Hepatitis B virus genotypes and subgenotypes and the natural history and epidemiology of hepatitis B.

INTRODUCTION AND OBJECTIVES: Espírito Santo state is considered a region with a higher frequency of hepatitis B virus infection. This study characterized demographic, epidemiological, laboratory, virological and clinical aspects of 587 chronic HBV carriers followed up at the University of Espírito Santo Hospital. MATERIALS AND METHODS: Demographic, epidemiological, laboratory and clinical data were extracted from medical records during the entire follow-up period. Classification of the evolutionary phases of chronic hepatitis B was defined as immunotolerant; inactive carrier; chronic active hepatitis HBeAg (+)  and HBeAg (-). Characterization of HBV genotypes/subgenotypes was performed by sequencing of overlapping surface antigens and HBV DNA polymerase genes. Phylogenetic relationships were determined using BEAST 1.8.3 software. RESULTS: and Conclusions: Genotypes found were A (132/65.3%) [A1 = 129 (63.9%) and A2 = 3 (1.5%)], D (66/32.7%) [D3 = 56 (27.7%), D4 = 8 (4.0%) and D2 = 2 (1.0%)] and F (4/2.0%) - all F2a. Subgenotypes A1 or D3 were not associated with age, sex, HIV/HCV co-infection, viral load, antiviral usage, HBeAg status or clinical stages of chronic hepatitis B. Mother -to-child-transmission (MTCT) was associated with the subgenotype A1 and intrafamilial transmission with subgenotype D3. Subgenotype A1 was more frequent than D3 among individuals born outside ES compared to those born in ES. CONCLUSIONS: The most predominant clinical phases were HBeAg (-), inactive carrier and chronic active hepatitis HBeAg (-). Subgenotypes A1 and D3 were most frequent and were associated were MTCT and intrafamilial transmission of HBV, respectively.

Modelling the impact of delaying vaccination against SARS-CoV-2 assuming unlimited vaccine supply.

BACKGROUND: At the moment we have more than 177 million cases and 3.8 million deaths (as of June 2021) around the world and vaccination represents the only hope to control the pandemic. Imperfections in planning vaccine acquisition and difficulties in implementing distribution among the population, however, have hampered the control of the virus so far. METHODS: We propose a new mathematical model to estimate the impact of vaccination delay against the 2019 coronavirus disease (COVID-19) on the number of cases and deaths due to the disease in Brazil. We apply the model to Brazil as a whole and to the State of Sao Paulo, the most affected by COVID-19 in Brazil. We simulated the model for the populations of the State of Sao Paulo and Brazil as a whole, varying the scenarios related to vaccine efficacy and compliance from the populations. RESULTS: The model projects that, in the absence of vaccination, almost 170 thousand deaths and more than 350 thousand deaths will occur by the end of 2021 for Sao Paulo and Brazil, respectively. If in contrast, Sao Paulo and Brazil had enough vaccine supply and so started a vaccination campaign in January with the maximum vaccination rate, compliance and efficacy, they could have averted more than 112 thousand deaths and 127 thousand deaths, respectively. In addition, for each month of delay the number of deaths increases monotonically in a logarithmic fashion, for both the State of Sao Paulo and Brazil as a whole. CONCLUSIONS: Our model shows that the current delay in the vaccination schedules that is observed in many countries has serious consequences in terms of mortality by the disease and should serve as an alert to health authorities to speed the process up such that the highest number of people to be immunized is reached in the shortest period of time.

Metabolic disorder and obesity in 5027 Brazilian postmenopausal women.

OBJECTIVES: To evaluate the frequency of obesity in postmenopausal women and assess the potential effects of increased body mass index (BMI) on lipoprotein profile and on risk factors for arterial hypertension and diabetes. DESIGN: A cross-sectional study was conducted with 5027 postmenopausal Brazilian women. Analyses were performed of BMI and cardiovascular factors (systemic blood pressure [BP], total cholesterol, low-density lipoprotein, high-density lipoprotein [HDL-C], triglyceride, and fast glucose). The statistical analysis included the chi-square and Mann-Whitney tests. The significance level was set at 5%. RESULTS: Obesity (BMI >30) in our study characterized approximately 30% of the 5027 postmenopausal women. The comparison of patients with normal BMI and those with high BMI showed that high BMI had a significant negative effect on BP, as evidenced by the increased frequency of hypertension in overweight and obese patients (>25) (p < 0.001), that it also negatively and significantly affected triglyceride (p < 0.001) and fast glucose levels (p < 0.001), and that it was linked significantly to low levels of HDL-C. CONCLUSION: Our data showed the high frequency of obesity in our population and of the cardiovascular risks (glucose, systemic arterial hypertension, and low HDL-C) associated with high BMI.

