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Abstract Background De-implementation of low-value care can increase health care sustainability. We evaluated the reporting of direct costs of de-implementation and subsequent change (increase or decrease) in health care costs in randomized trials of de-implementation research. Methods We searched MEDLINE and Scopus databases without any language restrictions up to May 2021. We conducted study screening and data extraction independently and in duplicate. We extracted information related to study characteristics, types and characteristics of interventions, de-implementation costs, and impacts on health care costs. We assessed risk of bias using a modified Cochrane risk-of-bias tool. Results We screened 10,733 articles, with 227 studies meeting the inclusion criteria, of which 50 included information on direct cost of de-implementation or impact of de-implementation on health care costs. Studies were mostly conducted in North America (36%) or Europe (32%) and in the primary care context (70%). The most common practice of interest was reduction in the use of antibiotics or other medications (74%). Most studies used education strategies (meetings, materials) (64%). Studies used either a single strategy (52%) or were multifaceted (48%). Of the 227 eligible studies, 18 (8%) reported on direct costs of the used de-implementation strategy; of which, 13 reported total costs, and 12 reported per unit costs (7 reported both). The costs of de-implementation strategies varied considerably. Of the 227 eligible studies, 43 (19%) reported on impact of de-implementation on health care costs. Health care costs decreased in 27 studies (63%), increased in 2 (5%), and were unchanged in 14 (33%). Conclusion De-implementation randomized controlled trials typically did not report direct costs of the de-implementation strategies (92%) or the impacts of de-implementation on health care costs (81%). Lack of cost information may limit the value of de-implementation trials to decision-makers. Trial registration OSF (Open Science Framework): https://osf.io/ueq32 .

In this prospective two-center feasibility study, we evaluate the diagnostic value of intraoperative ex vivo specimenPET/CT imaging of radical prostatectomy (RP) and lymphadenectomy specimens. Ten patients with high-risk prostate cancer underwent clinical prostate-specific membrane antigen (PSMA) positron emission tomography/computed tomography (PET/CT) preoperatively on the day of surgery. Six patients received 68Ga-PSMA-11 and four 18F-PSMA-1007. Radioactivity of the resected specimen was measured again using a novel specimenPET/CT device (AURA10; XEOS Medical, Gent, Belgium) developed for intraoperative margin assessment. All index lesions of staging multiparametric magnetic resonance imaging could be visualized. Overall, specimenPET/CT correlated well with conventional PET/CT regarding detection of suspicious tracer foci (Pearson coefficient 0.935). In addition, specimenPET/CT demonstrated all lymph node metastases detected on conventional PET/CT (n = 3), as well as three previously undetected lymph node metastases. Importantly, all positive or close (

Abstract Background Healthcare costs are rising, and a substantial proportion of medical care is of little value. De-implementation of low-value practices is important for improving overall health outcomes and reducing costs. We aimed to identify and synthesize randomized controlled trials (RCTs) on de-implementation interventions and to provide guidance to improve future research. Methods MEDLINE and Scopus up to May 24, 2021, for individual and cluster RCTs comparing de-implementation interventions to usual care, another intervention, or placebo. We applied independent duplicate assessment of eligibility, study characteristics, outcomes, intervention categories, implementation theories, and risk of bias. Results Of the 227 eligible trials, 145 (64%) were cluster randomized trials (median 24 clusters; median follow-up time 305 days), and 82 (36%) were individually randomized trials (median follow-up time 274 days). Of the trials, 118 (52%) were published after 2010, 149 (66%) were conducted in a primary care setting, 163 (72%) aimed to reduce the use of drug treatment, 194 (85%) measured the total volume of care, and 64 (28%) low-value care use as outcomes. Of the trials, 48 (21%) described a theoretical basis for the intervention, and 40 (18%) had the study tailored by context-specific factors. Of the de-implementation interventions, 193 (85%) were targeted at physicians, 115 (51%) tested educational sessions, and 152 (67%) multicomponent interventions. Missing data led to high risk of bias in 137 (60%) trials, followed by baseline imbalances in 99 (44%), and deficiencies in allocation concealment in 56 (25%). Conclusions De-implementation trials were mainly conducted in primary care and typically aimed to reduce low-value drug treatments. Limitations of current de-implementation research may have led to unreliable effect estimates and decreased clinical applicability of studied de-implementation strategies. We identified potential research gaps, including de-implementation in secondary and tertiary care settings, and interventions targeted at other than physicians. Future trials could be improved by favoring simpler intervention designs, better control of potential confounders, larger number of clusters in cluster trials, considering context-specific factors when planning the intervention (tailoring), and using a theoretical basis in intervention design. Registration OSF Open Science Framework hk4b2

