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Resume Introduction La Therapie Comportementale Dialectique (TCD) vise a diminuer la dysregulation emotionnelle, notamment par l’apprentissage en groupe de competences. En mars 2020, le confinement du a la COVID-19 a interrompu brutalement ces groupes. Nous avons poursuivi cet apprentissage par videos YouTube. Notre objectif est d’evaluer la faisabilite de ce format pendant le confinement. Methode Tous les participants a des groupes d’entrainement aux competences TCD realises a Strasbourg ont ete inclus (n = 37). Les videos psychoeducatives ont ete publiees, de facon bihebdomadaire, durant le confinement sur la chaine YouTube « GREMO HUS ». Les participants ont ete encourages a visionner ces videos par appels/messages. Un mois apres la fin du confinement, un questionnaire en ligne a evalue la satisfaction. Resultats Au total, 92 % des patients ont repondu. Sur les 34 repondeurs, 28 (82 %) avaient regarde au moins une video, et 32 % plus de 6 videos. Une tres large majorite des utilisateurs etaient satisfaits des videos. Au total, 79 % se disaient fortement aides dans la comprehension des competences, et 77 % pensaient avoir utilise plus frequemment les competences TCD. Tous sauf un se sont dit aides par les competences pour mieux surmonter les difficultes en periode de confinement. Discussion Notre etude est la premiere a interroger directement des patients concernant des videos YouTube. Ces videos sont jugees pertinentes par les participants en periode de confinement. Leur utilisation pourrait etre un complement des groupes hors confinement, ainsi que pour la formation des therapeutes.

Key Points Question Are results of universal and selective screening for suicide risk implemented in a pediatric emergency department associated with future suicidal behaviors? Findings In this cohort study of 15 003 youths aged 8 to 18 years, positive screens were significantly associated with subsequent suicide-related hospital visits compared with standard emergency department procedures. Screening also more than doubled the detection of suicide risk compared with treatment as usual. Meaning These findings suggest that screening for suicide risk in pediatric emergency departments is an effective approach to identify risk for subsequent suicide-related emergency department visits., This cohort study examines the association between results of universal and selective screening for suicide risk in a pediatric emergency department using the Ask Suicide-Screening Questions (ASQ) instrument and subsequent suicide-related outcomes., Importance According to National Patient Safety Goal 15.01.01, all individuals being treated or evaluated for behavioral health conditions as their primary reason for care in hospitals and behavioral health care organizations accredited by The Joint Commission should be screened for suicide risk using a validated tool. Existing suicide risk screens have minimal or no high-quality evidence of association with future suicide-related outcomes. Objective To test the association between results of the Ask Suicide-Screening Questions (ASQ) instrument in a pediatric emergency department (ED), implemented through selective and universal screening approaches, and subsequent suicide-related outcomes. Design, Setting, and Participants In this retrospective cohort study at an urban pediatric ED in the United States, the ASQ was administered to youths aged 8 to 18 years with behavioral and psychiatric presenting problems from March 18, 2013, to December 31, 2016 (selective condition), and then to youths aged 10 to 18 years with medical presenting problems (in addition to those aged 8-18 years with behavioral and psychiatric presenting problems) from January 1, 2017, to December 31, 2018 (universal condition). Exposure Positive ASQ screen at baseline ED visit. Main Outcomes and Measures The main outcomes were subsequent ED visits with suicide-related presenting problems (ie, ideation or attempts) based on electronic health records and death by suicide identified through state medical examiner records. Association with suicide-related outcomes was calculated over the entire study period using survival analyses and at 3-month follow-up for both conditions using relative risk. Results The complete sample was 15 003 youths (7044 [47.0%] male; 10 209 [68.0%] black; mean [SD] age, 14.5 [3.1] years at baseline). The follow-up for the selective condition was a mean (SD) of 1133.7 (433.3) days; for the universal condition, it was 366.2 (209.2) days. In the selective condition, there were 275 suicide-related ED visits and 3 deaths by suicide. In the universal condition, there were 118 suicide-related ED visits and no deaths during the follow-up period. Adjusting for demographic characteristics and baseline presenting problem, positive ASQ screens were associated with greater risk of suicide-related outcomes among both the universal sample (hazard ratio, 6.8 [95% CI, 4.2-11.1]) and the selective sample (hazard ratio, 4.8 [95% CI, 3.5-6.5]). Conclusions and Relevance Positive results of both selective and universal screening for suicide risk in pediatric EDs appear to be associated with subsequent suicidal behavior. Screening may be a particularly effective way to detect suicide risk among those who did not present with ideation or attempt. Future studies should examine the impact of screening in combination with other policies and procedures aimed at reducing suicide risk.

Glioblastoma (GBM) is the most common primary malignant brain tumor in adults. Homocysteine (Hcy) has a detrimental influence on human neurons, considering that human GBM cells undergo cell death already at D,L-Hcy concentrations in culture medium of 50 μM. This data demonstrate that Hcy is a potent gliotoxic agent capable of inducing the death of human glial cells already at concentrations reached in brain during hyperhomocysteinemia. The one retrospective study found that the serum vitamin B12 level can be used to predict survival time in metastatic cancer patients including neurological cancer. Cancer risk increases with elevated vitamin B12 level, mostly within the first year of the follow-up period, suggesting that vitamin B12 level could be used as a cancer diagnostic marker. In addition, the relationship between elevated vitamin B12 level and poor cancer survival time has been reported. Previous investigation suggests that the folate supplementation could be used as an adjuvant in antiglioma therapy to limit the low DNA methylation level because this confers a poor prognosis in glioblastoma multiforme patients. Taking into account all presented data, it can be concluded that effect of homocystein, folic acid and vitamin B12 on formation, development and outcome of treatment in patients with carcinoma is very intriguing question, whose response requires additional both experimental and clinical research. There lack of data in the literature on the incidence of elevated levels of Hcy in the blood, as well as the disorders of folic acid and vitamin B12, at malignant tumors of the brain.

Sulfur-containing amino acids are integral part of molecular mechanisms which underlie many aspects of cellular function and homeostasis, facilitated by reversible changes in oxidation states of sulfur atoms. Dysregulation of these pathways is associated with diverse pathologies, notably of the cardiovascular system, which are typically characterized by inappropriate plasma levels of sulfur-containing amino acids. The aim of this study was to assess the acute, direct effects of sulfur-containing amino acids and inorganic NaHS, as H2S donor, on cardiodynamic parameters in homocysteine treated rats. Moderate hyperhomocysteinemia did not cause significant decrease in myocardial contractility, but our findings suggest that NaHS and L-methionine cause negative effects on cardiac function in hearts of the rats treated with homocysteine, even in a single administration. Further investigations need to be carried out with purpose of better understanding and highlightening the impact of Hcy and sulphur amino acids on cardiac function.

Noise spectroscopy elucidates the fundamental noise sources in spin systems, which is essential for developing spin qubits with long coherence times for quantum information processing, communication, and sensing. But noise spectroscopy typically relies on microwave coherent spin control to extract the noise spectrum, which becomes infeasible when there are high-frequency noise components stronger than the available microwave power. Here, we demonstrate an alternative all-optical approach to performing noise spectroscopy. Our approach utilises coherent Raman rotations of the spin state with controlled timing and phase to implement Carr-Purcell-Meiboom-Gill (CPMG) pulse sequences. Analysing the spin dynamics under these sequences enables us to extract the noise spectrum of a dense ensemble of nuclear spins interacting with a single spin in a quantum dot, which has thus far only been modelled theoretically. By providing large spectral bandwidths of over 100 MHz, our Raman-based approach could serve as an important tool to study spin dynamics and decoherence mechanisms for a broad range of solid-state spin qubits.

Multi-view classification with limited sample size and data augmentation is a very common machine learning (ML) problem in medicine. With limited data, a triplet network approach for two-stage representation learning has been proposed. However, effective training and verifying the features from the representation network for their suitability in subsequent classifiers are still unsolved problems. Although typical distance-based metrics for the training capture the overall class separability of the features, the performance according to these metrics does not always lead to an optimal classification. Consequently, an exhaustive tuning with all feature-classifier combinations is required to search for the best end result. To overcome this challenge, we developed a novel nearest-neighbor (NN) validation strategy based on the triplet metric. This strategy is supported by a theoretical foundation to provide the best selection of the features with a lower bound of the highest end performance. The proposed strategy is a transparent approach to identify whether to improve the features or the classifier. This avoids the need for repeated tuning. Our evaluations on real-world medical imaging tasks (i.e., radiation therapy delivery error prediction and sarcoma survival prediction) show that our strategy is superior to other common deep representation learning baselines [i.e., autoencoder (AE) and softmax]. The strategy addresses the issue of feature's interpretability which enables more holistic feature creation such that the medical experts can focus on specifying relevant data as opposed to tedious feature engineering.

