Blood pressure reduction and clinical outcomes with angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers: protocol for a systematic review and meta-regression analysis

Background Angiotensin-converting enzyme inhibitors (ACEis) and angiotensin II receptor blockers (ARBs) efficaciously reduce systolic blood pressure (BP), a well-established risk factor for myocardial infarction (MI). Both inhibit the renin-angiotensin system, albeit through different mechanisms, and produce similar reductions in BP. However, in parallel meta-analyses of ACEi and ARB trials, ACEis reduce risk of MI whereas ARBs do not—a phenomenon described as the ‘ARB-MI paradox’. In addition, ACEis reduce all-cause mortality, whereas ARBs do not, which appears to be independent of BP lowering. The divergent cardiovascular effects of ACE inhibitors and ARBs, despite similar BP reductions, are counter-intuitive. This systematic review aims to ascertain the extent to which clinical outcomes in randomised trials of ACEi and ARBs are attributable to reductions in systolic BP. Methods A comprehensive search of bibliographic databases will be performed to identify all randomised studies of agents of the ACEi and ARB class. Placebo and active comparator-controlled studies that report clinical outcomes, with greater than 500 person-years of follow-up in each study arm, will be included. Two independent reviewers will screen study records against a priori-defined eligibility criteria and perform data extraction. The Cochrane Risk of Bias Tool will be applied to all included studies. Studies retracted subsequent to initial publication will be excluded. Primary outcomes of interest include MI and all-cause mortality; secondary outcomes include stroke, heart failure, revascularisation and cardiovascular mortality. Meta-regression will be performed, evaluating the relationship between attained reduction in systolic BP and relative risk of each outcome, stratified by drug class. Where a BP-dependent effect exists (two-tailed p value < 0.05), relative risks, standardised per 10 mmHg difference in BP, will be reported for each study outcome. Publication bias will be examined using Funnel plots, and calculation of Egger’s statistic. Discussion This systematic review will provide a detailed synthesis of evidence regarding the relationship between BP reduction and clinical outcomes with ACEi and ARBs. Greater understanding of the dependency of the effect of each class on BP reduction will advance insight into the nature of the ARB-MI paradox and guide the future usage of these agents. Systematic review registration PROSPERO CRD4201707298

Childhood neurodevelopment after prescription of maintenance methadone for opioid dependency in pregnancy:a systematic review and meta-analysis

Aim: To systematically review and meta‐analyse studies of neurodevelopmental outcome of children born to mothers prescribed methadone in pregnancy. Method: MEDLINE, Embase, and PsycINFO were searched for studies published from 1975 to 2017 reporting neurodevelopmental outcomes in children with prenatal methadone exposure. Results: Forty‐one studies were identified (2283 participants). Eight studies were amenable to meta‐analysis: at 2 years the Mental Development Index weighted mean difference of children with prenatal methadone exposure compared with unexposed infants was −4.3 (95% confidence interval [CI] −7.24 to −1.63), and the Psychomotor Development Index weighted mean difference was −5.42 (95% CI −10.55 to −0.28). Seven studies reported behavioural scores and six found scores to be lower among methadone‐exposed children. Twelve studies reported visual outcomes: nystagmus and strabismus were common; five studies reported visual evoked potentials of which four described abnormalities. Factors that limited the quality of some studies, and introduced risk of bias, included absence of blinding, small sample size, high attrition, uncertainty about polydrug exposure, and lack of comparison group validity. Interpretation: Children born to mothers prescribed methadone in pregnancy are at risk of neurodevelopmental problems but risk of bias limits inference about harm. Research into management of opioid use disorder in pregnancy should include evaluation of childhood neurodevelopmental outcome

Discomfort experienced at the daily life of relatives of people admitted at ICU

This is a qualitative research that aimed to get to know the discomforts experienced at the daily life of relatives of people admitted at the intensive care unit (ICU). It happened on a general ICU at a public hospital, in Salvador-BA, by the second half of 2009. Nine relatives of people admitted were interviewed. The technique used was the analysis from the Grounded Theory. The results showed that the interaction of the families with the reality of life threat from the relative admitted, had as main discomfort, the discontinuity in their daily life, which was characterized by four categories: Living the distress of a possible loss, difficulties to take care of themselves, facing a separation in the family, suffering with changes in their social and professional lives. These discomforts can be minimized by the healthcare team’s effectiveness to the demands of the family and the support of its social network

