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Purpose of Review: This article aims to review and synthesize the current research evidence regarding the efficacy of telepsychiatry-delivered substance use disorder treatment using a narrative review with a focus on the effects of remote healthcare delivery within the substance abuse treatment space. Recent Findings: The COVID-19 pandemic exerted substantial pressures on all levels of society. Social isolation, loss of employment, stress, physical illness, overburdened health services, unmet medical needs, and rapidly changing pandemic restrictions had particularly severe consequences for people with mental health issues and substance use disorders. Since the start of the pandemic, addiction treatment (and medical treatment overall) using remote health platforms has significantly expanded to different platforms and delivery systems. The USA, in particular, reported transformational policy developments to enable the delivery of telehealth during the COVID-19 pandemic. However, systemic barriers such as a widespread lack of internet access and insufficient patient and provider digital skills remain. Summary: Overall, telepsychiatry is a promising approach for the treatment of substance use disorders, but more randomized controlled trials are needed in the future to assess the evidence base of available interventions.

PURPOSE OF REVIEW: This article aims to review and synthesize the current research evidence regarding the efficacy of telepsychiatry-delivered substance use disorder treatment using a narrative review with a focus on the effects of remote healthcare delivery within the substance abuse treatment space. RECENT FINDINGS: The COVID-19 pandemic exerted substantial pressures on all levels of society. Social isolation, loss of employment, stress, physical illness, overburdened health services, unmet medical needs, and rapidly changing pandemic restrictions had particularly severe consequences for people with mental health issues and substance use disorders. Since the start of the pandemic, addiction treatment (and medical treatment overall) using remote health platforms has significantly expanded to different platforms and delivery systems. The USA, in particular, reported transformational policy developments to enable the delivery of telehealth during the COVID-19 pandemic. However, systemic barriers such as a widespread lack of internet access and insufficient patient and provider digital skills remain. SUMMARY: Overall, telepsychiatry is a promising approach for the treatment of substance use disorders, but more randomized controlled trials are needed in the future to assess the evidence base of available interventions.

BackgroundOsteoporosis is often considered to be a disease of women. Over the last few years, owing to the increasing clinical and economic burden, the awareness and imperative for identifying and managing osteoporosis in men have increased substantially. With the approval of agents to treat men with osteoporosis, more economic evaluations have been conducted to assess the potential economic benefits of these interventions. Despite this concern, there is no specific overview of cost-effectiveness analyses for the treatment of osteoporosis in men.ObjectivesThis study aims (1) to systematically review economic evaluations of interventions for osteoporosis in men; (2) to critically appraise the quality of included studies and the source of model input data; and (3) to investigate the comparability of results for studies including both men and women.MethodsA literature search mainly using MEDLINE (via Ovid) and Embase databases was undertaken to identify original articles published between 1 January, 2000 and 30 June, 2022. Studies that assessed the cost effectiveness of interventions for osteoporosis in men were included. The Economic Aspects of Osteoporosis, Osteoarthritis and Musculoskeletal Diseases and the International Osteoporosis Foundation osteoporosis-specific guideline was used to assess the quality of design, conduct, and reporting of included studies.ResultsOf 2973 articles identified, 25 studies fulfilled the inclusion criteria, classified into economic evaluations of active drugs (n = 8) or nutritional supplements (n = 4), intervention thresholds (n = 5), screening strategies (n = 6), and post-fracture care programs (n = 2). Most studies were conducted in European countries (n = 15), followed by North America (n = 9). Bisphosphonates (namely alendronate) and nutritional supplements were shown to be generally cost effective compared with no treatment in men over 60 years of age with osteoporosis or prior fractures. Two other studies suggested that denosumab was cost effective in men aged 75 years and older with osteoporosis compared with bisphosphates and teriparatide. Intervention thresholds at which bisphosphonates were found to be cost effective varied among studies with a 10-year probability of a major osteoporotic fracture that ranged from 8.9 to 34.2% for different age categories. A few studies suggested cost effectiveness of screening strategies and post-fracture care programs in men. Similar findings regarding the cost effectiveness of drugs and intervention thresholds in women and men were captured, with slightly greater incremental cost-effectiveness ratios in men. The quality of the studies included had an average score of 18.8 out of 25 (range 13-23.5). Hip fracture incidence and mortality risk were mainly derived from studies in men, while fracture cost, treatment efficacy, and disutility were commonly derived from studies in women or studies combining both sexes.ConclusionsAnti-osteoporosis drugs and nutritional supplements are generally cost effective in men with osteoporosis. Screening strategies and post-fracture care programs also showed economic benefits for men. Cost-effectiveness and intervention thresholds were generally similar in studies conducted in both men and women, with slightly greater incremental cost-effectiveness ratios in men.

