Impact of the immune profiles of hypertensive patients with and without obesity on COVID-19 severity.

BACKGROUND: Comorbidities such as obesity, hypertension, and diabetes are associated with COVID-19 development and severity, probably due to immune dysregulation; however, the mechanisms underlying these associations are not clear. The immune signatures of hypertensive patients with obesity with COVID-19 may provide new insight into the mechanisms of immune dysregulation and progression to severe disease in these patients. METHODS: Hypertensive patients were selected prospectively from a multicenter registry of adults hospitalized with COVID-19 and stratified according to obesity (BMI ≥ 30 kg/m²). Clinical data including baseline characteristics, complications, treatment, and 46 immune markers were compared between groups. Logistic regression was performed to identify variables associated with the risk of COVID-19 progression in each group. RESULTS: The sample comprised 213 patients (89 with and 124 without obesity). The clinical profiles of patients with and without obesity differed, suggesting potential interactions with COVID-19 severity. Relative to patients without obesity, patients with obesity were younger and fewer had cardiac disease and myocardial injury. Patients with obesity had higher EGF, GCSF, GMCSF, interleukin (IL)-1ra, IL-5, IL-7, IL-8, IL-15, IL-1ß, MCP 1, and VEGF levels, total lymphocyte counts, and CD8+ CD38+ mean fluorescence intensity (MFI), and lower NK-NKG2A MFI and percentage of CD8+ CD38+ T cells. Significant correlations between cytokine and immune cell expression were observed in both groups. Five variables best predicted progression to severe COVID-19 in patients with obesity: diabetes, the EGF, IL-10, and IL-13 levels, and the percentage of CD8+ HLA-DR+ CD38+ cells. Three variables were predictive for patients without obesity: myocardial injury and the percentages of B lymphocytes and HLA-DR+ CD38+ cells. CONCLUSION: Our findings suggest that clinical and immune variables and obesity interact synergistically to increase the COVID-19 progression risk. The immune signatures of hypertensive patients with and without obesity severe COVID-19 highlight differences in immune dysregulation mechanisms, with potential therapeutic applications.

Durability of the improvement of collagen I and collagen III with the use of oral isotretinoin in the treatment of photoaging.

BACKGROUND: Oral isotretinoin (ISO) is the drug of choice for the treatment of severe acne. For photoaging treatment, ISO has been proved to be effective in some controlled and noncontrolled trials and is an alternative to topical retinoic acid (RA) therapy, which causes an expected skin irritation. OBJECTIVE: To evaluate and compare the skin remodeling in patients taking ISO 20 mg 3 times a week for 12 weeks and 12 weeks after the end of the treatment to quantify collagen I and collagen III augmentation. MATERIAL AND METHODS: Immunohistochemical studies were performed to evaluate the expression of collagen I and collagen III, metalloproteinases (MMPs) -1, -3, -7, -9, -12, and the tissue inhibitor of MMP type-1 (TIMP-1) of the skin of 20 45 to 50-year-old women through morphometry in a semiquantitative method. The inclusion criteria were facial aging 2 and 3 of Glogau's classification, with phototypes between II and V who had not entered menopause. Biopsies of the skin of the left preauricular region were performed at three different times: pre-treatment (T0), end of 12-week treatment (T1), and 12 weeks posttreatment (T2). RESULTS: Collagen fibers I and III increased with statistical significance in T1 (50.7%; P = 0.012) but not in T2 (49.7%), which in turn was higher than in T0 (47.2%) for collagen I and T1 (33.3%; P = 0.002) but not in T2 (32.7%), and also was higher than T0 (32.0%) for collagen III. MMP-9 presented a decreased activity with statistical significance in T1 (P = 0.047) and T2 (P = 0.058). MMP-1 showed a reduction in T2 only (P = 0.015). MMPs -3, -7, -12, and TIMP-1 did not present significant modification in their expressions during or after the treatment. CONCLUSIONS: Low-dose ISO is effective in remodeling the extracellular matrix (ECM). This study found that the increase of collagen occurs through the augmentation of both collagen I and collagen III fibers. With originality, it was possible to verify the durability of these fibers for at least 12 weeks. This may be related to the decrease in MMP-9 expression verified at the end of the treatment and 12 weeks posttreatment.

