Prevalence of rheumatic heart disease in Zambian school children.

BACKGROUND: The large global burden of rheumatic heart disease (RHD) has come to light in recent years following robust epidemiologic studies. As an operational research component of a broad program aimed at primary and secondary prevention of RHD, we sought to determine the current prevalence of RHD in the country's capital, Lusaka, using a modern imaging-based screening methodology. In addition, we wished to evaluate the practicality of training local radiographers in echocardiography screening methods. METHODS: Echocardiography was conducted on a random sample of students in 15 schools utilizing a previously validated, abbreviated screening protocol. Through a task-shifting scheme, and in the spirit of capacity-building to enhance local diagnostic and research skills, general radiographers based at Lusaka University Teaching Hospital (UTH) were newly trained to use portable echocardiography devices. Students deemed as screen-positive were referred for comprehensive echocardiography and clinical examination at UTH. Cardiac abnormalities were classified according to standard World Heart Federation criteria. RESULTS: Of 1102 students that were consented and screened, 53 students were referred for confirmatory echocardiography. Three students had definite RHD, 10 had borderline RHD, 29 were normal, and 11 students were lost to follow-up. The rates of definite, borderline, and total RHD were 2.7 per 1000, 9.1 per 1000, and 11.8 per 1000, respectively. Anterior mitral valve leaflet thickening and chordal thickening were the most common morphological defects. The pairwise kappa test showed fair agreement between the local radiographers and an echocardiographer quality assurance specialist. CONCLUSION: The prevalence of asymptomatic RHD in urban communities in Zambia is within the range of results reported in other sub-Saharan African countries using the WHF criteria. Task-shifting local radiographers to conduct echocardiography was feasible. The results of this study will be used to inform ongoing efforts in Zambia to control and eventually eliminate RHD. TRIAL REGISTRATION: The study was registered on clinicaltrials.gov ( #NCT02661763 ).

The Next Generation Scientist program: capacity-building for future scientific leaders in low- and middle-income countries.

BACKGROUND: Scientific and professional development opportunities for early career scientists in low- and middle- income countries (LMICs) are limited and not consistent. There is a disproportionately low number of biomedical and clinical researchers in LMIC's relative to their high burden of disease, a disparity that is aggravated by emigration of up to 70% of scientists from their countries of birth for education and employment elsewhere. To help address this need, a novel University-accredited, immersive fellowship program was established by a large public-academic-private network. We sought to describe the program and summarize progress and lessons learned over its first 7-years. METHODS: Hallmarks of the program are a structured learning curriculum and bespoke research activities tailored to the needs of each fellow. Research projects expose the scientists to state-of-the-art methodologies and leading experts in their fields while also ensuring that learnings are implementable within their home infrastructure. Fellows run seminars on drug discovery and development that reinforce themes of scientific leadership and teamwork together with practical modules on addressing healthcare challenges within their local systems. Industry mentors achieve mutual learning to better understand healthcare needs in traditionally underserved settings. We evaluated the impact of the program through an online survey of participants and by assessing research output. RESULTS: More than 140 scientists and clinicians from 25 countries participated over the 7-year period. Evaluation revealed strong evidence of knowledge and skills transfer, and beneficial self-reported impact on fellow's research output and career trajectories. Examples of program impact included completion of post-graduate qualifications; establishment and implementation of good laboratory- and clinical- practice mechanisms; and becoming lead investigators in local programs. There was a high retention of fellows in their home countries (> 75%) and an enduring professional network among the fellows and their mentors. CONCLUSIONS: Our experience demonstrates an example for how multi-sectoral partners can contribute to scientific and professional development of researchers in LMICs and supports the idea that capacity-building efforts should be tailored to the specific needs of beneficiaries to be maximally effective. Lessons learned may be applied to the design and conduct of other programs to strengthen science ecosystems in LMICs.

Diversity of culturable filamentous Ascomycetes in the eastern South Pacific Ocean off Chile.

