Effect of a Hospital and Postdischarge Quality Improvement Intervention on Clinical Outcomes and Quality of Care for Patients With Heart Failure With Reduced Ejection Fraction: The CONNECT-HF Randomized Clinical Trial

Importance: Adoption of guideline-directed medical therapy for patients with heart failure is variable. Interventions to improve guideline-directed medical therapy have failed to consistently achieve target metrics, and limited data exist to inform efforts to improve heart failure quality of care. Objective: To evaluate the effect of a hospital and postdischarge quality improvement intervention compared with usual care on heart failure outcomes and care. Design, Setting, and Participants: This cluster randomized clinical trial was conducted at 161 US hospitals and included 5647 patients (2675 intervention vs 2972 usual care) followed up after a hospital discharge for acute heart failure with reduced ejection fraction (HFrEF). The trial was performed from 2017 to 2020, and the date of final follow-up was August 31, 2020. Interventions: Hospitals (n = 82) randomized to a hospital and postdischarge quality improvement intervention received regular education of clinicians by a trained group of heart failure and quality improvement experts and audit and feedback on heart failure process measures (eg, use of guideline-directed medical therapy for HFrEF) and outcomes. Hospitals (n = 79) randomized to usual care received access to a generalized heart failure education website. Main Outcomes and Measures: The coprimary outcomes were a composite of first heart failure rehospitalization or all-cause mortality and change in an opportunity-based composite score for heart failure quality (percentage of recommendations followed). Results: Among 5647 patients (mean age, 63 years; 33% women; 38% Black; 87% chronic heart failure; 49% recent heart failure hospitalization), vital status was known for 5636 (99.8%). Heart failure rehospitalization or all-cause mortality occurred in 38.6% in the intervention group vs 39.2% in usual care (adjusted hazard ratio, 0.92 [95% CI, 0.81 to 1.05). The baseline quality-of-care score was 42.1% vs 45.5%, respectively, and the change from baseline to follow-up was 2.3% vs -1.0% (difference, 3.3% [95% CI, -0.8% to 7.3%]), with no significant difference between the 2 groups in the odds of achieving a higher composite quality score at last follow-up (adjusted odds ratio, 1.06 [95% CI, 0.93 to 1.21]). Conclusions and Relevance: Among patients with HFrEF in hospitals randomized to a hospital and postdischarge quality improvement intervention vs usual care, there was no significant difference in time to first heart failure rehospitalization or death, or in change in a composite heart failure quality-of-care score. Trial Registration: ClinicalTrials.gov Identifier: NCT03035474

Annex 2-4: Norway's contribution to women's participation in peacebuilding A Case Study Analysis from Afghanistan, Colombia and Nordic Women Mediators Network

The study is part of an evaluation of Norwegian efforts to increase women's participation in peacebuilding between 2000 - 2020 conducted by Norad’s evaluation department. The purpose is to generat e knowledge on how Norway has supported women’s participation in peace efforts and what the effects of this support have been. The case study analysis has brought together findings from country cases on Afghanistan and Colombia, and of the “Nordic Women Me diators N etwork” (NWM) on how Norway has worked to promote women’s participation in peace processes globally . In Afghanistan the focus has been on women ’ s participation in peace initiatives, in Colombia it has been on women ’ s participation in the implement ation of the Peace Agreement, and with the NWM it has support to women's participation in p eace negotiations around the world

New 2D and 3D Coordination Polymers by Dehydration of (1)(infinity)[M-II(tF-BDC)(H2O)(4)] (M-II = Zn2+, Co2+, Ni2+ and tF-BDC2- = Tetrafluoroterephthalate)

By dehydration of the known coordination polymers (1)(infinity)[M-II(tF-BDC)(H2O)(4)] (M-II = Co2+, Zn2+ and tF-BDC2- = tetrafluoroterephthalate) the homoleptic anhydrous coordination networks (3)(infinity)[M-II(tF-BDC)] were obtained as polycrystalline powders. Their crystal structures (C2/c, Z = 4) were solved and refined by means of synchrotron powder diffraction data. These structures are characterized by [(MO4)-O-II] tetrahedra, which are connected by the tF-BDC2- linkers to form a 3D non-porous coordination network. The dehydration leads to a change from a [(MO6)-O-II] octahedral coordination in the hydrate to a tetrahedral coordination sphere in the anhydrous compound. For the cobalt compounds this leads to a color change from pale rose to deep blue upon heating and dehydration, which was analyzed by means of UV/Vis/NIR spectroscopy and measurements of the magnetic susceptibilities. In contrast, (1)(infinity)[Ni-II(tF-BDC)(H2O)(4)] can only partly be dehydrated to form (2)(infinity)[Ni-II(tF-BDC)(H2O)(2)] (P1, Z = 1) with retention of the octahedral [(NiO6)-O-II] coordination in both compounds. At higher temperatures the tF-BDC2- linker starts to decompose, before a complete dehydration can take place

Large-scale Implementation of Fascia Iliaca Compartment Blocks in an Emergency Department

