cataract. METHODS: We compared LLMs' responses to three prompts. Prompt A requested they write a handout on paediatric cataract that was 'easily understandable by an average American.' Prompt B modified prompt A and requested the handout be written at a 'sixth-grade reading level, using the Simple Measure of Gobbledygook (SMOG) readability formula.' Prompt C rewrote existing PEMs on paediatric cataract 'to a sixth-grade reading level using the SMOG readability formula'. Responses were compared on their quality (DISCERN; 1 (low quality) to 5 (high quality)), understandability and actionability (Patient Education Materials Assessment Tool (≥70%: understandable, ≥70%: actionable)), accuracy (Likert misinformation; 1 (no misinformation) to 5 (high misinformation) and readability (SMOG, Flesch-Kincaid Grade Level (FKGL); grade level <7: highly readable). RESULTS: All LLM-generated responses were of high-quality (median DISCERN ≥4), understandability (≥70%), and accuracy (Likert=1). All LLM-generated responses were not actionable (<70%). ChatGPT-3.5 and ChatGPT-4 prompt B responses were more readable than prompt A responses (p<0.001). ChatGPT-4 generated more readable responses (lower SMOG and FKGL scores; 5.59±0.5 and 4.31±0.7, respectively) than the other two LLMs (p<0.001) and consistently rewrote them to or below the specified sixth-grade reading level (SMOG: 5.14±0.3). CONCLUSION: LLMs, particularly ChatGPT-4, proved valuable in generating high-quality, readable, accurate PEMs and in improving the readability of existing materials on paediatric cataract.

Injuries Related to Waterskiing Between 2012 and 2022: A National Database Study.

We conducted an epidemiological study by using the National Electronic Injury Surveillance System (NEISS) database to assess and quantify waterskiing injuries between 2012 and 2022. A total of 898 injuries were reported, primarily among Caucasian males during competition. Head (177, 20%), face (93, 10%), and knee (70, 8%) were the most prevalent types of injuries. Common physical examination findings included muscle strains, ligament sprains, lacerations, and fractures. Although rare, there were reported cases of dental injury, hemorrhage, crushing, foreign body, and amputation as well. These findings suggest that protective equipment, particularly headgear, is necessary to reduce the incidence of waterskiing injuries.

AUTO-TUNE: selecting the distance threshold for inferring HIV transmission clusters.

Molecular surveillance of viral pathogens and inference of transmission networks from genomic data play an increasingly important role in public health efforts, especially for HIV-1. For many methods, the genetic distance threshold used to connect sequences in the transmission network is a key parameter informing the properties of inferred networks. Using a distance threshold that is too high can result in a network with many spurious links, making it difficult to interpret. Conversely, a distance threshold that is too low can result in a network with too few links, which may not capture key insights into clusters of public health concern. Published research using the HIV-TRACE software package frequently uses the default threshold of 0.015 substitutions/site for HIV pol gene sequences, but in many cases, investigators heuristically select other threshold parameters to better capture the underlying dynamics of the epidemic they are studying. Here, we present a general heuristic scoring approach for tuning a distance threshold adaptively, which seeks to prevent the formation of giant clusters. We prioritize the ratio of the sizes of the largest and the second largest cluster, maximizing the number of clusters present in the network. We apply our scoring heuristic to outbreaks with different characteristics, such as regional or temporal variability, and demonstrate the utility of using the scoring mechanism's suggested distance threshold to identify clusters exhibiting risk factors that would have otherwise been more difficult to identify. For example, while we found that a 0.015 substitutions/site distance threshold is typical for US-like epidemics, recent outbreaks like the CRF07_BC subtype among men who have sex with men (MSM) in China have been found to have a lower optimal threshold of 0.005 to better capture the transition from injected drug use (IDU) to MSM as the primary risk factor. Alternatively, in communities surrounding Lake Victoria in Uganda, where there has been sustained heterosexual transmission for many years, we found that a larger distance threshold is necessary to capture a more risk factor-diverse population with sparse sampling over a longer period of time. Such identification may allow for more informed intervention action by respective public health officials.

Presenting a Framework to Professionalize Health Supply Chain Management.

