To determine whether a new triage system safely diverts a proportion of emergency department (ED) patients to a general practitioner cooperative (GPC).
Unblinded randomised controlled trial with ...weekends serving as clusters (three intervention clusters for each control). The intervention was triage by a nurse using a new extension to the Manchester Triage System assigning low-risk patients to the GPC. During intervention weekends, patients were encouraged to follow this assignment; it was not communicated during control weekends (all patients remained at the ED). The primary outcome was the proportion of patients assigned to and handled by the GPC during intervention weekends. The trial was randomised for the secondary outcome: the proportion of patients assigned to the GPC. Additional outcomes were association of these outcomes with possible confounders (study tool parameters, nurse, and patient characteristics), proportion of patients referred back to the ED by the GPC, hospitalisations, and performance of the study tool to detect primary care patients (the opinion of the treating physician was the gold standard).
In the intervention group, 838/6294 patients (13.3%, 95% CI 12.5 to 14.2) were assigned to the GPC, in the control group this was 431/1744 (24.7%, 95% CI 22.7 to 26.8). In total, 599/6294 patients (9.5%, 95% CI 8.8 to 10.3) experienced the primary outcome which was influenced by the reason for encounter, age, and the nurse. 24/599 patients (4.0%, 95% CI 2.7 to 5.9) were referred back to the ED, three were hospitalised. Positive and negative predictive values of the studied tool during intervention weekends were 0.96 (95%CI 0.94 to 0.97) and 0.60 (95% CI 0.58 to 0.62). Out of the patients assigned to the GPC, 2.4% (95% CI 1.7 to 3.4) were hospitalised.
ED nurses using a new tool safely diverted 9.5% of the included patients to primary care.
ClinicalTrials.gov Identifier: NCT03793972.
Objectives To determine whether a new triage system safely diverts a proportion of emergency department (ED) patients to a general practitioner cooperative (GPC). Methods Unblinded randomised ...controlled trial with weekends serving as clusters (three intervention clusters for each control). The intervention was triage by a nurse using a new extension to the Manchester Triage System assigning low-risk patients to the GPC. During intervention weekends, patients were encouraged to follow this assignment; it was not communicated during control weekends (all patients remained at the ED). The primary outcome was the proportion of patients assigned to and handled by the GPC during intervention weekends. The trial was randomised for the secondary outcome: the proportion of patients assigned to the GPC. Additional outcomes were association of these outcomes with possible confounders (study tool parameters, nurse, and patient characteristics), proportion of patients referred back to the ED by the GPC, hospitalisations, and performance of the study tool to detect primary care patients (the opinion of the treating physician was the gold standard). Results In the intervention group, 838/6294 patients (13.3%, 95% CI 12.5 to 14.2) were assigned to the GPC, in the control group this was 431/1744 (24.7%, 95% CI 22.7 to 26.8). In total, 599/6294 patients (9.5%, 95% CI 8.8 to 10.3) experienced the primary outcome which was influenced by the reason for encounter, age, and the nurse. 24/599 patients (4.0%, 95% CI 2.7 to 5.9) were referred back to the ED, three were hospitalised. Positive and negative predictive values of the studied tool during intervention weekends were 0.96 (95%CI 0.94 to 0.97) and 0.60 (95% CI 0.58 to 0.62). Out of the patients assigned to the GPC, 2.4% (95% CI 1.7 to 3.4) were hospitalised. Conclusions ED nurses using a new tool safely diverted 9.5% of the included patients to primary care. Trial registration ClinicalTrials.gov Identifier: NCT03793972
