People living with HIV co-infected with the Kaposi Sarcoma-associated Herpes Virus have a distinct HIV Tat profile and higher rates of antiretroviral virologic failure, more evident among those with Kaposi's sarcoma.

Kaposi sarcoma (KS) is a neoplasm of vascular origin that promotes angiogenesis and the growth of endothelial cells triggered by the Kaposi Sarcoma-associated Herpes Virus (KSHV). When associated with HIV, KSHV becomes more aggressive and rapidly evolves. The HIV-1 TAT protein can be essential in developing AIDS-associated KS by promoting angiogenesis and increasing KSHV replication. Therefore, we evaluated the genetic profile of the first exon of tat gene among groups of people living with HIV (PLHIV) with (case group, n = 36) or without KS, this later with (positive control group, n = 46) and without KSHV infection (negative control group, n = 24); all individuals under antiretroviral therapy. The genetic diversity, the DN/DS ratio, and the genetic entropy of the first exon of tat were higher in the case group, followed by the positive control group, which was higher than the negative control group. The number of tat codons under positive selection was seven in the case group, six in the positive control group, and one in the negative control group. The prevalence of HIV viral loads below the detection limit was equal in the case and positive control groups, which were lower than in the negative control group. The mean CD4+ T cell counts were higher in the negative control group, followed by the positive control group, and followed by the case group. These results emphasize the negative influence of KSHV in antiretroviral treatment, as well as the HIV-specific TAT profile among PLHIV who developed KS.

Dolutegravir-associated resistance mutations after first-line treatment failure in Brazil.

BACKGROUND: Since January 2017, the recommended first-line antiretroviral regimen in Brazil is the fixed-dose combination of tenofovir plus lamivudine with dolutegravir (TL + D). According to the literature, integrase resistance-associated mutations (INRAMs) are rarely found upon virologic failure to first-line dolutegravir plus two nucleoside reverse transcriptase inhibitors. We evaluated the HIV antiretroviral genotypic resistance profile of patients referred for genotyping in the public health system who failed first-line TL + D after at least six months of therapy on or before December 31, 2018. METHODS: HIV Sanger sequences of the pol gene were generated from plasma of patients with confirmed virologic failure to first-line TL + D in the Brazilian public health system before December 31, 2018. RESULTS: One hundred thirteen individuals were included in the analysis. Major INRAMs were detected in seven patients (6.19%), four with R263K, one with G118R, one with E138A, and one with G140R. Four patients with major INRAMs also had the K70E and M184V mutations in the RT gene. Sixteen (14.2%) additional individuals presented minor INRAMs, and five (4,42%) patients had both major and minor INRAMS. Thirteen (11.5%) patients also presented mutations in the RT gene selected by tenofovir and lamivudine, including four with both the K70E and M184V mutations and four with only M184V. The integrase mutations L101I and T124A, which are in the in vitro pathway for integrase inhibitor resistance, were found in 48 and 19 patients, respectively. Mutations not related to TL + D, thus probable transmitted resistance mutations (TDR), were present in 28 patients (24.8%): 25 (22.1%) to nucleoside reverse transcriptase inhibitors, 19 (16.8%) to non-nucleoside reverse transcriptase inhibitors, and 6 (5.31%) to protease inhibitors. CONCLUSIONS: In marked contrast to previous reports, we report a relatively high frequency of INRAMs among selected patients failing first-line TL + D in the public health system in Brazil. Possible reasons for this discrepancy include delays in detecting virologic failure, patients inadvertently on dolutegravir monotherapy, TDR, and/or infecting subtype.

Judicialization and cancer: quality of life of patients and caregivers in the COVID-19 pandemic.

