Efficacy of Doxycycline as Pre-exposure and/or Post-exposure Prophylaxis to Prevent Sexually Transmitted Diseases: A Systematic Review and Meta-analysis.

INTRODUCTION: Bacterial sexually transmitted infections (STIs), specifically infection by Chlamydia trachomatis, Neisseria gonorrhoeae, and Treponema pallidum, have an important burden worldwide. The use of doxycycline as Pre-Exposure Prophylaxis (PREP or Doxy-PREP) or Post-Exposure Prophylaxis (PEP or Doxy-PEP) might be effective as prophylaxis since it is effective against C. trachomatis and T. pallidum. AIMS: Our objective was to evaluate the efficacy of doxycycline as PREP or PEP against bacterial STIs (C. trachomatis, N. gonorrhoeae, and Treponema pallidum). METHODS: A systematic review and meta-analysis of randomized clinical trials of a high-risk group of individuals was conducted to evaluate whether doxycycline is as effective as PREP or PEP in preventing bacterial STIs. The PubMed-MEDLINE, Cohrane, Scielo, and LILACS databases were searched for randomized clinical trials published up to March 2024. Data were extracted from published reports. Hazard Ratios (HRs) and Risk Ratios (RR) with 95% CI were pooled across trials. MAIN OUTCOME MEASURE: The primary endpoints were any incidence of bacterial STIs and individual STI infections. RESULTS: A total of four studies were included in the analysis, three of which evaluated Doxy-PEP and one evaluated Doxy-PREP. In the Doxy-PEP group, a total of 1182 participants were evaluated. In the pooled analysis of Doxy-PEP studies, the incidence of the first STI was lower in the Doxy-PEP group (HR = 0.538 [95% CI = 0.337-0.859]) (I2 = 77%; P-value <0.05). Regarding individual infections, only two studies were included. In the Doxy-PEP group, the incidence of individual infection of C. trachomatis was lower compared to controls (RR = 0.291 [95% CI = 0.093-0.911]) (I2 = 89%; P-value <0.05). Since only one study evaluated Doxy-PREP, it was not possible to calculate a meta-analysis index; however, the use of doxycycline as pre-exposure prophylaxis was associated with a decrease in the rate of any STI. CONCLUSIONS: The use of Doxy-PEP might reduce the first STI, mainly C. trachomatis, if used within 72 h after condomless sex. The use of Doxy-PREP might also decrease the chance of any STI, however, only one study was evaluated.

Dengue outbreaks in Brazil and Latin America: the new and continuing challenges.

OBJECTIVES: To compare the number of suspected cases, severe cases, and deaths of dengue in 2023 and 2024 in Brazil and Latin America; and to describe its epidemiological profile. DESIGN: Observational study. METHODS: The data regarding dengue was retrieved from the Brazilian Ministry of Health website. The Chi-square test was used to compare the proportion of dengue cases in 2023 and 2024 according to gender, race, and age range. The odds ratio and the 95% confidence intervals were used to describe the data. The Spearman correlation test was used to compare the number of suspected cases, severe cases, and deaths of dengue with the number of distributed vaccines against dengue. RESULTS: Dengue is one of the most common zoonoses in Latin America. In 2023, Brazil registered a total of 1,658,814 suspected cases of dengue with 1094 deaths. For 2024, a total of 1,978,372 suspected cases of dengue were reported only until the 11th epidemiological week, with 656 deaths. When comparing dengue cases reported in 2024 and 2023, there is an increase in suspected cases, with 20% more cases reported during the first 11 epidemiological weeks of 2024 than in the entire 52 epidemiological weeks of 2023. At the same time, in 2024, the Pan American Health Organization reported suspected cases in 20 Latin American countries, with 3073 cases of severe dengue and 1187 deaths. In Brazil, a different racial profile for dengue was described since Black people [OR = 1.56 (95% CI = 1.54-1.57)], Mixed individuals [OR = 1.36 (95% CI = 1.35-1.37), and Indigenous peoples [OR = 1.77 (95% CI = 1.70-1.85)] were more likely to be suspected cases of dengue in 2024 compared to 2023. Also, a positive correlation between the distributed vaccines with deaths due to dengue and the number of severe cases was described. CONCLUSION: Brazil was responsible for more than 50% of suspected cases and deaths from dengue compared to the other Latin American countries in 2024. Furthermore, there is a different racial profile for dengue in Brazil, as Black people, Mixed individuals, and Indigenous peoples were more likely to be suspected cases of dengue in 2024 compared to 2023.

