Electronic health record-embedded individualized pain plans for emergency department treatment of vaso-occlusive episodes in adults with sickle cell disease: Protocol for a preimplementation and postimplementation study

BACKGROUND: Individuals living with sickle cell disease often require aggressive treatment of pain associated with vaso-occlusive episodes in the emergency department. Frequently, pain relief is poor. The 2014 National Heart, Lung, and Blood Institute evidence-based guidelines recommended an individualized treatment and monitoring protocol to improve pain management of vaso-occlusive episodes. OBJECTIVE: This study will implement an electronic health record-embedded individualized pain plan with provider and patient access in the emergency departments of 8 US academic centers to improve pain treatment for adult patients with sickle cell disease. This study will assess the overall effects of electronic health record-embedded individualized pain plans on improving patient and provider outcomes associated with pain treatment in the emergency department setting and explore barriers and facilitators to the implementation process. METHODS: A preimplementation and postimplementation study is being conducted by all 8 sites that are members of the National Heart, Lung, and Blood Institute-funded Sickle Cell Disease Implementation Consortium. Adults with sickle cell disease aged 18 to 45 years who had a visit to a participating emergency department for vaso-occlusive episodes within 90 days prior to enrollment will be eligible for inclusion. Patients will be enrolled in the clinic or remotely. The target analytical sample size of this study is 160 patient participants (20 per site) who have had an emergency department visit for vaso-occlusive episode treatment at participating emergency departments during the study period. Each site is expected to enroll approximately 40 participants to reach the analytical sample size. The electronic health record-embedded individualized pain plans will be written by the patient\u27s sickle cell disease provider, and sites will work with the local informatics team to identify the best method to build the electronic health record-embedded individualized pain plan with patient and provider access. Each site will adopt required patient and provider implementation strategies and can choose to adopt optional strategies to improve the uptake and sustainability of the intervention. The study is informed by the Technology Acceptance Model 2 and the Reach, Effectiveness, Adoption, Implementation, and Maintenance framework. Provider and patient baseline survey, follow-up survey within 96 hours of an emergency department vaso-occlusive episode visit, and selected qualitative interviews within 2 weeks of an emergency department visit will be performed to assess the primary outcome, patient-perceived quality of emergency department pain treatment, and additional implementation and intervention outcomes. Electronic health record data will be used to analyze individualized pain plan adherence and additional secondary outcomes, such as hospital admission and readmission rates. RESULTS: The study is currently enrolling study participants. The active implementation period is 18 months. CONCLUSIONS: This study proposes a structured, framework-informed approach to implement electronic health record-embedded individualized pain plans with both patient and provider access in routine emergency department practice. The results of the study will inform the implementation of electronic health record-embedded individualized pain plans at a larger scale outside of Sickle Cell Disease Implementation Consortium centers. TRIAL REGISTRATION: ClinicalTrials.gov NCT04584528; https://clinicaltrials.gov/ct2/show/NCT04584528. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/24818

Pilot Study Examining Pregnancy-specific Equations to Estimate Percent Body Fat in an Overweight/obese Pregnant Hispanic Population

Background and Purpose: Over half of women entering pregnancy are overweight or obese, increasing metabolic risk. This pilot study investigated whether established equations for estimating maternal percent body fat using anthropometry are accurate for Hispanic, overweight or obese pregnant women. Methods: The Siri technique of calculating percent body fat from direct measurements of body density and total body water was the gold-standard. Other pregnancy-specific equations were also examined. The study population included 15 normoglycemic, pregnant Hispanic women in their third trimester (33.2±1.9 gestational week) with a pre-pregnancy body mass index ≥25 to <40kg/m2 , and with no history of chronic disease, or illicit drug, cigarette or alcohol use. Five skinfold sites, pre-pregnancy weight, current weight, and wrist circumference were measured. Body density was measured using air displacement plethysmography. Total body water was measured using 2H2O. Results: Paired t-tests showed that the Paxton equation (intended for use at gestational week 37) overestimated percent body fat compared to the Siri method, p<0.001, whereas the Presley equation (intended for use at gestational week 30) produced statistically similar results to the gold-standard, p=0.842. Discussion: Using skinfold thickness measurements and the Presley equation to assess percent body fat may be useful and accessible for this population