BACKGROUND: In Brazil, cancer patients and caregivers of cancer patients seek judicial intervention for free access to medications from the public health system. Indeed, the COVID-19 pandemic potentially affected the health-related quality of life of cancer patients and caregivers of cancer patients. This study aimed to describe the sociodemographic profile and assess the health-related quality of life of patients and caregivers in the state of Goias, Brazil, in 2020. METHODS: A cross-sectional study was conducted using the Medical Outcomes Study 36-Item Short Form Health Survey (SF-36) and a sociodemographic questionnaire. RESULTS: A total of 88 (67,7%) patients and 42 (32,3%) caregivers participated in the study, mostly women (55,5%); aged from 18 to 60 (66%) years old; with up to nine years of education (73,1%) and monthly family income lower than the minimum wage (69,2%); married or in a stable union (92,3%); living with multiple people in the same household (73,8%). The quality of life domains with the best scores were mental health for patients and pain for caregivers. The most affected quality of life domain was physical limitation for patients and caregivers. Factors associated with better quality of life were female gender and age between 18 and 60 years in patients, more than 9 years of education, living with multiple people in the same house, and having a monthly family income higher than US$200 for caregivers. CONCLUSION: The study found evidence of physical and emotional vulnerability during the pandemic, highlighting the need to strengthen public policies of assistance support to this population.

Immunogenicity of personalized dendritic-cell therapy in HIV-1 infected individuals under suppressive antiretroviral treatment: interim analysis from a phase II clinical trial.

BACKGROUND: We developed a personalized Monocyte-Derived Dendritic-cell Therapy (MDDCT) for HIV-infected individuals on suppressive antiretroviral treatment and evaluated HIV-specific T-cell responses. METHODS: PBMCs were obtained from 10 HIV+ individuals enrolled in trial NCT02961829. Monocytes were differentiated into DCs using IFN-α and GM-CSF. After sequencing each patient's HIV-1 Gag and determining HLA profiles, autologous Gag peptides were selected based on the predicted individual immunogenicity and used to pulse MDDCs. Three doses of the MDDCT were administered every 15 days. To assess immunogenicity, patients' cells were stimulated in vitro with autologous peptides, and intracellular IL-2, TNF, and interferon-gamma (IFN-γ) production were measured in CD4+ and CD8+ T-cells. RESULTS: The protocol of ex-vivo treatment with IFN-α and GM-CSF was able to induce maturation of MDDCs, as well as to preserve their viability for reinfusion. MDDCT administration was associated with increased expression of IL-2 in CD4+ and CD8+ T-cells at 15 and/or 30 days after the first MDDCT administration. Moreover, intracellular TNF and IFN-γ expression was significantly increased in CD4+ T-cells. The number of candidates that increased in vitro the cytokine levels in CD4+ and CD8+ T cells upon stimulation with Gag peptides from baseline to day 15 and from baseline to day 30 and day 120 after MDDCT was significant as compared to Gag unstimulated response. This was accompanied by an increasing trend in the frequency of polyfunctional T-cells over time, which was visible when considering both cells expressing two and three out of the three cytokines examined. CONCLUSIONS: MDDC had a mature profile, and this MDDCT promoted in-vitro T-cell immune responses in HIV-infected patients undergoing long-term suppressive antiretroviral treatment. Trial registration NCT02961829: (Multi Interventional Study Exploring HIV-1 Residual Replication: a Step Towards HIV-1 Eradication and Sterilizing Cure, https://www.clinicaltrials.gov/ct2/show/NCT02961829 , posted November 11th, 2016).

Patient satisfaction with ball and Equator attachments for single-implant mandibular overdentures: A short-term randomised crossover clinical trial.

BACKGROUND: Retention and stabilisation of a single-implant mandibular overdenture (SIMO) are influenced by the biomechanical properties and clinical performance of the attachment system. PURPOSE: To compare clinical and patient-reported outcomes following the use of two retention systems, a ball and a stud-type Equator attachment used for SIMO. MATERIAL AND METHODS: Eighteen fully edentulous participants were treated with a SIMO opposing to a maxillary complete denture. They received two retentive attachments (ball and Equator) in alternate periods (sequences A-B and B-A) and outcomes were assessed after the 1 week (initial) and 3 months (final) periods. In the final assessment, patients were also asked about their preferred retention system. RESULTS: Compared with baseline, there was an improvement in patient satisfaction using both attachments, whilst no difference was observed between initial and final periods. Similarly, no significant differences were observed when comparing the ball and Equator at the initial (P = .330) and final (P = .08) periods. The multilevel mixed-model analysis revealed that the patients' satisfaction was predicted only by their satisfaction with dentures before implant placement. Although no significant difference was found between attachments regarding patient preference, this may be biased by the sequence of attachment use, which suggests that a learning effect might be present in this crossover study design. CONCLUSION: The use of a single midline implant to retain a mandibular overdenture significantly improves patient satisfaction irrespective of the attachment used, but patients' preference for the second treatment suggested a learning effect in this study.