Single-Base Gene Variants in MIR-146A and SCN1A Genes Related to the Epileptogenic Process in Drug-Responsive and Drug-Resistant Temporal Lobe Epilepsy-A Preliminary Study in a Brazilian Cohort Sample.

The drug-resistant temporal lobe epilepsy (TLE) has recently been associated with single nucleotide variants (SNVs) in microRNA(miR)-146a (MIR-146A) (rs2910164) and Sodium Voltage-Gated Channel Alpha Subunit 1 (SCN1A) (rs2298771 and rs3812718) genes. Moreover, no studies have shown an association between these SNVs and susceptibility to drug-resistant and drug-responsive TLE in Brazil. Thus, deoxyribonucleic acid (DNA) samples from 120 patients with TLE (55 drug-responsive and 65 drug-resistant) were evaluated by real-time polymerase chain reaction (RT-PCR). A total of 1171 healthy blood donor individuals from the Online Archive of Brazilian Mutations (ABraOM, from Portuguese Arquivo Brasileiro On-line de Mutações), a repository containing genomic variants of the Brazilian population, were added as a control population for the studied SNVs. MIR-146A and SCN1A relative expression was performed by quantitative RT-PCR (qRT-PCR). The statistical analysis protocol was performed using an alpha error of 0.05. TLE patient samples and ABraOM control samples were in Hardy-Weinberg equilibrium for all studied SNVs. For rs2910164, the frequencies of the homozygous genotype (CC) (15.00% vs. 9.65%) and C allele (37.80% vs. 29.97%) were superior in patients with TLE compared to controls with a higher risk for TLE disease [odds ratio (OR) = 1.89 (95% confidence interval (95%CI) = 1.06-3.37); OR = 1.38 (95%CI = 1.04-1.82), respectively]. Drug-responsive patients also presented higher frequencies of the CC genotype [21.81% vs. 9.65%; OR = 2.58 (95%CI = 1.25-5.30)] and C allele [39.09% vs. 29.97%; OR = 1.50 (95%CI = 1.01-2.22)] compared to controls. For rs2298771, the frequency of the heterozygous genotype (AG) (51.67% vs. 40.40%) was superior in patients with TLE compared to controls with a higher risk for TLE disease [OR = 2.42 (95%CI = 1.08-5.41)]. Drug-resistant patients presented a higher AG frequency [56.92% vs. 40.40%; OR = 3.36 (95%CI = 1.04-17.30)] compared to the control group. For rs3812718, the prevalence of genotypes and alleles were similar in both studied groups. The MIR-146A relative expression level was lower in drug-resistant compared to drug-responsive patients for GC (1.6 vs. 0.1, p-value = 0.049) and CC (1.8 vs. 0.6, p-value = 0.039). Also, the SCN1A relative expression levels in samples from TLE patients were significantly higher in AG [2.09 vs. 1.10, p-value = 0.038] and GG (3.19 vs. 1.10, p-value < 0.001) compared to the AA genotype. In conclusion, the rs2910164-CC and rs2298771-AG genotypes are exerting significant risk influence, respectively, on responsive disease and resistant disease, probably due to an upregulated nuclear factor kappa B (NF-kB) and SCN1A loss of function.

Overview of the Indigenous health of the Yanomami ethnic group in Brazil: A Public Health Emergency.