Abstract. Purpose: Teas are an essential part of traditional phytotherapy. The aim of this systematic review is to assess the clinical evidence using green tea catechins in cancer care. Methods: A systematic search was conducted searching five electronic databases concerning the effectiveness and risks of epigallocatechin gallate (EGCG) on cancer patients. Results: Seven studies with 371 patients were included. Patients were mainly suffering from breast and prostate cancer. Dosing ranged from 28 mg to 1600 mg EGCG, intervention time from 7 days to 6 months with different applications (topical 2 studies; oral 5 studies). The studies showed heterogeneous methodological quality and results leading not to conduct a meta-analysis. There was a small decrease in prostate-specific-antigen levels in one study (N=60; T0:(mean±SD) 9.6±5.2 ng/ml, T1: 8.4±4.3 ng/ml vs. T0: 9.9±8.5 ng/ml, T1: 10.0±9.0 ng/ml; p=0.04), whereas in a second study only a trend was seen. Topical green tea was as effective as metronidazole powder in reducing the odor of fungating malignant wounds (1 study; N=30) with a consequent increase in quality of life (QoL) (p

Item does not contain fulltext The purpose of this study was to describe the development and preliminary testing of a new scale assessing knowledge about melanoma risk factors and early detection/secondary prevention. Data was drawn from a longitudinal study assessing barriers and facilitators of skin self- examination among patients diagnosed with melanoma. For the current analysis, 191 patients who completed the new 9-item Knowledge About Melanoma Early Detection Scale and other study measures were included. Exploratory factor analysis with were conducted, which identified a robust scale comprised of 6 items with factor loadings ranging from .56 to .81. Higher scores on the Knowledge About Melanoma Early Detection Scale were associated with younger age and more positive attitudes about melanoma prevention, but not with biological sex, education, melanoma stage, or past self-administered and physician-provided skin checks. Further studies are needed to replicate these findings and to further establish the predictive validity of this scale and its usefulness for health research. 9 p.

Background: The EU LifeCycle Project was launched in 2017 to combine, harmonize, and analyze data from more than 250,000 participants across Europe and Australia, involving cohorts participating in the EU-funded LifeCycle Project. The purpose of this cohort description is to provide a detailed overview of the major measures within mental health domains that are available in 17 European and Australian cohorts participating in the LifeCycle Project. Methods: Data on cognitive, behavioral, and psychological development has been collected on participants from birth until adulthood through questionnaire and medical data. We developed an inventory of the available data by mapping individual instruments, domain types, and age groups, providing the basis for statistical harmonization across mental health measures. Results: The mental health data in LifeCycle contain longitudinal and cross-sectional data from birth throughout the life course, covering domains across a wide range of behavioral and psychopathology indicators and outcomes, including executive function, depression, ADHD, and cognition. These data span a unique combination of qualitative data collected through behavioral/cognitive/mental health questionnaires and examination, as well as data from biological samples and indices in the form of imaging (MRI, fetal ultrasound) and DNA methylation data. Harmonized variables on a subset of mental health domains have been developed, providing statistical equivalence of measures required for longitudinal meta-analyses across instruments and cohorts. Conclusion: Mental health data harmonized through the LifeCycle project can be used to study life-course trajectories and exposure-outcome models that examine early life risk factors for mental illness and develop predictive markers for later-life disease.

Background: Efforts to regulate tobacco products and reduce consumption in the European Union (EU) include the European Tobacco Products Directive (TPD), which went into force in May 2016. Despite the initial discussion to include a ban on sale of slim cigarettes, it was excluded in the final TPD. The main goal of this study was to examine support for a ban on slim cigarettes among smokers in six European Countries. Methods: Data from the 2018 (Wave 2) International Tobacco Control Policy Evaluation Project 6 European Country (ITC 6E) EUREST-PLUS project survey, a cross sectional study of adult smokers (n=5592) from Germany, Greece, Hungary, Poland, Romania, and Spain, was analysed. Descriptive statistics were used to estimate support for a ban on slim cigarettes by sociodemographic characteristics and smoking behaviors. Logistic regression analysis was used to examine factors associated with support for a ban on slim cigarettes and perceptions of harm. Results: Support for a ban on slims varied across countries, with highest support in Romania (33.8%), and lowest in Greece (18.0%). Female smokers (OR=0.77; 95%CI=0.66-0.90, daily smokers (OR=0.59; 95%CI=0.42-0.83), menthol smokers (OR=0.56; 95%CI=0.36-0.87), and smokers who did not have plans to quit within next six months (OR=0.45; 95%CI=0.36-0.57) had significantly lower odds of supporting a ban on slim cigarettes. Overall, 20% of smokers perceived slim cigarettes as less harmful than regular cigarettes. Conclusions: Support for a ban of slim cigarettes was relatively low among smokers, while misperceptions that slim cigarettes are less harmful is high, particularly among countries where slim cigarette use is more prevalent. Findings support a ban on slim cigarettes to reduce misperceptions around slim cigarettes being less harmful.

ObjectiveTo investigate gender differences in the use of diagnostic and therapeutic procedures for acute ischaemic heart disease (IHD) in Chinese adults and assess whether socioeconomic or health system factors contribute to such differences.MethodsIn 2004–2008, the China Kadoorie Biobank recruited 512 726 adults from 10 diverse areas in China. Data for 38 928 first hospitalisations with IHD (2911 acute myocardial infarction (AMI), 9817 angina and 26 200 other IHD) were obtained by electronic linkage to health insurance records until 31 December 2016. Multivariate Poisson regression models were used to estimate women-to-men rate ratios (RRs) of having cardiac enzyme tests, coronary angiography and coronary revascularisation.ResultsAmong the 38 928 individuals (61% women) with IHD admissions, women were less likely to have AMI (5% vs 12%), but more likely to have angina (26% vs 24%) or other IHD (69% vs 64%). For admissions with AMI, there were no differences in the use of cardiac enzymes between women and men (RR=1.00; 95% CI, 0.97 to 1.03), but women had lower use of coronary angiography (0.80, 0.68 to 0.93) and coronary revascularisation (0.85, 0.74 to 0.99). For angina, the corresponding RRs were: 0.97 (0.94 to 1.00), 0.66 (0.59 to 0.74) and 0.56 (0.47 to 0.67), respectively; while for other IHD, they were 0.97 (0.94 to 1.00), 0.87 (0.76 to 0.99) and 0.61 (0.51 to 0.73), respectively. Adjusting for socioeconomic and health system factors did not significantly alter the women-to-men RRs.ConclusionsAmong Chinese adults hospitalised with acute IHD, women were less likely than men to have coronary angiography and revascularisation, but socioeconomic and health system factors did not contribute to these differences.

Introduction: Understanding the underlying factors that influence the approach to overweight and obesity in children is basic to best support families searching a solution to this important public health problem. Objective: To assess attitudes and feelings of paediatric staff in addressing overweight and childhood obesity to parents, exploring perceived barriers and facilitators, for an effective care. Participants and method: Qualitative study by means of individual semi-structured questionnaires of paediatric staff (paediatricians and paediatrician nurses; n = 57; 68% female) of primary health care centres and hospitals in Mallorca. Thematic analysis was done. Results: Three themes emerged from the data: “Parents’ attitude in childhood obesity” (sub-themes “The conscience of parents”, “The parents ask for help”), “Paediatric staff and childhood obesity” (sub-themes “Approaching to the problem: The interview with parents”, “Looking together for the solution”), and “System barriers” (sub-themes “Improving teamwork and health policy”, “Family participation in addressing childhood obesity”). Conclusions: Paediatric staffs know how to treat childhood obesity, but demand training on motivation. Effectivity on therapy of childhood obesity will be obtained after parents/carers recognize the problem and establish a trustful relationship with paediatric staff. The health system is still a barrier to the activity of paediatric personnel. Resumen: Introducción: Comprender los factores que influyen en el tratamiento del sobrepeso y la obesidad infantil es crucial para ofrecer el mejor apoyo a las familias y solucionar este grave problema de salud pública. Objetivo: Describir las actitudes y sentimientos del personal de pediatría al tratar con los padres el sobrepeso y la obesidad de sus hijos, explorando los facilitadores y las barreras percibidas, a fin de realizar una atención efectiva. Sujetos y método: Estudio cualitativo por cuestionarios individuales semiestructurados de personal pediátrico (pediatras y enfermeras pediatras; n = 57; 68% mujeres) de centros de atención primaria y hospitales de la isla de Mallorca, sobre las que se aplicó un análisis temático. Resultados: Se identificaron 3 temas: “La actitud de los padres en la obesidad infantil” (subtemas “La conciencia de los padres”, “Los padres piden ayuda”), “El personal pediátrico y la obesidad infantil” (subtemas “Aproximación al problema: La entrevista con los padres”, “Buscando juntos la solución”) y “Barreras del Sistema” (subtemas “Mejorar el trabajo en equipo y la política de salud”, “Participación familiar al abordar y estudiar la obesidad infantile”). Conclusiones: El personal pediátrico sabe tratar la obesidad infantil, pero demanda entrenamiento en motivación. La terapia de la obesidad infantil será efectiva cuando los padres/cuidadores reconocen el problema y establecen confianza con los equipos pediátricos. El sistema de salud aún es una barrera a la actividad del personal pediátrico.