Impact of patient characteristics on edentulous subjects' preferences for prosthodontic rehabilitation with implants.

OBJECTIVE: The aim of this study was to assess the influence of patient characteristics on edentulous subjects' preferences for different prosthodontic treatments with implants. MATERIALS AND METHODS: A cross-sectional study was carried out with 131 edentulous subjects referred for treatment at a university clinic. Participants received detailed information about available treatment options and were asked to rank their preferences among three alternatives for rehabilitation of the maxilla and mandible: conventional dentures (CD), 2-implant-retained overdentures (IOD), or 4-implant fixed dentures (IFD). Individual data and prosthodontic-related variables were assessed through interviews. Oral health-related quality of life impacts was measured using the Brazilian version of the Oral Health Impact Profile for edentulous subjects (OHIP-Edent). Descriptive statistics, bivariate tests, and binary and multinomial logistic regressions were used for data analysis. RESULTS: The majority of participants chose CD as their most preferred treatment for the maxilla (45.8%), while IFD was the most prevalent choice for the mandible (38.9%). Regression analysis showed that the OHIP-Edent "oral pain and dysfunction" (OPD) domain scores were positively associated with IOD preference for the maxilla (OR = 1.31; p = 0.010) and mandible (OR = 1.46; p = 0.002) and with IFD preference for the mandible (OR = 1.20; p = 0.031). Subjects with lower levels of formal education and those with lower income levels were less likely to choose IFD. CONCLUSION: Level of education, income, and perceived quality of life impacts are potentially predictive variables of edentulous patients' preference for rehabilitation with implants. These factors may constitute important aspects to be considered by clinicians when treatment planning for edentulous patients.

Perceptions and experiences of patients following treatment with single-implant mandibular overdentures: A qualitative study.

OBJECTIVE: This study aimed to explore the perceptions and long-term experiences of edentulous patients rehabilitated with single-implant mandibular overdentures (SIMO). METHODS: Thirteen participants, mean age 65.7 years, 69.2% women, who had had their treatment completed for at least 1 year, were invited and included in the study. Focus groups including four to five participants each were conducted, audio and video recorded and transcribed verbatim. Subsequently, the transcripts were analysed according to the principles of thematic analysis. RESULTS: Four major themes emerged as follows: before decision to undergo treatment with SIMO, implant surgery experience, perception of treatment outcomes and impressions about the care received. Lack of information, cost, comorbidities, older age and fear were initial barriers to the decision for treatment. Dissatisfaction with previous treatment and a sense of opportunity motivated the decision. There were ambivalent reports of absence of pain during surgery and discomfort during anaesthesia. Post-surgical recovery exceeded the pre-surgical negative expectations in most cases. There was a tendency for a positive impact of SIMO on the patients' quality of life, comprising improved ability to chew and communicate, dietary diversification, greater comfort and safety, increased self-confidence and social interaction. Few minor inconveniences were reported such as the feeling of insecurity after an episode of denture fracture and the need to use adhesive paste. Satisfaction with the care received and the trust in the dentist and dental team were evident. CONCLUSION: In general, participants presented positive perceptions and rewarding experiences after rehabilitation with SIMO.

Association between severity of illicit drug dependence and quality of life in a psychosocial care center in BRAZIL: cross-sectional study.

