Early Treatment with Pegylated Interferon Lambda for Covid-19.

BACKGROUND: The efficacy of a single dose of pegylated interferon lambda in preventing clinical events among outpatients with acute symptomatic coronavirus disease 2019 (Covid-19) is unclear. METHODS: We conducted a randomized, controlled, adaptive platform trial involving predominantly vaccinated adults with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in Brazil and Canada. Outpatients who presented with an acute clinical condition consistent with Covid-19 within 7 days after the onset of symptoms received either pegylated interferon lambda (single subcutaneous injection, 180 µg) or placebo (single injection or oral). The primary composite outcome was hospitalization (or transfer to a tertiary hospital) or an emergency department visit (observation for >6 hours) due to Covid-19 within 28 days after randomization. RESULTS: A total of 933 patients were assigned to receive pegylated interferon lambda (2 were subsequently excluded owing to protocol deviations) and 1018 were assigned to receive placebo. Overall, 83% of the patients had been vaccinated, and during the trial, multiple SARS-CoV-2 variants had emerged. A total of 25 of 931 patients (2.7%) in the interferon group had a primary-outcome event, as compared with 57 of 1018 (5.6%) in the placebo group, a difference of 51% (relative risk, 0.49; 95% Bayesian credible interval, 0.30 to 0.76; posterior probability of superiority to placebo, >99.9%). Results were generally consistent in analyses of secondary outcomes, including time to hospitalization for Covid-19 (hazard ratio, 0.57; 95% Bayesian credible interval, 0.33 to 0.95) and Covid-19-related hospitalization or death (hazard ratio, 0.59; 95% Bayesian credible interval, 0.35 to 0.97). The effects were consistent across dominant variants and independent of vaccination status. Among patients with a high viral load at baseline, those who received pegylated interferon lambda had lower viral loads by day 7 than those who received placebo. The incidence of adverse events was similar in the two groups. CONCLUSIONS: Among predominantly vaccinated outpatients with Covid-19, the incidence of hospitalization or an emergency department visit (observation for >6 hours) was significantly lower among those who received a single dose of pegylated interferon lambda than among those who received placebo. (Funded by FastGrants and others; TOGETHER ClinicalTrials.gov number, NCT04727424.).

Effect of Early Treatment with Ivermectin among Patients with Covid-19.

BACKGROUND: The efficacy of ivermectin in preventing hospitalization or extended observation in an emergency setting among outpatients with acutely symptomatic coronavirus disease 2019 (Covid-19), the disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is unclear. METHODS: We conducted a double-blind, randomized, placebo-controlled, adaptive platform trial involving symptomatic SARS-CoV-2-positive adults recruited from 12 public health clinics in Brazil. Patients who had had symptoms of Covid-19 for up to 7 days and had at least one risk factor for disease progression were randomly assigned to receive ivermectin (400 µg per kilogram of body weight) once daily for 3 days or placebo. (The trial also involved other interventions that are not reported here.) The primary composite outcome was hospitalization due to Covid-19 within 28 days after randomization or an emergency department visit due to clinical worsening of Covid-19 (defined as the participant remaining under observation for >6 hours) within 28 days after randomization. RESULTS: A total of 3515 patients were randomly assigned to receive ivermectin (679 patients), placebo (679), or another intervention (2157). Overall, 100 patients (14.7%) in the ivermectin group had a primary-outcome event, as compared with 111 (16.3%) in the placebo group (relative risk, 0.90; 95% Bayesian credible interval, 0.70 to 1.16). Of the 211 primary-outcome events, 171 (81.0%) were hospital admissions. Findings were similar to the primary analysis in a modified intention-to-treat analysis that included only patients who received at least one dose of ivermectin or placebo (relative risk, 0.89; 95% Bayesian credible interval, 0.69 to 1.15) and in a per-protocol analysis that included only patients who reported 100% adherence to the assigned regimen (relative risk, 0.94; 95% Bayesian credible interval, 0.67 to 1.35). There were no significant effects of ivermectin use on secondary outcomes or adverse events. CONCLUSIONS: Treatment with ivermectin did not result in a lower incidence of medical admission to a hospital due to progression of Covid-19 or of prolonged emergency department observation among outpatients with an early diagnosis of Covid-19. (Funded by FastGrants and the Rainwater Charitable Foundation; TOGETHER ClinicalTrials.gov number, NCT04727424.).

Monte Carlo evaluation of occupational exposure during uterine artery embolization.

