Neutrophil extracellular traps in rheumatoid arthritis and periodontitis: Contribution of PADI4 gene polymorphisms.

AIM: We sought to investigate the release of neutrophil extracellular traps (NETs) in neutrophils from individuals with rheumatoid arthritis (RA) and controls and compare the presence of NETs in gingival tissues according to periodontal status. Also, the association between single nucleotide polymorphisms (SNPs) of the peptidyl arginine deaminase type 4 (PADI4) gene and the GTG haplotype with RA, periodontitis and NETs was evaluated in vitro. MATERIALS AND METHODS: Peripheral neutrophils were isolated by density gradient, and NET concentration was determined by the PicoGreen method. Immunofluorescence was studied to identify NETs by co-localization of myeloperoxidase (MPO)-citrullinated histone H3 (H3Cit). Genotyping for SNPs (PADI4_89; PADI4_90; PADI4_92; and PADI4_104) was performed in 87 individuals with RA and 111 controls. RESULTS: The release of NETs in vitro was significantly higher in individuals with RA and periodontitis and when stimulated with Porphyromonas gingivalis. Gingival tissues from subjects with RA and periodontitis revealed increased numbers of MPO-H3Cit-positive cells. Individuals with the GTG haplotype showed a higher release of NETs in vitro and worse periodontal parameters. CONCLUSIONS: The release of NETs by circulating neutrophils is associated with RA and periodontitis and is influenced by the presence of the GTG haplotype.

Preemptive effects of etoricoxib, acetaminophen, nimesulide, and ibuprofen on postoperative pain management after single-implant surgery: A randomized clinical trial.

BACKGROUND: There is insufficient evidence for pain control in preemptive analgesia (PA) after dental implant surgery, signaling the need for further studies. The objective of this study was to evaluate the efficacy of PA in single dental implant surgeries (SDIS), seeking to identify among the etoricoxib (ETOR), ibuprofen (IBU), nimesulide (NIME), and acetaminophen (ACETA)], which one has the higher efficacy effectiveness in relieving postoperative pain and reducing the use of rescue medication compared to placebo. METHODS: In this triple-blind, parallel, randomized controlled clinical trial, 135 individuals with a mean age of 57.6 years (±11.7), both genders, were randomly divided into five groups according to the test drug: I-PLACEBO; II-IBU (600 mg); III-NIME (100 mg); IV-ACETA (750 mg); and V-ETOR (90 mg). The occurrence, duration, and intensity of pain were analyzed using the Chi-square, Fisher's exact and ANOVA tests, and the generalized estimating equation models, when appropriate. RESULTS: Test drugs provided a reduction in postoperative pain scores and lower use of rescue medication when compared to placebo. The ETOR group presented significantly lower pain scores, when compared to other active treatments. The IBU group showed the highest mean number of rescue medication used. CONCLUSIONS: All test drugs provided a beneficial preemptive effect demonstrated by the reduced postoperative pain and reduced use of rescue medication. The ETOR group presented lower pain scores, and the IBU group showed the highest mean number of rescue medication used among the test groups.

Retrieval of HCV patients lost to follow-up as a strategy for Hepatitis C Microelimination: results of a Brazilian multicentre study.

BACKGROUND: Several HCV patients in Brazil were lost to follow-up (LTFU) in the last two decades before achievement of sustained virological response (SVR). Strategies to recall those diagnosed but untreated patients have been used elsewhere with different success rates. AIM: To identify and retrieve LTFU patients in order to offer them the treatment with the current highly effective direct acting antiviral agents (DAAs). METHODS: Registries ofall HCV patients from three large reference centers in Brazil were retrospectively reviewed to identify those with no registry of SVR. Reasons for non-achievement of SVR were elicited in HCV-RNA + patients. All patients who were not treated or cured were contacted to offer the therapy with DAAs. RESULTS: 10,289 HCV patients (50% males, mean age 52 ± 11 years) were identified. Only 4,293 (41.7%) had been successfully treated previously. From the remaining 5,996 most were LTFU (59%), were not treated for other reasons (14.7%) or were non-responders (26.3%). After revision of the charts 3,559 were considered eligible to be retrieved. The callback success of phone calls was 18%, 13% to cellphone messages (SMS or WhatsApp) and 7% to regular mail. Five-hundred sixty patients had been already treatedor were on treatment and 234 were reported to be dead or transplanted. Finally, 201 had made an appointment and initiated antiviral treatment. CONCLUSION: Even considering the low callback rate, retrieval of LTFU patients was shown to be an important strategy forhepatitis C micro-elimination in Brazil.

Adjunctive effects of photodynamic therapy using indocyanine green in residual pockets during periodontal maintenance therapy: A split-mouth randomized controlled trial.

