Developing and Testing the Usability of a Novel Child Abuse Clinical Decision Support System: Mixed Methods Study.

BACKGROUND: Despite the impact of physical abuse on children, it is often underdiagnosed, especially among children evaluated in emergency departments (EDs). Electronic clinical decision support (CDS) can improve the recognition of child physical abuse. OBJECTIVE: We aimed to develop and test the usability of a natural language processing-based child abuse CDS system, known as the Child Abuse Clinical Decision Support (CA-CDS), to alert ED clinicians about high-risk injuries suggestive of abuse in infants' charts. METHODS: Informed by available evidence, a multidisciplinary team, including an expert in user design, developed the CA-CDS prototype that provided evidence-based recommendations for the evaluation and management of suspected child abuse when triggered by documentation of a high-risk injury. Content was customized for medical versus nursing providers and initial versus subsequent exposure to the alert. To assess the usability of and refine the CA-CDS, we interviewed 24 clinicians from 4 EDs about their interactions with the prototype. Interview transcripts were coded and analyzed using conventional content analysis. RESULTS: Overall, 5 main categories of themes emerged from the study. CA-CDS benefits included providing an extra layer of protection, providing evidence-based recommendations, and alerting the entire clinical ED team. The user-centered, workflow-compatible design included soft-stop alert configuration, editable and automatic documentation, and attention-grabbing formatting. Recommendations for improvement included consolidating content, clearer design elements, and adding a hyperlink with additional resources. Barriers to future implementation included alert fatigue, hesitancy to change, and concerns regarding documentation. Facilitators of future implementation included stakeholder buy-in, provider education, and sharing the test characteristics. On the basis of user feedback, iterative modifications were made to the prototype. CONCLUSIONS: With its user-centered design and evidence-based content, the CA-CDS can aid providers in the real-time recognition and evaluation of infant physical abuse and has the potential to reduce the number of missed cases.

Correction: Developing and Testing the Usability of a Novel Child Abuse Clinical Decision Support System: Mixed Methods Study.

[This corrects the article DOI: 10.2196/51058.].

Voluntary risk mitigation behaviour can reduce impact of SARS-CoV-2: a real-time modelling study of the January 2022 Omicron wave in England.

BACKGROUND: Predicting the likely size of future SARS-CoV-2 waves is necessary for public health planning. In England, voluntary "plan B" mitigation measures were introduced in December 2021 including increased home working and face coverings in shops but stopped short of restrictions on social contacts. The impact of voluntary risk mitigation behaviours on future SARS-CoV-2 burden is unknown. METHODS: We developed a rapid online survey of risk mitigation behaviours ahead of the winter 2021 festive period and deployed in two longitudinal cohort studies in the UK (Avon Longitudinal Study of Parents and Children (ALSPAC) and TwinsUK/COVID Symptom Study (CSS) Biobank) in December 2021. Using an individual-based, probabilistic model of COVID-19 transmission between social contacts with SARS-CoV-2 Omicron variant parameters and realistic vaccine coverage in England, we predicted the potential impact of the SARS-CoV-2 Omicron wave in England in terms of the effective reproduction number and cumulative infections, hospital admissions and deaths. Using survey results, we estimated in real-time the impact of voluntary risk mitigation behaviours on the Omicron wave in England, if implemented for the entire epidemic wave. RESULTS: Over 95% of survey respondents (NALSPAC = 2686 and NTwins = 6155) reported some risk mitigation behaviours, with vaccination and using home testing kits reported most frequently. Less than half of those respondents reported that their behaviour was due to "plan B". We estimate that without risk mitigation behaviours, the Omicron variant is consistent with an effective reproduction number between 2.5 and 3.5. Due to the reduced vaccine effectiveness against infection with the Omicron variant, our modelled estimates suggest that between 55% and 60% of the English population could be infected during the current wave, translating into between 12,000 and 46,000 cumulative deaths, depending on assumptions about severity and vaccine effectiveness. The actual number of deaths was 15,208 (26 November 2021-1 March 2022). We estimate that voluntary risk reduction measures could reduce the effective reproduction number to between 1.8 and 2.2 and reduce the cumulative number of deaths by up to 24%. CONCLUSIONS: Predicting future infection burden is affected by uncertainty in disease severity and vaccine effectiveness estimates. In addition to biological uncertainty, we show that voluntary measures substantially reduce the projected impact of the SARS-CoV-2 Omicron variant but that voluntary measures alone would be unlikely to completely control transmission.