Our study reports the diversity of culturable mycoplankton in the eastern South Pacific Ocean off Chile to contribute with novel knowledge on taxonomy of filamentous fungi isolated from distinct physicochemical and biological marine environments. We characterized spatial distribution of isolates, evaluated their viability and assessed the influence of organic substrate availability on fungal development. Thirty-nine Operational Taxonomic Units were identified from 99 fungal strains isolated from coastal and oceanic waters by using Automatic Barcode Gap Discovery. All Operational Taxonomic Units belonged to phylum Ascomycota and orders Eurotiales, Dothideales, Sordariales and Hypocreales, mainly Penicillium sp. (82%); 11 sequences did not match existing species in GenBank, suggesting occurrence of novel fungal taxa. Our results suggest that fungal communities in the South Pacific Ocean off Chile appear to thrive in a wide range of environmental conditions in the ocean and that substrate availability may be a factor influencing fungal viability in the ocean.

Fungal parasites infect marine diatoms in the upwelling ecosystem of the Humboldt current system off central Chile.

This is the first report of fungal parasitism of diatoms in a highly productive coastal upwelling ecosystem, based on a year-round time series of diatom and parasitic Chytridiomycota abundance in the Humboldt Current System off Chile (36°30.80'S-73°07.70'W). Our results show co-variation in the presence of Skeletonema, Thalassiosira and Chaetoceros diatoms with attached and detached chytrid sporangia. High abundance of attached sporangia was observed during the austral spring, coinciding with a predominance of Thalassiosira and Skeletonema under active upwelling conditions. Towards the end of austral spring, a decreasing proportion of attached sporangia was accompanied by a decline in abundance of Skeletonema and Thalassiosira and the predominance of Chaetoceros, suggesting specificity and host density dependence of chytrid infection. The new findings on fungal parasitism of diatoms provide further support for the inclusion of Fungi in the current model of the role played by the marine microbial community in the coastal ocean. We propose a conceptual model where Fungi contribute to controlling the dynamics of phytoplankton populations, as well as the release of organic matter and the transfer of organic carbon through the pelagic trophic web in coastal upwelling ecosystems.

Melting glacier impacts community structure of Bacteria, Archaea and Fungi in a Chilean Patagonia fjord.

Jorge Montt glacier, located in the Patagonian Ice Fields, has undergone an unprecedented retreat during the past century. To study the impact of the meltwater discharge on the microbial community of the downstream fjord, we targeted Bacteria, Archaea and Fungi communities during austral autumn and winter. Our results showed a singular microbial community present in cold and low salinity surface waters during autumn, when a thicker meltwater layer was observed. Meltwater bacterial sequences were related to Cyanobacteria, Proteobacteria, Actinobacteria and Bacteriodetes previously identified in freshwater and cold ecosystems, suggesting the occurrence of microorganisms adapted to live in the extreme conditions of meltwater. For Fungi, representative sequences related to terrestrial and airborne fungal taxa indicated transport of allochthonous Fungi by the meltwater discharge. In contrast, bottom fjord waters from autumn and winter showed representative Operational Taxonomic Units (OTUs) related to sequences of marine microorganisms, which is consistent with current models of fjord circulation. We conclude that meltwater can significantly modify the structure of microbial communities and support the development of a major fraction of microorganisms in surface waters of Patagonian fjords.

Cadazolid, a novel antibiotic with potent activity against Clostridium difficile: safety, tolerability and pharmacokinetics in healthy subjects following single and multiple oral doses.

OBJECTIVES: Current treatment options for Clostridium difficile-associated diarrhoea (CDAD) leave a high unmet medical need for new therapies. Cadazolid is a new antibiotic in development for the treatment of CDAD. The objectives of this study were to evaluate its tolerability and pharmacokinetics following single ascending doses (AC-061-101) and multiple ascending doses (AC-061-102). METHODS: Single and multiple (twice daily for 10 days) oral doses of cadazolid between 30 mg and 3000 mg, or placebo, were tested in a total of 64 healthy male subjects. Safety assessments were conducted at regular intervals. Blood, urine and faeces were sampled, and cadazolid concentrations were measured. RESULTS: Cadazolid was well tolerated up to 3000 mg given twice daily for 10 days. The most common adverse event was headache, with no observed relationship between dose or treatment duration and adverse events. Plasma concentrations of cadazolid were low. No plasma concentrations >3.3 ng/mL were observed after single doses or >6.9 ng/mL after 10 days of multiple doses. Food increased the mean C(max) from 0.73 to 1.87 ng/mL and mean AUC(0-t) from 3.13 to 15.69 ng ·h/mL after a single 300 mg dose. The increase in systemic exposure to cadazolid across doses was less than dose-proportional. The mean cumulative faecal recovery was 81.0%-93.5%. Urinary recovery of unchanged compound was <0.015%. CONCLUSIONS: Cadazolid was well tolerated and its systemic exposure was low. The majority of compound was recovered unchanged in the faeces, thus resulting in high concentrations at the site of action (colon).

