Health policy and regulatory authorities: challenges of technology regulation in Public Health Emergencies. / Política de saúde e Autoridades Reguladoras: desafios da regulação de tecnologias nas Emergências em Saúde Pública.

Public Health Emergencies (PHE) have had repercussions on health systems on a global scale, and timely access to new health technologies is a challenge for health policy. The national regulatory authorities (NRA) play a key role in the evaluation and regulation of these technologies. The present study aims to analyze the main strategies and regulatory instruments used to deal with the challenges of regulating new technologies necessary for the health system's effective response during a PHE. This research, based on WHO and Brazilian NRA norms and documents, considered dimensions related to strategies for strengthening regulatory activities and regulatory instruments used to accelerate access to technologies, especially during PHEs. International cooperation between the NRA and the WHO were important strategies for strengthening the NRA, with emphasis on the use of reliance, regionalization, accelerated assessments, and work/information sharing, as well as the processes of regulatory harmonization and convergence. In addition to the use of existing regulatory instruments, efforts were also identified in order to implement new ones.

As Emergências em Saúde Pública (ESP) têm repercutido nos sistemas de saúde em escala global. O acesso às novas tecnologias em saúde em tempo oportuno é um desafio para a política de saúde. As autoridades reguladoras nacionais (ARN) têm papel fundamental na avaliação e regulação dessas tecnologias. O estudo objetiva analisar as principais estratégias e instrumentos regulatórios utilizados para lidar com os desafios da regulação de novas tecnologias necessárias à resposta do sistema de saúde durante as ESP. Trata-se de uma pesquisa normativa e documental, tendo como fonte a OMS e a ARN brasileira. Foram consideradas as dimensões relacionadas às estratégias para o fortalecimento das atividades regulatórias e os instrumentos regulatórios utilizados para acelerar o acesso às tecnologias, especialmente durante as ESP. A cooperação e a colaboração internacional entre as ARN e com a OMS foram importantes estratégias para o fortalecimento das ARN, com destaque para o uso de confiança, regionalização, avaliações aceleradas e compartilhamento de trabalho/informações, bem como os processos de harmonização e convergência regulatória. Identificou-se, além da utilização de instrumentos regulatórios já existentes, esforços na implementação de novos, com destaque para Autorização de Uso Emergencial.

Left bundle branch block cardiomyopathy (LBBB-CMP): from the not-so-benign finding of idiopathic LBBB to LBBB-CMP diagnosis and treatment.

Introduction Idiopathic left bundle branch block (iLBBB) is an uncommon finding. Its benignity has been increasingly questioned, though its natural history remains poorly clarified. Similarly, LBBB-cardiomyopathy (LBBB-CM) has been also increasingly recognized as a distinct entity, where electromechanical dyssynchrony seems to play a central role in left ventricular dysfunction (LVD) development. Still, it remains a scarcely studied topic. There is an urgent need for investigation and evidence reinforcement in these areas. OBJECTIVES: two main objectives: (1) to explore the natural history of "asymptomatic" iLBBB carriers; (2) to characterize the outcomes and therapeutic approach used in a "real-world" cohort of possible LBBB-CMP patients (pts). METHODS: tertiary care centre retrospective study of pts with iLBBB and possible LBBB-CMP, screened from a large hospital electrocardiographic database from 2011 to 2017 (LBBB = 347). To assign the 1st objective, only pts with left ventricular ejection fraction (LVEF) ≥ 50% and available follow-up (FU) data were included (n = 152). Regarding the 2nd objective, possible LBBB-CMP pts were selected and defined as iLBBB pts with LVD (LVEF < 50%) and no secondary causes for LVD (n = 53). Data were based on pts' careful review of medical records. RESULTS: focusing our 1st objective, 152 iLBBB carriers were identified. Median FU time were 8 years, and 61% were female. During FU, approximately 25% developed LVD, 20% needed ≥ 1 cardiovascular (CV) hospitalization, and 15% needed a cardiac device implantation. The majority (2/3) of pts with LVD on FU (n = 35) had no secondary causes for LVD, being classified as possible LBBB-CMP pts. Time-to-LVD analysis showed no differences between pts with a known cause for LVD vs LBBB-CMP pts (Log-rank = 0.713). Concerning the 2nd objective, 53 possible LBBB-CMP pts were identified. Median FU time were 10 years, and 51% were female. During the FU, 77% presented heart failure (HF) symptoms, and 42% needed ≥ 1 CV hospitalization, mainly due to HF. Half presented severe LVD at some point in time, and 55% needed a cardiac device, most of them a cardiac resynchronization therapy (CRT) device. Comparing CRT with non-CRT pts, no differences were found in terms of medical therapy, but better outcomes were observed in CRT group: LVEF improvement was higher (median LVEF improvement of 11% in non-CRT vs 27% in CRT; p < 0.001), and fully recovery from LVD was more frequent (50% of CRT vs 14% non-CRT; p = 0.028). CONCLUSION: our data strengthen current evidence on natural history of iLBBB, showing significant CV morbidity associated with the presence of iLBBB, and reinforces the need for a serial and proper FU of these carriers. Our data on "real-world" possible LBBB-CMP pts shows high rates of CV events, namely HF-related events, and supports the growing evidence pointing out CRT as this subgroup of pts' cornerstone of treatment. In conclusion, our work sheds additional light on these largely unknown topics and underlines the urgent need for larger and prospective studies addressing the identification of LVD development predictors in iLBBB carriers, as well as the establishment of diagnostic criteria and therapeutic approach for LBBB-CMP.