Impact of age and body mass on the intensity of menopausal symptoms in 5968 Brazilian women.

OBJECTIVE: To assess the relationship of onset of menopause and body mass on the menopausal symptoms in post-menopausal Brazilian women. DESIGN: Observational study conducted by the selection and inclusion of 5968 Brazilian women after menopause. The following variables were analyzed in this study: time at menopause; the relationship between age at menarche and age at menopause; vasomotor symptoms compared with age at the time of menopause and the time of menopause; Kupperman menopausal index (KMI) versus total time of menopause; body mass index (BMI) compared to the time of menopause, vasomotor symptoms, and KMI total score. We used the Chi-square test, and the significance level was set at 5%. RESULTS: The age at natural menopause ranged from 41 to 62 years (mean 48.1 ± 4.07 years). A younger age at menopause was associated with a high intensity of vasomotor symptoms. These symptoms were more intense in the first 5 years of menopause and decreased with time. The KMI total also decreased with time after menopause, with the exception of arthralgia, myalgia, and insomnia, which did not tend to improve over time. In addition, the vasomotor symptoms and total KMI were more frequent with increasing BMI. CONCLUSIONS: Our results suggested that the age of menopause and BMI may influence the intensity of vasomotor symptoms.

Core Promoter and Pre-Core Variants of the Hepatitis B Virus (HBV) Are Frequent in Chronic Hepatitis B HBeAg-Negative Patients Infected by Genotypes A and D.

In Brazil, hepatitis B virus endemicity is low, moderate, or high in some areas, such as Espírito Santo State in the southeast region. In this study, we intend to characterize the basal core promoter (BCP) and pre-core region (PC) variants and their association with clinical/epidemiological disease patterns in patients infected with genotypes A and D. The study included 116 chronic hepatitis B patients from Espírito Santo State, Southeast Brazil, infected with genotypes A and D. Basal core promoter (BCP) and pre-core mutations were analyzed in these patients. The frequency of BCP and PC mutations was compared with age, HBeAg status, HBV genotype and subgenotype, HBV-DNA level, clinical classification, and transmission route. HBeAg-negative status was found in 101 (87.1%) patients: 87 (75.0%) were infected with genotype A (A1 = 85; A2 = 2) and 29 (25.0%) were infected with genotype D (D3 = 24; D4 = 3; D2 = 2). BCP + PC variants altogether were more frequent (48.1%) in genotype D than in genotype A strains (6.0%) (p < 0.001). When this evaluation was performed considering the cases that presented only the A1762T and/or G1764A (BCP) mutations, it was observed that the frequency was higher in genotype A (67.5%) compared to genotype D (7.4%) (p < 0.001). On the other hand, considering the samples with mutations only in positions G1896A and/or G1899A (PC), the frequency was higher in genotype D (75.8%) than in genotype A (6.9%) (p < 0.001). Interestingly, HBV DNA was lower than 2000 IU/mL especially when both BCP/PC mutations were present (p < 0.001) or when only PC mutations were detected (p = 0.047), reinforcing their role in viral replication.

Acupuncture for Climacteric-Like Symptoms in Breast Cancer Improves Sleep, Mental and Emotional Health: A Randomized Trial.