INTRODUCTION: Many countries have an insufficient supply of adequately skilled supply chain workers to manage health commodities, and no global standards in education or experience exist for the supply chain management (SCM) workforce managing health products. We present a professionalization framework for the health SCM workforce that provides a systematic process that countries can use to standardize and elevate the health SCM profession. METHODS: In 2019, semistructured interviews were conducted with individuals from 10 leading organizations supporting in-country public health supply chains to explore approaches for an SCM professionalization framework. Interview data were analyzed using direct thematic analysis. Findings were then validated through a validation workshop with 11 individuals from 8 leading SCM organizations. RESULTS: Four associated components of this framework were developed: (1) The Library of Competencies and Designations contains management competencies grouped in 7 domains and supply chain technical competencies assigned to 5 professional designations; (2) The Collection of Roles and Job Descriptions contains 96 sample job descriptions; (3) The Mapping of Education displays the education offerings relevant to each competency across the 5 professional designations; and (4) The Implementation Approach for Health Supply Chains leads project teams to systematically apply these 3 tools in the supply chain context of a country. CONCLUSION: The SCM Professionalisation Framework provides a valuable tool to increase the supply of and demand for health SCM workers, increasing the recognition and use of SCM professionals within national health systems. Its utilization is a critical step in addressing the current workforce gap, particularly in low- and middle-income countries, and ensuring that the health SCM workforce possesses the right competencies, skills, and qualifications to fulfill its roles. The comprehensive framework can be used by governments, employers, and education institutions to define and align SCM professional standards, competencies, and curricula with job requirements.

Perceptions and preferences for environmentally sustainable food and associated factors: a cross-sectional analysis of a nationally representative survey of United States consumers.

BACKGROUND: Consumers are increasingly interested in environmentally sustainable dietary patterns. However, specific signals (e.g., language, labels, logos, or packaging) American consumers use to identify environmentally sustainable products are yet to be explored. OBJECTIVES: To determine perception and preferences for environmentally sustainable food and associated health and demographic factors associated with consumers' use of signals for environmentally sustainable food products in a nationally representative survey of United States consumers. METHODS: Repeated cross-sectional data were collected for the 2019 and 2020 annual online Food and Health Survey by the International Food Information Council. Three questions were analyzed: 1) the stated importance of environmentally sustainable food products, 2) signals consumers use to identify environmentally sustainable food/beverage products, and 3) the impact of environmental sustainability on food/beverage purchase decisions. Questions 2 and 3 were asked only from participants who stated environmental sustainability is important in question 1. Options provided for signals for environmentally sustainable products were recyclable packaging, minimal packaging, labeled organic, labeled locally grown, labeled sustainably sourced, and labeled non-genetically modified organisms (GMOs, not bioengineered). Poisson regression and logistic regressions were performed to assess associations. RESULTS: Of 1905 completers, 1059 (55.6%) answered that it was somewhat or very important that food products purchased/consumed were environmentally sustainable. Of those, 94% used ≥1 of the 6 signals to determine environmental sustainability when shopping. Some signals were selected despite little association with environmental sustainability (e.g., locally grown and non-GMO/not bioengineered). The number of signals consumers used was associated with education, race/ethnicity, health status, and the level of impact they reported that sustainability plays in their decisions. Associations between consumer characteristics and the use of different signals for environmental sustainability were heterogeneous. CONCLUSIONS: Even among consumers who value environmental sustainability in food products, specific signals used by different respondents varied across demographics and health characteristics.

Comparison of Pericapsular Nerve Group and Lateral Quadratus Lumborum Blocks for Analgesia after Primary Total Hip Arthroplasty: A Randomized Controlled Trial.