INTRODUCTION: The Indigenous population of the Yanomami ethnic group in Brazil is currently facing a public health emergency due to the high number of deaths, mainly of children. Taking that into consideration, this study aims to analyze this crisis impact on the health of this population in the period between 2018 and 2022. METHODS: The data presented were collected from the report called Yanomami Mission ("Missão Yanomami") published by the Brazilian Ministry of Health and, from it, a descriptive analysis of the Indigenous individuals' health was carried out for (i) the geographical distribution; ii) the number of deaths; (iii) the child death rate; (iv) the deaths of Indigenous individuals from preventable causes; (v) the causes of preventable diseases related to hygiene and basic sanitation, and the distribution of diarrheal diseases according to age groups; (vi) evaluation of the nutritional classification; vii) the percentage (%) of the complete vaccination scheme, and (viii) the coverage of prenatal appointments of Indigenous pregnant women. RESULTS: The report included 31,017 individuals belonging to the Yanomami ethnic group, most of the participants were up to 39 years old (N = 26,377; 85.0%) and men (N = 15,836; 51.1%). During the period described in the report, the number of deaths reached 1285/31,017 (4.1%). When analyzing the deaths, the most representative age groups were those of children under 1 year old (505/1285; 39.9%), from 1 to 4 years old (178/1285; 13.8%), and the elderly from 60 to 79 years old (150/1285; 11.6%). The Indigenous individuals from this ethnic group presented a child death rate ~ 1.5 to 3.5 higher than that of the total Indigenous population in the country. Regarding the child death rate, the neonatal component represented 57.8% of the deaths and, in 2022, 93.0% of the pregnant women had less than six prenatal appointments. This population shows a high number of deaths due to preventable causes (N = 538) and cases of illnesses associated with hygiene and sanitation, for example (N = 35,103 cases/notifications). As for vaccination, the full vaccination scheme targeting children below 5 years old has not been met since 2018. CONCLUSION: In the Indigenous population of the Yanomami ethnic group, a high number of deaths was observed, which affected mainly individuals under 1 year old. Among the factors associated with the deaths, mainly in children under 5 years old, most cases have preventable causes, which could be reduced by proper action promoting their health and preventing diseases.

Prevalence and risk predictors of onychomycosis in patients on hemodialysis: an observation, prospective, and unicenter study in Brazil.

