Description of Trichophoromyia jariensis, a new species of phlebotomine sand fly (Diptera: Psychodidae) from the eastern Amazon.

A new sand fly species, Trichophoromyia jariensis n. sp. Cavalcante, Rodrigues, & Galati, from the state of Amapá, Brazil, is described based on both male and female morphology and cytochrome c oxidase subunit I DNA barcodes. The DNA barcoding analysis clearly associated males and females of this new species.

Seasonality and Biting Behavior of Mansonia (Diptera, Culicidae) in Rural Settlements Near Porto Velho, State of Rondônia, Brazil.

Mansonia (Diptera: Culicidae) are known to cause discomfort to the local populations of Amazon. Considering the fact that the effective control of these mosquitoes can only be obtained by understanding their ecology and behavior, entomological monitoring becomes essential. In view of this, mosquitoes of the genus Mansonia were collected by human landing catches (HLC) from 2015 to 2019, in four locations of Porto Velho, Rondônia, Brazil. The collections were performed inside and outside the homes, once in every four months, uninterrupted for 24 hr. Human bite indices/hour was used to analyze the hourly activity of the species for different seasons and environment (indoor and outdoor). Moreover, nonparametric Mann-Whitney tests were conducted to indicate if there were differences between exophagic and endophagic behavior. The seasonality of Mansonia species was also analyzed. Overall, 96,766 specimens were collected over five years of sampling. Mansonia titillans (Walker) was found to be the most abundant species (76.9%). The highest percentage of mosquitoes was collected in February (48.4%), followed by October (39.6%) and June (12.0%). The biting activity of the two most abundant species showed peak host seeking activity/behavior during twilight and night, more perceptible in the outdoor environment (peridomiciliary). In general, seasonality showed a tendency towards a reduction in the abundance of Mansonia in the years after 2015. Our results will be essential in the formulation of effective control methodology for Mansonia in the studied area.

Tofacitinib in Patients Hospitalized with Covid-19 Pneumonia.

BACKGROUND: The efficacy and safety of tofacitinib, a Janus kinase inhibitor, in patients who are hospitalized with coronavirus disease 2019 (Covid-19) pneumonia are unclear. METHODS: We randomly assigned, in a 1:1 ratio, hospitalized adults with Covid-19 pneumonia to receive either tofacitinib at a dose of 10 mg or placebo twice daily for up to 14 days or until hospital discharge. The primary outcome was the occurrence of death or respiratory failure through day 28 as assessed with the use of an eight-level ordinal scale (with scores ranging from 1 to 8 and higher scores indicating a worse condition). All-cause mortality and safety were also assessed. RESULTS: A total of 289 patients underwent randomization at 15 sites in Brazil. Overall, 89.3% of the patients received glucocorticoids during hospitalization. The cumulative incidence of death or respiratory failure through day 28 was 18.1% in the tofacitinib group and 29.0% in the placebo group (risk ratio, 0.63; 95% confidence interval [CI], 0.41 to 0.97; P = 0.04). Death from any cause through day 28 occurred in 2.8% of the patients in the tofacitinib group and in 5.5% of those in the placebo group (hazard ratio, 0.49; 95% CI, 0.15 to 1.63). The proportional odds of having a worse score on the eight-level ordinal scale with tofacitinib, as compared with placebo, was 0.60 (95% CI, 0.36 to 1.00) at day 14 and 0.54 (95% CI, 0.27 to 1.06) at day 28. Serious adverse events occurred in 20 patients (14.1%) in the tofacitinib group and in 17 (12.0%) in the placebo group. CONCLUSIONS: Among patients hospitalized with Covid-19 pneumonia, tofacitinib led to a lower risk of death or respiratory failure through day 28 than placebo. (Funded by Pfizer; STOP-COVID ClinicalTrials.gov number, NCT04469114.).

