47 research outputs found
Clinical research challenges in rare genetic diseases in Brazil
Rare diseases are defined as conditions with a prevalence of no more than 6.5 per 10,000 people. Although each rare disease individually affects a small number of people, collectively, the 6,000 to 8,000 rare conditions (80% of them with genetic cause) affect around 8% of the world’s population. Research about the natural history and underlying pathophysiological mechanisms of rare diseases, as well as clinical trials with new drugs, are important and necessary to develop new strategies for the treatment of these conditions. This report describes the experience of a clinical research group working with rare diseases in a reference center for lysosomal diseases in Brazil (Medical Genetics Service, Hospital de Clínicas de Porto Alegre). The activities of this research group enabled its participation in several international multicenter clinical research protocols related to the natural history or therapy development for rare genetic diseases. This participation has allowed the development of personal skills and institutional facilities for clinical research. The clinical research developed in our center has raised the quality of the medical assistance provided to non-clinical research patients in addition to enabling early access to new therapies to many patients with orphan conditions
Validação do painel de sequenciamento de nova geração para osteogênese imperfeita : análise preliminar de mutações nos genes COL1A1 e COL1A2
Avaliação da idade gestacional do recém-nascido (RN), pelo método de Capurro, por enfermeiros e médicos que atuam na Unidade de Neonatologia do Hospital de Clínicas de Porto Alegre, UIN-HCPA
O estudo compara a avaliação da idade gestacional do RN, pelo método de Capurro, por médicos e enfermeiros da UIN-HCPA. Não houve diferença significativa entre as médias dos dias avaliados por estes profissionais. Recomenda-se o procedimento, uma vez que favorece a identificação precoce do RN com risco provável
Prevalência de variantes patogênicas nos genes COL1A1 e COL1A2 em Osteogênese imperfeita tipo III e IV
Identificação de mutações nos genes envolvidos nas modificações pós-traducionais dos procolágenos α1 e α2 em formas moderada a grave de Osteogênese imperfeita
Health-related quality of life of children and adolescents with osteogenesis imperfecta: a cross-sectional study using PedsQL
Background: Osteogenesis imperfecta (OI) is a disorder of bone formation leading to low mineral density and fractures. Children and adolescents with OI require periodic medical follow up, corrective surgery, drug therapy and physical therapy, as well as specific daily care practices. In addition, they have an increased incidence of fractures, which require immobilization and cause severe discomfort and short-term disability. This study evaluated the health-related quality of life of children and adolescents with OI in two reference centers for OI treatment in southern Brazil. Methods: In this prospective cross-sectional study, the Pediatric Quality of Life Inventory (PedsQLTM) was applied in two university-affiliated reference centers for OI treatment in southern Brazil. Children and adolescents aged ≥ 5 years with clinical diagnoses of OI were included. Clinical data and socioeconomic status was evaluated. Results: The sample consisted of 52 children and adolescents with OI (aged 5-17 years); 26 (50%) participants with type I OI, 13 (25%) type IV, 12 (23.1 %) type III, and 1 (1.9%) type V OI. Physical and social functioning domains differed significantly according to clinical presentation of OI with lowest scores in the severe type (OI type III). Pain seems to be the variable that is most associated with impact on the PedsQL domains. Conclusions: Overall, this study revealed differences in physical functioning and social functioning in relation to OI clinical presentation. These results reinforcing the importance of the clinical management of these patients with the aim of functional improvement and importance of pain control
Safety and efficacy of the ChAdOx1 nCoV-19 vaccine (AZD1222) against SARS-CoV-2 : an interim analysis of four randomised controlled trials in Brazil, South Africa, and the UK
Background A safe and efficacious vaccine against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), if deployed with high coverage, could contribute to the control of the COVID-19 pandemic. We evaluated the safety and efficacy of the ChAdOx1 nCoV-19 vaccine in a pooled interim analysis of four trials. Methods This analysis includes data from four ongoing blinded, randomised, controlled trials done across the UK, Brazil, and South Africa. Participants aged 18 years and older were randomly assigned (1:1) to ChAdOx1 nCoV-19 vaccine or control (meningococcal group A, C, W, and Y conjugate vaccine or saline). Participants in the ChAdOx1 nCoV-19 group received two doses containing 5 × 1010 viral particles (standard dose; SD/SD cohort); a subset in the UK trial received a half dose as their first dose (low dose) and a standard dose as their second dose (LD/SD cohort). The primary efficacy analysis included symptomatic COVID-19 in seronegative participants with a nucleic acid amplification test-positive swab more than 14 days after a second dose of vaccine. Participants were analysed according to treatment received, with data cutoff on Nov 4, 2020. Vaccine efficacy was calculated as 1 - relative risk derived from a robust Poisson regression model adjusted for age. Studies are registered at ISRCTN89951424 and ClinicalTrials.gov, NCT04324606, NCT04400838, and NCT04444674. Findings Between April 23 and Nov 4, 2020, 23 848 participants were enrolled and 11 636 participants (7548 in the UK, 4088 in Brazil) were included in the interim primary efficacy analysis. In participants who received two standard doses, vaccine efficacy was 62·1% (95% CI 41·0–75·7; 27 [0·6%] of 4440 in the ChAdOx1 nCoV-19 group vs71 [1·6%] of 4455 in the control group) and in participants who received a low dose followed by a standard dose, efficacy was 90·0% (67·4–97·0; three [0·2%] of 1367 vs 30 [2·2%] of 1374; pinteraction=0·010). Overall vaccine efficacy across both groups was 70·4% (95·8% CI 54·8–80·6; 30 [0·5%] of 5807 vs 101 [1·7%] of 5829). From 21 days after the first dose, there were ten cases hospitalised for COVID-19, all in the control arm; two were classified as severe COVID-19, including one death. There were 74 341 person-months of safety follow-up (median 3·4 months, IQR 1·3–4·8): 175 severe adverse events occurred in 168 participants, 84 events in the ChAdOx1 nCoV-19 group and 91 in the control group. Three events were classified as possibly related to a vaccine: one in the ChAdOx1 nCoV-19 group, one in the control group, and one in a participant who remains masked to group allocation. Interpretation ChAdOx1 nCoV-19 has an acceptable safety profile and has been found to be efficacious against symptomatic COVID-19 in this interim analysis of ongoing clinical trials