Background: Onychomycoses are fungal infections that can be seen in any component of the nail unit, including the matrix, bed, and plate, and are caused by dermatophyte fungi, non-dermatophyte fungi, and yeasts. This disease affects approximately 1 to 8% of the general population and occurs in approximately 19 to 51.9% of the patients on hemodialysis. The high incidence of onychomycosis in patients on hemodialysis is associated, mainly, with immunologic deficits and histological changes caused by uremia. Methods: Adult patients of the São Francisco University Hospital Hemodialysis Center were included. The following characteristics were evaluated: age, sex, body mass index, comorbidity, and household location. All patients were clinically evaluated and those with suspected onychomycosis had subungual debris of the affected nail plate collected for the direct mycological examination and fungal culture. The onychomycosis severity for those patients with a positive result in the fungal culture examination was evaluated using the Onychomycosis Severity Index system. Results: The study included 151 patients, and 70 out of the 151 patients (46.4%) showed nail alteration, and among them, 31 out of the 70 patients (44.3%) had the onychomycosis diagnosis confirmed by direct mycological examination. The pathogens observed in the patients were Trichophyton rubrum [8 out of 31 (25.8%)], Trichophyton mentagrophytes [7 out of 31 (22.6%)], Scytalidium spp. [6 out of 31 (19.4%)], Candida spp. [2 out of 31 (6.45%)], Rhodotorula spp. [1 out of 31 (3.2%)], Candida albicans [1/31 (3.2%)], Penicillium marneffei [1 out of 31 (3.22%)], and T. rubrum and Rhodotorula spp. [1 out of 31 (3.2%)]. Three participants presented negative results in the culture examination, and one did not allow the collection of material for the examination. The nail involvement severity score for the majority of them was severe [23 out of 27 (85.2%)], and only 1 out of the 27 (3.7%) and 3 out of the 27 (1.1%) patients presented moderate and mild scores, respectively. The distal subungual onychomycosis occurred in 12 out of 27 (44.4%) patients, a mixed pattern occurred in 14 out of 27 (51.9%) patients, and, white superficial occurred in only 1 out of 27 (3.7%) patients. In the bivariate analysis, a higher risk of onychomycosis was associated with the male sex [23/31 (74.2%) vs. 56/120 (46.7%); OR = 3.286 (95%CI = 1.362 to 7.928)] and obesity [8/31 (25.8%) vs. 12/120 (10.0%); OR = 3.130 (95%CI = 1.150 to 8.521)]. Patients with diabetes mellitus were more susceptible to onychomycosis attacks (p-value = 0.049; 16 out of 31 (51.6%) vs. 40 out of 120 (33.3%); however, OR was 2.133 (95%CI = 0.959 to 4.648). The patients with onychomycosis were older but without a significant difference between the groups (p-value = 0.073; 66 years old vs. 58 years old). The multivariable model using the logistic regression (backward model) confirmed our results and was able to predict (81.5%) the onychomycosis-positive diagnosis (chi-square = 27.73; p-value <0.001). The age [OR = 1.036; 95%CI = 1.004 to 1.069], male sex [OR = 5.746; 95%CI = 2.057 to 16.046], and presence of obesity [OR = 4.800; 95%CI = 1.435 to 16.055] were positive and significant in predicting the onychomycosis-positive diagnosis. Conclusion: In our study, onychomycosis in patients on hemodialysis was associated with a great variety of microorganisms, mainly Trichophyton species. The nail involvement severity score for the majority of patients was severe, and distal subungual onychomycosis and mixed pattern onychomycosis were the most prevalent clinical types. The main risk factors associated with onychomycosis were male sex, older age, and the presence of obesity.

COVID-19 in Brazil: a 3-year update.

Three years into the coronavirus disease (COVID)-19 pandemic and the world is still struggling with the aftermath of this global health crisis. In Brazil, we are witnessing serious economic, health, social, and political problems. The rapid spread of the virus in our country was the result of a shortage of vaccines and the lack of an effective national campaign to identify and report cases. This health crisis also intensified social inequalities, hitting Indigenous peoples hard due to the lack of access to health services. In addition, rising unemployment and overcrowding of the health system made contagion possible, especially among the most vulnerable, increasing the number of serious cases of the disease. It is important to highlight that emotional problems worsened, the educational system was severely affected, and domestic violence increased during the confinement period, in addition to the fact that the pandemic exposed the great disparities of regional inequalities that exist across the country, mainly concerning health management.

Phase 4 clinical trials in the era of the Coronavirus Disease (COVID-19) pandemic and their importance to optimize the COVID-19 vaccination.

Since the appearance of SARS-CoV-2, the scientific community has worked relentlessly to gather enough information about the illness caused by this virus infection. Such great effort has resulted in increased scientific publication, including phase 4 clinical trials addressing the applicability of COVID-19 vaccines. In those trials that investigated the properties of the vaccine among participants with morbidities, mainly immunocompromised individuals, the safety was recommended, but in the presence of immunogenicity, such protection was considered of short and medium terms. It was also observed that a physically active lifestyle might increase the immunogenicity of the COVID-19 vaccination in patients with autoimmune rheumatic diseases and in immunocompromised patients. The coadministration of different types of vaccine such as the combination of the recombinant adenovirus type 5 (AD5)-vectored Convidecia as heterologous reinforcement vs. CoronaVac with homologous reinforcement in adults previously vaccinated with CoronaVac, as well as the coadministration of inactivated COVID-19 vaccine followed by the administration of the tetravalent influenza vaccine (Fragmented, Inactivated) and the pneumococcal vaccine 23 presented satisfactory immunogenicity. However, the heterologous reinforcement had better immunogenicity when compared to the homologous reinforcement. Simultaneous COVID-19 vaccination and vaccines against seasonal influenza did not raise safety issues, producing acceptable levels of adverse reactions and preserving the antibody responses against SARS-CoV-2. In the lot-to-lot consistency evaluation, CoronaVac was seen to induce an immune response considered relatively high, and the lots presented a similar profile of stability and immunogenicity, thus enabling their large-scale distribution. In brief, this article addressed, mainly, the importance of evaluating the immunological response in the COVID-19 vaccination in patients with specific health conditions (e.g., immunocompromised individuals) aiming at enabling adjustments to the vaccine calendar in national vaccination programs.

