Prognostic impact of pretreatment cell-free DNA concentration in newly diagnosed peripheral T-cell lymphomas.

Peripheral T-cell lymphomas (PTCLs) have a poor prognosis and, to date, there are no reliable predictive biomarkers of response. In this work we explored the prognostic impact of cell-free DNA (cfDNA) concentration in 75 newly diagnosed patients enrolled in a prospective multicenter study. Pre-treatment cfDNA was strongly associated with clinical risk factors and was identified as a superior predictor for shorter progression-free survival in multivariable analysis, outweighing canonical risk parameters. Furthermore, we identified a cfDNA value above which survival worsens. In conclusion, pre-treatment cfDNA concentration represents an easily usable predictive biomarker that is highly associated with survival of PTCL patients.

Kounis syndrome: an underestimated emergency.

Summary: Background. Kounis syndrome (KS) is defined as a rare cause of an acute coronary syndrome associated with systemic allergic reactions. To establish the prevalence of KS among the patients with diagnosis of anaphylaxis, we described clinical features, cardiological and allergological outcomes of patients evaluated in our allergy outpatient clinic. Methods. A retrospective study was carried out in the Allergy Unit of Novara hospital, from January 2008 to March 2020. Skin tests and in vitro tests were performed with suspected etiological agents. Results. We found 9 adults with KS (2%) out of 444 subjects who had experienced anaphylactic reactions (4/9 to Hymenoptera stings, 5/9 to drugs). Conclusions. The present study highlights the importance of suspicion of KS that appears not so uncommon in patients with anaphylaxis. KS seems to be a rare disease because unrecognized in diagnosis of anaphylaxis.

Strength-based methods - a narrative review and comparative multilevel meta-analysis of positive interventions in clinical settings.

OBJECTIVE: In psychotherapy, strength-based methods (SBM) represent efforts to build on patients' strengths while addressing the deficits and challenges that led them to come to therapy. SBM are incorporated to some extent in all major psychotherapy approaches, but data on their unique contribution to psychotherapy efficacy is scarce. METHODS: First, we conducted a systematic review and narrative synthesis of eight process-outcome psychotherapy studies that investigated in-session SBM and their relation to immediate outcomes. Second, we conducted a systematic review and multilevel comparative meta-analysis contrasting strength-based bona fide psychotherapy vs. other bona fide psychotherapy at post-treatment (57 effect sizes nested in 9 trials). RESULTS: Despite their methodological variability, the pattern of results in the process-outcome studies was generally positive, such that SBM were linked with more favorable immediate, session-level patient outcomes. The comparative meta-analysis found an overall weighted average effect size of g = 0.17 (95% CIs [0.03, 0.31], p < .01) indicating a small but significant effect in favor of strength-based bona fide psychotherapies. There was non-significant heterogeneity among the effect sizes (Q(56) = 69.1, p = .11; I2 = 19%, CI [16%, 22%]). CONCLUSION: Our findings suggest that SBMs may not be a trivial by-product of treatment progress and may provide a unique contribution to psychotherapy outcomes. Thus, we recommend integration of SBM to clinical training and practice across treatment models.

Assessing the alliance-outcome association adjusted for patient characteristics and treatment processes: A meta-analytic summary of direct comparisons.

The alliance is widely recognized as a robust predictor of posttreatment outcomes. However, there is a debate regarding whether the alliance is an epiphenomenon of intake characteristics and/or treatment processes occurring over the course of treatment. This meta-analysis aimed to synthesize the evidence on this issue. We identified 125 effect sizes in 60 independent samples (6,061 participants) of studies that reported alliance-outcome correlations as well as parallel intake or process characteristics. We examined the impact of these potential confounds on the alliance-outcome correlations. We meta-analyzed the studies estimates by computing omnibus effects models as well as multivariate models. We identified 3 variable types that were used to adjust the alliance-outcome correlations: (a) intake characteristics (k = 35); (b) simultaneous processes, such as adherence or competence (k = 13); and (c) both intake and simultaneous processes (k = 24). We found moderate alliance-outcome correlations with or without adjustments for intake and simultaneous processes (range from r = .23 to r = .31). Our results provide robust empirical evidence for the assertion that the alliance-outcome association is an independent process-based factor. Findings suggest that alliance is positively related to outcome above and beyond the studied patient intake characteristics and treatment processes. (PsycInfo Database Record (c) 2020 APA, all rights reserved).

Antimicrobial effect of a local release system containing metronidazole against a Porphyromonas gingivalis biofilm.

