Using National Public Health Accreditation to Explore Quality Improvement and Performance Management in Small Local Health Departments.

CONTEXT: This article focuses on 4 small local health departments (LHDs) that were in the process of seeking Public Health Accreditation Board (PHAB) reaccreditation or Pathways Recognition using PHAB Standards & Measures Version 2022. OBJECTIVE: The objective of this study was to explore the experiences of 4 small LHDs related to Quality Improvement (QI) and Performance Management (PM) in their pursuit of PHAB reaccreditation or Pathways Recognition. DESIGN: A team of researchers conducted 22 qualitative interviews with health department leaders and staff. Findings relative to QI/PM represent an embedded case study since they were part of a larger investigation. SETTING: The research team conducted interviews remotely with health departments located in the West and Midwest. PARTICIPANTS: Participants included adults at least 18 years old and employed in 1 of 4 health departments. MAIN OUTCOME MEASURES: Emergent themes from this qualitative investigation included using QI/PM tracking systems, building staff buy-in for QI/PM, integrating QI/PM into daily work, and advice for other health departments regarding QI/PM. RESULTS: Participants suggested that tracking systems helped them manage QI/PM processes. Staff buy-in for QI/PM was strengthened by building a sense of ownership of the process and connecting improvement processes to outcomes. Health departments integrated QI/PM into daily work by leadership modeling and communicating expectations. Advice for other health departments included finding a QI system that was easy to follow and recognizing the role of QI/PM in improving performance to better support the wellbeing of the community. CONCLUSIONS: QI/PM are important tools for health department effectiveness. Participants affirmed that the primary purposes of QI/PM are to enhance internal processes and improve community health outcomes. Study findings demonstrate how 4 small health departments integrated QI/PM into their public health practice.

Comparing the Diagnostic Yield of Germline Exome Versus Panel Sequencing in the Diverse Population of the Texas KidsCanSeq Pediatric Cancer Study.

PURPOSE: To evaluate the relative diagnostic yield of clinical germline genomic tests in a diverse pediatric cancer population. PATIENTS AND METHODS: The KidsCanSeq study enrolled pediatric cancer patients across six sites in Texas. Germline analysis included both exome sequencing and a therapy-focused pediatric cancer gene panel. The results were categorized by participants demographics, the presence of pathogenic or likely pathogenic (P/LP) variants, and variants of uncertain significance (VUS) in cancer predisposition genes (CPGs). Pediatric actionable CPGs were defined as those with cancer surveillance recommendations during childhood. RESULTS: Cancer P/LP variants were reported by at least one platform in 103 of 578 (17.8%) participants of which 76 were dominant cancer genes (13.1%) with no significant differences by self-described race or Hispanic ethnicity. However, the proportion of participants with VUS was greater in Asian and African American participants (P = .0029). Diagnostic yield was 16.6% for exome versus 8.5% for panel (P < .0001) with 42 participants with concordant germline results. Exome-only results included P/LP variants in 30 different CPGs in 54 participants, whereas panel-only results included seven participants with a copy number or structural P/LP variants in CPGs. There was no significant difference in diagnostic yield limited to pediatric actionable CPGs (P = .6171). CONCLUSION: Approximately 18% of a diverse pediatric cancer population had germline diagnostic findings with 50% of P/LP variants reported by only one platform because of CPGs not on the targeted panel and copy number variants (CNVs)/rearrangements not reported by exome. Although diagnostic yields were similar in this diverse population, increases in VUS results were observed in Asian and African American populations. Given the clinical significance of CNVs/rearrangements in this cohort, detection is critical to optimize germline analysis of pediatric cancer populations.

Benchmarking soil organic carbon (SOC) concentration provides more robust soil health assessment than the SOC/clay ratio at European scale.

