Rastreio Anual de Cancro da Mama a Partir dos 40 Anos de Idade: Porque é que Portugal o Deve Implementar?

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Antiinflammatory Therapy with Canakinumab for Atherosclerotic Disease

Background: Experimental and clinical data suggest that reducing inflammation without affecting lipid levels may reduce the risk of cardiovascular disease. Yet, the inflammatory hypothesis of atherothrombosis has remained unproved. Methods: We conducted a randomized, double-blind trial of canakinumab, a therapeutic monoclonal antibody targeting interleukin-1β, involving 10,061 patients with previous myocardial infarction and a high-sensitivity C-reactive protein level of 2 mg or more per liter. The trial compared three doses of canakinumab (50 mg, 150 mg, and 300 mg, administered subcutaneously every 3 months) with placebo. The primary efficacy end point was nonfatal myocardial infarction, nonfatal stroke, or cardiovascular death. RESULTS: At 48 months, the median reduction from baseline in the high-sensitivity C-reactive protein level was 26 percentage points greater in the group that received the 50-mg dose of canakinumab, 37 percentage points greater in the 150-mg group, and 41 percentage points greater in the 300-mg group than in the placebo group. Canakinumab did not reduce lipid levels from baseline. At a median follow-up of 3.7 years, the incidence rate for the primary end point was 4.50 events per 100 person-years in the placebo group, 4.11 events per 100 person-years in the 50-mg group, 3.86 events per 100 person-years in the 150-mg group, and 3.90 events per 100 person-years in the 300-mg group. The hazard ratios as compared with placebo were as follows: in the 50-mg group, 0.93 (95% confidence interval [CI], 0.80 to 1.07; P = 0.30); in the 150-mg group, 0.85 (95% CI, 0.74 to 0.98; P = 0.021); and in the 300-mg group, 0.86 (95% CI, 0.75 to 0.99; P = 0.031). The 150-mg dose, but not the other doses, met the prespecified multiplicity-adjusted threshold for statistical significance for the primary end point and the secondary end point that additionally included hospitalization for unstable angina that led to urgent revascularization (hazard ratio vs. placebo, 0.83; 95% CI, 0.73 to 0.95; P = 0.005). Canakinumab was associated with a higher incidence of fatal infection than was placebo. There was no significant difference in all-cause mortality (hazard ratio for all canakinumab doses vs. placebo, 0.94; 95% CI, 0.83 to 1.06; P = 0.31). Conclusions: Antiinflammatory therapy targeting the interleukin-1β innate immunity pathway with canakinumab at a dose of 150 mg every 3 months led to a significantly lower rate of recurrent cardiovascular events than placebo, independent of lipid-level lowering. (Funded by Novartis; CANTOS ClinicalTrials.gov number, NCT01327846.

Optimizing integrated imaging service delivery by tier in low-resource health systems

Access to imaging diagnostics has been shown to result in accurate treatment, management, and optimal outcomes. Particularly in low-income and low-middle-income countries (LICs, LMICs), access is limited due to a lack of adequate resources. To achieve Sustainable Development Goal (SDG) 3, access to imaging services is critical at every tier of the health system. Optimizing imaging services in low-resource settings is best accomplished by prescriptive, integrated, and coordinated tiered service delivery that takes contextual factors into consideration. To our knowledge, this is the first recommendation for optimized, specific imaging care delivery by tier. A model for tier-based essential imaging services informs and guides policymakers as they set priorities and make budgetary decisions. In this paper, we recommend a framework for tiered imaging services essential to reduce the global burden of disease and attain universal health coverage (UHC). A lack of access to basic imaging services, even at the lowest tier of the health system, can no longer be justified by cost. Worldwide, affordable modalities of modern ultrasound and X-ray are becoming an accessible mainstay for the investigation of common conditions such as pregnancy, pneumonia, and fractures, and are safely performed and interpreted by qualified professionals. Finally, given the vast gap in access to imaging resources between LMICs and high-income countries (HICs), a scale-up of tiered imaging services in low-resource settings has the potential to reduce health disparities between, and within countries. As the access to appropriately integrated imaging services improves, UHC may be achieved