Objectives To determine whether a new triage system safely diverts a proportion of emergency department (ED) patients to a general practitioner cooperative (GPC). Methods Unblinded randomised ...controlled trial with weekends serving as clusters (three intervention clusters for each control). The intervention was triage by a nurse using a new extension to the Manchester Triage System assigning low-risk patients to the GPC. During intervention weekends, patients were encouraged to follow this assignment; it was not communicated during control weekends (all patients remained at the ED). The primary outcome was the proportion of patients assigned to and handled by the GPC during intervention weekends. The trial was randomised for the secondary outcome: the proportion of patients assigned to the GPC. Additional outcomes were association of these outcomes with possible confounders (study tool parameters, nurse, and patient characteristics), proportion of patients referred back to the ED by the GPC, hospitalisations, and performance of the study tool to detect primary care patients (the opinion of the treating physician was the gold standard). Results In the intervention group, 838/6294 patients (13.3%, 95% CI 12.5 to 14.2) were assigned to the GPC, in the control group this was 431/1744 (24.7%, 95% CI 22.7 to 26.8). In total, 599/6294 patients (9.5%, 95% CI 8.8 to 10.3) experienced the primary outcome which was influenced by the reason for encounter, age, and the nurse. 24/599 patients (4.0%, 95% CI 2.7 to 5.9) were referred back to the ED, three were hospitalised. Positive and negative predictive values of the studied tool during intervention weekends were 0.96 (95%CI 0.94 to 0.97) and 0.60 (95% CI 0.58 to 0.62). Out of the patients assigned to the GPC, 2.4% (95% CI 1.7 to 3.4) were hospitalised. Conclusions ED nurses using a new tool safely diverted 9.5% of the included patients to primary care. Trial registration ClinicalTrials.gov Identifier: NCT03793972
The ‘continuum of care’ is proposed as a key framework for the delivery of maternal, neonatal and child health services. This study examined the extent of dropout as well as factors associated with ...retention across the MNCH continuum from antenatal care (ANC), through skilled birth attendance (SBA), to postnatal care (PNC).
We analyzed data from 1931 women who delivered in the preceding 2–14 months, from a twostage cluster sampling household survey in four districts of Tanzania’s Morogoro region. The survey was conducted in 2011 as a part of a baseline for an independent evaluation of a maternal health program. Using the Anderson model of health care seeking, we fitted logistic models for three transition stages in the continuum.
Only 10% of women received the ‘recommended’care package (4+ANC visits, SBA, and 1+PNC visit), while 1% reported not having care at any stage. Receipt of four ANC visits was positively associated with women being older in age (age 20–34 years—OR: 1.77, 95% CI: 1.22–2.56; age 35–49 years—2.03, 1.29–3.2), and knowledge of danger signs (1.75, 1.39–2.1). A pro-rich bias was observed in facility-based deliveries (proxy for SBA), with women from the fourth (1.66, 1.12–2.47) and highest quintiles of household wealth (3.4, 2.04–5.66) and the top tertile of communities by wealth (2.9, 1.14–7.4). Higher rates of facility deliveries were also reported with antenatal complications (1.37, 1.05–1.79), and 4+ANC visits (1.55, 1.14–2.09). Returning for PNC was highest among the wealthiest communities (2.25, 1.21–4.44); catchment areas of a new PNC program (1.89, 1.03–3.45); knowledge of danger signs (1.78, 1.13–2.83); community health worker counselling (4.22, 1.97–9.05); complicated delivery (3.25, 1.84–5.73); and previous health provider counselling on family planning (2.39, 1.71–3.35).
Dropout from maternal care continuum is high, especially for the poorest, in rural Tanzania. Interactions with formal health system and perceived need for future services appear to be important factors for retention.