PURPOSE: Uterine fibroids affect women mainly of childbearing age, an alternative for the treatment of these fibroids is uterine artery embolization (UAE), a minimally invasive procedure which uses fluoroscopy, providing radiation doses often high, due to the fact that professionals remain in the room throughout the procedure. In this work, equivalent and effective doses were evaluated for the main physician, for the assistant and for the patient during the UAE procedure. METHODS: Doses were calculated using computer simulation with the Monte Carlo Method, and virtual anthropomorphic phantoms, in a typical scenario of interventional radiology with field sizes of 20 × 20, 25 × 25 and 32 × 32 cm2, tube voltages of 70, 80, 90 and 100 kV, and projections of LAO45, RAO45 and PA. RESULTS: The results showed that the highest doses received by the professionals were for the LAO45 projection with 32 × 32 cm2 field size and 100 kV tube voltage, which is in accordance with the existing literature. The highest equivalent doses, without the protective equipment, were in the eyes, skin, breast and stomach for the main physician, and for the assistant they were in the eyes, breast, thyroid and skin. When she used the protective equipment, the highest equivalent doses for the main physician were on the skin, brain, bone marrow and bone surface, and for the assistant they were on the skin, brain, red bone marrow and bone surface. CONCLUSIONS: Effective doses increased up to 3186% for the main physician, and 2462% for the assistant, without protective equipment, thus showing their importance.

Carbohydrate mouth rinse improves cycling performance carried out until the volitional exhaustion.

BACKGROUND: Carbohydrates (CHO) are among the most investigated nutritional ergogenic aids, and may be consumed in different forms, e.g., mouth rinse with carbohydrate solution (MRCS). In this sense, the aim of this study was to evaluate the impact of MRCS on the performance of physically active individuals undergoing a physical exercise session carried out until the volitional exhaustion. METHODS: This is a counter-balanced randomized study, with a double-blind design. The sample consisted of twenty-one physically active healthy men with a mean (±SD) of age of 22.4 (±2.7) years old, 76.7 (±6.0) cm of height,12.1% (±3.7) of body fat mass, and 23.9 (±2.4) kg/m2 of body mass index. After familiarizing the participants with the protocol (cycle ergometer, with oral mouth rinse procedure) and assessing the maximal lactate steady state the cycling exercise was performed until the volitional exhaustion in the following conditions: without mouth rinse (CONTROL), PLACEBO and MRCS. RESULTS: Time to reach exhaustion was statistically different (P<0.0001) between conditions (control: 43.0±27.5 minutes; placebo: 57.4±30.6 minutes; MRCS: 70.9±30.3 minutes). CONCLUSIONS: The administration of MRCS was shown to be effective in improving cycling performance, increasing the time to exhaustion until the volitional exhaustion. Thus, the use of methodology proposed by the present study may help coaches and practitioners improve the performance of physically active young adults.

Prevalence of and risk factors for bacterial vaginosis among women of reproductive age attending cervical screening in southeastern Brazil.

OBJECTIVE: To determine the prevalence of and risk factors for bacterial vaginosis. METHODS: A cross-sectional study of women aged 14-54 years attending 18 primary healthcare units in Botucatu, Brazil, for cervical screening was undertaken between September 1, 2012, and January 31, 2013. Data on sociodemographics, sexual behavior, and medical history were obtained by interview. Vaginal swabs were taken to classify the vaginal flora according to the Nugent scoring system. Candida sp. hyphae and infection by Trichomonas vaginalis were also evaluated by microscopy and culture, respectively. Stepwise logistic regression analysis was performed to identify risk factors independently associated with bacterial vaginosis. RESULTS: Among 1519 women included in analyses, 457 (30.1%) had bacterial vaginosis. Variables independently associated with bacterial vaginosis were a single marital status (OR 1.4; 95%CI 1.1-1.8), partner infidelity (OR 1.5; 95%CI 1.2-1.9), abnormal discharge in the previous year (OR 1.5; 95%CI 1.2-2.0), and concurrent trichomoniasis (OR 4.1; 95%CI 1.5-11.5). Current use of hormonal contraception (OR 0.7; 95%CI 0.5-0.9), luteal phase of menstrual cycle (OR 0.8; 95%CI 0.6-0.9), higher income (OR 0.8; 95%CI 0.6-0.9), and vaginal candidiasis (OR 0.5; 95%CI 0.3-0.9) all had protective effects. CONCLUSION: The prevalence of bacterial vaginosis in the study population is high. The epidemiological data provide evidence of the sexual transmissibility of bacterial vaginosis.