A longitudinal cohort study of the relationship between Thimerosal-containing hepatitis B vaccination and specific delays in development in the United States: Assessment of attributable risk and lifetime care costs

AbstractEpidemiological evidence suggests a link between mercury (Hg) exposure from Thimerosal-containing vaccines and specific delays in development. A hypothesis-testing longitudinal cohort study (n=49,835) using medical records in the Vaccine Safety Datalink (VSD) was undertaken to evaluate the relationship between exposure to Hg from Thimerosal-containing hepatitis B vaccines (T-HBVs) administered at specific intervals in the first 6months of life and specific delays in development [International Classification of Disease, 9th revision (ICD-9): 315.xx] among children born between 1991 and 1994 and continuously enrolled from birth for at least 5.81years. Infants receiving increased Hg doses from T-HBVs administered within the first month, the first 2months, and the first 6months of life were significantly more likely to be diagnosed with specific delays in development than infants receiving no Hg doses from T-HBVs. During the decade in which T-HBVs were routinely recommended and administered to US infants (1991–2001), an estimated 0.5–1million additional US children were diagnosed with specific delays in development as a consequence of 25μg or 37.5μg organic Hg from T-HBVs administered within the first 6months of life. The resulting lifetime costs to the United States may exceed $1 trillion

Effects of CO\u3csub\u3e2\u3c/sub\u3e on Growth Rate, C:N:P, and Fatty Acid Composition of Seven Marine Phytoplankton Species

Carbon dioxide (CO2) is the primary substrate for photosynthesis by the phytoplankton that form the base of the marine food web and mediate biogeochemical cycling of C and nutrient elements. Specific growth rate and elemental composition (C:N:P) were characterized for 7 cosmopolitan coastal and oceanic phytoplankton species (5 diatoms and 2 chlorophytes) using low density, nutrient-replete, semi-continuous culture experiments in which CO2 was manipulated to 4 levels ranging from post-bloom/glacial maxima (ppm) to geological maxima levels (\u3e2900 ppm). Specific growth rates at high CO2 were from 19 to 60% higher than in low CO2 treatments in 4 species and 44% lower in 1 species; there was no significant change in 2 species. Higher CO2 availability also resulted in elevated C:P and N:P molar ratios in Thalassiosira pseudonana (~60 to 90% higher), lower C:P and N:P molar ratios in 3 species (~20 to 50% lower), and no change in 3 species. Carbonate system-driven changes in growth rate did not necessarily result in changes in elemental composition, or vice versa. In a subset of 4 species for which fatty acid composition was examined, elevated CO2 did not affect the contribution of polyunsaturated fatty acids to total fatty acids significantly. These species show relatively little sensitivity between present day CO2 and predicted ocean acidification scenarios (year 2100). The results, however, demonstrate that CO2 availability at environmentally and geologically relevant scales can result in large changes in phytoplankton physiology, with potentially large feedbacks to ocean biogeochemical cycles and ecosystem structure

Malnutrition defined by GLIM criteria identifies a higher incidence of malnutrition and is associated with pulmonary complications after oesophagogastric cancer surgery, compared to ICD-10-defined malnutrition