Objective: Breast cancer is the most prevalent malignant neoplasm in women. Optimal treatment frequently includes a hormonal-blockage phase maintained for 5-10 years. Pharmacologic agents used for this blockage induce many climacteric-like symptoms, which often exact a heavy toll on patients' quality of life. Acupuncture has had promising results for treating climacteric-like symptoms induced by hormonal blockage, but there is no evidence of efficacy for controlling hot flashes. Materials and Methods: This trial used acupuncture to treat the climacteric-like symptoms of patients with breast cancer, focusing on the mental, physical, and genitourinary symptoms and sleep disturbances, to determine the influence of acupuncture treatment. The randomized placebo-controlled trial, at a university-based cancer center, with blinded data collectors, compared an Acupuncture group (A), a Sham-Acupuncture group (S), and a Wait-List Control group (C). The patients were receiving tamoxifen. Group A had 10 weekly sessions of manual Acupuncture; Group S had 10 weekly sessions of Sham Acupuncture; and Group C spent 10 weeks on a Wait-List. The main outcome measures were the Beck Depression Inventory-II (BDI-II), the Pittsburgh Sleep Quality Index (PSQI), and the Menopause Rating Scale (MRS). Results: Primary analysis revealed differences among the groups' improvements in scores for the 3 questionnaires (P < 0.001), The A group had significant improvements on the BDI-II (P < 0.001), PSQI (P < 0.002), and MRS (P < 0.004) compared to the S group in a post hoc analysis. Conclusions: Acupuncture improved sleep, and mental and emotional distress symptoms induced by hormonal blockage in patients with breast cancer. Clinical Trial: This trial was registered at CAAE as trial #: 37758414.8.0000.0065.

Modelling the impact of contact tracing of symptomatic individuals on the COVID-19 epidemic.

OBJECTIVES: With the declining numbers of coronavirus disease 2019 (COVID-19) cases in the state of São Paulo, Brazil, social distancing measures have gradually been lifted. However, the risk of a surge in the number of cases cannot be overlooked. Even with the adoption of nonpharmaceutical interventions, such as restrictions on mass gatherings, wearing of masks, and complete or partial closure of schools, other public health measures may help control the epidemic. We aimed to evaluate the impact of the contact tracing of symptomatic individuals on the COVID-19 epidemic regardless of the use of diagnostic testing. METHODS: We developed a mathematical model that includes isolation of symptomatic individuals and tracing of contacts to assess the effects of the contact tracing of symptomatic individuals on the COVID-19 epidemic in the state of São Paulo. RESULTS: For a selection efficacy (proportion of isolated contacts who are infected) of 80%, cases and deaths may be reduced by 80% after 60 days when 5000 symptomatic individuals are isolated per day, each of them together with 10 contacts. On the other hand, for a selection efficacy of 20%, the number of cases and deaths may be reduced by approximately 40% and 50%, respectively, compared with the scenario in which no contact-tracing strategy is implemented. CONCLUSION: Contact tracing of symptomatic individuals may potentially be an alternative strategy when the number of diagnostic tests available is not sufficient for massive testing.

Study protocol: epidemiological and clinical characteristics of acute viral hepatitis in Brazilian health services.

INTRODUCTION: Acute viral hepatitis is a disease of great clinical importance. This study proposes actions to better characterise cases of acute hepatitis in Brazil and to provide relevant information to institutionalised health policies within the Unified Health System. Available data on acute hepatitis in Brazil need to be re-evaluated regarding the different hepatotropic agent (hepatitis A to E virus) frequencies, as well as other agents that can cause similar clinical conditions, such as Herpes Simplex Virus 1 and 2(HSV1, HSV2), Varicella Zoster Virus (VZV), Cytomegalovirus (CMV), Epstein Barr Virus (EBV), Human Herpes Virus 6 and 7 (HHV6, HHV7), arbovirus (yellow fever, dengue, chikungunya, Zika), parvovirus B19, adenovirus, parechovirus, enterovirus, HIV, leptospirosis, toxoplasmosis and syphilis, in addition to autoimmune hepatitis. In this context, the primary aim of this study is the clinical-epidemiological and molecular characterisation of acute viral hepatitis in Brazilian health services from all geographical regions of the country. The present article describes the study protocol. METHODS AND ANALYSIS: This study will evaluate 2280 patients with symptoms and/or signs suggestive of acute liver disease in Brazilian health institutions in all five geographic Brazilian regions. Demographic, epidemiological and clinical data will be collected, as well as blood samples to be analysed at Hospital Israelita Albert Einstein Clinical Laboratory. ETHICS AND DISSEMINATION: Ethics approval was obtained at the national research ethics committee (Conselho Nacional de Ética em Pesquisa- CONEP-CAAE 00952818.4.1001.0071) and at all participating sites. Results will be published in journals and presented at scientific meetings.