Patient Blood Management (PBM) ist ein multidisziplinares Therapiekonzept, welches auf eine praoperative Anamiediagnostik und ggf. Anamietherapie, die Minimierung von iatrogenen Blutverlusten, ein optimales Gerinnungsmanagement sowie einen leitliniengerechten, rationalen Umgang mit Erythrozytenkonzentraten (EK) fokussiert. PBM optimiert die perioperative Versorgungsqualitat bei gleichzeitiger Reduktion haufig unterschatzter Behandlungskosten. Die Umsetzung von PBM wird seit 2011 von der Weltgesundheitsorganisation (WHO) gefordert.

The development of microbial products for cancer treatment has been in the spotlight in recent years. In order to accelerate the lengthy and expensive drug development process, in silico screening tools are systematically employed, especially during the initial discovery phase. Moreover, considering the steadily increasing number of molecules approved by authorities for commercial use, there is a demand for faster methods to repurpose such drugs. Here we present a review on virtual screening web tools, such as publicly available databases of molecular targets and libraries of ligands, with the aim to facilitate the discovery of potential anticancer drugs based on microbial products. We provide an entry-level step-by-step description of the workflow for virtual screening of microbial metabolites with known protein targets, as well as two practical examples using freely available web tools. The first case presents a virtual screening study of drugs developed from microbial products using Caver Web, a web tool that performs docking along a tunnel. The second case comprises a comparative analysis between a wild type isocitrate dehydrogenase 1 and a mutant that results in cancer, using the recently developed web tool PredictSNPOnco. In summary, this review provides the basic and essential background information necessary for virtual screening experiments, which may accelerate the discovery of novel anticancer drugs.

OBJECTIVE In 2004, government-funded routine eye exams were discontinued for individuals aged 20-64 years in Ontario. We assessed whether this policy change reduced the rate of new glaucoma diagnoses. DESIGN Cohort-based time-series analysis. PARTICIPANTS Ontarians aged 20+ years in 2000-2014. METHODS Province-wide physician billing data were analyzed using segmented regression analysis. New glaucoma diagnoses were defined as the first glaucoma diagnostic billing code submitted by an ophthalmologist or optometrist among Ontarians who did not visit an ophthalmologist or an optometrist in the year prior to the study year. RESULTS Post- versus pre-2004, the rate of new glaucoma billings was reduced in all age groups: -2.7‰ (p < 0.0001) in the age group 20-39 years, -8.2‰ (p < 0.0001) in the age group 40-64 years (p < 0.0001), and -2.1‰ (p = 0.0003) in the age group 65+ years. This corresponds to a decreased number of individuals with a new glaucoma billing after 2004 versus before 2004: -8,800 (p < 0.001) in the age group 20-39 years, -32,234 (p < 0.0001) in the age group 40-64 years, and -3,255 (p = 0.0012) in the age group 65+ years. Reduced rates of new glaucoma diagnostic billings were seen in males, females and rural and urban residents among policy-affected and policy-unaffected age groups. Ontarians living in the wealthiest neighbourhood areas also had a significantly reduced rate after versus before 2004: -2.7‰ (p < 0.0001) for the age group 20-39 years, -9.0‰ (p < 0.0001) for the age group 40-64 years, and -2.3‰ (p < 0.001) for the age group 65+ years. CONCLUSIONS Discontinuation of government-funding for routine eye exams was associated with a significantly reduced rate of new glaucoma diagnostic billings irrespective of sociodemographics. More research is needed to understand the reduced glaucoma billings in unaffected seniors and those living in the wealthiest neighbourhood areas.

Purpose: Aim was to analyze demographic and tumor characteristics, treatment, and survival of patients with lung cancer younger than 40 years of age (U40) compared to older subgroups (41–70 and >70...

There is growing use of technology-enabled contact tracing, the process of identifying potentially infected COVID-19 patients by notifying all recent contacts of an infected person. Governments, technology companies, and research groups alike have been working towards releasing smartphone apps, using IoT devices, and distributing wearable technology to automatically track "close contacts" and identify prior contacts in the event an individual tests positive. However, there has been significant public discussion about the tensions between effective technology-based contact tracing and the privacy of individuals. To inform this discussion, we present the results of seven months of online surveys focused on contact tracing and privacy, each with 100 participants. Our first surveys were on April 1 and 3, before the first peak of the virus in the US, and we continued to conduct the surveys weekly for 10 weeks (through June), and then fortnightly through November, adding topical questions to reflect current discussions about contact tracing and COVID-19. Our results present the diversity of public opinion and can inform policy makers, technologists, researchers, and public health experts on whether and how to leverage technology to reduce the spread of COVID-19, while considering potential privacy concerns. We are continuing to conduct longitudinal measurements and will update this report over time; citations to this version of the report should reference Report Version 2.0, December 4, 2020., 37 pages, 11 figures. Supercedes arXiv:2005.06056

International audience; Since the emergence of the coronavirus disease (COVID-19), more than 165 million people have been infected all around the world (as of May 2021). The COVID-19 virus is highly contagious, especially in large crowded spaces. To prevent the infection and slow the transmission of the virus, the World Health Organization recommends wearing a mask, washing hands regularly, and maintaining a distance of at least one meter between people. To support this prevention, we propose a connected object based on LoRa technology to monitor the social distancing of one meter between people in queues. The proposed system uses infrared array sensor MLX60940 to detect people through their body temperature. Based on this output, we developed an algorithm to verify social distancing. The main advantage of this node is its ability to preserve the privacy of detected people and consume less energy compared to camera-based systems. Experimental results show that the proposed node can detect up to six persons per queue with an accuracy of 93% when the distance between people is below 80 cm.

Objectif : Dresser un bilan des outils quantitatifs disponibles pour mesurer les représentations de la maladie et analyser leur utilisation empirique auprès de patients atteints de cancer. Matériel et méthodes : Revue de la littérature. Résultats : Sept outils de mesure des représentations de la maladie existent dont un spécifique au cancer. L’Illness Perception Questionnaire est utilisé dans 29 des 33 études retenues. Conclusion : Associer ces échelles avec des méthodes reposant sur des approches davantage centrées sur le contexte socioculturel semble à privilégier.

Since its first use several decades ago, scanning electron microscopy has been used in numerous investigations dedicated to biological systems. This contribution focuses on observations on pathological calcifications in order to review several major applications of primary importance to the clinician. Among these, we highlight such observations as medical diagnostic tools in pathologies arising from primary hyperoxaluria and urinary infections.

Idiopathic hypersomnia (IH) is characterized by excessive daytime sleepiness despite normal or prolonged sleep. IH is distinguished from narcolepsy by the female predominance, severe morning inertia, continuous drowsiness (rather than sleep attacks), unrefreshing naps, absence of cataplexy, sleep onset in REM periods, and hypocretin deficiency. In IH, the multiple sleep latency test demonstrates low sensitivity, specificity, and reproducibility, compared with prolonged sleep monitoring. In some IH cases, an endogenous hypnotic peptide stimulating GABA receptors during wakefulness is suspected, which are improved by anti-GABA drugs. The benefits of modafinil, sodium oxybate, mazindol, and pitolisant were found in mostly retrospective studies.