New Insights on the Mechanisms of Myocardial Injury in Hypertensive Patients With COVID-19.

PURPOSE: Myocardial injury is common in hypertensive patients with 2019 coronavirus disease (COVID-19). Immune dysregulation could be associated to cardiac injury in these patients, but the underlying mechanism has not been fully elucidated. METHODS: All patients were selected prospectively from a multicenter registry of adults hospitalized with confirmed COVID-19. Cases had hypertension and myocardial injury, defined by troponin levels above the 99th percentile upper reference limit, and controls were hypertensive patients with no myocardial injury. Biomarkers and immune cell subsets were quantified and compared between the two groups. A multiple logistic regression model was used to analyze the associations of clinical and immune variables with myocardial injury. RESULTS: The sample comprised 193 patients divided into two groups: 47 cases and 146 controls. Relative to controls, cases had lower total lymphocyte count, percentage of T lymphocytes, CD8+CD38+ mean fluorescence intensity (MFI), and percentage of CD8+ human leukocyte antigen DR isotope (HLA-DR)+ CD38-cells and higher percentage of natural killer lymphocytes, natural killer group 2A (NKG2A)+ MFI, percentage of CD8+CD38+cells, CD8+HLA-DR+MFI, CD8+NKG2A+MFI, and percentage of CD8+HLA-DR-CD38+cells. On multivariate regression, the CD8+HLA-DR+MFI, CD8+CD38+MFI, and total lymphocyte count were associated significantly with myocardial injury. CONCLUSION: Our findings suggest that lymphopenia, CD8+CD38+MFI, and CD8+HLA-DR+MFI are immune biomarkers of myocardial injury in hypertensive patients with COVID-19. The immune signature described here may aid in understanding the mechanisms underlying myocardial injury in these patients. The study data might open a new window for improvement in the treatment of hypertensive patients with COVID-19 and myocardial injury.

Troponin in COVID-19: To Measure or Not to Measure? Insights from a Prospective Cohort Study.

Myocardial injury (MI), defined by troponin elevation, has been associated with increased mortality and adverse outcomes in patients with coronavirus disease 2019 (COVID-19), but the role of this biomarker as a risk predictor remains unclear. Data from adult patients hospitalized with COVID-19 were recorded prospectively. A multiple logistic regression model was used to quantify associations of all variables with in-hospital mortality, including the calculation of odds ratios (ORs) and confidence intervals (CI). Troponin measurement was performed in 1476 of 4628 included patients, and MI was detected in 353 patients, with a prevalence of 23.9%; [95% CI, 21.8-26.1%]. The total in-hospital mortality rate was 10.9% [95% CI, 9.8-12.0%]. The mortality was much higher among patients with MI than among those without MI, with a prevalence of 22.7% [95% CI, 18.5-27.3%] vs. 5.5% [95% CI, 4.3-7.0%] and increased with each troponin level. After adjustment for age and comorbidities, the model revealed that the mortality risk was greater for patients with MI [OR = 2.99; 95% CI, 2.06-4.36%], and for those who did not undergo troponin measurement [OR = 2.2; 95% CI, 1.62-2.97%], compared to those without MI. Our data support the role of troponin as an important risk predictor for these patients, capable of discriminating between those with a low or increased mortality rate. In addition, our findings suggest that this biomarker has a remarkable negative predictive value in COVID-19.

NKG2A Expression among CD8 Cells Is Associated with COVID-19 Progression in Hypertensive Patients: Insights from the BRACE CORONA Randomized Trial.

Cardiovascular comorbidities and immune-response dysregulation are associated with COVID-19 severity. We aimed to explore the key immune cell profile and understand its association with disease progression in 156 patients with hypertension that were hospitalized due to COVID-19. The primary outcome was progression to severe disease. The probability of progression to severe disease was estimated using a logistic regression model that included clinical variables and immune cell subsets associated with the primary outcome. Obesity; diabetes; oxygen saturation; lung involvement on computed tomography (CT) examination; the C-reactive protein concentration; total lymphocyte count; proportions of CD4+ and CD8+ T cells; CD4/CD8 ratio; CD8+ HLA-DR MFI; and CD8+ NKG2A MFI on admission were all associated with progression to severe COVID-19. This study demonstrated that increased CD8+ NKG2A MFI at hospital admission, in combination with some clinical variables, is associated with a high risk of COVID-19 progression in hypertensive patients. These findings reinforce the hypothesis of the functional exhaustion of T cells with the increased expression of NKG2A in patients with severe COVID-19, elucidating how severe acute respiratory syndrome coronavirus 2 infection may break down the innate antiviral immune response at an early stage of the disease, with future potential therapeutic implications.

