Canagliflozin and renal outcomes in type 2 diabetes and nephropathy

BACKGROUND Type 2 diabetes mellitus is the leading cause of kidney failure worldwide, but few effective long-term treatments are available. In cardiovascular trials of inhibitors of sodium–glucose cotransporter 2 (SGLT2), exploratory results have suggested that such drugs may improve renal outcomes in patients with type 2 diabetes. METHODS In this double-blind, randomized trial, we assigned patients with type 2 diabetes and albuminuric chronic kidney disease to receive canagliflozin, an oral SGLT2 inhibitor, at a dose of 100 mg daily or placebo. All the patients had an estimated glomerular filtration rate (GFR) of 30 to <90 ml per minute per 1.73 m2 of body-surface area and albuminuria (ratio of albumin [mg] to creatinine [g], >300 to 5000) and were treated with renin–angiotensin system blockade. The primary outcome was a composite of end-stage kidney disease (dialysis, transplantation, or a sustained estimated GFR of <15 ml per minute per 1.73 m2), a doubling of the serum creatinine level, or death from renal or cardiovascular causes. Prespecified secondary outcomes were tested hierarchically. RESULTS The trial was stopped early after a planned interim analysis on the recommendation of the data and safety monitoring committee. At that time, 4401 patients had undergone randomization, with a median follow-up of 2.62 years. The relative risk of the primary outcome was 30% lower in the canagliflozin group than in the placebo group, with event rates of 43.2 and 61.2 per 1000 patient-years, respectively (hazard ratio, 0.70; 95% confidence interval [CI], 0.59 to 0.82; P=0.00001). The relative risk of the renal-specific composite of end-stage kidney disease, a doubling of the creatinine level, or death from renal causes was lower by 34% (hazard ratio, 0.66; 95% CI, 0.53 to 0.81; P<0.001), and the relative risk of end-stage kidney disease was lower by 32% (hazard ratio, 0.68; 95% CI, 0.54 to 0.86; P=0.002). The canagliflozin group also had a lower risk of cardiovascular death, myocardial infarction, or stroke (hazard ratio, 0.80; 95% CI, 0.67 to 0.95; P=0.01) and hospitalization for heart failure (hazard ratio, 0.61; 95% CI, 0.47 to 0.80; P<0.001). There were no significant differences in rates of amputation or fracture. CONCLUSIONS In patients with type 2 diabetes and kidney disease, the risk of kidney failure and cardiovascular events was lower in the canagliflozin group than in the placebo group at a median follow-up of 2.62 years

Risk profiles and one-year outcomes of patients with newly diagnosed atrial fibrillation in India: Insights from the GARFIELD-AF Registry.

BACKGROUND: The Global Anticoagulant Registry in the FIELD-Atrial Fibrillation (GARFIELD-AF) is an ongoing prospective noninterventional registry, which is providing important information on the baseline characteristics, treatment patterns, and 1-year outcomes in patients with newly diagnosed non-valvular atrial fibrillation (NVAF). This report describes data from Indian patients recruited in this registry. METHODS AND RESULTS: A total of 52,014 patients with newly diagnosed AF were enrolled globally; of these, 1388 patients were recruited from 26 sites within India (2012-2016). In India, the mean age was 65.8 years at diagnosis of NVAF. Hypertension was the most prevalent risk factor for AF, present in 68.5% of patients from India and in 76.3% of patients globally (P < 0.001). Diabetes and coronary artery disease (CAD) were prevalent in 36.2% and 28.1% of patients as compared with global prevalence of 22.2% and 21.6%, respectively (P < 0.001 for both). Antiplatelet therapy was the most common antithrombotic treatment in India. With increasing stroke risk, however, patients were more likely to receive oral anticoagulant therapy [mainly vitamin K antagonist (VKA)], but average international normalized ratio (INR) was lower among Indian patients [median INR value 1.6 (interquartile range {IQR}: 1.3-2.3) versus 2.3 (IQR 1.8-2.8) (P < 0.001)]. Compared with other countries, patients from India had markedly higher rates of all-cause mortality [7.68 per 100 person-years (95% confidence interval 6.32-9.35) vs 4.34 (4.16-4.53), P < 0.0001], while rates of stroke/systemic embolism and major bleeding were lower after 1 year of follow-up. CONCLUSION: Compared to previously published registries from India, the GARFIELD-AF registry describes clinical profiles and outcomes in Indian patients with AF of a different etiology. The registry data show that compared to the rest of the world, Indian AF patients are younger in age and have more diabetes and CAD. Patients with a higher stroke risk are more likely to receive anticoagulation therapy with VKA but are underdosed compared with the global average in the GARFIELD-AF. CLINICAL TRIAL REGISTRATION-URL: http://www.clinicaltrials.gov. Unique identifier: NCT01090362