Introduction: The quadratus lumborum block (QLB) and the pericapsular nerve group (PENG) block both provide effective postoperative analgesia after hip surgery while minimizing impact on motor function. This study aimed to compare QLB and PENG in patients undergoing primary total hip arthroplasty. Methods: This superiority trial randomized patients scheduled for elective total hip arthroplasty to receive a lateral QLB or PENG with lateral femoral cutaneous nerve blocks for postoperative analgesia. Perioperative analgesic protocols were standardized. The primary outcome was postoperative cumulative opioid consumption at 72 hours. Secondary outcome was postoperative pain scores. Additional outcomes of interest included time to first ambulation, length of stay, patient reported outcome measures, and opioid-related side effects. Results: This trial consented and randomized 106 subjects and 101 were included in analysis: PENG (n=50), QLB (n=51). Mean (95% CI) opioid consumption (IV MME) in the first 72 hours did not differ between PENG [109.6 (93.6, 125.6)] and QL [92.3 (76.6, 107.9)] groups (p=0.129) There were no significant differences between treatment arms in average pain score, time to ambulation, distance ambulated, rate of same day discharge, or hospital length of stay. There were also no differences in patient reported outcomes using HOOS-JR and PROMIS-10 scores. Conclusion: Patients undergoing primary THA receiving preoperative PENG vs QLB had similar opioid consumption, pain scores, time to ambulation, and hospital length of stay. Both QL and PENG blocks are analgesic options in patients undergoing primary THA. Clinical Trials Registration: NCT05710107; www.ClinicalTrial.gov IRB Protocol ID: Pro00124880. Key message: Pericapsular nerve group (PENG) block may provide analgesia after hip arthroplasty and improve early functional recovery. This study evaluated postoperative opioid consumption in patients randomized to PENG or lateral quadratus lumborum block (QLB).Opioid consumption, pain scores, motor recovery, and functional outcome measures did not differ in patients randomized to PENG vs lateral QLB.PENG and lateral QLBs are analgesic options following total hip arthroplasty with similar rates of same day discharge.

Guilt by association: Plant-based foods can be incorporated into both healthy and unhealthy plant-based diet indices associated with coronary heart disease.

Background: One approach to test for differential associations between plant foods with health uses a scoring approach: foods categorized into animal or 'healthy' plant-based or 'unhealthy' plant-based groups to construct a plant-based diet index (PDI), healthy PDI (hPDI), and unhealthy PDI (uPDI). Objective: To evaluate robustness of associations between diet indices and incident coronary heart disease (CHD) risk when recategorizing food groups in indices. Methods: Using REasons for Geographic and Racial Differences in Stroke (REGARDS) data, we replicated a published use of the scoring approach. Using Cox proportional hazards regression, we assessed ramifications of the following on associations between diet indices and CHD risk: 1) reconfiguring foods within and among food groups, using potatoes as an example, 2) leave-one-out analysis for each of 12 plant-based food groups, and 3) agnostically redefining each food group as 'healthy' or 'unhealthy'. Results: Over 153,286 person-years of follow-up, there were 868 cases of CHD. Replication analyses did not reach statistical significance. General patterns of magnitude of hazard ratios (HRs) in replication and reconfiguration models were PDI HRs < hPDI HRs < uPDI HRs for women, and hPDI < PDI < uPDI for men. Five models reconfiguring potatoes resulted in small, varied differences in PDI, hPDI, and uPDI associations. Leave-one-out analyses resulted in greater variation of associations between indices and CHD. In agnostic models, each plant-based food group was classified in indices as 'healthy' and 'unhealthy' with statistically significant beneficial or deleterious associations with CHD. Averaged over 4,096 models, HRs' shifts were small when food groups were moved between 'healthy' and 'unhealthy'. Conclusion: Statistically significant associations between hPDI, uPDI, and PDI and incident CHD were not replicated. Small perturbations of the scoring approach had varied impacts on HRs. Agnostically constructing diet indices demonstrated the potential for guilt (or benefit) by association: any of the food groups we studied could be categorized with others in an index showing beneficial or deleterious associations.

Benefits of calorie restriction in mice are mediated via energy imbalance, not absolute energy or protein intake.

Caloric restriction (CR) results in reduced energy and protein intake, raising questions about protein restriction's contribution to CR longevity benefits. We kept ad libitum (AL)-fed male C57BL/6J mice at 27°C (AL27) and pair-fed (PF) mice at 22°C (22(PF27)). The 22(PF27) group was fed to match AL27 while restricted for calories due to cold-induced metabolism. The 22(PF27) mice had significantly lower body weight, lean mass, fat mass, leptin, IGF-1, and TNF-α levels than AL27 mice (p<0.001 for all). Manipulations over ~11 weeks resulted in significant differences in body temperature, physical activity, and expression of key genes linked to hunger in the hypothalamus. Survival was significantly greater in 22(PF27) compared to AL27 overall (p<0.001). CR in the context of equivalent energy and protein intake resulted in hormonal, metabolic, and physiological benefits and extended longevity. Hence, energy imbalance, rather than low energy or protein intake per se, mediates the benefits of CR.

Mixed responses to targeted therapy driven by chromosomal instability through p53 dysfunction and genome doubling.