Evaluation of multigenerational effects of 2-ethylhexyl 4-hydroxybenzoate in Japanese medaka.

The Japanese medaka (Oryzias latipes) extended one-generation reproduction test (MEOGRT) (Test Guideline 890.2200) is a Tier 2 test within the Endocrine Disruptor Screening Program of the US Environmental Protection Agency (US EPA). A modified MEOGRT was used to evaluate multigenerational effects of 2-ethylhexyl 4-hydroxybenzoate (2-EHHB) under flow-through conditions starting with adults (parent generation, F0) through a 3-week reproductive phase of the second generation (F2). Fish were exposed to one of five 2-EHHB test concentrations or a dechlorinated tap water control. Fecundity was affected at the lowest exposure (5.32 µg/L) and greater sensitivity occurred in the F1 and F2 generations. Percent fertility was also diminished from no effect level observed in the F0 generation to 101 and 48.8 µg/L in the F1 and F2 generations, respectively. Growth indices were decreased for F0 adult females and F1 subadults and adults at 48.8 µg/L 2-EHHB. Histopathologic examination of gonads, liver, kidney, and thyroid yielded possible delayed reproductive tract development in F1 subadult males, masculinization of the renal phenotype in F1 adult females (renal tubular eosinophilia) and reduced hepatic energy storage (liver glycogen vacuoles) in F1 (11.3 and 48.8 µg/L) and F2 (48.8 and 101 µg/L) males and females, respectively. Endocrine-related findings included a decrease in anal fin papillae in F2 adult males at 101 µg/L. Results of this study demonstrate effects on growth, development, and reproduction that may be mediated by endocrine (weak estrogenic) and nonendocrine mechanisms. Duration of the MEOGRT should not be routinely extended beyond the OCSPP 890 guideline study design.

The inhibitory effect of copper, zinc, and manganese on Legionella longbeachae and other Legionella spp. in vitro.

Legionella longbeachae is an important cause of Legionnaires' disease in Australasia and is associated with exposure to potting soils. Our aim was to identify ways to reduce the load of L. longbeachae in potting soils. Inductively-coupled plasma optical emission spectrometry (ICP-OES) of an all-purpose potting mix showed copper (Cu) concentrations (mg/kg) range from 15.8 to 23.6. Zinc (Zn) and manganese (Mn) were significantly higher than Cu ranging from 88.6-106 to 171-203, respectively. Minimal inhibitory and bactericidal concentrations of 10 salts used in the horticultural industry were determined for Legionella species in buffered yeast extract (BYE) broth. For L. longbeachae (n = 9) the median (range) minimum inhibitory concentration (MIC) (mg/L) of copper sulfate was 31.25 (15.6-31.25), zinc sulfate 31.25 (7.81-31.25), and manganese sulfate 31.25 (7.81-62.5). The MIC and minimum bactericidal concentration (MBC) were within one dilution of each other. Susceptibility to Cu and Zn salts increased as the concentration of pyrophosphate iron in the media decreased. The MIC values for these three metals against Legionella pneumophila (n = 3) and Legionella micdadei (n = 4) were similar. Combinations of Cu, Zn, and Mn were additive. Legionella longbeachae has similar susceptibility to Cu and other metal ions in comparison to L. pneumophila.

Dexmedetomidine: A Sedation Alternative in the Intensive Care Setting.