”连续照护”是孕产妇、新生儿和儿童健康服务提供的关键框 架。MNCH 连续照护是从产前护理 （ANC） 、熟练助产护 理 （SBA） 到产后护理（PNC） 的连续过程, 本研究调查中途 退出 MNCH连续照护和继续使用的相关因素。
我们在坦桑尼亚莫罗戈罗省的四个区采用二阶段整群抽样住 户调查, 收集并分析了过去2-14个月分娩的 1931 位妇女的数 据并分析。该调查于 2011 年进行, 是一项孕产妇健康项目独 立评估基线调查的一部分。采用安德森模型分析求医行为, 建 立 Logistic 模型分析连续照护中的三个过渡阶段。
仅10%的妇女接受了推荐的整体护理 （4+ANC, SBA和1+PNC）, 1%的妇女未在任何阶段使用 MUCH 护理。接受四次 ANC 检查与年龄呈正相关（20–34 岁： OR=1.77, 95%CI 1.22–2.56； 35–49 岁： OR=2.03, 95%CI 1.29–3.2）, 与对危 险体征的了解也呈正相关 （1.75, 1.39–2.1） 。院内分娩 （SBA 的代理变量） 显示偏向富人的偏倚, 最富裕五分之一 和其次家庭的妇女院内分娩较高 （3.4, 2.04–5.66； 1.66, 1.12–2.47）, 最富裕的三分之一社区的妇女院内分娩也较高 （2.9, 1.14–7.4） 。 高院内分娩率还与产前并发症 （1.37, 1.05–1.79） 和接受4þ ANC 检查相关（1.55, 1.14–2.09） 。 与 返回医疗机构接受PNC 关联最强的是最富裕社区 （2.25, 1.21–4.44） ；新 PNC 项目服务地区 （1.89, 1.03–3.45） ； 了 解危险体征 （1.78, 1.13–2.83） ； 有社区卫生工作者咨询服务 （4.22, 1.97–9.05） ； 并发症分娩 （3.25, 1.84–5.73）； 和既 往计划生育咨询 （2.39, 1.71–3.35） 。
中途退出连续孕产妇保健的比例较高, 尤其是在坦桑尼亚贫困 人口和农村地区。与卫生体系的接触和对未来医疗服务需求 的预估可能是继续使用孕产妇保健的重要因素。
El ‘continuo de la atención’ se propone como un marco clave para la prestación de servicios de salud materna, neonatal e infantil (SMNI). Este estudio examinó el grado de deserción, así como los factores asociados con la retención a través del continuo de SMNI desde el cuidado prenatal (CPN), a través de la asistencia especializada en el parto (AEP), a la atención postnatal (APN).
Analizamos los datos de 1931 mujeres que dieron a luz entre los 2 y 14 meses anteriores, de una encuesta de hogares de muestreo por grupos de dos etapas en cuatro distritos de la región de Morogoro en Tanzania. La encuesta se llevó a cabo en 2011 como parte de una línea de base para una evaluación independiente de un programa de salud materna. Usando el modelo de Anderson de la búsqueda de atención de salud, ajustamos los modelos logísticos para tres etapas de transición en el continuo.
Sólo el 10% de las mujeres recibieron el paquete de atención “recomendado” (4+ visitas de CPN, AEP y 1 visita APN), mientras que el 1% informó que no había recibido atención en ninguna etapa. Haber recibido cuatro visitas de CPN se asoció positivamente con mujeres mayores en edad (edad 20-34 años—RP: 1.77, IC 95%: 1.22-2.56, edad 35 a 49 años—2.03, 1.29-3.2) y conocimiento de las señales de peligro (1.75, 1.39 – 2.1). Se observó un sesgo favorable a los ricos en los partos basados en instalaciones (lo cual representa la AEP), con las mujeres del cuarto quintil (1.66, 1.12-2.47) y el quintil más altos de la riqueza de los hogares (3.4, 2.04-5.66) y el tercio superior de las comunidades por riqueza (2.9, 1.14-7.4). También se reportaron tasas más altas de partos en instalaciones con complicaciones prenatales (1.37, 1.05-1.79), y 4+ visitas de CPN (1.55, 1.14- 2.09). El regreso a la APN fue mayor entre las comunidades más ricas (2.25, 1.21-4.44); áreas de captación de un nuevo programa de APN (1.89, 1.03-3.45); conocimiento de señales de peligro (1.78, 1.13-2.83); asesoramiento de trabajadores comunitarios de salud (4.22, 1.97-9.05); parto complicado (3.25, 1.84 – 5.73); y asesoramiento previo de proveedores de salud sobre planeación familiar (2.39, 1.71-3.35).