Non suicidal self-injury is defined as intentional self-inflicted injury without the intent to die. Suicide attempt is defined as a nonfatal, self-directed, potentially injurious behavior with the intent to die. Although distinct behaviors, they are frequently associated and possibly clinically related. The aims of this study are to explore demographic data, social-demographic differences between genders, co-occurrence of non-suicidal self-injuries with suicide attempt, their association with gender and clinical variables. Retrospective cohort study on 143 patient admitted in Clinic for mental disorders „Dr Laza Lazarevic“, aged 14 to 18 years, between January 2015 and January 2016. Information were obtained from database and included two categories of variables: socio-demographic (age, gender, education level, current living situation) and clinical variables (abuse, neglect, peer violence, aggressive behavior, non-suicidal self-injuries, suicide attempt and others). The mean age of adolescents was 15.8 years, with female being more frequent in the sample (51.4%). The incidence of Mood disorders was significantly higher (p

Background The differential risk of incident dementia associated with receiving various overactive bladder (OAB) drugs is unknown. Objective To estimate the association of antimuscarinic OAB drug (exposure), compared with a β-3 agonist (mirabegron), and incident dementia. Design, setting, and participants A population-based nested case-control study was conducted in patients treated with OAB medications in Ontario, Canada. A total of 11 392 patients aged ≥66 yr with a new diagnosis of dementia between 2010 and 2017, and 29 881 age- and sex-matched controls without dementia were included in the study. Intervention Receipt of an antimuscarinic OAB drug or receipt of mirabegron, within the previous 6–12 mo. Outcome measurements and statistical analysis Cases developed dementia and Alzheimer’s disease. Controls were derived from the general population and matched to cases based on important baseline characteristics. Odds ratios (ORs) for incident dementia, adjusted for demographic and health-related characteristics, were determined. Results and limitations Patients receiving solifenacin (OR 1.24; 95% confidence interval 1.08–1.43) and darifenacin (OR 1.30; 95% CI 1.08–1.56) in the prior 6 mo had increased odds of incident dementia compared with those receiving mirabegron. In the 6 mo to 1 yr prior to diagnosis, receipt of solifenacin (OR 1.34; 95% CI 1.11–1.60), darifenacin (OR 1.49; 95% CI 1.19–1.86), tolterodine (OR 1.21; 95% CI 1.02–1.45), and fesoterodine (OR 1.39; 95% CI 1.14–1.71) was associated with increased odds of incident dementia compared with receipt of mirabegron. No effect was seen with oxybutynin or trospium. Limitations included misclassification of the outcome and residual confounding associated with the use of health administrative databases. Conclusions Older adults receiving solifenacin and darifenacin in the 6 mo prior to diagnosis, and those receiving solifenacin, darifenacin, tolterodine, or fesoterodine in the year prior to diagnosis, have increased odds of incident dementia, compared with those receiving mirabegron. Oxybutynin and trospium were not associated with dementia, likely due to a protopathic bias. Careful drug selection is warranted when treating patients with OAB. Patient summary In a large Canadian cohort of patients who developed dementia after starting an overactive bladder (OAB) medication, those taking some anticholinergic medications for OAB have an increased risk of dementia compared with those taking mirabegron.

Cardiovascular complications from drugs of abuse are becoming more apparent because of increased usage worldwide. Substance abuse can cause acute and chronic cardiovascular complications and is increasing in prevalence especially in young adults. These substances contribute to the development of acute coronary syndrome, type 2 myocardial injury, arrhythmias, and cardiomyopathies, and have numerous other cardiovascular complications. Although no screening guidelines exist, clinical awareness of these potential complications and their prevention, clinical presentation, diagnosis, and treatment are critically important. Management of cardiovascular disease should be coupled with appropriate social and mental health interventions to provide sustained clinical benefit. The higher the number of substances used recreationally, the greater the risk of premature heart disease. Epidemiological studies showed that 1 in 5 young adults misuse several substances and often start using at younger ages with a greater risk for adverse health outcomes over the long term. The aim of this review is to highlight the basic epidemiology, cardiac complications, and disease-specific treatment options of commonly abused substances including methamphetamine, cocaine, alcohol, anabolic-androgenic steroids, cannabis, and tobacco.

Background:Randomized controlled trials play a central role in evidence-based practice, but recruitment of participants, and retention of them once in the trial, is challenging. Moreover, there is a dearth of evidence that research teams can use to inform the development of their recruitment and retention strategies. As with other healthcare initiatives, the fairest test of the effectiveness of a recruitment strategy is a trial comparing alternatives, which for recruitment would mean embedding a recruitment trial within an ongoing host trial. Systematic reviews indicate that such studies are rare. Embedded trials are largely delivered in anad hocway, with interventions almost always developed in isolation and tested in the context of a single host trial, limiting their ability to contribute to a body of evidence with regard to a single recruitment intervention and to researchers working in different contexts. Methods/Design:The Systematic Techniques for Assisting Recruitment to Trials (START) program is funded by the United Kingdom Medical Research Council (MRC) Methodology Research Programme to support the routine adoption of embedded trials to test standardized recruitment interventions across ongoing host trials. To achieve this aim, the program involves three interrelated work packages: (1) methodology - to develop guidelines for the design, analysis and reporting of embedded recruitment studies; (2) interventions - to develop effective and useful recruitment interventions; and (3) implementation - to recruit host trials and test interventions through embedded studies. Discussion:Successful completion of the START program will provide a model for a platform for the wider trials community to use to evaluate recruitment interventions or, potentially, other types of intervention linked to trial conduct. It will also increase the evidence base for two types of recruitment intervention. Trial registration:The START protocol covers the methodology for embedded trials. Each embedded trial is registered separately or as a substudy of the host trial.

Type 2 diabetes mellitus (T2DM) disproportionately affects Indigenous populations. It is possible that exposure to complex mixtures of environmental contaminants contribute to T2DM development. This study examined the association between complex environmental contaminant mixtures and T2DM among Canadian Indigenous communities from the Eeyou Istchee territory, Quebec, Canada. Using data from the cross-sectional Multi-Community Environment-and-Health Study (2005–2009) Principal Component Analysis (PCA) was used to reduce the dimensionality of the following contaminants: 9-polychlorinated biphenyl congeners; 7-organic pesticides; and 4-metal/metalloids. Following this data reduction technique, we estimated T2DM prevalence ratios (PR) and 95% confidence intervals using modified Poisson regression with robust error variance across derived principal components, adjusting for a priori covariates. For both First Nation adult males (n = 303) and females (n = 419), factor loadings showed dichlorodiphenyltrichloroethane (DDT) and lead (Pb) highly loaded on the second principal component (PC) axis: DDT negatively loaded, and Pb positively loaded. T2DM was significantly associated with PC-2 across all adjusted models. Because PCA produces orthogonal axes, increasing PC-2 scores in the fully adjusted model for females and males showed (PR = 0.84; 95% CI 0.72, 0.98) and (PR = 0.78; 95% CI 0.62, 0.98), respectively. This cross-sectional study suggests that our observed association with T2DM is the result of DDT, and less likely the result of Pb exposure. Further, detectable levels of DDT among individuals may possibly contribute to disease etiology.

The aim of this study was to assess the efficacy of quantitative ultrasound imaging in characterizing cancer cell death caused by enhanced radiation treatments. This investigation focused on developing this ultrasound modality as an imaging-based non-invasive method that can be used to monitor therapeutic ultrasound and radiation effects. High-frequency (25 MHz) ultrasound was used to image tumor responses caused by ultrasound-stimulated microbubbles in combination with radiation. Human prostate xenografts grown in severe combined immunodeficiency (SCID) mice were treated using 8, 80, or 1000 µL/kg of microbubbles stimulated with ultrasound at 250, 570, or 750 kPa, and exposed to 0, 2, or 8 Gy of radiation. Tumors were imaged prior to treatment and 24 hours after treatment. Spectral analysis of images acquired from treated tumors revealed overall increases in ultrasound backscatter intensity and the spectral intercept parameter. The increase in backscatter intensity compared to the control ranged from 1.9±1.6 dB for the clinical imaging dose of microbubbles (8 µL/kg, 250 kPa, 2 Gy) to 7.0±4.1 dB for the most extreme treatment condition (1000 µL/kg, 750 kPa, 8 Gy). In parallel, in situ end-labelling (ISEL) staining, ceramide, and cyclophilin A staining demonstrated increases in cell death due to DNA fragmentation, ceramide-mediated apoptosis, and release of cyclophilin A as a result of cell membrane permeabilization, respectively. Quantitative ultrasound results indicated changes that paralleled increases in cell death observed from histology analyses supporting its use for non-invasive monitoring of cancer treatment outcomes.