In the last 20 years, the occurrences of drug shortages have increased in frequency as well as duration before returning to the mainstream market. This has prompted intensive care unit nurses and medical staff to seek alternate medication infusion options that provide safe yet effective sedation for patients admitted to intensive care units across the country. Dexmedetomidine (PRECEDEX) emerged in 1999 after the Federal Drug Administration approved it for intensive care use but was quickly embraced by anesthesia providers as it rendered patients undergoing procedures or surgery with adequate analgesia and sedation. Dexmedetomidine (PRECEDEX) continued to maintain patients who required short-term intubation and mechanical ventilation with adequate sedation throughout the entire perioperative period. With patients remaining hemodynamically stable in the initial postoperative period, critical care nurses embraced the use of dexmedetomidine (PRECEDEX) in the intensive care unit setting. As dexmedetomidine (PRECEDEX) gained popularity, it has been used to help manage multiple disease processes such as delirium, agitation, alcoholic withdrawal, and anxiety. Dexmedetomidine (PRECEDEX) has been indicated to be a safer alternative to benzodiazepines, narcotics, or propofol (Diprivan), while providing adequate sedation and allowing patients to maintain hemodynamic stability.

Transferring critical pediatric patients from emergency department to intensive care: A quality improvement initiative.

BACKGROUND: Transfer of care, moving hospitalized patients between care areas, is a critical point of vulnerability for healthcare organizations. Patient information handoff is an essential activity occurring frequently in hospital environments. Poor communication has been linked with adverse events and poor patient outcomes. This evidence-based quality project aimed to enhance the handoff process between the Emergency Department (ED) and Pediatric Intensive Care Unit (PICU) by standardizing transfer of care steps. This was accomplished through customizing a reporting tool to contain all the information the receiving department deemed necessary for safe patient care. METHODS: A customized situation, background, assessment, recommendation (SBAR) form handoff tool was developed for ED to PICU transfers. This SBAR tool included information that PICU nurses identified as critical to transfer of care. Nurse perceptions were surveyed pre- and post-implementation. Patient safety event reports were tracked to evaluate events related to transfer of care before and after the practice change. FINDINGS: An increased number of PICU nurses agreed the customized handoff tool was complete and organized. Additionally, more nurses agreed that handoff gave all information needed to safely care for critically ill patients transferred from the ED. Lastly, bedside patient checks increased, and patient safety events related to transfer of care decreased. DISCUSSION: This project demonstrated that implementation of a standardized transfer of care process coupled with a customized handoff tool increased PICU nurse perceptions that handoff was organized, and all information needed to safely care for critically ill patients was conveyed. APPLICATION TO PRACTICE: Transfer of care processes between the ED and PICU should be standardized. The use of customized tools may improve information exchange between nurses and ensure that all vital patient information is communicated.

Neferine Targets the Oncogenic Characteristics of Androgen-Dependent Prostate Cancer Cells via Inducing Reactive Oxygen Species.

Castration resistance poses a significant challenge in the management of advanced prostate cancer (PCa), with androgen deprivation therapy (ADT) or chemotherapy being the primary treatment options. However, these approaches often lead to significant side effects and the development of therapeutic resistance. Therefore, it is crucial to explore novel treatment options that can efficiently target PCa, improve patient survival, and enhance their quality of life. Neferine (Nef), a bioactive compound derived from plants, has emerged as a promising candidate for cancer treatment due to its ability to induce apoptosis, autophagy, and cell cycle arrest. In this study, we investigated the potential anticancer effects of Nef in androgen receptor (AR)-positive LNCaP and VCaP cells, representative models of androgen-dependent PCa. Our findings demonstrate that Nef effectively inhibits cell growth, proliferation, and the tumorigenic potential of androgen-dependent PCa cells. Furthermore, Nef treatment resulted in the excessive production of reactive oxygen species (ROS), leading to the activation of key markers of autophagy and apoptosis. These results suggest that Nef has the potential to target the oncogenic characteristics of androgen-dependent PCa cells by exploiting the potency of ROS and inducing autophagy and apoptosis in AR-positive PCa cells. These findings shed light on the therapeutic potential of Nef as a novel treatment option with reduced side effects for androgen-dependent prostate cancer. Further investigations are warranted to assess its efficacy and safety in preclinical and clinical settings.

Land degradation neutrality: Testing the indicator in a temperate agricultural landscape.

