The Advantages of Flexibility: The Role of Entropy in Crystal Structures Containing C-H···F Interactions.

Molecular crystal structures are often interpreted in terms of strong, structure directing, intermolecular interactions, especially those with distinct geometric signatures such as H-bonds or π-stacking interactions. Other interactions can be overlooked, perhaps because they are weak or lack a characteristic geometry. We show that although the cumulative effect of weak interactions is significant, their deformability also leads to occupation of low energy vibrational energy levels, which provides an additional stabilizing entropic contribution. The entropies of five fluorobenzene derivatives have been calculated by periodic DFT calculations to assess the entropic influence of C-H···F interactions in stabilizing their crystal structures. Calculations reproduce inelastic neutron scattering data and experimental entropies from heat capacity measurements. C-H···F contacts are shown to have force constants which are around half of those of more familiar interactions such as hydrogen bonds, halogen bonds, and C-H···π interactions. This feature, in combination with the relatively high mass of F, means that the lowest energy vibrations in crystalline fluorobenzenes are dominated by C-H···F contributions. C-H···F contacts occur much more frequently than would be expected from their enthalpic contributions alone, but at 150 K, the stabilizing contribution of entropy provides, at -10 to -15 kJ mol-1, a similar level of stabilization to the N-H···N hydrogen bond in ammonia and O-H···O hydrogen bond in water.

Characterization of K562 cells: uncovering novel chromosomes, assessing transferrin receptor expression, and probing pharmacological therapies.

Human erythroleukemic K562 cells represent the prototypical cell culture model of chronic myeloid leukemia (CML). The cells are pseudo-triploid and positive for the Philadelphia chromosome. Therefore, K562 cells have been widely used for investigating the BCR/ABL1 oncogene and the tyrosine kinase inhibitor, imatinib-mesylate. Further, K562 cells overexpress transferrin receptors (TfR) and have been used as a model for targeting cytotoxic therapies, via receptor-mediated endocytosis. Here, we have characterized K562 cells focusing on the karyotype of cells in prolonged culture, regulation of expression of TfR in wildtype (WT) and doxorubicin-resistant cells, and responses to histone deacetylase inhibition (HDACi). Karyotype analysis indicates novel chromosomes and gene expression analysis suggests a shift of cultured K562 cells away from patient-derived leukemic cells. We confirm the high expression of TfR on K562 cells using immunofluorescence and cell-surface receptor binding radioassays. Importantly, high TfR expression is observed in patient-derived cells, and we highlight the persistent expression of TfR following doxorubicin acquired resistance. Epigenetic analysis indicates that permissive histone acetylation and methylation at the promoter region regulates the transcription of TfR in K562 cells. Finally, we show relatively high expression of HDAC enzymes in K562 cells and demonstrate the chemotoxic effects of HDACi, using the FDA-approved hydroxamic acid, vorinostat. Together with a description of morphology, infrared spectral analysis, and examination of metabolic properties, we provide a comprehensive characterization of K562 cells. Overall, K562 cell culture systems remain widely used for the investigation of novel therapeutics for CML, which is particularly important in cases of imatinib-mesylate resistance.

Prothrombinex®-VF in chronic liver disease: Friend or foe?

OBJECTIVE: Management of coagulopathy in chronic liver disease (CLD) poses a challenge for critical care physicians. Prothrombinex®-VF is a low-volume product with rapid onset of action. Evidence for its efficacy and safety in CLD is limited and cases of acute intravascular coagulation and fibrinolysis (AICF) and/or disseminated intravascular coagulation (DIC) have been reported. Our objective was to evaluate the role of Prothrombinex®-VF in reversal of coagulopathy and the incidence AICF/DIC, thromboembolic events and mortality. METHODS: This was a retrospective, multi-centre study of Prothrombinex®-VF use in CLD across 11 hospitals over a 2-year period, excluding those on therapeutic anticoagulation. Patients were subclassified into acute on chronic liver failure (ACLF), acute decompensation (ADC) and compensated cirrhosis. Reversal of coagulopathy was defined as international normalised ratio (INR) <1.5× upper limit normal (ULN), prothrombin time <1.5× ULN, activated partial thromboplastin time <1.5× ULN and fibrinogen >1 g/L. Markers of AICF/DIC were recorded. RESULTS: Thirty CLD patients were included, and the median model for end-stage liver disease score was 23.5. Acute bleeding was the most common indication for Prothrombinex®-VF (60%). All had baseline coagulopathy and the majority did not achieve reversal. Key indicators of AICF/DIC were mainly observed in those with ACLF; bleeding from mucosa or lines (53%), worsening hypofibrinogenaemia (60%), worsening thrombocytopaenia (60%). The ADC and compensated cirrhosis groups were relatively unaffected. Incidence of venous thromboembolism was 6%. Overall mortality was 43% and 70% in ACLF. CONCLUSION: Prothrombinex®-VF did not lead to meaningful reversal of coagulopathy and should be used with caution in CLD. Patients with ACLF were more likely to develop AICF/DIC following Prothrombinex®-VF, although the association is uncertain. Further studies are needed to evaluate the safety and efficacy of Prothrombinex®-VF use in CLD.

Electrochemical Exfoliation of Graphite to Graphene-Based Nanomaterials.

Here, we report on a new automated electrochemical process for the production of graphene oxide (GO) from graphite though electrochemical exfoliation. The effects of the electrolyte and applied voltage were investigated and optimized. The morphology, structure and composition of the electrochemically exfoliated GO (EGO) were probed by scanning electron microscopy (SEM), transmission electron microscopy (TEM), X-ray diffraction (XRD), energy dispersive X-ray (EDX) spectroscopy, X-ray photoelectron spectroscopy (XPS), FTIR spectroscopy and Raman spectroscopy. Important metrics such as the oxygen content (25.3 at.%), defect density (ID/IG = 0.85) and number of layers of the formed EGO were determined. The EGO was also compared with the GO prepared using the traditional chemical method, demonstrating the effectiveness of the automated electrochemical process. The electrochemical properties of the EGO, CGO and other carbon-based materials were further investigated and compared. The automated electrochemical exfoliation of natural graphite powder demonstrated in the present study does not require any binders; it is facile, cost-effective and easy to scale up for a large-scale production of graphene-based nanomaterials for various applications.