The expansion of the medical Cannabis market in Brazil and regulatory gaps / A expansão do mercado da Cannabis medicinal no Brasil e as lacunas regulatórias

Expenditures with public provision of Cannabis products in Brazil are rising and have reached over 150 million reais. Growing interest in these products is the result of initiatives by various manufacturers, which are authorized to produce and sell, and by importers, that enable entry of more than 500 different products, from several countries. The present scenario is of increase in demand and of insufficient regulation, compounded by low quality of evidence for possible indications. Regulatory voids open pathways for market practices that may be unaligned with public health interests. The result is an ever-greater number of companies striving to operate in this lucrative and flexible market niche. Anvisa has created alternatives for patient access to Cannabis-containing products, which are not recognized as medicines, and which therefore have not been assessed as to effectiveness, safety or quality. This amounts to a serious regulatory breach, since these products that are supplied through the SUS do not comply to legal health standards. Anvisa is expected to take a firm stance in relation to Cannabis products regulation, regarding indications, acknowledged scientific evidence and availability of those authorized for sale and importation in the country.

Os gastos com fornecimento público de produtos contendo Cannabis no Brasil é crescente e atualmente atinge mais de R$ 150 milhões. O crescente interesse por esses produtos é resultado da atuação de diversas indústrias no Brasil, que possuem autorização sanitária para fabricação e comercialização, e de importadores, que viabilizam a entrada de mais de 500 produtos atualmente autorizados para importação, originários de diversos países. O cenário atual é de demanda crescente e regulação insuficiente, complementado pela baixa qualidade de evidências para possíveis indicações. As lacunas normativas abrem caminhos para um mercado nem sempre alinhado aos interesses sanitários. O resultado é o aumento progressivo do número de empresas buscando atuar nesse nicho, que se mostra lucrativo e permeável. A Anvisa criou alternativas para permitir que os produtos contendo Cannabis, que não são medicamentos e, portanto, que não foram avaliados quanto a eficácia, segurança ou qualidade, sejam acessados por pacientes, o que torna grave o fornecimento, pelo SUS, pois os produtos não atendem ou não se adequam aos requisitos sanitários previstos na legislação. Espera-se que a Anvisa se posicione mais assertivamente no que tange à regulação da Cannabis, tanto em relação aos usos indicados, de acordo com evidências disponíveis, como em relação à disponibilidade de produtos autorizados para importação e comercialização no país.

Long-term prognosis of idiopathic ventricular fibrillation: An eighteen-year experience from a tertiary center.

INTRODUCTION AND OBJECTIVES: Idiopathic ventricular fibrillation (IVF) is diagnosed in patients who survive sudden cardiac arrest (SCA), preferably with documented ventricular fibrillation (VF), without any identifiable structural or electrical abnormality. Current evidence provides limited guidance on the diagnosis and follow-up of these patients. Our aim was to assess the clinical outcomes of survivors of an aborted SCA attributed to IVF. METHODS: We retrospectively collected clinical data from all patients who survived SCA and implanted a cardiac defibrillator (ICD) between 2005 and 2023. RESULTS: A total of 38 patients, 36.8% female, with a mean age of 44±14 years old were included. Median follow-up time was 8.7 years (interquartile range (IQR) 4.7-14.7 years). All patients underwent a comprehensive diagnostic evaluation that excluded structural and coronary disease. During follow-up, underlying diagnoses were established in 34.2% of the whole cohort. Genetic testing, performed in 37.2%, revealed underlying diagnoses in 57.1% of those tested, compared to only 26.3% of patients who did not undergo genetic testing [p=0.035, OR=5.1 (95% confidence interval (CI) 1.2-21.5)]. Mortality was 10.5% (due to non-arrhythmic causes) and 36.8% patients received appropriate therapies with a median time to first ICD therapy of 39 [5.4-47.3] months. CONCLUSION(S): Etiological diagnosis and recurrence prediction in patients with IVF remains challenging, even with extensive diagnostic evaluation and long-term follow-up. In our study, genetic testing enhanced diagnostic yield. Consistent with previous findings, our cohort experienced a notable arrhythmic recurrence, with no cardiac deaths, underlining the pivotal role of ICD implantation in these patients.