BACKGROUND: Prospective studies have reported conflicting results regarding the adjunctive effect of antimicrobial photodynamic therapy (aPDT) on clinical and microbiological parameters in individuals under periodontal maintenance therapy (PMT). This study aimed to evaluate the clinical and microbiological adjunctive effects of aPDT using indocyanine green (ICG) in residual sites with probing depth (PD) ≥5 mm during PMT in comparison with scaling and root planing (SRP) alone. METHODS: A split-mouth randomized controlled clinical trial was conducted with 24 individuals in a PMT program. Contralateral quadrants with eligible residual sites were randomly assigned to either SRP + aPDT (test group) or SRP alone (control). aPDT included ICG dye and diode laser (909 nm) performed together with SRP and repeated 15 days after. Periodontal clinical parameters, periodontal inflamed surface area (PISA) index, and subgingival biofilm samples were collected at baseline (T1), 3 (T2), and 6 months later (T3). Microbiological analyses were performed by quantitative real-time polymerase chain reaction. RESULTS: Significant improvements were observed in all clinical and microbiological parameters in both groups from T1 to T3. However, no significant differences were observed regarding plaque index, PD, and clinical attachment level. Test group showed significantly greater reductions in bleeding on probing (BOP), PISA index, and Porphyromonas gingivalis and Aggregatibacter actinomycetemcomitans levels, when compared with controls. CONCLUSIONS: Both treatments resulted in significant clinical periodontal improvements, but with no significant differences between groups except from inflammation parameters. aPDT using ICG resulted in significant reductions in BOP and PISA index, as well as in P. gingivalis and A. actinomycetemcomitans levels.

Natural History of Hepatosplenic Schistosomiasis (HSS) Non-Cirrhotic Portal Hypertension (NCPH): Influence of Gastrointestinal Bleeding and Decompensation in Prognosis.

BACKGROUND: Hepatosplenic schistosomiasis (HSS) is a peculiar form of non-cirrhotic portal hypertension (NCPH). Although HSS patients present normal hepatic function, some evolve signs of hepatocellular failure and features of decompensated cirrhosis. The natural history of HSS-NCPH is unknown. METHODS: A retrospective study was conducted that evaluated patients who fulfilled clinical-laboratorial criteria for HSS. RESULTS: A total of 105 patients were included. Eleven patients already presented with decompensated disease and had lower transplant-free survival at 5 years than those without (61% vs. 95%, p = 0.015). Among 94 patients without prior decompensation, the median follow-up was 62 months and 44% of them had varicose bleeding (two or more episodes in 27%). Twenty-one patients presented at least one episode of decompensation (10-year probability 38%). Upon multivariate analysis, varicose bleeding and higher bilirubin levels were associated with decompensation. The 10-year probability of survival was 87%. Development of decompensation and age were predictive of mortality. CONCLUSION: HSS is characterized by multiple episodes of GI bleeding, a high probability of decompensation and reduced survival at the end of the first decade. Decompensation is more common in patients with varicose esophageal bleeding and is associated with lower survival.

Validation of the Baveno VI criteria to rule out high-risk varices using hepatic shear-wave elastography.

INTRODUCTION AND OBJECTIVES: Liver stiffness measurement (LSM) by transient elastography has been validated to predict high-risk varices (HRV). We aimed to evaluate the accuracy of shear-wave elastography (SWE) and platelet count (Baveno VI criteria) to rule out HRV in patients with compensated advanced chronic liver disease (c-ACLD). METHODS: This retrospective study analyzed data of patients with c-ACLD (transient elastography ≥ 10 kPa) submitted to two-dimensional SWE (2D-SWE) (GE-LOGIQ-S8) and/or point SWE (p-SWE) (ElastPQ) who had a gastrointestinal endoscopy within 24 months. HRV definition was a large size and presence of red wale marks or sequelae from previous treatment. Optimal thresholds of SWE systems for HRV were identified. The proportion of spared gastrointestinal endoscopies and missing HRV considering a favorable SWE Baveno VI criteria were assessed. RESULTS: Eighty patients [36% male, median age = 63 (interquartile range, 57-69) years] were included. The prevalence of HRV was 34% ( n  = 27/80). The optimal thresholds to predict HRV were 10 kPa and 12 kPa for 2D-SWE and p-SWE, respectively. A favorable 2D-SWE Baveno VI criteria (LSM < 10 kPa and platelets count > 150 × 10 9 /mm 3 ) avoided 19% of gastrointestinal endoscopies without missing HRVs. A favorable p-SWE Baveno VI criteria (LSM < 12 kPa and platelets count > 150 × 10 9 /mm 3 ) spared 20% of gastrointestinal endoscopy without missing HRVs. Using a lower threshold of platelet count (<110 × 10 9 /mm 3 , expanded Baveno VI), 2D-SWE (<10 kPa) avoided 33% of gastrointestinal endoscopy with 8% of missing HRVs, while p-SWE (<12 kPa) avoided 36% of gastrointestinal endoscopy with 5% of missing HRVs. CONCLUSION: LSM by p-SWE or 2D-SWE combined with platelet count (Baveno VI criteria) can spare a considerable number of gastrointestinal endoscopies missing a negligible proportion of HRV.