A Review of Cultural Practices for Botrytis Bunch Rot Management in New Zealand Vineyards.

Botrytis bunch rot of grapes (BBR) causes substantial crop and wine quality issues globally. Past and present foundations for BBR control are based upon synthetic fungicides and varying forms of canopy management. Many authors regard the continued dependence on fungicides as unsustainable and have urged greater deployment of cultural, biological and nutritional strategies. However, in contrast to organic wine production, the uptake of alternative strategies in conventional vineyards has been slow based on cost and perceived reliability issues. This review summarises research from many different wine growing regions in New Zealand with the aim of demonstrating how traditional and newly developed cultural control practices have cost-effectively reduced BBR. In addition to reviewing traditional cultural practices (e.g., leaf removal), mechanical tools are described that remove floral trash and mechanically shake the vines. Multi-omics has improved our knowledge of the underlying changes to grape berries after mechanical shaking. Exogenous applications of calcium may correct calcium deficiencies in the berry skin and reduce BBR but the outcome varies between cultivar and regions. Nitrogen aids in grapevine defence against BBR but remains a complex and difficult nutrient to manage. The sustainable growth of organics and The European Green Deal will stimulate researchers to evaluate new combinations of non-chemical BBR strategies in the next decade.

Telemonitoring and protocolized case management for hypertensive community dwelling older adults (TECHNOMED): a randomized controlled trial.

BACKGROUND: Home blood pressure (BP) telemonitoring combined with case management leads to BP reductions in individuals with hypertension. However, its benefits are less clear in older (age ≥ 65 years) adults. METHODS: Twelve-month, open-label, randomized trial of community-dwelling older adults comparing the combination of home BP telemonitoring (HBPM) and pharmacist-led case management, vs. enhanced usual care with HBPM alone. The primary outcome was the proportion achieving systolic BP targets on 24-h ambulatory BP monitoring (ABPM). Changes in HBPM were also examined. Logistic and linear regressions were used for analyses, adjusted for baseline BP. RESULTS: Enrollment was stopped early due to coronavirus disease 2019. Participants randomized to intervention (n = 61) and control (n = 59) groups were mostly female (77%), with mean age 79.5 years. The adjusted odds ratio for ABPM BP target achievement was 1.48 (95% confidence interval 0.87-2.52, P = 0.15). At 12 months, the mean difference in BP changes between intervention and control groups was -1.6/-1.1 for ABPM (P-value 0.26 for systolic BP and 0.10 for diastolic BP), and -4.9/-3.1 for HBPM (P-value 0.04 for systolic BP and 0.01 for diastolic BP), favoring the intervention. Intervention group participants had hypotension (systolic BP < 110) more frequently (21% vs. 5%, P = 0.009), but no differences in orthostatic symptoms, syncope, non-mechanical falls, or emergency department visits. CONCLUSIONS: Home BP telemonitoring and pharmacist case management did not improve achievement of target range ambulatory BP, but did reduce home BP. It did not result in major adverse consequences.

Real-World Effectiveness of Lipid-Lowering Medications on Outcomes after Stroke: Potential Implications of the New-User Design.

INTRODUCTION: Observational studies are increasingly being used to provide evidence on the real-world effectiveness of medications for preventing vascular diseases, such as stroke. We investigated whether the real-world effectiveness of treatment with lipid-lowering medications after ischemic stroke is affected by prevalent-user bias. METHODS: An observational cohort study of 90-day survivors of ischemic stroke using person-level data from the Australian Stroke Clinical Registry (2012-2016; 45 hospitals) linked to administrative (pharmaceutical, hospital, death) records. The use of, and adherence to (proportion of days covered <80% [poor adherence] vs. ≥80% [good adherence]), lipid-lowering medications within 90 days post-discharge was determined from pharmaceutical records. Users were further classified as prevalent (continuing) or new users, based on dispensing within 90 days prior to stroke. A propensity score-adjusted Cox regression was used to evaluate the effectiveness of lipid-lowering medications on outcomes (all-cause mortality, all-cause and cardiovascular disease readmission) within the subsequent year. Analyses were undertaken using prevalent-user (all users vs. nonusers) and new-user designs (new users vs. nonusers). RESULTS: Of 11,217 eligible patients (median age 72 years, 42% female), 9,294 (83%) used lipid-lowering medications within 90 days post-discharge, including 5,479 new users. In both prevalent-user and new-user designs, nonusers (vs. users) had significantly greater rates of mortality (hazard ratio [HR] 2.35, 95% CI: 1.89-2.92) or all-cause readmissions (HR 1.22, 95% CI: 1.05-1.40) but not cardiovascular disease readmission. In contrast, associations between having poor (vs. good) adherence on outcomes were stronger among new users than all users. Among new users, having poor adherence was associated with greater rates of mortality (HR 1.48, 95% CI: 1.12-1.96), all-cause readmission (HR 1.14, 95% CI: 1.02-1.27), and cardiovascular disease readmission (HR 1.20, 95% CI: 1.01-1.42). CONCLUSIONS: The real-world effectiveness of treatment with lipid-lowering medications after stroke is attenuated when evaluated based on prevalent-user rather than new-user design. These findings may have implications for designing studies on the real-world effectiveness of secondary prevention medications.

Drivers and scorecards to improve hypertension control in primary care practice: Recommendations from the HEARTS in the Americas Innovation Group.