A randomized clinical trial to evaluate the efficacy and safety of rivaroxaban in patients with bioprosthetic mitral valve and atrial fibrillation or flutter: rationale and design of the RIVER trial

Background The efficacy and safety of rivaroxaban in patients with bioprosthetic mitral valves and atrial fibrillation or flutter remain uncertain. Design RIVER was an academic-led, multicenter, open-label, randomized, non-inferiority trial with blinded outcome adjudication that enrolled 1005 patients from 49 sites in Brazil. Patients with a bioprosthetic mitral valve and atrial fibrillation or flutter were randomly assigned (1:1) to rivaroxaban 20 mg once daily (15 mg in those with creatinine clearance <50 mL/min) or dose-adjusted warfarin (target international normalized ratio 2.0-30.); the follow-up period was 12 months. The primary outcome was a composite of all-cause mortality, stroke, transient ischemic attack, major bleeding, valve thrombosis, systemic embolism, or hospitalization for heart failure. Secondary outcomes included individual components of the primary composite outcome, bleeding events, and venous thromboembolism. Summary RIVER represents the largest trial specifically designed to assess the efficacy and safety of a direct oral anticoagulant in patients with bioprosthetic mitral valves and atrial fibrillation or flutter. The results of this trial can inform clinical practice and international guidelines.

A randomized clinical trial to evaluate the efficacy and safety of rivaroxaban in patients with bioprosthetic mitral valve and atrial fibrillation or flutter: Rationale and design of the RIVER trial.

The efficacy and safety of rivaroxaban in patients with bioprosthetic mitral valves and atrial fibrillation or flutter remain uncertain. DESIGN: RIVER was an academic-led, multicenter, open-label, randomized, non-inferiority trial with blinded outcome adjudication that enrolled 1005 patients from 49 sites in Brazil. Patients with a bioprosthetic mitral valve and atrial fibrillation or flutter were randomly assigned (1:1) to rivaroxaban 20 mg once daily (15 mg in those with creatinine clearance <50 mL/min) or dose-adjusted warfarin (target international normalized ratio 2.0-30.); the follow-up period was 12 months. The primary outcome was a composite of all-cause mortality, stroke, transient ischemic attack, major bleeding, valve thrombosis, systemic embolism, or hospitalization for heart failure. Secondary outcomes included individual components of the primary composite outcome, bleeding events, and venous thromboembolism. SUMMARY: RIVER represents the largest trial specifically designed to assess the efficacy and safety of a direct oral anticoagulant in patients with bioprosthetic mitral valves and atrial fibrillation or flutter. The results of this trial can inform clinical practice and international guidelines.

Rivaroxaban in patients with atrial fibrillation and a bioprosthetic mitral valve

BACKGROUND The effects of rivaroxaban in patients with atrial fibrillation and a bioprosthetic mitral valve remain uncertain. METHODS In this randomized trial, we compared rivaroxaban (20 mg once daily) with dose adjusted warfarin (target international normalized ratio, 2.0 to 3.0) in patients with atrial fibrillation and a bioprosthetic mitral valve. The primary outcome was a composite of death, major cardiovascular events (stroke, transient ischemic attack, systemic embolism, valve thrombosis, or hospitalization for heart failure), or major bleeding at 12 months. RESULTS A total of 1005 patients were enrolled at 49 sites in Brazil. A primary-outcome event occurred at a mean of 347.5 days in the rivaroxaban group and 340.1 days in the warfarin group (difference calculated as restricted mean survival time, 7.4 days; 95% confidence interval [CI], −1.4 to 16.3; P<0.001 for noninferiority). Death from cardiovascular causes or thromboembolic events occurred in 17 patients (3.4%) in the rivaroxaban group and in 26 (5.1%) in the warfarin group (hazard ratio, 0.65; 95% CI, 0.35 to 1.20). The incidence of stroke was 0.6% in the rivaroxaban group and 2.4% in the warfarin group (hazard ratio, 0.25; 95% CI, 0.07 to 0.88). Major bleeding occurred in 7 patients (1.4%) in the rivaroxaban group and in 13 (2.6%) in the warfarin group (hazard ratio, 0.54; 95% CI, 0.21 to 1.35). The frequency of other serious adverse events was similar in the two groups. CONCLUSIONS In patients with atrial fibrillation and a bioprosthetic mitral valve, rivaroxaban was noninferior to warfarin with respect to the mean time until the primary outcome of death, major cardiovascular events, or major bleeding at 12 months.