The phenomenon of mixed/heterogenous treatment responses to cancer therapies within an individual patient presents a challenging clinical scenario. Furthermore, the molecular basis of mixed intra-patient tumor responses remains unclear. Here, we show that patients with metastatic lung adenocarcinoma harbouring co-mutations of EGFR and TP53, are more likely to have mixed intra-patient tumor responses to EGFR tyrosine kinase inhibition (TKI), compared to those with an EGFR mutation alone. The combined presence of whole genome doubling (WGD) and TP53 co-mutations leads to increased genome instability and genomic copy number aberrations in genes implicated in EGFR TKI resistance. Using mouse models and an in vitro isogenic p53-mutant model system, we provide evidence that WGD provides diverse routes to drug resistance by increasing the probability of acquiring copy-number gains or losses relative to non-WGD cells. These data provide a molecular basis for mixed tumor responses to targeted therapy, within an individual patient, with implications for therapeutic strategies.

Changes in opioid prescribing during the COVID-19 pandemic in England: an interrupted time-series analysis in the OpenSAFELY-TTP cohort.

BACKGROUND: The COVID-19 pandemic disrupted health-care delivery, including difficulty accessing in-person care, which could have increased the need for strong pharmacological pain relief. Due to the risks associated with overprescribing of opioids, especially to vulnerable populations, we aimed to quantify changes to measures during the COVID-19 pandemic, overall, and by key subgroups. METHODS: For this interrupted time-series analysis study conducted in England, with National Health Service England approval, we used routine clinical data from more than 20 million general practice adult patients in OpenSAFELY-TPP, which is a a secure software platform for analysis of electronic health records. We included all adults registered with a primary care practice using TPP-SystmOne software. Using interrupted time-series analysis, we quantified prevalent and new opioid prescribing before the COVID-19 pandemic (January, 2018-February, 2020), during the lockdown (March, 2020-March, 2021), and recovery periods (April, 2021-June, 2022), overall and stratified by demographics (age, sex, deprivation, ethnicity, and geographical region) and in people in care homes identified via an address-matching algorithm. FINDINGS: There was little change in prevalent prescribing during the pandemic, except for a temporary increase in March, 2020. We observed a 9·8% (95% CI -14·5 to -6·5) reduction in new opioid prescribing from March, 2020, with a levelling of the downward trend, and rebounding slightly after April, 2021 (4·1%, 95% CI -0·9 to 9·4). Opioid prescribing rates varied by demographics, but we found a reduction in new prescribing for all subgroups except people aged 80 years or older. Among care home residents, in April, 2020, parenteral opioid prescribing increased by 186·3% (153·1 to 223·9). INTERPRETATION: Opioid prescribing increased temporarily among older people and care home residents, likely reflecting use to treat end-of-life COVID-19 symptoms. Despite vulnerable populations being more affected by health-care disruptions, disparities in opioid prescribing by most demographic subgroups did not widen during the pandemic. Further research is needed to understand what is driving the changes in new opioid prescribing and its relation to changes to health-care provision during the pandemic. FUNDING: The Wellcome Trust, Medical Research Council, The National Institute for Health and Care Research, UK Research and Innovation, and Health Data Research UK.

Opposing roles of resident and infiltrating immune cells in the defense against Legionella longbeachae via IL-18R/IFN-γ/ROS axis in mice.

The immune response against Legionella longbeachae, a causative agent of the often-fatal Legionnaires' pneumonia, is poorly understood. Here, we investigated the specific roles of tissue-resident alveolar macrophages (AMs) and infiltrating phagocytes during infection with this pathogen. AMs were the predominant cell type that internalized bacteria 1 day after infection. A total of 3 and 5 days after infection, AM numbers were greatly reduced, whereas there was an influx of neutrophils and, later, monocyte-derived cells (MCs) into lung tissue. AMs carried greater numbers of viable L. longbeachae than neutrophils and MCs, which correlated with a higher capacity of L. longbeachae to translocate bacterial effector proteins required for bacterial replication into the AM cytosol. Cell ablation experiments demonstrated that AM promoted infection, whereas neutrophils and MC were required for efficient bacterial clearance. Interleukin (IL)-18 was important for interferon-γ production by IL-18R+ natural killer cells and T cells, which, in turn, stimulated reactive oxygen species-mediated bactericidal activity in neutrophils, resulting in the restriction of L. longbeachae infection. Ciliated bronchiolar epithelial cells also expressed IL-18R but did not play a role in IL-18-mediated L. longbeachae clearance. Our results have identified opposing innate functions of tissue-resident and infiltrating immune cells during L. longbeachae infection that may be manipulated to improve protective responses.

