Understanding the clinical spectrum of complicated Plasmodium vivax malaria: a systematic review on the contributions of the Brazilian literature

The resurgence of the malaria eradication agenda and the increasing number of severe manifestation reports has contributed to a renewed interested in the Plasmodium vivax infection. It is the most geographically widespread parasite causing human malaria, with around 2.85 billion people living under risk of infection. The Brazilian Amazon region reports more than 50% of the malaria cases in Latin America and since 1990 there is a marked predominance of this species, responsible for 85% of cases in 2009. However, only a few complicated cases of P. vivax have been reported from this region. A systematic review of the Brazilian indexed and non-indexed literature on complicated cases of vivax malaria was performed including published articles, masters' dissertations, doctoral theses and national congresses' abstracts. The following information was retrieved: patient characteristics (demographic, presence of co-morbidities and, whenever possible, associated genetic disorders); description of each major clinical manifestation. As a result, 27 articles, 28 abstracts from scientific events' annals and 13 theses/dissertations were found, only after 1987. Most of the reported information was described in small case series and case reports of patients from all the Amazonian states, and also in travellers from Brazilian non-endemic areas. The more relevant clinical complications were anaemia, thrombocytopaenia, jaundice and acute respiratory distress syndrome, present in all age groups, in addition to other more rare clinical pictures. Complications in pregnant women were also reported. Acute and chronic co-morbidities were frequent, however death was occasional. Clinical atypical cases of malaria are more frequent than published in the indexed literature, probably due to a publication bias. In the Brazilian Amazon (considered to be a low to moderate intensity area of transmission), clinical data are in accordance with the recent findings of severity described in diverse P. vivax endemic areas (especially anaemia in Southeast Asia), however in this region both children and adults are affected. Finally, gaps of knowledge and areas for future research are opportunely pointed out

Spatiotemporal dynamics and recurrence of chikungunya virus in Brazil: an epidemiological study

BACKGROUND: Chikungunya virus (CHIKV) is an Aedes mosquito-borne virus that has caused large epidemics linked to acute, chronic, and severe clinical outcomes. Currently, Brazil has the highest number of chikungunya cases in the Americas. We aimed to investigate the spatiotemporal dynamics and recurrence pattern of chikungunya in Brazil since its introduction in 2013. METHODS: In this epidemiological study, we used CHIKV genomic sequencing data, CHIKV vector information, and aggregate clinical data on chikungunya cases from Brazil. The genomic data comprised 241 Brazilian CHIKV genome sequences from GenBank (n=180) and the 2022 CHIKV outbreak in Ceará state (n=61). The vector data (Breteau index and House index) were obtained from the Brazilian Ministry of Health for all 184 municipalities in Ceará state and 116 municipalities in Tocantins state in 2022. Epidemiological data on laboratory-confirmed cases of chikungunya between 2013 and 2022 were obtained from the Brazilian Ministry of Health and Laboratory of Public Health of Ceará. We assessed the spatiotemporal dynamics of chikungunya in Brazil via time series, mapping, age-sex distribution, cumulative case-fatality, linear correlation, logistic regression, and phylogenetic analyses. FINDINGS: Between March 3, 2013, and June 4, 2022, 253 545 laboratory-confirmed chikungunya cases were reported in 3316 (59·5%) of 5570 municipalities, mainly distributed in seven epidemic waves from 2016 to 2022. To date, Ceará in the northeast has been the most affected state, with 77 418 cases during the two largest epidemic waves in 2016 and 2017 and the third wave in 2022. From 2016 to 2022 in Ceará, the odds of being CHIKV-positive were higher in females than in males (odds ratio 0·87, 95% CI 0·85-0·89, p<0·0001), and the cumulative case-fatality ratio was 1·3 deaths per 1000 cases. Chikungunya recurrences in the states of Ceará, Tocantins (recurrence in 2022), and Pernambuco (recurrence in 2021) were limited to municipalities with few or no previously reported cases in the previous epidemic waves. The recurrence of chikungunya in Ceará in 2022 was associated with a new East-Central-South-African lineage. Population density metrics of the main CHIKV vector in Brazil, Aedes aegypti, were not correlated spatially with locations of chikungunya recurrence in Ceará and Tocantins. INTERPRETATION: Spatial heterogeneity of CHIKV spread and population immunity might explain the recurrence pattern of chikungunya in Brazil. These results can be used to inform public health interventions to prevent future chikungunya epidemic waves in urban settings. FUNDING: Global Virus Network, Burroughs Wellcome Fund, Wellcome Trust, US National Institutes of Health, São Paulo Research Foundation, Brazil Ministry of Education, UK Medical Research Council, Brazilian National Council for Scientific and Technological Development, and UK Royal Society. TRANSLATION: For the Portuguese translation of the abstract see Supplementary Materials section