The aim of this study was to evaluate a semi-solid system containing metronidazole (MDZ) in presence of challenging conditions for drug release, as well its antimicrobial effect against Porphyromonas gingivalis biofilm. Biofilms grown in culture medium were exposed to a formulation containing MDZ or its vehicle. After 24, 48, and 72 h, biofilm viability were analyzed while MDZ was quantified in culture medium and buffer solution (control). MDZ formulation reduced bacterial viability when compared to control groups. The vehicle formulation also affected bacterial viability in relation to control at all periods. Culture medium impaired MDZ release compared to buffer solution at 24 h. The semi-solid system reported herein is able to release MDZ and maintain its levels at concentrations that control viability of P. gingivalis in 1- to 3-day-old biofilms.

Survival in HIV-infected patients with lymphoma according to the choice of antiretroviral treatment: an observational multicentre study.

OBJECTIVES: Lymphoproliferative disorders are often observed in HIV-positive patients. Combination antiretroviral treatment (cART) during antineoplastic chemotherapy is beneficial, but little is known about the clinical outcome according to different antiretroviral combinations. The aim of the study was to address this gap in current knowledge. METHODS: A retrospective study was conducted in five large Italian centres for the period from 1998 to 2015; HIV-positive patients diagnosed with lymphoma were included and demographic, clinical and therapeutic variables were recorded and associated with clinical outcomes. Bivariate and multivariate analyses were performed, including Cox proportional hazard models for survival. RESULTS: A total of 399 patients were included in the study. The most common types of lymphoma were diffuse large B-cell lymphoma (DLCLB; n = 164), Hodgkin lymphoma (HL; n = 99) and Burkitt lymphoma (BL; n = 57), followed by plasmablastic lymphoma (PBL; n = 38), T-cell lymphoma (TCL; n = 17), indolent lymphoma (n = 10) and other less common types (n = 14). cART was given to 327 (out of 387 evaluable) patients: in 216 subjects it was protease inhibitor (PI)-based, in 73 it was nonnucleoside reverse transcriptase inhibitor (NNRTI)-based and in 18 it was integrase strand transfer inhibitor (INSTI)-based (the remaining 20 individuals received other regimens). The 5-year overall survival was 57.5% (52.8% for DLCLB, 67.8% for HL, 42.3% for BL, 60.6% for PBL and 64.7% for TCL). PI-based ART compared with other compounds was associated with worse survival in non-Hodgkin lymphoma (NHL) and HL patients combined (P ≤ 0.001) and in NHL patients alone (P < 0.001); grade 3-4 haematological toxicities were more commonly observed in PI-treated individuals. Lymphoma diagnosis in recent years, better immunovirological status, lower lymphoma stage and better prognostic indexes were associated with better survival. CONCLUSIONS: PI-based cART while on chemotherapy was associated with worse overall survival and more frequent haematological complications in HIV-positive patients with lymphoma.

Effect size calculation in meta-analyses of psychotherapy outcome research.

Meta-analysis of psychotherapy intervention research normally examines differences between treatment groups and some form of comparison group (e.g., wait list control; alternative treatment group). The effect of treatment is normally quantified as a standardized mean difference (SMD). We describe procedures for computing unbiased estimates of the population SMD from sample data (e.g., group Ms and SDs), and provide guidance about a number of complications that may arise related to effect size computation. These complications include (a) incomplete data in research reports; (b) use of baseline data in computing SMDs and estimating the population standard deviation (σ); (c) combining effect size data from studies using different research designs; and (d) appropriate techniques for analysis of data from studies providing multiple estimates of the effect of interest (i.e., dependent effect sizes). Clinical or Methodological Significance of this article: Meta-analysis is a set of techniques for producing valid summaries of existing research. The initial computational step for meta-analyses of research on intervention outcomes involves computing an effect size quantifying the change attributable to the intervention. We discuss common issues in the computation of effect sizes and provide recommended procedures to address them.

In pursuit of truth: A critical examination of meta-analyses of cognitive behavior therapy.

OBJECTIVE: Three recent meta-analyses have made the claim, albeit with some caveats, that cognitive-behavioral treatments (CBT) are superior to other psychotherapies, in general or for specific disorders (e.g., social phobia). METHOD: The purpose of the present article was to examine four issues in meta-analysis that mitigate claims of CBT superiority: (a) effect size, power, and statistical significance, (b) focusing on disorder-specific symptom measures and ignoring other important indicators of psychological functioning, (c) problems inherent in classifying treatments provided in primary studies into classes of treatments, and (d) the inclusion of problematic trials, which biases the results, and the exclusion of trials that fail to find differences among treatments. RESULTS: When these issues are examined, the effects demonstrating the superiority of CBT are small, nonsignificant for the most part, limited to targeted symptoms, or are due to flawed primary studies. CONCLUSION: Meta-analytic evidence for the superiority of CBT in the three meta-analysis are nonexistent or weak.