Nitazoxanide in Patients Hospitalized With COVID-19 Pneumonia: A Multicentre, Randomized, Double-Blind, Placebo-Controlled Trial.

Background: Nitazoxanide exerts antiviral activity in vitro and in vivo and anti-inflammatory effects, but its impact on patients hospitalized with COVID-19 pneumonia is uncertain. Methods: A multicentre, randomized, double-blind, placebo-controlled trial was conducted in 19 hospitals in Brazil. Hospitalized adult patients requiring supplemental oxygen, with COVID-19 symptoms and a chest computed tomography scan suggestive of viral pneumonia or positive RT-PCR test for COVID-19 were enrolled. Patients were randomized 1:1 to receive nitazoxanide (500 mg) or placebo, 3 times daily, for 5 days, and were followed for 14 days. The primary outcome was intensive care unit admission due to the need for invasive mechanical ventilation. Secondary outcomes included clinical improvement, hospital discharge, oxygen requirements, death, and adverse events within 14 days. Results: Of the 498 patients, 405 (202 in the nitazoxanide group and 203 in the placebo group) were included in the analyses. Admission to the intensive care unit did not differ between the groups (hazard ratio [95% confidence interval], 0.68 [0.38-1.20], p = 0.179); death rates also did not differ. Nitazoxanide improved the clinical outcome (2.75 [2.21-3.43], p < 0.0001), time to hospital discharge (1.37 [1.11-1.71], p = 0.005), and reduced oxygen requirements (0.77 [0.64-0.94], p = 0.011). C-reactive protein, D-dimer, and ferritin levels were lower in the nitazoxanide group than the placebo group on day 7. No serious adverse events were observed. Conclusions: Nitazoxanide, compared with placebo, did not prevent admission to the intensive care unit for patients hospitalized with COVID-19 pneumonia. Clinical Trial Registration: Brazilian Registry of Clinical Trials (REBEC) RBR88bs9x; ClinicalTrials.gov, NCT04561219.

Lower bone density and microarchitecture alterations in HIV-infected Brazilian men aged 50 years and older are associated with estradiol levels.

OBJECTIVE: Combination antiretroviral treatment (cART) allows for longer survival for people living with HIV and hence long-term complications of both disease and treatment are common. Our purpose was to evaluate bone alterations in men living with HIV (MLWH) and receiving cART and to identify associated factors that can be corrected or mitigated. PATIENTS AND DESIGN: Thirty MLWH and 36 healthy controls (≥50 years) were studied for areal bone mineral density (aBMD) and body composition (dual-energy X-ray absorptiometry), volumetric bone mineral density (vBMD) and bone microstructure (high-resolution peripheral quantitative computed tomography [HR-pQCT]), serum calcium, phosphate, parathyroid hormone, 25(OH)D, testosterone (T), estradiol (E2 ), glucose, creatinine, and albumin levels. RESULTS: The proportion of patients classified as osteoporosis (according to the lowest aBMD T-score) was higher among MLWH as compared to controls (17.9% vs. 5.9%, p = .011). The MLWH showed significant alterations in cortical and trabecular bone on HR-pQCT, which were not associated with the duration of HIV infection or cART. These differences in vBMD and bone microstructure seen in HR-pQCT persisted in the nonosteoporotic MLWH as compared to nonosteoporotic control subjects. Body mass index (BMI) and fat mass were lower in MLWH and positively associated with total vBMD, cortical bone area, and thickness. E2 and E2 /T ratios were lower in MLWH than in controls and significantly correlated with several cortical and trabecular bone parameters. Multivariate regression analysis entering simultaneously age, BMI, and E2 defined that E2 is an independent influence on bone parameters evaluated by HR-pQCT. CONCLUSION: MLWH have alterations in bone volumetric density and microstructure when compared with controls, irrespective of aBMD, which are associated with lower E2 and BMI.