Early versus late cardiac magnetic resonance in the diagnosis of myocardial infarction with non-obstructive coronary arteries.

INTRODUCTION AND OBJECTIVES: Myocardial infarction with non-obstructive coronary arteries (MINOCA) is responsible for about 10% of all acute myocardial infarctions (AMI). Therapeutic strategies and prognosis depend on the underlying etiology, and a multimodal approach is essential. The objectives of this study were to characterize the group of patients diagnosed with MINOCA and to valuate the diagnostic yield of cardiovascular magnetic resonance (CMR). METHODS: This was a retrospective, observational, and analytical study, including 516 patients admitted for a non-ST-elevation MI and with no significant coronary disease on coronary angiography between January 2016 and September 2021. RESULTS: After the inclusion criteria, 163 patients remained of the 516 admitted to the study. They were divided into four groups based on the CMR results: MINOCA (n=51), Takotsubo syndrome (n=37), myocarditis (n=33), and without diagnosis (n=42). Most patients diagnosed with MINOCA were female with a mean age of 61.06±13.83 years. CMR identified the diagnosis in 74.2% of patients admitted for suspected acute MI, in which coronary angiography showed the absence of significant obstructions. The median time between hospital admission and CMR was significantly shorter in the groups that had a diagnosis compared with the group with no diagnosis (p=0.038), with a significant increase in diagnostic profitability if CMR was performed up to 14 days after admission (p=0.022). There were no deaths of cardiovascular etiology during the follow-up period. CONCLUSIONS: CMR was fundamental as it identified the diagnosis in three out of four patients; it should be performed in the first 14 days.

Reliability of the serial reaction time task: If at first you don't succeed, try, try, try again.

Procedural memory is involved in the acquisition and control of skills and habits that underlie rule and procedural learning, including the acquisition of grammar and phonology. The serial reaction time task (SRTT), commonly used to assess procedural learning, has been shown to have poor stability (test-retest reliability). We investigated factors that may affect the stability of the SRTT in adults. Experiment 1 examined whether the similarity of sequences learned in two sessions would impact stability: test-retest correlations were low regardless of sequence similarity (r < .31). Experiment 2 added a third session to examine whether individual differences in learning would stabilise with further training. There was a small (but nonsignificant) improvement in stability for later sessions (Sessions 1 and 2: r = .42; Sessions 2 and 3: r = .60). Stability of procedural learning on the SRTT remained suboptimal in all conditions, posing a serious obstacle to the use of this task as a sensitive predictor of individual differences and ultimately theoretical advance.

Authors' Response.

Dear Editor, We would like to thank Dr. Madias for his valuable comment on our original article entitled "QT interval prolongation in Takotsubo Syndrome: a frightening feature with no major prognostic impact" published in Monaldi Archives for Chest Disease on December 6, 2023...

A emergência do Zika vírus no Brasil e a resposta federal dos Sistemas Nacionais de Vigilância em Saúde e de Vigilância Sanitária / The Zika virus emergency in Brazil and the federal response of the National Public Health Surveillance and Brazilian Health Regulatory Systems

Resumo O artigo analisa a resposta federal dos Sistemas Nacionais de Vigilância em Saúde e de Vigilância Sanitária frente à epidemia do Zika vírus no Brasil, de 2015 a 2018, com foco nos contextos político-institucionais e no conteúdo das medidas governamentais desenvolvidas no período. O estudo ancorou-se na abordagem institucionalista histórica, compreendendo análise documental e entrevistas com atores-chave. A resposta se caracterizou pela priorização inicial da emergência sanitária na agenda política do governo federal, reduzindo-se ao longo do período, influenciada pelas crises financeira e política. Verificou-se multiplicidade de atores e instâncias voltadas à contingência, com certa articulação entre os dois sistemas, a partir de experiências pré-emergência próprias. O controle vetorial teve centralidade, valorizando ações intersetoriais e comunitárias, induzidas sobretudo pela Secretaria de Vigilância em Saúde do Ministério da Saúde e complementarmente pela Agência Nacional de Vigilância Sanitária. Observaram-se expressivas limitações alocativas de recursos financeiros novos e mudanças no aparato organizativo de resposta, com efeitos para a continuidade das políticas no pós-emergência, incluindo o desenvolvimento de medicamentos, vacinas e testes. A Emergência em Saúde Pública do Zika Vírus no Brasil foi marcada por limitada institucionalização de aprendizados e estratégias estruturantes, reduzindo oportunidades para a (re)organização das vigilâncias no Sistema Único de Saúde.