Background: Cardiovascular disease (CVD) is the leading cause of morbidity and mortality in the Americas, and hypertension is the most significant modifiable risk factor. However, hypertension control rates remain low, and CVD mortality is stagnant or rising after decades of continuing reduction. In 2016, the World Health Organization (WHO) launched the HEARTS technical package to improve hypertension control. The Pan American Health Organization (PAHO) designed the HEARTS in the Americas Initiative to improve CVD risk management, emphasizing hypertension control, to date implemented in 21 countries. Methods: To advance implementation, an interdisciplinary group of practitioners was engaged to select the key evidence-based drivers of hypertension control and to design a comprehensive scorecard to monitor their implementation at primary care health facilities (PHC). The group studied high-performing health systems that achieve high hypertension control through quality improvement programs focusing on specific process measures, with regular feedback to providers at health facilities. Findings: The final selected eight drivers were categorized into five main domains: (1) diagnosis (blood pressure measurement accuracy and CVD risk evaluation); (2) treatment (standardized treatment protocol and treatment intensification); (3) continuity of care and follow-up; (4) delivery system (team-based care, medication refill), and (5) system for performance evaluation. The drivers and recommendations were then translated into process measures, resulting in two interconnected scorecards integrated into the HEARTS in the Americas monitoring and evaluation system. Interpretation: Focus on these key hypertension drivers and resulting scorecards, will guide the quality improvement process to achieve population control goals at the participating health centers in HEARTS implementing countries. Funding: No funding to declare.

[Drivers and scorecards to improve hypertension control in primary care practice: Recommendations from the HEARTS in the Americas Innovation GroupFactores impulsores y métodos de puntuación para mejorar el control de la hipertensión en la práctica clínica de la atención primaria: recomendaciones del grupo de innovación de HEARTS en las Américas]. / Fatores impulsionadores e scorecards para melhorar o controle da hipertensão arterial na atenção primária: recomendações do Grupo de Inovação da Iniciativa HEARTS nas Américas.

Background: Cardiovascular disease (CVD) is the leading cause of morbidity and mortality in the Americas, and hypertension is the most significant modifiable risk factor. However, hypertension control rates remain low, and CVD mortality is stagnant or rising after decades of continuing reduction. In 2016, the World Health Organization (WHO) launched the HEARTS technical package to improve hypertension control. The Pan American Health Organization (PAHO) designed the HEARTS in the Americas Initiative to improve CVD risk management, emphasizing hypertension control, to date implemented in 21 countries. Methods: To advance implementation, an interdisciplinary group of practitioners was engaged to select the key evidence-based drivers of hypertension control and to design a comprehensive scorecard to monitor their implementation at primary care health facilities (PHC). The group studied high-performing health systems that achieve high hypertension control through quality improvement programs focusing on specific process measures, with regular feedback to providers at health facilities. Findings: The final selected eight drivers were categorized into five main domains: (1) diagnosis (blood pressure measurement accuracy and CVD risk evaluation); (2) treatment (standardized treatment protocol and treatment intensification); (3) continuity of care and follow-up; (4) delivery system (team-based care, medication refill), and (5) system for performance evaluation. The drivers and recommendations were then translated into process measures, resulting in two interconnected scorecards integrated into the HEARTS in the Americas monitoring and evaluation system. Interpretation: Focus on these key hypertension drivers and resulting scorecards, will guide the quality improvement process to achieve population control goals at the participating health centers in HEARTS implementing countries.

Antecedentes: Las enfermedades cardiovasculares (ECV) son la principal causa de morbilidad y mortalidad en la Región de las Américas y la hipertensión es el factor de riesgo modificable asociado más importante. Sin embargo, las tasas de control de la hipertensión siguen siendo bajas y la mortalidad por ECV está estancada o en aumento después de décadas de reducción continua. En el 2016, la Organización Mundial de la Salud (OMS) presentó el paquete técnico HEARTS para mejorar el control de la hipertensión. La Organización Panamericana de la Salud (OPS) diseñó la iniciativa HEARTS en las Américas para mejorar el control del riesgo de ECV, que hace hincapié en el control de la hipertensión y que, hasta la fecha, se ha implementado en 21 países. Métodos: Para avanzar en la implementación, se creó un grupo interdisciplinario de profesionales de la salud con el objetivo de seleccionar los factores impulsores claves del control de la hipertensión basados en la evidencia y diseñar un método de puntuación integral para dar seguimiento a su implementación en los centros de atención de salud primaria (APS). El grupo estudió los sistemas de salud de alto desempeño que logran un control elevado de la hipertensión mediante programas de mejora de la calidad que se centran en medidas específicas con respecto a los procesos, con retroalimentación regular a los prestadores en los centros de salud. Resultados: Los ocho factores impulsores finales seleccionados se clasificaron en cinco dominios principales: 1) diagnóstico (exactitud de la medición de la presión arterial y evaluación del riesgo de ECV); 2) tratamiento (protocolo de tratamiento e intensificación del tratamiento estandarizados); 3) continuidad de la atención y seguimiento; 4) sistema de prestación del tratamiento (atención basada en un trabajo en equipo, reposición de la medicación) y 5) sistema para la evaluación del desempeño. Los factores impulsores y las recomendaciones se tradujeron en medidas con respecto a los procesos, lo que llevó a dos métodos de puntuación integrados e interconectados en el sistema de seguimiento y evaluación del programa HEARTS en las Américas. Conclusiones: El enfoque que se centra en estos factores impulsores clave de la hipertensión y los métodos de puntuación resultantes servirá de guía para el proceso de mejora de la calidad con objeto de alcanzar los objetivos de control a nivel poblacional en los centros de salud participantes de los países que implementan el programa HEARTS.

[Drivers and scorecards to improve hypertension control in primary care practice: Recommendations from the HEARTS in the Americas Innovation GroupFatores impulsionadores e scorecards para melhorar o controle da hipertensão arterial na atenção primária: recomendações do Grupo de Inovação da Iniciativa HEARTS nas Américas]. / Factores impulsores y métodos de puntuación para mejorar el control de la hipertensión en la práctica clínica de la atención primaria: recomendaciones del grupo de innovación de HEARTS en las Américas.