Malária durante a gravidez: efeito sobre o curso da gestação na região amazônica Impact of malaria during pregnancy in the Amazon region

OBJETIVO: Estimar o efeito da malária sobre o curso da gestação em mulheres na região amazônica e investigar possíveis fatores de risco nessa população. MÉTODOS: Este estudo transversal é parte de um projeto maior para estudar malária e gravidez na região amazônica. Foram incluídas gestantes com malária atendidas na Fundação de Medicina Tropical do Amazonas que responderam a entrevistas estruturadas. Dados socio-econômicos, comportamentais e clínicos foram levantados na primeira consulta relacionada a cada novo episódio de malária na gestante. Todas as gestantes foram acompanhadas ao longo de sua gestação. Foram considerados os seguintes fatores de risco para alterações no curso da gestação: idade materna menor do que 20 anos, primeira gestação, primeira infecção malárica e espécie de plasmódio infectante. RESULTADOS: Foram avaliados 535 episódios de malária em 417 gestantes, sendo 20,56% causados pelo P. falciparum, 78,69% pelo P. vivax e 0,75% pela associação dos dois parasitas. Alteração no curso da gestação foi um evento muito frequente (26,2%). Ameaça de aborto ocorreu em 49 casos (25,5%), aborto em dois (1,0%), ameaça de parto prematuro em 74 (25,1%) e parto prematuro em três (1,0%). Ser primigesta e adolescente apresentou associação estatisticamente significativa com ameaça de parto prematuro e abortamento. CONCLUSÃO: A alteração no curso da gestação foi um evento muito frequente durante o episódio agudo de malária, embora a interrupção da gestação tenha tido baixa ocorrência em nossa casuística. Os resultados não evidenciaram um fator de risco de destaque, sugerindo que qualquer gestante pode apresentar ameaça de interrupção ou interrupção da gestação na vigência de episódio agudo de malária.OBJECTIVE: To estimate the impact of malaria on the course of pregnancy in women from the Amazon region and to investigate possible risk factors in this population. METHODS: This cross-sectional study is part of a larger project to study malaria and pregnancy in the Amazon region. Pregnant women with malaria receiving care at the Amazon Tropical Medicine Foundation (Fundação de Medicina Tropical do Amazonas) who answered a structured interview were included in the study. Socioeconomic, behavioral and clinical data were collected in the first consultation relating to each new malaria attack. All the women were followed-up throughout their pregnancy. The following risk factors for impact of malaria on the course of pregnancy were considered: being younger than 20 years of age, first pregnancy, first malaria infection, and type of infecting plasmodium species. RESULTS: Five hundred and thirty-five malaria episodes were evaluated in 417 pregnant women, with 20.56% being caused by P. falciparum, 78.69% by P. vivax and 0.75% by the association of both parasites. Changes in the course of pregnancy were very frequent (26.2%). Threat of abortion was observed in 49 cases (25.5%), abortion in two (1.0%), threat of premature birth in 74 (25.1%), and premature birth in three (1.0%). First pregnancy and age < 20 years were significantly associated with threat of premature birth and abortion. CONCLUSION: Changes in the course of pregnancy were very frequent during acute malaria attacks, despite the low frequency of abortion. The present results do not highlight specific risk factors, suggesting that any pregnant woman may be at risk for the threat of abortion or for abortion during acute malaria attacks