Quinze anos de experiência do centro de referencia para tratamento de osteogênese imperfeita no Hospital de Clinicas de Porto Alegre
Single-dose administration and the influence of the timing of the booster dose on immunogenicity and efficacy of ChAdOx1 nCoV-19 (AZD1222) vaccine : a pooled analysis of four randomised trials
Background The ChAdOx1 nCoV-19 (AZD1222) vaccine has been approved for emergency use by the UK regulatory authority, Medicines and Healthcare products Regulatory Agency, with a regimen of two standard doses given with an interval of 4–12 weeks. The planned roll-out in the UK will involve vaccinating people in high-risk categories with their first dose immediately, and delivering the second dose 12 weeks later. Here, we provide both a further prespecified pooled analysis of trials of ChAdOx1 nCoV-19 and exploratory analyses of the impact on immunogenicity and efficacy of extending the interval between priming and booster doses. In addition, we show the immunogenicity and protection afforded by the first dose, before a booster dose has been offered. Methods We present data from three single-blind randomised controlled trials—one phase 1/2 study in the UK (COV001), one phase 2/3 study in the UK (COV002), and a phase 3 study in Brazil (COV003)—and one double-blind phase 1/2 study in South Africa (COV005). As previously described, individuals 18 years and older were randomly assigned 1:1 to receive two standard doses of ChAdOx1 nCoV-19 (5×10¹⁰ viral particles) or a control vaccine or saline placebo. In the UK trial, a subset of participants received a lower dose (2·2×10¹⁰ viral particles) of the ChAdOx1 nCoV-19 for the first dose. The primary outcome was virologically confirmed symptomatic COVID-19 disease, defined as a nucleic acid amplification test (NAAT)-positive swab combined with at least one qualifying symptom (fever ≥37·8°C, cough, shortness of breath, or anosmia or ageusia) more than 14 days after the second dose. Secondary efficacy analyses included cases occuring at least 22 days after the first dose. Antibody responses measured by immunoassay and by pseudovirus neutralisation were exploratory outcomes. All cases of COVID-19 with a NAATpositive swab were adjudicated for inclusion in the analysis by a masked independent endpoint review committee. The primary analysis included all participants who were SARS-CoV-2 N protein seronegative at baseline, had had at least 14 days of follow-up after the second dose, and had no evidence of previous SARS-CoV-2 infection from NAAT swabs. Safety was assessed in all participants who received at least one dose. The four trials are registered at ISRCTN89951424 (COV003) and ClinicalTrials.gov, NCT04324606 (COV001), NCT04400838 (COV002), and NCT04444674 (COV005). Findings Between April 23 and Dec 6, 2020, 24422 participants were recruited and vaccinated across the four studies, of whom 17178 were included in the primary analysis (8597 receiving ChAdOx1 nCoV-19 and 8581 receiving control vaccine). The data cutoff for these analyses was Dec 7, 2020. 332 NAAT-positive infections met the primary endpoint of symptomatic infection more than 14 days after the second dose. Overall vaccine efficacy more than 14 days after the second dose was 66·7% (95% CI 57·4–74·0), with 84 (1·0%) cases in the 8597 participants in the ChAdOx1 nCoV-19 group and 248 (2·9%) in the 8581 participants in the control group. There were no hospital admissions for COVID-19 in the ChAdOx1 nCoV-19 group after the initial 21-day exclusion period, and 15 in the control group. 108 (0·9%) of 12282 participants in the ChAdOx1 nCoV-19 group and 127 (1·1%) of 11962 participants in the control group had serious adverse events. There were seven deaths considered unrelated to vaccination (two in the ChAdOx1 nCov-19 group and five in the control group), including one COVID-19-related death in one participant in the control group. Exploratory analyses showed that vaccine efficacy after a single standard dose of vaccine from day 22 to day 90 after vaccination was 76·0% (59·3–85·9). Our modelling analysis indicated that protection did not wane during this initial 3-month period. Similarly, antibody levels were maintained during this period with minimal waning by day 90 (geometric mean ratio [GMR] 0·66 [95% CI 0·59–0·74]). In the participants who received two standard doses, after the second dose, efficacy was higher in those with a longer prime-boost interval (vaccine efficacy 81·3% [95% CI 60·3–91·2] at ≥12 weeks) than in those with a short interval (vaccine efficacy 55·1% [33·0–69·9] at <6 weeks). These observations are supported by immunogenicity data that showed binding antibody responses more than two-fold higher after an interval of 12 or more weeks compared with an interval of less than 6 weeks in those who were aged 18–55 years (GMR 2·32 [2·01–2·68]). Interpretation The results of this primary analysis of two doses of ChAdOx1 nCoV-19 were consistent with those seen in the interim analysis of the trials and confirm that the vaccine is efficacious, with results varying by dose interval in exploratory analyses. A 3-month dose interval might have advantages over a programme with a short dose interval for roll-out of a pandemic vaccine to protect the largest number of individuals in the population as early as possible when supplies are scarce, while also improving protection after receiving a second dose