Colony environment and absence of brood enhance tolerance to a neonicotinoid in winter honey bee workers, Apis mellifera.

In eusocial insects, worker longevity is essential to ensure colony survival in brood-free periods. Trade-offs between longevity and other traits may render long-living workers in brood-free periods more susceptible to pesticides compared to short-lived ones. Further, colony environment (e.g., adequate nutrition) may enable workers to better cope with pesticides, yet data comparing long vs. short-living workers and the role of the colony environment for pesticide tolerance are scarce. Here, we show that long-living honey bee workers, Apis mellifera, are less susceptible to the neonicotinoid thiamethoxam than short-lived workers, and that susceptibility was further reduced when workers were acclimatized under colony compared to laboratory conditions. Following an OECD protocol, freshly-emerged workers were exposed to thiamethoxam in summer and winter and either acclimatized within their colony or in the laboratory. Mortality and sucrose consumption were measured daily and revealed that winter workers were significantly less susceptible than summer workers, despite being exposed to higher thiamethoxam dosages due to increased food consumption. Disparencies in fat body activity, which is key for detoxification, may explain why winter bees were less susceptible. Furthermore, colony acclimatization significantly reduced susceptibility towards thiamethoxam in winter workers likely due to enhanced protein nutrition. Brood absence and colony environment seem to govern workers' ability to cope with pesticides, which should be considered in risk assessments. Since honey bee colony losses occur mostly over winter, long-term studies assessing the effects of pesticide exposure on winter bees are required to better understand the underlying mechanisms.

Are Gait Patterns during In-Lab Running Representative of Gait Patterns during Real-World Training? An Experimental Study.

Biomechanical assessments of running typically take place inside motion capture laboratories. However, it is unclear whether data from these in-lab gait assessments are representative of gait during real-world running. This study sought to test how well real-world gait patterns are represented by in-lab gait data in two cohorts of runners equipped with consumer-grade wearable sensors measuring speed, step length, vertical oscillation, stance time, and leg stiffness. Cohort 1 (N = 49) completed an in-lab treadmill run plus five real-world runs of self-selected distances on self-selected courses. Cohort 2 (N = 19) completed a 2.4 km outdoor run on a known course plus five real-world runs of self-selected distances on self-selected courses. The degree to which in-lab gait reflected real-world gait was quantified using univariate overlap and multivariate depth overlap statistics, both for all real-world running and for real-world running on flat, straight segments only. When comparing in-lab and real-world data from the same subject, univariate overlap ranged from 65.7% (leg stiffness) to 95.2% (speed). When considering all gait metrics together, only 32.5% of real-world data were well-represented by in-lab data from the same subject. Pooling in-lab gait data across multiple subjects led to greater distributional overlap between in-lab and real-world data (depth overlap 89.3-90.3%) due to the broader variability in gait seen across (as opposed to within) subjects. Stratifying real-world running to only include flat, straight segments did not meaningfully increase the overlap between in-lab and real-world running (changes of <1%). Individual gait patterns during real-world running, as characterized by consumer-grade wearable sensors, are not well-represented by the same runner's in-lab data. Researchers and clinicians should consider "borrowing" information from a pool of many runners to predict individual gait behavior when using biomechanical data to make clinical or sports performance decisions.

Incidence and treatment of group A streptococcal infections during covid-19 pandemic and 2022 outbreak: retrospective cohort study in England using OpenSAFELY-TPP.

