Cost-effectiveness of blended vs. face-to-face cognitive behavioural therapy for severe anxiety disorders: study protocol of a randomized controlled trial

Background: Anxiety disorders are among the most prevalent psychiatric conditions, and are associated with poor quality of life and substantial economic burden. Cognitive behavioural therapy is an effective treatment to reduce anxiety symptoms, but is also costly and labour intensive. Cost-effectiveness could possibly be improved by delivering cognitive behavioural therapy in a blended format, where face-to-face sessions are partially replaced by online sessions. The aim of this trial is to determine the cost-effectiveness of blended cognitive behavioural therapy for adults with anxiety disorders, i.e. panic disorder, social phobia or generalized anxiety disorder, in specialized mental health care settings compared to face-to-face cognitive behavioural therapy. In this paper, we present the study protocol. It is hypothesized that blended cognitive behavioural therapy for anxiety disorders is clinically as effective as face-to-face cognitive behavioural therapy, but that intervention costs may be reduced. We thus hypothesize that blended cognitive behavioural therapy is more cost-effective than face-to-face cognitive behavioural therapy. Methods/design: In a randomised controlled equivalence trial 156 patients will be included (n = 78 in blended cognitive behavioural therapy, n = 78 in face-to-face cognitive behavioural therapy) based on a power of 0.80, calculated by using a formula to estimate the power of a cost-effectiveness analysis: $n = \frac{2(z_\alpha + z_\beta)^2(sd^2 + (W^2sd^2) - (2Wpsd_csd_q))}{(WE-C)^2}$ Measurements will take place at baseline, midway treatment (7 weeks), immediately after treatment (15 weeks) and 12-month follow-up. At baseline a diagnostic interview will be administered. Primary clinical outcomes are changes in anxiety symptom severity as measured with the Beck Anxiety Inventory. An incremental cost-effectiveness ratio will be calculated to obtain the costs per quality-adjusted life years (QALYs) measured by the EQ-5D (5-level version). Health-economic outcomes will be explored from a societal and health care perspective. Discussion: This trial will be one of the first to provide information on the cost-effectiveness of blended cognitive behavioural therapy for anxiety disorders in routine specialized mental health care settings, both from a societal and a health care perspective

Chemotherapy and Tyrosine Kinase Inhibitors in the last month of life in patients with metastatic lung cancer: A patient file study in the Netherlands

Objective: Chemotherapy in the last month of life for patients with metastatic lung cancer is often considered as aggressive end-of-life care. Targeted therapy with Tyrosine Kinase Inhibitors (TKIs) is a relatively new treatment of which not much is known yet about use in the last month of life. We examined what percentage of patients received chemotherapy or TKIs in the last month of life in the Netherlands. Methods: Patient files were drawn from 10 hospitals across the Netherlands. Patients had to meet the following eligibility criteria: metastatic lung cancer; died between June 1, 2013 and July 31, 2015. Results: From the included 1,322 patients, 39% received no treatment for metastatic lung cancer, 52% received chemotherapy and 9% received TKIs. A total of 232 patients (18%) received treatment in the last month of life (11% chemotherapy, 7% TKIs). From the patients who received chemotherapy, 145 (21%) received this in the last month of life and 79 (11%) started this treatment in the last month of life. TKIs were given and started more often in the last month of life: from the patients who received TKIs, 87 (72%) received this treatment in the last month of life and 15 (12%) started

Uncovering Genes with Divergent mRNA-Protein Dynamics in Streptomyces coelicolor

Many biological processes are intrinsically dynamic, incurring profound changes at both molecular and physiological levels. Systems analyses of such processes incorporating large-scale transcriptome or proteome profiling can be quite revealing. Although consistency between mRNA and proteins is often implicitly assumed in many studies, examples of divergent trends are frequently observed. Here, we present a comparative transcriptome and proteome analysis of growth and stationary phase adaptation in Streptomyces coelicolor, taking the time-dynamics of process into consideration. These processes are of immense interest in microbiology as they pertain to the physiological transformations eliciting biosynthesis of many naturally occurring therapeutic agents. A shotgun proteomics approach based on mass spectrometric analysis of isobaric stable isotope labeled peptides (iTRAQ™) enabled identification and rapid quantification of approximately 14% of the theoretical proteome of S. coelicolor. Independent principal component analyses of this and DNA microarray-derived transcriptome data revealed that the prominent patterns in both protein and mRNA domains are surprisingly well correlated. Despite this overall correlation, by employing a systematic concordance analysis, we estimated that over 30% of the analyzed genes likely exhibited significantly divergent patterns, of which nearly one-third displayed even opposing trends. Integrating this data with biological information, we discovered that certain groups of functionally related genes exhibit mRNA-protein discordance in a similar fashion. Our observations suggest that differences between mRNA and protein synthesis/degradation mechanisms are prominent in microbes while reaffirming the plausibility of such mechanisms acting in a concerted fashion at a protein complex or sub-pathway level

