Healthcare-associated infections on the intensive care unit in 21 Brazilian hospitals during the early months of the coronavirus disease 2019 (COVID-19) pandemic: An ecological study.

OBJECTIVE: The coronavirus disease 2019 (COVID-19) pandemic has caused a global health crisis and may have affected healthcare-associated infection (HAI) prevention strategies. We evaluated the impact of the COVID-19 pandemic on HAI incidence in Brazilian intensive care units (ICUs). METHODS: In this ecological study, we compared adult patients admitted to the ICU from April through June 2020 (pandemic period) with the same period in 2019 (prepandemic period) in 21 Brazilian hospitals. We used the Wilcoxon signed rank-sum test in a pairwise analysis to compare the following differences between the pandemic and the prepandemic periods: microbiologically confirmed central-line-associated bloodstream infection (CLABSI) and ventilator-associated pneumonia (VAP) incidence density (cases per 1,000 central line and ventilator days, respectively), the proportion of organisms that caused HAI, and antibiotic consumption (DDD). RESULTS: We detected a significant increase in median CLABSI incidence during the pandemic: 1.60 (IQR, 0.44-4.20) vs 2.81 (IQR, 1.35-6.89) (P = .002). We did not detect a significant difference in VAP incidence between the 2 periods. In addition, we detected a significant increase in the proportion of CLABSI caused by Enterococcus faecalis and Candida spp during the pandemic, although only the latter retained statistical significance after correction for multiple comparisons. We did not detect a significant change in ceftriaxone, piperacillin-tazobactam, meropenem, or vancomycin consumption between the studied periods. CONCLUSIONS: There was an increase in CLABSI incidence in Brazilian ICUs during the first months of COVID-19 pandemic. Additionally, we detected an increase in the proportion of CLABSI caused by E. faecalis and Candida spp during this period. CLABSI prevention strategies must be reinforced in ICUs during the COVID-19 pandemic.

Evolution to permanent or transient conditions in children with positive neonatal TSH screening tests in Sergipe, Brazil.

OBJECTIVES: To assess the evolution to permanent or transient conditions in children with positive neonatal TSH tests in Sergipe, Brazil, from 2004 to 2010. SUBJECTS AND METHODS: Out of 193,794 screened newborns, 713 presented a neonatal TSH level higher than the local cutoff (5.2 µU/mL). From the confirmatory serum TSH values, the children were diagnosed with initial congenital hypothyroidism (CH) or suspect CH. From the evolution, they were classified as permanent CH, hyperthyrotropinemia, or transient TSH elevation. The mean incidence of each final condition was calculated for the total period of time. RESULTS: The initial diagnosis included 37 CH (18.1%) and 167 suspect CH (81.9%) cases. The final diagnosis included 46 cases of permanent CH (22.5%), 56 of hyperthyrotropinemia (27.5%), and 102 of transient TSH elevation (50.0%). Out of the 37 cases of initial CH, 23 (62.2%) had permanent CH, nine (24.3%) had hyperthyrotropinemia, and five (13.5%) had transient TSH elevation. Out of the 167 suspect CH cases, 23 (13.8%) had permanent CH, 47 (28.1%) had hyperthyrotropinemia and 97 (58.1%) had transient TSH elevation. The mean incidence after the follow up was 1:4,166 for permanent CH, 1:3,448 for hyperthyrotropinemia, and 1:1,887 for transient TSH elevation. Eighty-six percent of the children with an initial diagnosis of CH and 41.9% with suspect CH had a permanent condition (CH or hyperthyrotropinemia). CONCLUSIONS: The follow-up of children with an initial diagnosis of CH or suspect CH is necessary to determine whether the disorder is permanent because predicting the evolution of the condition is difficult.