Sequencing of E2 and NS5A regions of HCV genotype 3a in Brazilian patients with chronic hepatitis.

Hepatitis C virus (HCV) is a major cause of liver disease throughout the world. The NS5A and E2 proteins of HCV genotype 1 were reported to inhibit the double-stranded (ds) RNA-dependent protein kinase (PKR), which is involved in the cellular antiviral response induced by interferon (IFN). The response to IFN therapy is quite different between genotypes, with response rates among patients infected with types 2 and 3 that are two-three-fold higher than in patients infected with type 1. Interestingly, a significant percentage of HCV genotype 3-infected patients do not respond to treatment at all. The aim of this paper was to analyse the sequences of fragments of the E2 and NS5A regions from 33 outpatients infected with genotype 3a, including patients that have responded (SVR) or not responded (NR) to treatment. HCV RNA was extracted and amplified with specific primers for the NS5A and E2 regions and the PCR products were then sequenced. The sequences obtained covered amino acids (aa) 636-708 in E2 and in NS5A [including the IFN sensitivity determining region (ISDR), PKR-binding domain and extended V3 region)]. In the E2 and NS5A regions, we did observe aa changes among patients, but these changes were not statistically significant between the SVR and NR groups. In conclusion, our results suggest that the ISDR domain is not predictive of treatment success in patients infected with HCV genotype 3a.

HBV markers in haemodialysis Brazilian patients: a prospective 12-month follow-up.

The aim of this study was to determine the prevalence and the incidence of hepatitis B virus (HBV) among haemodialysis (HD) subjects and to evaluate whether testing for serological markers at the time of admission is suitable for HBV screening in this population. One hundred twenty-three patients belonging to two HD centres from São Paulo, Brazil, were tested prospectively. HBV DNA was detected by polymerase chain reaction (PCR) in each of the prospective subjects (n = 123) during one year. Additionally, all samples (n = 1,476) were analysed for HBV serological markers. The prevalence of hepatitis B core antibody (anti-HBc), hepatitis B surface antigen (HBsAg) and HBV DNA were 34.1%, 15.4% and 8.1%, respectively, while the incidence was null. Fluctuation in HBV serology was observed in one patient. Only 37.8% (17/45) of cases responded to the HBV vaccine. Our results suggest that employing more than one HBV marker and repeated follow-up evaluations may improve HBV screening in HD units.

Genetic Subtypes of Systemic Anaplastic Large Cell Lymphoma Show Distinct Differences in PD-L1 Expression and Regulatory and Cytotoxic T Cells in the Tumor Microenvironment.

Anaplastic large cell lymphomas (ALCL) encompass several subgroups that differ in their clinical presentation, genetic features, and prognosis. We characterized the genetic subgroups of 74 patients with ALCL and correlated programmed death ligand 1 (PD-L1) protein expression and compared the densities and ratios of FOXP3+ T regulatory cells and CD8+ tumor-infiltrating lymphocytes (TILs) in tumor cells and the immune microenvironment. The subgroups included anaplastic lymphoma kinase (ALK)-positive (ALK+) ALCL and ALK-negative (ALK-) ALCL and DUSP22-rearranged and nonrearranged ALK- ALCL. None of our cases represented the TP63-rearrangement ALK- ALCL subgroup. Our results showed that ALK+ ALCL had a higher expression of PD-L1 in the tumor cells, in contrast to ALK- ALCL, which expressed high PD-L1 in tumor-associated macrophages (TAMs). DUSP22-rearranged ALK- ALCL lacked PD-L1 expression in the tumor cells and instead expressed PD-L1 only in TAMs. There was a significant positive correlation of PD-L1 expression between tumor and TAMs in ALK+ ALCL with a negative correlation in ALK- ALCL. Systemic ALCL subgroups had similar densities of CD8+ tumor-infiltrating lymphocytes and FOXP3 T regulatory cells, but differences were observed in the ratio of CD8/FOXP3. Our results suggest that alterations in tumor microenvironment and immune responses exist among systemic ALCL subgroups and these features may account for different clinical behavior and prognosis.