Ticagrelor vs Clopidogrel After Fibrinolytic Therapy in Patients With ST-Elevation Myocardial Infarction: A Randomized Clinical Trial.

Importance: The bleeding safety of ticagrelor in patients with ST-elevation myocardial infarction treated with fibrinolytic therapy remains uncertain. Objective: To evaluate the short-term safety of ticagrelor when compared with clopidogrel in patients with ST-elevation myocardial infarction treated with fibrinolytic therapy. Design, Setting and Participants: We conducted a multicenter, randomized, open-label with blinded end point adjudication trial that enrolled 3799 patients (younger than 75 years) with ST-segment elevation myocardial infarction receiving fibrinolytic therapy in 152 sites from 10 countries from November 2015 through November 2017. The prespecified upper boundary for noninferiority for bleeding was an absolute margin of 1.0%. Interventions: Patients were randomized to ticagrelor (180-mg loading dose, 90 mg twice daily thereafter) or clopidogrel (300-mg to 600-mg loading dose, 75 mg daily thereafter). Patients were randomized with a median of 11.4 hours after fibrinolysis, and 90% were pretreated with clopidogrel. Main Outcomes and Measures: The primary outcome was thrombolysis in myocardial infarction (TIMI) major bleeding through 30 days. Results: The mean (SD) age was 58.0 (9.5) years, 2928 of 3799 patients (77.1%) were men, and 2177 of 3799 patients (57.3%) were white. At 30 days, TIMI major bleeding had occurred in 14 of 1913 patients (0.73%) receiving ticagrelor and in 13 of 1886 patients (0.69%) receiving clopidogrel (absolute difference, 0.04%; 95% CI, -0.49% to 0.58%; P < .001 for noninferiority). Major bleeding defined by the Platelet Inhibition and Patient Outcomes criteria and by the Bleeding Academic Research Consortium types 3 to 5 bleeding occurred in 23 patients (1.20%) in the ticagrelor group and in 26 patients (1.38%) in the clopidogrel group (absolute difference, -0.18%; 95% CI, -0.89% to 0.54; P = .001 for noninferiority). The rates of fatal (0.16% vs 0.11%; P = .67) and intracranial bleeding (0.42% vs 0.37%; P = .82) were similar between the ticagrelor and clopidogrel groups, respectively. Minor and minimal bleeding were more common with ticagrelor than with clopidogrel. The composite of death from vascular causes, myocardial infarction, or stroke occurred in 76 patients (4.0%) treated with ticagrelor and in 82 patients (4.3%) receiving clopidogrel (hazard ratio, 0.91; 95% CI, 0.67-1.25; P = .57). Conclusions and Relevance: In patients younger than 75 years with ST-segment elevation myocardial infarction, delayed administration of ticagrelor after fibrinolytic therapy was noninferior to clopidogrel for TIMI major bleeding at 30 days. Trial Registration: clinicaltrials.gov Identifier: NCT02298088.

Avaliação da segurança e eficácia da combinação ramipril/ anlodipino versus anlodipino em monoterapia no tratamento da hipertensão arterial pela monitorização ambulatorial da pressão arterial: estudo ATAR-MAPA / Evaluation of security and efficiency of the combination ramipril/amlopidine versus amlopidine in monotherapy for the treatment of arterial hypertension by the outpatient monitoring of blood pressure: study ATAR-ABPM