Abstract The article analyzes the federal response of the National Public Health Surveillance and Brazilian Health Regulatory Systems to the Zika virus epidemic in Brazil, from 2015 to 2018, focusing on the political-institutional contexts and the content of government measures developed during the period. The study was anchored in the historical institutionalist approach, comprising documentary analysis and interviews with key actors. The response was characterized by the initial prioritization of the health emergency on the federal government's political agenda, which was reduced over the period, influenced by the financial and political crises. There was a multiplicity of actors and instances focused on contingency, with a certain articulation between the two systems, based on their own pre-emergency experiences. Vector control had centrality, valuing intersectoral and community actions, induced mainly by the Health Surveillance Secretariat of the Ministry of Health and additionally by the National Health Surveillance Agency. Significant allocation limitations of new financial resources and changes in the organizational response apparatus were observed, with effects on the continuity of post-emergency policies, including the development of medicines, vaccines and tests. The Zika Virus Public Health Emergency in Brazil was marked by limited institutionalization of learning and structuring strategies, reducing opportunities for the (re)organization of surveillance in the Unified Health System.

Respostas do sistema de saúde brasileiro à emergência do Zika vírus: as distintas estratégias adotadas pelos estados do Ceará e do Rio de Janeiro / Responses of the Brazilian health system to the emergency of the Zika virus: different strategies adopted by the states of Ceará and Rio de Janeiro

Resumo O artigo analisa os casos de reprogramação do sistema de saúde em resposta à emergência de zika dos estados do Ceará (CE) e do Rio de Janeiro (RJ), no período de 2015 a 2017. A pesquisa ancorou-se na abordagem institucionalista histórica e na literatura sobre regionalização e redes de atenção à saúde. Envolveu a análise de documentos governamentais e a realização de entrevistas com atores-chave mobilizados na resposta dos estados à epidemia. Para cada estado, foram explorados, prioritariamente, os seguintes aspectos: contexto, conjuntura político-financeira e agenda da saúde no momento da epidemia; e o desenho e implementação das respostas (sentidos, atores, recursos, estratégias e repercussões). A reprogramação do sistema de saúde nos estados do CE e RJ apresentou distintas condições e diferentes sentidos das ações, estratégias, atores mobilizados e desdobramentos, com foco nas iniciativas de atenção às crianças com síndrome congênita do Zika vírus (SCZV). Evidenciou-se a importância: da rede regionalizada e coordenada, com desconcentração da oferta de serviços especializados e dos procedimentos de estimulação precoce; do papel coordenador e investidor do governo estadual; das iniciativas de qualificação dos profissionais de saúde; da atuação de instituições de pesquisa no atendimento, produção de conhecimento e no diálogo com famílias afetadas.

Abstract The article analyzes the cases of health system reprogramming in response to the Zika emergency in the states of Ceará (CE) and Rio de Janeiro (RJ), from 2015 to 2017. The research was anchored in the historical and institutionalist approach and the literature on regionalization and health care networks. It involved analyzing government documents and conducting interviews with key actors mobilized in the states' response to the epidemic. For each state, the following aspects were primarily explored: context, political-financial situation and health agenda at the time of the epidemic; and the design and implementation of responses (meanings, actors, resources, strategies and repercussions). The reprogramming of the health system in the states of CE and RJ presented different conditions and different meanings of actions, strategies, mobilized actors and developments, with a focus on care initiatives for children with Congenital Zika Virus Syndrome (SCZV). The importance of the regionalized and coordinated network was highlighted, with deconcentration of the offer of specialized services and early stimulation procedures; the coordinating and investing role of the state government; the qualification initiatives of health professionals; of the performance of research institutions in the service, production of knowledge and in the dialogue with affected families.

QT interval prolongation in Takotsubo syndrome: a frightening feature with no major prognostic impact.

