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Τρίτη 27 Σεπτεμβρίου 2022

Salvage of Declined Extended-criteria DCD Livers Using In Situ Normothermic Regional Perfusion

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imageObjective: This study investigates whether liver grafts donated after circulatory death (DCD) that are declined by the entire Eurotransplant region can be salvaged with abdominal normothermic regional perfusion (aNRP). Background: aNRP is increasingly used for DCD liver grafts because it prevents typical complications. However, it is unclear whether aNRP is capable to rescue pretransplant declined liver grafts by providing the opportunity to test function during donation. Methods: Donor livers from DCD donors, declined by all centers in the Eurotransplant region, were included for this study. The comparator cohort included standard DCD livers and livers donated after brain death, transplanted in the same time period. Results: After the withdrawal of life-sustaining treatment, 28 from the 43 donors had a circulatory death within 2 hours, in which case aNRP was initiated. Of these 28 cases, in 3 cases perfusion problems occurred, 5 grafts were declined based on liver assessment, and 20 liver grafts were transplanted. The main differences during aNRP between the transplanted grafts and the assessed nontransplanted grafts were alanine transaminase levels of 53 U/L (34–68 U/L) versus 367 U/L (318–488 U/L) (P=0.001) and bile production in 100% versus 50% of the grafts (P=0.024). The 12-month graft and patient survival were both 95%, similar to the comparator cohort. The incidence of ischemic cholangiopathy was 11%, which was lower than in the standard DCD cohort (18%). Conclusion: aNRP can safely select and thus is able to rescue DCD liver grafts that were deemed unsuitable for transplantation, while preventing primary nonfunction and minimizing ischemic cholangiopathy.
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Long-Term Exposure to Oxidant Gases and Mortality: Effect Modification by PM2.5Transition Metals and Oxidative Potential

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Background: Populations are simultaneously exposed to outdoor concentrations of oxidant gases (i.e., O3 and NO2) and fine particulate air pollution (PM2.5). Since oxidative stress is thought to be an important mechanism explaining air pollution health effects, the adverse health impacts of oxidant gases may be greater in locations where PM2.5 is more capable of causing oxidative stress. Methods: We conducted a cohort study of 2 million adults in Canada between 2001-2016 living within 10-km of ground-level monitoring sites for outdoor PM2.5 components and oxidative potential. Ox exposures (i.e., the redox weighted average of O3 and NO2) were estimated using a combination of chemical transport models, land use regression models, and ground level data. Cox proportional hazards models were used to estimate associations between 3-year moving average Ox and mortality outcomes across strata of transition metals and sulfur in PM2.5 and three measures of PM2.5 oxidative potential adjusting for possible confounding factors. Results: Associations between Ox and mortality were consistently stronger in regions with elevated PM2.5 transition metal/sulfur content and oxidative potential. For example, each interquartile increase (6.27 ppb) in Ox was associated with a 14.9% (95% CI: 13.0, 16.9) increased risk of nonaccidental mortality in locations with glutathione-related oxidative potential (OPGSH) above the median whereas a 2.50% (95% CI: 0.600, 4.40) increase was observed in regions with OPGSH levels below the median (interaction p-value
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Using Latent Profile Analysis to Identify Associations Between Gestational Chemical Mixtures and Child Neurodevelopment

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Background: Unsupervised machine learning techniques have become increasingly popular for studying associations between gestational exposure mixtures and human health. Latent profile analysis is one method that has not been fully explored. Methods: We estimated associations between gestational chemical mixtures and child neurodevelopment using latent profile analysis. Using data from the Maternal-Infant Research on Environmental Chemicals (MIREC) research platform, a longitudinal cohort of pregnant Canadian women and their children, we generated latent profiles from 27 gestational exposure biomarkers. We then examined the associations between these profiles and child Verbal IQ, Performance IQ, and Full-Scale IQ, measured with the Wechsler Preschool and Primary Scale of Intelligence (WPPSI-III). We validated our findings using k-means clustering. Results: Latent profile analysis detected five latent profiles of exposure: a reference profile containing 61% of the study participants, a high Mono-ethyl Phthalate (MEP) profile with moderately low persistent organic pollutants (POPs) containing 26%, a high POP profile containing 6%, a low POP profile containing 4%, and a smoking chemicals profile containing 3%. We observed negative associations between both the smoking chemicals and high MEP profiles and all IQ scores, and between the high POP profile and Full-Scale and Verbal IQ scores. We also found a positive association between the low POP profile and Full-Scale and Performance IQ scores. All associations had wide 95% confidence intervals. Conclusion: Latent profile analysis is a promising technique for identifying patterns of chemical exposure, and is worthy of further study for its use in examining complicated exposure mixtures. Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.
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Are detailed behavioral, psychosocial, and environmental variables necessary to control for confounding in pregnancy weight gain research?