Introduction: A robust body of literature supports the use of fascia iliaca compartment blocks (FICB) for improving outcomes in hip fractures, especially in the geriatric population. Our objective in this project was to implement consistent pre-surgical, emergency department (ED) FICB for hip fracture patients and to address barriers to implementation.Methods: With the support of a multidisciplinary team, including orthopedic surgery and anesthesia, a core team of emergency physicians developed and implemented a departmentwide FICB training and credentialing program. The goal was to have 80% of all emergency physicians credentialed to provide pre-surgical FICB to all hip fracture patients seen in the ED who met the criteria. Following implementation, we assessed approximately one year of data on hip fracture patients presenting to the ED. We evaluated whether or not they were eligible for FICB and, if so, whether or not they received it.Results: Emergency physician education has resulted in 86% of clinicians credentialed to perform FICB. Of 486 patients presenting for hip fracture, 295 (61%) were considered eligible for a block. Of those eligible, (54%) consented and underwent a FICB in the ED.Conclusion: A collaborative, multidisciplinary effort is vital for success. The primary barrier to achieving a higher percentage of eligible patients receiving blocks was the deficit of emergency physicians initially credentialed. Continuing education is ongoing, including credentialing and early identification of patients eligible for the fascia iliaca compartment block

Controls of the molecular distribution and carbon isotopic composition of alkenones in certain haptophyte algae

[1] Although the biochemical functions and biosynthetic pathways of alkenones are still largely unknown, alkenone unsaturation ratios are now used extensively to infer ancient sea surface temperature, and their isotopic compositions have been used to reconstruct ancient atmospheric CO2 levels. The inferred relationships between alkenone unsaturation ratios, isotopic compositions, and growth conditions are based on empirical laboratory and field studies and, in the case of isotope fractionation, on simple models of carbon acquisition and fixation. Significant uncertainty still exists concerning the physiological and ecological factors affecting cellular production of alkenones, unsaturation ratios, and isotopic composition. Phytoplankton culture conditions have been shown to affect alkenone unsaturation (U37K′), cellular alkenone content, intracellular isotopic compositions (Δδ), and changes in fractionation (εP) as a function of the quotient of algal growth rate and aqueous carbon dioxide concentration (μ/CO2). Such studies imply that plant physiology can affect the interpretation of environmental signals. The factor(s) controlling cellular alkenone concentrations and unsaturation ratios are reviewed, as well as the carbon isotopic composition of the alkenone-producing algae. A new technique is presented to determine growth rates of the alkenone-containing algae in natural settings that will facilitate testing laboratory-based hypotheses concerning the carbon isotopic fractionation and its relationship to growth rate/growth status of alkenone-producing algae in the field

Development and characterization of a preclinical model of breast cancer lung micrometastatic to macrometastatic progression.

Most cancer patients die with metastatic disease, thus, good models that recapitulate the natural process of metastasis including a dormancy period with micrometastatic cells would be beneficial in developing treatment strategies. Herein we report a model of natural metastasis that balances time to complete experiments with a reasonable dormancy period, which can be used to better study metastatic progression. The basis for the model is a 4T1 triple negative syngeneic breast cancer model without resection of the primary tumor. A cell titration from 500 to 15,000 GFP tagged 4T1 cells implanted into fat pad number four of immune proficient eight week female BALB/cJ mice optimized speed of the model while possessing metastatic processes including dormancy and beginning of reactivation. The frequency of primary tumors was less than 50% in animals implanted with 500-1500 cells. Although implantation with over 10,000 cells resulted in 100% primary tumor development, the tumors and macrometastases formed were highly aggressive, lacked dormancy, and offered no opportunity for treatment. Implantation of 7,500 cells resulted in >90% tumor take by 10 days; in 30-60 micrometastases in the lung (with many animals also having 2-30 brain micrometastases) two weeks post-implantation, with the first small macrometastases present at five weeks; many animals displaying macrometastases at five weeks and animals becoming moribund by six weeks post-implantation. Using the optimum of 7,500 cells the efficacy of a chemotherapeutic agent for breast cancer, doxorubicin, given at its maximal tolerated dose (MTD; 1 mg/kg weekly) was tested for an effect on metastasis. Doxorubicin treatment significantly reduced primary tumor growth and lung micrometastases but the number of macrometastases at experiment end was not significantly affected. This model should prove useful for development of drugs to target metastasis and to study the biology of metastasis

Summary of optimal cell number determination in the development of the metastatic mouse model.

<p>(<b>A</b>) Chart indicating the benefits of optimizing cell number for primary tumor take and metastatic progression in the 4T1 breast cancer model. (<b>B</b>) Percent tumor take in immune-proficient BALB/cJ mice implanted with 4T1-Luc2GFP cells into the number four mammary fat pad. Data are actual percent tumor take based on number of animals indicated above each bar from no fewer than nine independent experiments. Micrometastasis (<b>C</b>) and macrometastasis (<b>D</b>) in lung six weeks after implantation. Data are mean ± <i>SEM</i> from two independent experiments with <i>n</i> = 5 for experiment one, <i>n</i> = 10 for experiment two.</p

Growth of 4T1-Luc2GFP primary tumors: Timecourse.

<p>Primary tumor growth was recorded over a five week period from BALB/cJ mice implanted with 7,500 4T1-Luc2GFP cells into the mammary fat pad. (<b>A</b>) Tumor volume (mm³). (<b>B</b>) Tumor weight (mg). (<b>C</b>) Animal weights (g). Tumor volumes were calculated using the ellipsoidal method, volume (mm³) = 0.52×length × width². All data are mean ± <i>SEM</i> from two independent experiments with 5–8 mice for experiment one and 7–11 mice for experiment two and are fitted to a Gomperzian growth curve by Prism 6.0 software.</p

Review of literature on the 4T1 model being used for metastasis evaluation.

<p>Review of literature on the 4T1 model being used for metastasis evaluation.</p