Tolerability and pharmacokinetics of ACT-280778, a novel nondihydropyridine dual L/T-type calcium channel blocker: early clinical studies in healthy male subjects using adaptive designs.

ACT-280778 is a novel nondihydropyridine dual L/T-type calcium channel blocker. Two clinical studies (AC-067-101 and AC-067-102) were conducted to characterize its safety, tolerability, and pharmacokinetics in healthy male subjects after oral administration of single and multiple doses. Both trials were single-center, randomized, double-blind, placebo-controlled, adaptive design, ascending-dose studies, in which ACT-280778 was administrated as single doses of 2, 5, 15, or 40 mg, or as once-daily doses of 5 or 15 mg for 7 days. Single and multiple doses up to and including 15 mg were well tolerated, and no serious or severe adverse event was reported in either study. A single dose of 40 mg was associated with abnormal electrocardiogram findings resulting in the discontinuation of further treatment at this dose or higher doses. ACT-280778 was rapidly absorbed, and larger than dose-proportional increases of the maximum plasma concentration and area under the plasma concentration-time curve were observed. Food intake delayed the time to maximum plasma concentration and doubled exposure. Urinary excretion of unchanged ACT-280778 was negligible, and accumulation at steady state was modest. Overall, pharmacokinetic and tolerability profiles of ACT-280778 observed in these 2 studies warranted further evaluation of ACT-280778 in a proof-of-concept study in patients with hypertension.

Pharmacokinetics, pharmacodynamics, and tolerability of ACT-077825, a new direct renin inhibitor after multiple-ascending doses in healthy subjects.

This study was conducted to characterize the multiple-dose tolerability, pharmacokinetics, and pharmacodynamics of ACT-077825, a new direct renin inhibitor, in healthy male subjects. In this single-center, double-blind, placebo-controlled, active-controlled (20 mg of enalapril), randomized multiple-ascending dose study, ACT-077825 was administered once a day. for 7 days in the 50-1000 mg dose range to sodium- and potassium-restricted subjects. ACT-077825 pharmacokinetics on days 1 and 7 were characterized by dose-proportional increases in Cmax and AUCτ. At steady state, accumulation was modest (1.5- to 1.7-fold). Enalapril caused an increase in plasma active renin concentration and plasma renin activity (PRA). ACT-077825 dose dependently increased active renin on days 1 and 7 and inhibited PRA dose dependently only on day 1. On day 7, the maximal PRA inhibition was attained after 250 mg of ACT-077825. In contrast to enalapril, ACT-077825 did not induce any consistent lowering effect on blood pressure when compared with placebo. Of the reported adverse events, diarrhea, headache, and postural dizziness were more frequent. The incidence of diarrhea was greater in the 1000-mg group and a dose of 500 mg of ACT-077825 was identified as the maximum tolerated dose. Overall, pharmacokinetic, pharmacodynamic, and tolerability profiles warrant the further investigation of ACT-077825 in patients with hypertension.

Relative bioavailability of a newly developed pediatric formulation of bosentan vs. the adult formulation.