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Background: Associations between pregnancy weight gain and adverse outcomes may be spurious due to confounding by factors not typically measured in cohort studies. We determined the extent to which the addition of detailed behavioral, psychosocial, and environmental measurements to commonly available covariates improved control of confounding. Methods: We used data from a prospective U.S. pregnancy cohort study (2010‒2013, n=8978). We calculated two propensity scores for low and high pregnancy weight gain (vs. adequate gain) using 11 standard confounders (e.g., age, education). We examined the balance of characteristics between weight gain groups before and after propensity score matching. We used negative binomial regression to estimate the association between weight gain and small- and large-for-gestational-age birth, preterm birth, and unplanned Cesarean delivery, controlling for propensity score. To this model we then added 17 detailed behavioral, psychosocial, and environmental measurements ('fully adjusted'). We calculated the risk ratio due to confounding as the ratio of the standard confounder-adjusted risk ratio to the fully adjusted risk ratio. Results: There were minimal imbalances between weight gain groups in detailed measures after matching for a propensity score of standard covariates. Accordingly, the inclusion of detailed covariates had minimal impact on estimated associations between low or high pregnancy weight gain and adverse pregnancy outcomes: risk ratios due to confounding were null for all outcomes (e.g., 1.1 [95% CI: 1.0, 1.1] for low weight gain and preterm birth). Conclusions: Adjustment for detailed behavioral, psychosocial, and environmental measurements had minimal impact on estimated associations between pregnancy weight gain and adverse perinatal outcomes. Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.
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Accounting for misclassification and selection bias in estimating effectiveness of self-managed medication abortion

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Background: Studies on the effectiveness of self-managed medication abortion may suffer from misclassification and selection bias due to self-reported outcomes and loss to follow-up. Monte Carlo sensitivity analysis can estimate self-managed abortion effectiveness accounting for these potential biases. Methods: We conducted a Monte Carlo sensitivity analysis based on data from the Studying Accompaniment model Feasibility and Effectiveness Study (the SAFE Study), to generate bias-adjusted estimates of effectiveness of self-managed abortion with accompaniment group support. Between July 2019 and April 2020, we enrolled a total of 1051 callers who contacted accompaniment groups in Argentina and Nigeria for self-managed abortion information; 961 took abortion medications and completed at least one follow-up. Using these data, we calculated measures of effectiveness adjusted for ineligibility, misclassification, and selection bias across 50,000 simulations with bias parameters drawn from pre-specified Beta distributions in R. Results: After accounting for potential influence of various sources of bias, bias-adjusted estimates of effectiveness were similar to observed estimates, conditional on chosen bias parameters: 92.68% (95% simulation interval: 87.80%, 95.74%) for mifepristone in combination with misoprostol (versus 93.7% in the observed data) and 98.47% (95% simulation interval: 96.79%, 99.39%) for misoprostol alone (versus 99.3% in the observed data). Conclusions: After adjustment for multiple potential sources of bias, estimates of self-managed medication abortion effectiveness remain high. Monte Carlo sensitivity analysis may be useful in studies measuring an epidemiologic proportion (i.e., effectiveness, prevalence, cumulative incidence), while accounting for possible selection or misclassification bias. Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.
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Δευτέρα 26 Σεπτεμβρίου 2022

Effectiveness of adjunct therapy for the treatment of apical periodontitis: a systematic review and meta‐analysis

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Abstract

Background

Adjunct therapy refers to any intracanal procedure going beyond chemomechanical preparation with instruments and traditionally delivered irrigants (excluding interim dressings). It is not clear whether and which of these adjunct therapies have a significant impact on the outcome of root canal treatment (healing of apical periodontitis and other patient-related outcomes).

Objectives

This systematic review aimed to analyse available evidence on the effectiveness of adjunct therapy for the treatment of apical periodontitis in permanent teeth, according to a population, intervention, comparison, outcome, time and study design (PICOTS) framework formulated a priori by the European Society of Endodontology.