Selenium status is positively associated with bone mineral density in healthy aging European men

Objective It is still a matter of debate if subtle changes in selenium (Se) status affect thyroid function tests (TFTs) and bone mineral density (BMD). This is particularly relevant for the elderly, whose nutritional status is more vulnerable. Design and Methods We investigated Se status in a cohort of 387 healthy elderly men (median age 77 yrs; inter quartile range 75-80 yrs) in relation to TFTs and BMD. Se status was determined by measuring both plasma selenoprotein P (SePP) and Se. Results The overall Se status in our population was low normal with only 0.5% (2/387) of subjects meeting the criteria for Se deficiency. SePP and Se levels were not associated with thyroid stimulating hormone (TSH), free thyroxine (FT4), thyroxine (T4), triiodothyronine (T3) or reverse triiodothyronine (rT3) levels. The T3/T4 and T3/rT3 ratios, reflecting peripheral metabolism of thyroid hormone, were not associated with Se status either. SePP and Se were positively associated with total BMD and femoral trochanter BMD. Se, but not SePP, was positively associated with femoral neck and ward's BMD. Multivariate linear analyses showed that these associations remain statistically significant in a model including TSH, FT4, body mass index, physical performance score, age, smoking, diabetes mellitus and number of medication use. Conclusion Our study demonstrates that Se status, within the normal European marginally supplied range, is positively associated with BMD in healthy aging men, independent of thyroid function. Thyroid function tests appear unaffected by Se status in this population

Antimicrobial resistance among migrants in Europe: a systematic review and meta-analysis

BACKGROUND: Rates of antimicrobial resistance (AMR) are rising globally and there is concern that increased migration is contributing to the burden of antibiotic resistance in Europe. However, the effect of migration on the burden of AMR in Europe has not yet been comprehensively examined. Therefore, we did a systematic review and meta-analysis to identify and synthesise data for AMR carriage or infection in migrants to Europe to examine differences in patterns of AMR across migrant groups and in different settings. METHODS: For this systematic review and meta-analysis, we searched MEDLINE, Embase, PubMed, and Scopus with no language restrictions from Jan 1, 2000, to Jan 18, 2017, for primary data from observational studies reporting antibacterial resistance in common bacterial pathogens among migrants to 21 European Union-15 and European Economic Area countries. To be eligible for inclusion, studies had to report data on carriage or infection with laboratory-confirmed antibiotic-resistant organisms in migrant populations. We extracted data from eligible studies and assessed quality using piloted, standardised forms. We did not examine drug resistance in tuberculosis and excluded articles solely reporting on this parameter. We also excluded articles in which migrant status was determined by ethnicity, country of birth of participants' parents, or was not defined, and articles in which data were not disaggregated by migrant status. Outcomes were carriage of or infection with antibiotic-resistant organisms. We used random-effects models to calculate the pooled prevalence of each outcome. The study protocol is registered with PROSPERO, number CRD42016043681. FINDINGS: We identified 2274 articles, of which 23 observational studies reporting on antibiotic resistance in 2319 migrants were included. The pooled prevalence of any AMR carriage or AMR infection in migrants was 25·4% (95% CI 19·1-31·8; I2 =98%), including meticillin-resistant Staphylococcus aureus (7·8%, 4·8-10·7; I2 =92%) and antibiotic-resistant Gram-negative bacteria (27·2%, 17·6-36·8; I2 =94%). The pooled prevalence of any AMR carriage or infection was higher in refugees and asylum seekers (33·0%, 18·3-47·6; I2 =98%) than in other migrant groups (6·6%, 1·8-11·3; I2 =92%). The pooled prevalence of antibiotic-resistant organisms was slightly higher in high-migrant community settings (33·1%, 11·1-55·1; I2 =96%) than in migrants in hospitals (24·3%, 16·1-32·6; I2 =98%). We did not find evidence of high rates of transmission of AMR from migrant to host populations. INTERPRETATION: Migrants are exposed to conditions favouring the emergence of drug resistance during transit and in host countries in Europe. Increased antibiotic resistance among refugees and asylum seekers and in high-migrant community settings (such as refugee camps and detention facilities) highlights the need for improved living conditions, access to health care, and initiatives to facilitate detection of and appropriate high-quality treatment for antibiotic-resistant infections during transit and in host countries. Protocols for the prevention and control of infection and for antibiotic surveillance need to be integrated in all aspects of health care, which should be accessible for all migrant groups, and should target determinants of AMR before, during, and after migration. FUNDING: UK National Institute for Health Research Imperial Biomedical Research Centre, Imperial College Healthcare Charity, the Wellcome Trust, and UK National Institute for Health Research Health Protection Research Unit in Healthcare-associated Infections and Antimictobial Resistance at Imperial College London