Technical aspects of mediastinal ultrasound for pediatric pulmonary tuberculosis

Diagnosing childhood pulmonary tuberculosis (TB) may be challenging due to difficulties in obtaining adequate sputum samples, paucibacillary disease and the low sensitivity of diagnostic tests. Chest radiography is an important diagnostic tool for pulmonary TB, but it involves radiation exposure, requires facilities that can house X-ray equipment and has poor inter-reader agreement. The cardinal radiologic finding of mediastinal lymphadenopathy may be detected using mediastinal ultrasound (US). We describe technical aspects of performing mediastinal US, which may assist diagnosis of paediatric pulmonary T

Effect of Deletion or Overexpression of the 19-Kilodalton Lipoprotein Rv3763 on the Innate Response to Mycobacterium tuberculosis

The 19-kDa lipoprotein of Mycobacterium tuberculosis is an important target of the innate immune response. To investigate the immune biology of this antigen in the context of the whole bacillus, we derived a recombinant M. tuberculosis H37Rv that lacked the 19-kDa-lipoprotein gene (Δ19) and complemented this strain by reintroduction of the 19-kDa-lipoprotein gene on a multicopy vector to produce Δ19::pSMT181. The Δ19 strain multiplied less well than Δ19::pSMT181 in human monocyte-derived macrophages (MDM) (P = 0.039). Surface expression of major histocompatibility complex class II molecules was reduced in phagocytes infected with M. tuberculosis; this effect was not seen in cells infected with Δ19. Δ19 induced lower interleukin 1β (IL-1β) secretion from monocytes and MDM. Overexpression of the 19-kDa protein increased IL-1β, IL-12p40, and tumor necrosis factor alpha secretion irrespective of phagocyte maturity. These data support reports that the 19-kDa lipoprotein has pleiotropic effects on the interaction of M. tuberculosis with phagocytes. However, this analysis indicates that in the context of the whole bacillus, the 19-kDa lipoprotein is only one of a number of molecules that mediate the innate response to M. tuberculosis

Training Course in Focused Assessment with Sonography for HIV/TB in HIV Prevalent Medical Centers in Malawi

Purpose: This article describes the process of training medical providers of different backgrounds about the “focused assessment with sonography for HIV-associated TB” (FASH) exam to expand the availability of ultrasound for TB diagnosis in resource poor settings in the central region of Malawi. Methods and Materials: A survey was completed by the 19 eligible participants before and after a 4-day training course regarding the utility of the FASH exam. A six-question quiz was used to assess knowledge of the use of ultrasound in the FASH exam before and after the course. Results: Participants’ knowledge of the FASH technique significantly improved after the four-day course with a 32% increase in total quiz questions answered correctly (p<0.001). Ninety-five percent (n= 18) of participants answered that they would “likely” incorporate FASH in their clinical practice. Furthermore, 100% (n=19) of participants agreed that the FASH exam would improve their ability to diagnose TB and 95% (n=18) agreed that FASH would improve patient care in their clinic. Conclusions: After completing a 4-day training course, medical providers were more knowledgeable about the FASH exam and its findings, and felt more comfortable using ultrasound for the diagnosis of TB. Participants were also unanimous in opinion that the FASH ultrasound exam would improve their ability to diagnose TB

Association between neonatal neuroimaging and clinical outcomes in Zika-exposed infants from Rio de Janeiro, Brazil