Despite the frequent and often severe repolarization abnormalities seen in Takotsubo syndrome (TTS), the underlying mechanism of life-threatening arrhythmias is incompletely understood, and the risk remains uncertain. TTS is considered a potential cause of acquired long QT syndrome; however, there is no robust evidence that QT prolongation has a major prognostic impact on these patients' outcomes. Our aim was to assess the prevalence and clinical implications of acquired long QT during TTS events and compare in-hospital and long-term outcomes between patients with and without corrected QT interval (QTc) prolongation. This is a retrospective cohort study that included 113 patients admitted to our tertiary care hospital with a diagnosis of TTS. The cohort was divided into two groups: a long QTc group (QTc≥460 milliseconds in any electrocardiogram at admission or during hospitalization) and a normal QTc group. Baseline characteristics, occurrences during hospitalization, and outcome data were obtained from the revision of medical registries and hospital visits. Of the 113 patients, 107 (94.7%) were female. The mean age was 67.6±11.7 years. QTc prolongation was found in 38%. Demographic characteristics, relevant chronic medication, prevalence of cardiovascular risk factors, and other comorbidities were similar between the groups, except for history of atrial fibrillation, which was more common in the long QTc group. Syncope was more prevalent in the long QTc group. In-hospital complications were not statistically different between patients with long and normal QTc (48.8% versus 44.2%, p=0.637), including ventricular arrhythmias and complete atrioventricular block (both 4.7% versus 1.4%, p=0.556). In-hospital mortality was 0.9%, corresponding to one patient in the long QTc group. The mean follow-up time was 4.8±3.8 years. 5-year all-cause mortality and the occurrence of the composite endpoint of major adverse cardiac and cerebrovascular events did not differ between the groups (p=0.511 and p=0.538, respectively). Our study found no association between prolonged QTc interval during TTS events and adverse prognosis, since in-hospital and long-term outcomes were similar between the groups. Our findings suggest that, although QT prolongation is usually a frightening feature on ECG, this repolarization abnormality during the acute phase has no major prognostic implications in the TTS population.

Sixty years of the Bruce protocol: reappraising the contemporary role of exercise stress testing with electrocardiographic monitoring.

The cardiovascular response to exercise has long been a focus of interest. Over a century ago, the first descriptions of electrocardiographic changes occurring during exercise highlighted the possible relevance of this dynamic assessment. In this background, the inception of the Bruce protocol circa 60 years ago allowed for a major leap in this field by providing a standardized framework with which to address this issue, by means of an integrated and structured methodology. Since then, exercise stress testing with electrocardiographic monitoring (ExECG) has become one of the most widely appraised tests in cardiovascular medicine. Notably, past few decades have been profoundly marked by substantial advances in the approach to cardiovascular disease, challenging prior notions concerning both its physiopathology and overall management. Among these, the ever-evolving presentations of cardiovascular disease coupled with the development and implementation of several novel diagnostic modalities (both invasive and noninvasive) has led to a shifting paradigm in the application of ExECG. This technique, however, has continuously shown to be of added value across various momentums of the cardiovascular continuum, as depicted in several contemporary guidelines. This review provides a pragmatical reflexion on the development of ExECG, presenting a comprehensive overview concerning the current role of this modality, its challenges, and its future perspectives.

The reliability of the serial reaction time task: meta-analysis of test-retest correlations.

The Serial Reaction Time task, one of the most widely used tasks to index procedural memory, has been increasingly employed in individual differences research examining the role of procedural memory in language and other cognitive abilities. Yet, despite consistently producing robust procedural learning effects at the group level (i.e. faster responses to sequenced/probable trials versus random/improbable trials), these effects have recently been found to have poor reliability. In this meta-analysis (N = 7), comprising 719 participants (M = 20.81, s.d. = 7.13), we confirm this 'reliability paradox'. The overall retest reliability of the robust procedural learning effect elicited by the SRTT was found to be well below acceptable psychometric standards (r < 0.40). However, split-half reliability within a session is better, with an overall estimate of 0.66. There were no significant effects of sampling (participants' age), methodology (e.g. number of trials, sequence type) and analytical decisions (whether all trials were included when computing the procedural learning scores; using different indexes of procedural learning). Thus, despite producing robust effects at the group-level, until we have a better understanding of the factors that improve the reliability of this task using the SRTT for individual differences research should be done with caution.

Limited Evidence of an Association Between Language, Literacy, and Procedural Learning in Typical and Atypical Development: A Meta-Analysis.