WHAT IS KNOWN: Bosentan is a dual endothelin receptor antagonist approved for the treatment of pulmonary arterial hypertension (PAH). Since bosentan is frequently used to treat pediatric PAH patients, a pediatric formulation was developed. AIM: To evaluate the pharmacokinetic properties of bosentan and its active metabolite, Ro 48-5033, of the quadrisected, dispersible pediatric vs. the adult tablet after single-dose administration to healthy subjects. Secondary objectives of the study were to compare the pharmacokinetics of two inactive metabolites and the safety of both formulations. MATERIALS AND METHODS: In this open-label, two-way crossover study, subjects (20 - 43 years) were randomized to receive single oral doses of 62.5 mg of bosentan as 1 adult tablet and 64 mg as 2 pediatric tablets of 32 mg. Blood samples were drawn over a 48-hour period to measure bosentan and its metabolites. RESULTS: 16 subjects were enrolled and completed the study. Following treatment with the pediatric formulation, values for Cmax and AUC0-∞ of bosentan were lower than with the adult formulation with geometric mean ratios (90% confidence interval) of 0.82 (0.65, 1.04) and 0.87 (0.78, 0.97), respectively. Similar results were obtained for the primary active metabolite Ro 48-5033. Both treatments were well tolerated. WHAT IS NEW AND CONCLUSION: Although the 90% confidence intervals of the geometric mean ratios of Cmax and AUC0-∞ were not entirely within the conventional bioequivalence range (0.80 - 1.25), no clinically relevant effect of formulation on the pharmacokinetics of bosentan and Ro 48-5033 was detected. Both formulations were well tolerated.

Integrated pharmacokinetics and pharmacodynamics of epoprostenol in healthy subjects.

AIM: The aim of the study was to report the first thorough characterization of the pharmacokinetics (PK) and pharmacodynamics (PD) of epoprostenol in an integrated manner. METHOD: Twenty healthy male subjects received two formulations of i.v. epoprostenol, in a crossover design, in sequential infusions of 2, 4, 6 and 8 ng kg(-1) min(-1) for 2 h each. A sensitive assay was developed which allowed accurate PK characterization of epoprostenol via analysis of the concentration-time profiles of its two primary metabolites, 6-keto-prostacyclin F(1α) and 6,15-diketo-13,14-dihydro-prostacyclin F(1α) . PD parameters included cardiac output (CO), cardiac index (CIn) and heart rate (HR). RESULTS: The pharmacokinetics of epoprostenol deviated slightly from dose-proportionality, probably due to a food effect. After infusion of the two formulations of epoprostenol, the t(1/2) values expressed as geometric mean (95% confidence interval) were 0.25 h (0.14, 0.46) and 0.22 h (0.13, 0.38) for 6-keto-prostacyclin F(1α) , and 0.32 h (0.22, 0.45) and 0.34 h (0.26, 0.46) for 6,15-diketo-13,14-dihydro-prostacyclin F(1α) . A single compartment infusion model with first order elimination adequately described the PK of 6-keto-prostacyclin F(1α) . This model also characterized the food effect. Stepwise infusions with epoprostenol resulted in a progressive increase in CO, CIn and HR. CONCLUSION: Of the two metabolites analyzed, the appearance of 6-keto-prostacyclin F(1α) in plasma was more closely associated with the haemodynamic effects of i.v. epoprostenol. PK and PD profiles showed that CIn relates proportionally and linearly to the plasma concentrations of 6-keto-prostacyclin F(1α) . These results suggest that 6-keto-prostacyclin F(1α) is a suitable surrogate marker of plasma concentrations of epoprostenol.

Entry-into-humans study with a new direct renin inhibitor.

PURPOSE: To evaluate the pharmacokinetics, pharmacodynamics, safety, and tolerability of escalating single oral doses of ACT-077825, a novel orally active renin inhibitor, in healthy male subjects. METHODS: In this single-center, double-blind, placebo- and active-controlled (with enalapril) randomized study, 70 subjects received a single dose of ACT-077825 (1-1,000 mg), placebo, or enalapril 20 mg under fasted conditions. The main pharmacokinetic endpoints were area under the plasma ACT-077825 concentration-time curve from time zero to infinity and the terminal half-life (t(1/2)). The pharmacodynamic endpoints included immunoactive active renin (iAR) plasma concentrations and plasma renin activity (PRA). Standard laboratory and safety data were collected. RESULTS: Of the few adverse events reported, diarrhea and headache were the most frequent. The pharmacokinetics of ACT-077825 were dose-proportional in the dose range 100 to 1,000 mg. Terminal t(1/2), best characterized following a dose of 1,000 mg, was 41.6 h and t(max) 4-5 h post-dose. ACT-077825 dose-dependently increased iAR and decreased PRA, effects that were associated with a decrease in blood pressure at 1,000 mg, similar to following treatment with enalapril. CONCLUSION: The results provide evidence that ACT-077825, with a pharmacokinetic profile consistent with a once-a-day dosing regimen, may represent an effective antihypertensive agent and pave the way toward a multiple-ascending dose study.