Geographic Distribution and Time Trends of Colorectal Cancer in Brazil from 2005 to 2018.

BACKGROUND: Colorectal cancer (CRC) is the third most common malignancy and the second leading cause of cancer-related death in the world. The aim of this study was to investigate the geographic distribution and time trends of CRC in Brazil. METHODS: Data were retrospectively retrieved from January 2005 to December 2018 from the Brazilian Public Health System. The incidence and lethality rates of CRC per 100,000 inhabitants in each municipality were estimated from hospitalizations and in-hospital deaths and were classified by age, sex, and demographic features. RESULTS: During the study period, the mean incidence of CRC estimated from hospitalizations and adjusted to available hospital beds more than tripled from 14.6 to 51.4 per 100,000 inhabitants (352%). Increases in CRC incidence were detected in all age ranges, particularly among people aged 50-69 years (266%). Incidence rates increased in all 5 macroregions, with a clear South to North gradient. The greatest changes in incidence and lethality rates were registered in small-sized municipalities. CRC lethality estimated from in-hospital deaths decreased similarly in both sexes, from 12 to 8% for males and females, from 2005 to 2018. The decline in lethality rates was seen in all age ranges, mainly in people aged 50 to 69 years (- 38%). CONCLUSIONS: CRC incidence is increasing, predominantly above fifty years of age, and also in areas previously considered as having low incidence, but the increase is not paralleled by lethality rates. This suggests recent improvements in CRC screening programs and treatment, but also supports the spread of environmental risk factors throughout the country.

Anxiety about dental treatment - a gender issue.

This study compared prevalence and risk factors of dental anxiety between men and women. The sample consisted of 244 participants (n = 122 men) aged 18 years or older who sought dental care at a public Dental Education Institution from March 2018 to November 2019. The Modified Dental Anxiety Scale was used to determine presence of dental anxiety. The following risk factors were recorded: age, years of schooling, preoperative pain, and type of dental treatment. Bivariate analysis was used to assess the difference in dental anxiety between the sexes. Multivariate logistic regression was used to analyze the association between dental anxiety and gender, regardless of the influence of other variables. Total prevalence of dental anxiety was 18% (n = 44), 22.9% (28/122) in women and 13.1% (16/122) in men (p = 0.04). Gender (odds ratio: 1.83, 95% confidence interval: 0.92-3.62) and preoperative pain (odds ratio: 2.095, 95% confidence interval: 0.97-4.49) were associated with dental anxiety. We concluded that women had a higher prevalence of dental anxiety. Preoperative pain was associated with dental anxiety regardless of gender.

Este estudo avaliou a prevalência e os fatores de risco da ansiedade odontológica entre homens e mulheres. O cálculo amostral foi composto por 244 participantes (n = 122 homens) com 18 anos ou mais que procuraram atendimento odontológico em uma instituição pública de Educação Odontológica no período de março de 2018 a novembro de 2019. A Escala de Ansiedade Odontológica Modificada foi utilizada para determinar a presença de ansiedade odontológica. Os seguintes fatores de risco também foram coletados: idade, anos de estudo, dor pré-operatória e tipo de tratamento odontológico. A análise bivariada foi usada para avaliar a diferença na ansiedade odontológica entre os gêneros. A regressão logística multivariada foi utilizada para analisar a associação entre ansiedade odontológica e gênero, independentemente da influência de outras variáveis. A prevalência total de ansiedade odontológica foi de 18% (n = 44), 22,9% (28/122) nas mulheres e 13,1% (16/122) nos homens (p = 0,04). O gênero (odds ratio: 1,83, intervalo de confiança de 95%: 0,92­3,62) e a dor pré-operatória (odds ratio: 2,095, intervalo de confiança de 95%: 0,97­4,49) foram associados à ansiedade odontológica. Concluímos que as mulheres apresentaram maior prevalência de ansiedade odontológica. A dor pré-operatória foi associada à ansiedade odontológica, independentemente do gênero.