The economics literature emphasizes the importance of the elasticity of substitution between capital and labour in several economic contexts. However, analyses of the effect of the elasticity of substitution on the direction of technological change are often overlooked. Most assessments of the direction of technological change rely on a Constant Elasticity of Substitution (CES) production framework. This strand of empirical work considers the elasticity of substitution between capital and labour as a deep and fixed parameter. In this article, we show that the change in the elasticity of substitution that has occurred in recent decades might be an alternative source of change of factor income shares in addition to changes in factor-augmenting technological change. We construct a theoretical environment in which the elasticity of substitution is determined endogenously by the capital share and capital intensity. Rolling window estimates and non-linear estimation methods show that the elasticity of substitution in nine OECD economies observed between 1950 and 2017 was not constant and that, in fact, in the latter half of the 1970s, the elasticity of substitution increased, in the presence of labour-augmenting technical change.

This study examines the framing of the social movement in Iran launched on 29 December 2017, by analyzing the news texts of six national Turkish newspapers. It discusses the movement in the context of news framing, focusing on problem definition, causal interpretation, moral evaluation, and treatment recommendation. The findings suggest that each newspaper has reported the social movement in Iran quite differently. The most obvious difference is that the left-wing, anti-government press mainly explained the events in terms of political, economic, and social factors while the right-wing, pro-government press attributed the events to ‘foreign forces’ and reflected the dominant discourse of political power while framing the news. Thus, the way Turkish newspapers frame a social movement outside the country reveals the intense polarization in the Turkish press.

BackgroundThe relationship between the interventionist’s experience and outcomes of endovascular thrombectomy (EVT) for acute ischemic stroke of the anterior circulation, is unclear.ObjectiveTo assess the effect of the interventionist’s level of experience on clinical, imaging, and workflow outcomes. Secondly, to determine which of the three experience definitions is most strongly associated with these outcome measures.MethodsWe analysed data from 2700 patients, included in the MR CLEAN Registry. We defined interventionist’s experience as the number of procedures performed in the year preceding the intervention (EXPfreq), total number of procedures performed (EXPno), and years of experience (EXPyears). Our outcomes were the baseline-adjusted National Institutes of Health Stroke Scale (NIHSS) score at 24–48 hours post-EVT, recanalization (extended Thrombolysis in Cerebral Infarction (eTICI) score ≥2B), and procedural duration. We used multilevel regression models with interventionists as random intercept. For EXPfreq and EXPno results were expressed per 10 procedures.ResultsIncreased EXPfreq was associated with lower 24–48 hour NIHSS scores (adjusted (a)β:−0.46, 95% CI −0.70 to −0.21). EXPno and EXPyears were not associated with short-term neurological outcomes. Increased EXPfreq and EXPno were both associated with recanalization (aOR=1.20, 95% CI 1.11 to 1.31 and aOR=1.08, 95% CI 1.04 to 1.12, respectively), and increased EXPfreq, EXPno, and EXPyears were all associated with shorter procedure times (aβ:−3.08, 95% CI−4.32 to −1.84; aβ:−1.34, 95% CI−1.84 to −0.85; and aβ:−0.79, 95% CI−1.45 to −0.13, respectively).ConclusionsHigher levels of interventionist’s experience are associated with better outcomes after EVT, in particular when experience is defined as the number of patients treated in the preceding year. Every 20 procedures more per year is associated with approximately one NIHSS score point decrease, an increased probability for recanalization (aOR=1.44), and a 6-minute shorter procedure time.

Context: Although have been proven able to control the prevalence of coronavirus disease-19 (COVID-19), Pfizer-BioNTech and Moderna COVID-19 vaccines are reported to have possible side effects on the heart. Aims: To know the magnitude of adverse events in the cardiac after messenger ribonucleic acid (mRNA)-based vaccination. Methods: An electronic search in PubMed, Web of Science, Scopus, and Ebsco/Cinahl was performed. The keywords were: “COVID-19 vaccine”, “SARS-CoV-2 vaccine”, “myocarditis”, “myopericarditis”, “pericarditis”, “myocardial infarction”, and “myocardial injury”. The electronic search was updated until March 2022. STATA/MP Statistical Software: Release 14 (StataCorp LLC, College Station, Texas) was used in this study to perform a meta-analysis of a random-effect for myocarditis, pericarditis, myocarditis, myocardial infarction, and myocardial injury. Results: Twenty-one case reports/case series studies with a total of 62 individuals who had been vaccinated against COVID-19 mRNA (Pfizer-BioNTech and Moderna) were included in the systematic review. Whereas seven observational cohort studies had 170,053,333 people who had been vaccinated, 245 of whom had myocarditis. In addition, two observational cohort studies with 13,948,595 vaccinated individuals, 16 of whom developed pericarditis. There was only one observational cohort study that had a total of 7,183,889 people who had been vaccinated and 11 had myopericarditis. Based on the pooled incidence, the result is