Background: Empirical evidence pertaining to the influence of treatment preferences on attrition, adherence and outcomes in intervention evaluation trials is inconsistent. The inconsistency can be explained by the method used for allocating treatment and measuring preferences. The current methodological study is designed to address these factors by implementing the two-stage partially randomized or preference trial design, and administering a validated measure to assess participants’ preferences for the treatments under evaluation. It aims to compare attrition, adherence and outcomes for participants allocated randomly or by preference to treatment. The study is in its final stages of data collection; its protocol is presented in this paper. Methods/Design: A partially randomized clinical or preference trial is used. Eligible participants are randomized to two trial arms. First is the random arm involving random assignment to treatments, and second is the preference arm involving allocation to the chosen treatment. Participants with chronic insomnia are targeted. Two behavioral treatments are offered, stimulus control therapy and sleep restriction therapy, in the same format (small group) and dose (two sessions given over a 4-week period). A participant log is used to collect data on attrition. Adherence is evaluated in terms of exposure and enactment of treatment. Sleep-related outcomes (sleep parameters and perceived insomnia severity) are measured at pretest, posttest, 6 and 12 month follow-up. Treatment preferences, adherence and outcomes are assessed with reliable and valid measures. Discussion: The advantages and limitations of the preference trial design are highlighted. The challenges in implementing the trial are discussed relative to the distribution of participants in the groups defined by treatment received and method of treatment allocation. Trial registration: ClinicalTrials.gov Registry NCT02513017

Background: Elevated blood pressure after endovascular thrombectomy (EVT) has been associated with an increased risk of hemorrhagic transformation and poor functional outcomes. However, the optimal hemodynamic management after EVT remains unknown, and the blood pressure course in the acute phase of ischemic stroke has not been well characterized. This study aimed to identify patient subgroups with distinct blood pressure trajectories after EVT and study their association with radiographic and functional outcomes. Methods: This multicenter retrospective cohort study included consecutive patients with anterior circulation large-vessel occlusion ischemic stroke who underwent EVT. Repeated time-stamped blood pressure data were recorded for the first 72 hours after thrombectomy. Latent variable mixture modeling was used to separate subjects into five groups with distinct postprocedural systolic blood pressure (SBP) trajectories. The primary outcome was functional status, measured on the modified Rankin Scale 90 days after stroke. Secondary outcomes included hemorrhagic transformation, symptomatic intracranial hemorrhage, and death. Results: Two thousand two hundred sixty-eight patients (mean age [±SD] 69±15, mean National Institutes of Health Stroke Scale 15±7) were included in the analysis. Five distinct SBP trajectories were observed: low (18%), moderate (37%), moderate-to-high (20%), high-to-moderate (18%), and high (6%). SBP trajectory group was independently associated with functional outcome at 90 days ( P P =0.0003 and adjusted odds ratio, 2.2 [95% CI, 1.5–3.2], P P =0.04). No significant association was found between trajectory group and hemorrhagic transformation. Conclusions: Patients with acute ischemic stroke demonstrate distinct SBP trajectories during the first 72 hours after EVT that have differing associations with functional outcome. These findings may help identify potential candidates for future blood pressure modulation trials.

The Predictive Approaches to Treatment Effect Heterogeneity statement focused on baseline risk as a robust predictor of treatment effect and provided guidance on risk-based assessment of treatment effect heterogeneity in the RCT setting. The aim of this study was to extend this approach to the observational setting using a standardized scalable framework. The proposed framework consists of five steps: 1) definition of the research aim, i.e., the population, the treatment, the comparator and the outcome(s) of interest; 2) identification of relevant databases; 3) development of a prediction model for the outcome(s) of interest; 4) estimation of relative and absolute treatment effect within strata of predicted risk, after adjusting for observed confounding; 5) presentation of the results. We demonstrate our framework by evaluating heterogeneity of the effect of angiotensin-converting enzyme (ACE) inhibitors versus beta blockers on three efficacy and six safety outcomes across three observational databases. The proposed framework can supplement any comparative effectiveness study. We provide a publicly available R software package for applying this framework to any database mapped to the Observational Medical Outcomes Partnership Common Data Model. In our demonstration, patients at low risk of acute myocardial infarction received negligible absolute benefits for all three efficacy outcomes, though they were more pronounced in the highest risk quarter, especially for hospitalization with heart failure. However, failing diagnostics showed evidence of residual imbalances even after adjustment for observed confounding. Our framework allows for the evaluation of differential treatment effects across risk strata, which offers the opportunity to consider the benefit-harm trade-off between alternative treatments.

In response to the COVID-19 pandemic, many countries have adopted a broad spectrum of containment measures, from recommendations to stay at home to quarantines of large geographic regions. As part of this response, corporations and governments alike have strongly encouraged workers to telecommute where possible. More than 3.4 billion people in 84 countries have been confined to their homes, as estimated in late March 2020, which potentially translates to many millions of workers temporarily exposed to telecommuting. Since 2000, the emergence of digital and broadband internet has facilitated the development of home telework. Despite limited research interest on its impact on occupational health, several health benefits and risks of telework have been identified in academic or grey literature (table 1) (for a review see Ref. 1). …

SummaryWith the increasing availability of biobank-scale datasets that incorporate both genomic data and electronic health records, many associations between genetic variants and phenotypes of interest have been discovered. Polygenic risk scores (PRS), which are being widely explored in precision medicine, use the results of association studies to predict the genetic component of disease risk by accumulating risk alleles weighted by their effect sizes. However, few studies have thoroughly investigated best practices for PRS in global populations across different diseases. In this study, we utilize data from the Global-Biobank Meta-analysis Initiative (GBMI), which consists of individuals from diverse ancestries and across continents, to explore methodological considerations and PRS prediction performance in 9 different biobanks for 14 disease endpoints. Specifically, we constructed PRS using heuristic (pruning and thresholding, P+T) and Bayesian (PRS-CS) methods. We found that the genetic architecture, such as SNP-based heritability and polygenicity, varied greatly among endpoints. For both PRS construction methods, using a European ancestry LD reference panel resulted in comparable or higher prediction accuracy compared to several other non-European based panels; this is largely attributable to European descent populations still comprising the majority of GBMI participants. PRS-CS overall outperformed the classic P+T method, especially for endpoints with higher SNP-based heritability. For example, substantial improvements are observed in East-Asian ancestry (EAS) using PRS- CS compared to P+T for heart failure (HF) and chronic obstructive pulmonary disease (COPD). Notably, prediction accuracy is heterogeneous across endpoints, biobanks, and ancestries, especially for asthma which has known variation in disease prevalence across global populations. Overall, we provide lessons for PRS construction, evaluation, and interpretation using the GBMI and highlight the importance of best practices for PRS in the biobank-scale genomics era.

The voltage-gated sodium (Nav) channel subtype Nav1.7 plays a critical role in pain signaling, making it an important drug target. A number of peptide toxins from cone snails (conotoxins) bind to the extracellular vestibule of the Nav channel pore and block ion conduction. While the known conotoxins have variable selectivity among Nav channel subtypes, they form potential scaffolds for engineering of selective and potent channel inhibitors. Here we studied the molecular interactions between μ-conotoxin KIIIA (KIIIA) and the human Nav1.7 channel (hNav1.7). Using the cryo-electron microscopy (cryo-EM) structure of the electric eel Nav1.4 channel as a template we developed a structural model of hNav1.7 with Rosetta computational modeling. We performed in silico docking of KIIIA using RosettaDock and identified residues forming specific pairwise contacts between KIIIA and hNav1.7. Pairwise interactions were experimentally validated using mutant cycle analysis. Comparison with a recently published cryo-EM structure of the KIIIA-hNav1.2 channel complex revealed key similarities and differences between channel subtypes with potential implications for the molecular mechanism of toxin block. Our integrative approach, combining high-resolution structural data with computational modeling and experimental validation, will be useful for engineering of molecular probes to study Nav channels function and for rational design of novel biologics to treat chronic pain, cardiac arrhythmias, and epilepsy.

Background: A combination of fluticasone propionate and formoterol fumarate (FLUT/FORM; flutiform®) in a single aerosol inhaler has been developed. This study investigated the efficacy and safety of the combination compared to its individual components administered concurrently (FLUT+FORM). Methods: Patients aged 12 years or over (N=210) with mild to moderate-severe persistent, reversible asthma were randomized in a 1:1 ratio to 12 weeks of twice daily treatment with one of two doses of FLUT/FORM or FLUT+FORM in an open-label, parallel group, multicentre study in Europe. Total daily doses were FLUT/FORM: 200/20μg or 500/20μg; FLUT+FORM: 200/24μg or 500/24μg. The primary objective was to show non-inferiority of FLUT/FORM compared to FLUT+FORM based on post-dose forced expiratory volume in 1 second (FEV1) on Day 84. Results: FLUT/FORM had comparable efficacy to FLUT+FORM in the treatment of asthma with mean FEV1 30 to 60 minutes post-dose on Day 84 of 2.6L in both groups (per protocol groups; least squares mean difference: -0.03 L; 95%CI: -0.148, 0.081; p=0.004). The lower limit of the 95% CI was above the pre-defined non-inferiority threshold of ≥-0.2L. Analysis of other pulmonary function tests, patient reported outcomes, rescue medication use, asthma exacerbations and quality of life questionnaires were also comparable. The safety profiles of the two study groups were similar overall. Conclusions: Fluticasone/formoterol combination therapy has comparable efficacy to its individual components administered concurrently. The safety and tolerability profile of fluticasone/formoterol combination therapy is similar to that of its individual components.