Objective: To investigate the effect of the covid-19 pandemic on the number of patients with group A streptococcal infections and related antibiotic prescriptions. Design: Retrospective cohort study in England using OpenSAFELY-TPP. Setting: Primary care practices in England that used TPP SystmOne software, 1 January 2018 to 31 March 2023, with the approval of NHS England. Participants: Patients registered at a TPP practice at the start of each month of the study period. Patients with missing data for sex or age were excluded, resulting in a population of 23 816 470 in January 2018, increasing to 25 541 940 by March 2023. Main outcome measures: Monthly counts and crude rates of patients with group A streptococcal infections (sore throat or tonsillitis, scarlet fever, and invasive group A streptococcal infections), and recommended firstline, alternative, and reserved antibiotic prescriptions linked with a group A streptococcal infection before (pre-April 2020), during, and after (post-April 2021) covid-19 restrictions. Maximum and minimum count and rate for each infectious season (time from September to August), as well as the rate ratio of the 2022-23 season compared with the last comparably high season (2017-18). Results: The number of patients with group A streptococcal infections, and antibiotic prescriptions linked to an indication of group A streptococcal infection, peaked in December 2022, higher than the peak in 2017-18. The rate ratios for monthly sore throat or tonsillitis (possible group A streptococcal throat infection), scarlet fever, and invasive group A streptococcal infection in 2022-23 relative to 2017-18 were 1.39 (95% confidence interval (CI) 1.38 to 1.40), 2.68 (2.59 to 2.77), and 4.37 (2.94 to 6.48), respectively. The rate ratio for prescriptions of first line, alternative, and reserved antibiotics to patients with group A streptococcal infections in 2022-23 relative to 2017-18 were 1.37 (95% CI 1.35 to 1.38), 2.30 (2.26 to 2.34), and 2.42 (2.24 to 2.61), respectively. For individual antibiotic prescriptions in 2022-23, azithromycin showed the greatest relative increase versus 2017-18, with a rate ratio of 7.37 (6.22 to 8.74). This finding followed a marked decrease in the recording of patients with group A streptococcal infections and associated prescriptions during the period of covid-19 restrictions where the maximum count and rates were lower than any minimum rates before the covid-19 pandemic. Conclusions: Recording of rates of scarlet fever, sore throat or tonsillitis, and invasive group A streptococcal infections, and associated antibiotic prescribing, peaked in December 2022. Primary care data can supplement existing infectious disease surveillance through linkages with relevant prescribing data and detailed analysis of clinical and demographic subgroups.

A paREDOX in the control of cholesterol biosynthesis: Does the NADPH sensor and E3 ubiquitin ligase MARCHF6 protect mammalian cells during oxidative stress by controlling sterol biosynthesis?

Sterols and the reductant nicotinamide adenine dinucleotide phosphate (NADPH), essential for eukaryotic life, arose because of, and as an adaptation to, rising levels of molecular oxygen (O2). Hence, the NADPH and O2-intensive process of sterol biosynthesis is inextricably linked to redox status. In mammals, cholesterol biosynthesis is exquisitely regulated post-translationally by multiple E3 ubiquitin ligases, with membrane associated Really Interesting New Gene (RING) C3HC4 finger 6 (MARCHF6) degrading at least six enzymes in the pathway. Intriguingly, all these MARCHF6-dependent enzymes require NADPH. Moreover, MARCHF6 is activated by NADPH, although what this means for control of cholesterol synthesis is unclear. Indeed, this presents a paradox for how NADPH regulates this vital pathway, since NADPH is a cofactor in cholesterol biosynthesis and yet, low levels of NADPH should spare cholesterol biosynthesis enzymes targeted by MARCHF6 by reducing its activity. We speculate MARCHF6 helps mammalian cells adapt to oxidative stress (signified by low NADPH levels) by reducing degradation of cholesterogenic enzymes, thereby maintaining synthesis of protective cholesterol.

Safety and efficacy of peptide receptor radionuclide therapy in neuroendocrine tumors: A single center experience.