Context: Although have been proven able to control the prevalence of coronavirus disease-19 (COVID-19), Pfizer-BioNTech and Moderna COVID-19 vaccines are reported to have possible side effects on the heart. Aims: To know the magnitude of adverse events in the cardiac after messenger ribonucleic acid (mRNA)-based vaccination. Methods: An electronic search in PubMed, Web of Science, Scopus, and Ebsco/Cinahl was performed. The keywords were: “COVID-19 vaccine”, “SARS-CoV-2 vaccine”, “myocarditis”, “myopericarditis”, “pericarditis”, “myocardial infarction”, and “myocardial injury”. The electronic search was updated until March 2022. STATA/MP Statistical Software: Release 14 (StataCorp LLC, College Station, Texas) was used in this study to perform a meta-analysis of a random-effect for myocarditis, pericarditis, myocarditis, myocardial infarction, and myocardial injury. Results: Twenty-one case reports/case series studies with a total of 62 individuals who had been vaccinated against COVID-19 mRNA (Pfizer-BioNTech and Moderna) were included in the systematic review. Whereas seven observational cohort studies had 170,053,333 people who had been vaccinated, 245 of whom had myocarditis. In addition, two observational cohort studies with 13,948,595 vaccinated individuals, 16 of whom developed pericarditis. There was only one observational cohort study that had a total of 7,183,889 people who had been vaccinated and 11 had myopericarditis. Based on the pooled incidence, the result is

The field of international business (IB) has been successful in developing a unique body of knowledge on the multinational corporation and on country-level contexts. A recurring debate concerns its claim to uniqueness, and to associated scholarly characteristics that distinguish IB from other fields of research. I discuss what makes IB research unique by looking at what IB theory can explain and predict. To that end, I leverage key theoretical arguments and empirical insights to advance an understanding of IB centered around a firm's ability to create added value in more than one location. I introduce a stylized model of the multi-locational firm embedded in multiple business systems characterized by equifinality. As a result of the qualitative disjunctures that separate one place from another, multi-locational firms are confronted with additional managerial and organizational challenges. These challenges are rooted in the process of "othering". Theorizing on the critical constructs of place, space, and organization, I argue that IB offers the most generalizable approach to understanding firms doing business in more than one location. IB's ultimate uniqueness lies in the potential of advancing a general theory of the firm in space.Le domaine des affaires internationales (International Business - IB) a réussi à développer un corpus unique de connaissances sur l’entreprise multinationale et les contextes au niveau du pays. Un débat récurrent porte sur sa prétention à l'unicité et les caractéristiques scientifiques associées qui distinguent l'IB des autres domaines de recherche. Je discute de ce qui rend la recherche en IB unique en examinant ce que la théorie de l'IB peut expliquer et prévoir. Pour ce faire, je m'appuie sur des évidences empiriques et des arguments théoriques clés afin d’élaborer une meilleure compréhension de l’IB centrée sur la capacité d'une entreprise à créer de la valeur ajoutée dans plus d'une localisation. J'introduis un modèle stylisé de l'entreprise multi-localisée encastrée dans de multiples systèmes commerciaux caractérisés par l'équifinalité. En raison des disjonctions qualitatives qui séparent un lieu d'un autre, les entreprises multi-localisées sont confrontées à des défis organisationnels et managériaux supplémentaires. Ces défis sont ancrés dans le processus d'« altérisation ». M'appuyant sur les construits cardinaux de lieu, d'espace et d'organisation, j’argumente que l'IB apporte l'approche la plus généralisable pour comprendre les entreprises opérant dans plus d'une localisation. L'unicité suprême de l'IB réside dans son potentiel à faire progresser une théorie générale de l'entreprise dans l'espace.El campo de negocios internacionales (IB por sus iniciales en inglés) ha venido desarrollando exitosamente un cuerpo de conocimientos único sobre la empresa multinacional y los contextos nacionales. Un debate recurrente se refiere a su pretensión de ser único y a las características académicas asociadas que distinguen a las empresas internacionales de otros campos de investigación. Discuto lo que hace que la investigación sobre negocios internacionales sea única examinando lo que la teoría de negocios internacionales puede explicar y predecir. Para esa finalidad, me apalanco en los principales argumentos teóricos y las ideas empíricas para avanzar en la comprensión de la IB centrada en la capacidad de una empresa para crear valor agregado en más de un lugar. Introduzco un modelo estilizado de empresa multilocalizada integrada en múltiples sistemas empresariales caracterizados por la equifinalidad. Como resultado de las disyuntivas cualitativas que separan un lugar de otro, las empresas multilocalizadas se enfrentan a retos adicionales de gestión y organización. Estos retos tienen su origen en el proceso de “otredad”. Teorizando sobre los conceptos críticos de lugar, espacio y organización, sostengo que negocios internacionales ofrece el enfoque más generalizable para entender a las empresas que hacen negocios en más de un lugar. La particularidad fundamental de la negocios internacionales radica en el potencial de avance de una teoría general de la empresa en el espacio.A área de negócios internacionais (IB) tem tido sucesso no desenvolvimento de um corpo único de conhecimento sobre a corporação multinacional e contextos em nível de país. Um debate recorrente diz respeito à sua reivindicação de singularidade e características acadêmicas associadas que distinguem IB de outros campos de pesquisa. Discuto o que torna a pesquisa em IB única ao observar o que a teoria em IB pode explicar e prever. Para esse fim, utilizo essenciais argumentos teóricos e insights empíricos para avançar na compreensão de IB centrado na capacidade de uma empresa de criar valor agregado em mais de um local. Apresento um modelo estilizado da empresa multilocalizada incorporada em vários sistemas de negócios caracterizados pela equifinalidade. Como resultado das disjunções qualitativas que separam um lugar do outro, as empresas multilocais são confrontadas com desafios administrativos e organizacionais adicionais. Esses desafios estão enraizados no processo de ostracismo. Teorizando sobre os construtos críticos de lugar, espaço e organização, argumento que IB oferece a abordagem mais generalizável para entender empresas que fazem negócios em mais de um local. A singularidade decisiva de IB está no potencial de avançar uma teoria geral da firma no espaço.国际商务 (IB) 领域成功地开发了关于跨国公司和国家层面情境的独特知识体系。一个反复出现的争论涉及其声称的独特性， 以及将 IB 与其它研究领域区分开来的相关学术特征。我通过审视 IB 理论可解释和预测的内容来讨论是什么让 IB 研究与众不同。为此， 我利用关键的理论论据和实证见解来增进对以公司在多于一个地点创造附加值的能力为中心的IB 的理解， 我提出了一个以等价性为特征的嵌入多业务系统中的多地点公司的程式化模型。由于将一个地方与另一个地方分隔开来的性质脱节， 多地点公司面临额外的管理和组织挑战。这些挑战植根于“他者化”过程。通过对场地、空间和组织的关键概念进行理论化， 我认为 IB 提供了一种最通用的方法来理解在多个地点开展业务的公司。IB 的最终独特性在于在空间发展公司通用理论的潜力。.