O objetivo do estudo é comparar a eficácia e a tolerabilidade da combinação fixa ramipril/anlodipino e do anlodipino em monoterapia para o tratamento de hipertensão arterial. Após um período de duas semanas de retirada de anti-hipertensivos e uso de placebo (washout), 265 pacientes hipertensos com idades entre 40 e 79 anos foram randomizados para iniciar tratamento com 2,5/2,5 mg de ramipril/anlodipino em combinação fixa ou 2,5 mg de anlodipino, que foram titulados para 5/5 mg e 10/10 mg de ramipril/anlodipino, ou 5 e 10 mg de anlodipino, se necessário. No total, 131 pacientes foram randomizados para terapia combinada e 134 para monoterapia sem diferenças significativas entre os grupos nas características basais e nos níveis de pressão arterial (PA) inicial. A redução média da PA sistólica nos períodos do dia (20,36 ± 13,42 versus 15,86 ± 12,71 mmHg; p = 0,003) e da noite (17,6 ± 17,61 versus 14,09 ± 14,32 mmHg; p = 0,051), avaliada pela monitorização ambulatorial de pressão arterial (MAPA), foi significativamente maior no grupo tratamento com combinação fixa. A redução média da PA diastólica durante o dia à MAPA (11,28 ± 8,29 versus 8,96 ± 8,16 versus mmHg; p = 0,009) foi maior no grupo terapia combinada, mas não durante a noite (8,42 ± 11,16 mmHg versus 7,70 ± 8,63; p = 0,567). A redução média da PA sistólica e diastólica em 24 horas à MAPA também foi maior no grupo tratamento combinado. Ambas as opções terapêuticas promoveram redução significativa da PA sistólica e diastólica; porém, os resultados observados foram melhores no grupo de combinação fixa ramipril/anlodipino

This study aims to compare the efficacy and tolerability of a fixed-dose ramipril/amlodipine combination and amlodipine monotherapy for the treatment of hypertension. After a 2-week placebo washout, 265 hypertensive patients aged 40 to 79 years were randomized for 2.5/2.5 mg ramipril/amlodipine or 2.5 mg amlodipine, titrated to ramipril/amlodipine 5/5 mg and 10/10 mg , or amlodipine 5 and 10 mg, if necessary. A total of 131 patients were assigned to combination therapy, and 134 to monotherapy with no significant differences among them in basal characteristics and blood pressure (BP) levels at the ambulatory blood pressure monitoring (ABPM). Mean reduction in daytime (20.36 ± 13.42 versus 15.86 ± 12.71 mmHg; p = 0.003) and night-time systolic BP on ABPM (17.6 ± 17.61 versus 14.09 ± 14.32 mmHg; p = 0.051) were significantly higher in the combination therapy. Mean daytime diastolic BP reduction on ABPM (11.28 ± 8.29 versus 8.96 ± 8.16 versus mmHg; p = 0.009) was greater in the combination group, but not at night-time (8.42 ± 11.16 mmHg versus 7.70 ± 8.63; p = 0.567). Mean change in 24-h systolic and diastolic BP on ABPM were also greater in the combination treatment. Both treatments promoted a marked reduction in systolic and diastolic BP, and the results observed were better in the ramipril/amlodipine combination group.

Association of lipoprotein lipase D9N polymorphism with myocardial infarction in type 2 diabetes: the genetics, outcomes, and lipids in type 2 diabetes (GOLD) study.

The association of polymorphisms affecting lipid metabolism with the risk of myocardial infarction (MI) in type 2 diabetes mellitus was investigated. The Genetics, Outcomes and Lipids in type 2 Diabetes (GOLD) Study is a prospective, multicenter study, conducted on 990 patients presenting diabetes and MI (n=386), or diabetes without previous manifestation of stroke, peripheral or coronary arterial disease (n=604), recruited from 27 institutions in Brazil. APO A1 (A/G -75 and C/T +83) and APO C3 (C/G 3'UTR) non-coding sequences, CETP (Taq 1B), LPL (D9N), APO E (epsilon2, epsilon3, epsilon4,), PON-1 (Q192R), and two LCAT variants Arg(147)-->Trp and Tyr(171)-->Stop were tested by PCR-RFLP. There was a higher prevalence of LPL DN genotype (19% vs.12%, p=0.03) and a higher frequency of the N allele (11% vs. 7%) among subjects with MI when compared to controls, with an odds ratio of MI for carriers of 9N allele of 2.46 (95% CI=1.79-3.39, p<0.0001). This association was present in men and women, in non-smokers and in hypertensive patients. A logistic regression model including gender, duration of diabetes, systolic blood pressure, HDL-C, left ventricle hypertrophy and D9N polymorphism showed that the latter still remained significantly associated with MI (OR=1.50, 95% CI=1.02-2.25, p=0.049). These findings suggest that D9N polymorphism can be a useful risk marker for myocardial infarction and that further potential candidate genes should be screened for exploratory analysis and for future therapeutic intervention in diabetes.