Electrospun biodegradable polymers have emerged as promising materials for their applications in several fields, including biomedicine and food industry. For this reason, the susceptibility of these materials to be colonized by different pathogens is a critical issue for public health, and their study can provide future knowledge to develop new strategies against bacterial infections. In this work, the ability of three pathogenic bacterial species (Pseudomonas aeruginosa, Acinetobacter baumannii, and Listeria monocytogenes) to adhere and form biofilm in electrospun polycaprolactone (PCL) microfibrous meshes was investigated. Bacterial attachment was analyzed in meshes with different microstructure, and comparisons with other materials (borosilicate glass and electrospun polylactic acid (PLA)) fibers were assessed. Analysis included colony forming unit (CFU) counts, scanning electron microscopy (SEM), and crystal violet (CV) staining. All the obtained data suggest that PCL meshes, regardless of their microstructure, are highly susceptible to be colonized by the pathogenic relevant bacteria used in this study, so a pretreatment or a functionalization with compounds that present some antimicrobial activity or antibiofilm properties is highly recommended before their application. Moreover, an experiment designed to simulate a chronic wound environment was used to demonstrate the ability of these meshes to detach biofilms from the substratum where they have developed, thus making them promising candidates to be used in wound cleaning and disinfection., European Union’s H2020 research and innovation programme under the Marie Skłodowska-Curie grant agreement no. 691095 and Junta de Castilla y Leon-FEDER (projects BU079U16 and BU092U16).

International audience; The opportunistic Gram-negative bacterium Pseudomonas aeruginosa is a leading pathogen for infections of immuno-compromised patients and those suffering from cystic fibrosis. Its ability to switch from planktonic life to aggregates, forming the so-called biofilms, is a front-line mechanism of antimicrobial resistance. The bacterial carbohydrate binding protein LecB is an integral component and necessary for biofilm formation. Here, we report a new class of drug-like low molecular weight inhibitors of the lectin LecB with nanomolar affinities and excellent receptor binding kinetics and thermodynamics. This class of glycomimetic inhibitors efficiently blocked biofilm formation of P. aeruginosa in vitro while the natural monovalent carbohydrate ligands failed. Furthermore, excellent selectivity and pharmacokinetic properties were achieved. Notably, two compounds showed good oral bioavailability, and high compound concentrations in plasma and urine were achieved in vivo.

A better assessment of prostate cancer (PrCa) risk is needed to improve screening. The PROFILE pilot study explored the feasibility of single nucleotide polymorphism profiling in men with a family history (FH) of PrCa to investigate the probability of detecting PrCa at prostate biopsy (PB). The results of the present pilot study have demonstrated that PB is a feasible and safe method of PrCa screening in men with a FH., Background. A better assessment of individualized prostate cancer (PrCa) risk is needed to improve screening. The use of the prostate-specific antigen (PSA) level for screening in the general population has limitations and is not currently advocated. Approximately 100 common single nucleotide polymorphisms (SNPs) have been identified that are associated with the risk of developing PrCa. The PROFILE pilot study explored the feasibility of using SNP profiling in men with a family history (FH) of PrCa to investigate the probability of detecting PrCa at prostate biopsy (PB). The primary aim of this pilot study was to determine the safety and feasibility of PrCa screening using transrectal ultrasound-guided PB with or without diffusion-weighted magnetic resonance imaging (DW-MRI) in men with a FH. A secondary aim was to evaluate the potential use of SNP profiling as a screening tool in this population. Patients and Methods. A total of 100 men aged 40–69 years with a FH of PrCa underwent PB, regardless of their baseline PSA level. Polygenic risk scores (PRSs) were calculated for each participant using 71 common PrCa susceptibility alleles. We treated the disease outcome at PB as the outcome variable and evaluated its associations with the PRS, PSA level, and DW-MRI findings using univariate logistic regression. Results. Of the 100 men, 25 were diagnosed with PrCa, of whom 12 (48%) had clinically significant disease. Four adverse events occurred and no deaths. The PSA level and age at study entry were associated with PrCa at PB (p = .00037 and p = .00004, respectively). Conclusion. The results of the present pilot study have demonstrated that PB is a feasible and safe method of PrCa screening in men with a FH, with a high proportion of PrCa identified requiring radical treatment. It is feasible to collect data on PrCa-risk SNPs to evaluate their combined effect as a potential screening tool. A larger prospective study powered to detect statistical associations is in progress. Implications for Practice: Prostate biopsy is a feasible and safe approach to prostate cancer screening in men with a family history and detects a high proportion of prostate cancer that needs radical treatment. Calculating a polygenic risk score using prostate cancer risk single nucleotide polymorphisms could be a potential future screening tool for prostate cancer.

Background Pharmacist-led transitions of care (TOC) interventions have been associated with improved health outcomes. Community pharmacists’ (CP) TOC communications have been described whereas limited evidence is available for hospital pharmacists (HP) and none for non-dispensing pharmacists, integrated into Family Medicine Groups (FMG). Objective To assess information needs and perceptions about TOC communications of HP, FMG pharmacists (FMG-P) and CP and to identify optimal TOC practices and their barriers. Methods In a cross-sectional design, a survey was distributed via email to the 70 pharmacists who participated in a multicenter, single group, longitudinal TOC intervention study for older adults at risk of medication-related harm. All pharmacists were surveyed on their TOC practices before the TOC study, as part of usual care. Pharmacists who followed TOC study patients were also surveyed on their TOC practices during the TOC study. Results Survey responses were received from 35 pharmacists (50%), including 8 HP, 6 FMG-P and 21 CP. The frequency of communication between pharmacists of different settings increased significantly during the TOC study, with more than 80% of pharmacists reporting satisfaction with the quality of the information provided. At hospital discharge, in optimal TOC, the FMG-P and CP reported that the most important information to transfer was the reasons of hospitalization, patient weight and height, and the therapeutic intent of the medications. The main barriers to TOC implementation were the lack of clinical information about patients for FMG-P and CP and understaffing for HP. FMG-P and CP reported a similar high degree of interest in assuming responsibility for the new extended scope of practice activities of medication adjustments according to therapeutic targets or laboratory results and the implementation of a plan for gradual dose increases or drug tapering. Conclusions The surveyed pharmacists reported an increased frequency of communication and satisfaction with the information exchanged between the pharmacists of different settings during the TOC study compared to usual care, before the study. The pharmacists extended scope of practice offers new opportunities to optimize TOC interventions.

Background Mandatory disclosure of the price of prescription drugs within direct-to-consumer pharmaceutical advertisements (DTCA) has been proposed as a potential means of curbing rising drug costs in the United States. While price transparency in DTCA has widespread public support, empirical evidence regarding the effects of such drug prices disclosures remains limited. Objectives This study assessed the degree to which a price disclosure was noticed, the individual characteristics associated with price disclosure recognition, and the impact on perceived drug affordability, effectiveness, and safety. Methods A randomized experiment was conducted among 2,138 members of the Amerispeak online panel. Participants were shown a television commercial for a drug treating either type II diabetes, deep vein thrombosis/pulmonary embolism (DVT/PE), or rheumatoid arthritis (RA) that disclosed the list price, disclosed the list price plus the average out-of-pocket cost, or had no price disclosure. Results Roughly forty percent of participants noticed when a price was disclosed while 20–24% noticed information about individual costs varying (the higher of these percentages occurred when the average out-of-pocket cost was provided). Attention did not vary systematically with the cost amount. Recognition of the different elements of the price disclosure were most predicted by sociodemographic variables such as race, education, and income as well as health characteristics. Price disclosure altered perceived affordability of the advertised medication in a manner consistent with the costs provided, but such consistent significant effects were not found for perceived drug effectiveness and safety. Conclusions Repeated exposure to price disclosure in television DTCA or supplementary sources of price information may be necessary to increase attention to drug price information, especially among those who are most vulnerable to the burden of drug costs. Price transparency appears useful for adjusting affordability perceptions, but additional research needs to examine how such perceptions factor into healthcare decision-making and drug pricing.