Supply/demand ratio for medical consultations, diagnostic tests and chronic kidney disease monitoring in the Brazilian National Health System: a descriptive study, state of São Paulo, Brazil, 2019. / Razão oferta/necessidade de consultas médicas, exames de diagnóstico e acompanhamento da doença renal crônica no Sistema Único de Saúde: estudo descritivo, estado de São Paulo, 2019.

OBJECTIVE: To determine the supply/demand ratio for procedures related to diagnosis and treatment for chronic kidney disease in the Brazilian National Health System (SUS), in the state of São Paulo, Brazil, 2019. METHODS: This was a descriptive study, using data from the SUS outpatient and hospital information systems. The numbers of medical consultations, diagnostic and chronic kidney disease monitoring tests, performed in the period, were compared with the demand estimation, obtained through ministerial guidelines. RESULTS: Exclusive SUS users were 28,791,244, and individuals with arterial hypertension and/or diabetes mellitus, 5,176,188. The number of procedures performed and the ratio between this number and the needs of the population were 389,414 consultations with nephrologists (85%); 11,540,371 serum creatinine tests (223%); 705,709 proteinuria tests (14%); 438,123 kidney ultrasounds (190%); and 1,045 kidney biopsies (36%). CONCLUSION: In the chronic kidney disease care in the SUS it could be seen simultaneous existence of lack of supply, waste and inadequate screening of important procedures.

Five new species of yeasts from fresh water and marine habitats in the Florida Everglades.

Yeast populations in the Shark River Slough of the Florida Everglades, USA, were examined during a 3-year period (2002-2005) at six locations ranging from fresh water marshes to marine mangroves. Seventy-four described species (33 ascomycetes and 41 basidiomycetes) and an approximately equal number of undescribed species were isolated during the course of the investigation. Serious human pathogens, such as Candida tropicalis, were not observed, which indicates that their presence in coastal waters is due to sources of pollution. Some of the observed species were widespread throughout the fresh water and marine habitats, whereas others appeared to be habitat restricted. Species occurrence ranged from prevalent to rare. Five representative unknown species were selected for formal description. The five species comprise two ascomycetes: Candida sharkiensis sp. nov. (CBS 11368(T)) and Candida rhizophoriensis sp. nov. (CBS 11402(T)) (Saccharomycetales, Metschnikowiaceae), and three basidiomycetes: Rhodotorula cladiensis sp. nov. (CBS 10878(T)) in the Sakaguchia clade (Cystobasidiomycetes), Rhodotorula evergladiensis sp. nov. (CBS 10880(T)) in the Rhodosporidium toruloides clade (Microbotryomycetes, Sporidiobolales) and Cryptococcus mangaliensis sp. nov. (CBS 10870(T)) in the Bulleromyces clade (Agaricomycotina, Tremellales).

The Effect of Salmon Food-Derived DOM and Glacial Melting on Activity and Diversity of Free-Living Bacterioplankton in Chilean Patagonian Fjords.

Fjord ecosystems cycle and export significant amounts of carbon and appear to be extremely sensitive to climate change and anthropogenic perturbations. To identify patterns of microbial responses to ongoing natural and human-derived changes in the fjords of Chilean Patagonia, we examined the effect of organic enrichment associated with salmon aquaculture and freshening produced by glacial melting on bacterial production (BP), extracellular enzymatic activity (EEA), and community diversity of free-living bacterioplankton. We assayed the effects of salmon food-derived dissolved organic matter (SF-DOM) and meltwaters through microcosm experiments containing waters from Puyuhuapi Fjord and the proglacial fjords of the Southern Patagonia Icefield, respectively. Rates of BP and EEA were 2 times higher in the presence of SF-DOM than in controls, whereas the addition of autochthonous organic matter derived from diatoms (D-DOM) resulted in rates of BP and EEA similar to those measured in the controls. The addition of SF-DOM also reduced species richness and abundance of a significant fraction of the representative taxa of bacterioplankton of Puyuhuapi Fjord. In the proglacial fjords, bacterioplankton diversity was reduced in areas more heavily influenced by meltwaters and was accompanied by moderate positive changes in BP and EEA. Our findings strongly suggest that SF-DOM is highly reactive, promoting enhanced rates of microbial activity while could be influencing the diversity of bacterioplankton communities in Patagonian fjords with a strong salmon farming activity. These findings challenge the traditional view of phytoplankton production as the primary source of labile DOM that fuels heterotrophic activity in coastal ecosystems impacted by anthropogenic organic enrichment. Given the intensive local production of salmon, we analyze the significance of this emerging source of rich "allochthonous" organic substrates for autotrophic/heterotrophic balance, carbon exportation, and hypoxia in Patagonian fjords. The effect of human DOM enrichment can be enhanced in proglacial fjords, where progressive glacial melting exerts additional selective pressure on bacterioplankton diversity.