Accuracy and concordance of two-dimensional shear-wave elastography using transient elastography as the reference in chronic viral hepatitis and HIV infection in Rio de Janeiro, Brazil.

OBJECTIVES: Evaluate the accuracy and agreement of two-dimensional shear-wave elastography (2D-SWE) LOGIQ-S8 with transient elastography in patients from Rio de Janeiro, Brazil. METHOD: This retrospective study compared liver stiffness measurements (LSMs) using transient elastography (M and XL probes) and 2D-SWE GE-LOGIQ-S8 performed by a single experienced operator on the same day in 348 consecutive individuals with viral hepatitis or HIV infection. Suggestive and highly suggestive compensated-advanced chronic liver disease (c-ACLD) were defined by transient elastography-LSM ≥10 kPa and ≥15 kPa, respectively. Agreement between techniques and accuracy of 2D-SWE using transient elastography-M probe as the reference was assessed. Optimal cut-offs for 2D-SWE were identified using the maximal Youden index. RESULTS: Three hundred five patients [61.3% male, median age = 51 [interquartile range (IQR), 42-62] years, 24% with hepatitis C virus (HCV) ± HIV; 17% with hepatitis B virus (HBV) ± HIV; 31% were HIV mono-infected and 28% had HCV ± HIV post-sustained virological response] were included. The overall correlation (Spearman's ρ ) was moderate between 2D-SWE and transient elastography-M ( ρ = 0.639) and weak between 2D-SWE and transient elastography-XL ( ρ = 0.566). Agreements were strong ( ρ > 0.800) in people with HCV or HBV mono-infection, and poor in HIV mono-infected ( ρ > 0.400). Accuracy of 2D-SWE for transient elastography-M ≥ 10 kPa [area under the receiver operating characteristic (AUROC) = 0.91 (95% confidence interval [CI], 0.86-0.96); optimal cut-off = 6.4 kPa, sensitivity = 84% (95% CI, 72-92), specificity = 89% (95% CI, 84-92)] and for transient elastography-M ≥ 15 kPa [AUROC = 0.93 (95% CI, 0.88-0.98); optimal cut-off = 7.1 kPa; sensitivity = 91% (95% CI, 75-98), specificity = 89% (95% CI, 85-93)] were excellent. CONCLUSION: 2D-SWE LOGIQ-S8 system had a good agreement with transient elastography and an excellent accuracy to identify individuals at high risk for c-ACLD.

Long-term impact of patients' compliance to peri-implant maintenance therapy on the incidence of peri-implant diseases: An 11-year prospective follow-up clinical study.

OBJECTIVE: To prospectively evaluate the incidence of peri-implant diseases and the associated risk factors during 11 years of peri-implant maintenance therapy (PIMT). MATERIAL AND METHODS: A sample of 80 partially edentulous individuals rehabilitated with dental implants was invited to participate in a PIMT program (T1-prior to entering the PIMT program). After 11 years, 51 individuals remained regularly or irregularly adherent to PIMT (T2-last recall after 11 years) and were classified as regular (RC; n = 27) or irregular (IC; n = 24) compliers. Data of interest were analyzed using univariate and multivariate logistic regression analyses. RESULTS: The incidence of peri-implant mucositis and peri-implantitis observed at T2 in the IC group (70.8% and 37.5%, respectively) were significantly higher than those observed in the RC group (37.0% and 11.1%, respectively). The incidence of peri-implant diseases was mostly attributable to potentially modifiable risk factors, as such: RC group-PM (p = 0.013); IC group-high plaque index (p < 0.001), irregular compliance (p < 0.001), the presence of PM (p = 0.015) and periodontitis (p < 0.039). CONCLUSION: Regular compliance during PIMT had a strong effect in minimizing the incidence of peri-implant diseases. Increasing regular dental visits and improving oral hygiene would provide benefits for preventing peri-implant diseases.

Effect of supragingival plaque control on recurrent periodontitis and clinical stability among individuals under periodontal maintenance therapy: 10-year follow-up.