Epidemiological Profile of Hospitalized Patients with Cystic Fibrosis in Brazil Due to Severe Acute Respiratory Infection during the COVID-19 Pandemic and a Systematic Review of Worldwide COVID-19 in Those with Cystic Fibrosis.

Since the onset of the coronavirus disease, COVID-19 pandemic, concern arose for those who might be at higher risk of a worse COVID-19 prognosis, such as those with cystic fibrosis (CF). In this context, we evaluated the features of hospitalized patients with CF due to severe acute respiratory infection (SARI) in Brazil and we also performed a systematic review including all the studies published from the beginning of the first case of COVID-19 (17 November 2019) to the date of this search (23 May 2022) which included, concomitantly, patients with CF and COVID-19 in the worldwide population. In our Brazilian data, we evaluated the period from December 2019 to March 2022, and we included 33 demographical and clinical patients' features. We classified the patients into groups: (G1) SARI due to another viral infection than severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) (23; 5.4%), (G2) SARI due to an unknown etiological agent (286; 67.1%), and (G3) SARI due to SARS-CoV-2 infection (117; 27.5%). The individuals in G3 tended to be older, especially over 50 years old, and presented a higher prevalence of dyspnea, peripheral capillary oxygen saturation (SpO2) <95%, and cardiopathy. The highest prevalence for intensive care unit (ICU) treatment (52; 44.4%) and invasive mechanical ventilation (29; 24.8%) was for patients in G3. Almost half of the patients in G3 died (51; 43.6%); in contrast, none in G1 died. However, we observed 43 (15.0%) deaths in G2. In addition, 12 (4.2%) and one (0.9%) death not associated with SARI occurred, respectively, in the G2 and G3. The patients who died due to SARS-CoV-2 infection had a higher frequency of SpO2 <95% (46; 90.2%), ICU treatment (34; 66.7%), and invasive mechanical ventilation (27; 52.9%) when compared to those who recovered. The systematic review comprised a total of 31 papers published as observational studies. These studies comprised 661,386 patients in total, including children, adults, and elderly age groups. However, only 19,150 (2.9%) patients were diagnosed with CF and, from these patients, 2523 (0.4%) were diagnosed with both CF and COVID-19. It was observed that the most common outcome was the need for hospitalization (n = 322 patients with CF), and the need for oxygen support (n = 139 patients with CF). One hundred patients with CF needed intensive care units, fifty patients needed non-invasive mechanical ventilation support, and only three patients were described as receiving invasive mechanical ventilation support. Deaths were described in 38 patients with CF. Importantly, lung-transplanted patients with CF represented an increased risk of death in one publication; in accordance, another study described that lung transplantation and moderate to severe lung disease were independent risk factors for severe outcomes after SARS-CoV-2 infection. In contrast with the literature, in conclusion, Brazilian patients in G3 presented a severe phenotype, even though most of the other studies did not observe worse outcomes in patients with CF and COVID-19.