Patrícia Brasil. Fundação Oswaldo Cruz. Instituto Nacional de Infectologia Evandro Chagas. Documento produzido em parceria ou por autor vinculado à Fiocruz, mas não consta a informação no documento. David Geffen School of Medicine, University of California, Los Angeles (Pool, Adachi, Karnezis, Salamon, Romero, Nielsen-Saines, M. I. Boechat, Tsui); Fundação Oswaldo Cruz, Rio de Janeiro, Brazil (S. Pone, M. Boechat, Aibe, Gomes da Silva, C. T. M. Ribeiro, Brasil, Zin, Vasconcelos, Pereira, Saad Salles, Barbosa, Moreira, M. Pone); University of California San Francisco School of Medicine (Gaw); Clinica de Diagnostico por Imagem CDPI, Rio de Janeiro, Brazil (Daltro, B. G. Ribeiro, Fazecas, Hygino da Cruz, Nogueira); University of Southern California School of Medicine, Los Angeles (Chen, Foo, Jung).Submitted by Janaína Nascimento ([email protected]) on 2019-09-12T13:36:36Z No. of bitstreams: 1 ve_Pool_Kara-Lee_etal_INI_2019.pdf: 2677168 bytes, checksum: 2080fb1eb7c68dd65def7e946107c304 (MD5)Approved for entry into archive by Janaína Nascimento ([email protected]) on 2019-09-12T14:05:01Z (GMT) No. of bitstreams: 1 ve_Pool_Kara-Lee_etal_INI_2019.pdf: 2677168 bytes, checksum: 2080fb1eb7c68dd65def7e946107c304 (MD5)Made available in DSpace on 2019-09-12T14:05:01Z (GMT). No. of bitstreams: 1 ve_Pool_Kara-Lee_etal_INI_2019.pdf: 2677168 bytes, checksum: 2080fb1eb7c68dd65def7e946107c304 (MD5) Previous issue date: 2019Múltipla - Ver em Notas.IMPORTANCE: Congenital Zika virus (ZIKV) infection may present with a spectrum of clinical and neuroradiographic findings. OBJECTIVE: To determine whether neuroimaging findings for infants with a history of ZIKV exposure are associated with infant clinical outcomes and gestational age at antenatal ZIKV infection. DESIGN, SETTING, AND PARTICIPANTS This cohort study retrospectively reviewed neuroimaging results (computed tomography and/or magnetic resonance imaging scans) of 110 ZIKV-exposed infants from a maternity and children’s hospital in Rio de Janeiro, Brazil, following the 2015 to 2016 ZIKV epidemic. Neuroimaging from March 1, 2016, to June 30, 2017, was evaluated to determine whether findings were associated with clinical outcomes and the timing of maternal ZIKV infection. Data were analyzed from July 1, 2017, to August 30, 2018. EXPOSURES: Neuroimaging (computed tomography and/or magnetic resonance imaging) was performed on ZIKV-exposed infants after birth. Blood and/or urine specimens from mothers and infants were tested for ZIKV by polymerase chain reaction assay. MAIN OUTCOMES AND MEASURES: Neuroimaging studies were evaluated for structural abnormalities and other forms of brain injury. RESULTS: A total of 110 infants with a mean (SD) gestational age of 38.4 (2.1) weeks had neuroimaging and clinical outcome data reviewed. Of these, 71 (65%) had abnormal neuroimaging findings, with the majority (96%) classified as having severe ZIKV infection at birth. The most common neuroimaging abnormalities were structural abnormalities including brain calcifications, especially at the cortico-subcortical white matter junction, cortex malformations, ventriculomegaly, and reduced brain volumes, followed by brainstem hypoplasia, cerebellar hypoplasia, and corpus callosum abnormalities. Frequency of abnormal imaging was higher in infants with specific clinical findings as opposed to those without them; these findings included fetal brain disruption sequence (100% vs 35%), microcephaly (100% vs 30%), congenital contractures (100% vs 58%), ophthalmologic abnormalities (95% vs 44%), hearing abnormalities (100% vs 58%), and neurologic symptoms (94% vs 10%). Four of 39 infants (10%) without initial evidence of severe ZIKV infection and normal findings on neurologic evaluation at birth had abnormal neuroimaging findings. Neuroimaging abnormalities differed by trimester of maternal ZIKV infection, with 63% of infants born to mothers infected in the first trimester, 13% of infants born to mothers infected in the second trimester, and 1% of infants born to mothers infected in the third trimester exhibiting neuroimaging abnormalities. The odds of abnormal neuroimaging were 7.9 times greater for infants with first trimester ZIKV exposure compared with other trimesters combined (odds ratio, 7.9; 95% CI, 3.0-20.4; P < .001). CONCLUSIONS AND RELEVANCE: Neuroimaging abnormalities of computed tomography and/or magnetic resonance imaging scans were common in ZIKV-exposed infants. While neuroimaging abnormalities were seen in 10% of infants without clinically severe ZIKV, most occurred almost exclusively among those with clinically severe ZIKV, especially among those with a history of ZIKV exposure in the first trimester