BACKGROUND: The aim of this study was to evaluate the effect of supragingival plaque control on the recurrence of periodontitis (RP) and the achievement of a stable periodontal clinical endpoint after 10 years of periodontal maintenance therapy (PMT). METHODS: The present retrospective cohort study included 225 individuals in continuous PMT. The plaque index (PI) determining the oral hygiene (OH) status, periodontal clinical parameters, and other variables of interest were collected at three time points: T1 (prior to active periodontal therapy [APT]), T2 (after APT), and T3 (10 years after T2). According to PI records at T3, participants were categorized into: (1) good OH (GOH; PI ≤ 30%, n = 63); (2) fair OH (FOH; PI > 30% and ≤40%, n = 73); and (3) poor OH (POH; PI > 40%, n = 88). Data were analyzed using the chi-square and Student t tests, analysis of variance (ANOVA), and mediation and regression analyses. RESULTS: Significant differences in all periodontal clinical parameters between the GOH, FOH, and POH groups were observed at T3. The POH group exhibited higher mean bleeding on probing (BOP), periodontal probing depth (PD), and clinical attachment level (CAL), as well as higher tooth loss (POH > FOH > GOH; P < .001). There was an increased risk for RP in the FOH (odds ratio [OR] 2.02; CI, 1.10-4.38) and POH (OR 4.33; CI, 2.17-8.65) groups. Moreover, the FOH and POH groups had an approximately 2.5 and 6.0 times greater chance of not achieving a stable periodontal clinical endpoint, respectively. CONCLUSIONS: After 10 years of monitoring in PMT, individuals with higher PI scores (>30%) presented an unhealthier periodontal status, a higher risk for RP, and a lower chance of achieving ≤4 sites with PD ≥ 5 mm.

National Brazilian survey on the outcomes of hepatitis c retreatment in patients non-responders to direct antiviral agents.

BACKGROUND AND AIMS: Treatment of hepatitis C with direct antiviral agents (DAA) is associated with almost 95% of sustained virological response. However, some patients need retreatment. In Brazil, it should be done according to the Ministry of Health guidelines, frequently updated to include newly available drugs. This study aimed to conduct a national survey about the characteristics and outcomes of retreatment of hepatitis C in previously non-responders to DAAs. PATIENTS AND METHODS: Institutions from all over the country were invited to participate in a national registry for retreatment, including information about clinical and epidemiological characteristics of the patients, type and outcomes of retreatment regimens. Only patients previously treated with interferon-free regimens were included. RESULTS: As previous treatments the distribution was: SOF/DCV (56%), SOF/SIM (22%), 3D (11%), SOF/LED (6%) and SOF/RBV (5%). For retreatment the most frequently used drugs were SOF/GP (46%), SOF/DCV (23%) and SOF/VEL (11%). From 159 patients retreated, 132/159 (83%) had complete information in the registry and among them only seven patients were non-responders (SVR of 94.6%). All retreatments were well tolerated, without any serious adverse events or interruptions. CONCLUSION: The retreatment of patients previously non-responders to DAAs was associated with high rate of SVR in this sample of Brazilian patients. This finding allows us to conclude that the retreatment options available in the public health system in Brazil are effective and safe and are an important component of the strategy of elimination of hepatitis C in our country.

Association between cumulative smoking exposure, span since smoking cessation, and peri-implantitis: a cross-sectional study.

OBJECTIVES: To investigate the association of cumulative smoking exposure and span since smoking cessation with the occurrence of peri-implantitis. METHODS: A sample of 350 individuals aged ≥ 35 years, with the presence of at least one osseointegrated implant functioning for > 5 years, were enrolled in the study. According to smoking habits, participants were categorized into 3 groups: non-smokers (NS; n = 212), former smokers (FC; n = 66), and current smokers (CS; n = 72). Complete peri-implant and periodontal examinations were evaluated. Associations between the occurrence of peri-implantitis and smoking habits, as well as potential confounders, were evaluated through univariate and multivariate analyses. RESULTS: The occurrence of peri-implantitis in the NS, FS, and CS groups was 18.2%, 19.7%, and 30.5%, respectively. A high prevalence of the overall number of cases with periodontitis (54.2%) was observed in the CS group when compared to the FS and NS groups. After adjusting for confounders, the odds ratio (OR) for the occurrence of peri-implantitis was 2.63 (1.39-6.77; p < 0.001) for CS compared to NS. There was a significant dose-response relationship between pack/year of smoking and the occurrence of peri-implantitis, as well as a significant decrease in the risk as the years of smoking cessation increased. CONCLUSIONS: The occurrence of peri-implantitis among CS was high. The cumulative smoking exposure in an incremental manner and the shorter smoking cessation span was directly associated with a higher risk for peri-implantitis. CLINICAL RELEVANCE: Educational and preventive strategies in general health services must attempt to reduce the adverse effects of cumulative smoking exposure and to explore the beneficial effects of smoking cessation on peri-implant status.