Anxiety about dental treatment / Ansiedade em relação ao tratamento dentário

ABSTRACT This study compared prevalence and risk factors of dental anxiety between men and women. The sample consisted of 244 participants (n = 122 men) aged 18 years or older who sought dental care at a public Dental Education Institution from March 2018 to November 2019. The Modified Dental Anxiety Scale was used to determine presence of dental anxiety. The following risk factors were recorded: age, years of schooling, preoperative pain, and type of dental treatment. Bivariate analysis was used to assess the difference in dental anxiety between the sexes. Multivariate logistic regression was used to analyze the association between dental anxiety and gender, regardless of the influence of other variables. Total prevalence of dental anxiety was 18% (n = 44), 22.9% (28/122) in women and 13.1% (16/122) in men (p = 0.04). Gender (odds ratio: 1.83, 95% confidence interval: 0.92-3.62) and preoperative pain (odds ratio: 2.095, 95% confidence interval: 0.97-4.49) were associated with dental anxiety. We concluded that women had a higher prevalence of dental anxiety. Preoperative pain was associated with dental anxiety regardless of gender.

RESUMO Este estudo avaliou a prevalência e os fatores de risco da ansiedade odontológica entre homens e mulheres. O cálculo amostral foi composto por 244 participantes (n = 122 homens) com 18 anos ou mais que procuraram atendimento odontológico em uma instituição pública de Educação Odontológica no período de março de 2018 a novembro de 2019. A Escala de Ansiedade Odontológica Modificada foi utilizada para determinar a presença de ansiedade odontológica. Os seguintes fatores de risco também foram coletados: idade, anos de estudo, dor pré-operatória e tipo de tratamento odontológico. A análise bivariada foi usada para avaliar a diferença na ansiedade odontológica entre os gêneros. A regressão logística multivariada foi utilizada para analisar a associação entre ansiedade odontológica e gênero, independentemente da influência de outras variáveis. A prevalência total de ansiedade odontológica foi de 18% (n = 44), 22,9% (28/122) nas mulheres e 13,1% (16/122) nos homens (p = 0,04). O gênero (odds ratio: 1,83, intervalo de confiança de 95%: 0,92-3,62) e a dor pré-operatória (odds ratio: 2,095, intervalo de confiança de 95%: 0,97-4,49) foram associados à ansiedade odontológica. Concluímos que as mulheres apresentaram maior prevalência de ansiedade odontológica. A dor pré-operatória foi associada à ansiedade odontológica, independentemente do gênero.

Prevalence, Indirect Costs, and Risk Factors for Work Disability in Patients with Crohn's Disease at a Tertiary Care Center in Rio de Janeiro.

BACKGROUND AND AIMS: Crohn's disease (CD) can lead to work disability with social and economic impacts worldwide. In Brazil, where its prevalence is increasing, we assessed the indirect costs, prevalence, and risk factors for work disability in the state of Rio de Janeiro and in a tertiary care referral center of the state. METHODS: Data were retrieved from the database of the Single System of Social Security Benefits Information, with a cross-check for aid pension and disability retirement. A subanalysis was performed with CD patients followed up at the tertiary care referral center using a prospective CD database, including clinical variables assessed as possible risk factors for work disability. RESULTS: From 2010 to 2018, the estimated prevalence of CD was 26.05 per 100,000 inhabitants, while the associated work disability was 16.6%, with indirect costs of US$ 8,562,195.86. Permanent disability occurred more frequently in those aged 40 to 49 years. In the referral center, the prevalence of work disability was 16.7%, with a mean interval of 3 years between diagnosis and the first benefit. Risk factors for absence from work were predominantly abdominal surgery, anovaginal fistulas, disease duration, and the A2 profile of the Montreal classification. CONCLUSIONS: In Rio de Janeiro, work disability affects one-sixth of CD patients, and risk factors are associated with disease duration and complications. In the context of increasing prevalence, as this disability compromises young patients after a relatively short period of disease, the socioeconomic burden of CD is expected to increase in the future.

Early use of nitazoxanide in mild COVID-19 disease: randomised, placebo-controlled trial.