Local antibiotic delivery in periodontitis: drug release and its effect on supragingival biofilms.

The effect of a drug-delivery system containing antibacterial metronidazole (MDZ) prescribed for periodontitis on supragingival biofilm was evaluated, and possible interference by this biofilm in the drug release profile was investigated. Streptococcus mutans biofilms were grown and exposed to a controlled-release formulation of MDZ or the same formulation without MDZ (vehicle control). Untreated biofilms were used as a negative control (NC). Biofilms and culture medium (containing detached cells) were collected 24, 48, 72, and 96 h after first exposure to treatments. The biomass of the MDZ group was lower than that of the NC group at all times. Although MDZ yielded low drug-release rates in the presence of the biofilm, it was sufficient for reducing viability for 24 h and affecting bacterial metabolism for 48 h. These results suggest that MDZ appears to destabilize supragingival biofilm. This biofilm may interfere with MDZ release from the formulation.

Open access meta-analysis for psychotherapy research.

Meta-analysis has played a key role in psychotherapy research for nearly 40 years. There is now an opportunity for technology to assist with transparent and open meta-analyses. The authors describe an open-access database of effect sizes and a corresponding web application for performing meta-analyses, viewing the database, and downloading effect sizes. The initial databases provide effect sizes for family therapy for delinquency studies and for alliance-outcome correlations in individual psychotherapy. Disciplinary norms about data sharing and openness are shifting. Furthermore, meta-analyses of behavioral interventions have been criticized for lacking transparency and openness. The database and web application are aimed at facilitating data sharing and improving the transparency of meta-analyses. The authors conclude with a discussion of future directions for the database.

A meta-analysis of topiramate's effects for individuals with alcohol use disorders.

BACKGROUND: Influenced by several trials and reviews highlighting positive outcomes, topiramate is increasingly prescribed as a treatment for alcohol use disorders (AUDs). The only previously published meta-analysis of topiramate for AUDs was limited by a sample of only 3 randomized, placebo-controlled trials (RCTs). METHODS: A systematic search identified 7 RCTs (including a total of 1,125 participants) that compared topiramate to placebo for the treatment for AUDs. This meta-analysis estimated the overall effects of topiramate on abstinence, heavy drinking, craving, and γ-glutamyltranspeptidase (GGT) outcomes and included several sensitivity analyses to account for the small sample of studies. RESULTS: Overall, the small to moderate effects favored topiramate, although the effect on craving was not quite significantly different from 0. The largest effect was found on abstinence (g = 0.468, p < 0.01), followed by heavy drinking (g = 0.406, p < 0.01), GGT (g = 0.324, p = 0.02), and craving (g = 0.312, p = 0.07) outcomes. Sensitivity analyses did not change the magnitude or direction of the results, and tests did not indicate significant publication bias. The small sample size did not allow for examination of specific moderators of the effects of topiramate. CONCLUSIONS: Topiramate can be a useful tool in the treatment of AUDs. Its efficacy, based on the current sample of studies, seems to be of somewhat greater magnitude than that of the most commonly prescribed medications for AUDs (naltrexone and acamprosate). Further research will help to identify the contexts in which topiramate is most beneficial (e.g., dose, concurrent psychotherapy, patient characteristics).

The impact of neurobehavioral features on medication adherence in HIV: evidence from longitudinal models.

Effective antiretroviral therapy has led to substantial improvements in health-related outcomes among individuals with HIV. Despite advances in HIV pharmacotherapy, suboptimal medication adherence remains a significant barrier to successful treatment. Although several factors have been associated with medication adherence in the extant literature, study assessing the effects of some of the neurobehavioral features specific to HIV has been limited. Moreover, although there is a growing body of literature measuring medication adherence in HIV prospectively, few employ advanced statistical methodologies suited to handle advanced models with multiple predictors that would strengthen our understanding of medication adherence trajectories in HIV. This study sought to integrate traditionally assessed predictors of medication adherence with neurobehavioral features of HIV in a longitudinal study of medication adherence to combined antiretroviral therapy (cART). The current study used multilevel modeling to examine a wide arrangement of categories of factors - demographic, medication related, psychosocial, and neurobehavioral - on medication adherence. The sample consisted of 235 HIV+ individuals whose medication adherence was monitored over the course of six months using electronic monitoring devices. After controlling for the effects of demographic, medication, and psychosocial factors, neurobehavioral features added predictive validity to the model. In the final model, simultaneously controlling for the effects of each of the predictors within all the categories, age, self-efficacy, executive functioning, apathy, and frequency of stimulant use emerged as unique individual predictors of average medication adherence across the 6-month study. Self-efficacy and irritability predicted changes in medication adherence over time. Adherence behavior is multidetermined. Adequate assessment of these factors, combined with timely intervention, appears to be warranted in order to boost adherence rates.