The loss of molars in supportive periodontal care: A 10-year follow-up for tooth- and patient-related factors.

AIM: To determine the impact of the degree of furcation involvement (FI) on the longevity of molar teeth and assess the risk variables (tooth- and patient-related factors) associated with the loss of molars (LM) in individuals treated for periodontitis and monitored in a private programme of supportive periodontal care (SPC). MATERIALS AND METHODS: The present retrospective cohort study included 222 individuals with 1329 molars under a 10-year monitoring period in SPC. Periodontal clinical parameters, FI, the type of molar, pulp vitality, and other variables of interest were collected at approximately 50 days after active periodontal therapy and after 10 years. The association of tooth- and patient-related factors with LM was assessed using a multilevel Cox regression analysis. RESULTS: Two-hundred and thirty-five molars were extracted during the SPC period of 12.4 ± 1.9 years. Age >50 years, male gender, diabetes, smoking, and non-compliance were identified as relevant patient-related factors for LM during SPC (p < .05). Significant tooth-related factors for LM were bleeding on probing (BoP) and probing depth (PD) ≥5 mm, tooth non-vitality, and class II and III FI (p < .05). CONCLUSIONS: Class III FI, tooth non-vitality, higher mean PD and BoP, age, male gender, diabetes, and smoking all strongly influenced the prognosis of molars during SPC.

Association between liver cirrhosis and peri-implant diseases: a case-control study on implant- and patient-related risk factors.

OBJECTIVE: The objective of this study was to evaluate the potential association between liver cirrhosis and peri-implant diseases, as well as the influence of different risk indicators on this association. METHODS: This case-control study included 64 cases with liver cirrhosis and 128 controls without liver diseases that presented the same socio-demographic and economic profile. The specific inclusion criteria were the following: aged group of 35-55 years and presenting at least one osseointegrated implant functioning for >5 years. A full-mouth peri-implant and periodontal examination was performed and risk variables were recorded. The association between risk variables and the occurrence of peri-implant diseases was tested through univariate analysis and multivariate logistic regression, stratified by alcohol status. Additionally, a mediation analysis was performed to examine the mediating effect of age with peri-implantitis. RESULTS: A high prevalence of peri-implantitis (29.7%) was observed among cases when compared to controls (18.0%). Individuals with cirrhosis presented ~2.5 higher chance of having peri-implantitis than controls (p<0.001). Significant variables associated with the occurrence of peri-implantitis in the final logistic model were the following: cirrhosis, alcohol use, age (>55 years), male sex, smoking, periodontitis, and number of ≤14. CONCLUSIONS: An important risk association between liver cirrhosis and peri-implantitis was reported. Future studies with a larger sample size controlling for the patient- and implant-related confounders are needed to better understand the link between peri-implantitis and liver cirrhosis. CLINICAL RELEVANCE: Cirrhosis individuals, age, and periodontitis, as well as alcohol use and smoking interaction, should be considered as potential risk indicators for peri-implantitis.

Noninvasive predictors of esophageal varices in patients with hepatosplenic schistosomiasis mansoni.

BACKGROUND: No previous study have evaluated transient elastography for predicting esophageal varices in hepatosplenic schistosomiasis. AIM: To investigate noninvasive methods of predicting esophageal varices in patients with hepatosplenic schistosomiasis mansoni. METHODS: Cross-sectional multicentric study included 51 patients with hepatosplenic schistosomiasis. Patients underwent ultrasonography-dopplerfluxometry, upper endoscopy, complete blood cell count and transient elastography (Fibroscan®) for liver and spleen stiffness measurement (LSM and SSM). Noninvasive scores previously established for cirrhotic population were studied: platelet count to spleen diameter ratio (PSR), LSM-spleen diameter to platelet ratio score (LSPS) and varices risk score (VRS). We proposed a version of LSPS and VRS by replacing LSM with SSM and named them SSPS and modified-VRS, respectively. RESULTS: Esophageal varices were detected in 42 (82.4%) subjects. Individuals with varices presented higher SSM (73.5 vs 36.3 Kpa, p = 0.001), splenic vein diameter (10.8 vs 8.0 mm, p = 0.017), SSPS (18.7 vs 6.7, p = 0.003) and modified-VRS (4.0 vs 1.4, p = 0.013), besides lower PSR (332 vs 542, p = 0.038), than those without varices. SSPS was independently associated with varices presence (OR=1.19, 95%CI 1.03-1.37, p = 0.020) after multivariate analysis. In a model excluding noninvasive scores, SSM was independently associated with varices diagnosis (OR=1.09, 95%CI 1.03-1.16, p = 0.004). AUROC was 0.856 (95%CI 0.752-0.961, p = 0.001) for SSM and 0.816 (95%CI 0.699-0.932, p = 0.003) for SSPS (p = 0.551). CONCLUSIONS: Spleen-related variables were predictors of esophageal varices: SSM, splenic vein diameter, SSPS, modified-VRS and PSR. Multivariate models indicated that SSM and SSPS are useful tools for predicting varices in non-cirrhotic portal hypertension by hepatosplenic schistosomiasis and may be used in clinical practice.