BACKGROUND: Quality of life must be one of the main purposes for the treatment of drug users, requiring a better understanding of the association between the quality of life and the severity of dependency. This study aimed to investigate the correlation between severity of substance use in various areas of human functioning and quality of life of illicit drug users in a psychosocial care center for alcohol and drugs. METHODS: This cross-sectional study included 60 participants - illicit drug users - treated at a psychosocial care center for alcohol and drugs. Participants were evaluated with the short version of World Health Organization Quality of Life (WHOQOL-Bref) instrument to measure the quality of life, the 6th version of Addiction Severity Index (ASI-6) to assess the severity of dependence in several areas and the Mini International Neuropsychiatric Interview (MINI) to identify the presence of psychiatric disorders. Pearson and Spearman correlation tests and linear regression were applied to verify the association between the severity of dependence and the quality of life, and Student's t-test to compare the mean quality of life between individuals with and without psychiatric comorbidities. RESULTS: Negative correlation was found between the severity of dependence on the drugs dimensions: alcohol, psychiatric, medical, legal, family/social support and family/social problems of ASI-6, and the quality of life domains measured by the WHOQOL-Bref. The evidence was strongest in the psychiatric and medical dimensions. There was a significant difference in the quality of life mean among participants presenting or not presenting psychiatric comorbidities, for the psychological domain in anxiety disorders, and for the physical and psychological domains in mood disorders. CONCLUSION: The quality of life decreased as the severity of dependence increased, with different results in the various areas of the participant's life. This result emphasizes the need for training the professional team which works in the substance use disorders area for more comprehensive diagnostic evaluations and more appropriate therapeutic interventions for each area. The associations were more evident in the medical and psychiatric fields, indicating the need for greater attention to be paid in relation to medical and psychiatric comorbidities.

Marginal bone level changes and implant stability after loading are not influenced by baseline microstructural bone characteristics: 1-year follow-up.

OBJECTIVE: The aim of this study was to investigate the influence of different bone tissue characteristics of implant sites on changes in marginal bone level and implant stability over time. MATERIAL AND METHODS: One hundred and one implants were inserted in 41 patients. Cortical bone thickness of the alveolar ridge was measured on computed tomography (CT) images. Histomorphometric and microtomographic analyses (microCT) were performed in bone specimens obtained by using a trephine bur, at first drilling. Implant stability quotient (ISQ) measured by resonance frequency analysis (RFA) was registered at implant insertion. Implant stability quotient was measured also at the stages of uncovering, loading and at the 1-year follow-up, when standardized periapical radiographs were taken to measure the marginal bone level (MBL). Descriptive statistics, Spearman's rho correlation and multiple linear regression were used for data analysis (P < 0.05). RESULTS: Comparison between groups of higher and lower values of ISQ changes and between groups of higher and lower values of MBL changes revealed no differences in histomorphometric and microtomographic parameters, according to non-parametric comparison tests, (P > 0.05). Bivariate correlation also showed no association among these microstructural parameters and the outcomes evaluated. There was no correlation between cortical thickness and MBL changes (r = -0.029; P = 0.832) and between cortical thickness and ISQ changes (r = 0.145; P = 0.292). CONCLUSION: Microstructural bone characteristics of implant sites have no effect on changes in marginal bone level and implant stability as measured by RFA. Bone morphology cannot predict implant treatment success over time.

The effect of marginal bone level changes on the stability of dental implants in a short-term evaluation.

OBJECTIVES: To evaluate whether changes in marginal bone level (MBL) around implants, in sites with different bone types, affect the over time implant stability measured by resonance frequency analysis (RFA). MATERIAL AND METHODS: Seventy-eight implants were inserted into jawbones of 32 patients using a two-stage surgical protocol, and implant bone sites were grouped according to the Lekholm and Zarb bone classification. The implant stability quotient (ISQ) was measured by RFA at four time points: implant placement, uncovering, rehabilitation, and at 1-year follow-up after loading. The MBL was measured on periapical radiographs at uncovering and at 1-year follow-up. Percent change in bone level was calculated based on the difference between the implant length and height from the crestal bone level to the implant apex. Descriptive statistics, Pearson's correlation, and repeated-measures ANOVA were used for data analysis. RESULTS: Significant improvement of ISQ was found between implant insertion and uncovering surgery (P < 0.001), while no significant changes were detected throughout the remaining follow-up period. The greatest improvement of ISQ was observed for bone type 4, compared with the other groups (P < 0.001). Percent change in bone level had no effect on longitudinal measures of ISQ (P = 0.337). The ISQ difference between uncovering and 1 year after loading was not correlated with percent change in bone level (r = 0.16; P = 0.157). CONCLUSION: There was increased implant stability after implant placement, but it was not affected by changes in marginal bone level during the first year of loading.

Bone tissue microarchitectural characteristics at dental implant sites part 2: correlation with bone classification and primary stability.

