ABSTRACT Objective: Thymidine-dependent small-colony variants (TD-SCVs) of Staphylococcus aureus are being isolated with increasing frequency from patients with cystic fibrosis (CF). The aim of this study was to evaluate the relationship between TD-SCV isolation and pulmonary function in patients with CF, as well as to determine whether the emergence of TD-SCVs was associated with trimethoprim-sulfamethoxazole (TMP-SMX) use and with coinfection with other microorganisms. Methods: This was a retrospective case-control study including patients with CF who visited the Clinical Hospital Complex of the Federal University of Paraná, in Curitiba, Brazil, between 2013 and 2022. Demographic, clinical, and spirometric data, as well as information on TD-SCVs and other isolated microorganisms, were collected from the medical records of patients with CF and TD-SCVs (TD-SCV group; n = 32) and compared with those of a matched group of patients with CF without TD-SCVs (control group; n = 64). Results: Isolation of TD-SCVs was positively associated with TMP-SMX use (p = 0.009), hospitalization (p < 0.001), and impaired pulmonary function (p = 0.04). Conclusions: The use of TMP-SMX seems to contribute to the emergence of TD-SCVs, the isolation of which was directly associated with worse pulmonary function in our sample. Objective Thymidinedependent Thymidine dependent smallcolony small colony TDSCVs TD SCVs (TD-SCVs CF. . (CF) TDSCV SCV trimethoprimsulfamethoxazole trimethoprim sulfamethoxazole TMPSMX TMP SMX (TMP-SMX microorganisms Methods casecontrol case control Paraná Curitiba Brazil 201 2022 Demographic clinical data 32 64. 64 64) Results p 0.009, 0009 0.009 , 0 009 0.009) 0.001, 0001 0.001 001 0.001) 0.04. 004 0.04 04 0.04) Conclusions TDSCVs, SCVs, sample (CF 20 202 3 6 000 0.00 00 0.0 2 0.

ABSTRACT Cystic fibrosis (CF) is a genetic disease that results in dysfunction of the CF transmembrane conductance regulator (CFTR) protein, which is a chloride and bicarbonate channel expressed in the apical portion of epithelial cells of various organs. Dysfunction of that protein results in diverse clinical manifestations, primarily involving the respiratory and gastrointestinal systems, impairing quality of life and reducing life expectancy. Although CF is still an incurable pathology, the therapeutic and prognostic perspectives are now totally different and much more favorable. The purpose of these guidelines is to define evidence-based recommendations regarding the use of pharmacological agents in the treatment of the pulmonary symptoms of CF in Brazil. Questions in the Patients of interest, Intervention to be studied, Comparison of interventions, and Outcome of interest (PICO) format were employed to address aspects related to the use of modulators of this protein (ivacaftor, lumacaftor+ivacaftor, and tezacaftor+ivacaftor), use of dornase alfa, eradication therapy and chronic suppression of Pseudomonas aeruginosa, and eradication of methicillin-resistant Staphylococcus aureus and Burkholderia cepacia complex. To formulate the PICO questions, a group of Brazilian specialists was assembled and a systematic review was carried out on the themes, with meta-analysis when applicable. The results obtained were analyzed in terms of the strength of the evidence compiled, the recommendations being devised by employing the GRADE approach. We believe that these guidelines represent a major advance to be incorporated into the approach to patients with CF, mainly aiming to favor the management of the disease, and could become an auxiliary tool in the definition of public policies related to CF. (CF CFTR (CFTR organs manifestations systems expectancy pathology favorable evidencebased based Brazil studied interventions (PICO ivacaftor, ivacaftor (ivacaftor lumacaftorivacaftor lumacaftor lumacaftor+ivacaftor tezacaftor+ivacaftor, tezacaftorivacaftor tezacaftor+ivacaftor , tezacaftor tezacaftor+ivacaftor) alfa aeruginosa methicillinresistant methicillin resistant complex questions themes metaanalysis meta analysis applicable compiled