The ability to extract patterns from sensory input across time and space is thought to underlie the development and acquisition of language and literacy skills, particularly the subdomains marked by the learning of probabilistic knowledge. Thus, impairments in procedural learning are hypothesized to underlie neurodevelopmental disorders, such as dyslexia and developmental language disorder. In the present meta-analysis, comprising 2396 participants from 39 independent studies, the continuous relationship between language, literacy, and procedural learning on the Serial Reaction Time task (SRTT) was assessed across children and adults with typical development (TD), dyslexia, and Developmental Language Disorder (DLD). Despite a significant, but very small, relationship between procedural learning and overall language and literacy measures, this pattern was not observed at the group-level when examining TD, dyslexic, and DLD groups separately. Based on the procedural/declarative model, a positive relationship was expected between procedural learning and language and literacy measures for the typically developing group; however, no such relationship was observed. This was also the case for the disordered groups (ps > .05). Also counter to expectations, the magnitude of the relationship between procedural learning and grammar and phonology did not differ between TD and DLD (ps > .05), nor between the TD and dyslexic group on reading, spelling, and phonology (ps > .05). While lending little support to the procedural/declarative model, we consider that these results may be the consequence of poor psychometric properties of the SRTT as a measure of procedural learning.

Nutrition and Outcome of 100 Endoscopic Gastrostomy-Fed Citizens with Severe Dementia.

Dementia is a rising public health concern. Feeding and nutritional problems increase as the disease progresses, affecting the clinical course and caregiver burden. While some guidelines advise against percutaneous endoscopic gastrostomy (PEG) and tube feeding in advanced dementia, conflicting evidence exists. This study aims to evaluate the nutritional status and influence of PEG feeding on the outcome and evolution of nutritional/prognosis markers of patients with severe dementia (PWSD) who underwent gastrostomy for nutritional support. We conducted a 16-year retrospective study on 100 PEG-fed PWSD with strong familial support. We evaluated the survival PEG-feeding period, safety, and objective nutritional/prognosis data on the gastrostomy day and after 3 months: Body Mass Index (BMI), Mid Upper Arm Circumference, Tricipital Skinfold, Mid-Arm Muscle Circumference, albumin, transferrin, total cholesterol, and hemoglobin. Most patients presented low values in these nutritional/prognosis parameters. No major life-threatening PEG complications were reported. The mean survival time after gastrostomy was 27.9 months (median of 17 months). Female sex, BMI recovery at 3 months, and higher baseline hemoglobin levels were associated with a reduced risk of death and increased survival time. The study concluded that, in carefully selected PWSD with strong familial support, PEG feeding can improve nutritional status and have a positive impact on survival.

Teaching open and reproducible scholarship: a critical review of the evidence base for current pedagogical methods and their outcomes.

In recent years, the scientific community has called for improvements in the credibility, robustness and reproducibility of research, characterized by increased interest and promotion of open and transparent research practices. While progress has been positive, there is a lack of consideration about how this approach can be embedded into undergraduate and postgraduate research training. Specifically, a critical overview of the literature which investigates how integrating open and reproducible science may influence student outcomes is needed. In this paper, we provide the first critical review of literature surrounding the integration of open and reproducible scholarship into teaching and learning and its associated outcomes in students. Our review highlighted how embedding open and reproducible scholarship appears to be associated with (i) students' scientific literacies (i.e. students' understanding of open research, consumption of science and the development of transferable skills); (ii) student engagement (i.e. motivation and engagement with learning, collaboration and engagement in open research) and (iii) students' attitudes towards science (i.e. trust in science and confidence in research findings). However, our review also identified a need for more robust and rigorous methods within pedagogical research, including more interventional and experimental evaluations of teaching practice. We discuss implications for teaching and learning scholarship.

Long-Term Intestinal Failure and Home Parenteral Support: A Single Center Experience.