OBJECTIVE: To investigate in vivo the correlation between the bone microarchitecture of implant bone sites, bone tissue classification subjectively assessed in radiographs and primary implant stability. MATERIAL AND METHODS: Periapical and panoramic radiographs were obtained from 32 partially edentulous patients. Three surgeons classified bone quality at implant sites using two different methods: assessments in periapical and panoramic radiographs (PP) and according to the classification proposed by Lekholm and Zarb (L&Z). During the implant insertion, bone biopsies were taken, and three-dimensional parameters were measured by microcomputed tomography (microCT). Insertion torque value (ITV) and initial implant stability quotient (ISQ) were recorded at the moment of the implantation. ISQ was also recorded at the uncovering stage of a traditional implant protocol. RESULTS: Bone types 2 and 3 were the most prevalent classifications according to PP (54.3%) and L&Z (58.7%). The mean and standard deviation values of primary stability variables were 38.7(16.7) for ITV, 75.3 (7.7) for initial ISQ and 79.3 (6.8) for uncovering ISQ. Several microCT original and factor variables were found to correlate with bone tissue classifications and primary stability variables. L&Z correlated with architecture (r = 0.31; P < 0.05), density (r = -0.43; P < 0.01) and bulk (r = -0.35; P < 0.05), whereas ITV correlated with architecture (r = -0.40; P < 0.01) and density (r = 0.51; P < 0.01). Multiple linear regression analysis revealed that density and bulk explained 32% of the variability of L&Z bone classification, while density and architecture explained 42% of the variability of ITV. CONCLUSIONS: This study demonstrates the first step in validating L&Z classification. MicroCT provides objective and detailed quantitative data on bone microarchitecture. Intraosseous implant stability is mainly determined by the density of the bone. ITVs could be a good indicator of primary implant stability, whereas ISQs measurements have some limitations and should not be used alone.

Anaerobic adhesives effect on counter-torque of abutment screws on implants with external hexagon and conical connections: An in vitro study.

BACKGROUND: Abutment screw loosening is a common complication of implant supported prostheses, especially for single crowns. In engineering, anaerobic adhesives (AA) are used to provide chemical locking between screw surfaces, but their application in implantology remains unclear. PURPOSE: The purpose of this article is to evaluate, in vitro, the effect of AA on counter-torque of abutment screws for cemented prosthesis on dental implants with external hexagon connection (EHC) and conical connection (CC). MATERIALS AND METHODS: Sample was composed by 60 specimens, 30 dental implants with EHC and 30 with CC. Abutments (transmucosal 3 mm straight universal abutment) were installed without AA (control group) or with application of AA with two different adhesive strength: medium strength (LOCTITE® 242) and high strength (LOCTITE® 277). The specimens were subjected to mechanical cycling at 37°C, with a load setting of 133 N, a 1.3 Hz frequency, and 1 200 000 cycles. The abutments were removed, and the counter-torque values were registered. Screws and implants were inspected using a stereomicroscope to verify the presence of residual adhesive and damage the internal structures. The data were analyzed using descriptive statistics and comparison tests (p < 0.05). RESULTS: Comparing to the torque of installation, the medium strength AA kept the counter-torque values for CC implants and the high strength AA kept the counter-torque for EHC implants and increased for CC implants. In the intergroup comparisons, control group presented significantly lower counter-torque values than other groups, both for EHC and CC implants. High strength AA presented similar results to medium strength AA in the EHC implants, but in the CC implants presented higher counter-torque values. Damage in threads was more frequent in the groups that received high strength AA. CONCLUSION: The use of AA increased the counter-torque of abutment screws, both in implants with EHC and CC.

Expected and perceived burdens in patients receiving mandibular overdentures retained by one or two implants.