Land degradation directly affects around 25% of land globally, undermining progress on most of the UN Sustainable Development Goals (SDG), particularly target 15.3. To assess land degradation, SDG indicator 15.3.1 combines sub-indicators of productivity, soil carbon and land cover. Over 100 countries have set Land Degradation Neutrality (LDN) targets. Here, we demonstrate application of the indicator for a well-established agricultural landscape using the case study of Great Britain. We explore detection of degradation in such landscapes by: 1) transparently evaluating land cover transitions; 2) comparing assessments using global and national data; 3) identifying misleading trends; and 4) including extra sub-indicators for additional forms of degradation. Our results demonstrate significant impacts on the indicator both from the land cover transition evaluation and choice or availability of data. Critically, we identify a misleading improvement trend due to a trade-off between improvement detected by the productivity sub-indicator, and 30-year soil carbon loss trends in croplands (11% from 1978 to 2007). This carbon loss trend would not be identified without additional data from Countryside Survey (CS). Thus, without incorporating field survey data we risk overlooking the degradation of regulating and supporting ecosystem services (linked to soil carbon), in favour of signals from improving provisioning services (productivity sub-indicator). Relative importance of these services will vary between socioeconomic contexts. Including extra sub-indicators for erosion or critical load exceedance, as additional forms of degradation, produced a switch from net area improving (9%) to net area degraded (58%). CS data also identified additional degradation for soil health, including 44% arable soils exceeding bulk density thresholds and 35% of CS squares exceeding contamination thresholds for metals.

Monoclonal Antibodies and Invasive Aspergillosis: Diagnostic and Therapeutic Perspectives.

Invasive aspergillosis (IA) is a life-threatening fungal disease that causes high morbidity and mortality in immunosuppressed patients. Early and accurate diagnosis and treatment of IA remain challenging. Given the broad range of non-specific clinical symptoms and the shortcomings of current diagnostic techniques, most patients are either diagnosed as "possible" or "probable" cases but not "proven". Moreover, because of the lack of sensitive and specific tests, many high-risk patients receive an empirical therapy or a prolonged treatment of high-priced antifungal agents, leading to unnecessary adverse effects and a high risk of drug resistance. More precise diagnostic techniques alongside a targeted antifungal treatment are fundamental requirements for reducing the morbidity and mortality of IA. Monoclonal antibodies (mAbs) with high specificity in targeting the corresponding antigen(s) may have the potential to improve diagnostic tests and form the basis for novel IA treatments. This review summarizes the up-to-date application of mAb-based approaches in assisting IA diagnosis and therapy.

Hydrogen Sulfide and Substance P Levels in Patients with Escherichia coli and Klebsiella pneumoniae Bacteraemia.

Hydrogen sulfide (H2S) and substance P (SP) are known from animal models and in vitro studies as proinflammatory mediators. In this study, peripheral blood concentrations of H2S and SP were measured in patients with Escherichia coli or Klebsiella pneumoniae bacteraemia. Fifty patients were recruited from general wards at Christchurch Hospital, during 2020-2021. Samples from age- and sex-matched healthy subjects previously recruited as controls for studies of cardiovascular disease were used as controls. The concentrations of H2S were higher than controls on day 0, day 1, and day 2, and SP was higher than controls on all 4 days. The concentrations of H2S were highest on day 0, whereas SP concentrations were higher on day 2 than other days. Interleukin-6 and C-reactive protein were significantly higher on day 0 and day 1, respectively. The concentrations of H2S and SP did not differ between 15 non-septic (SIRS 0-1) and the 35 septic subjects (SIRS ≥ 2). Substance P concentrations were higher in subjects with abdominal infection than urinary tract infections on day 0 (p = 0.0002) and day 1 (p = 0.0091). In conclusion, the peak H2S concentrations precede the SP peak in patients with Gram-negative bacteraemia, but this response varies with the site of infection.

A 'debt' based approach to land degradation as an indicator of global change.

We propose a way to synthesize different approaches to globally map land degradation by combining vegetation and soil indicators into a consistent framework for assessing land degradation as an environmental 'debt'. our combined approach reveals a broader lens for land degradation through global change, in particular, identifying hot-spots for the different kinds of land degradation.

Perspectives of Aging Adults Who Frequently Seek Emergency Department Care.