Caracterização da silagem de milho, produzida em propriedades rurais do sudoeste do Paraná

O objetivo deste trabalho foi caracterizar a produção e utilização da silagem, nos sistemas produtivos, em propriedades leiteiras do sudoeste do Paraná. A coleta dos dados foi realizada de março a maio de 2009, em propriedades produtoras de leite, em sete municípios paranaenses, totalizando 108 propriedades visitadas. O questionário, de caráter qualiquantitativo, compreendia 28 questões pré-definidas. A produção leiteira pode ser ampliada pela utilização de técnicas de manejo, como a escolha correta do híbrido e o planejamento e escalonamento adequado da semeadura. A região sudoeste do Paraná caracteriza-se por apresentar pequenas propriedades rurais (agricultura familiar), com 15,65 vacas em lactação e 17,2 litros de leite/dia, em média, e que armazenam a silagem em silos trincheira, em sua maioria. As lavouras cultivadas para confecção de silagem produzem em média 40 a 50 ton ha-1 de matéria verde. Além disso, os principais híbridos utilizados para a confecção da silagem são do grupo semi-duro e precoce, com sementes certificadas e tratadas

Efeitos agudos do treinamento concorrente sobre os níveis séricos de leptina e cortisol em adultos jovens sobrepesados

OBJETIVO: Este estudo teve como objetivo analisar os efeitos imediatos do treinamento concorrente sobre a leptina e os níveis de cortisol em adultos jovens com sobrepeso. MÉTODOS: Este estudo utilizou uma metodologia quase-experimental. Foram 20 indivíduos voluntários de ambos os sexos, divididos em um grupo sobrepesado treinamento (GST n = 10) e um grupo sobrepesado controle (n = 10). A coleta de sangue foi realizada com os indivíduos em repouso após jejum de 12 horas. Os níveis de leptina e cortisol foram analisados por radioimunoensaio e ensaio por quimioluminescência chimiluminescence antes e imediatamente após o treinamento. ANOVA two way foi utilizada para análise estatística com nível de significância de p < 0,05. RESULTADOS: Na análise da leptina sérica, observou-se diferença significativa intergrupos (GST x GSC) nos momentos pré-intervenção (p = 0,02) e pós-intervenção (p = 0,01). Na análise intragrupos, não foram observadas alterações significativas. E na análise do cortisol sérico intergrupos (GST x GSC), foi observada uma diferença significativa nos momentos pré-intervenção (p = 0,01) e pós-intervenção (p = 0,01), porém, na análise intragrupos, não houve alterações significativas. CONCLUSÃO: Uma única sessão de treinamento concorrente não é suficiente para promover alterações agudas nos níveis de leptina e cortisol dos jovens adultos sobrepesados voluntários deste estudo

Implementation of a publication strategy in the context of reporting biases. A case study based on new documents from Neurontin® litigation

<p>Abstract</p> <p>Background</p> <p>Previous studies have documented strategies to promote off-label use of drugs using journal publications and other means. Few studies have presented internal company communications that discussed financial reasons for manipulating the scholarly record related to off-label indications. The objective of this study was to build on previous studies to illustrate implementation of a publication strategy by the drug manufacturer for four off-label uses of gabapentin (Neurontin®, Pfizer, Inc.): migraine prophylaxis, treatment of bipolar disorders, neuropathic pain, and nociceptive pain.</p> <p>Methods</p> <p>We included in this study internal company documents, email correspondence, memoranda, study protocols and reports that were made publicly available in 2008 as part of litigation brought by consumers and health insurers against Pfizer for fraudulent sales practices in its marketing of gabapentin (see <url>http://pacer.mad.uscourts.gov/dc/cgi-bin/recentops.pl?filename=saris/pdf/ucl%20opinion.pdf</url> for the Court’s findings).</p> <p>We reviewed documents pertaining to 20 clinical trials, 12 of which were published. We categorized our observations related to reporting biases and linked them with topics covered in internal documents, that is, deciding what should and should not be published and how to spin the study findings (re-framing study results to explain away unfavorable findings or to emphasize favorable findings); and where and when findings should be published and by whom.</p> <p>Results</p> <p>We present extracts from internal company marketing assessments recommending that Pfizer and Parke-Davis (Pfizer acquired Parke-Davis in 2000) adopt a publication strategy to conduct trials and disseminate trial findings for unapproved uses rather than an indication strategy to obtain regulatory approval. We show internal company email correspondence and documents revealing how publication content was influenced and spin was applied; how the company selected where trial findings would be presented or published; how publication of study results was delayed; and the role of ghost authorship.</p> <p>Conclusions</p> <p>Taken together, the extracts we present from internal company documents illustrate implementation of a strategy at odds with unbiased study conduct and dissemination. Our findings suggest that Pfizer and Parke-Davis’s publication strategy had the potential to distort the scientific literature, and thus misinform healthcare decision-makers.</p