PURPOSE: This study aimed to assess patients' expected burdens before treatment and their perceived burdens after the surgical and prosthodontic procedures of mandibular overdenture treatment and to evaluate factors influencing patients' perceptions. METHODS: Data were collected from 47 participants enrolled in a randomized clinical trial comparing mandibular overdentures retained by one or two implants. A 20-item questionnaire measured on a four-point Likert scale covering the surgical and prosthetic treatment procedures was used to assess the patients' perception of the procedural burdens before (expected burdens) and immediately after (experienced burdens) each procedure. Operators' perceptions of intercurrences associated with the procedures were also assessed as an independent variable. RESULTS: Low levels of perceived burdens were observed both before and after treatment. The mean overall scores of 1.65 ± 0.46 and 1.53 ± 0.33 for expected and experienced burdens, respectively, indicated that most items ranged between "not burdensome at all" and "somewhat burdensome." Significant differences between expected and experienced burdens were found for eight items (P < 0.001). Considering the treatment stages, expected burdens scored higher in the pre-surgical, surgical, and prosthetic stages and lower in the post-surgical phase than experienced burdens. Overall, the experienced burdens were significantly affected by the expected burdens (P < 0.001) and operator's perceived burdens(P = 0.045). CONCLUSIONS: Treatments were associated with low levels of perceived burdens related to surgical and prosthodontic procedures and were highly correlated with the expected burdens before treatment. However, patients tend to overestimate the expected burdens before treatment, especially for surgical procedures.

Grafting biomaterials associated to topical glucocorticoid: effects on pre-osteoblastic cells (MC3T3-E1).

The topical glucocorticoid budesonide has been prescribed before and after sinus lift surgery as adjuvant drug treatment for maxillary sinus membrane inflammation. However, there is no study on the effects of budesonide on the regenerative process of bone grafting biomaterials. We investigated the effect of the association of budesonide with some biomaterials on the growth and differentiation capacity of pre-osteoblastic cells (MC3T3-E1 subclone 4). Xenogeneic (Bio-Oss and Bio-Gen) and synthetic hydroxyapatites (Osteogen, Bonesynth, and HAP-91) were tested in conditioned medium (1% w/v). The conditioned medium was then supplemented with budesonide (0.5% v/v). Cell viability was assessed using the MTT assay (48, 96, and 144 h), and mineralized nodules were quantified after 14 days of culture using the Alizarin Red Staining. Alkaline phosphatase activity was assessed through the release of thymolphthalein at day seven. All biomaterials showed little or no cytotoxicity. The Bio-Gen allowed significantly less growth than the control group regardless of the experimental time. Regarding differentiation potential of MC3T3-E1, the HAP-91-conditioned medium showed remarkable osteoinductive properties. In osteodifferentiation, the addition of budesonide favored the formation of mineral nodules when cells were cultured in medium conditioned with synthetic materials, whereas it weakened the mineralization potential of cells cultured in xenogeneic medium. Regardless of whether budesonide was added or not, Osteogen and Bio-Oss showed higher alkaline phosphatase activity than the other groups. Budesonide may improve bone formation when associated with synthetic biomaterials. Conversely, the presence of this glucocorticoid weakens the mineralization potential of pre-osteoblastic cells cultured with xenogeneic hydroxyapatites.

Adjunctive therapies for in vitro carious lesions: Antimicrobial activity, activation of dentin metalloproteinases and effects on dental pulp cells.

BACKGROUND: Adjunctive therapies used before dental restorative procedures may encourage carious tissue removal. Beyond promising antimicrobial properties, treatments could positively modulate the dentin-pulp complex while not interfering with restoration survival. Herein, we evaluated a set of substances and their effects on carious lesions and the underlying dentin or pulp cells. METHODS: Artificial caries lesions were developed in bovine teeth cavities immersed in Streptococcus mutans and Lactobacillus casei co-cultures. The cavities were treated according to the following groups: Phosphate Buffer Saline (PBS), Chlorhexidine (CHX), Papacárie® (Papain gel), Ozone (O3), and antimicrobial Photodynamic Therapy (aPDT). After treatments, samples were cultivated to count isolated microbial colonies. The zymography assay evaluated the activity of dentin metalloproteinases (MMP-2 and MMP-9). Cell viability was indirectly assessed on human dental pulp cells after 24, 72, or 120 h, whereas the odontodifferentiation potential was evaluated after ten days of cell culture. RESULTS: CHX and aPDT led to around 1 log bacterial load reduction. PBS, CHX, and aPDT showed the eventual expression of MMP-2 and MMP-9. Cell viability was reduced (< 30%) after 120 h for all groups compared to the control. CHX, O3, and aPDT induced greater odontodifferentiation (≈ 20% higher) than PBS and papain gel. CONCLUSION: Adjunctive therapies presented little or no biological significance in reducing bacterial load in artificial carious lesions. Although the activation of endogenous metalloproteinases may represent a possible concern for adhesive restorations, some of these treatments may have a positive role in dental pulp tissue repair.