Relationship among epidemiological parameters of six childhood infections in a non-immunized Brazilian community.

Epidemiological parameters, such as age-dependent force of infection and average age at infection () were estimated for rubella, varicella, rotavirus A, respiratory syncytial virus, hepatitis A and parvovirus B19 infections for a non-immunized Brazilian community, using the same sera samples. The for the aforementioned diseases were 8.45 years (yr) [95% CI: (7.23, 9.48) yr], 3.90 yr [95% CI: (3.51, 4.28) yr], 1.03 yr [95% CI: (0.96, 1.09) yr], 1.58 yr [95% CI: (1.39, 1.79) yr], 7.17 yr [95% CI: (6.48, 7.80) yr] and 7.43 yr [95% CI: (5.68, 9.59) yr], respectively. The differences between average ages could be explained by factors such as differences in the effectiveness of the protection conferred to newborns by maternally derived antibodies, competition between virus species and age-dependent host susceptibility. Our seroprevalence data may illustrate a case of the above-mentioned mechanisms working together within the same population.

Gynecological cancer and metabolic screening of 1001 elderly Brazilian women.

OBJECTIVE: The aim of this study was to evaluate gynecological cancer and metabolic screening of Brazilian women aged 65 years or older. METHODS: This retrospective descriptive study was conducted by including 1,001 Brazilian patients of the gynecological geriatric outpatient office of our institution to evaluate the influence of age on gynecological cancer and metabolic screening parameters at the first clinical visit. All patients were divided into three groups: a) 65 to 69 years; b) 70 to 74 years; c) ≥ 75 years. We considered clinical, laboratorial, and image data as variables of this study. The Chi-square test was used to assess the proportion of differences among the age groups, and Kruskal-Wallis was used for quantitative variables. RESULTS: The values of BMI and height in the group over 75 years was lower than that of the 65 to 69 years (p = 0.001). Regardless of the age group, high arterial blood pressure levels were found in 85.45% of participants. Also, many patients had glucose intolerance in the blood. The pelvic ultrasonography showed abnormal endometrial echo thickness (> 5 mm) in 6.14% of patients, but with no significant statistical difference between the age groups. A total of 4.04% of patients had ovaries with high volume values ( > 6.1 mL). Abnormal mammography (BI-RADS 3 or 4) was observed in 12.21%. CONCLUSIONS: our data suggest that a great reduction in BMI and stature is more frequent in the group over 75 years. Also, systemic arterial hypertension and carbohydrate disturbance are frequent morbidities in women over 65 years.

Clinicopathologic and microenvironmental analysis of primary cutaneous CD30-positive lymphoproliferative disorders: a 26 year experience from an academic medical center in Brazil.

BACKGROUND: Primary cutaneous CD30+ lymphoproliferative disorders (pc-CD30-LPD) are a group of clonal T cell lymphoproliferative disorders that despite very similar tumor histology follow different and characteristic clinical courses, suggesting a homeostatic role of the tumor microenvironment. Little is known about tumor microenvironment and there is almost no literature about PD-L1 expression in pc-CD30-LPD. METHODS: This retrospective study presents a fully clinicopathologically characterized series of pc-CD30-LPDs from an academic medical center in Brazil, including 8 lymphomatoid papulomatosis (LyP), 9 primary cutaneous anaplastic large cell lymphoma (pcALCL) and 4 borderline lesions. All the cases were scored for FOXP3+ regulatory T-cells (Treg) and CD8+ cytotoxic tumor infiltrating lymphocytes (TIL) densities, as well as PD-L1 expression in tumor cells and tissue associated macrophages. The CD8+/FOXP3+ ratio was also evaluated. RESULTS: Among the 21 cases of pc-CD30-LPD, PD-L1 expression is frequent in both tumor cells and tissue associated macrophages in pc-CD30-LPD across categories, suggesting that the PD-L1 axis may be a common feature of pc-CD30-LPDs. While reactive T cell infiltrates vary widely from case to case, a common feature across pc-CD30-LPDs is higher density of CD8 than FOXP3 + T cells. The distribution of T cells within the lesions however differed between LyP and pcALCL: we found that LyP lesions tend to be permeated by CD8+ and FOXP3+ T cells, whereas pcALCL tend to be surrounded by a rim of CD8+ TIL and FOXP3+ Tregs with relatively lower density infiltrates in the center of the lesion. CONCLUSIONS: LyP has a trend to have denser immune cells throughout the lesion, with higher FOXP3+ Treg and CD8+ TIL in the center than the edge comparing with pcALCL. PD-L1+ is frequent in tumor cells and tissue associated macrophages in pc-CD30-LPD. The differential distribution of CD8+ and FOXP3+ TILs in LyP as compared to pcALCL could provide a clue to the relapsing/remitting course of LyP as compared to the less frequent spontaneous regression of pcALCL.