National Brazilian survey on the outcomes of hepatitis c retreatment in patients non-responders to direct antiviral agents

ABSTRACT Background and aims: Treatment of hepatitis C with direct antiviral agents (DAA) is associated with almost 95% of sustained virological response. However, some patients need retreatment. In Brazil, it should be done according to the Ministry of Health guidelines, frequently updated to include newly available drugs. This study aimed to conduct a national survey about the characteristics and outcomes of retreatment of hepatitis C in previously non-responders to DAAs. Patients and methods: Institutions from all over the country were invited to participate in a national registry for retreatment, including information about clinical and epidemiological characteristics of the patients, type and outcomes of retreatment regimens. Only patients previously treated with interferon-free regimens were included. Results: As previous treatments the distribution was: SOF/DCV (56%), SOF/SIM (22%), 3D (11%), SOF/LED (6%) and SOF/RBV (5%). For retreatment the most frequently used drugs were SOF/GP (46%), SOF/DCV (23%) and SOF/VEL (11%). From 159 patients retreated, 132/159 (83%) had complete information in the registry and among them only seven patients were non-responders (SVR of 94.6%). All retreatments were well tolerated, without any serious adverse events or interruptions. Conclusion: The retreatment of patients previously non-responders to DAAs was associated with high rate of SVR in this sample of Brazilian patients. This finding allows us to conclude that the retreatment options available in the public health system in Brazil are effective and safe and are an important component of the strategy of elimination of hepatitis C in our country.

Analgesia preemptiva em cirurgias de implantes dentais: (i) revisão sistemática e meta-análise; (ii) ensaio clínico triplo-cego, paralelo, randomizado e controlado por placebo / Preemptive analgesia in dental implant surgery: (i) systematic review and meta analysis; (ii) triple-blind, parallel, randomized and placebo-controlled clinical trial

Não existem evidências suficientes, para recomendar um regime analgésico específico, para o controle da dor em analgesia preemptiva, após cirurgia de implante dentário. Isto sinaliza a necessidade de estudos adicionais. Esta pesquisa apresenta dois estudos com objetivos distintos: (1) avaliar a eficácia da analgesia preemptiva em cirurgias de implantes dentais por meio de uma revisão sistemática e meta-análise de ensaios clínicos randomizados. (2) avaliar e comparar por meio de um ensaio clínico randomizado (ECR), paralelo, controlado por placebo, a efetividade da analgesia preemptiva em cirurgias de implantes dentais unitários, buscando identificar dentre os analgésicos e anti-inflamatórios não esteroidais (AINES) [eterocoxibe (ETERO), ibuprofeno (IBU), nimesulida (NIME) e acetaminofeno (ACETA)], qual possui maior eficácia no alívio da dor pós-operatória e na redução do uso da medicação de resgate comparados ao uso do placebo. Esta revisão sistemática com meta-análise seguiu as diretrizes PRISMA e foi registrada no PROSPERO (CRD42020168757). Cinco estudos foram incluídos na revisão e quatro foram incorporados à meta-análise. Uma meta-análise de efeito randômico comparou a eficácia da medicação preventiva em comparação ao placebo. Para a interpretação dos resultados utlizamos a certeza da evidência usando a abordagem Grading of Recommendations, Assessment, Development and Evaluation (GRADE) e a magnitude do efeito, de acordo com as diretrizes do GRADE. Todos os estudos demonstraram que a medicação preemptiva contribuiu para uma melhora significativa da dor pós-operatória. No entanto, o desvio médio padrão (DMP) geral agrupado mostrou, que, a medicação preventiva teve um efeito pequeno em comparação com o placebo, na redução da dor (DMP: -0,43; IC: -0,71; -0,15), com baixa certeza da evidência. Essa metanálise mostrou que a magnitude do efeito foi maior seis a oito horas após a cirurgia (efeito grande), comparada ao tempo de uma a duas horas, após a cirurgia (efeito pequeno). Concluiu-se que a analgesia preventiva pode ter um efeito positivo na redução da dor em comparação ao não uso de medicação preemptiva. No entanto, as evidências são ainda insuficientes. O ECR com inserção de implante dental unitário envolveu 135 indivíduos, com média de idade de 57,1 (±11,2), de ambos os gêneros alocados em 5 grupos (ETERO, IBU, NIME, ACETA e placebo). A ocorrência, tempo e a intensidade da dor foram analisados por meio testes de teste Qui-quadrado, Exato de Fisher, ANOVA e modelos de equações de estimativas generalizadas quando adequados. Todos os medicamentos testados proporcionaram um efeito benéfico da analgesia preemptiva. Isso foi demonstrado pela redução da dor pós-operatória e do menor uso de medicação de resgaste. O grupo IBU apresentou significativamente maiores escores de dor que os outros três grupos testes (IBU>ETERO=NIME=ACETA), que foram equivalentes entre si. Apesar da ocorrência de significância estatística, do ponto de vista da relevância clínica, a diferença entre os grupos foi pequena e todos os grupos apresentaram baixos escores de dor. Assim, sugerimos que a tomada de decisão em relação à escolha do medicamento deve considerar, também, a relação de custo-benefício, efeitos adversos e características individuais dos pacientes. Em adição, estudos futuros em cirurgias implantodônticas extensas (maior número de implantes inseridos e com enxertos ósseos/gengivais) apresentando alto rigor metodológico, ainda se faz necessário. (CAEE 83534618.5.0000.5149)