Combined multi-channel intraluminal impedance measurement and pHmetry in the detection of gastroesophageal reflux disease in children with cystic fibrosis

Abstract Objective To assess the prevalence of GERD exclusively by means of multichannel intraluminal impedanciometry associated with pH monitoring (MIIpH) and compare it with respiratory symptoms in children with CF. To compare MIIpH with pHmetry alone to perform GERD diagnosis. Methods An analytical cross-sectional study was conducted with children diagnosed with CF who underwent MIIpH. Clinical and laboratory markers, including respiratory and digestive symptoms, were used for comparative analyses. High-resolution chest computed tomography was performed on patients with symptoms of chronic lung disease. Severity was classified according to the Bhalla score. Results A total of 29 children < 10 yo (18 girls) were evaluated; 19 of whom with physiological GER and 10 with GERD. Of the children with GERD, seven had predominantly acid GER, two acid+non-acid GER, and one non-acid GER. Three patients had GERD diagnosed only by MIIpH. Bhalla scores ranged from seven to 17.75 with no significant relationship with GERD. The number of pulmonary exacerbations was associated with a decrease in esophageal clearance regardless of the position in pHmetry and MIIpH. Conclusions The prevalence of GERD was 34% in children with CF. There was no association between respiratory disease severity and GER types. MIIpH detected 30% more patients with GERD than pHmetry.

Epidemiological profile and risk factors associated with death in patients receiving invasive mechanical ventilation in an adult intensive care unit from Brazil: a retrospective study.

Introduction: Understanding the epidemiological profile and risk factors associated with invasive mechanical ventilation (IMV) is essential to manage the patients better and to improve health services. Therefore, our objective was to describe the epidemiological profile of adult patients in intensive care that required IMV in-hospital treatment. Also, to evaluate the risks associated with death and the influence of positive end-expiratory pressure (PEEP) and arterial oxygen pressure (PaO2) at admission in the clinical outcome. Methods: We conducted an epidemiological study analyzing medical records of inpatients who received IMV from January 2016 to December 2019 prior to the Coronavirus Disease (COVID)-19 pandemic in Brazil. We considered the following characteristics in the statistical analysis: demographic data, diagnostic hypothesis, hospitalization data, and PEEP and PaO2 during IMV. We associated the patients' features with the risk of death using a multivariate binary logistic regression analysis. We adopted an alpha error of 0.05. Results: We analyzed 1,443 medical records; out of those, 570 (39.5%) recorded the patients' deaths. The binary logistic regression was significant in predicting the patients' risk of death [X2(9) = 288.335; p < 0.001]. Among predictors, the most significant in relation to death risk were: age [elderly ≥65 years old; OR = 2.226 (95%CI = 1.728-2.867)]; male sex (OR = 0.754; 95%CI = 0.593-0.959); sepsis diagnosis (OR = 1.961; 95%CI = 1.481-2.595); need for elective surgery (OR = 0.469; 95%CI = 0.362-0.608); the presence of cerebrovascular accident (OR = 2.304; 95%CI = 1.502-3.534); time of hospital care (OR = 0.946; 95%CI = 0.935-0.956); hypoxemia at admission (OR = 1.635; 95%CI = 1.024-2.611), and PEEP >8 cmH2O at admission (OR = 2.153; 95%CI = 1.426-3.250). Conclusion: The death rate of the studied intensive care unit was equivalent to that of other similar units. Regarding risk predictors, several demographic and clinical characteristics were associated with enhanced mortality in intensive care unit patients under mechanical ventilation, such as diabetes mellitus, systemic arterial hypertension, and older age. The PEEP >8 cmH2O at admission was also associated with increased mortality since this value is a marker of initially severe hypoxia.

Hospitalized patients with X-linked disease and infected with SARS-CoV-2 in Brazil: A serial case report from the first two years of the pandemic.