Background: Cardiovascular disease (CVD) is the leading cause of morbidity and mortality in the Americas, and hypertension is the most significant modifiable risk factor. However, hypertension control rates remain low, and CVD mortality is stagnant or rising after decades of continuing reduction. In 2016, the World Health Organization (WHO) launched the HEARTS technical package to improve hypertension control. The Pan American Health Organization (PAHO) designed the HEARTS in the Americas Initiative to improve CVD risk management, emphasizing hypertension control, to date implemented in 21 countries. Methods: To advance implementation, an interdisciplinary group of practitioners was engaged to select the key evidence-based drivers of hypertension control and to design a comprehensive scorecard to monitor their implementation at primary care health facilities (PHC). The group studied high-performing health systems that achieve high hypertension control through quality improvement programs focusing on specific process measures, with regular feedback to providers at health facilities. Findings: The final selected eight drivers were categorized into five main domains: (1) diagnosis (blood pressure measurement accuracy and CVD risk evaluation); (2) treatment (standardized treatment protocol and treatment intensification); (3) continuity of care and follow-up; (4) delivery system (team-based care, medication refill), and (5) system for performance evaluation. The drivers and recommendations were then translated into process measures, resulting in two interconnected scorecards integrated into the HEARTS in the Americas monitoring and evaluation system. Interpretation: Focus on these key hypertension drivers and resulting scorecards, will guide the quality improvement process to achieve population control goals at the participating health centers in HEARTS implementing countries.

Fundamentos: As doenças cardiovasculares (DCV) são as principais causas de morbimortalidade nas Américas, e a hipertensão arterial (HÁ) é o fator de risco modificável mais importante. Porém, as taxas de controle da HA continuam baixas, e a mortalidade por DCV está estagnada ou aumentando após décadas de redução contínua. Em 2016, a Organização Mundial da Saúde (OMS) lançou o pacote de medidas técnicas HEARTS para melhorar o controle da HA. A Organização Pan-Americana da Saúde (OPAS) criou a iniciativa HEARTS nas Américas para melhorar a gestão do risco cardiovascular (RCV), com ênfase no controle da HA. Até agora, essa iniciativa foi implementada em 21 países. Métodos: Para impulsionar a implementação, recrutou-se um grupo multidisciplinar de profissionais para selecionar impulsionadores-chave do controle da HA com base em evidências e elaborar um scorecard completo para monitorar sua implementação em unidades de atenção primária à saúde (APS). O grupo estudou sistemas de saúde com alto desempenho que haviam conseguido atingir um alto nível de controle da HA por meio de programas de melhoria da qualidade focados em medidas específicas de processo, com feedback regular para os profissionais das unidades de saúde. Resultados: Os oito fatores impulsionadores incluídos na seleção final foram categorizados em cinco domínios principais: (1) diagnóstico (exatidão da medição da pressão arterial e avaliação do RCV); (2) tratamento (protocolo padronizado de tratamento e intensificação do tratamento); (3) continuidade do cuidado e acompanhamento; (4) modelo de atenção (atendimento baseado em equipe, renovação da prescrição); e (5) sistema de avaliação do desempenho. Em seguida, os impulsionadores e as recomendações foram transformados em medidas de processo, gerando dois scorecards inter-relacionados integrados ao sistema de monitoramento e avaliação da Iniciativa HEARTS nas Américas. Interpretação: O foco nesses impulsionadores-chave da HA e nos scorecards resultantes orientará o processo de melhoria da qualidade para atingir as metas de controle, em nível populacional, dos centros de saúde participantes nos países que estão implementando a iniciativa HEARTS.

Fatores impulsionadores e scorecards para melhorar o controle da hipertensão arterial na atenção primária: recomendações do Grupo de Inovação da Iniciativa HEARTS nas Américas

[RESUMO]. Fundamentos. As doenças cardiovasculares (DCV) são as principais causas de morbimortalidade nas Américas, e a hipertensão arterial (HÁ) é o fator de risco modificável mais importante. Porém, as taxas de controle da HA continuam baixas, e a mortalidade por DCV está estagnada ou aumentando após décadas de redução contínua. Em 2016, a Organização Mundial da Saúde (OMS) lançou o pacote de medidas técnicas HEARTS para melhorar o controle da HA. A Organização Pan-Americana da Saúde (OPAS) criou a iniciativa HEARTS nas Américas para melhorar a gestão do risco cardiovascular (RCV), com ênfase no controle da HA. Até agora, essa iniciativa foi implementada em 21 países. Métodos. Para impulsionar a implementação, recrutou-se um grupo multidisciplinar de profissionais para selecionar impulsionadores-chave do controle da HA com base em evidências e elaborar um scorecard completo para monitorar sua implementação em unidades de atenção primária à saúde (APS). O grupo estudou sistemas de saúde com alto desempenho que haviam conseguido atingir um alto nível de controle da HA por meio de programas de melhoria da qualidade focados em medidas específicas de processo, com feedback regular para os profissionais das unidades de saúde. Resultados. Os oito fatores impulsionadores incluídos na seleção final foram categorizados em cinco domínios principais: (1) diagnóstico (exatidão da medição da pressão arterial e avaliação do RCV); (2) tratamento (protocolo padronizado de tratamento e intensificação do tratamento); (3) continuidade do cuidado e acompanhamento; (4) modelo de atenção (atendimento baseado em equipe, renovação da prescrição); e (5) sistema de avaliação do desempenho. Em seguida, os fatores impulsionadores e as recomendações foram transformados em medidas de processo, gerando dois scorecards inter-relacionados integrados ao sistema de monitoramento e avaliação da Iniciativa HEARTS nas Américas. Interpretação. O foco nesses impulsionadores-chave da HA e nos scorecards resultantes orientará o processo de melhoria da qualidade para atingir as metas de controle, a nível populacional, dos centros de saúde participantes nos países que estão implementando a iniciativa HEARTS.

[ABSTRACT]. Background. Cardiovascular disease (CVD) is the leading cause of morbidity and mortality in the Americas, and hypertension is the most significant modifiable risk factor. However, hypertension control rates remain low, and CVD mortality is stagnant or rising after decades of continuing reduction. In 2016, the World Health Organization (WHO) launched the HEARTS technical package to improve hypertension control. The Pan American Health Organization (PAHO) designed the HEARTS in the Americas Initiative to improve CVD risk management, emphasizing hypertension control, to date implemented in 21 countries. Methods. To advance implementation, an interdisciplinary group of practitioners was engaged to select the key evidence-based drivers of hypertension control and to design a comprehensive scorecard to monitor their implementation at primary care health facilities (PHC). The group studied high-performing health systems that achieve high hypertension control through quality improvement programs focusing on specific process measures, with regular feedback to providers at health facilities. Findings. The final selected eight drivers were categorized into five main domains: (1) diagnosis (blood pressure measurement accuracy and CVD risk evaluation); (2) treatment (standardized treatment protocol and treatment intensification); (3) continuity of care and follow-up; (4) delivery system (team-based care, medication refill), and (5) system for performance evaluation. The drivers and recommendations were then translated into process measures, resulting in two interconnected scorecards integrated into the HEARTS in the Americas monitoring and evaluation system. Interpretation. Focus on these key hypertension drivers and resulting scorecards, will guide the quality improvement process to achieve population control goals at the participating health centers in HEARTS implementing countries.