Serological patterns and temporal trends of HTLV-1/2 infection in high-risk populations attending Public Health Units in São Paulo, Brazil.

BACKGROUND: HTLV-1/2 diagnosis in high-risk populations from São Paulo, Brazil has been problematic due a high proportion of seroindeterminate results. OBJECTIVES: To confirm and extend previous findings regarding HTLV-1/2 diagnosis in this geographic area. STUDY DESIGN: Sera from 2312 patients were tested for HTLV-1/2 antibodies using enzyme immunoassay (EIA) and Western blot (WB) analysis. Patients were from AIDS Reference Centers (Group I; 1393 patients) and HTLV out-patient clinics (Group II; 919 patients). Results were analyzed according to patients' age, gender, and clinic type. RESULTS: HTLV-1 and HTLV-2 were detected in both groups. Among seropositive females, HTLV-2 was slightly more common in Group I (54.5%), while HTLV-1 prevailed in Group II (73.9%). Males from Group II had a higher percentage of HTLV-seroindeterminate results. No correlation between HTLV serological results and age was detected. Temporal analyses disclosed a high number of HTLV-seroindeterminate samples, and a large spectrum of indeterminate WB profiles. GD21 and/or rgp46-II bands were detected in 34.6% of sera from Group I, and a p24 or p19 band was detected in 35.3% of sera from Group II. CONCLUSIONS: High rates of HTLV-indeterminate serological patterns during temporal analyses were confirmed in high-risk populations from São Paulo, Brazil.

Performances of HTLV serological tests in diagnosing HTLV infection in high-risk population of São Paulo, Brazil.

Testing problems in diagnosing human T-lymphotropic virus (HTLV) infection, mostly HTLV-II, have been documented in HIV/AIDS patients. Since December 1998, the Immunology Department of Instituto Adolfo Lutz (IAL) offers HTLV-I/II serology to Public Health Units that attend HTLV high-risk individuals. Two thousand, three hundred and twelve serum samples: 1,393 from AIDS Reference Centers (Group I), and 919 from HTLV out-patient clinics (Group II) were sent to IAL for HTLV-I/II antibodies detection. The majority of them were screened by two enzyme immunoassays (EIAs), and confirmed by Western Blot (WB 2.4, Genelabs). Seven different EIA kits were employed during the period, and according to WB results, the best performance was obtained by EIAs that contain HTLV-I and HTLV-II viral lysates and rgp21 as antigens. Neither 1st and 2nd, nor 3rd generation EIA kits were 100% sensitive in detecting truly HTLV-I/II reactive samples. HTLV-I and HTLV-II prevalence rates of 3.3% and 2.5% were detected in Group I, and of 9.6% and 3.6% in Group II, respectively. High percentages of HTLV-seroindeterminate WB sera were detected in both Groups. The algorithm testing to be employed in HTLV high-risk population from São Paulo, Brazil, needs the use of two EIA kits of different formats and compounds as screening, and because of high seroindeterminate WB, may be another confirmatory assay.

Electronic health record in the internal medicine clinic of a Brazilian university hospital: Expectations and satisfaction of physicians and patients.