Melanoma is the most aggressive form of skin cancer and the leading cause of death from cutaneous tumors. Several studies have associated alterations in the TERT promoter region (pTERT) with gene overexpression, aggressiveness and poor prognosis of the disease. The aim of this study was to clarify the role of pTERT molecular status in paired samples of primary melanoma and metastasis using tissue and plasma to establish a correlation with disease progression and survival.A total of 88 FFPE tissue samples from 53 patients with advanced melanoma were analyzed. Of these, 35 had paired samples. We also examined cfDNA samples from plasma of 25 patients. We detected a good correlation between primary tumors and metastases in pTERT mutation and methylation status. We were also able to identify pTERT mutations in plasma samples that correlated with mutational status in tissue samples. Interestingly, the C250T mutation was associated with worse survival and higher TERT mRNA expression, compared to the other most common mutation: C228T. In addition, hyper-methylation of the promoter region seems to be related to the progression of pTERT wild type (WT) patients. These results suggest that TERT gene alterations plays an important role during tumor progression, with the detection of the C250T mutation in tissue and plasma as a potential biomarker of poor prognosis in patients with advanced melanoma.

IntroductionViolence against healthcare workers is a global health problem threatening healthcare workforce retention and health system resilience in a fragile post-COVID ‘normalisation’ period. In this perspective article, we argue that violence against healthcare workers must be made a greater priority. Our novel contribution to the debate is a comparative health system and policy approach.MethodsWe have chosen a most different systems comparative approach concerning the epidemiological, political, and geographic contexts. Brazil (under the Bolsonaro government) and the United Kingdom (under the Johnson government) serve as examples of countries that were strongly hit by the pandemic in epidemiological terms while also displaying policy failures. New Zealand and Germany represent the opposite. A rapid assessment was undertaken based on secondary sources and country expertise.ResultsWe found similar problems across countries. A global crisis makes healthcare workers vulnerable to violence. Furthermore, insufficient data and monitoring hamper effective prevention, and lack of attention may threaten women, the nursing profession, and migrant/minority groups the most. There were also relevant differences. No clear health system pattern can be identified. At the same time, professional associations and partly the media are strong policy actors against violence.ConclusionIn all countries, muchmore involvement from political leadership is needed. In addition, attention to the political dimension and all forms of violence are essential.

IntroductionDecision-makers initially had limited data to inform their policy responses to the COVID-19 pandemic. The research community developed several online databases to track cases, deaths, and hospitalizations; however, a major deficiency was the lack of detailed information on how health systems were responding to the pandemic and how they would need to be transformed going forward.ApproachIn an effort to fill this information gap, in March 2020, the European Observatory on Health Systems and Policies, the WHO European Regional Office and the European Commission created the COVID-19 Health System Response Monitor (HSRM) to collect and organise up-to-date information on how health systems, mainly in the WHO European Region, were responding to the COVID-19 pandemic.FindingsThe HSRM analysis and broader Observatory work on COVID-19 shone light on a range of health system challenges and weaknesses and catalogued policy options countries put in place during the pandemic to address these. Countries prioritised policies on investing in public health, supporting the workforce, maintaining financial stability, and strengthening governance in their response to COVID-19.OutlookCOVID-19 is likely to continue to impact health systems for the foreseeable future; the ability to cope with this pressure, and other shocks, depends on having good information on what other countries have done so that health systems develop adequate policy options. In support of this, the country information on the COVID-19 HSRM will remain available as a repository to inform decision makers on options for actions and possible measures against COVID-19 and other public health emergencies. Building on its previous work on health systems resilience, the European Observatory on Health Systems and Policies will sustain its focus on analysing key issues related to the recovery from the pandemic and making health systems more resilient. This includes policy knowledge transfer between countries and systematic resilience testing, aiming at contributing to an improved understanding of health system response, recovery, and preparedness.Contribution to the literature in non-technical languageThe COVID-19 Health System Response Monitor (HSRM) was the first database in the WHO European Region to collect and organise up-to-date information on how health systems were responding to the COVID-19 pandemic. The HSRM provides a repository of policies which can be used to inform decision makers in health and other policy domains on options for action and possible measures against COVID-19 and other public health emergencies. This initiative proved particularly valuable, especially during the early phases of the pandemic, when there was limited information for countries to draw on as they formulated their own policy response to the pandemic. Our perspectives paper highlights some key challenges within health systems that the HSRM was able to identify during the pandemic and considers policy options countries put in place in response. Our research contributes to literature on emergency responses and recovery, health systems performance assessment, particularly health system resilience, and showcases the Observatory experience on how to design such a data collection tool, as well as how to leverage its findings to support cross-country learning.