Evolution to permanent or transient conditions in children with positive neonatal TSH screening tests in Sergipe, Brazil

ABSTRACT Objectives To assess the evolution to permanent or transient conditions in children with positive neonatal TSH tests in Sergipe, Brazil, from 2004 to 2010. Subjects and methods Out of 193,794 screened newborns, 713 presented a neonatal TSH level higher than the local cutoff (5.2 µU/mL). From the confirmatory serum TSH values, the children were diagnosed with initial congenital hypothyroidism (CH) or suspect CH. From the evolution, they were classified as permanent CH, hyperthyrotropinemia, or transient TSH elevation. The mean incidence of each final condition was calculated for the total period of time. Results The initial diagnosis included 37 CH (18.1%) and 167 suspect CH (81.9%) cases. The final diagnosis included 46 cases of permanent CH (22.5%), 56 of hyperthyrotropinemia (27.5%), and 102 of transient TSH elevation (50.0%). Out of the 37 cases of initial CH, 23 (62.2%) had permanent CH, nine (24.3%) had hyperthyrotropinemia, and five (13.5%) had transient TSH elevation. Out of the 167 suspect CH cases, 23 (13.8%) had permanent CH, 47 (28.1%) had hyperthyrotropinemia and 97 (58.1%) had transient TSH elevation. The mean incidence after the follow up was 1:4,166 for permanent CH, 1:3,448 for hyperthyrotropinemia, and 1:1,887 for transient TSH elevation. Eighty-six percent of the children with an initial diagnosis of CH and 41.9% with suspect CH had a permanent condition (CH or hyperthyrotropinemia). Conclusions The follow-up of children with an initial diagnosis of CH or suspect CH is necessary to determine whether the disorder is permanent because predicting the evolution of the condition is difficult.

Residência médica integrada para o Programa de Saúde da Família / Integrated medical residency for the Family Health Program

Este artigo discute a estrutura do programa de Residência Médica, visando à formação de médicos generalistas capazes de atuar em cidades do interior atendendo ao Programa de Saúde da Família e as áreas básicas da Medicina: Pediatria, Ginecologia e Obstetrícia, Cirurgia Geral, Clínica Médica, urgência, trauma e Anestesiologia. O que se observa é que a maioria dos programas de residência não tem preparado profissionais com esse perfil. A formação desses profissionais se torna imprescindível para que ocorra a interiorização do médico e, com isso, a melhoria da assistência médica no interior.

This article discusses the structure of the Medical Residency program aimed at training general practitioners capable of working in countryside towns and who will practice in the Family Health Program in the basic medical areas of Pediatrics, Obstetrics and Gynecology, General Surgery, Internal Medicine, Urgent Care, Trauma, and Anesthesiology. Most residency programs have not been training professionals with this profile. Such training is paramount for doctors who relocate to the countryside so as to improve medical care in these regions.

Prevalence of discordant immunologic and virologic responses in patients with AIDS under antiretroviral therapy in a specialized care center in Brazil.

Some patients under antiretroviral therapy (ART) do not reach immune recovery when the viral load becomes undetectable. This is called discordant immunologic and virologic responses. Its prevalence varies between 8% and 24%. This study describes its prevalence and the characteristics of the affected subjects in the outpatient clinic of a Brazilian specialized-care center. Of 934 patients on ART, 536 had undetectable viral loads. Prevalence was 51/536 or 9% (95% confidence interval: 6.6% to 11.4%). Median age at the beginning of ART was 37 years (interquartile range - IQR: 31 to 45). Male gender and mixed race predominated (76.5% and 47.1% respectively). AIDS-defining illnesses were absent at the beginning of ART in 60.8%. Fifty-one percent were taking protease inhibitors, 43.2% Efavirenz and 5.8% both. Median time on ART was 36 months (IQR: 17-81 months). Irregular treatment was recorded for 21.6%. ART had been modified for 63% prior to the study, and 15.7% had used monotherapy or double therapy. Median CD4 count was 255 cells/mm³ (IQR: 200-284). Median viral load before ART was 4.7 log10 copies/mL (IQR: 4.5-5.2). Discordant responders were not different from AIDS patients in general, but there was a high frequency of multiple schedules of treatment.

Prevalence of discordant immunologic and virologic responses in patients with AIDS under antiretroviral therapy in a specialized care center in Brazil / Prevalência da resposta imunológica e virológica discordante em pacientes com AIDS sob terapêutica antirretroviral em ambulatório de centro de cuidados especializados no Brasil