Efficacy, safety and tolerability of sildenafil in Brazilian hypertensive patients on multiple antihypertensive drugs.

OBJECTIVE: To evaluate the efficacy, safety and tolerability of sildenafil among Brazilian patients with hypertension treated with combinations of anti-hypertensive drugs. MATERIALS AND METHODS: One hundred twenty hypertensive men aged 30 to 81 years old under treatment with 2 or more anti-hypertensive drugs and with erectile dysfunction (ED) lasting for at least 6 months were enrolled at 7 research centers in Brazil. Patients were randomized to receive treatment with either sildenafil or placebo taken 1 hour before sexual intercourse (initial dose of 50 mg, adjusted to 25 mg or 100 mg according to efficacy and toxicity). During the following 8 weeks, patients were evaluated regarding vital signs, adverse events, therapeutic efficacy, satisfaction with treatment and use of concurrent medications. RESULTS: The primary evaluation of efficacy, which was based on responses to questions 3 and 4 of the International Index of Erectile Function, showed significant differences regarding treatment with sildenafil (p = 0.0002 and p < 0.0001, respectively). In the assessment of global efficacy, 87% of the patients treated with sildenafil reported improved erections, as compared with 37% of patients given placebos (p < 0.0001). The other secondary evaluations supported the results favoring sildenafil. The most frequent adverse events among patients treated with sildenafil were headaches (11.4%), vasodilation (11.4%) and dyspepsia (6.5%). There were no significant changes in blood pressure measurements in both groups. CONCLUSION: Sildenafil is efficacious and safe for the treatment of hypertensive patients with ED who receive concurrent combinations of anti-hypertensive drugs.

Efficacy, safety and tolerability of sildenafil in Brazilian hypertensive patients on multiple antihypertensive drugs

OBJECTIVE: To evaluate the efficacy, safety and tolerability of sildenafil among Brazilian patients with hypertension treated with combinations of anti-hypertensive drugs. MATERIALS AND METHODS: One hundred twenty hypertensive men aged 30 to 81 years old under treatment with 2 or more anti-hypertensive drugs and with erectile dysfunction (ED) lasting for at least 6 months were enrolled at 7 research centers in Brazil. Patients were randomized to receive treatment with either sildenafil or placebo taken 1 hour before sexual intercourse (initial dose of 50 mg, adjusted to 25 mg or 100 mg according to efficacy and toxicity). During the following 8 weeks, patients were evaluated regarding vital signs, adverse events, therapeutic efficacy, satisfaction with treatment and use of concurrent medications. RESULTS: The primary evaluation of efficacy, which was based on responses to questions 3 and 4 of the International Index of Erectile Function, showed significant differences regarding treatment with sildenafil (p = 0.0002 and p < 0.0001, respectively). In the assessment of global efficacy, 87 percent of the patients treated with sildenafil reported improved erections, as compared with 37 percent of patients given placebos (p < 0.0001). The other secondary evaluations supported the results favoring sildenafil. The most frequent adverse events among patients treated with sildenafil were headaches (11.4 percent), vasodilation (11.4 percent) and dyspepsia (6.5 percent). There were no significant changes in blood pressure measurements in both groups. CONCLUSION: Sildenafil is efficacious and safe for the treatment of hypertensive patients with ED who receive concurrent combinations of anti-hypertensive drugs.