ObjectivesTo describe the global trends of pulmonary nontuberculous mycobacteria (NTM) infection and disease.MethodsA systematic review of studies including culture-based NTM data over time. Studies reporting on pulmonary NTM infection and/or disease were included. Information on the use of guideline-based criteria for disease were collected, in which, infection is defined as the absence of symptoms and radiological findings compatible with NTM pulmonary disease. The trends of change for incidence/prevalence were evaluated using linear regressions, and the corresponding pooled estimates were calculated.ResultsMost studies reported increasing pulmonary NTM infection (82.1%) and disease (66.7%) trends. The overall annual rate of change for NTM infection and disease per 100,000 persons/year was 4.0% (95% confidence interval [CI]: 3.2-4.8) and 4.1% (95% CI: 3.2-5.0), respectively. For absolute numbers of NTM infection and disease, the overall annual change was 2.0 (95% CI: 1.6-2.3) and 0.5 (95% CI: 0.3-0.7), respectively. An increasing trend was also seen for Mycobacterium avium complex infection (n = 15/19, 78.9%) and disease (n = 10/12, 83.9%) and for Mycobacterium abscessus complex (n = 15/23, 65.2%) infection (n = 11/17, 64.7%) but less so for disease (n = 2/8, 25.0%).ConclusionOur data indicate an overall increase in NTM worldwide for both infection and disease. The explanation to this phenomenon warrants further investigation. Objectives: To describe the global trends of pulmonary nontuberculous mycobacteria (NTM) infection and disease.Methods: A systematic review of studies including culture-based NTM data over time. Studies reporting on pulmonary NTM infection and/or disease were included. Information on the use of guideline-based criteria for disease were collected, in which, infection is defined as the absence of symptoms and radiological findings compatible with NTM pulmonary disease. The trends of change for incidence/prevalence were evaluated using linear regressions, and the corresponding pooled estimates were calculated.Results: Most studies reported increasing pulmonary NTM infection (82.1%) and disease (66.7%) trends. The overall annual rate of change for NTM infection and disease per 10 0,000 persons/year was 4.0% (95% confidence interval [CI]: 3.2-4.8) and 4.1% (95% CI: 3.2-5.0), respectively. For absolute numbers of NTM infection and disease, the overall annual change was 2.0 (95% CI: 1.6-2.3) and 0.5 (95% CI: 0.3-0.7), respectively. An increasing trend was also seen for Mycobacterium avium complex infection (n = 15/19, 78.9%) and disease (n = 10/12, 83.9%) and for Mycobacterium abscessus complex (n = 15/23, 65.2%) infection (n = 11/17, 64.7%) but less so for disease (n = 2/8, 25.0%).Conclusion: Our data indicate an overall increase in NTM worldwide for both infection and disease. The explanation to this phenomenon warrants further investigation.(c) 2022 The Author(s). Published by Elsevier Ltd on behalf of International Society for Infectious Diseases. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/)