The Social Democratic victory in the 2019 Danish general election was a surprising and notable event. The election stands out as an important win for Social Democrats as this party family has experienced a significant decline in voter support across Europe in recent decades. At the same time, the election was marked by controversy as Denmark’s Social Democrats not only doubled-down on their traditional support for the welfare state but also took a sharp turn to the right on immigration policies. This article analyses the effects of political systems, ideology and polarisation, as well as issue salience and framing on party strategies. These variables help to account for the abrupt policy shift adopted by the Social Democrats in Denmark and why similar anti-immigration platforms were not embraced by Social Democratic parties in other Nordic countries. Further examination of voter survey data suggests that the adoption of stronger anti-immigration policies is likely to be an ineffective strategy for Social Democrats going forward.

This commentary considers the impact of the coronavirus disease 2019 (COVID-19) pandemic on the study of populist radical right (PRR) politicians and their influence on public health and health policy. A systematic review of recent research on the influence of PRR politicians on the health and welfare policies shows that health is not a policy arena that these politicians have much experience in. In office, their effects can be destructive, primarily because they subordinate health to their other goals. Brazil, the US and the UK all show this pattern. PRR politicians in opposition such as the Freedom Party of Austria (FPÖ) in Austria or the Lega in Italy, said very little during the actual health crisis, but once the public no longer appeared afraid they lost no time in reactivating anti-European Union (EU) sentiments. Whether in government or in opposition, PRR politicians opted for distraction and denial. Their effects ranged from making the pandemic worse.

A possível ocorrência de Thekopsora minima causando ferrugem em mirtilileiro foi observada em três pomares em Santa Catarina. Observações morfológicas e moleculares, bem como teste de patogenicidade, foram consistentes em mostrar que T. minima é o agente causal da ferrugem nos pomares de mirtilo. Diante da confirmação de T. minima no mirtileiro, fruticultores terão um grande desafio para manejar a ferrugem nos pomares catarinenses devido às condições ambientais adequadas à doença e a predominância de cultivares suscetíveis ao patógeno.

Hundreds of mRNA binding proteins (mRBPs) have been described in mammalian cells. Here, the authors identify RBPs differentially regulated in melanoma, and show the RBP CELF1 controlling a distinct set of protumorigenic factors.

Health technology assessment (HTA) refers to the systematic evaluation of the properties, effects, and/or impacts of health technology. The main purpose of the assessment is to inform decisionmakers in order to better support the introduction of new health technologies. New digital healthcare solutions like mHealth, artificial intelligence (AI), and robotics have brought with them a great potential to further develop healthcare services, but their introduction should follow the same criteria as that of other healthcare methods. They must provide evidence-based benefits and be safe to use, and their impacts on patients and organizations need to be clarified. The first objective of this study was to describe the state-of-the-art HTA methods for mHealth, AI, and robotics. The second objective of this study was to evaluate the domains needed in the assessment. The final aim was to develop an HTA framework for digital healthcare services to support the introduction of novel technologies into Finnish healthcare. In this study, the state-of-the-art HTA methods were evaluated using a literature review and interviews. It was noted that some good practices already existed, but the overall picture showed that further development is still needed, especially in the AI and robotics fields. With the cooperation of professionals, key aspects and domains that should be taken into account to make fast but comprehensive assessments were identified. Based on this information, we created a new framework which supports the HTA process for digital healthcare services. The framework was named Digi-HTA.

O presente estudo foi realizado no município de Caxias do Sul com o objetivo de investigar como a mudança constitucional de redução da maioridade penal influenciaria nos índices de crimes cometidos por menores. Trata-se de uma pesquisa de caráter exploratório, com delineamento de campo, com coleta de dados realizada com o Centro de Atendimento Socioeducativo (CASE) do município de Caxias do Sul - RS e o 12º Batalhão de Polícia Militar de Caxias do Sul, por meio de entrevista e questionário. Constatou-se que mudanças administrativas tiveram impacto positivo para o município, porém a estrutura familiar presente na vida dos jovens que vão para a marginalidade é um aspecto importante para a redução dos índices de crimes cometidos por menores.