Introduction: Home parenteral nutrition (HPN) and/or home parenteral hydration (HPH) are the gold-standard treatment for patients with long-term intestinal failure (IF). The authors aimed to assess the impact of HPN/HPH on nutritional status and survival of long-term IF patients, as well as HPN/HPH-related complications. Methods: This was a retrospective study including IF patients under HPN/HPH followed in a single large tertiary Portuguese hospital. The data collected included demographics, underlying conditions, anatomical characteristics, type and duration of parenteral support, IF functional, pathophysiological, and clinical classifications, body mass index (BMI) at the beginning and end of follow-up, complications/hospitalizations, current patient status (deceased, alive with HPN/HPH, and alive without HPN/HPH), and cause of death. Survival after HPN/HPH beginning, until death or August 2021, was recorded in months. Results: Overall 13 patients were included (53.9% female, mean age 63.46 years), and 84.6% of patients presented type III IF and 15.4% type II. Short bowel syndrome caused 76.9% of IF. Nine patients received HPN and 4 HPH. Eight patients (61.5%) were underweight at the beginning of HPN/HPH. At the end of follow-up, 4 patients were alive without HPN/HPH, 4 maintained HPN/HPH, and 5 died. All patients improved their BMI (mean initial BMI 18.9 vs. 23.5 at the end, p < 0.001). Eight patients (61.5%) were hospitalized due to catheter-related complications, mainly infectious (mean hospitalization episodes 2.25, mean hospital stay of 24.5 days). No deaths were related to HPN/HPH. Conclusion: HPN/HPH significantly improved IF patients' BMI. HPN/HPH-related hospitalizations were common, however causing no deaths, reinforcing that HPN/HPH is an adequate and safe therapy for long-term IF patients.

Introdução: A nutrição parentérica domiciliária (NPD) e/ou a hidratação parentérica domiciliária (HPD) constituem o tratamento gold-standard para doentes com falência intestinal (FI) crónica. O objetivo do presente estudo foi avaliar o impacto da NPD/HPD no status nutricional e sobrevivência dos doentes com FI crónica, bem como as complicações relacionadas à NPD/HPD. Métodos: Estudo retrospetivo, incluindo doentes com FI sob NPD/HPD, seguidos num hospital terciário em Portugal. Informação recolhida para cada doente: dados demográficos, patologia de base, características anatómicas, tipo e duração do suporte parentérico, classificação funcional, fisiopatológica e clínica da FI, índice de massa corporal (IMC) no início e final do seguimento, complicações/hospitalizações, estado atual do doente (falecido, vivo sob NPD/HPD e vivo sem NPD/HPD) e causa de morte. A sobrevida após início da NPD/HPD foi calculada em meses, até à data da morte ou agosto de 2021. Resultados: Incluídos 13 doentes (53.9% do sexo feminino, idade média 63.46 anos), 84.6% com FI tipo III e 15.4% com FI tipo II. A síndrome do intestino curto foi causa de 76.9% das FI. Nove doentes foram tratados com NPD e 4 com HPD. Oito doentes (61.5%) apresentavam IMC baixo no início da NPD/HPD. No final do seguimento, 4 doentes estavam vivos sem NPD/HPD, 4 mantinham NPD/HPD e 5 faleceram. Todos os doentes melhoraram significativamente o seu IMC (IMC médio no início do seguimento 18.9kg/m2 vs 23.5kg/m2 no final, p<0.001). Oito doentes (61.5%) tiveram de ser hospitalizados devido a complicações relacionadas com o cateter, sobretudo de causa infeciosa (número médio de hospitalizações por doente 2.25, duração média de internamento 24.5 dias). Não houve mortes relacionadas com a NPD/ HPD. Conclusão: A NPD/HPD melhorou significativamente o IMC dos doentes com FI. As hospitalizações relacionadas com a NPD/HPD foram comuns, contudo não causaram mortes, reforçando o facto que a NPD/HPD é uma terapêutica segura e adequada para doentes com FI crónica.

Exploiting the Integrated Valorization of Eucalyptus globulus Leaves: Chemical Composition and Biological Potential of the Lipophilic Fraction before and after Hydrodistillation.

E. globulus leaves have been mainly exploited for essential oil recovery or for energy generation in industrial pulp mills, neglecting the abundance of valuable families of extractives, namely, triterpenic acids, that might open new ways for the integrated valorization of this biomass. Therefore, this study highlights the lipophilic characterization of E. globulus leaves before and after hydrodistillation, aiming at the integrated valorization of both essential oils and triterpenic acids. The lipophilic composition of E. globulus leaves after hydrodistillation is reported for the first time. Extracts were obtained by dichloromethane Soxhlet extraction and analyzed by gas chromatography-mass spectrometry. In addition, their cytotoxicity on different cell lines representative of the innate immune system, skin, liver, and intestine were evaluated. Triterpenic acids, such as betulonic, oleanolic, betulinic and ursolic acids, were found to be the main components of these lipophilic extracts, ranging from 30.63-37.14 g kg-1 of dry weight (dw), and representing 87.7-89.0% w/w of the total content of the identified compounds. In particular, ursolic acid was the major constituent of all extracts, representing 46.8-50.7% w/w of the total content of the identified compounds. Other constituents, such as fatty acids, long-chain aliphatic alcohols and ß-sitosterol were also found in smaller amounts in the studied extracts. This study also demonstrates that the hydrodistillation process does not affect the recovery of compounds of greatest interest, namely, triterpenic acids. Therefore, the results establish that this biomass residue can be considered as a promising source of value-added bioactive compounds, opening new strategies for upgrading pulp industry residues within an integrated biorefinery context.