PURPOSE: To evaluate the satisfaction and expectations of patients and physicians before and after the implementation of an electronic health record (EHR) in the outpatient clinic of a university hospital. METHODS: We conducted 389 interviews with patients and 151 with physicians before and after the implementation of a commercial EHR at the internal medicine clinic of Hospital das Clínicas of the Faculty of Medicine of the University of São Paulo (HC-FMUSP), Brazil. The physicians were identified by their connection to the outpatient clinic and categorized by their years since graduation: residents and preceptors (with 10 years or less of graduation) or assistants (with more than 10 years of graduation). The answers to the questionnaire given by the physicians were classified as favorable or against the use of EHR, before and after the implementation of this system in this clinic, receiving 1 or 0 points, respectively. The sum of these points generated a multiple regression score to determine which factors contribute to the acceptance of EHR by physicians. We also did a third survey, after the EHR was routinely established in the outpatient clinic. RESULTS: The degree of patient satisfaction was the same before and after implementation, with more than 90% positive evaluations. They noted the use of the computer during the consultation and valued such use. Resident (younger) physicians had more positive expectations than assistants (older physicians) before EHR implementation. This optimism was reduced after implementation. In the third evaluation the use of EHR was higher among resident physicians. Resident physicians perceived and valued the EHR more and used it more. In 28 of the 57 questions on performance of clinical tasks, resident physicians found it easier to use EHR than assistant physicians with significant differences (p<0.05). When questioned specifically about EHR satisfaction, resident physicians responded "good" and "excellent" to a greater extent than assistant physicians (p=0.002). CONCLUSIONS: Our results reinforce the idea that the EHR introduction in a clinical setting should be preceded by careful planning to improve physician's adherence to the use of EHR. Patients do not seem to notice much difference to the quality of the consultation done using paper or EHR. It became clear after the third evaluation with the physicians that the younger (residents and some preceptors) perceived the advantages of the EHR more than the older physicians. Resident physicians use the EHR more and are more satisfied with it.

Histological Grading of Hepatocellular Carcinoma-A Systematic Review of Literature.

BACKGROUND: Histological grading typically reflects the biological behavior of solid tumors, thus providing valuable prognostic information. This is also expected in hepatocellular carcinoma (HCC), although limited access to biopsy samples and a lack of standardization might hinder its full predictive value in this cancer. OBJECTIVES: In order to better understand the current practices of histological grading in HCC, we examined the latest publications addressing its impact on the outcome of patients following surgical treatment. METHODS: We searched the PubMed (MEDLINE) database under the headings "hepatocellular carcinoma," "grade OR grading," and "prognosis." Qualitative and quantitative assessment of publications was performed according to the reference they used to grade their tumors (e.g., Edmondson-Steiner, World Health Organization). RESULTS: We reviewed a total of 216 articles: 114 enclosed adequate information and were included herein. Among these, we found divergences and inaccuracies in the histological grade assessment of this cancer, which might have led to a non-standardized grade distribution, with further impact on data analysis. Nevertheless, in most of them, poor tumor differentiation correlated with worse prognosis, expressed by lower overall and/or disease-free survival. CONCLUSION: While histological grading of HCC has an important prognostic role, there is an unsatisfactory heterogeneity on the microscopic assessment of this tumor, urging for a movement toward standardization.

Brazilian Women's Health after 65 Years of Age.

Purpose The aim of this study was to evaluate the health aspects of Brazilian women older than 65 years of age. Design This was a retrospective study that included 1,001 Brazilian women cared for in the gynecological geriatric outpatient office of our institution. We report a cross-sectional analysis of female adults aged over 65 years, including data on demographics, clinical symptoms such as vasomotor symptoms, associated morbidities, physical examination and sexual intercourse. We used the chi-squared test to assess the data. Results The age of the patients on their first clinic visit ranged from 65 to 98 years, with a mean age of 68.56 ± 4.47 years; their mean age at the time of natural menopause was 48.76 ± 5.07 years. The most frequent clinical symptoms reported during the analyzed period were hot flashes (n = 188), followed by arthropathy, asthenia, and dry vagina. The most frequent associated morbidities after 65 years of age were systemic arterial hypertension, gastrointestinal disturbance, diabetes mellitus, and depression, among others. The assessment of the body mass index (BMI) found decreases in BMI with increased age. At the time of the visit, 78 patients reported sexual intercourse. The majority of women reporting sexual intercourse (89.75%, n = 70) were between 65 and 69 years of age, 8.97% (n = 7) were between 70 and 74 years of age, and only 1.28% (n = 1) of those were aged older than 75 years. Conclusions Our findings suggested that vasomotor symptoms can persist after 65 years of age. There was a significant decrease in sexual intercourse with increased age. The cardiovascular disturbances in our study are health concerns in these women.