Olive trees showing decline symptoms were reported in an orchard in Santa Catarina, Southern Brazil. The symptoms included foliar browning and leaf drop, dieback of twigs and branches, dark streaks in internal crown wood and necrotic lesions in bark. A grapevine sample exhibiting browning streaks in the vascular tissue of branches, trunk and roots, was also analysed. A Phialophora-like fungus was isolated from symptomatic tissues of both hosts, and monosporic cultures were established. Based on morphology and analysis of ITS, tub2 and tef sequences, the fungus was identified as Pleurostomophora richardsiae. Isolates inoculated onto young nursery olive trees and grapevines produced brown streaking in the wood in most of the inoculated plants. This is the first report of P. richardsiae occurring in olive trees and grapevines in Brazil.

Cytoplasmic polyadenylated transcripts have been poorly characterized, particularly in cancer. Here the authors identify a lineage-specific requirement of the cytoplasmic polyadenylation binding protein 4 (CPEB4) in malignant melanoma and show that it controls melanoma drivers MITF and RAB27A.

This paper aims at identifying in two English textbooks, High Up (2013) and Freeway (2010), suggested by the Programa Nacional do Livro Didático (PNLD), which activities have greater potential to promote writing abilities for communication. To achieve such objective, both books were analyzed and compared taking into consideration the conceptions of language, text genres, teaching sequence, and writing as a process in English as an additional language. The conclusion of this examination shows that there is a distance between the textbooks authors’ intention of dealing with written language, in an interactionist perspective, and the teaching material. Throughout the article, some suggestions were put forward in order to improve the sequences by adjusting them to the theoretical views of the books. The findings reveal that one of the books explored activities that consider aspects of genre, audience, text purpose, and writing as a process

Epidemiological associations linking between obstructive sleep apnea and poorer solid malignant tumor outcomes have recently emerged. Putative pathways proposed to explain that these associations have included enhanced hypoxia inducible factor (HIF)-1α and vascular endothelial growth factor (VEGF) cell expression in the tumor and altered immune functions via intermittent hypoxia (IH). Here, we examined relationships between HIF-1α and VEGF expression and nocturnal IH in cutaneous melanoma (CM) tumor samples. Prospectively recruited patients with CM tumor samples were included and underwent overnight polygraphy. General clinical features, apnea–hypopnea index (AHI), desaturation index (DI4%), and CM characteristics were recorded. Histochemical assessments of VEGF and HIF-1α were performed, and the percentage of positive cells (0, 75%) was blindly tabulated for VEGF expression, and as 0, 0–5.9, 6.0–10.0, >10.0% for HIF-1α expression, respectively. Cases with HIF-1α expression >6% (high expression) were compared with those 75% of cells was compared with those with

Pigment epithelium-derived factor (PEDF), a member of the serine protease inhibitor superfamily, has potent anti-metastatic effects in cutaneous melanoma through its direct actions on endothelial and melanoma cells. Here we show that PEDF expression positively correlates with microphthalmia-associated transcription factor (MITF) in melanoma cell lines and human samples. High PEDF and MITF expression is characteristic of low aggressive melanomas classified according to molecular and pathological criteria, whereas both factors are decreased in senescent melanocytes and naevi. Importantly, MITF silencing down-regulates PEDF expression in melanoma cell lines and primary melanocytes, suggesting that the correlation in the expression reflects a causal relationship. In agreement, analysis of Chromatin immunoprecipitation coupled to high throughput sequencing (ChIP-seq) data sets revealed three MITF binding regions within the first intron of SERPINF1, and reporter assays demonstrated that the binding of MITF to these regions is sufficient to drive transcription. Finally, we demonstrate that exogenous PEDF expression efficiently halts in vitro migration and invasion, as well as in vivo dissemination of melanoma cells induced by MITF silencing. In summary, these results identify PEDF as a novel transcriptional target of MITF and support a relevant functional role for the MITF-PEDF axis in the biology of melanoma.

The present study assessed the psychometric properties and construct validity of two self-report measures of psychopathy in a male-college sample: the Levenson Psychopathy scales (LPS; Levenson, Kiehl, & Fitzpatrick, 1995) and the Psychopathic Personality Inventory (PPI; Lilienfeld & Andrews, 1996). Both the LPS and the PPI demonstrated good internal consistency, although selected items from the PPI correlated weakly with their respective factor scores, suggesting the need for further investigation of the factors' item content. The PPI showed stronger validity than the LPS in terms of convergent and discriminant validity of its factor scores and factor associations with two criterion variables, aggression, and anxiety. Overall, the current study provides greater support for the use of the PPI over the LPS in studies investigating psychopathic traits in nonclinical and nonforensic samples. (Contains 4 tables and 3 notes.) [This study was presented as a paper at the 2005 Annual Meeting of the American Psychology-Law Society, La Jolla, CA.]