Many parasites induce decreased host movement, known as lethargy, which can impact disease spread and the evolution of virulence. Mathematical models have investigated virulence evolution when parasites cause host death, but disease-induced decreased host movement has received relatively less attention. Here, we consider a model where, due to the within-host parasite replication rate, an infected host can become lethargic and shift from a moving to a resting state, where it can die. We find that when the lethargy and disease-induced mortality costs to the parasites are not high, then evolutionary bistability can arise, and either moderate or high virulence can evolve depending on the initial virulence and the magnitude of mutation. These results suggest, firstly, the transient coexistence of strains with different virulence, which may explain the coexistence of low- and high-pathogenic strains of avian influenza and human immunodeficiency viruses, and secondly, that medical interventions to treat the symptoms of lethargy or prevent disease-induced host deaths can result in a large jump in virulence and the rapid evolution of high virulence. In complement to existing results that show bistability when hosts are heterogeneous at the population-level, we show that evolutionary bistability may arise due to transmission heterogeneity at the individual host-level.

Background: Pathological Q waves are correlated with infarct size, and Q-wave regression is associated with left ventricular ejection fraction improvement. There are limited data regarding the association of Q-wave regression and clinical outcomes. Our main objective was to assess the association of pathological Q wave evolution after re-perfusion with clinical outcomes after anterior STEMI.Methods: Standard 12-lead electrocardiograms (ECGs) were recorded in 780 anterior STEMI patients treated with primary percutaneous coronary intervention (PCI) from the CIRCUS trial. ECGs were recorded before and 90 min following PCI, as well as at hospitalization discharge and 12 months of follow-up. The number of classic ECG criteria Q waves was scored for each ECG. Patients were classified in the Q wave regression group if they had re-gression of at least one Q wave between the post-PCI, the discharge and/or one year ECGs. Patients were classified in the Q wave persistent group if they had the same number or greater between the post-PCI, the discharge and/ or 1 and one year ECGs. All-cause death and heart failure events were assessed for all patients at one year.Results: There were 323(43%) patients with persistent Q waves (PQ group), 378(49%) patients with Q wave re-gression (RQ group) and 60(8%) patients with non-Q wave MI (NQ group). Infarct size as measured by the peak creatine kinase was significantly greater in the PQ group compared to the RQ and NQ groups (4633 +/- 2784 IU/l vs. 3814 +/- 2595 IU/l vs. 1733 +/- 1583 IU/l respectively, p b 0.0001). At one year, there were 22 deaths (7%) in the PQ-group, 15 (4%) in the RQ-group and none in the NQ-group (p = 0.04). There was a 4-fold increase in the risk of death or heart failure in the PQ compared to the NQ group (HR 4.7 [1.1; 19.3]; p = 0.03), but there was no significant difference between NQ and RQ groups (HR 3.3 [0.8; 13.8]; p = 0.09).Conclusion: Ina population of anterior STEMI patients, persistent Q waves defined according to the classic ECG criteria after reperfusion was associated with a 4-fold increase in the risk of heart failure or death compared to non-Q-wave MI, while Q-wave regression was associated with significantly lower risk of events.(c) 2019 Elsevier Inc. All rights reserved.

International audience; Purpose: No therapeutic consensus has been established about proximal ruptures of the rectus femoris muscle. The objective of this literature review is to determine a therapeutic course of action. Methods: We conducted a literature review on the PubMed database using the following keywords (in French and English, respectively): "quadriceps/quadriceps", "droit ant erieur/rectus femoris", "proximal/ proximal", "chirurgie/surgical", "avulsion/avulsion". We collected 266 articles, 36 of them were selected, which were related to our topic: proximal rupture of the anterior rectus femoris. Patients with a proximal rupture of the rectus femoris, minor or major patient of traumatic origin were included in this study. Patients injured at another lesion level, or non-traumatic lesions of the proximal rectus femoris (tendinitis without ruptures, tumor or others) were excluded. For each patient, the indications, the type of treatment and the functional result were analyzed, with the time to recovery and the level of recovery from sports and professional activities (same sport/profession or not, same level or not) as the main criterion of judgment. Fisher exact test was used for statistical comparison. Results: The aims of conservative treatment are to be pain free for the patient, to fight hematoma and to rehabilitate the injury as quickly as possible. The surgical techniques are varied, with most consisting of either a reinsertion of the musculo-tendon stump or a resection of the scar tissue with myo-tendinoaponeurotic suture in place. The functional results are good for the majority of the treatments proposed, but the conservative treatment has a shorter recovery time (3 months vs. 4 months for the best surgical results). Highly displaced bone avulsion is the only indication for first-line surgical treatment. Conclusion: The main disadvantage of conservative treatment is the risk of residual pain beyond 3 months (10%), justifying an MRI to guide secondary surgical treatment. We propose a treatment plan for proximal rupture of the proximal rectus femoris rupture.

Objective Gynecological cancer (GC) survivors have unmet needs when they complete primary cancer treatment. Despite this, no known research has summarized these needs and survivors’ suggestions to address them. We conducted a scoping review to fill these gaps and develop a model useful to guide clinical discussions and/or intervention. Methods English, full length, and accessible primary studies describing the needs of GC survivors were included. No restrictions on date nor country of publication were applied. Two reviewers extracted data, which was verified by a third reviewer. Results Seventy-one studies met the inclusion criteria for data extraction. Results were thematically grouped into seven dimensions: physical needs, sexuality-related concerns, altered self-image, psychological wellbeing, social support needs, supporting the return to work, and healthcare challenges and preferences. After consulting with a stakeholder group (a GC survivor, clinicians, and researchers), the dimensions were summarized into a proposed model to guide clinical assessments and/or intervention. Conclusion Results illuminate the diverse needs of GC survivors as they complete primary cancer treatment and their recommendations for care to meet these needs. Practice Implications The resulting model can be used to guide assessments, discussions and/or interventions to optimally prepare GC survivors for transition out of primary cancer treatment.

Background Feather duvet lung (FDL) is an underestimated form of acute and chronic hypersensitivity pneumonitis. Serological tests for FDL need to be validated. We investigated the ability of recombinant pigeon Proproteinase E (r-PROE) and Immunoglobulin-lambda-like-polypeptide-1 (r-IGLL1) proteins to support the serological diagnosis of FDL, and propose them as a serological tool for clinicians to differentiate cases from FDL and Bird fancier's lung (BFL). Methods Specific IgG antibodies against r-PROE and r-IGLL1, analyzed with ELISA, were measured in patients diagnosed with FDL (n = 31), BFL (n = 15) controls exposed (n = 15) and unexposed to feathers (n = 15). Results The sensitivity and specificity of the r-PROE ELISA for the serological diagnosis of FDL cases versus exposed and unexposed controls were 74.2% and 86.7% respectively, with an index threshold of 0.5 (AUC: 0.89). In addition, this serological test was effective to support the serological diagnosis of FDL and BFL cases with significantly different thresholds. The r-IGLL1 ELISA was only effective for the serological diagnosis of BFL. Also, these two serological tests were useful for the diagnosis of both chronic and acute forms. Conclusions The new diagnostic test for FDL using r-PROE protein should help to detect overt and hidden cases of FDL. The combination of both test will help the clinician in distinguish between the etiology of birds or feathers duvet.

Background Women who were born overseas represent an increasing proportion of women giving birth in the Australian healthcare system. Problem Women from migrant and refugee backgrounds have an increased risk of poor pregnancy and birth outcomes, including experiences of care. Aim To understand how women from migrant and refugee backgrounds perceive and experience the continuum of maternity care (pregnancy, birth, postnatal) in Australia. Methodology We conducted a qualitative evidence synthesis, searching MEDLINE, CIHAHL, and PsycInfo for studies published from inception to 23/05/2020. We included studies that used qualitative methods for data collection and analysis, that explored migrant/refugee women’s experiences or perceptions of maternity care in Australia. We used a thematic synthesis approach, assessed the methodological limitations of included studies, and used GRADE-CERQual to assess confidence in qualitative review findings. Results 27 studies met the inclusion criteria, representing women in Australia from 42 countries. Key themes were developed into 24 findings, including access to interpreters, structural barriers to service utilisation, experiences with health workers, trust in healthcare, experiences of discrimination, preferences for care, and conflicts between traditional cultural expectations and the Australian medical system. Conclusion This review can help policy makers and organisations who provide care to women from migrant and refugee backgrounds to improve their experiences with maternity care. It highlights factors linked to negative experiences of care as well as factors associated with more positive experiences to identify potential changes to practices and policies that would be well received by this population.