Topological crystalline insulator states in Pb(1-x)Sn(x)Se

Topological insulators are a novel class of quantum materials in which time-reversal symmetry, relativistic (spin-orbit) effects and an inverted band structure result in electronic metallic states on the surfaces of bulk crystals. These helical states exhibit a Dirac-like energy dispersion across the bulk bandgap, and they are topologically protected. Recent theoretical proposals have suggested the existence of topological crystalline insulators, a novel class of topological insulators in which crystalline symmetry replaces the role of time-reversal symmetry in topological protection [1,2]. In this study, we show that the narrow-gap semiconductor Pb(1-x)Sn(x)Se is a topological crystalline insulator for x=0.23. Temperature-dependent magnetotransport measurements and angle-resolved photoelectron spectroscopy demonstrate that the material undergoes a temperature-driven topological phase transition from a trivial insulator to a topological crystalline insulator. These experimental findings add a new class to the family of topological insulators. We expect these results to be the beginning of both a considerable body of additional research on topological crystalline insulators as well as detailed studies of topological phase transitions.Comment: v2: published revised manuscript (6 pages, 3 figures) and supplementary information (5 pages, 8 figures

Methods for the synthesis of qualitative research: a critical review

<p>Abstract</p> <p>Background</p> <p>In recent years, a growing number of methods for synthesising qualitative research have emerged, particularly in relation to health-related research. There is a need for both researchers and commissioners to be able to distinguish between these methods and to select which method is the most appropriate to their situation.</p> <p>Discussion</p> <p>A number of methodological and conceptual links between these methods were identified and explored, while contrasting epistemological positions explained differences in approaches to issues such as quality assessment and extent of iteration. Methods broadly fall into 'realist' or 'idealist' epistemologies, which partly accounts for these differences.</p> <p>Summary</p> <p>Methods for qualitative synthesis vary across a range of dimensions. Commissioners of qualitative syntheses might wish to consider the kind of product they want and select their method – or type of method – accordingly.</p

Phenoloxidase activity acts as a mosquito innate immune response against infection with semliki forest virus

Several components of the mosquito immune system including the RNA interference (RNAi), JAK/STAT, Toll and IMD pathways have previously been implicated in controlling arbovirus infections. In contrast, the role of the phenoloxidase (PO) cascade in mosquito antiviral immunity is unknown. Here we show that conditioned medium from the Aedes albopictus-derived U4.4 cell line contains a functional PO cascade, which is activated by the bacterium Escherichia coli and the arbovirus Semliki Forest virus (SFV) (Togaviridae; Alphavirus). Production of recombinant SFV expressing the PO cascade inhibitor Egf1.0 blocked PO activity in U4.4 cell- conditioned medium, which resulted in enhanced spread of SFV. Infection of adult female Aedes aegypti by feeding mosquitoes a bloodmeal containing Egf1.0-expressing SFV increased virus replication and mosquito mortality. Collectively, these results suggest the PO cascade of mosquitoes plays an important role in immune defence against arboviruses

A phase II study evaluating neo-/adjuvant EIA chemotherapy, surgical resection and radiotherapy in high-risk soft tissue sarcoma