BACKGROUND: Nitazoxanide is widely available and exerts broad-spectrum antiviral activity in vitro. However, there is no evidence of its impact on severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. METHODS: In a multicentre, randomised, double-blind, placebo-controlled trial, adult patients presenting up to 3 days after onset of coronavirus disease 2019 (COVID-19) symptoms (dry cough, fever and/or fatigue) were enrolled. After confirmation of SARS-CoV-2 infection using reverse transcriptase PCR on a nasopharyngeal swab, patients were randomised 1:1 to receive either nitazoxanide (500 mg) or placebo, three times daily, for 5 days. The primary outcome was complete resolution of symptoms. Secondary outcomes were viral load, laboratory tests, serum biomarkers of inflammation and hospitalisation rate. Adverse events were also assessed. RESULTS: From June 8 to August 20, 2020, 1575 patients were screened. Of these, 392 (198 placebo, 194 nitazoxanide) were analysed. Median (interquartile range) time from symptom onset to first dose of study drug was 5 (4-5) days. At the 5-day study visit, symptom resolution did not differ between the nitazoxanide and placebo arms. Swabs collected were negative for SARS-CoV-2 in 29.9% of patients in the nitazoxanide arm versus 18.2% in the placebo arm (p=0.009). Viral load was reduced after nitazoxanide compared to placebo (p=0.006). The percentage viral load reduction from onset to end of therapy was higher with nitazoxanide (55%) than placebo (45%) (p=0.013). Other secondary outcomes were not significantly different. No serious adverse events were observed. CONCLUSIONS: In patients with mild COVID-19, symptom resolution did not differ between nitazoxanide and placebo groups after 5 days of therapy. However, early nitazoxanide therapy was safe and reduced viral load significantly.

Metal mixtures in pregnant women and umbilical cord blood at urban populations-Rio de Janeiro, Brazil.

This study aims to assess interrelationships between serum lead (Pb), cadmium (Cd), arsenic (As), and mercury (Hg) concentrations in pregnant women in their third trimester and umbilical cord blood, while inter-metal correlations were also determined. This study is part of the PIPA project (Childhood and Environmental Pollutant Project), whose pilot study was carried out from October 2017 to August 2018 and will be presented here. Blood samples were obtained from 117 mother-umbilical cord pairs and analyzed concerning metal concentrations. A positive correlation was found between metal concentrations in mother and cord blood (R > 0.7, p < 0.001). The results indicate that mother metal concentrations are able to determine child metal concentrations (p < 0.001). The correlations between maternal blood metal concentrations were positive for all assessed metals except for As and Hg. The strongest correlations in this matrix were observed between Cd and Pb (R = 0.471 p = 0.000), Cd and Hg (R = 0.425 p = 0.000), and Pb and Hg (R = 0.427 p = 0.000). Umbilical cord correlations were lower compared to mother blood correlations. In general, the four analyzed metals displayed significant correlations to serum concentrations in both maternal and cord blood.

Allogenic Adipose Tissue-Derived Stromal/Stem Cells and Vitamin D Supplementation in Patients With Recent-Onset Type 1 Diabetes Mellitus: A 3-Month Follow-Up Pilot Study.

Objective: To evaluate the short term safety and potential therapeutic effect of allogenic adipose tissue-derived stromal/stem cells (ASCs) + cholecalciferol in patients with recent-onset T1D. Methods: Prospective, phase II, open trial, pilot study in which patients with recent onset T1D received ASCs (1 × 106 cells/kg) and cholecalciferol 2000 UI/day for 3 months (group 1) and were compared to controls with standard insulin therapy (group 2). Adverse events, C-peptide (CP), insulin dose, HbA1c, time in range (TIR), glucose variability (continuous glucose monitoring) and frequency of CD4+FoxP3+ T-cells (flow cytometry) were evaluated at baseline (T0) and after 3 months (T3). Results: 13 patients were included (8: group 1; 5: group 2). Their mean age and disease duration were 26.7 ± 6.1 years and 2.9 ± 1.05 months. Adverse events were transient headache (n = 8), mild local reactions (n = 7), tachycardia (n = 4), abdominal cramps (n = 1), thrombophlebitis (n = 4), mild floaters (n = 2), central retinal vein occlusion (n = 1, complete resolution). At T3, group 1 had lower insulin requirement (0.22 ± 0.17 vs. 0.61±0.26IU/Kg; p = 0.01) and HbA1c (6.47 ± 0.86 vs. 7.48 ± 0.52%; p = 0.03) than group 2. In group 1, 2 patients became insulin free (for 4 and 8 weeks) and all were in honeymoon at T3 (vs. none in group 2; p = 0.01). CP variations did not differ between groups (-4.6 ± 29.1% vs. +2.3 ± 59.65%; p = 0.83). Conclusions: Allogenic ASCs + cholecalciferol without immunosuppression was associated with stability of CP and unanticipated mild transient adverse events in patients with recent onset T1D. ClinicalTrials.gov registration: NCT03920397.