Graphical abstract, Introduction Face masks are regarded as effective Personal Protective Equipment (PPE) during the COVID-19 pandemic. However, the dominant polypropylene (PP)-based masks are devoid of antiviral/antibacterial activities and create enormous environmental burdens after disposal. Objectives Here we report a facile and potentially scalable method to fabricate biodegradable, breathable, and biocidal cellulose nonwovens (BCNWs) to address both environmental and hygienic problems of commercially available face masks. Methods TEMPO-oxidized cellulose nonwovens are rendered antiviral/antibacterial via covalent bonding with disinfecting polyhexamethylene guanidine or neomycin sulfate through carbodiimide coupling chemistry. Results The obtained results showed that the BCNWs have virucidal rate of >99.14%, bactericidal efficiency of >99.51%, no leaching-out effect, and excellent air permeability of >1111.5 mm s−1. More importantly, the as-prepared BCNWs can inactivate SARS-CoV-2 instantly. Conclusions This strategy provides a new platform for the green fabrication of multifunctional cellulose nonwovens as scalable bio-protective layers with superior performance for various PPE in fighting COVID-19 or future pandemics. Additionally, replacing the non-biodegradable non-antimicrobial PP-based masks with the cellulose-based masks can reduce the plastic wastes and lower the greenhouse gas production from the incineration of disposed masks.

Oral anticoagulants are a group of drugs used for the prevention and treatment of venous thrombosis and venous thromboembolism. For the last ten years, direct oral anticoagulants (DOAC) have been available and are equally effective, but significantly safer than vitamin K antagonists. In the case of an overdose, their most important side effect is still bleeding. Due to their widespread use, as well as increased toxicological importance there is a need to develop an analytical method for the determination of DOAC in biological material. The aim of this paper was to establish a method for the quantification of apixaban as one of the representatives of DOAC. The methodology of the study included the measurement of apixaban in the plasma of patients treated in the intensive care unit. Plasma apixaban concentrations were determined by LC-MS/MS technique using carbamazepine as an internal standard. Obtained validation parameters indicate that the introduced method is sensitive, reliable, precise and accurate. Using this method, apixaban can be quickly and easily detected and quantified in plasma in patients who are suspected of overdosing with this drug.

Funding Information: Source(s) of financial support: The study was supported by State funding for University‐level health research (TYH 2013311, Y122417012, and Y102218018), the Signe and Ane Gyllenberg Foundation, the Emil Aaltonen Foundation, and the Finnish Medical Foundation. Funding Information: Eija Kalso has received personal fees for participation in advisory board meetings of Pfizer and Orion Pharma, unrelated to this work. Dr. Juhani Ojala reports grants from Suomen Lääketieteen säätiö, outside the submitted work. Dr. Jukka Vanhanen reports grants from The Emil Aaltonen Foundation, grants from State funding for university‐level health research, during the conduct of the study. Part of Dr. Mari A. Kaunisto's salary is covered by a large Finnish biobank study FinnGen, funded by 12 international pharmaceutical companies (Abbvie, AstraZeneca, Biogen, Celgene, Genentech, a member of the Roche Group, GSK, Janssen, Maze Therapeutics, Merck/MSD, Novartis, Pfizer, and Sanofi) and Business Finland. Pantelis Lioumis has been consulting Nexstim Ltd. for issues not related to this study, such as motor and speech functional mapping until 2016. Dr. Jukka Putaala reports personal fees from Boehringer‐Ingelheim, personal fees and other from Bayer, grants and personal fees from BMS‐Pfizer, grants and personal fees from Abbott/St. Jude Medical, other from Vital Signum, other from Nokia Technologies, other from Bittium, other from BcB Medical, personal fees from Portola, personal fees from Terve Media, grants from Business Finland, grants from Amgen, personal fees from Herantis Pharma, other from Medixine, outside the submitted work; and he has participated in the European Stroke Organisation's guideline working groups on 1) poststroke hyperglycemia and 2) secondary prevention in patients with AF. He also has participated in the Finnish Duodecim Society's guideline working group on Ischemic stroke and TIA. The remaining authors have no potential conflicts to disclose. Conflict of Interest: Publisher Copyright: ©2021 The Authors. Neuromodulation: Technology at the Neural Interface published by Wiley Periodicals LLC on behalf of International Neuromodulation Society. Objectives: Central poststroke pain (CPSP), a neuropathic pain condition, is difficult to treat. Repetitive transcranial magnetic stimulation (rTMS) targeted to the primary motor cortex (M1) can alleviate the condition, but not all patients respond. We aimed to assess a promising alternative rTMS target, the secondary somatosensory cortex (S2), for CPSP treatment. Materials and Methods: This prospective, randomized, double-blind, Sham-controlled three-arm crossover trial assessed navigated rTMS (nrTMS) targeted to M1 and S2 (10 sessions, 5050 pulses per session at 10 Hz). Participants were evaluated for pain, depression, anxiety, health-related quality of life, upper limb function, and three plasticity-related gene polymorphisms including Dopamine D2 Receptor (DRD2). We monitored pain intensity and interference before and during stimulations, and at one month. A conditioned pain modulation test was performed using the cold pressor test. This assessed the efficacy of the descending inhibitory system, which maytransmit TMS effects in pain control. Results: We prescreened 73 patients, screened 29, and included 21, of whom 17 completed the trial. NrTMS targeted to S2 resulted in long-term (from baseline to one-month follow-up) pain intensity reduction of ≥30% in 18% (3/17) of participants. All stimulations showed a short-term effect on pain (17–20% pain relief), with no difference between M1, S2, or Sham stimulations, indicating a strong placebo effect. Only nrTMS targeted to S2 resulted in a significant long-term pain intensity reduction (15% pain relief). The cold pressor test reduced CPSP pain intensity significantly (p = 0.001), indicating functioning descending inhibitory controls. The homozygous DRD2 T/T genotype is associated with the M1 stimulation response. Conclusions: S2 is a promising nrTMS target in the treatment of CPSP. The DRD2 T/T genotype might be a biomarker for M1 nrTMS response, but this needs confirmation from a larger study.

Burn injuries can cause traumatic and debilitating physical trauma, with burn wounds prone to bacterial infection. This study examined in vitro the effectiveness of the silver nanoparticle based antimicrobial dressing, Acticoat™, in combination with a range of antimicrobial compounds against Staphylococcus aureus and Pseudomonas aeruginosa and investigated potential cytotoxic effects in multi-layered differentiated keratinocyte models. Acticoat™ with chlorhexidine was found to be highly effective against S. aureus and P. aeruginosa across a 3 day incubation period on pig skin models. MTT assays and histological staining of keratinocyte models revealed Acticoat™ had a cytotoxic effect following initial contact with the cells and cytotoxicity was exacerbated when dressings were coated with chlorhexidine and antimicrobial peptide formulations. Spectrophotometric analysis suggested that the silver nanoparticles may mobilise from the dressing as nanoclusters or silver salts, which may relate to the observed cytotoxicity. The bacterial strains used in this study showed a substantial tolerance to Acticoat™ with biofilm-like communities observed on the dressing surfaces. This could be mitigated with chlorhexidine, albeit with an increase in cytotoxicity. The clinical significance of these findings in terms of infection control and wound healing remain to be determined; the potential benefit of bactericidal activity must be balanced against cytotoxicity, and the prevalence and potential transmission of the silver tolerant phenotype must also be assessed.

Objective: The co-occurrence of substance use disorders (SUD) and trauma-exposure is a risk factor for suicidal thoughts and behaviors (STB). However, traditional methods of measurement for suicidal thoughts and behaviors are limited by an overreliance on dichotomous (i.e., yes or no) and averaged/summed scale score measurements. Further, among trauma-exposed individuals with SUD, it remains unclear which specific demographic factors, types of SUDs, and trauma sequelae (e.g., posttraumatic stress disorder [PTSD] symptom clusters) may be associated with elevated STB. The present study utilized item response theory to (a) generate empirically derived STB severity scores and, (b) examine which demographic factors, SUD diagnoses, and DSM-IV PTSD symptom clusters are associated with suicidality in a trauma-exposed sample with SUDs. Method: Female trauma-exposed participants with SUDs (N = 544) were recruited from community substance use treatment facilities in the National Drug Abuse Treatment Clinical Trials Network (CTN). Clinician-administered interviews assessed STB, SUDs, and PTSD symptoms. Results: Results indicated that the unidimensional item response theory (IRT) model used to estimate latent STB severity scores fit well, with strong local reliability at higher levels of latent STB severity. Regression predictors of elevated STB severity included younger age, opioid dependence, and higher PTSD reexperiencing symptoms. Conclusions: Clinicians are advised to screen for and target opioid use disorders and reexperiencing symptoms when addressing suicidal thoughts and behavior in trauma-exposed individuals with SUDs. (PsycInfo Database Record (c) 2022 APA, all rights reserved).