We described the characteristics of 18 patients with coronavirus disease (COVID)-19 and X-linked disorders in a cohort of 2,066,678 Brazilian patients hospitalized due to COVID-19. The patients were diagnosed with Hemophilia B (one patient), Klinefelter syndrome [eight patients- three deaths occurred, one unrelated to Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection], and Turner syndrome (nine patients- two patients died). Half of the patients with X-linked disorders and COVID-19 (9/18) were male, the age varied from 1 to 71 years, and most patients were White (9/12; six patients had missing data). The most common symptoms were cough (13/17; one patient had missing data) and fever (12/16; two patients had missing data), whereas the most common comorbidities were diabetes mellitus (3/11; seven patients had missing data) and cardiopathy (2/12; six patients had missing data). Nearly half of the patients needed intensive care unit (8/17; one patient had missing data), and a quarter required invasive mechanical ventilation (4/16; two patients had missing data). Our study accounted for a total of five deaths, one unrelated to COVID-19. There may be several reasons for the low number of X-linked patients found in our data, such as limited access to genetic diagnosis tools causing underdiagnosis and a lack of knowledge by health professionals to identify the necessity of a genetic diagnosis or even forgetting to fill in the Brazilian database for hospitalization due to severe acute respiratory syndrome.

Cross-sectional evaluation of the saccharin transit time test for primary ciliary dyskinesia: did we discard this tool too soon?

BACKGROUND: Primary ciliary dyskinesia (PCD) is a rare and heterogeneous disease that is difficult to diagnose and requires complex and expensive diagnostic tools. The saccharin transit time test is a simple and inexpensive tool that may assist in screening patients with PCD. OBJECTIVES: This study aimed to compare changes in the electron microscopy findings with clinical variables and saccharin tests in individuals diagnosed with clinical PCD (cPCD) and a control group. DESIGN AND SETTING: An observational cross-sectional study was conducted in an otorhinolaryngology outpatient clinic from August 2012 to April 2021. METHOD: Patients with cPCD underwent clinical screening questionnaires, nasal endoscopy, the saccharin transit time test, and nasal biopsy for transmission electron microscopy. RESULTS: Thirty-four patients with cPCD were evaluated. The most prevalent clinical comorbidities in the cPCD group were recurrent pneumonia, bronchiectasis, and chronic rhinosinusitis. Electron microscopy confirmed the clinical diagnosis of PCD in 16 of the 34 (47.1%) patients. CONCLUSION: The saccharin test could assist in screening patients with PCD due to its association with clinical alterations related to PCD.

Identification of single nucleotide variants in SLC26A9 gene in patients with cystic fibrosis (p.Phe508del homozygous) and its association to Orkambi® (Lumacaftor and Ivacaftor) response in vitro.

BACKGROUND: Since patients with cystic fibrosis with different Cystic Fibrosis Transmembrane Regulator (CFTR) genotypes present a wide response variability for modulator drugs such as Orkambi®, it is important to screen variants in candidate genes with an impact on precision and personalized medicine, such as Solute Carrier Family 26, member 9 (SLC26A9) gene. METHODS: Sanger sequencing for the exons and intron-exon boundary junctions of the SLC26A9 gene was employed in nine individuals with p.Phe508del homozygous genotype for the CFTR gene who were not under CFTR modulators therapy. The sequencing variants were evaluated by in silico prediction tools. The CFTR function was measured by cAMP-stimulated current (ΔIsc-eq-FSK) in polarized CFTR of human nasal epithelial cells cultured in micro-Ussing chambers with Orkambi®. RESULTS: We found 24 intronic variants, three in the coding region (missense variants - rs74146719 and rs16856462 and synonymous - rs33943971), and three in the three prime untranslated region (3' UTR) region in the SLC26A9 gene. Twenty variants were considered benign according to American College of Medical Genetics and Genomics guidelines, and ten were classified as uncertain significance. Although some variants had deleterious predictions or possible alterations in splicing, the majority of predictions were benign or neutral. When we analyzed the ΔIsc-eq-FSK response to Orkambi®, there were no significant differences within the genotypes and alleles for all 30 variants in the SLC26A9 gene. CONCLUSIONS: Among the nine individuals with p.Phe508del homozygous genotype for the CFTR gene, no pathogenic SLC26A9 variants were found, and we did not detect associations from the 30 SLC26A9 variants and the response to the Orkambi® in vitro.

Cystic Fibrosis: A Descriptive Analysis of Deaths in a Two-Decade Period in Brazil According to Age, Race, and Sex.