Prevalence of comorbid substance use disorders with anxiety disorders or post-traumatic stress disorder in people seeking treatment for substance abuse: a systematic review protocol.

OBJECTIVE: This systematic review will aim to assess evidence of the prevalence of comorbid substance use disorders with anxiety disorders or post-traumatic stress disorder in people seeking treatment for substance use. INTRODUCTION: Research shows that anxiety disorders and post-traumatic stress disorder are highly prevalent in people with substance use disorders and can worsen the treatment outcomes, increasing the risk of relapse and poor adherence. However, evidence from systematic reviews on the prevalence of these comorbidities in substance use treatment settings is limited. INCLUSION CRITERIA: Participants will be people seeking treatment for substance use. Studies will be included if they have investigated the prevalence of the comorbid substance use disorders with anxiety disorders or post-traumatic stress disorder in treatment settings. METHODS: Primary studies will be screened from the databases MEDLINE, PsycINFO, CINAHL, and Embase, and from searches to source gray literature. Eligible cross-sectional and cohort studies published after 1994 with no language limits will be retrieved, and their methodological quality will be assessed. Data extraction will include study details, methods, and outcomes. Results will be described by narrative summary or, if studies are sufficiently similar, a meta-analysis will be performed. Prevalence data will be pooled for meta-analysis by a random effects model. The results will be presented graphically in a forest plot. Data heterogeneity will be statistically tested using χ2 and I2 tests. If substantial heterogeneity is detected, sources of heterogeneity will be explored by subgroup analysis and meta-regression, and results will be presented by a narrative summary. SYSTEMATIC REVIEW REGISTRATION NUMBER: PROSPERO CRD42020149956.

Corrigendum to "Nitazoxanide superiority to placebo to treat moderate COVID-19 - A Pilot prove of concept randomized double-blind clinical trial." [EClinicalMedicine 37 (2021) 100981].

[This corrects the article DOI: 10.1016/j.eclinm.2021.100981.].

Nitazoxanide superiority to placebo to treat moderate COVID-19 - A Pilot prove of concept randomized double-blind clinical trial.

BACKGROUND: The absence of specific antivirals to treat COVID-19 leads to the repositioning of candidates' drugs. Nitazoxanide (NTZ) has a broad antiviral effect. METHODS: This was a randomized, double-blind pilot clinical trial comparing NTZ 600 mg BID versus Placebo for seven days among 50 individuals (25 each arm) with SARS-COV-2 RT-PCR+ (PCR) that were hospitalized with mild respiratory insufficiency from May 20th, 2020, to September 21st, 2020 (ClinicalTrials.gov NCT04348409). Clinical and virologic endpoints and inflammatory biomarkers were evaluated. A five-point scale for disease severity (SSD) was used. FINDINGS: Two patients died in the NTZ arm compared to 6 in the placebo arm (p = 0.564). NTZ was superior to placebo when considering SSD (p < 0001), the mean time for hospital discharge (6.6 vs. 14 days, p = 0.021), and negative PCR at day 21 (p = 0.035), whereas the placebo group presented more adverse events (p = 0.04). Among adverse events likely related to the study drug, 14 were detected in the NTZ group and 22 in placebo (p = 0.24). Among the 30 adverse events unlikely related, 21 occurred in the placebo group (p = 0.04). A decrease from baseline was higher in the NTZ group for d-Dimer (p = 0.001), US-RCP (p < 0.002), TNF (p < 0.038), IL-6 (p < 0.001), IL-8 (p = 0.014), HLA DR. on CD4+ T lymphocytes (p < 0.05), CD38 in CD4+ and CD8+ T (both p < 0.05), and CD38 and HLA-DR. on CD4+ (p < 0.01). INTERPRETATION: Compared to placebo in clinical and virologic outcomes and improvement of inflammatory outcomes, the superiority of NTZ warrants further investigation of this drug for moderate COVID-19 in larger clinical trials. A higher incidence of adverse events in the placebo arm might be attributed to COVID-19 related symptoms.