Methods

Five electronic databases (PubMed, Embase, Scopus, Cochrane, and Web of Science) were searched up to October 2021 to identify clinical studies comparing adjunct therapy to no adjunct therapy in adult patients with apical periodontitis. Animal studies, reviews, studies with less than 10 patients per arm, studies with a follow-up time of less than 1 year, or less than 7 days for postoperative pain, were excluded. The quality of the included studies was appraised by the appropriate tools (Risk of Bias 2 (RoB2) for randomized clinical trials (RCTs) and Newcastle Ottawa Scale for observational studies). Meta-analysis was performed using a random-effects model. The certainty of the evidence was assessed using the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) approach.

Results

Fourteen studies (13 RCTs, and 1 retrospective cohort) fulfilled the inclusion criteria for this review. They evaluated different types of adjunct therapy: antimicrobial photodynamic therapy (aPDT) (3 studies), diode laser canal irradiation (3), Nd:YAG laser canal irradiation (2), Er;Cr:YSGG laser canal irradiation (1), ozone therapy (2), and ultrasonically activated irrigation (UAI) (4). Radiographical healing was reported in 7 studies, but meta-analysis was only possible for UAI (2 studies), showing no statistically significant difference in healing after 12 months. Pain after 7 days was reported in 7 studies. Meta-analysis on three studies that used aPDT, and on 2 studies using diode laser irradiation showed no significant difference in the prevalence of pain after 7 days between the control and adjunct therapy. According to RoB2 tool, 6 studies had a high risk of bias, 5 studies had some concerns, and 2 studies low risk of bias. The GRADE assessment revealed a very low str ength of evidence for diode laser, and low strength of evidence for PDT, ozone, and UAI studies.

Discussion

The included studies displayed significant heterogeneity in terms of type of adjunct therapy, technical details per adjunct therapy, outcome reporting, and several combinations of these, limiting the potential for meta-analysis.

Conclusions

There is insufficient evidence to recommend any adjunctive therapy for the treatment of apical periodontitis.
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Κυριακή 25 Σεπτεμβρίου 2022

Antibody response six months after the booster dose of Pfizer in previous recipients of CoronaVac

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Abstract

The most widely used vaccines were mRNA, viral vector, and inactivated virus with two-dose schedules. In Brazil, the CoronaVac (Sinovac) was the first vaccine approved for emergency use and the third dose was administered, preferably, with the BNT162b2 vaccine. We evaluated antibody levels after six months of the booster dose with BNT162B2 in previous recipients of CoronaVac and whether a subsequent SARS-COV-2 infection enhances the antibody response. We analyze of the humoral response, S IgM for the SARS-CoV-2, S IgG and N IgG in samples collected before the third dose and six months after the third dose. The presence of antibodies was measured by using Abbott Architect i2000SR. The IgM and IgG anti-spike were stimulated mainly in 30D/3D with a decline over time. The IgG anti-N was stimulated predominantly in 90/3D and 180/3D. The N IgG levels were 50 and 35 times higher in the positive PCR group in 90/3D and 180/3D, respectively. The S IgG titers were 1.5 times elevated in the positive PCR group, in 180/3D. The BNT162b2 boosted the S IgG levels, decreasing after the 60 days. The booster shot induced IgM and IgG antibodies against Spike protein. Infection after vaccination increased antibodies against protein N.

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Patient‐centric outcome assessment of endodontic microsurgery using periapical radiography versus Cone Beam Computed Tomography ‐ A randomized clinical trial

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Abstract

Aim

This study aimed to evaluate whether utilizing additional CBCT imaging has any effect on quality of life and healing outcome following periapical surgery compared to PR.

Methodology

The study was registered in ClinicalTrials.gov (NCT04333940). In this parallel group randomized controlled trial, fifty-two patients (88 teeth) with persistent apical periodontitis and periapical radiographic evidence of periapical lesion were randomly assigned to either PR or CBCT group. The primary predictor was the type of the imaging method (PR only or with additional CBCT). The primary outcome was patient's quality of life during the first week after periapical surgery and the secondary outcomes were duration of surgery and healing outcome at 12-month follow-up. Participants of both groups received periapical surgery based on the presurgical plan provided by the radiographic imaging methods. QoL was assessed using Modified Shugars questionnaire. Radiographic analysis for healing was conducted using Molven's criteria and modified P ENN 3D criteria. The categorical data between groups were analysed using the Chi-square test, while intragroup comparisons were analysed using the McNemar test. The average scores for each component of QoL (oral functions, general functions, pain, swelling and other symptoms), combined QoL scores (overall average of values of 13 variables) and analgesic usage on each day were calculated and analysed.