Water column circulation drives microplastic distribution in the Martínez-Baker channels; A large fjord ecosystem in Chilean Patagonia.

We investigated the distribution of microplastics in the water column along a large remote estuarine system located between the Northern and Southern Patagonian Ice Fields in Chilean Patagonia, and connected with the Pacific Ocean through the Gulf of Penas. Microplastic particles were found in all samples, with abundances ranging from 0.1 to 7 particles/m3. Polymers identified were principally acrylics, PET, and cellophane. The average abundance of microplastics in surface waters was similar along the whole estuary (0.4 ± 0.3 particles/m3) with acrylics and epoxy resins being more abundant near Caleta Tortel, the only small village in the area. The observed higher abundance of microplastics in the deeper waters towards the Gulf of Penas points to intrusions of subsurface waters transporting plastic particles from the ocean into the channel system. This underlines the potential of ocean currents in transporting plastic pollution into pristine fjords and channels in Chilean Patagonia.

Schwannoma de nervio facial con reanimación facial con Neurotizacion Hipoglosofacial / SCHWANNOMA OF THE FACIAL NERVE WITH FACIAL RESUSCITATION WITH FACIAL HYPOGLOSSAL NEUROTIZATION

El schwannoma es una patología rara del nervio facial. Su diagnóstico preoperatorio es dificultoso dado que no tiene síntomas ni signos patognomónico de la enfermedad. La disección del nervio facial en su tronco y sus ramas con electroestimulacion es la forma de quirúrgica de sospecharlo intraoperatoriamente. La descompresión parcial o exeresis completa deberá ser considerado de acuerdo a la experiencia del equipo quirúrgico en reconstrucción nerviosa. La reparación del nervio facial como primera opción debe el injerto inmediato o sutura termino terminal. La neurotización es un procedimiento quirúrgico que le provoca al paciente simetría facial con manejo de oclusión ocular y manejo de comisura bucal, debe ser realizado antes del año de la injuria nerviosa. La rehabilitación del nervio facial necesita de un equipo multidisciplinario y la colaboración permanente del paciente para conseguir los objetivos propuestos.

Schwannoma is a rare pathology of the facial nerve. Its preoperative diagnosis is difficult since it has no symptoms or pathognomonic signs of the disease. The dissection of the facial nerve in its trunk and its branches with electrostimulation is the surgical way to suspect it intraoperatively. Partial decompression or complete exeresis should be considered according to the experience of the surgical team in nerve reconstruction. The repair of the facial nerve as a first option should be the immediate graft or end-to-end suture. Neurotization is a surgical procedure that causes the patient facial symmetry with management of ocular occlusion and management of the corner of the mouth, it must be performed within a year of the nerve injury. The rehabilitation of the facial nerve requires a multidisciplinary team and the permanent collaboration of the patient to achieve the proposed objectives.

Razão oferta/necessidade de consultas médicas, exames de diagnóstico e acompanhamento da doença renal crônica no Sistema Único de Saúde: estudo descritivo, estado de São Paulo, 2019 / Relación oferta/necesidad de consultas médicas, pruebas diagnósticas y seguimiento de la enfermedad renal crónica en el Sistema Único de Salud: estudio descriptivo, São Paulo, Brasil, 2019 / Supply/demand ratio for medical consultations, diagnostic tests and chronic kidney disease monitoring in the Brazilian National Health System: a descriptive study, state of São Paulo, Brazil, 2019