Malária durante a gravidez: efeito sobre o curso da gestação na região amazônica

Submitted by Patricia Stilpen ([email protected]) on 2011-04-14T11:37:37Z No. of bitstreams: 1 Malária durante a gravidez.pdf: 177675 bytes, checksum: 4d24675984ec33c6302e1eb0cd5f8734 (MD5)Made available in DSpace on 2011-04-14T11:37:37Z (GMT). No. of bitstreams: 1 Malária durante a gravidez.pdf: 177675 bytes, checksum: 4d24675984ec33c6302e1eb0cd5f8734 (MD5) Previous issue date: 2009Fundação de Medicina Tropical do Amazonas. Manaus, AM, Brasil.Fundação de Medicina Tropical do Amazonas. Manaus, AM, Brasil.Fundação de Medicina Tropical do Amazonas. Manaus, AM, Brasil.Universidade Federal do Amazonas. Manaus, AM, Brasil.Fundação de Medicina Tropical do Amazonas, Manaus, AM, Brasil / Fundação Oswaldo Cruz. Centro de Pesquisas Leônidas e Maria Deane. Manaus, AM, Brasil.Objetivo. Estimar o efeito da malária sobre o curso da gestação em mulheres na região amazônica e investigar possíveis fatores de risco nessa população. Métodos. Este estudo transversal é parte de um projeto maior para estudar malária e gravidez na região amazônica. Foram incluídas gestantes com malária atendidas na Fundação de Medicina Tropical do Amazonas que responderam a entrevistas estruturadas. Dados socioeconômicos, comportamentais e clínicos foram levantados na primeira consulta relacionada a cada novo episódio de malária na gestante. Todas as gestantes foram acompanhadas ao longo de sua gestação. Foram considerados os seguintes fatores de risco para alterações no curso da gestação: idade materna menor do que 20 anos, primeira gestação, primeira infecção malárica e espécie de plasmódio infectante. Resultados. Foram avaliados 535 episódios de malária em 417 gestantes, sendo 20,56% causados pelo P. falciparum, 78,69% pelo P. vivax e 0,75% pela associação dos dois parasitas. Alteração no curso da gestação foi um evento muito frequente (26,2%). Ameaça de aborto ocorreu em 49 casos (25,5%), aborto em dois (1,0%), ameaça de parto prematuro em 74 (25,1%) e parto prematuro em três (1,0%). Ser primigesta e adolescente apresentou associação estatisticamente significativa com ameaça de parto prematuro e abortamento. Conclusão. A alteração no curso da gestação foi um evento muito frequente durante o episódio agudo de malária, embora a interrupção da gestação tenha tido baixa ocorrência em nossa casuística. Os resultados não evidenciaram um fator de risco de destaque, sugerindo que qualquer gestante pode apresentar ameaça de interrupção ou interrupção da gestação na vigência de episódio agudo de malária

Analysis of Single-Nucleotide Polymorphisms in the crt-o and mdr1 Genes of Plasmodium vivax among Chloroquine-Resistant Isolates from the Brazilian Amazon Region▿ †

Plasmodium vivax parasites with chloroquine resistance (CQR) are already circulating in the Brazilian Amazon. Complete single-nucleotide polymorphism (SNP) analyses of coding and noncoding sequences of the pvmdr1 and pvcrt-o genes revealed no associations with CQR, even if some mutations had not been randomly selected. In addition, striking differences in the topologies and numbers of SNPs in these transporter genes between P. vivax and P. falciparum reinforce the idea that mechanisms other than mutations may explain this virulent phenotype in P. vivax

Plasmodium vivax Malaria in Pregnant Women in the Brazilian Amazon and the Risk Factors Associated with Prematurity and Low Birth Weight: A Descriptive Study.

INTRODUCTION:Plasmodium vivax is the most prevalent malaria species in the American region. Brazil accounts for the higher number of the malaria cases reported in pregnant women in the Americas. This study aims to describe the characteristics of pregnant women with malaria in an endemic area of the Brazilian Amazon and the risk factors associated with prematurity and low birth weight (LBW). METHODS/PRINCIPAL FINDINGS:Between December 2005 and March 2008, 503 pregnant women with malaria that attended a tertiary health centre were enrolled and followed up until delivery and reported a total of 1016 malaria episodes. More than half of study women (54%) were between 20-29 years old, and almost a third were adolescents. The prevalence of anaemia at enrolment was 59%. Most women (286/503) reported more than one malaria episode and most malaria episodes (84.5%, 846/1001) were due to P. vivax infection. Among women with only P. vivax malaria, the risk of preterm birth and low birth weight decreased in multigravidae (OR, 0.36 [95% CI, 0.16-0.82]; p = 0.015 and OR 0.24 [95% CI, 0.10-0.58]; p = 0.001, respectively). The risk of preterm birth decreased with higher maternal age (OR 0.43 [95% CI, 0.19-0.95]; p = 0.037) and among those women who reported higher antenatal care (ANC) attendance (OR, 0.32 [95% CI, 0.15-0.70]; p = 0.005). CONCLUSION:This study shows that P. vivax is the prevailing species among pregnant women with malaria in the region and shows that vivax clinical malaria may represent harmful consequences for the health of the mother and their offsprings particularly on specific groups such as adolescents, primigravidae and those women with lower ANC attendance

Correlation between gestational age and birth weight and graphical representation of the 10th and 90th percentiles for females (A) and males (B) based on Brazilian-specific growth curves.

<p>SGA: Small for gestational age (< 10th percentile); AGA: Appropriate for gestational age (10th-90th percentile); LGA: Large for gestational age (>90th percentile); LBW: Low birth weight (<2500 g); Premature newborn (< 37 weeks). The intra-uterine growth retardation (IUGR) was defined as the newborn SGA. No differences were found by gender to IUGR (p = 0.686), LBW (p = 0.406) and prematurity (p = 0.968).</p