Lead is an environmental hazard that should be addressed worldwide. Over time, human lead exposure in the western world has decreased drastically to levels comparable to those among humans living in the preindustrial era, who were mainly exposed to natural sources of lead. To re-evaluate the potential health risks associated with present-day lead exposure, a two-pronged approach was applied. First, recently published population metrics describing the adverse health effects associated with lead exposure at the population level were critically assessed. Next, the key results of the Study for Promotion of Health in Recycling Lead (SPHERL; NCT02243904) were summarized and put in perspective with those of the published population metrics. To our knowledge, SPHERL is the first prospective study that accounted for interindividual variability between people with respect to their vulnerability to the toxic effects of lead exposure by assessing the participants' health status before and after occupational lead exposure. The overall conclusion of this comprehensive review is that mainstream ideas about the public and occupational health risks related to lead exposure urgently need to be updated because a large portion of the available literature became obsolete given the sharp decrease in exposure levels over the past 40 years. ispartof: HYPERTENSION RESEARCH vol:46 issue:2 pages:395-407 ispartof: location:England status: published

An increasing number of states permit dual citizenship, but there are public concerns about divided loyalties of dual citizens which might lead to intolerance of their political rights. We propose and test whether these concerns depend on the emotional versus instrumental reasons immigrants express for acquiring their second, host society citizenship. Using a survey experiment on a nationally representative sample of native-born Dutch, we find that emotional (vs. instrumental) reasons for a second citizenship lead to higher perceived host society loyalty, which is related to greater political tolerance of dual citizens. Instrumental reason for dual citizenship leads to higher perceived loyalty to the country of origin; however, this is not related to political tolerance of such dual citizens. Implications for theory and society are considered.

Purpose To design a model based on the three pillars of new institutional theory (NIT), that facilitates cross-country comparison of labor participation (LP) of people with chronic diseases. This model should support getting a comprehensive overview of factors representing country differences, understanding these differences and should support estimating cross-country transferability of policies and interventions in the context of Work Disability Prevention. Methods Based on NIT, a draft model was designed by means of (1) a literature review of empirical studies; (2) theoretical books and articles; (3) a focus group with six expert researchers. This draft model was (4) adapted in the context of academic education. Literature was searched on Web of Science and EBSCO host. Feedback on (use of) the model was received from the focus group, four different academic courses at 28 occasions and two international conferences. Results The cross-country comparison model for labor participation (CCC model for LP) of persons with chronic diseases is proposed consisting of five factors: (1) Legislation; (2) Norms & values in practice; (3) Culture; (4) Organization of WDP in practice; (5) Labor market characteristics. Within these factors and based on (in)direct empirical evidence, subfactors are distinguished. The feedback received led to renaming (sub) factors, improved visual representation and a tool for estimating transferability. Conclusions The CCC model for LP of persons with chronic diseases allows for a comprehensive understanding of country differences and cross-country transferability of policies and interventions. The CCC model can be used for other populations when population-specific subfactors are included.

Significant maternal and fetal morbidity and mortality risk has been shown to be associated with cardiovascular disease in pregnancy. Several determinants, such as the increasing number of females with corrected congenital heart disease in reproductive age, a more advanced maternal age associated with cardiovascular risk factors, and a greater prevalence of preexisting comorbidities related to cardiac disorders such as cancer and COVID-19), lead to a higher incidence of cardiac complications in pregnancy in the last few decades. However, adopting a multidisciplinary strategy may influence maternal and neonatal outcomes. This review aims at assessing the role of the Pregnancy Heart Team, which should ensure careful pre-pregnancy counseling, pregnancy monitoring, and delivery planning for both congenital and other cardiac or metabolic disorders, addressing several emerging aspects in the multidisciplinary team-based approach.