BACKGROUND: The number of people managing chronic conditions is growing with the rapidly aging population. Visits to the emergency department are steadily rising, but little is known about the rationale of those seeking emergent care. AIMS: The goal of this study was to better understand, from the patients' perspective, the reasons for seeking care in an emergency department setting. DESIGN: A qualitative descriptive design was used to interview aging adults with at least two chronic conditions who made three or more visits to the emergency department within a year. PARTICIPANTS/SUBJECTS: The eight-person sample was 88% female and 75% white, with an average age of 54 years. METHODS: Participant interviews were conducted with a semistructured interview guide. Conventional content analysis was used to examine words and phrases in professionally transcribed documents. Qualitative methods for testing and confirming conclusions were performed. RESULTS: We discovered that aging adults visit the emergency department to seek relief from unrelenting pain and to overcome barriers to receiving treatment for pain in ambulatory settings. Participants reported feeling judged when seeking emergency department care for pain management. CONCLUSIONS: Participants described emergency department care as the only option in response to several barriers to healthcare access. Most commonly, emergency department care was sought when relief from persistent or acute pain was required. One way to reduce strain on EDs from pain-related visits is to manage patients with persistent pain more proactively in their community environment.

Two Monoclonal Antibodies That Specifically Recognize Aspergillus Cell Wall Antigens and Can Detect Circulating Antigens in Infected Mice.

Invasive aspergillosis (IA) is a life-threatening disease mainly caused by Aspergillus fumigatus and Aspergillus flavus. Early diagnosis of this condition is crucial for patient treatment and survival. As current diagnostic techniques for IA lack sufficient accuracy, we have raised two monoclonal antibodies (1D2 and 4E4) against A. fumigatus cell wall fragments that may provide a platform for a new diagnostic approach. The immunoreactivity of these antibodies was tested by immunofluorescence and ELISA against various Aspergillus and Candida species in vitro and by immunohistochemistry in A. fumigatus infected mouse tissues. Both monoclonal antibodies (mAbs) showed intensive fluorescence with the hyphae wall of A. fumigatus and A. flavus, but there was no staining with other Aspergillus species or Candida species. Both mAbs also showed strong immunoreactivity to the cell wall of A. fumigatus hyphae in the infected liver, spleen and kidney of mice with IA. The antigens identified by 1D2 and 4E4 might be glycoproteins and the epitopes are most likely a protein or peptide rather than a carbohydrate. An antibody-based antigen capture ELISA detected the extracellular antigens released by A. fumigatus, A. flavus, A. niger and A. terreus, but not in Candida species. The antigen could be detected in the plasma of mice after 48 h of infection by double-sandwich ELISA. In conclusion, both 1D2 and 4E4 mAbs are potentially promising diagnostic tools to investigate invasive aspergillosis.

Enhancement of Culture of Legionella longbeachae from Respiratory Samples by Use of Immunomagnetic Separation and Antimicrobial Decontamination.

Legionella longbeachae is the commonest Legionella species identified in patients with community-acquired pneumonia in New Zealand. Isolation of the organism on culture is the gold standard for the diagnosis of Legionnaires disease, but it has poor sensitivity (40%) compared with quantitative PCR (qPCR). We have developed a selective decontamination process using glycine, vancomycin, polymyxin, and cycloheximide (GVPC) with immunomagnetic separation (IMS) for culturing L. longbeachae A polyclonal antibody specific for L. longbeachae was produced from New Zealand White rabbits and coupled to tosyl-activated magnetic beads. Stored L. longbeachae qPCR-positive respiratory samples were retrieved from -80°C storage for testing. One portion of test samples was mixed with GVPC and the antibody bead complex, separated, washed, and cultured on modified Wadowsky and Yee agar (MWY) agar. Another portion was exposed to HCl-KCl acidic buffer (pH 2.2) before incubation on MWY agar. qPCR used probes specific for the ITS (internal transcribed spacer) region of the L. longbeachae genome. Cultures were positive in 10/53 (19%) samples after acid wash and 26/53 (49%) after GVPC-IMS (P = 0.001). Growth of contaminants was rare. The mean qPCR threshold cycle values were lower in culture-positive samples after acid wash than in the culture-negative samples (mean, 29.9 versus 34.8; difference, 4.9; 95% confidence interval [CI], ±2.9; P = 0.001) but not after GVPC-IMS (mean, 33.0 versus 34.7; difference, 1.7; 95% CI, ±2.48; P = 0.16). The sensitivity of culture for L. longbeachae in respiratory specimens may be improved by using GVPC-IMS rather than acid wash for decontamination, but this should be confirmed in a prospective study of fresh specimens.