La deserción del continuo de la atención materna es alta, especialmente para los más pobres, en las zonas rurales de Tanzania. Las interacciones con el sistema formal de la salud y la necesidad percibida de servicios futuros parecen ser factores importantes para la retención.
•Restoration should address underlying causes of degradation.•The Playbook addresses political-economic perspectives within specific contexts.•Ten principles address how to achieve resilient and ...equitable ecosystem restoration.•Local and landscape processes are intricately linked to national and global scales.•Restoration aims to achieve ecologically, socially and economically just landscapes.
The urgency of restoring ecosystems to improve human wellbeing and mitigate climate and biodiversity crises is attracting global attention. The UN Decade on Ecosystem Restoration (2021–2030) is a global call to action to support the restoration of degraded ecosystems. And yet, many forest restoration efforts, for instance, have failed to meet restoration goals; indeed, they worsened social precarities and ecological conditions. By merely focusing on symptoms of forest loss and degradation, these interventions have neglected the underlying issues of equity and justice driving forest decline. To address these root causes, thus creating socially just and sustainable solutions, we develop the Political Ecology Playbook for Ecosystem Restoration. We outline a set of ten principles for achieving long-lasting, resilient, and equitable ecosystem restoration. These principles are guided by political ecology, a framework that addresses environmental concerns from a broadly political economic perspective, attending to power, politics, and equity within specific geographic and historical contexts. Drawing on the chain of explanation, this multi-scale, cross-landscapes Playbook aims to produce healthy relationships between people and nature that are ecologically, socially, and economically just – and thus sustainable and resilient – while recognizing the political nature of such relationships. We argue that the Political Ecology Playbook should guide ecosystem restoration worldwide.
The congenital bone marrow failure syndrome Diamond-Blackfan anemia (DBA) is typically associated with variants in ribosomal protein (RP) genes impairing erythroid cell development. Here we report ...multiple individuals with biallelic HEATR3 variants exhibiting bone marrow failure, short stature, facial and acromelic dysmorphic features, and intellectual disability. These variants destabilize a protein whose yeast homolog is known to synchronize the nuclear import of RPs uL5 (RPL11) and uL18 (RPL5), which are both critical for producing ribosomal subunits and for stabilizing the p53 tumor suppressor when ribosome biogenesis is compromised. Expression of HEATR3 variants or repression of HEATR3 expression in primary cells, cell lines of various origins, and yeast models impairs growth, differentiation, pre–ribosomal RNA processing, and ribosomal subunit formation reminiscent of DBA models of large subunit RP gene variants. Consistent with a role of HEATR3 in RP import, HEATR3-depleted cells or patient-derived fibroblasts display reduced nuclear accumulation of uL18. Hematopoietic progenitor cells expressing HEATR3 variants or small-hairpin RNAs knocking down HEATR3 synthesis reveal abnormal acceleration of erythrocyte maturation coupled to severe proliferation defects that are independent of p53 activation. Our study uncovers a new pathophysiological mechanism leading to DBA driven by biallelic HEATR3 variants and the destabilization of a nuclear import protein important for ribosome biogenesis.
•Biallelic variants in HEATR3 are associated with DBA and other clinical features in humans.•HEATR3 variants destabilize the protein, resulting in a reduction of nuclear uL18 and impaired ribosome biogenesis.
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Active rheumatoid arthritis originates from few joints but subsequently affects the majority of joints. Thus far, the pathways of the progression of the disease are largely unknown. As rheumatoid ...arthritis synovial fibroblasts (RASFs) which can be found in RA synovium are key players in joint destruction and are able to migrate in vitro, we evaluated the potential of RASFs to spread the disease in vivo. To simulate the primary joint of origin, we implanted healthy human cartilage together with RASFs subcutaneously into severe combined immunodeficient (SCID) mice. At the contralateral flank, we implanted healthy cartilage without cells. RASFs showed an active movement to the naive cartilage via the vasculature independent of the site of application of RASFs into the SCID mouse, leading to a marked destruction of the target cartilage. These findings support the hypothesis that the characteristic clinical phenomenon of destructive arthritis spreading between joints is mediated, at least in part, by the transmigration of activated RASFs.