Objetivo: Determinar a razão oferta/necessidade de procedimentos relacionados com o diagnóstico e assistência à doença renal crônica no Sistema Único de Saúde (SUS), no estado de São Paulo, Brasil, 2019. Métodos: Estudo descritivo, utilizando dados dos sistemas de informações ambulatoriais e hospitalares do SUS. Os números de consultas médicas e exames diagnósticos e de acompanhamento da doença renal realizados no período foram comparados com as estimativas de necessidade obtidas por diretrizes ministeriais. Resultados: Usuários exclusivos do SUS eram 28.791.244, e indivíduos com hipertensão e/ou diabetes mellitus, 5.176.188. O número de procedimentos realizados e a razão entre esse número e a necessidade da população foram de 389.414 consultas com nefrologista (85%); 11.540.371 dosagens de creatinina sérica (223%); 705.709 dosagens de proteinúria (14%); 438.123 ultrassonografias renais (190%); e 1.045 biópsias renais (36%). Conclusão: Na assistência à doença renal crônica no SUS existem, simultaneamente, falta de oferta, desperdício e rastreamento deficiente de procedimentos importantes.

Objetivo: Determinar la relación oferta/necesidad de procedimientos relacionados con el diagnóstico y atención de la enfermedad renal crónica en Sistema Único de Salud (SUS) del Estado de São Paulo, Brasil, en 2019. Métodos: Estudio descriptivo utilizando datos de los sistemas de información ambulatoria y hospitalaria del SUS. Se comparó el número de consultas médicas, pruebas de diagnóstico y seguimiento de la enfermedad renal realizados con las estimaciones de necesidad recomendadas por directrices ministeriales. Resultados: Los usuarios exclusivos de SUS fueron 28.791.244 e hipertensos y/o diabéticos, 5.176.188. El número de procedimientos realizados y la relación entre este número y la necesidad de la población fueran de 389.414 consultas con nefrólogo (85%); 11.540.371 determinaciones de creatinina sérica (223%); 705.709 determinaciones de proteinuria (14%); 438.123 ecografías renales (190%); y 1.045 biopsias renales (36%). Conclusión: En la atención de enfermedad renal en SUS existe, simultáneamente, falta de oferta, desperdicio y seguimiento deficiente de procedimientos importantes.

Objective: To determine the supply/demand ratio for procedures related to diagnosis and treatment for chronic kidney disease in the Brazilian National Health System (SUS), in the state of São Paulo, Brazil, 2019. Methods: This was a descriptive study, using data from the SUS outpatient and hospital information systems. The numbers of medical consultations, diagnostic and chronic kidney disease monitoring tests, performed in the period, were compared with the demand estimation, obtained through ministerial guidelines. Results: Exclusive SUS users were 28,791,244, and individuals with arterial hypertension and/or diabetes mellitus, 5,176,188. The number of procedures performed and the ratio between this number and the needs of the population were 389,414 consultations with nephrologists (85%); 11,540,371 serum creatinine tests (223%); 705,709 proteinuria tests (14%); 438,123 kidney ultrasounds (190%); and 1,045 kidney biopsies (36%). Conclusion: In the chronic kidney disease care in the SUS it could be seen simultaneous existence of lack of supply, waste and inadequate screening of important procedures.

A randomized, placebo-controlled trial of citalopram for the treatment of major depression in children and adolescents.

OBJECTIVE: Open-label trials with the selective serotonin reuptake inhibitor citalopram suggest that this agent is effective and safe for the treatment of depressive symptoms in children and adolescents. The current study investigated the efficacy and safety of citalopram compared with placebo in the treatment of pediatric patients with major depression. METHOD: An 8-week, randomized, double-blind, placebo-controlled study compared the safety and efficacy of citalopram with placebo in the treatment of children (ages 7-11) and adolescents (ages 12-17) with major depressive disorder. Diagnosis was established with the Schedule for Affective Disorders and Schizophrenia for School-Age Children-Present and Lifetime Version. Patients (N=174) were treated initially with placebo or 20 mg/day of citalopram, with an option to increase the dose to 40 mg/day at week 4 if clinically indicated. The primary outcome measure was score on the Children's Depression Rating Scale-Revised; the response criterion was defined as a score of < or =28. RESULTS: The overall mean citalopram dose was approximately 24 mg/day. Mean Children's Depression Rating Scale-Revised scores decreased significantly more from baseline in the citalopram treatment group than in the placebo treatment group, beginning at week 1 and continuing at every observation point to the end of the study (effect size=2.9). The difference in response rate at week 8 between placebo (24%) and citalopram (36%) also was statistically significant. Citalopram treatment was well tolerated. Rates of discontinuation due to adverse events were comparable in the placebo and citalopram groups (5.9% versus 5.6%, respectively). Rhinitis, nausea, and abdominal pain were the only adverse events to occur with a frequency exceeding 10% in either treatment group. CONCLUSIONS: In this population of children and adolescents, treatment with citalopram reduced depressive symptoms to a significantly greater extent than placebo treatment and was well tolerated.