Increasing soil organic carbon (SOC) confers benefits to soil health, biodiversity, underpins carbon sequestration and ameliorates land degradation. One recommendation is to increase SOC such that the SOC to clay ratio (SOC/clay) exceeds 1/13, yet normalising SOC levels based on clay alone gives misleading indications of soil structure and the potential to store additional carbon. Building on work by Poeplau & Don (2023) to benchmark observed against predicted SOC, we advance an alternative indicator: the ratio between observed and "typical" SOC (O/T SOC) for pan-European application. Here, "typical" SOC is the average concentration in different pedo-climate zones, PCZs (which, unlike existing SOC indicators, incorporate land cover and climate, alongside soil texture) across Europe, determined from mineral (<20 % organic matter) topsoils (0-20 cm) sampled during 2009-2018 in LUCAS, Europe's largest soil monitoring scheme (n = 19,855). Regression tree modelling derived 12 PCZs, with typical SOC values ranging 5.99-39.65 g kg-1. New index classes for comparison with SOC/clay grades were established from the quartiles of each PCZ's O/T SOC distribution; these were termed: "Low" (below the 25th percentile), "Intermediate" (between the 25th and 50th percentiles), "High" (between the 50th and 75th percentiles), and "Very high" (above the 75th percentile). Compared with SOC/clay, O/T SOC was less sensitive to clay content, land cover, and climate, less geographically skewed, and better reflected differences in soil porosity and SOC stock, supporting 2 EU Soil Health Mission objectives (consolidating SOC stocks; improving soil structure for crops and biota). These patterns held for 2 independent datasets, and O/T SOC grades were sensitive enough to reflect land management differences across several long-term field experiments. O/T SOC used in conjunction with several other physical, chemical and biological soil health indicators can help support the EU Soil Monitoring Law and achieve several United Nations Sustainable Development Goals.

The inhibitory effect of copper, zinc, and manganese on Legionella longbeachae in potting mix leachate.

Legionella longbeachae is the leading cause of Legionnaires' disease (LD) in Australasia and has been linked to exposure to compost and potting soils. Adding antimicrobial metal ions such as copper (Cu2+), zinc (Zn2+), and manganese (Mn2+) to potting soils may reduce the load of L. longbeachae bacteria and infection risk. Baseline concentrations of metal ions in leachate from peat, bark dust, bagging base, and an all-purpose potting soil were: iron 0.40-0.99 µg/ml, Cu of 0.003-0.03 µg/ml, Zn 0.01-0.06 µg/ml and Mn 0.11-0.29 µg/ml. Addition of Cu2+ ions to leachate reduced L. longbeachae viability in a concentration dependent manner. A similar effect was seen in potting soil with Zn2+ and Mn2+ but 10-fold higher concentrations were needed. These metal ions have potential to reduce the load of L. longbeachae in potting soils but toxicity in plants needs to be determined.

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.].

Co-located ecological data for exploring top- and subsoil carbon dynamics across grassland-woodland contrasts.

Soil organic carbon (SOC) is a soil health indicator and understanding dynamics changing SOC stocks will help achieving net zero goals. Here we present four datasets featuring 11,750 data points covering co-located aboveground and below-ground metrics for exploring ecosystem SOC dynamics. Five sites across England with an established land use contrast, grassland and woodland next to each other, were rigorously sampled for aboveground (n = 109), surface (n = 33 soil water release curves), topsoil, and subsoil metrics. Commonly measured soil metrics were analysed in five soil increments for 0-1 metre (n = 4550). Less commonly measured soil metrics which were assumed to change across the soil profile were measured on a subset of samples only (n = 3762). Additionally, we developed a simple method for soil organic matter fractionation using density fractionation which is part of the less common metrics. Finally, soil metrics which may impact SOC dynamics, but with less confidence as to their importance across the soil profile were only measured on topsoil (~5-15 cm = mineral soil) and subsoil (below 50 cm) samples (n = 2567).

Detection of SARS-CoV-2-specific mucosal antibodies in saliva following concomitant COVID-19 and influenza vaccination in the ComFluCOV trial.