RESUMO A fibrose cística (FC) é uma doença genética que resulta em disfunção da proteína reguladora de condutância transmembrana da FC (CFTR), que é um canal de cloro e bicarbonato expresso na porção apical de células epiteliais de diversos órgãos. A disfunção dessa proteína resulta em manifestações clínicas diversas, envolvendo primariamente os sistemas respiratório e gastrointestinal com redução da qualidade e expectativa de vida. A FC ainda é uma patologia incurável, porém o horizonte terapêutico e prognóstico é hoje totalmente distinto e muito mais favorável. O objetivo destas diretrizes foi definir recomendações brasileiras baseadas em evidências em relação ao emprego de agentes farmacológicos no tratamento pulmonar da FC. As perguntas PICO (acrônimo baseado em perguntas referentes aos Pacientes de interesse, Intervenção a ser estudada, Comparação da intervenção e Outcome [desfecho] de interesse) abordaram aspectos relativos ao uso de moduladores de CFTR (ivacaftor, lumacaftor + ivacaftor e tezacaftor + ivacaftor), uso de dornase alfa, terapia de erradicação e supressão crônica de Pseudomonas aeruginosa, e erradicação de Staphylococcus aureus resistente a meticilina e do complexo Burkholderia cepacia. Para a formulação das perguntas, um grupo de especialistas brasileiros foi reunido e realizou-se uma revisão sistemática sobre os temas, com meta-análise quando aplicável. Os resultados encontrados foram analisados quanto à força das evidências compiladas, sendo concebidas recomendações seguindo a metodologia GRADE. Os autores acreditam que o presente documento represente um importante avanço a ser incorporado na abordagem de pacientes com FC, objetivando principalmente favorecer seu manejo, podendo se tornar uma ferramenta auxiliar na definição de políticas públicas relacionadas à FC. (FC CFTR, , (CFTR) órgãos diversas vida incurável favorável acrônimo interesse estudada desfecho [desfecho ivacaftor, (ivacaftor ivacaftor) alfa aeruginosa cepacia realizouse realizou temas metaanálise meta análise aplicável compiladas GRADE manejo (CFTR

OBJETIVO: A prevalência de conjuntivite alérgica (CA) não foi estabelecida. Estimativas sugerem que alergias oculares afetam de 15 a 20% da população mundial, ainda que a maioria dos estudos epidemiológicos abranjam sintomas de alergia nasal e ocular e não sejam específicos a respeito da CA. O objetivo deste estudo foi verificar a prevalência de sintomas, comorbidades e o impacto da alergia ocular em adolescentes. MÉTODOS: Os adolescentes foram selecionados de uma amostra de escolas e preencheram, em sala de aula, um questionário previamente validado sobre os sintomas da CA. O seu diagnóstico foi considerado quando mais de três episódios de prurido ocular foram relatados nos últimos 12 meses. Sintomas relacionados, como lacrimejamento, fotofobia, sensação de corpo estranho, impacto sobre as atividades diárias e diagnóstico de conjuntivite alérgica, foram analisados. RESULTADOS: Foram obtidos questionários de 3.120 adolescentes (média de 13,3±1,1 ano). Nos últimos 12 meses, 1.592 (51%) adolescentes tiveram prurido ocular. O sintoma relacionado mais frequente foi lacrimejamento (74%), seguido de fotofobia (50,1%) e sensação de corpo estranho (37,1%). A prevalência de conjuntivite alérgica foi de 20,7%, afetando mais pessoas do sexo feminino do que do masculino (56,1% em comparação a 45,9%; p = 0,01). O risco de um adolescente com alergia ocular apresentar asma, rinite e eczema atópico foi (RC = 5,7; IC de 95%: 4,5 a 7,1); (RC = 3,6; IC de 95%: 3,0 a 4,3) e (RC = 2,6; IC de 95%: 2,0 a 3,5), respectivamente. Uma interferência grave nas atividades diárias foi relatada por 30,5%. CONCLUSÕES: Sintomas de alergia ocular são comuns, frequentemente relacionados a outras doenças alérgicas, e causam impacto sobre as atividades diárias de adolescentes.

OBJECTIVE: The prevalence of allergic conjunctivitis (AC) has not been established. Estimates suggest that ocular allergies affect 15% to 20% of the worldwide population, yet most epidemiological studies encompass nasal and ocular allergy symptoms and have not been specific to AC. The aim of this study was to verify the prevalence of ocular allergy symptoms, co-morbidities, and their impact on adolescents. METHODS: Adolescents were selected from a sample of schools, and completed in classrooms a previously validated questionnaire on symptoms of AC. AC diagnosis was considered when more than three episodes of ocular itching were reported in the past 12 months. Related symptoms such as tearing, photophobia, foreign body sensation, impact on daily activities, and diagnosis of AC were analyzed. RESULTS: Questionnaires were obtained from 3,120 adolescents (mean age 13.3 ± 1.1 years). Ocular itching in the past 12 months occurred in 1,592 (51%). The most frequently associated symptom was tearing (74%), followed by photophobia (50.1%) and foreign body sensation (37.1%). The prevalence of AC was 20.7%, affecting more females than males (56.1% versus 45.9%; p = 0.01). The risks of an adolescent with ocular allergy to present asthma, rhinitis, and atopic eczema were (OR = 5.7; 95% CI: 4.5 to 7.1), (OR = 3.6; 95% CI: 3.0 to 4.3), and (OR = 2.6; 95% CI: 2.0 to 3.5), respectively. Severe interference in daily activities was reported by 30.5%. CONCLUSIONS: Symptoms of ocular allergy are common, frequently associated to other allergic diseases, and impact the daily activities of adolescents.