Results

At 12 months follow-up, fifty patients were evaluated. Participants in PR group reported significantly more swelling on first three days compared with CBCT group. The analgesic use was higher in the PR group on 2nd and 3rd day (Mann Whitney U test with Bonferroni correction; p < 0.007). A significant difference in the limitation of general functions was observed at the second day (p<0.07) with the higher values in the PR group. The combined QoL score between the two groups was found to be non-significant. However, none of the patients experienced intraoperative complications or neurovascular exposure. The mean surgical time was lesser in the CBCT group (p <0.05). Radiographic healing revealed a success rate of 96.2% for the PR group and 95.8% for the CBCT group with no significant difference between the groups.

Conclusion

Participants in the CBCT group experienced substantially less early postoperative swelling and limitation in general functions, in comparison with the PR group. However, preoperative CBCT had no effect on other QoL parameters and intraoperative complications in medium-risk patients. Furthermore, CBCT did not exhibit any added advantage over periapical radiography in terms of assessing healing outcome following endodontic microsurgery. CBCT offered surgically relevant anatomic information for presurgical planning and ensured the treatment rendition with a significantly reduced operative time.
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Association of treated and untreated chronic hepatitis C with the incidence of active tuberculosis disease: a population-based cohort study.

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Abstract
Background
Hepatitis C virus (HCV) infection causes dysregulation and suppression of immune pathways involved in the control of tuberculosis (TB) infection. However, data on the role of chronic hepatitis C as a risk factor for active TB are lacking. We sought to evaluate the association between HCV infection and the development of active TB.
Methods
We conducted a cohort study in Georgia among adults tested for HCV antibodies (January 2015 – September 2o2o) and followed longitudinally for the development of newly diagnosed active TB. Data were obtained from the Georgian National programs of hepatitis C and TB. The exposures of interest were untreated and treated HCV infection. Cox proportional hazards model was used to calculate adjusted hazards ratios.
Results
A total of 1,828,808 adults were included (median follow-up time: 26 months, IQR: 13-39 months). Active TB was diagnosed in 3,163 (0.17%) individuals after a median of 6 months follow-up (IQR: 1-18 months). The incidence rate per 100,000 person-years was 296 among persons with untreated HCV infection, 109 among those with treated HCV infection, and 65 among HCV-negative persons. In multivariable analysis, both untreated (aHR = 2.9, 95%CI: 2.4-3.4) and treated (aHR = 1.6, 95%CI: 1.4-2.0) HCV infection were associated with a higher hazard of active TB, compared to HCV-negative persons.
Conclusions
Adults with HCV infection, particularly untreated i ndividuals, were at higher risk of developing active TB disease. Screening for latent TB infection and active TB disease should be part of clinical evaluation of people with HCV infection, especially in high TB burden areas.
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Co-administration of Oral Cholera Vaccine with Oral Polio Vaccine among Bangladeshi Young Children: A Randomized Controlled Open Label Trial to Assess Interference

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Abstract
Background
Cholera remains a public health threat for low- and middle-income countries, particularly in Asia and Africa. ShancholTM, an inactivated oral cholera vaccine (OCV) is currently in use globally. OCV and oral poliovirus vaccines (OPV) could be administered concomitantly but the immunogenicity and safety of coadministration among children aged 1-3 years is unknown.
Method
We undertook an open-label, randomized, controlled, inequality trial in Dhaka city, Bangladesh. Healthy children aged 1-3 years were randomly assigned to one of the three groups: bivalent OPV (bOPV)-alone, OCV-alone, or combined bOPV + OCV and received vaccines on the day of enrollment and 28 days later. Blood samples were collected on the day of enrollment, day 28, and day 56. Serum poliovirus neutralizing antibodies and vibriocidal antibodies against V. cholerae O1 were assessed using microneutralization assays.
Results
A total of 579 children aged 1‒3 years were recruited, 193 children per group. More than 90% of the children completed visits at day 56. Few adverse events following immunization were recorded and were equivalent among study arms. On day 28, 60% (90% Confidence interval, 53%-67%) and 54% (46%-61%) of participants with co-administration of bOPV + OCV responded to polioviruses type 1 and 3 respectively, compared to 55% (47%-62%) and 46% (38%-53%) in the bOPV-only group. Additionally, >50% of participants showed a ≥4-fold increase in vibriocidal antibody titre responses on day 28, comparable to the responses observed in OCV-only arm.
Conclusions
Co-administration of bOPV and OCV is safe and effective in children aged 1-3 years and can be cost-beneficial.
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