Background This study aims to assess the uptake of maternal pertussis and COVID-19 vaccination and the intention towards accepting the maternal influenza vaccination. Insights into different socio-demographic factors related to maternal vaccination coverage might help to address vaccine acceptance and improve maternal vaccine uptake in the future. Methods We conducted a cross-sectional survey among pregnant women and recent mothers, up to 6 months post-partum. The primary outcome measures of this study were behaviour for maternal pertussis and COVID-19 vaccination, and maternal influenza vaccination intention. Associations between socio-demographic factors and maternal pertussis vaccination and maternal COVID-19 vaccination behaviour; and socio-demographic factors and maternal influenza vaccination intention were assessed using binary logistic regression analyses. Results In total 1361 respondents filled out the questionnaire. Almost all women (95%) were vaccinated against pertussis during pregnancy, while almost two-third were vaccinated against COVID-19 during pregnancy (58%) and almost one-third (28%) had a positive intention towards receiving the maternal influenza vaccination. Results show that young maternal age and low education level were associated with lower maternal vaccination acceptance. Conclusion Vaccination campaigns focusing on the severity of diseases that are prevented, are needed to increase maternal vaccine acceptance in younger and low-educated pregnant women. We expect that differences in vaccination coverage between the three maternal vaccinations might partly be explained by existing recommendations, campaigns and whether the vaccination is part of the national immunisation program.

Purpose With increased concomitant chronic diseases in type 2 diabetes mellitus (T2DM), the use of multiple drugs increases as well as the risk of drug–drug interactions (DDI) and adverse drug reactions (ADR). Nevertheless, how medication patterns vary in T2DM patients across different sex and age groups is unclear. This study aims to identify and quantify common drug combinations in first-time metformin users with polypharmacy (≥5 co-medications). Methods New users of metformin were identified from the IQVIA Medical Research Data incorporating data from THIN, A Cegedim Database (2016–2019). A descriptive cohort study explored prescription patterns in patients with polypharmacy. The Apriori algorithm, used to find frequent item-sets in databases, was first-time applied to identify and quantify drug combinations of up to seven drugs to investigate potential harmful polypharmacy patterns. Results The cohort included 34 169 new-users of metformin, of which 20 854 (61.0%) received polypharmacy. Atorvastatin was the most frequently co-prescribed drug with metformin overall (38.7%), in women (34.3%) and men (42.6%). In the stratified analysis, a higher proportion of women received polypharmacy (65.6%) compared to men (57.4%). Moreover, the proportion of patients receiving polypharmacy increased with age (18–39 years = 30.4%, 40–59 years = 50.5%, 60–74 years = 70.9%, and ≥75 years = 84.3%). Conclusion This study is the first to identify and quantify commonly prescribed combinations of drugs compounds in patients with polypharmacy using the Apriori algorithm. The high polypharmacy prevalence at all strata indicates the need to optimize polypharmacy to minimize DDI and ADR., Pharmacoepidemiology and Drug Safety, 32 (3), ISSN:1053-8569, ISSN:1099-1557

Purpose: To compare napabucasin (generator of reactive oxygen species) plus paclitaxel with paclitaxel only in patients with second-line advanced gastric or gastroesophageal junction (GEJ) adenocarcinoma. Patients and Methods: In the double-blind, phase III BRIGHTER study (NCT02178956), patients were randomized (1:1) to napabucasin (480 mg orally twice daily) plus paclitaxel (80 mg/m2 i.v. weekly for 3 of 4 weeks) or placebo plus paclitaxel. The primary endpoint was overall survival (OS). Secondary endpoints included progression-free survival (PFS), objective response rate (ORR), disease control rate (DCR), and safety. Results: Overall, 714 patients were randomized (napabucasin plus paclitaxel, n = 357; placebo plus paclitaxel, n = 357). 72.1% were male, 74.6% had gastric adenocarcinoma, and 46.2% had peritoneal metastases. The study was unblinded following an interim analysis at 380 deaths. The final efficacy analysis was performed on 565 deaths (median follow-up, 6.8 months). No significant differences were observed between napabucasin plus paclitaxel and placebo plus paclitaxel for OS (6.93 vs. 7.36 months), PFS (3.55 vs. 3.68 months), ORR (16% vs. 18%), or DCR (55% vs. 58%). Grade ≥3 adverse events occurred in 69.5% and 59.7% of patients administered napabucasin plus paclitaxel and placebo plus paclitaxel, respectively, with grade ≥3 diarrhea reported in 16.2% and 1.4%, respectively. Conclusions: Adding napabucasin to paclitaxel did not improve survival in patients with pretreated advanced gastric or GEJ adenocarcinoma. Consistent with previous reports, the safety profile of napabucasin was driven by manageable gastrointestinal events; grade ≥3 diarrhea occurred at a higher frequency with napabucasin plus paclitaxel versus placebo plus paclitaxel.