The self-report version of the Antisocial Process Screening Device (APSD) has become a popular measure for assessing psychopathic features in justice-involved adolescents. However, the internal consistency reliability of its component scales (Narcissism, Callous-Unemotional, and Impulsivity) has been questioned in several studies. This study evaluates the internal consistency reliability of the self-report APSD by examining various indices (e.g., Cronbach's alpha, mean interitem correlation) across 11 studies. Whereas the Narcissism and Impulsivity scales display moderate to good reliability, internal consistency indices for the Callous-Unemotional scale are consistently poor across studies. Suggestions are made for revisions to this scale that would substantially improve its internal consistency reliability. (Contains 6 notes and 1 table.)

O presente estudo tem como problema de investigação compreender como a escola e as aulas de Educação Física apresentam condições de acessibilidade e de inclusão para uma aluna com deficiência visual na escola comum. O objetivo é investigar o processo de inclusão e de acessibilidade de uma aluna com deficiência visual nas aulas de Educação Física, bem como este processo repercute na aprendizagem e no desenvolvimento da aluna. A metodologia do estudo é de caráter qualitativo, na modalidade do estudo de caso. O estudo conclui que a inclusão de uma aluna com deficiência visual na escola contribui para um aprendizado mútuo entre os alunos, bem como de que a escola e sua comunidade precisam manter-se em contínua qualificação e busca de avanços de conhecimentos nessa área.

El presente estudio investiga la temática de la inclusión social de niños con necesidades en la práctica pedagógica de la Educación Física en la educación infantil. La metodología utilizada en este trabajo es cualitativa, y los participantes son profesores de la red regular de la enseñanza que abarca niños con necesidades especiales. La búsqueda por informaciones ocurrió a través de los siguientes instrumentos: entrevistas y observaciones. Los resultados del estudio son presentados en categorías: comprensión de la inclusión en la práctica de educación física; experiencias relacionales del profesor con niños con necesidades especiales; perspectivas de calificación profesional; soporte pedagógico para el desarrollo de la inclusión. El estudio muestra que los profesores de educación física reconocen la inclusión como una necesidad pedagógica, sin embargo hace falta una formación progresiva, y la práctica de enseñanza con más aprendizaje y avanzos.

O presente estudo investigou as práticas pedagógicas da educação física desenvolvidas nas Escolas de Educação Infantil. Objetivou estudar a organização pedagógica da educação física e a compreensão das professoras de educação infantil sobre a educação física como prática pedagógica. De corte qualitativo, o estudo se caracteriza como um estudo de casos. O estudo permitiu compreender sobre o significado da educação física, os fundamentos teóricos e a organização pedagógica da educação física na escola, bem como a relação da educação física com a prática educativa que as professoras desenvolvem.

Office market modelling has attracted a mounting amount of interest among researchers and practitioners during past decades. Growing research activity in the area is not surprising considering the importance of rent on property values. Nonetheless, very little quantitative research on Finnish rental markets has been carried out. The objective of this study is to respond to that lack of research by examining office rent determination in the Helsinki central business district (CBD) in reduced form single equation context. We discover that changes in central Helsinki office rents are subject to variations in new office completions and changes in the added value of services sector. As historical fit does not necessarily translate into a satisfactory predictive fit, the forecasting adequacy of the final model is also tested by constructing out of the sample forecast over 2007-2009. We find that the model outperforms two naïve forecasting methods, but fails to perfectly trail the actual index.

The article describes "The Marista Child Project". The purpose of the project is to provide the children's knowledge and development through ludical-educational activities in Phisical Education and Arts. Here are some activities: movement, games, exercises envolving the psychomotive power, graphical expression, pictures, drawings and paintings. The activities which have been doing suggest the importance the Phisical Education and Arts in the school today, considering Vygotskys problems in formal discipline. The project makes reflections, studies, analyses and thinks about the relationship between child-teacher, the meaning of learning, the interdisciplinary in the educative action to improve the better understanding between children's fantasy and reality. It also recognizes the simbolic components and imagination which are in everything the children do. These children's actions propose the knowledge.

The article studies the development of the public real estate equity sector. The paper describes and analyses the legislative development regarding the sector and the vehicles provided. It discusses the past development of public commercial real estate equity investments in Finland and their role as a market participant. In addition, the paper analyses the historical performance of the sector.