Some patients under antiretroviral therapy (ART) do not reach immune recovery when the viral load becomes undetectable. This is called discordant immunologic and virologic responses. Its prevalence varies between 8 percent and 24 percent. This study describes its prevalence and the characteristics of the affected subjects in the outpatient clinic of a Brazilian specialized-care center. Of 934 patients on ART, 536 had undetectable viral loads. Prevalence was 51/536 or 9 percent (95 percent confidence interval: 6.6 percent to 11.4 percent). Median age at the beginning of ART was 37 years (interquartile range - IQR: 31 to 45). Male gender and mixed race predominated (76.5 percent and 47.1 percent respectively). AIDS-defining illnesses were absent at the beginning of ART in 60.8 percent. Fifty-one percent were taking protease inhibitors, 43.2 percent Efavirenz and 5.8 percent both. Median time on ART was 36 months (IQR: 17-81 months). Irregular treatment was recorded for 21.6 percent. ART had been modified for 63 percent prior to the study, and 15.7 percent had used monotherapy or double therapy. Median CD4 count was 255 cells/mm³ (IQR: 200-284). Median viral load before ART was 4.7 log10 copies/mL (IQR: 4.5-5.2). Discordant responders were not different from AIDS patients in general, but there was a high frequency of multiple schedules of treatment.

Alguns pacientes sob terapêutica antirretroviral (TARV) não obtêm recuperação imune quando a carga viral se torna indetectável. Isto é chamado resposta imunológica e virológica discordante. A prevalência varia entre 8 por cento e 24 por cento. Este estudo descreve sua prevalência e características dos afetados em ambulatório de um centro de cuidados especializados brasileiro. De 934 pacientes sob TARV, 536 tinham carga viral indetectável. A prevalência foi 51/536, ou 9 por cento (Intervalo de Confiança de 95 por cento de 6,6 por cento a 11,4 por cento). Idade mediana no início da TARV foi 37 anos (distância interquartílica - DQ: 31 a 45). Gênero masculino e cor parda predominaram (76,5 por cento e 47,1 por cento, respectivamente). Doenças definidoras de Aids estavam ausentes no início da TARV em 60,8 por cento. Cinquenta e um por cento recebiam inibidores da Protease, 43,2 por cento Efavirenz e 5,8 por cento ambos. Tempo mediano de TARV foi 36 meses (DQ: 17-81). Tratamento irregular foi registrado em 21,6 por cento. TARV havia sido anteriormente modificado em 63 por cento e 15,7 por cento haviam usado mono ou dupla terapêutica. A contagem mediana de CD4 foi 255 células/mm³ (DQ: 200-284). O logaritmo mediano da carga viral antes do TARV foi 4,7 (DQ: 4,5-5,2). Aqueles com resposta discordante não eram diferentes dos pacientes com AIDS em geral, mas houve alta frequência de múltiplos esquemas terapêuticos.

Factors associated with paradoxical immune response to antiretroviral therapy in HIV infected patients: a case control study.

BACKGROUND: A paradoxical immunologic response (PIR) to Highly Active Antiretroviral Therapy (HAART), defined as viral suppression without CD4 cell-count improvement, has been reported in the literature as 8 to 42%, around 15% in most instances. The present study aims to determine, in a cohort of HIV infected patients in Brazil, what factors were independently associated with such a discordant response to HAART. METHODS: A case-control study (1:4) matched by gender was conducted among 934 HIV infected patients on HAART in Brazil. CASES: patients with PIR, defined as CD4 < 350 cells/mm(3) (hazard ratio for AIDS or death of at least 8.5) and undetectable HIV viral load on HAART for at least one year. CONTROLS: similar to cases, but with CD4 counts ≥ 350 cells/mm(3). Eligibility criteria were applied. Data were collected from medical records using a standardized form. Variables were introduced in a hierarchical logistic regression model if a p-value < 0.1 was determined in a bivariate analysis. RESULTS: Among 934 patients, 39 cases and 160 controls were consecutively selected. Factors associated with PIR in the logistic regression model were: total time in use of HAART (OR 0.981; CI 95%: 0.96-0.99), nadir CD4-count (OR 0.985; CI 95%: 0.97-0.99), and time of undetectable HIV viral load (OR 0.969; CI 95%: 0.94-0.99). CONCLUSIONS: PIR seems to be related to a delay in the management of immunodeficient patients, as shown by its negative association with nadir CD4-count. Strategies should be implemented to avoid such a delay and improve the adherence to HAART as a way to implement concordant responses.