Fragmentation and thresholds in hydrological flow-based ecosystem services.

Loss and fragmentation of natural land cover due to expansion of agricultural areas is a global issue. These changes alter the configuration and composition of the landscape, particularly affecting those ecosystem services (benefits people receive from ecosystems) that depend on interactions between landscape components. Hydrological mitigation describes the bundle of ecosystem services provided by landscape features such as woodland that interrupt the flow of runoff to rivers. These services include sediment retention, nutrient retention and mitigation of overland water flow. The position of woodland in the landscape and the landscape topography are both important for hydrological mitigation. Therefore, it is crucial to consider landscape configuration and flow pathways in a spatially explicit manner when examining the impacts of fragmentation. Here we test the effects of landscape configuration using a large number (>7,000) of virtual landscape configurations. We created virtual landscapes of woodland patches within grassland, superimposed onto real topography and stream networks. Woodland patches were generated with user-defined combinations of patch number and total woodland area, placed randomly in the landscape. The Ecosystem Service model used hydrological routing to map the "mitigated area" upslope of each woodland patch. We found that more fragmented woodland mitigated a greater proportion of the catchment. Larger woodland area also increased mitigation, however, this increase was nonlinear, with a threshold at 50% coverage, above which there was a decline in service provision. This nonlinearity suggests that the benefit of any additional woodland depends on two factors: the level of fragmentation and the existing area of woodland. Edge density (total edge of patches divided by area of catchment) was the best single metric in predicting mitigated area. Distance from woodland to stream was not a significant predictor of mitigation, suggesting that agri-environment schemes planting riparian woodland should consider additional controls such as the amount of fragmentation in the landscape. These findings highlight the potential benefits of fragmentation to hydrological mitigation services. However, benefits for hydrological services must be balanced against any negative effects of fragmentation or habitat loss on biodiversity and other services.

Zones of influence for soil organic matter dynamics: A conceptual framework for data and models.

Soil organic matter (SOM) is an indicator of sustainable land management as stated in the global indicator framework of the United Nations Sustainable Development Goals (SDG Indicator 15.3.1). Improved forecasting of future changes in SOM is needed to support the development of more sustainable land management under a changing climate. Current models fail to reproduce historical trends in SOM both within and during transition between ecosystems. More realistic spatio-temporal SOM dynamics require inclusion of the recent paradigm shift from SOM recalcitrance as an 'intrinsic property' to SOM persistence as an 'ecosystem interaction'. We present a soil profile, or pedon-explicit, ecosystem-scale framework for data and models of SOM distribution and dynamics which can better represent land use transitions. Ecosystem-scale drivers are integrated with pedon-scale processes in two zones of influence. In the upper vegetation zone, SOM is affected primarily by plant inputs (above- and belowground), climate, microbial activity and physical aggregation and is prone to destabilization. In the lower mineral matrix zone, SOM inputs from the vegetation zone are controlled primarily by mineral phase and chemical interactions, resulting in more favourable conditions for SOM persistence. Vegetation zone boundary conditions vary spatially at landscape scales (vegetation cover) and temporally at decadal scales (climate). Mineral matrix zone boundary conditions vary spatially at landscape scales (geology, topography) but change only slowly. The thicknesses of the two zones and their transport connectivity are dynamic and affected by plant cover, land use practices, climate and feedbacks from current SOM stock in each layer. Using this framework, we identify several areas where greater knowledge is needed to advance the emerging paradigm of SOM dynamics-improved representation of plant-derived carbon inputs, contributions of soil biota to SOM storage and effect of dynamic soil structure on SOM storage-and how this can be combined with robust and efficient soil monitoring.