Análise da tendência da mortalidade por causas externas em pessoas idosas no Brasil, 2000 a 2022 / Analysis of the trend of mortality from external causes in older adults in Brazil, 2000 to 2022

Resumo Objetivo analisar a tendência de mortalidade por causas externas em pessoas idosas no Brasil no intervalo temporal entre os anos 2000 e 2022 e identificar o perfil sociodemográfico de mortalidade. Método estudo ecológico de série temporal utilizando dados secundários, envolvendo a mortalidade em pessoas idosas por causas externas no Brasil, no período de 2000 a 2022. Os dados foram coletados a partir das bases de dados do Departamento de Informática do Sistema Único de Saúde, das estimativas da população residente e de dados populacionais censitários disponibilizados pelo Instituto Brasileiro de Geografia e Estatística. A frequência absoluta e relativa dos dados foi analisada a partir do software Excel 2010. As análises das tendências das taxas de mortalidade e regressão linear segmentada foram realizadas por meio do Joinpoint, com significância estatística avaliada por meio do teste de Monte Carl Resultados No período investigado, foram identificados 572.608 óbitos por causas externas em pessoas idosas com 60 anos ou mais. Em relação ao comportamento da mortalidade por causas externas em pessoas idosas, observou-se tendência de aumento nas taxas de mortalidade na maior parte do período estudado (2000 a 2013) com uma variação percentual anual (VPA: 1,86; IC95%: 1,5-2,2). Conclusão os resultados indicam uma tendência de crescimento da mortalidade de pessoas idosas por causas externas, refletindo a necessidade de priorização de políticas públicas que intervenham sobre esse evento.

Abstract Objective To analyze the trend of mortality due to external causes in older adults in Brazil within the temporal interval spanning from 2000 to 2022 and to identify the sociodemographic profile of mortality. Method Ecological time-series study utilizing secondary data, encompassing mortality in older adults due to external causes in Brazil, spanning the period from 2000 to 2022. The data were collected from the databases of the Department of Informatics of the Unified Health System, population estimates, and census population data provided by the Brazilian Institute of Geography and Statistics. The absolute and relative frequency of the data were analyzed using Microsoft Excel 2010 software. The analysis of trends in mortality rates and segmented linear regression was conducted using Joinpoint, with statistical significance assessed through the Monte Carlo test. Results During the investigated period, 572,608 deaths due to external causes were identified in individuals aged 60 years or older. Regarding the mortality pattern due to external causes in older adults, an increasing trend in mortality rates was observed for the majority of the studied period (2000 to 2013) with an annual percent change (APC) of 1.86 (95% CI: 1.5-2.2). Conclusion The results indicate a growing trend in mortality among older individuals due to external causes, highlighting the need for prioritizing public policies that address this issue.

Potential impact of the antirheumatic agent auranofin on proviral HIV-1 DNA in individuals under intensified antiretroviral therapy: Results from a randomised clinical trial.

Antiretroviral therapy (ART) is typically composed of a combination of three antiretroviral drugs and is the treatment of choice for people with human immunodeficiency virus type 1/acquired immune deficiency syndrome (HIV-1/AIDS). However, it is unable to impact on viral reservoirs, which harbour latent HIV-1 genomes that are able to reignite the infection upon treatment suspension. The aim of this study was to provide an estimate of the safety of the disease-modifying antirheumatic agent auranofin and its impact on the HIV-1 reservoir in humans under intensified ART. For this purpose, an interim analysis was conducted of three of the six arms of the NCT02961829 clinical trial (five patients each) with: no intervention, i.e. continuation of first-line ART; intensified ART (ART + dolutegravir and maraviroc); and intensified ART plus auranofin. Auranofin treatment was found to be well tolerated. No major adverse events were detected apart from a transient decrease in CD4+ T-cell counts at Weeks 8 and 12. Auranofin decreased total viral DNA in peripheral blood mononuclear cells compared with ART-only regimens at Week 20 (P = 0.036) and induced a decrease in integrated viral DNA as quantified by Alu PCR. Despite the limited number of patient-derived sequences available in this study, phylogenetic analyses of nef sequences support the idea that auranofin may impact on the viral reservoir. [ClinicalTrials.gov ID: NCT02961829].