[RESUMEN]. Antecedentes. Las enfermedades cardiovasculares (ECV) son la principal causa de morbilidad y mortalidad en la Región de las Américas y la hipertensión es el factor de riesgo modificable asociado más importante. Sin embargo, las tasas de control de la hipertensión siguen siendo bajas y la mortalidad por ECV está estancada o en aumento después de décadas de reducción continua. En el 2016, la Organización Mundial de la Salud (OMS) presentó el paquete técnico HEARTS para mejorar el control de la hipertensión. La Organización Panamericana de la Salud (OPS) diseñó la iniciativa HEARTS en las Américas para mejorar el control del riesgo de ECV, que hace hincapié en el control de la hipertensión y que, hasta la fecha, se ha implementado en 21 países. Métodos. Para avanzar en la implementación, se creó un grupo interdisciplinario de profesionales de la salud con el objetivo de seleccionar los factores impulsores claves del control de la hipertensión basados en la evidencia y diseñar un método de puntuación integral para dar seguimiento a su implementación en los centros de atención de salud primaria (APS). El grupo estudió los sistemas de salud de alto desempeño que logran un control elevado de la hipertensión mediante programas de mejora de la calidad que se centran en medidas específicas con respecto a los procesos, con retroalimentación regular a los prestadores en los centros de salud. Resultados. Los ocho factores impulsores finales seleccionados se clasificaron en cinco dominios principales: 1) diagnóstico (exactitud de la medición de la presión arterial y evaluación del riesgo de ECV); 2) tratamiento (protocolo de tratamiento e intensificación del tratamiento estandarizados); 3) continuidad de la atención y seguimiento; 4) sistema de prestación del tratamiento (atención basada en un trabajo en equipo, reposición de la medicación) y 5) sistema para la evaluación del desempeño. Los factores impulsores y las recomendaciones se tradujeron en medidas con respecto a los procesos, lo que llevó a dos métodos de puntuación integrados e interconectados en el sistema de seguimiento y evaluación del programa HEARTS en las Américas. Conclusiones. El enfoque que se centra en estos factores impulsores clave de la hipertensión y los métodos de puntuación resultantes servirá de guía para el proceso de mejora de la calidad con objeto de alcanzar los objetivos de control a nivel poblacional en los centros de salud participantes de los países que implementan el programa HEARTS.

Factores impulsores y métodos de puntuación para mejorar el control de la hipertensión en la práctica clínica de la atención primaria: recomendaciones del grupo de innovación de HEARTS en las Américas

[RESUMEN]. Antecedentes. Las enfermedades cardiovasculares (ECV) son la principal causa de morbilidad y mortalidad en la Región de las Américas y la hipertensión es el factor de riesgo modificable asociado más importante. Sin embargo, las tasas de control de la hipertensión siguen siendo bajas y la mortalidad por ECV está estancada o en aumento después de décadas de reducción continua. En el 2016, la Organización Mundial de la Salud (OMS) presentó el paquete técnico HEARTS para mejorar el control de la hipertensión. La Organización Panamericana de la Salud (OPS) diseñó la iniciativa HEARTS en las Américas para mejorar el control del riesgo de ECV, que hace hincapié en el control de la hipertensión y que, hasta la fecha, se ha implementado en 21 países. Métodos. Para avanzar en la implementación, se creó un grupo interdisciplinario de profesionales de la salud con el objetivo de seleccionar los factores impulsores claves del control de la hipertensión basados en la evidencia y diseñar un método de puntuación integral para dar seguimiento a su implementación en los centros de atención de salud primaria (APS). El grupo estudió los sistemas de salud de alto desempeño que logran un control elevado de la hipertensión mediante programas de mejora de la calidad que se centran en medidas específicas con respecto a los procesos, con retroalimentación regular a los prestadores en los centros de salud. Resultados. Los ocho factores impulsores finales seleccionados se clasificaron en cinco dominios principales: 1) diagnóstico (exactitud de la medición de la presión arterial y evaluación del riesgo de ECV); 2) tratamiento (protocolo de tratamiento e intensificación del tratamiento estandarizados); 3) continuidad de la atención y seguimiento; 4) sistema de prestación del tratamiento (atención basada en un trabajo en equipo, reposición de la medicación) y 5) sistema para la evaluación del desempeño. Los factores impulsores y las recomendaciones se tradujeron en medidas con respecto a los procesos, lo que llevó a dos métodos de puntuación integrados e interconectados en el sistema de seguimiento y evaluación del programa HEARTS en las Américas. Conclusiones. El enfoque que se centra en estos factores impulsores clave de la hipertensión y los métodos de puntuación resultantes servirá de guía para el proceso de mejora de la calidad con objeto de alcanzar los objetivos de control a nivel poblacional en los centros de salud participantes de los países que implementan el programa HEARTS.

[ABSTRACT]. Background. Cardiovascular disease (CVD) is the leading cause of morbidity and mortality in the Americas, and hypertension is the most significant modifiable risk factor. However, hypertension control rates remain low, and CVD mortality is stagnant or rising after decades of continuing reduction. In 2016, the World Health Organization (WHO) launched the HEARTS technical package to improve hypertension control. The Pan American Health Organization (PAHO) designed the HEARTS in the Americas Initiative to improve CVD risk management, emphasizing hypertension control, to date implemented in 21 countries. Methods. To advance implementation, an interdisciplinary group of practitioners was engaged to select the key evidence-based drivers of hypertension control and to design a comprehensive scorecard to monitor their implementation at primary care health facilities (PHC). The group studied high-performing health systems that achieve high hypertension control through quality improvement programs focusing on specific process measures, with regular feedback to providers at health facilities. Findings. The final selected eight drivers were categorized into five main domains: (1) diagnosis (blood pressure measurement accuracy and CVD risk evaluation); (2) treatment (standardized treatment protocol and treatment intensification); (3) continuity of care and follow-up; (4) delivery system (team-based care, medication refill), and (5) system for performance evaluation. The drivers and recommendations were then translated into process measures, resulting in two interconnected scorecards integrated into the HEARTS in the Americas monitoring and evaluation system. Interpretation. Focus on these key hypertension drivers and resulting scorecards, will guide the quality improvement process to achieve population control goals at the participating health centers in HEARTS implementing countries.