<p>Abstract</p> <p>Background</p> <p>The role of chemotherapy in high-risk soft tissue sarcoma is controversial. Though many patients undergo initial curative resection, distant metastasis is a frequent event, resulting in 5-year overall survival rates of only 50-60%. Neo-adjuvant and adjuvant chemotherapy (CTX) has been applied to achieve pre-operative cytoreduction, assess chemosensitivity, and to eliminate occult metastasis. Here we report on the results of our non-randomized phase II study on neo-adjuvant treatment for high-risk STS.</p> <p>Method</p> <p>Patients with potentially curative high-risk STS (size ≥ 5 cm, deep/extracompartimental localization, tumor grades II-III [FNCLCC]) were included. The protocol comprised 4 cycles of neo-adjuvant chemotherapy (EIA, etoposide 125 mg/m²iv days 1 and 4, ifosfamide 1500 mg/m²iv days 1 - 4, doxorubicin 50 mg/m²day 1, pegfilgrastim 6 mg sc day 5), definitive surgery with intra-operative radiotherapy, adjuvant radiotherapy and 4 adjuvant cycles of EIA.</p> <p>Result</p> <p>Between 06/2005 and 03/2010 a total of 50 subjects (male = 33, female = 17, median age 50.1 years) were enrolled. Median follow-up was 30.5 months. The majority of primary tumors were located in the extremities or trunk (92%), 6% originated in the abdomen/retroperitoneum. Response by RECIST criteria to neo-adjuvant CTX was 6% CR (n = 3), 24% PR (n = 12), 62% SD (n = 31) and 8% PD (n = 4). Local recurrence occurred in 3 subjects (6%). Distant metastasis was observed in 12 patients (24%). Overall survival (OS) and disease-free survival (DFS) at 2 years was 83% and 68%, respectively. Multivariate analysis failed to prove influence of resection status or grade of histological necrosis on OS or DFS. Severe toxicities included neutropenic fever (4/50), cardiac toxicity (2/50), and CNS toxicity (4/50) leading to CTX dose reductions in 4 subjects. No cases of secondary leukemias were observed so far.</p> <p>Conclusion</p> <p>The current protocol is feasible for achieving local control rates, as well as OS and DFS comparable to previously published data on neo-/adjuvant chemotherapy in this setting. However, the definitive role of chemotherapy remains unclear in the absence of large, randomized trials. Therefore, the current regimen can only be recommended within a clinical study, and a possibly increased risk of secondary leukemias has to be taken into account.</p> <p>Trial registration</p> <p>ClinicalTrials.gov <a href="http://www.clinicaltrials.gov/ct2/show/NCT01382030">NCT01382030</a>, EudraCT 2004-002501-72</p

O cuidado de enfermagem como prática empreendedora: oportunidades e possibilidades

OBJETIVOS: Compreender o significado do cuidado de enfermagem como prática social empreendedora. MÉTODOS: Foi baseada na Grounded Theory que, de forma sistemática, criativa e interativa possibilitou o desenvolvimento da teoria: "Vislumbrando o cuidado de enfermagem como prática social empreendedora". Amostra teórica constituiu-se de 35 sujeitos entrevistados, distribuídos em diferentes grupos amostrais. RESULTADOS: O cuidado de enfermagem como prática social empreendedora está associado ao sistema de relações e interações, à capacidade de interagir com os diferentes atores sociais, na capacidade de criar novos canais de comunicação e ações pró-ativas. CONCLUSÃO: A partir do cuidado como prática social empreendedora é possível atuar de forma pró-ativa, inovadora e participativa, sem desconsiderar as contradições sociais emergentes.OBJETIVO: Comprender el significado y desarrollar una teoría sustantiva sobre el cuidado de enfermería como una práctica social emprendedora. METODOS: Se basó en la Grounded Theory que, como un proceso sistemático, creativo e interactivo permitió el desarrollo de la teoría sustantiva: "Vislumbrando el cuidado de enfermería como una práctica social emprendedora". La muestra teórica estuvo constituida por treinta y cinco entrevistados distribuidos en diferentes grupos de muestras. RESULTADOS: El cuidado de enfermería como una práctica social emprendedora se asocia con el sistema de relaciones e interacciones, con la capacidad de interactuar con diferentes actores sociales y, con la capacidad de crear nuevos canales de comunicación y de acciones proactivas. CONCLUSIÓN: A partir del cuidado como una práctica emprendedora es posible actuar de manera proactiva, innovadora y participativa, sin dejar de lado las contradicciones sociales emergentes.OBJECTIVE: To understand the meaning and to develop a substantive theory about nursing care as an enterprising social practice. The METHODS: Was based on the Grounded Theory which, in a systematic, creative and interactive manner allowed the development of the substantive theory: "Realizing the nursing care as an enterprising social practice." The theoretical sample consisted of thirty-five subjects distributed among different groups of samples. RESULTS: The nursing care as an enterprising social practice is associated with the system of relationships and interactions, the ability to interact with different social actors and, the ability to create new channels of communication and proactive actions. CONCLUSION: Considering the care as an enterprising practice is possible to act in a proactive, innovative and participatory way, without neglecting the emerging aspects of social contradictions