An evaluation of the potential for pharmacokinetic interaction between escitalopram and the cytochrome P450 3A4 inhibitor ritonavir.

BACKGROUND: Depression often coexists with a number of disease states, and patients with a diagnosis of depression often receive multiple medications. Thus, it is desirable to avoid coadministration of agents that have a potential for drug interactions in these patients. Although escitalopram and its metabolites are weak to negligible inhibitors of the cytochrome P450 (CYP) 3A4 isozyme and are therefore unlikely to affect plasma concentrations of ritonavir (a CYP3A4 substrate and prototype CYP3A4 inhibitor), ritonavir may potentially affect plasma concentrations of escitalopram, as CYP3A4 is partially responsible for conversion of escitalopram to its major metabolite, S-demethylcitalopram (S-DCT). OBJECTIVES: The aim of this study was to investigate the potential for pharmacokinetic interaction between escitalopram and ritonavir after concomitant administration of a single dose of each in healthy young subjects. METHODS: In this single-center, randomized, open-label, 3-way crossover study, subjects received each of the following: a single dose of escitalopram 20 mg, a single dose of ritonavir 600 mg, and single doses of both escitalopram 20 mg and ritonavir 600 mg. Blood was collected and plasma was analyzed for the pharmacokinetic parameters (maximum plasma concentration [C(max)], time to C(max) [T(max)], area under the plasma concentration-time curve, plasma elimination half-life, oral clearance, and apparent volume of distribution) of escitalopram, S-DCT, and ritonavir. RESULTS: Of 21 subjects (11 men, 10 women; mean [SD] age, 28.4 [4.4] years) who were enrolled, 18 completed the study. After concomitant administration of escitalopram and ritonavir, no statistically significant differences were noted in the pharmacokinetics of escitalopram, with the exception of apparent volume of distribution, which was reduced by approximately 10% (P < 0.001). The pharmacokinetics of S-DCT were unaffected by coadministration of ritonavir, with the exception of T(max), which was increased in the presence of ritonavir. The pharmacokinetic parameters of ritonavir were also unaffected by coadministration of escitalopram. CONCLUSION: In general, no pharmacokinetic interaction was observed between escitalopram and ritonavir in the present study.

Two-step upflow anaerobic sludge bed system for sewage treatment under subtropical conditions with posttreatment in waste stabilization ponds.

A pilot-scale sewage treatment system consisting of two upflow anaerobic sludge bed (UASB) reactors followed by five waste stabilization ponds (WSPs) in series was studied under subtropical conditions. The first UASB reactor started up in only 1 mo (stable operation, high chemical oxygen demand [COD] removal efficiency, low volatile fatty acids concentration in the effluent, alkalinity ratio above 0.7, biogas production above 0.1 Nm3/kg of CODremoved). Removal efficiencies up to 90% were obtained in the anaerobic steps at a hydraulic retention time of 6 + 4 h (80% removal in the first step). Fecal coliform removal in the whole system was 99.9999% (99.94% in anaerobic steps and 99.98% in WSPs). COD balances over UASB reactors are provided. A minimum set of data necessary to build COD balances is proposed. Intermittent sludge washout was detected in the reactors with the COD balances. Sludge washout from single-step UASB reactors should be monitored and minimized in order to ensure constant compliance with discharge standards, especially when no posttreatment is provided. The system combined high COD and fecal coliform removal efficiency with an extremely low effluent concentration, complying with discharge standards, and making it an attractive option for sewage treatment in subtropical regions.