The secret ingredient in mindfulness interventions? A case for practice quality over quantity.

As mindfulness-based interventions become increasingly widespread, interest has grown in better understanding which features of these treatments produce beneficial effects. The present study examined the relative contribution of mindfulness practice time and practice quality in predicting psychological functioning (negative affect, emotion regulation, quality of life, mindfulness). Data were drawn from a randomized clinical trial of mindfulness training for smokers and assessed outcomes at posttreatment (n = 43) and 5-month follow-up (n = 38). The intervention included instruction in mindfulness techniques targeted to smoking cessation and relapse prevention and was composed of 10 group meetings over 8 weeks. Data from 8 treatment groups were used. Mindfulness practice quality was measured weekly over the course of treatment, and multilevel modeling was used to estimate trajectories of change in practice quality. The measure of practice quality was shown to be valid and reliable, with change in practice quality predicting change in psychological functioning at both posttreatment (ß = .31, 95% CI = [0.04, 0.56], p = .022) and follow-up (ß = .45 [0.16, 0.73], p = .002), even when controlling for practice time. Practice time predicted outcomes at posttreatment (ß = .31 [0.05, 0.57], p = .019) but not at follow-up (ß = .16 [-0.14, 0.47], p = .293). Neither practice time nor change in practice quality predicted smoking abstinence at 1 month or 6 months postquit. Results support the importance of practice quality as a relevant aspect of mindfulness interventions.

Holistic evaluation of the environmental impacts of shipping in the sensitive region of Ria de Aveiro.

Shipping activity can be a substantial source of pollution and impact on the environment, including air, water and ecosystems, as well as adverse health and climatic effects. Due to the distribution of maritime transport activity routes in the EU, a large portion of the population is exposed to shipping pollution throughout Europe. The ongoing European project EMERGE aims to investigate and quantify these impacts over Europe, and in more detail, in specific case studies regions. The Aveiro lagoon region in Portugal is one of these case studies. This region is a Natura 2000 area, and also includes a medium-sized port. Both air quality and water modelling tools were applied to assess the impact of the emissions and discharges from shipping (to air and water) in the region in 2018. Additionally, ecotoxicological impacts were determined by bioassays to evaluate the impact of scrubber-water discharges on the most sensitive stages of marine invertebrates, and on the post-exposure feeding inhibition of crustacean and bivalve species. The results show that there was a substantial increase in atmospheric pollutant concentrations due to emissions attributed to shipping, which was most relevant for NOx and SO2 (up to a 30 % shipping contribution). There was no significant degradation of the water quality, mainly as the ships operating in this area did not have scrubber equipment. The ecotoxicological tests were performed with three samples of scrubber water, including one artificial sample and two samples collected on-board ships. If scrubber water would have been discharged in this area, the results indicated that the majority of the tested species would be exposed to lowest observed effect concentration (LOEC) for the different scrubber-water samples, as well as to substantial concentrations of metals, PAHs, and alkylated PAHs.

AURA: Atlas of UTR Regulatory Activity.

SUMMARY: The Atlas of UTR Regulatory Activity (AURA) is a manually curated and comprehensive catalog of human mRNA untranslated regions (UTRs) and UTR regulatory annotations. Through its intuitive web interface, it provides full access to a wealth of information on UTRs that integrates phylogenetic conservation, RNA sequence and structure data, single nucleotide variation, gene expression and gene functional descriptions from literature and specialized databases. AVAILABILITY: http://aura.science.unitn.it CONTACT: aura@science.unitn.it; dassi@science.unitn SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

Placebo group improvement in trials of pharmacotherapies for alcohol use disorders: a multivariate meta-analysis examining change over time.