Control of swine influenza A virus (swIAV) in North America and Europe is complicated because multiple antigenically distinct swIAV strains co-circulate in the field, and no vaccine is available that can provide broad cross-protection against all these swIAVs. In 2017, the first live attenuated influenza vaccine (LAIV) for swine was licensed in the US. The non-structural protein 1 (NS1)-truncated cluster I H3N2 strain A/swine/Texas/4199-2/98 NS1del126 (TX98 LAIV) in this vaccine provides partial cross-protection against heterologous North American cluster II and IV H3N2 swIAV strains. Its efficacy against European or more recent North American H3N2 lineages remains to be investigated. In this study, we evaluated the level of cross-protection against heterologous IAVs representative of the major H3N2 swIAV lineages in Europe and North America. TX98 LAIV prevented both nasal shedding and replication in the lungs of a North American cluster IV H3N2 swIAV for 2/4 pigs, prevented considerable nasal shedding of a North American novel human-like H3N2 swIAV for 2/4 pigs, and reduced replication of a European H3N2 swIAV in the lower respiratory tract to minimal titers for 1/3 pigs. Although TX98 LAIV elicited neutralizing antibodies against the homologous virus in serum and to a lesser extent in nose and lungs, no significant cross-reactive antibody titers against the heterologous swIAVs were detected. Partial cross-protection therefore likely relies on cellular and mucosal immune responses against conserved parts of the swIAV proteins. Since TX98 LAIV can offer partial protection against a broad range of H3N2 swIAVs, it might be a suitable priming vaccine for use in a heterologous prime-boost vaccination strategy.

Objective To determine whether high-flow nasal cannula oxygen (HFNCO) provided enhanced respiratory support in bronchiolitis than low-flow oxygen (LFO). Methods We conducted a prospective, randomized controlled trial in children between 1 and 24 months diagnosed with moderate-to-severe bronchiolitis requiring oxygen therapy. Participants received LFO via face mask (6-10 L/min) or HFNCO (2 L/kg/min). Primary outcomes were the time that heart rate (HR) and respiratory rate (RR) return to their normal range for age and the time that baseline clinical respiratory score (CRS) regress to a lower severity score. Secondary outcomes were changes in HR, RR, and CRS over time, length of stay (LOS), duration of oxygen requirement, treatment failure, and adverse event (AE). Results Eighty-seven children were enrolled (48 in LFO; 39 in HFNCO). The time that HR and RR baseline values reached their normal range for age was shorter in HFNCO therapy (2.0 h [1.0-4.0] vs. 12.0 h [2.0-24.0], and 4.0 h [2.0-12.0] vs. 24.0 h [4.0-48.0], respectively; p < 0.001); additionally, the improvement in CRS emerged more quickly in children treated with HFNCO (2.0 h [1.0-4.0] vs. 4.0 h [2.0-24.0]; p = 0.003). While the duration of oxygen requirement (19.0 h [4.0-30.0] vs. 29.5 h [14.0-45.7]; p = 0.009) and treatment failure (3% vs. 21%) was statistically lower in children who received HFNCO, there were no differences in LOS and AE between groups. Conclusion HFNCO may provide enhanced respiratory support with a notable improvement in HR, RR, and CRS than LFO. Comprehensive studies are needed to assess the clinical efficacy of HFNCO therapy., Ege University Research Foundation [17-2.1/18], Ege University Research Foundation, Grant/Award Number: 17-2.1/18

Purpose: To evaluate patient-reported sexual outcomes after chemoradiation therapy and image-guided adaptive brachytherapy for locally advanced cervical cancer in the observational, prospective, multicenter EMBRACE-I study. Methods and Materials: Sexual outcomes were assessed prospectively with the European Organization for Research and Treatment of Cancer Qualify of Life Questionnaire (EORTC-QLQ-CX24) at baseline and follow-up. Crude incidence and prevalence rates of sexual activity, vaginal functioning problems (dryness, shortening, tightening, pain during intercourse), and sexual enjoyment were evaluated. Associations between pain during intercourse and vaginal functioning problems or sexual enjoyment were calculated, pooling observations over all follow-ups (Spearman correlation coefficient). In patients who were frequently sexually active (≥50% of follow-ups), the effects of regular hormonal replacement therapy (HRT) on vaginal functioning problems were evaluated (Pearson χ 2). Results: The analysis involved 1045 patients with a median follow-up of 50 months. Sexual activity was reported by 22% of patients at baseline and by 40% to 47% of patients during follow-up (prevalence rates). Vaginal functioning problems in follow-up were dryness (18%-21%), shortening (15%-22%), tightening (16%-22%), pain during intercourse (9%-21%), and compromised enjoyment (37%-47%). Pain during intercourse was significantly associated with vaginal tightening (r = 0.544), shortening (r = 0.532), and dryness (r = 0.408) and negatively correlated with sexual enjoyment (r = –0.407). Regular HRT was associated with significantly less vaginal dryness (P = .015), shortening (P = .024), pain during intercourse (P = .003), and borderline higher sexual enjoyment (P = .062). Conclusions: Vaginal functioning problems are associated with pain and compromised sexual enjoyment. Further effort is required for the primary prevention of vaginal morbidity with dose optimization and adaptation. Secondary prevention strategies, including HRT for vaginal and sexual health after radiation therapy in locally advanced cervical cancer, should be considered and sexual rehabilitation programs should be developed further.