The ComFluCOV trial randomized 679 participants to receive an age-appropriate influenza vaccine, or placebo, alongside their second COVID-19 vaccine. Concomitant administration was shown to be safe, and to preserve systemic immune responses to both vaccines. Here we report on a secondary outcome of the trial investigating SARS-CoV-2-specific mucosal antibody responses. Anti-spike IgG and IgA levels in saliva were measured with in-house ELISAs. Concomitant administration of an influenza vaccine did not affect salivary anti-spike IgG positivity rates to Pfizer/BioNTech BNT162b2 (99.1 cf. 95.6%), or AstraZeneca ChAdOx1 (67.8% cf. 64.9%), at 3-weeks post-vaccination relative to placebo. Furthermore, saliva IgG positively correlated with serum titres highlighting the potential utility of saliva for assessing differences in immunogenicity in future vaccine studies. Mucosal IgA was not detected in response to either COVID-19 vaccine, reinforcing the need for novel vaccines capable of inducing sterilising immunity or otherwise reducing transmission. The trial is registered as ISRCTN 14391248.

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.

Metformin in the prevention of type 2 diabetes after gestational diabetes in postnatal women (OMAhA): a UK multicentre randomised, placebo-controlled, double-blind feasibility trial with nested qualitative study.

OBJECTIVE: To determine the feasibility of a definitive trial of metformin to prevent type 2 diabetes in the postnatal period in women with gestational diabetes. DESIGN: A multicentre, placebo-controlled, double-blind randomised feasibility trial with qualitative evaluation. SETTING: Three inner-city UK National Health Service hospitals in London. PARTICIPANTS: Pregnant women with gestational diabetes treated with medication. INTERVENTIONS: 2 g of metformin (intervention) or placebo (control) from delivery until 1 year postnatally. PRIMARY OUTCOME MEASURES: Rates of recruitment, randomisation, follow-up, attrition and adherence to the intervention. SECONDARY OUTCOME MEASURES: Preliminary estimates of glycaemic effects, qualitative exploration, acceptability of the intervention and costs. RESULTS: Out of 302 eligible women, 57.9% (175/302) were recruited. We randomised 82.3% (144/175) of those recruited, with 71 women in the metformin group and 73 women in the placebo group. Of the participants remaining in the study and providing any adherence information, 54.1% (59/109) took at least 75% of the target intervention dose; the overall mean adherence was 64% (SD 33.6). Study procedures were found to be acceptable to women and healthcare professionals. An increased perceived risk of developing type 2 diabetes, or a positive experience of taking metformin during pregnancy, encouraged participation and adherence to the intervention. Barriers to adherence included disruption to the medication schedule caused by the washout periods ahead of each study visit or having insufficient daily reminders. CONCLUSIONS: It is feasible to run a full-scale definitive trial on the effectiveness of metformin to prevent type 2 diabetes in women with gestational diabetes, during the early postnatal period. Adherence and engagement with the study could be improved with more regular reminders and potentially the addition of ongoing educational or peer support to reinforce messages around type 2 diabetes prevention. TRIAL REGISTRATION NUMBER: ISRCTN20930880.

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.

Tumor-Specific CD8+ T Cells from the Bone Marrow Resist Exhaustion and Exhibit Increased Persistence in Tumor-Bearing Hosts as Compared to Tumor Infiltrating Lymphocytes.

Immunotherapy is now an integral aspect of cancer therapy. Strategies employing adoptive cell therapy (ACT) have seen the establishment of chimeric antigen receptor (CAR)-T cells using peripheral blood lymphocytes as well as tumor infiltrating lymphocytes (TILs) with significant clinical results. Despite these successes, the limitations of the current strategies are also emerging and novel approaches are needed. The bone marrow (BM) is an immunological niche that houses T cells with specificity for previously encountered antigens, including tumor-associated antigens from certain solid cancers. This study sought to improve our understanding of tumor-specific BM T cells in the context of solid tumors by comparing them with TILs, and to assess whether there is a rationale for using the BM as a source of T cells for ACT against solid malignancies. Herein, we demonstrate that T cells from the BM appear superior to TILs as a source of cells for cellular therapy. Specifically, they possess a memory-enriched phenotype and exhibit improved effector function, greater persistence within a tumor-bearing host, and the capacity for increased tumor infiltration. Taken together, these data provide a foundation for further exploring the BM as a source of tumor-specific T cells for ACT in solid malignancies.