[RESUMO]. Fundamentos. As doenças cardiovasculares (DCV) são as principais causas de morbimortalidade nas Américas, e a hipertensão arterial (HÁ) é o fator de risco modificável mais importante. Porém, as taxas de controle da HA continuam baixas, e a mortalidade por DCV está estagnada ou aumentando após décadas de redução contínua. Em 2016, a Organização Mundial da Saúde (OMS) lançou o pacote de medidas técnicas HEARTS para melhorar o controle da HA. A Organização Pan-Americana da Saúde (OPAS) criou a iniciativa HEARTS nas Américas para melhorar a gestão do risco cardiovascular (RCV), com ênfase no controle da HA. Até agora, essa iniciativa foi implementada em 21 países. Métodos. Para impulsionar a implementação, recrutou-se um grupo multidisciplinar de profissionais para selecionar impulsionadores-chave do controle da HA com base em evidências e elaborar um scorecard completo para monitorar sua implementação em unidades de atenção primária à saúde (APS). O grupo estudou sistemas de saúde com alto desempenho que haviam conseguido atingir um alto nível de controle da HA por meio de programas de melhoria da qualidade focados em medidas específicas de processo, com feedback regular para os profissionais das unidades de saúde. Resultados. Os oito fatores impulsionadores incluídos na seleção final foram categorizados em cinco domínios principais: (1) diagnóstico (exatidão da medição da pressão arterial e avaliação do RCV); (2) tratamento (protocolo padronizado de tratamento e intensificação do tratamento); (3) continuidade do cuidado e acompanhamento; (4) modelo de atenção (atendimento baseado em equipe, renovação da prescrição); e (5) sistema de avaliação do desempenho. Em seguida, os impulsionadores e as recomendações foram transformados em medidas de processo, gerando dois scorecards inter-relacionados integrados ao sistema de monitoramento e avaliação da Iniciativa HEARTS nas Américas. Interpretação. O foco nesses impulsionadores-chave da HA e nos scorecards resultantes orientará o processo de melhoria da qualidade para atingir as metas de controle, em nível populacional, dos centros de saúde participantes nos países que estão implementando a iniciativa HEARTS.

Behavior of Occupied and Void Space in Molecular Crystal Structures at High Pressure.

We report a Monte Carlo algorithm for calculation of occupied ("network") and unoccupied ("void") space in crystal structures. The variation of the volumes of the voids and the network of intermolecular contacts with pressure sensitively reveals discontinuities associated with first- and second-order phase transitions, providing insights into the effect of compression (and, in principle, other external stimuli) at a level between those observed in individual contact distances and the overall unit cell dimensions. The method is shown to be especially useful for the correlation of high-pressure crystallographic and spectroscopic data, illustrated for naphthalene, where a phase transition previously detected by vibrational spectroscopy, and debated in the literature for over 80 years, has been revealed unambiguously in crystallographic data for the first time. Premonitory behavior before a phase transition and crystal collapse at the end of a compression series has also been detected. The network and void volumes for 129 high-pressure studies taken from the Cambridge Structural Database (CSD) were fitted to equation of state to show that networks typically have bulk moduli between 40 and 150 GPa, while those of voids fall into a much smaller range, 2-5 GPa. These figures are shown to reproduce the narrow range of overall bulk moduli of molecular solids (ca. 5-20 GPa). The program, called CellVol, has been written in Python using the CSD Python API and can be run through the command line or through the Cambridge Crystallographic Data Centre's Mercury interface.

Fatores impulsionadores e scorecards para melhorar o controle da hipertensão arterial na atenção primária: recomendações do Grupo de Inovação da Iniciativa HEARTS nas Américas / Drivers and scorecards to improve hypertension control in primary care practice: Recommendations from the HEARTS in the Americas Innovation Group / Factores impulsores y métodos de puntuación para mejorar el control de la hipertensión en la práctica clínica de la atención primaria: recomendaciones del grupo de innovación de HEARTS en las Américas

RESUMO Fundamentos. As doenças cardiovasculares (DCV) são as principais causas de morbimortalidade nas Américas, e a hipertensão arterial (HÁ) é o fator de risco modificável mais importante. Porém, as taxas de controle da HA continuam baixas, e a mortalidade por DCV está estagnada ou aumentando após décadas de redução contínua. Em 2016, a Organização Mundial da Saúde (OMS) lançou o pacote de medidas técnicas HEARTS para melhorar o controle da HA. A Organização Pan-Americana da Saúde (OPAS) criou a iniciativa HEARTS nas Américas para melhorar a gestão do risco cardiovascular (RCV), com ênfase no controle da HA. Até agora, essa iniciativa foi implementada em 21 países. Métodos. Para impulsionar a implementação, recrutou-se um grupo multidisciplinar de profissionais para selecionar impulsionadores-chave do controle da HA com base em evidências e elaborar um scorecard completo para monitorar sua implementação em unidades de atenção primária à saúde (APS). O grupo estudou sistemas de saúde com alto desempenho que haviam conseguido atingir um alto nível de controle da HA por meio de programas de melhoria da qualidade focados em medidas específicas de processo, com feedback regular para os profissionais das unidades de saúde. Resultados. Os oito fatores impulsionadores incluídos na seleção final foram categorizados em cinco domínios principais: (1) diagnóstico (exatidão da medição da pressão arterial e avaliação do RCV); (2) tratamento (protocolo padronizado de tratamento e intensificação do tratamento); (3) continuidade do cuidado e acompanhamento; (4) modelo de atenção (atendimento baseado em equipe, renovação da prescrição); e (5) sistema de avaliação do desempenho. Em seguida, os fatores impulsionadores e as recomendações foram transformados em medidas de processo, gerando dois scorecards inter-relacionados integrados ao sistema de monitoramento e avaliação da Iniciativa HEARTS nas Américas. Interpretação. O foco nesses impulsionadores-chave da HA e nos scorecards resultantes orientará o processo de melhoria da qualidade para atingir as metas de controle, a nível populacional, dos centros de saúde participantes nos países que estão implementando a iniciativa HEARTS.