There is insufficient evidence to recommend a specific analgesic regimen for pain management in preemptive analgesia after dental implant surgery, signaling the need for further studies. This research presents two studies with different objectives: (1) to evaluate the effectiveness of preemptive analgesia in dental implant surgeries through a systematic review and meta-analysis of randomized clinical trials. (2) to evaluate and compare, through a randomized clinical trial (RCT), parallel, controlled by placebo, the effectiveness of preemptive analgesia in single dental implant surgeries, seeking to identify among analgesics and non-steroidal anti-inflammatory drugs (NSAIDs) [ eterocoxib (ETERO), ibuprofen (IBU), nimesulide (NIME) and acetaminophen (ACETA)], which is more effective in relieving postoperative pain and reducing the use of rescue medication compared to the use of placebo. The systematic review with meta-analysis was conducted by PRISMA guidelines and registered in PROSPERO (CRD42020168757). Five studies were included in the review and four were incorporated into the meta-analysis. A random-effect meta- analysis compared the effectiveness of preventive medication compared to placebo. The interpretation of the results followed the certainty of the evidence using the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) approach together with the magnitude of the effect according to the GRADE guidelines. All studies demonstrated that preemptive medication contributed to a significant improvement in postoperative pain. However, the pooled overall mean standard deviation (SMD) showed that preventive medication had a small effect compared with placebo in reducing pain (SMD: -0.43; CI: -0.71; -0.15) with low certainty of evidence. Our meta-analysis showed that the magnitude of the effect was greater six to eight hours after surgery (large effect), compared to one to two hours after surgery (small effect). It was concluded that preventive analgesia can have a positive effect in reducing pain compared to not using preemptive medication, but the evidence is still insufficient. The RCT with single dental implant insertion involved 135 individuals, with a mean age of 57.1 (±11.2), of both genders allocated into 5 groups (ETERO, IBU, NIME, ACETA and placebo). The occurrence, duration and intensity of pain were analyzed using Chi- square, Fisher's Exact, ANOVA and generalized estimating equation models when appropriate. All drugs tested provided a beneficial effect of preemptive analgesia demonstrated by reduced postoperative pain and reduced use of rescue medication. The IBU group had significantly higher pain scores than the other three test groups (ETERO, NIME and ACETA), which were equivalent to each other. Despite the occurrence of statistical significance, from the point of view of clinical relevance, the difference between the groups was small and all had low pain scores. Thus, we suggest that the decision making regarding the choice of medication should also consider the cost-benefit ratio, adverse effects and individual characteristics of patients. In addition, future studies in extensive implant dentistry surgeries (greater number of implants inserted and with bone/gingival grafts) presenting high methodological rigor are still necessary. (CAEE 83534618.5.0000.5149)

Is Implantoplasty Efficacious at Treating Peri-Implantitis? A Systematic Review and Meta-Analysis.