OBJECTIVE: Placebo group improvement in pharmacotherapy trials has been increasing over time across several pharmacological treatment areas. However, it is unknown to what degree increasing improvement has occurred in pharmacotherapy trials for alcohol use disorders or what factors may account for placebo group improvement. This meta-analysis of 47 alcohol pharmacotherapy trials evaluated (1) the magnitude of placebo group improvement, (2) the extent to which placebo group improvement has been increasing over time, and (3) several potential moderators that might account for variation in placebo group improvement. METHOD: Random-effects univariate and multivariate analyses were conducted that examined the magnitude of placebo group improvement in the 47 studies and several potential moderators of improvement: (a) publication year, (b) country in which the study was conducted, (c) outcome data source/type, (d) number of placebo administrations, (e) overall severity of study participants, and (f) additional psychosocial treatment. RESULTS: Substantial placebo group improvement was found overall and improvement was larger in more recent studies. Greater improvement was found on moderately subjective outcomes, with more frequent administrations of the placebo, and in studies with greater participant severity of illness. However, even after controlling for these moderators, placebo group improvement remained significant, as did placebo group improvement over time. CONCLUSIONS: Similar to previous pharmacotherapy placebo research, substantial pretest to posttest placebo group improvement has occurred in alcohol pharmacotherapy trials, an effect that has been increasing over time. However, several plausible moderator variables were not able to explain why placebo group improvement has been increasing over time.

The declining efficacy of naltrexone pharmacotherapy for alcohol use disorders over time: a multivariate meta-analysis.

BACKGROUND: Oral naltrexone is an FDA-approved medication for treating alcohol use disorders. Although its efficacy has been supported in multiple clinical trials, an earlier review found that its effect sizes (ESs) on relapse to heavy drinking and, to a lesser extent, percent days drinking were smaller in more recent trials and in multicenter than in single-site studies. We examined whether these findings held when studies from 2004 to 2009 were taken into account, and whether single-site versus multicenter trials, the use of placebo run-in periods, and placebo group improvement accounted for variation in naltrexone effects and decreasing effects over time. METHODS: A multivariate meta-analysis of naltrexone pharmacotherapy trials for alcohol use disorders was conducted. All analyses simultaneously modeled ESs on outcomes of percent days abstinent and relapse to heavy drinking. Potential moderators of medication effects that were examined included publication year, multicenter design (vs. single site), placebo run-in period, and placebo group improvement. RESULTS: Statistically significant between-group differences on percent days abstinent (the inverse of percent days drinking) and relapse to heavy drinking favored naltrexone over placebo. Year of publication was a significant moderator for both outcomes, with more recent trials having smaller ESs. Neither multi- versus single-site study, the interaction between multi- versus single-site study and year of publication, nor placebo run-in period was a significant moderator of naltrexone effects. Although placebo group improvement was modestly associated with smaller between-group naltrexone versus placebo ESs, only 21 studies provided usable information on placebo group improvement. Within those studies, there was no relationship between naltrexone ESs and time, so placebo group improvement was not examined as a moderator of that relationship. CONCLUSIONS: Naltrexone ESs have attenuated over time. Moderators that explain why effects have been decreasing remain to be determined.

Monitoring mindfulness practice quality: an important consideration in mindfulness practice.

Mindfulness-Based Stress Reduction (MBSR) is an experientially based group intervention empirically supported to reduce psychological symptomology. Although MBSR has shown to be an effective intervention, little is known about which facets of the intervention are important in producing positive outcomes. This study tested several aspects of mindfulness practice (total practice duration, practice frequency and practice quality) with the primary focus being on validating (i.e., predictive and convergent validity) a new measure of mindfulness practice quality (PQ-M). The PQ-M fit a two-factor solution via a Maximum Likelihood Exploratory Factor Analysis (n=99). Using longitudinal multilevel modeling on a smaller subsample (n=19), preliminary support was found for changes in practice quality over the course of the MBSR intervention. Further, change in practice quality was associated with improvements in psychological symptoms. While this study was exploratory, these findings suggest that practice quality is a relevant factor to promote positive outcomes and may guide mindfulness instructors in providing highly tailored interventions.

Expanding the product portfolio of carbon dioxide and hydrogen-based gas fermentation with an evolved strain of Clostridium carboxidivorans.

CO2:H2-based gas fermentation with acetogenic Clostridium species are at an early stage of development. This work exploited the Adaptive Laboratory Evolution technique to improve the growth of C. carboxidivorans P7 on CO2 and H2. An adapted strain with decreased growth lag phase and improved biomass production was obtained. Genomic analysis revealed a conserved frameshift mutation in the catalytic subunit of the hexameric hydrogenase gene. The resulted truncated protein variant, most likely lacking its functionality, suggests that other hydrogenases might be more efficient for H2-based growth of this strain. Furthermore, the adapted strain generated hexanol as primary fermentation product. For the first time, hexanol was produced directly from CO2:H2 blend, achieving the highest maximum productivity reported so far via gas fermentation. Traces of valerate, pentanol, eptanol and octanol were observed in the fermentation broth. The adapted strain shows promising to enrich the product spectrum targetable by future gas fermentation processes.