Olaparib is an inhibitor of the human poly-(ADP-ribose)-polymerase enzymes (PARP1/2) needed to repair single-strand DNA breaks. It is used in breast, ovarian, prostate and pancreatic cancer.
This ...work aimed to describe the pharmacokinetics/pharmacodynamics (PK/PD) relationship between olaparib plasma concentrations and common adverse effects (i.e. anaemia and hypercreatininaemia), in a real-life setting, to propose a target concentration for therapeutic drug monitoring.
Two PK/PD models describing the evolution of haemoglobinaemia and creatininaemia as a function of time were developed, based on data from, respectively, 38 and 37 patients receiving olaparib. The final model estimates were used to calculate the incidence of anaemia and creatinine increase according to plasma trough concentrations for 1000 virtual subjects to define target exposure.
The final models correctly described the temporal evolution of haemoglobinaemia and creatininaemia for all patients. The haemoglobinaemia PK/PD model is inspired by Friberg's model, and the creatininaemia PK/PD model is an indirect response model. Model parameters were in agreement with physiological values and close to literature values for similar models. The mean (population) plasma haemoglobin concentration at treatment initiation, as estimated by the model, was 11.62 g/dL, while creatinine concentration was 71.91 µmol/L. Using simulations, we have identified a target trough concentration of 3500-4000 ng/mL, above which more than 20% of patients would report grade ≥3 anaemia.
Based on real-world data, we were able to properly describe the time course of haemoglobinaemia and plasma creatininaemia during olaparib treatment.
Obesity is a risk factor for many diseases, such as type 2 diabetes and cardiovascular diseases. In line with the need for precision medicine, the search for biomarkers reporting the progression of ...obesity- and diet-associated disorders is urgent. We used NMR to determine the metabolomics profile of key organs (lung, liver, heart, skeletal muscle, kidney, and brain) and serum from male C57Bl/6J mice (5 weeks old) fed for 6, 10, and 14 weeks on a high-fat and high-sucrose diet (HFHSD) vs. a standard diet (STD). We determined metabolite concentrations in the organs at each time point, which allowed us to discriminate age- and diet-related effects as well as the interactions between both, highlighting the need to evaluate the influence of age as a confounding factor on metabolic signatures. Notably, the analysis revealed the influence of time on metabolite concentrations in the STD condition, probably reflecting the juvenile-to-adult transition. Variations impacted the liver and lung metabolites, revealing the strong influence of the HFHS diet on normal metabolism maturation during youth.
A genomic cluster of
Braenderup ST22, a serovar of
subsp.
which causes symptoms of gastrointestinal illness, was notified by Danish authorities to the European Centre for Disease Prevention and ...Control (ECDC) on 3 May 2021. By 6 July 2021,
Braenderup outbreak cases (n = 348) had been reported from 12 countries in the European Union/European Economic Area (EU/EEA) and the United Kingdom (UK), including 68 hospitalised cases. With support from affected EU/EEA countries, and in partnership with the European Food Safety Authority (EFSA), ECDC established an international outbreak investigation team to rapidly identify the source and prevent outbreak spread. Consumption information was shared with affected countries through a standard line list, revealing that 124 of 197 cases (63%) reported having eaten (any) melons within 7 days prior to disease onset. The speed and completeness of the investigation, which identified the outbreak vehicle as galia melons imported from Honduras in June 2021, was a direct result of extensive collaboration and information sharing between countries' national food safety and public health authorities. This article describes the outbreak and the benefits, successes, and challenges of multi-country collaboration for consideration in future large foodborne outbreaks across Europe.
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