Geographic distribution and time trends of esophageal cancer in Brazil from 2005 to 2015.

The purpose of the present study was to investigate the geographical distribution and time trends of the incidence and lethality of esophageal cancer (EC) in Brazil. The present study conducted an ecological study of EC using records from January 2005 to December 2015 in the Health Informatics Department of the Brazilian Ministry of Health (DATASUS) registry. In addition to demographical data on the population, EC incidence and lethality rates were estimated from hospitalizations and in-hospital mortalities and were adjusted by total available hospital beds. The adjusted EC rates per 100,000 increased from 9.1 in 2005 to 12.1 in 2015. The prevalence among males increased from 69 to 78%, while the female rates remained stable over the same period. Although EC was the most common in South and Southeast Brazil, the rates increased proportionately more in the other regions of the country, especially among males. Geographical analysis revealed higher rates of EC in more urbanized areas, with a coast-to-inland gradient. While rates increased in people older than 50 years, they decreased among people below this age. However, the lethality rates remained stable and high during the study period, overlapping with hospital admission rates. The recent increasing trend in the EC incidence, with shifts from the south towards the north and from more urbanized towards rural areas, suggests that environmental factors are crucial in EC pathogenesis. The concentration of EC in South Brazil may reflect the presence of major environmental factors in association with a possible genetic predisposition. The unchanging high mortality associated with EC in the rapidly aging population suggests that EC will continue to impose a significant social and economic burden in the future.

Increasing pancreatic cancer is not paralleled by pancreaticoduodenectomy volumes in Brazil: A time trend analysis.

BACKGROUND: Currently, surgical resection represents the only curative treatment for pancreatic cancer (PC), however, the majority of tumors are no longer resectable by the time of diagnosis. The aim of this study was to describe time trends and distribution of pancreaticoduodenectomies (PDs) performed for treating PC in Brazil in recent years. METHODS: Data were retrospectively obtained from Brazilian Health Public System (namely DATASUS) regarding hospitalizations for PC and PD in Brazil from January 2008 to December 2015. PC and PD rates and their mortalities were estimated from DATASUS hospitalizations and analyzed for age, gender and demographic characteristics. RESULTS: A total of 2364 PDs were retrieved. Albeit PC incidence more than doubled, the number of PDs increased only 37%. Most PDs were performed in men (52.2%) and patients between 50 and 69 years old (59.5%). Patients not surgically treated and those 70 years or older had the highest in-hospital mortality rates. The most developed regions (Southeast and South) as well as large metropolitan integrated municipalities registered 76.2% and 54.8% of the procedures, respectively. LMIM PD mortality fluctuated, ranging from 13.6% in 2008 to 11.8% in 2015. CONCLUSIONS: This study suggests a trend towards regionalization and volume-outcome relationships for PD due to PC, as large metropolitan integrated municipalities registered most of the PDs and more stable mortality rates. The substantial differences between PD and PC increasing rates reveals a limiting step on the health system resoluteness. Reduction in the number of hospital beds and late access to hospitalization, despite improvement in diagnostic methods, could at least in part explain these findings.

Staging hand-wrist and cervical vertebrae images: a comparison of reproducibility.