Perfil dos pacientes com necessidades especiais de uma clínica de odontopediatria / Profile of special needs patients at a pediatric dentistry clinic

Objetivo: Avaliar o perfil dos Pacientes com Necessidades Especiais atendidos na Clínica de Odontopediatria da Faculdade de Odontologia da Universidade Federal do Pará. Métodos: Estudo observacional descritivo, realizado no período de março de 2007 a dezembro de 2009, analisando 137 prontuários, dos quais se extraíram os seguintes dados: gênero, idade, procedência, história médica atual e pregressa, tipo de necessidades especiais e principais doenças bucais. Aplicou-se a estatística descritiva, tabela unidimensional de frequência e elaboraram-se gráficos dos resultados. Resultados: Encontraram-se 77 (56,2%) pacientes do gênero masculino, com média de idade de 8,1 anos; 118 (86,2%) residentes na capital do Estado do Pará; 21 (15,3%) com problemas respiratórios; 37 (27,3%) com alguma alergia a medicamentos e 54 (39,4%) fazendo uso de medicamento controlado. Quanto ao tipo de necessidade especial, verificou-se que 29 (28,3%) apresentaram atraso no desenvolvimento neuropsicomotor, e a principal doença bucal encontrada foi a cárie, atingindo 84 (61,3%) indivíduos. Conclusão: O perfil avaliado dos pacientes com necessidades especiais caracteriza-se por pacientes residentes na capital do Estado do Pará, predominância de crianças do sexo masculino, portadores de atraso de desenvolvimento neuropsicomotor, com idade média de 8,1 anos, apresentando, principalmente, cárie.

Objective: To assess the characteristics of special needs patients assisted at the Clinic of Pediatric Dentistry, Faculty of Dentistry, Federal University of Pará. Methods: A descriptive observational study conducted from March 2007 to December 2009, assessing 137 records of which were extracted the following data: gender, age, origin, current and past medical history, type of special needs and major oral diseases. We applied descriptive statistics, one-dimensional frequency table and prepared graphs of the results. Results: We found 77 (56.2%) male patients, with mean age of 8.1 years; 118 (86.2%) living in the state capital of Para, 21 (15.3%) with respiratory problems, 37 (27.3%) with some allergy to medications and 54 (39.4%) making use of controlled drugs. Regarding the type of special need, we observed that 29 (28.3%) had neurologic and psychomotor delay and the primary oral disease found was dental caries, affecting 84 (61.3%) subjects. Conclusion: The assessed profile of patients with special needs is characterized by patients residing in the state capital of Para, with predominance of male children, with neurologic and psychomotor delay, with a mean age of 8.1 years, presenting mainly caries.

The role of integrated home-based care in patient adherence to antiretroviral therapy

O sucesso da terapia antiretroviral depende da adesão ao tratamento. A Assistência Domiciliar Terapêutica é um programa de atendimento multidisciplinar a pacientes com HIV/AIDS e com dificuldades de se deslocar para atendimento ambulatorial. Este estudo compara a adesão de pacientes ao esquema ARV em um programa ADT com aqueles em tratamento ambulatorial convencional. Foram estudados: Grupo 1 - 15 pacientes no programa de ADT, Grupo 2 - 21 pacientes em tratamento ambulatorial convencional, Grupo 3 - 20 pacientes em tratamento ambulatorial convencional que nunca freqüentaram o programa ADT. Os pacientes inscritos no programa ADT apresentaram significativamente maior adesão ao tratamento do que pacientes ambulatoriais (F = 6.66, p= 0,003). Os resultados observados não foram influenciados pelas características demográficas, características socioeconômicas, ou histórico médico. Pacientes em programa de ADT também mostraram uma tendência a melhor resposta terapêutica do que os ambulatoriais. Este estudo sugere a utilização das características do ADT como estratégia para melhorar a adesão à terapia antiretroviral.

The role of integrated home-based care in patient adherence to antiretroviral therapy.

Non-adherence is one of the primary obstacles to successful antiretroviral therapy in HIV+ patients worldwide. In Brazil, the Domiciliary Therapeutic Assistance is a multidisciplinary and integrated home-based assistance program provided for HIV+ patients confined in their homes due to physical deficiency. This study investigated ADT's ability to monitor and promote appropriate adherence to ARV therapy. Fifty-six individuals were recruited from three study groups: Group 1 -- patients currently in the ADT program, Group 2 -- 21 patients previously treated by the ADT program, and Group 3 -- 20 patients who have always been treated using conventional ambulatory care. Using multivariable self-reporting to evaluate adherence, patients in the ADT program had significantly better adherence than patients in ambulatory care (F = 6.66, p = 0.003). This effect was independent of demographic and socioeconomic characteristics as well as medical history. Patients in the ADT program also showed a trend towards greater therapeutic success than ambulatory patients. These results suggest the incorporation of characteristics of ADT in conventional ambulatory care as a strategy to increase adherence to ARV therapy.