ABSTRACT Background. Cardiovascular disease (CVD) is the leading cause of morbidity and mortality in the Americas, and hypertension is the most significant modifiable risk factor. However, hypertension control rates remain low, and CVD mortality is stagnant or rising after decades of continuing reduction. In 2016, the World Health Organization (WHO) launched the HEARTS technical package to improve hypertension control. The Pan American Health Organization (PAHO) designed the HEARTS in the Americas Initiative to improve CVD risk management, emphasizing hypertension control, to date implemented in 21 countries. Methods. To advance implementation, an interdisciplinary group of practitioners was engaged to select the key evidence-based drivers of hypertension control and to design a comprehensive scorecard to monitor their implementation at primary care health facilities (PHC). The group studied high-performing health systems that achieve high hypertension control through quality improvement programs focusing on specific process measures, with regular feedback to providers at health facilities. Findings. The final selected eight drivers were categorized into five main domains: (1) diagnosis (blood pressure measurement accuracy and CVD risk evaluation); (2) treatment (standardized treatment protocol and treatment intensification); (3) continuity of care and follow-up; (4) delivery system (team-based care, medication refill), and (5) system for performance evaluation. The drivers and recommendations were then translated into process measures, resulting in two interconnected scorecards integrated into the HEARTS in the Americas monitoring and evaluation system. Interpretation. Focus on these key hypertension drivers and resulting scorecards, will guide the quality improvement process to achieve population control goals at the participating health centers in HEARTS implementing countries.

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Factores impulsores y métodos de puntuación para mejorar el control de la hipertensión en la práctica clínica de la atención primaria: recomendaciones del grupo de innovación de HEARTS en las Américas / Drivers and scorecards to improve hypertension control in primary care practice: Recommendations from the HEARTS in the Americas Innovation Group / Fatores impulsionadores e scorecards para melhorar o controle da hipertensão arterial na atenção primária: recomendações do Grupo de Inovação da Iniciativa HEARTS nas Américas

resumen está disponible en el texto completo

ABSTRACT Background. Cardiovascular disease (CVD) is the leading cause of morbidity and mortality in the Americas, and hypertension is the most significant modifiable risk factor. However, hypertension control rates remain low, and CVD mortality is stagnant or rising after decades of continuing reduction. In 2016, the World Health Organization (WHO) launched the HEARTS technical package to improve hypertension control. The Pan American Health Organization (PAHO) designed the HEARTS in the Americas Initiative to improve CVD risk management, emphasizing hypertension control, to date implemented in 21 countries. Methods. To advance implementation, an interdisciplinary group of practitioners was engaged to select the key evidence-based drivers of hypertension control and to design a comprehensive scorecard to monitor their implementation at primary care health facilities (PHC). The group studied high-performing health systems that achieve high hypertension control through quality improvement programs focusing on specific process measures, with regular feedback to providers at health facilities. Findings. The final selected eight drivers were categorized into five main domains: (1) diagnosis (blood pressure measurement accuracy and CVD risk evaluation); (2) treatment (standardized treatment protocol and treatment intensification); (3) continuity of care and follow-up; (4) delivery system (team-based care, medication refill), and (5) system for performance evaluation. The drivers and recommendations were then translated into process measures, resulting in two interconnected scorecards integrated into the HEARTS in the Americas monitoring and evaluation system. Interpretation. Focus on these key hypertension drivers and resulting scorecards, will guide the quality improvement process to achieve population control goals at the participating health centers in HEARTS implementing countries.

RESUMO Fundamentos. As doenças cardiovasculares (DCV) são as principais causas de morbimortalidade nas Américas, e a hipertensão arterial (HÁ) é o fator de risco modificável mais importante. Porém, as taxas de controle da HA continuam baixas, e a mortalidade por DCV está estagnada ou aumentando após décadas de redução contínua. Em 2016, a Organização Mundial da Saúde (OMS) lançou o pacote de medidas técnicas HEARTS para melhorar o controle da HA. A Organização Pan-Americana da Saúde (OPAS) criou a iniciativa HEARTS nas Américas para melhorar a gestão do risco cardiovascular (RCV), com ênfase no controle da HA. Até agora, essa iniciativa foi implementada em 21 países. Métodos. Para impulsionar a implementação, recrutou-se um grupo multidisciplinar de profissionais para selecionar impulsionadores-chave do controle da HA com base em evidências e elaborar um scorecard completo para monitorar sua implementação em unidades de atenção primária à saúde (APS). O grupo estudou sistemas de saúde com alto desempenho que haviam conseguido atingir um alto nível de controle da HA por meio de programas de melhoria da qualidade focados em medidas específicas de processo, com feedback regular para os profissionais das unidades de saúde. Resultados. Os oito fatores impulsionadores incluídos na seleção final foram categorizados em cinco domínios principais: (1) diagnóstico (exatidão da medição da pressão arterial e avaliação do RCV); (2) tratamento (protocolo padronizado de tratamento e intensificação do tratamento); (3) continuidade do cuidado e acompanhamento; (4) modelo de atenção (atendimento baseado em equipe, renovação da prescrição); e (5) sistema de avaliação do desempenho. Em seguida, os impulsionadores e as recomendações foram transformados em medidas de processo, gerando dois scorecards inter-relacionados integrados ao sistema de monitoramento e avaliação da Iniciativa HEARTS nas Américas. Interpretação. O foco nesses impulsionadores-chave da HA e nos scorecards resultantes orientará o processo de melhoria da qualidade para atingir as metas de controle, em nível populacional, dos centros de saúde participantes nos países que estão implementando a iniciativa HEARTS.