Biomaterial-associated infections (BAIs) are an increasing problem where antibiotic therapies are often ineffective. The design of novel strategies to prevent or combat infection requires a better understanding of how an implanted foreign body prevents the immune system from eradicating surface-colonizing pathogens. The objective of this review is to chart factors resulting in sub-optimal clearance of Staphylococcus aureus bacteria involved in BAIs. To this end, we first describe three categories of bacterial mechanisms to counter the host immune system around foreign bodies: direct interaction with host cells, modulation of intercellular communication, and evasion of the immune system. These mechanisms take place in a time frame that differentiates sterile foreign body reactions, BAIs, and soft tissue infections. In addition, we identify experimental interventions in S. aureus BAI that may impact infectious mechanisms. Most experimental treatments modulate the host response to infection or alter the course of BAI through implant surface modulation. In conclusion, the first week after implantation and infection is crucial for the establishment of an S. aureus biofilm that resists the local immune reaction and antibiotic treatment. Although established and chronic S. aureus BAI is still treatable and manageable, the focus of interventions should lie on this first period.

BACKGROUND AND AIMS: Increased fatty acid (FA) flux from adipose tissue to the liver contributes to the development of NAFLD. Because free FAs are key lipotoxic triggers accelerating disease progression, inhibiting adipose triglyceride lipase (ATGL)/patatin-like phospholipase domain containing 2 (PNPLA2), the main enzyme driving lipolysis, may attenuate steatohepatitis. APPROACH AND RESULTS: Hepatocyte-specific ATGL knockout (ATGL LKO) mice were challenged with methionine-choline-deficient (MCD) or high-fat high-carbohydrate (HFHC) diet. Serum biochemistry, hepatic lipid content and liver histology were assessed. Mechanistically, hepatic gene and protein expression of lipid metabolism, inflammation, fibrosis, apoptosis, and endoplasmic reticulum (ER) stress markers were investigated. DNA binding activity for peroxisome proliferator-activated receptor (PPAR) α and PPARδ was measured. After short hairpin RNA-mediated ATGL knockdown, HepG2 cells were treated with lipopolysaccharide (LPS) or oleic acid:palmitic acid 2:1 (OP21) to explore the direct role of ATGL in inflammation in vitro. On MCD and HFHC challenge, ATGL LKO mice showed reduced PPARα and increased PPARδ DNA binding activity when compared with challenged wild-type (WT) mice. Despite histologically and biochemically pronounced hepatic steatosis, dietary-challenged ATGL LKO mice showed lower hepatic inflammation, reflected by the reduced number of Galectin3/MAC-2 and myeloperoxidase-positive cells and low mRNA expression levels of inflammatory markers (such as IL-1β and F4/80) when compared with WT mice. In line with this, protein levels of the ER stress markers protein kinase R-like endoplasmic reticulum kinase and inositol-requiring enzyme 1α were reduced in ATGL LKO mice fed with MCD diet. Accordingly, pretreatment of LPS-treated HepG2 cells with the PPARδ agonist GW0742 suppressed mRNA expression of inflammatory markers. Additionally, ATGL knockdown in HepG2 cells attenuated LPS/OP21-induced expression of proinflammatory cytokines and chemokines such as chemokine (C-X-C motif) ligand 5, chemokine (C-C motif) ligand (Ccl) 2, and Ccl5. CONCLUSIONS: Low hepatic lipolysis and increased PPARδ activity in ATGL/PNPLA2 deficiency may counteract hepatic inflammation and ER stress despite increased steatosis. Therefore, lowering hepatocyte lipolysis through ATGL inhibition represents a promising therapeutic strategy for the treatment of steatohepatitis. ispartof: HEPATOLOGY vol:75 issue:1 pages:125-139 ispartof: location:United States status: published