Single step polymerase chain reaction (PCR) for the diagnosis of the Leishmania (Viannia) subgenus

No Brasil, o principal agente etiológico da leishmaniose, apresentando freqüentemente comprometimento das mucosas, pertence ao subgênero (Viannia). A conduta terapêutica no tratamento da leishmaniose depende de seu diagnóstico parasitológico e os métodos clássicos restringem sua identificação. Neste trabalho, descrevemos uma reação de PCR, utilizando primers desenhados a partir de seqüências repetitivas de mini-exons, que amplificam um fragmento de 177pb e que são capazes de distinguir o subgênero (Viannia) do subgênero (Leishmania), tornando-se uma ferramenta útil no diagnóstico desta doença.

Interaction between ants and fruits of Guapira opposita (Nyctaginaceae) in a Brazilian sandy plain rainforest: ant effects on seeds and seedlings.

This study examines the dispersal system of Guapira opposita in a tropical sandy rainforest in southeast Brazil. Guapira trees produce small fruits with a high protein content (28.4%) and low lipid content (0.3%), and the plant is primarily dispersed by birds. Mature fruits of G. opposita can fall spontaneously with the pulp intact, or be dropped by birds with bits of pulp attached. In either case, ground-dwelling ants rapidly remove the fruits to their nest (93% after 12 h). The ponerine ants Odontomachus chelifer and Pachycondyla striata are the main seed vectors among the ants, and together account for 56% (20 of 36) of the ant-fruit interactions recorded on the forest floor. Individual workers of O. chelifer and P. striata transport single fruits to their nests. Bits of pulp are fed to larvae and worker nestmates, and intact seeds are discarded outside the nest. Germination success in Guapira is higher for cleaned seeds (pulp removed) than for seeds coated by pulp. Guapira seedlings and juveniles are more frequent close to Odontomachus nests than at sites without such nests. Soil samples from Odontomachus nests had greater penetrability, and higher concentrations of P, K, and Ca than random soil samples. Field experiments suggest that the association between G. opposita seedlings and O. chelifer nests can potentially render the plant some protection against herbivores. Results indicate that fruit displacement by ponerine ants play an important role in the biology of G. opposita seeds and seedlings in the sandy forest, and illustrate the complex nature of the dispersal ecology of tropical tree species.

Single step polymerase chain reaction (PCR) for the diagnosis of the Leishmania (Viannia) subgenus.

In Brazil, the main etiologic agent of Leishmaniasis that frequently presents with mucosal involvement belongs to the Viannia subgenus. The therapeutic conduct in this disease depends on the parasitological diagnosis, and classical methods are restricted in identifying the agent. In this paper we describe a polymerase chain reaction (PCR), which uses primers designed from mini-exons repetitive sequences. The PCR amplifies a 177bp fragment that can distinguish (Viannia) from (Leishmania) subgenus. This test could be a useful diagnostic tool.

Estudo do perfil clínico-epidemiológico dos pacientes atendidos pelo Programa de Assistência Domiciliar Terapêutica em AIDS: Vitória, ES - Brasil / Clinical and epidemiological profile of patients attended at home care assistance in AIDS - Vitória, ES - Brazil

Estudo do perfil da clientela exposta à infecção pelo HIV para detectar possíveis falhas e traçar estratégias preventivas e terapêuticas

Frutooligossacarídeos: implicaçöes na saúde humana e utilizaçäo em alimentos / Fructooligosaccharides: implications in human health being and use in foods

Os frutooligossacarídeos (FOS) säo açúcares näo convencionais, näo metabolizados pelo organismo humano e näo calóricos. Säo considerados prebióticos uma vez que promovem seletivamente o crescimento de probióticos como Acidophillus e Bifidus. Essa característica faz com que os FOS promovam uma série de benefícios à saúde humana, desde a reduçäo de colesterol sérico até o auxílio na prevençäo de alguns tipos de câncer. Esta revisäo aborda principalmente os efeitos da ingestäo de FOS na saúde humana, e algumas de suas aplicaçöes, principalmente na indústria de alimentos.