The Effect of Sacubitril-Valsartan on Ventricular Arrhythmia Burden in Patients With Heart Failure With Reduced Ejection Fraction.

Introduction Heart failure with reduced ejection fraction (HFrEF) patients are prone to developing ventricular arrhythmias. In the PARADIGM-HF trial, sacubitril-valsartan (SV) showed a reduction in the composite endpoint of death and HF hospitalization in HFrEF patients; subgroup analysis of this trial revealed a reduction in both sudden death and deaths from worsening HF. The mechanism by which SV may affect the incidence of ventricular arrhythmias is currently under debate, and the literature provides conflicting results. The aim of our study was to evaluate the potential antiarrhythmic effect of this drug in patients with HFrEF carrying an implantable cardiac defibrillator (ICD) or a cardiac resynchronization therapy with a defibrillator (CRT-D). Methods This was a single-center, observational and retrospective study. Inclusion criteria were implantation of an ICD or CRT-D device between 2009 and 2019, age ≥18 years, left ventricle ejection fraction (LVEF) ≤40%, New York Heart Association (NYHA) functional class ≥II, and treatment with an angiotensin-converting enzyme inhibitor or an angiotensin receptor blocker for at least 12 months, followed by replacement with SV. Exclusion criteria were NYHA class IV, frequent alterations in chronic medication for HFrEF, and implantation of an ICD or CRT-D after the introduction of SV. The primary outcome was the occurrence of ventricular arrhythmias in the form of appropriate device shocks, ventricular fibrillation, or ventricular tachycardia. The comparisons were performed between two periods of time (12 months before and 12 months after SV) in the same group of patients. Results Fifty-four patients met the inclusion criteria. The mean age was 69.5 ± 1.65 years, and 74.1% of patients were male. The number of patients experiencing appropriate shocks was significantly lower after SV initiation (2% vs. 18%; p=0.016). The percentage of VT (13 vs. 20%; p=0.549) and VF episodes (4% vs. 13% for VF; p=0.289) were also lower, but these differences were not statistically significant. There were no significant differences in the value of NT-proBNP (1128 vs. 775 pg/mL; p=0.858), LVEF (28.4 vs. 29.6%; p=0.315), and left ventricular end-diastolic diameter (65.0 vs. 66.0 mm; p=0.5492). Conclusion SV seems to reduce the risk of arrhythmic events requiring appropriate shock therapy.

Malnutrition, Cancer Stage and Gastrostomy Timing as Markers of Poor Outcomes in Gastrostomy-Fed Head and Neck Cancer Patients.

For percutaneous endoscopic gastrostomy (PEG)-fed head and neck cancer (HNC) patients, risk markers of poor outcomes may identify those needing more intensive support. This retrospective study aimed to evaluate markers of poor outcomes using TNM-defined stages, initial anthropometry [body mass index (BMI), mid-upper arm circumference (MUAC), tricipital skinfold (TSF), mid-arm muscle circumference (MAMC)] and laboratory data (albumin, transferrin, cholesterol), with 138 patients, 42-94 years old, enrolled. The patients had cancer, most frequently in the larynx (n = 52), predominantly stage IV (n = 109). Stage IVc presented a four times greater death risk than stage I (OR 3.998). Most patients presented low parameters: low BMI (n = 76), MUAC (n = 114), TSF (n = 58), MAMC (n = 81), albumin (n = 47), transferrin (n = 93), and cholesterol (n = 53). In stages I, III, IVa, and IVb, MAMC and PEG-timing were major survival determinants. Each MAMC unit increase resulted in 16% death risk decrease. Additional 10 PEG-feeding days resulted in 1% mortality decrease. Comparing IVa/IVb vs. IVc, albumin and transferrin presented significant differences (p = 0.042; p = 0.008). All parameters decreased as severity of stages increased. HNC patients were malnourished before PEG, with advanced cancer stages, and poor outcomes. Initial MAMC, reflecting lean tissue, significantly increases survival time, highlighting the importance of preserving muscle mass. PEG duration correlated positively with increased survival, lowering death risk by 1% for every additional 10 PEG-feeding days, signaling the need for early gastrostomy.