Peptide receptor radionucleotide therapy (PRRT) with 177Lu-dotatate is widely used for the treatment of patients with neuroendocrine tumors (NETs). We analyzed data from 104 patients with NETs treated with 177Lu -dotatate at a US academic center between December 2017 and October 2020 to better understand patterns of long-term efficacy, safety, and toxicity in the real-world setting. 177Lu-dotatate (200 mCi) was administered every eight weeks for four doses. The most common sites of primary disease were small intestine NETs (n = 49, 47%), pancreatic NETs (n = 32, 31%), and lung NETs (n = 7, 7%). Twenty-seven percent had Ki-67 <3%, 49% had Ki-67 between 3-20%, and 13.5% had Ki-67 >20%. The cohort had been pretreated with a median of two prior lines of treatment. Forty percent had received prior liver-directed treatment. Seventy-four percent of patients completed all four doses of treatment. The objective response rate was 18%. The median time-to-treatment failure/death was significantly longer for small-bowel NETs when compared to pancreatic NETs (37.3 months vs. 13.2 months, p = 0.001). In a multivariate model, Ki-67, primary site, and liver tumor burden ≥50% were found to independently predict time-to-treatment failure/death. Around 40% of patients experienced adverse events of ≥grade 3 severity. Treatment-related adverse events leading to discontinuation of therapy happened in 10% of patients. Preexisting mesenteric/peritoneal disease was present in 33 patients; seven of these patients developed bowel-related toxicities including two grade 5 events. We also report two cases of delayed-onset minimal change nephrotic syndrome, which occurred 14 and 27 months after the last dose of PRRT. Lastly, we describe six patients who developed rapid tumor progression in the liver leading to terminal liver failure within 7.3 months from the start of PRRT, and identify potential risk factors associated with this occurrence, which will need further study.

Co-designing restrictive practice elimination: A systems thinking approach with mental health service users and practitioners in rural/regional Australia.

Elimination of restrictive practices (physical/mechanical restraint and seclusion) from adult acute mental health care services has been demanded internationally for many decades. This study aimed to: (1) Identify priority issues in the elimination of and use of alternative approaches to restrictive practices (seclusion and physical/mechanical restraint) in rural/regional acute adult mental healthcare services, as told by mental healthcare service users and practitioners, (2) identify the community-based, system-level feedback loops that enhance or reduce the use of restrictive practices and viable alternatives and, (3) identify potential action areas to improve system structures to increase regional mental healthcare services' ability to eliminate restrictive practices and use alternative approaches. Group model building (GMB) workshops were held with a small group (n = 9) of mental healthcare practitioners and service users with lived experience of restrictive practice use. This participatory approach enables exploration and visual mapping of local structures causing behaviour patterns of practitioner and service user concern over time - in this case, the barriers, and enablers to alternative approaches to restrictive practices in adult acute mental healthcare services within the Geelong-Barwon region. This is the first study that specifically applies GMB in the discussion of the elimination of restrictive practices in mental health in the non-metropolitan regional/rural context. Participants identified four key priorities in relation to eliminating restrictive practices: (1) self-advocacy, (2) continuity of care, (3) early intervention, and (4) safety for all. The study findings were distilled into a novel preliminary set of mental healthcare practitioner and service user action ideas.

A protocol of a pilot randomised trial (Action-RESPOND) to support rural and regional communities with implementing community-based systems thinking obesity prevention initiatives.

BACKGROUND: Over a quarter of children aged 2-17 years living in Australia are overweight or obese, with a higher prevalence reported in regional and remote communities. Systems thinking approaches that seek to support communities to generate and implement locally appropriate solutions targeting intertwined environmental, political, sociocultural, and individual determinants of obesity have the potential to ameliorate this. There have however been reported challenges with implementation of such initiatives, which may be strengthened by incorporating implementation science methods. METHODS: This pilot randomised controlled trial protocol outlines the development and proposed evaluation of a multicomponent implementation strategy (Action-RESPOND). to increase the implementation of community-based systems thinking child obesity prevention initiatives The target of this intervention is ten rural and regional communities (or local government areas as the unit of allocation) within Northeast Victoria who were participants in a whole-of-systems intervention (RESPOND). Action-RESPOND builds on this intervention by assessing the impact of offering additional implementation strategies to five communities relative to usual care. The development of the multicomponent implementation strategy was informed by the Promoting Action on Research Implementation in Health Services (PARIHS) framework and consists of seven implementation strategies primarily delivered via 'facilitation' methods. Implementation strategies aimed to ensure initiatives implemented are i) evidence-based, ii) address community's specific needs and iii) are suitable for local context. Strategies also aimed to increase the community's capacity to implement, through iv) improving the health promotion team's implementation knowledge and skills, fostering v) leadership, vi) physical resources and vii) community culture to drive implementation. The feasibility, acceptability, potential impact, and cost of the strategy will be assessed at baseline and follow up using surveys administered to key representatives within the community and internal records maintained by the research team. DISCUSSION: By leveraging an existing community-based whole-of-systems intervention, Action-RESPOND offers a unique opportunity to collect pilot feasibility and early empirical data on how to apply implementation and systems science approaches to support obesity prevention in rural and regional communities in Victoria.