Avaliação da reação em cadeia de polimerase (PCR) no diagnóstico da leishmaniose cutânea no Estado do Espírito Santo, Brasil / Evaluation of polymerase chain reaction (PCR) in the diagnosis cutaneous leishmaniasis in the Espírito Santo State, Brazil

A confirmação diagnóstica e a identificação de espécies de Leishmania é crucial na condução clínica da leishmaniose cutânea, com implicações terapêuticas e prognósticas, especialmente em áreas onde convivem várias espécies destes protozoários. Com o objetivo de avaliar a eficiência da reação em cadeia por polimerase (PCR) em diagnosticar e determinar a espécie envolvida na leishmaniose / The adequate management of patients with cutaneous leishmaniasis depends on confirmed diagnosis and identification of the species of the infecting agent, with therapeutic and prognostic implications, especially on endemic areas when coexist several species of this protozoan. Looking for the efficiency of a polymerase chain reaction in the diagnosis and species identification in patients with cutaneous leishmaniasis from the State of Espírito Santo, Brazil, we used this reaction...

Toxoplasma encephalitis in AIDS patients in São Paulo during 1988 and 1991: a comparative retrospective analysis

We conducted a retrospective analysis of Toxoplasma encephalitis patients from Instituto de Infectologia Emílio Ribas, the main AIDS hospital of São Paulo, Brazil, during two different stages of the HIV epidemics, in 1988 (38 patients) and 1991 (33 patients). There were AIDS-related demographic differences, but the clinical presentation and diagnostic efficiency were similar, usually based on tomography and clinical response to therapy, with a clear distinction from other CNS infections, based on clinical and laboratory findings. Specific serologic studies were performed less often in 1991, with a high frequency of therapy change. The direct acute death rate from Toxoplasma encephalitis was high during both periods, i.e. 8/38 in 1988 and 10/33 in 1991. The direct acute death rate for the patients from the two periods as a whole was 25.4 percent (18/71), related to the time of HIV infection, absence of fever and presence of meningeal irritation at presentation, blood leukocytes higher than 10,000/mm3 and blood lymphocytes lower than 350/mm3. Toxoplasma encephalitis is a preventable disease when adequate prophylactic therapy is used and is relatively easy to treat in diagnosed HIV patients. Unfortunately, this severe and deadly disorder is the HIV diagnostic disease in several patients, and our data support the need for careful management of these patients, especially in those countries with a high toxoplasmosis prevalence where AIDS is concurrent with economic and public health problems.

Encefalite por toxoplasma Gondii e AIDS: avaliaçäo retrospectova do quadro clínico e evoluçäo de pacientes de Säo Paulo, Brasil, em dois períodos, 1988 e 1991 / Toxoplasma Gondii Encephalitis and AIDS: retrospective analysis of clinical presentation and evolution of patients from Säo Paulo, Brazil, during two distinct periods, 1988 and 1991

A encefalite por T. gondii (ET) tem alta incidência, morbidade emortalidade em pacientes com AIDS, afetando de 25 a 80 por cento destes. Estuda a ET em dois períodos da epidemia de AIDS em pacientes do principal hospital de referência para esta doença em Säo Paulo, comparando com outras doenças do SNC. O estudo foi feito pela análise retrospectiva de 71 prontuários de pacientes com ET e 62 com outras doenças de SNC, em 1988 e 1991. A evoluçäo da epidemia de AIDS gerou maior número de mulheres, heterossexuais e usuários de droga em 1991, assim como um maior intervalo de tempo entre diagnóstico de infecçäo pelo HIV e de ET. Os fatores para pior prognóstico foram idade avançada, maior tempo de doença pelo HIV, apresentaçäo com sinais neurológicos difusos e ausência de febre, sem diferenças entre os dois períodos. A ET foi distinta das outras doenças pela maior positividade e títulos mais elevados de anticorpos específicos no sangue e LCR, embora estes testes tenham sido mais realizados em 1988. Outros dados clínicos e epidemiológicos relevantes säo discutidos. A ET em 1991 foi considerada doença rotineira, sem necessidade de estudo ou vigilância maior, com possível risco para os pacientes