Control and elimination of lymphatic filariasis in Oceania: Prevalence, geographical distribution, mass drug administration, and surveillance in Samoa, 1998-2017.

Lymphatic filariasis (LF) is a major public health problem globally and in the Pacific Region. The Global Programme to Eliminate LF has made great progress but LF is persistent and resurgent in some Pacific countries and territories. Samoa remains endemic for LF despite elimination efforts through multiple two-drug mass drug administrations (MDA) since 1965, including renewed elimination efforts started in 1999 under the Pacific Programme for Elimination of LF (PacELF). Despite eight rounds of national and two rounds of subnational MDA under PacELF, Samoa failed transmission assessment surveys (TAS) in all three evaluation units in 2017. In 2018, Samoa was the first to distribute countrywide triple-drug MDA using ivermectin, diethylcarbamazine (DEC), and albendazole. This paper provides a review of MDAs and historical survey results from 1998 to 2017 in Samoa and highlights lessons learnt from LF elimination efforts, including challenges and potential ways to overcome them to successfully achieve elimination.

Automated tracking of emergency department abdominal CT findings during the COVID-19 pandemic using natural language processing.

PURPOSE: During the COVID-19 pandemic, emergency department (ED) volumes have fluctuated. We hypothesized that natural language processing (NLP) models could quantify changes in detection of acute abdominal pathology (acute appendicitis (AA), acute diverticulitis (AD), or bowel obstruction (BO)) on CT reports. METHODS: This retrospective study included 22,182 radiology reports from CT abdomen/pelvis studies performed at an urban ED between January 1, 2018 to August 14, 2020. Using a subset of 2448 manually annotated reports, we trained random forest NLP models to classify the presence of AA, AD, and BO in report impressions. Performance was assessed using 5-fold cross validation. The NLP classifiers were then applied to all reports. RESULTS: The NLP classifiers for AA, AD, and BO demonstrated cross-validation classification accuracies between 0.97 and 0.99 and F1-scores between 0.86 and 0.91. When applied to all CT reports, the estimated numbers of AA, AD, and BO cases decreased 43-57% in April 2020 (first regional peak of COVID-19 cases) compared to 2018-2019. However, the number of abdominal pathologies detected rebounded in May-July 2020, with increases above historical averages for AD. The proportions of CT studies with these pathologies did not significantly increase during the pandemic period. CONCLUSION: Dramatic decreases in numbers of acute abdominal pathologies detected by ED CT studies were observed early on during the COVID-19 pandemic, though these numbers rapidly rebounded. The proportions of CT cases with these pathologies did not increase, which suggests patients deferred care during the first pandemic peak. NLP can help automatically track findings in ED radiology reporting.

Lipid-Based Natural Food Extracts for Effective Control of Botrytis Bunch Rot and Powdery Mildew on Field-Grown Winegrapes in New Zealand.

Synthetic controls of crop pathogens are increasingly associated with harm to the environment and human health, and pathogen resistance. Pesticide residues in crops can also act as non-tariff trade barriers. There is therefore a strong imperative to develop biologically based and natural product (NP) biofungicides as more sustainable alternatives for crop pathogen control. We demonstrate the field efficacy, over multiple seasons, of NP biofungicides, NP1 (based on anhydrous milk fat) and NP2 (based on soybean oil), on two major diseases of winegrapes-Botrytis bunch rot (Botrytis) and powdery mildew (PM). The NPs were integrated into a season-long integrated disease management programme that has produced chemical-residue-free wines. Efficacies for Botrytis control on three different varieties were: 63-97% on Chardonnay, 0-96% for Sauvignon Blanc and 46-58% on Riesling; with 65-98% PM control on Chardonnay and Riesling. NP2 exhibited the significant control of Botrytis latent infections, making it a viable alternative to mid-season synthetic fungicides. Disease control was significantly better than the untreated control and usually as efficacious as the synthetic fungicide treatment(s). Yields and wine quality in NP-treated crops were normally equivalent to those in the synthetic fungicide treatments. The results indicate that NP-mediated disease control of Botrytis and powdery mildew can be obtained in the vineyard, without synthetic fungicide input.

Intracerebral haemorrhage in patients with brain metastases receiving therapeutic anticoagulation.

BACKGROUND: Venous thromboembolism is common in patients with solid malignancies and brain metastases. Whether to anticoagulate such patients is controversial given the possibility of intracerebral haemorrhage (ICH). We evaluated the added risk of ICH in patients with brain metastases receiving therapeutic anticoagulation. METHODS: We performed a matched, retrospective cohort study of 291 patients (100 receiving therapeutic anticoagulation vs 191 controls) with brain metastases managed at Brigham and Women's Hospital/Dana-Farber Cancer Institute between 1998 and 2015. For each patient, all MRI studies of the brain were reviewed to identify ICH. Propensity score matching and multivariable Cox regression were used to mitigate confounding. RESULTS: The risk of ICH was comparable in patients receiving anticoagulation versus controls preanticoagulation. Postanticoagulation, we observed significant or borderline-significant associations between anticoagulation and development of any ICH (HR 1.31, 95% CI 0.96 to 1.79, p=0.09), ICH as identified by gradient echo/susceptibility-weighted imaging (HR 1.46, 95% CI 1.06 to 2.01, p=0.02), symptomatic ICH (HR 1.80, 95% CI 1.01 to 3.22, p=0.05), extralesional ICH (HR 5.82, 95% CI 1.56 to 21.7, p=0.009) and fatal ICH (HR 5.68, 95% CI 0.60 to 54.2, p=0.13). Anticoagulation was associated with differentially higher ICH risk in patients with prior ICH versus no prior ICH (HR 2.20 vs 0.68, respectively, p interaction <0.001) and symptomatic ICH risk in melanoma versus other primary malignancies (HR 6.46 vs 1.36, respectively, p interaction=0.02). CONCLUSIONS: Anticoagulation is associated with clinically significant ICH in patients with brain metastases, especially those with melanoma or prior ICH. The indication for anticoagulation and risk of intracerebral bleeding should be considered on an individual basis among such patients.