Background & Objectives Low muscle mass, measured using computed tomography (CT), is associated with poor surgical outcomes. We aimed to include CT-muscle mass in malnutrition diagnosis using the Global Leadership Initiative on Malnutrition (GLIM) criteria, compare it to the International Classification of Diseases 10th Revision (ICD-10) criteria, and assess the impact on postoperative outcomes after oesophagogastric (OG) cancer surgery. Methods One hundred and eight patients who underwent radical OG cancer surgery and had preoperative abdominal CT imaging were included. GLIM and ICD-10 malnutrition data were assessed against complication and survival outcomes. Low CT-muscle mass was determined using predefined cut-points. Results GLIM-defined malnutrition prevalence was significantly higher than ICD-10-malnutrition (72.2% vs. 40.7%, p < 0.001). Of the 78 patients with GLIM-defined malnutrition, low muscle mass (84.6%) was the predominant phenotypic criterion. GLIM-defined malnutrition was associated with pneumonia (26.9% vs. 6.7%, p = 0.010) and pleural effusions (12.8% vs. 0%, p = 0.029). Postoperative complications did not correlate with ICD-10 malnutrition. Severe GLIM (HR: 2.51, p = 0.014) and ICD-10 (HR: 2.15, p = 0.039) malnutrition were independently associated with poorer 5-year survival. Conclusions GLIM criteria appear to identify more malnourished patients and more closely relate to surgical risk than ICD-10 malnutrition, likely due to incorporating objective muscle mass assessment

Tuning the structure of cerium phosphate nanorods

The one-pot, shape selective synthesis of cerium phosphate nanorods has been explored and developed to give nanoparticles with aspect ratios between 3–24.8. Studies of the surface with photo induced force microscopy show for the first time that despite the hexagonal phase bulk structure, mixed monoclinic and hexagonal domains are present in the surface layer demonstrating the importance of surface sensitive, nanoscale vibrational spectroscopy in nanoparticle science. There is also evidence that carbonate is adsorbed preferentially on the monoclinic domains, though whether the carbonate is the cause of the domains or merely adsorbs more easily on this structure has not been determined. Co, Ni and Mn-doped cerium phosphate rods were prepared successfully with aspect ratios of >20. The introduction of dopant ions has a measurable effect upon the magnetic susceptibility but a more significant effect on the bulk crystal phase of the nanoparticles, introducing up to ∼30% monoclinic phosphate in the doped rods

Phosphorus and nitrogen limitation and impairment of headwater streams relative to rivers in Great Britain: a national perspective on eutrophication

This study provides a first national-scale assessment of the nutrient status of British headwater streams within the wider river network, by joint analysis of the national Countryside Survey Headwater Stream and Harmonised River Monitoring Scheme datasets. We apply a novel Nutrient Limitation Assessment methodology to explore the extent to which nutrients may potentially limit primary production in headwater streams and rivers, by coupling ternary assessment of nitrogen (N), phosphorus (P), and carbon (C) depletion, with N:P stoichiometry, and threshold P and N concentrations. P limitation was more commonly seen in the rivers, with greater prevalence of N limitation in the headwater streams. High levels of potential P and N co-limitation were found in the headwater streams, especially the Upland-Low-Alkalinity streams. This suggests that managing both P and N inputs may be needed to minimise risks of degradation of these sensitive headwater stream environments. Although localised nutrient impairment of headwater streams can occur, there were markedly lower rates of P and N impairment of headwater streams relative to downstream rivers at the national scale. Nutrient source contributions, relative to hydrological dilution, increased with catchment scale, corresponding with increases in the extent of agricultural and urban land-use. The estimated nutrient reductions needed to achieve compliance with Water Framework Directive standards, and to reach limiting concentrations, were greatest for the Lowland-High-Alkalinity rivers and streams. Preliminary assessments suggest that reducing P concentrations in the Lowland-High-Alkalinity headwater streams, and N concentrations in the Upland-Low-Alkalinity rivers, might offer greater overall benefits for water-quality remediation at the national scale, relative to the magnitude of nutrient reductions required. This approach could help inform the prioritisation of nutrient remediation, as part of a directional approach to water quality management based on closing the gaps between current and target nutrient concentrations

Long-term surveillance study of rituximab originator treated patients with granulomatosis with polyangiitis (GPA) or microscopic polyangiitis (MPA)