OBJECTIVES: The aim of this study was to compare the reproducibility of skeletal maturation assessments by raters with similar orthodontic experience using hand-wrist (HW) and cervical vertebral maturation (CVM) methods. METHODS: HW and lateral cephalometric radiographs from 15 subjects (8 males and 7 females; ages, 9-16 years) were selected randomly. HW skeletal maturation was evaluated by the method of Greulich and Pyle, and CVM staging was evaluated by the method of Baccetti et al. Six orthodontic residents evaluated all images at three time periods: T1, initial evaluation; T2, re-evaluation after 7 days and T3, final evaluation after 5 weeks. Intra- and interexaminer reproducibility was evaluated with the intraclass correlation coefficient; the limits of agreement (LoA) were determined by using the Bland-Altman method. RESULTS: The intraexaminer reliability assessed by intraclass correlation coefficient was scored as good for both of methods (T1-T2-T3 HW = 0.89 and CVM = 0.80; T1-T2 HW = 0.87 and CVM = 0.77; T2-T3 HW0 = 0.90 and CVM = 0.81), as well as the interexaminer evaluation, with the exception of HW-T1, which scored excellent (0.92). The width of LoA from Bland-Altman plot of cervical vertebra method was narrower (CVM T1-T2: -2.3 and +1.8; CVM T2-T3: -2.0 and +2.0) than the HW method (HW T1-T2: -3.9 and +4.8; HW T2-T3: -4.0 and +3.5). CONCLUSIONS: Both HW and CVM methods presented good reproducibility for intra- and interexaminer correlation assessments. The small LoA indicated that the CVM is a reproducible method.

The socio-economic impact of work disability due to inflammatory bowel disease in Brazil.

BACKGROUND: Inflammatory bowel disease (IBD) might have economic and social impacts in Brazil, where its prevalence has increased recently. This study aimed to assess disability due to IBD in the Brazilian population and demographic factors potentially associated with absence from work. METHODS: Analysis was performed using the computerized Single System of Social Security Benefits Information, with a cross-check for aid pension and disability retirement, for Crohn's disease (CD) and ulcerative colitis (UC). Additional data were obtained from the platform, including the average values, benefit duration, age, gender and region of the country. RESULTS: Temporary disability occurred more frequently with UC, whereas permanent disability was more frequent with CD. Temporary disability affected more younger patients with CD than patients with UC. Temporary work absences due to UC and CD were greater in the South, and the lowest absence rates due to CD were noted in the North and Northeast. Absence from work was longer (extending for nearly a year) in patients with CD compared to those with UC. The rates of temporary and permanent disability were greater among women. Permanent disability rates were higher in the South (UC) and Southeast (CD). The value of benefits paid for IBD represented approximately 1% of all social security benefits. The benefits paid for CD were higher than for UC, whereas both tended to decrease from 2010 to 2014. CONCLUSIONS: In Brazil, IBD frequently causes disability for prolonged periods and contributes to early retirement. Reduction trends may reflect improvements in access to health care and medication. Vocational rehabilitation programs may positively impact social security and the patients' quality of life.

Pancreatic Cancer Incidence and Lethality Rates in Brazil: An Ecological Study.

OBJECTIVES: To describe incidence and lethality time trends rates of pancreatic cancer (PC) in Brazil. METHODS: Data from Brazilian Health National Public System (SUS) were retrospectively collected with regard to PC from January 2005 to December 2012. Pancreatic cancer incidence and lethality rates were estimated from SUS hospitalizations and in-hospital PC deaths and adjusted to total available hospital beds. RESULTS: From 2005 to 2012, a total of 36,332 admissions for PC were registered in Brazil. Pancreatic cancer incidence nearly doubled from 2.4/100,000 to 4.5/100,000, particularly among patients older than 70 years, whereas no difference in sex was noted. The greatest incidence rates increase (+109%) occurred in the northeast, a less developed region that has recently achieved significant economic advances. Dynamic changes were observed, notably a shift to increasing PC incidence in rural areas. Lethality rates increased from mean 25% to 27%, the highest rates registered in those 70 years or older. CONCLUSIONS: Overall increase trends in PC incidence and lethality were observed. Pancreatic cancer remains an urban disease in Brazil, the highest incidence found in the most developed regions as in large metropolitan integrated municipalities. Improvement in diagnosis, notification quality, a rapidly aging population, and a great demographic dynamism could in part explain this fact.