PURPOSE: Peri-implantitis is an inflammatory disease, characterized by the progressive loss of the peri-implant support bone tissue. The objective of this study was to assess whether implantoplasty is efficacious in promoting peri-implant health. METHODS: In this systematic review and meta-analysis, a search without restrictions regarding language or date of publication was conducted across different databases. Grey literature search, Google Scholar search and manual searches were also carried out. Studies evaluating periimplant clinical parameters of individuals with peri-implantitis who had been submitted to implantoplasty were included. Study selection, data extraction, and risk of bias assessment were conducted. The outcome variables were implant probing depth, the percentage of implants with bleeding on probing or suppuration on probing, and the success rate of implants after implantoplasty. The predictor variable was implantoplasty and the follow-up time after implantoplasty. Data on sample size, implant location, implant diameter, and diagnostic criteria for peri-implantitis were also collected during data extraction. Meta-analysis, sensitivity analysis, and analysis of the probability of implant success after implantoplasty with the Kalan-Meier method were performed. RESULTS: Ninety-four studies were assessed. Eight articles were included and 7 were incorporated into quantitative analyses. Subjects' mean age ranged between 50 to 70.7 years. The studies demonstrated that implantoplasty contributed to a significant improvement in the peri-implant condition, reducing the probing depth, bleeding and suppuration on probing. Overall, the included studies exhibited low risk of bias. Meta-analysis demonstrated that probing depth before implantoplasty was significantly higher than after implantoplasty (mean difference = -3.37 mm, confidence interval = -4.74; -2.00). This result was confirmed in the sensitivity analysis. The probability of success of implants at 6 months of follow-up after implantoplasty was 97.5% and at 24 months of follow-up was 94.7%. CONCLUSIONS: There is some evidence in the literature to recommend implantoplasty as a potential treatment for periimplantitis.

Effectiveness of direct-acting agents for chronic hepatitis C treatment in South America: A systematic review and meta-analysis.

The effectiveness of direct-acting agents (DAAs) for hepatitis C treatment in limited-resource settings remains unclear. We estimated the pooled sustained virological response rates of DAA therapy in South America. We searched online databases for studies that reported 12-week sustained virological response (SVR12) to hepatitis C virus (HCV) treatment in individuals living in South America. Pooled SVR12 in intention-to-treat (ITT) and per-protocol were estimated. Additionally, using all studies with available data, the pooled relative risk (RR) of SVR12 using a random-effects model (DerSimonian-Laird) was estimated to compare effectiveness of DAAs in patients with or without cirrhosis, HIV co-infection or previous HCV therapy. Heterogeneity was assessed using the I2 statistics. We identified 20 studies [14 manuscripts and 6 conference abstracts] comprising 7393 individuals from five countries [Brazil (n = 11), Argentina (n = 4), Chile (n = 1), Colombia (n = 1) and Peru (n = 1)] and two South-American collaborations. The pooled overall SVR12 rates [95% confidence interval (CI)] were 92.6% [90.2-94.7] and 95.5% [94.3-96.6] by ITT (11 studies; n = 4,153; I2  = 84.2%) and per-protocol analysis (15 studies; n = 4,833; I2  = 64.5%), respectively. The RR of SVR12 was similar in patients with or without HIV co-infection [4 studies; RR = 1.03 (0.99-1.07)] and those naive compared with treatment experimented-individuals [9 studies; RR = 1.01 (1.00-1.03)], but significantly higher in patients without cirrhosis compared with those with cirrhosis [11 studies; RR = 1.04 (1.02-1.05), P < .001]. DAAs are highly effective for HCV treatment in South America. The use of DAAs should be considered in limited-resource settings to decrease the burden of liver disease in HCV-infected patients. PROSPERO[CRD 42019134603].

RECOMMENDATIONS FOR INVASIVE PROCEDURES IN PATIENTS WITH DISEASES OF THE LIVER AND BILIARY TRACT: REPORT OF A JOINT MEETING OF THE BRAZILIAN SOCIETY OF HEPATOLOGY (SBH), BRAZILIAN SOCIETY OF DIGESTIVE ENDOSCOPY (SOBED) AND BRAZILIAN SOCIETY OF INTERVENTIONAL RADIOLOGY AND ENDOVASCULAR SURGERY (SOBRICE).

Liver and biliary tract diseases are common causes of morbidity and mortality worldwide. Invasive procedures are usually performed in those patients with hepatobiliary diseases for both diagnostic and therapeutic purposes. Defining proper indications and restraints of commonly used techniques is crucial for proper patient selection, maximizing positive results and limiting complications. In 2018, the Brazilian Society of Hepato-logy (SBH) in cooperation with the Brazilian Society of Interventional Radiology and Endovascular surgery (SOBRICE) and the Brazilian Society of Digestive Endoscopy (SOBED) sponsored a joint single-topic meeting on invasive procedures in patients with hepatobiliary diseases. This paper summarizes the proceedings of the aforementioned meeting. It is intended to guide clinicians, gastroenterologists, hepatologists, radiologists, and endoscopists for the proper use of invasive procedures for management of patients with hepatobiliary diseases.