Lay Summary: What does this mean for patients? Rituximab is used to treat active disease and to prevent relapses in anti-neutrophil cytoplasmic antibody-associated vasculitis (AAV). Serious complications, including infections, low natural antibody levels, cancers, low white blood cell levels, heart disease and blood clots are common in AAV patients in general. Whether these complications are more or less common with rituximab is unclear. This study assessed the frequency of serious complications and compared time to first serious complications between patients, either treated with or without rituximab. Over 40% of the patients in this study experienced at least one serious complication. Overall, first serious complication occurred earlier and higher risk of serious infection was seen in rituximab patients. However, these findings should be interpreted with caution as the rituximab patients had been diagnosed with vasculitis for longer and had received a greater amount of immunosuppression in the past, compared with the patients who had not been treated with rituximab

Assessing climate action progress of the City of Toronto

The Canadian City of Toronto’s progress is evaluated for the implementation of its climate action plan, TransformTO, and its effectiveness in reducing sectoral emissions. Following a brief history of climate action in Toronto, the key climate policies and programs are subjected to a content analysis and assessed using an aggregate evaluation framework composed of qualitative indicators commonly used to track municipal climate action. The results of this assessment reveal that the city has made steady progress in reducing emissions, surpassing its 2020 greenhouse gas emissions reduction target of 30% reduction below 1990 levels. However, Toronto is not on track to meet its 2030 target of a 65% emissions reduction from 1990 levels. Without transformational action across all sectors, it is unlikely to meet the 2030 and 2040 targets. The results are intended to strengthen implementation and evaluation efforts in Toronto. The discussion will be of interest to decision-makers and practitioners who seek to accelerate implementation of municipal climate action plans. Policy relevance This paper is intended to support and strengthen the City of Toronto’s implementation of its climate action plan, TransformTO, and supporting Net Zero Strategies. Of potential relevance to policymakers in other Canadian cities is the role of ambitious top-down target-setting of the municipal organization and city at large for pursuing bold climate action, even in the face of significant constraints (e.g. provincial building code and energy grid, difficulties in accessing utilities energy use data). Policymakers may also draw insights from the Toronto context for leveraging staff and community commitment to climate action by involving them in planning and implementation of emissions reductions strategies. Useful recommendations are provided for overcoming modeling deficiencies and data limitations, while advancing transformative climate action through multi-sectoral partnerships, policies that support market transformation, the scale-up of low carbon programs and investments in low carbon infrastructure

Bioactive Recombinant Human Oncostatin M for NMR-Based Screening in Drug Discovery

Oncostatin M (OSM) is a pleiotropic, interleukin-6 family inflammatory cytokine that plays an important role in inflammatory diseases, including inflammatory bowel disease, rheumatoid arthritis, and cancer progression and metastasis. Recently, elevated OSM levels have been found in the serum of COVID-19 patients in intensive care units. Multiple anti-OSM therapeutics have been investigated, but to date no OSM small molecule inhibitors are clinically available. To pursue a high-throughput screening and structure-based drug discovery strategy to design a small molecule inhibitor of OSM, milligram quantities of highly pure, bioactive OSM are required. Here, we developed a reliable protocol to produce highly pure unlabeled and isotope enriched OSM from E. coli for biochemical and NMR studies. High yields (ca. 10 mg/L culture) were obtained in rich and minimal defined media cultures. Purified OSM was characterized by mass spectrometry and circular dichroism. The bioactivity was confirmed by induction of OSM/OSM receptor signaling through STAT3 phosphorylation in human breast cancer cells. Optimized buffer conditions yielded 1H, 15N HSQC NMR spectra with intense, well-dispersed peaks. Titration of 15N OSM with a small molecule inhibitor showed chemical shift perturbations for several key residues with a binding affinity of 12.2 ± 3.9 μM. These results demonstrate the value of bioactive recombinant human OSM for NMR-based small molecule screening