Objetivo Avaliar os aspectos de saúde das mulheres brasileiras após os 65 anos de idade. Métodos O estudo foi retrospectivo, e incluiu 1.001 mulheres brasileiras atendidas no ambulatório de ginecologia geriátrica de nossa instituição. Foi feita uma análise transversal de mulheres com idade acima de 65 anos, incluindo dados demográficos, sintomas clínicos (sintomas vasomotores), morbidades associadas, bem como alterações no exame físico e queixas em relação à atividade sexual. Utilizamos o teste qui-quadrado para avaliar os dados. Resultados A idade das pacientes na primeira visita clínica variou de 65 a 98 anos, com média etária de 68,56 ± 4,47 anos. A média etária de entrada na menopausa foi de 48,76 ± 5,07 anos. Os sintomas clínicos mais frequentes relatados durante o período analisado foram os sintomas vasomotores (n = 188), seguidos de artropatia, astenia e vagina seca. As morbidades associadas mais frequentes após os 65 anos foram hipertensão arterial sistêmica, distúrbios gastrintestinais, diabete melito e depressão, entre outras. A avaliação do índice de massa corporal (IMC) mostrou redução deste parâmetro antropométrico com o progredir da idade. No momento da visita, 78 pacientes relataram ter relações sexuais. A maioria das mulheres que relatou ter relações sexuais (89,75%, n = 70) estava entre 65 e 69 anos, 8,97% (n = 7) tinham entre 70 e 74 anos, e apenas 1,28% (n = 1) eram mais velhas do que 75 anos de idade. Conclusões Nossos achados sugerem que os sintomas vasomotores podem persistir após os 65 anos. Houve uma diminuição significativa na relação sexual com o aumento da idade. Os distúrbios cardiovasculares em nosso estudo são preocupações de saúde nestas mulheres.

Secondary myeloid neoplasms: bone marrow cytogenetic and histological features may be relevant to prognosis.

BACKGROUND: Secondary myeloid neoplasms comprise a group of diseases arising after chemotherapy, radiation, immunosuppressive therapy or from aplastic anemia. Few studies have addressed prognostic factors in these neoplasms. METHOD: Forty-two patients diagnosed from 1987 to 2008 with secondary myeloid neoplasms were retrospectively evaluated concerning clinical, biochemical, peripheral blood, bone marrow aspirate, biopsy, and immunohistochemistry and cytogenetic features at diagnosis as prognostic factors. The International Prognostic Scoring System was applied. Statistical analysis employed the Kaplan-Meier method, log-rank and Fisher's exact test. RESULTS: Twenty-three patients (54.8%) were male and the median age was 53.5 years (range: 4-88 years) at diagnosis of secondary myeloid neoplasms. Previous diseases included hematologic malignancies, solid tumors, aplastic anemia, autoimmune diseases and conditions requiring solid organ transplantations. One third of patients (33%) were submitted to chemotherapy alone, 2% to radiotherapy, 26% to both modalities and 28% to immunosuppressive agents. Five patients (11.9%) had undergone autologous hematopoietic stem cell transplantation. The median latency between the primary disease and secondary myeloid neoplasms was 85 months (range: 23-221 months). Eight patients were submitted to allogeneic hematopoietic stem cell transplantation to treat secondary myeloid neoplasms. Important changes in bone marrow were detected mainly by biopsy, immunohistochemistry and cytogenetics. The presence of clusters of CD117+ cells and p53+ cells were associated with low survival. p53 was associated to a higher risk according to the International Prognostic Scoring System. High prevalence of clonal abnormalities (84.3%) and thrombocytopenia (78.6%) were independent factors for poor survival. CONCLUSION: This study demonstrated that cytogenetics, bone marrow biopsy and immunohistochemistry are very important prognostic tools in secondary myeloid neoplasms.