The diagnosis of cystic fibrosis has improved in the last few years due to greater access to diagnostic tools and the evolution of molecular biology; the knowledge obtained has contributed to the understanding of its death profile. In this context, an epidemiological study was developed focusing on deaths from cystic fibrosis in Brazil from 1996 to 2019. The data were collected from the Data-SUS (Unified National Health System Information Technology Department from Brazil). The epidemiological analysis included patients' age groups, racial groups, and sex. In our data, between 1996 and 2019, Σ3050 deaths were recorded, totaling a ≅330% increase in the number of deaths resulting from cystic fibrosis. This fact might be related to a better diagnosis of the disease, mainly in patients from racial groups that are not commonly associated with cystic fibrosis, such as Black individuals, Hispanic or Latino (mixed individuals/Pardos) individuals, and American Indians (Indigenous peoples from Brazil). Regarding of race, the Σ of deaths was: nine (0.3%) in the American Indian group, 12 (0.4%) in the Asian group, 99 (3.6%) in the Black or African American group, 787 (28.6%) in the Hispanic or Latino group, and 1843 (67.0%) in the White group. The White group showed the highest prevalence of deaths, and the increase in mortality was ≅150 times in this group, while, in the Hispanic or Latino group, it was ≅75 times. Regarding sex, the numbers and percentage of deaths of both male (N = 1492; 48.9%) and female (N = 1557; 51.1%) patients were seen to be relatively close. As for age groups, the >60-year-old group presented the most significant results, with an increase of ≅60 times in the registered deaths. In conclusion, in Brazil, despite the number of deaths from cystic fibrosis being prevalent in the White group, it increased in all racial groups (Hispanic or Latino, Black or African American, American Indian, or Asian individuals) and was associated with older age.

Retraction of Clinical Trials about the SARS-CoV-2 Infection: An Unaddressed Problem and Its Possible Impact on Coronavirus Disease (COVID)-19 Treatment.

We are presenting an overview of the retracted clinical trials about the Coronavirus Disease (COVID)-19 published in PubMed using the descriptors ((COVID-19 OR SARS-CoV-2) AND (Clinical Trial)). We collected the information for i) the first author's country; ii) the journal name where the study was published; iii) the impact factor of the journal; iv) the main objective of the study; v) methods including population, intervention, study design, and outcomes; and vi) results and conclusions. We collected complete information from the retraction notes published by the journals and the number of publications/retractions related to non-COVID-19 clinical trials published simultaneously. We also included the Altmetric index for the clinical trials and the retraction notes about COVID-19 to compare the accessibility to both studies' indexes. The retraction of clinical trials occurred in four countries (one in Lebanon, one in India, one in Brazil, and five in Egypt) and six journals (one in Viruses, one in Archives of Virology, one in Expert Review of Anti-infective Therapy, one in Frontiers in Medicine, two in Scientific Reports, and two in The American Journal of Tropical Medicine and Hygiene). Eight drugs were tested (Ivermectin, Vitamin D, Proxalutamide, Hydroxychloroquine, Remdesevir, Favipiravir, and Sofosbuvir + Daclatasvir) in the studies. One of the retractions was suggested by the authors due to an error in the statistical analysis, which compromised their results and conclusions. Also, the methods, mainly the allocation, were not well conducted in the two studies, and the studies were retracted. In addition, the studies performed by Dabbous et al. presented several issues, mainly including several raw datasets that did not prove their findings. Moreover, two studies were retracted due to data overlap and copying. Significant concerns were raised about the integrity of the data and reported results in another article. We identified a higher Altmetric index for the original studies, proving that the retracted studies were accessed more than the retraction notes. Interestingly, the impact of the original articles is much higher than their retraction notes. The different Altmetric indexes show that possibly people who read those retracted articles are not reading their retraction notes and are unaware of the erroneous information they share. COVID-19- related clinical trials were ~two-time times more retracted than the other clinical trials performed during the same time.