How is tailored implementation undertaken using a self-guided toolkit? Qualitative study of the ItFits-toolkit in the ImpleMentAll project

BackgroundThe process of tailored implementation is ill-defined and under-explored. The ItFits-toolkit was developed and subsequently tested as a self-guided online platform to facilitate implementation of tailored strategies for internet-based cognitive behavioural therapy (iCBT) services. In ImpleMentAll, ItFits-toolkit had a small but positive effect on the primary outcome of iCBT normalisation. This paper investigates, from a qualitative perspective, how implementation teams developed and undertook tailored implementation using the toolkit within the trial.MethodsImplementation teams in thirteen sites from nine countries (Europe and Australia) used the ItFits-toolkit for six months minimum, consistent with the trial protocol. A qualitative process evaluation was conducted. Descriptive data regarding goals, barriers, strategies, and implementation plans collected within the toolkit informed qualitative data collection in real time. Qualitative data included remote longitudinal interviews (n = 55) with implementation team members (n = 30) and observations of support calls (n = 19) with study sites. Qualitative data were analysed thematically, using a team-based approach.ResultsImplementation teams developed and executed tailored implementation projects across all steps in the toolkit process. Working in a structured way but with room for flexibility, decisions were shaped by team members' ideas and goals, iterative stakeholder engagement, internal and external influences, and the context of the ImpleMentAll project. Although teams reported some positive impacts of their projects, 'time', both for undertaking the work, and for seeing project impacts, was described as a key factor in decisions about implementation strategies and assessments of success.ConclusionThis study responds directly to McHugh et al.'s (2022) call for empirical description of what implementation tailoring looks like in action, in service settings. Self-guided facilitation of tailored implementation enables implementers in service settings to undertake tailoring within their organisations. Implementation tailoring takes considerable time and involves detailed work but can be supported through the provision of implementation science informed guidance and materials, iterative and ongoing stakeholder engagement, and working reflectively in response to external influencing factors. Directions for advancement of tailored implementation are suggested

The association between alcohol use, alcohol use disorders and tuberculosis (TB). A systematic review

<p>Abstract</p> <p>Background</p> <p>In 2004, tuberculosis (TB) was responsible for 2.5% of global mortality (among men 3.1%; among women 1.8%) and 2.2% of global burden of disease (men 2.7%; women 1.7%). The present work portrays accumulated evidence on the association between alcohol consumption and TB with the aim to clarify the nature of the relationship.</p> <p>Methods</p> <p>A systematic review of existing scientific data on the association between alcohol consumption and TB, and on studies relevant for clarification of causality was undertaken.</p> <p>Results</p> <p>There is a strong association between heavy alcohol use/alcohol use disorders (AUD) and TB. A meta-analysis on the risk of TB for these factors yielded a pooled relative risk of 2.94 (95% CI: 1.89-4.59). Numerous studies show pathogenic impact of alcohol on the immune system causing susceptibility to TB among heavy drinkers. In addition, there are potential social pathways linking AUD and TB. Heavy alcohol use strongly influences both the incidence and the outcome of the disease and was found to be linked to altered pharmacokinetics of medicines used in treatment of TB, social marginalization and drift, higher rate of re-infection, higher rate of treatment defaults and development of drug-resistant forms of TB. Based on the available data, about 10% of the TB cases globally were estimated to be attributable to alcohol.</p> <p>Conclusion</p> <p>The epidemiological and other evidence presented indicates that heavy alcohol use/AUD constitute a risk factor for incidence and re-infection of TB. Consequences for prevention and clinical interventions are discussed.</p

Application of a risk-management framework for integration of stromal tumor-infiltrating lymphocytes in clinical trials

Stromal tumor-infiltrating lymphocytes (sTILs) are a potential predictive biomarker for immunotherapy response in metastatic triple-negative breast cancer (TNBC). To incorporate sTILs into clinical trials and diagnostics, reliable assessment is essential. In this review, we propose a new concept, namely the implementation of a risk-management framework that enables the use of sTILs as a stratification factor in clinical trials. We present the design of a biomarker risk-mitigation workflow that can be applied to any biomarker incorporation in clinical trials. We demonstrate the implementation of this concept using sTILs as an integral biomarker in a single-center phase II immunotherapy trial for metastatic TNBC (TONIC trial, NCT02499367), using this workflow to mitigate risks of suboptimal inclusion of sTILs in this specific trial. In this review, we demonstrate that a web-based scoring platform can mitigate potential risk factors when including sTILs in clinical trials, and we argue that this framework can be applied for any future biomarker-driven clinical trial setting