Low Vitamin C Concentrations in Patients with Community-Acquired Pneumonia Resolved with Pragmatic Administration of Intravenous and Oral Vitamin C.

Community-acquired pneumonia (CAP) is characterized by elevated markers of inflammation and oxidative stress and depleted circulating concentrations of the antioxidant nutrient vitamin C. A feasibility trial of intravenous and oral vitamin C supplementation, matched to the timing of intravenous and oral antibiotic formulations, was carried out and changes in vitamin C status were monitored to determine whether saturating status could be achieved throughout the administration period. Patients with moderate and severe CAP (CURB-65 ≥ 2; n = 75) who were receiving intravenous antimicrobial therapy were randomized to placebo (n = 39) or intravenous vitamin C (2.5 g per 8 h; n = 36) before moving to oral vitamin C (1 g three times daily) when prescribed oral antimicrobials. Blood samples were collected at baseline and then daily whilst in the hospital. Vitamin C concentrations were determined by high-performance liquid chromatography. The inflammatory and infection biomarkers C-reactive protein and procalcitonin were elevated at baseline (158 (61, 277) mg/L and 414 (155, 1708) ng/L, respectively), and vitamin C concentrations were depleted (15 (7, 25) µmol/L). There was an inverse association between vitamin C and C-reactive protein concentrations (r = -0.312, p = 0.01). Within one day of intervention initiation, plasma vitamin C concentrations in the vitamin C group reached median concentrations of 227 (109, 422) µmol/L, and circulating concentrations remained at ≥150 µmol/L for the duration of the intervention, whilst median vitamin C concentrations in the placebo group remained low (≤35 µmol/L). There was a trend toward decreased duration of hospital stay (p = 0.07) and time to clinical stability (p = 0.08) in the vitamin C group. In conclusion, patients with moderate to severe CAP have inadequate plasma vitamin C concentrations for the duration of their hospital stay. The administration of intravenous or oral vitamin C, titrated to match the antimicrobial formulation, provided saturating plasma vitamin C concentrations whilst in the hospital. There were trends toward shorter duration of hospital stay and time to clinical stability. Thus, larger trials assessing the impact of intravenous and oral vitamin C intervention on CAP clinical outcomes are indicated.

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.

Adjunctive intravenous then oral vitamin C for moderate and severe community-acquired pneumonia in hospitalized adults: feasibility of randomized controlled trial.

Patients hospitalised with community acquired pneumonia (CAP) have low peripheral blood vitamin C concentrations and limited antioxidant capacity. The feasibility of a trial of vitamin C supplementation to improve patient outcomes was assessed. Participants with moderate and severe CAP (CURB-65 ≥ 2) on intravenous antimicrobial treatment were randomised to either intravenous vitamin C (2.5 g 8 hourly) or placebo before switching to oral intervention (1 g tds) for 7 days when they were prescribed oral antimicrobial therapy. Of 344 patients screened 75 (22%) were randomised and analysed. The median age was 76 years, and 43 (57%) were male. In each group, one serious adverse event that was potentially intervention related occurred, and one subject discontinued treatment. Vitamin C concentrations were 226 µmol/L in the vitamin C group and 19 µmol/L in the placebo group (p < 0.001) after 3 intravneous doses. There were no signficant differences between the vitamin C and placebo groups for death within 28 days (0 vs. 2; p = 0.49), median length of stay (69 vs. 121 h; p = 0.07), time to clinical stability (22 vs. 49 h; p = 0.08), or readmission within 30 days (1 vs. 4; p = 0.22). The vitamin C doses given were safe, well tolerated and saturating. A randomised controlled trial to assess the efficacy of vitamin C in patients with CAP would require 932 participants (CURB-65 ≥ 2) to observe a difference in mortality and 200 participants to observe a difference with a composite endpoint such as mortality plus discharge after 7 days in hospital. These studies are feasible in a multicentre setting.

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.