Tuberculosis among HIV-1-infected subjects in a tertiary out-patient service in São Paulo city, Brazil / Tuberculose entre pacientes infectados pelo HIV-1 em ambulatório terciário de São Paulo, Brasil

TB is currently considered to be the most important infectious disease among HIV-1-infected subjects in developing countries, such as Brazil. A retrospective analysis of TB cases was performed, occurring from January 1995 to December 2010 in our cohort of 599 HIV positive patients. The primary outcome was the occurrence of active TB. Forty-one TB cases were diagnosed over this period of 16 years, among 599 HIV positive patients in an open cohort setting in the city of Sao Paulo, Brazil. All-time lowest mean CD4 T cell count at the time of TB diagnosis was 146 and 186 cells/mm³, respectively. The mean HIV viral load was 5.19 log10 copies/mL, and 59% of the patients were on HAART. TB incidence was 1.47 per 100 person-years, for a total follow-up time of 2775 person-years. The probability of surviving up to 10 years after diagnosis was 75% for TB patients as opposed to 96% for patients with other, non-TB opportunistic diseases (p = 0.03). TB can be considered a public health problem among people living with HIV in Brazil despite of the widespread use of antiretrovirals for the treatment of HIV infection/AIDS.

Atualmente, a tuberculose (TB) é considerada a doença infecciosa mais importante entre os pacientes infectados pelo HIV-1 nos países em desenvolvimento, como o Brasil. Análise retrospectiva dos casos de tuberculose ocorridos a partir de janeiro 1995 até dezembro de 2010 foi realizada em nossa coorte de 599 pacientes HIV positivos. O desfecho primário foi a ocorrência de TB ativa, e 41 casos da doença foram diagnosticados durante este período de 16 anos. As contagens médias do nadir de células T CD4 e ao momento do diagnóstico de TB foram de 146 e 217 células/mm³, respectivamente. A carga viral média de HIV foi de 5,19 log10 cópias/mL, e 59% dos pacientes estavam em tratamento com ART. A incidência de TB foi de 1,47 casos por 100 pessoas-ano, para um tempo total de seguimento da coorte de 2775 pessoas-ano. A probabilidade de sobreviver até 10 anos após o diagnóstico foi de 75% para pacientes com TB, em oposição a 96% para pacientes com outras doenças oportunistas não-TB (p = 0,03). A tuberculose pode ser considerada problema de saúde pública entre as pessoas que vivem com HIV no Brasil, apesar da ampla utilização de anti-retrovirais para o tratamento da infecção pelo HIV / AIDS.

Tuberculosis among HIV-1-infected subjects in a tertiary out-patient service in São Paulo city, Brazil.

TB is currently considered to be the most important infectious disease among HIV-1-infected subjects in developing countries, such as Brazil. A retrospective analysis of TB cases was performed, occurring from January 1995 to December 2010 in our cohort of 599 HIV positive patients. The primary outcome was the occurrence of active TB. Forty-one TB cases were diagnosed over this period of 16 years, among 599 HIV positive patients in an open cohort setting in the city of Sao Paulo, Brazil. All-time lowest mean CD4 T cell count at the time of TB diagnosis was 146 and 186 cells/mm³, respectively. The mean HIV viral load was 5.19 log10 copies/mL, and 59% of the patients were on HAART. TB incidence was 1.47 per 100 person-years, for a total follow-up time of 2775 person-years. The probability of surviving up to 10 years after diagnosis was 75% for TB patients as opposed to 96% for patients with other, non-TB opportunistic diseases (p = 0.03). TB can be considered a public health problem among people living with HIV in Brazil despite of the widespread use of antiretrovirals for the treatment of HIV infection/AIDS.

Involvement of forebrain imidazoline and alpha(2)-adrenergic receptors in the antidipsogenic response to moxonidine.

We investigated the participation of central alpha(2)-adrenoceptors and imidazoline receptors in the inhibition of water deprivation-induced water intake in rats. The alpha(2)-adrenoceptor and imidazoline antagonist idazoxan (320 nmol), but not the alpha(2)-adrenoceptor antagonist yohimbine, abolished the antidipsogenic effect of moxonidine (alpha(2)-adrenoceptor and imidazoline agonist, 20 nmol) microinjected into the medial septal area. Yohimbine abolished the antidipsogenic effect of moxonidine intracerebroventricularly. Therefore, central moxonidine may inhibit water intake acting independently on both imidazoline receptors and alpha(2)-adrenoceptors at different forebrain sites.