Risk of criminal victimisation in outpatients with common mental health disorders

Crime victimisation is a serious problem in psychiatric patients. However, research has focused on patients with severe mental illness and few studies exist that address victimisation in other outpatient groups, such as patients with depression. Due to large differences in methodology of the studies that address crime victimisation, a comparison of prevalence between psychiatric diagnostic groups is hard to make. Objectives of this study were to determine and compare one-year prevalence of violent and non-violent criminal victimisation among outpatients from different diagnostic psychiatric groups and to examine prevalence differences with the general population.Criminal victimisation prevalence was measured in 300 outpatients living in Amsterdam, The Netherlands. Face-to-face interviews were conducted with outpatients with depressive disorder (n = 102), substance use disorder (SUD, n = 106) and severe mental illness (SMI, n = 92) using a National Crime Victimisation Survey, and compared with a matched general population sample (n = 10865).Of all outpatients, 61% reported experiencing some kind of victimisation over the past year; 33% reported violent victimisation (3.5 times more than the general population) and 36% reported property crimes (1.2 times more than the general population). Outpatients with depression (67%) and SUD (76%) were victimised more often than SMI outpatients (39%). Younger age and hostile behaviour were associated with violent victimisation, while being male and living alone were associated with non-violent victimisation. Moreover, SUD was associated with both violent and non-violent victimisation.Outpatients with depression, SUD, and SMI are at increased risk of victimisation compared to the general population. Furthermore, our results indicate that victimisation of violent and non-violent crimes is more common in outpatients with depression and SUD than in outpatients with SMI living independently in the community

Serum IL-15 in patients with early systemic sclerosis: a potential novel marker of lung disease

The pathogenesis of systemic sclerosis (SSc) is characterized by autoimmunity, vasculopathy and fibrosis. IL-15 is a pleiotropic cytokine that has impact on immune, vascular and connective tissue cells. We therefore investigated IL-15 in the circulation of patients with early SSc and explored possible associations of serum IL-15 with vasculopathy and fibrosis. Serum levels of IL-15 were analysed in 63 consecutive patients with SSc of disease duration less than 4 years and without disease-modifying treatment. Thirty-three age-matched healthy control individuals were enrolled. Serum IL-15 levels were increased in the sera of SSc patients compared with that of healthy control individuals (P < 0.01). Serum IL-15 levels correlated with impaired lung function, assessed both by the vital capacity (P < 0.05) and by the carbon monoxide diffusion capacity (P < 0.05). The association between IL-15 and the vital capacity remained after multiple linear regression analysis. Patients with intermediate serum IL-15 levels had a higher prevalence of increased systolic pulmonary pressure compared with patients with either low or high serum IL-15 levels (P < 0.05). Moreover, increased serum IL-15 levels were associated with a reduced nailfold capillary density in multivariable logistic regression analysis (P < 0.01). Serum IL-15 levels also correlated inversely with the systolic blood pressure (P < 0.01). We conclude that IL-15 is associated with fibrotic as well as vascular lung disease and vasculopathy in early SSc. IL-15 may contribute to the pathogenesis of SSc. IL-15 could also be a candidate biomarker for pulmonary involvement and a target for therapy in SSc

The formation, properties and impact of secondary organic aerosol: current and emerging issues

Secondary organic aerosol (SOA) accounts for a significant fraction of ambient tropospheric aerosol and a detailed knowledge of the formation, properties and transformation of SOA is therefore required to evaluate its impact on atmospheric processes, climate and human health. The chemical and physical processes associated with SOA formation are complex and varied, and, despite considerable progress in recent years, a quantitative and predictive understanding of SOA formation does not exist and therefore represents a major research challenge in atmospheric science. This review begins with an update on the current state of knowledge on the global SOA budget and is followed by an overview of the atmospheric degradation mechanisms for SOA precursors, gas-particle partitioning theory and the analytical techniques used to determine the chemical composition of SOA. A survey of recent laboratory, field and modeling studies is also presented. The following topical and emerging issues are highlighted and discussed in detail: molecular characterization of biogenic SOA constituents, condensed phase reactions and oligomerization, the interaction of atmospheric organic components with sulfuric acid, the chemical and photochemical processing of organics in the atmospheric aqueous phase, aerosol formation from real plant emissions, interaction of atmospheric organic components with water, thermodynamics and mixtures in atmospheric models. Finally, the major challenges ahead in laboratory, field and modeling studies of SOA are discussed and recommendations for future research directions are proposed

Irreversible impacts of heat on the emissions of monoterpenes, sesquiterpenes, phenolic BVOC and green leaf volatiles from several tree species

Climate change will induce extended heat waves to parts of the vegetation more frequently. High temperatures may act as stress (thermal stress) on plants changing emissions of biogenic volatile organic compounds (BVOCs). As BVOCs impact the atmospheric oxidation cycle and aerosol formation, it is important to explore possible alterations of BVOC emissions under high temperature conditions. Applying heat to European beech, Palestine oak, Scots pine, and Norway spruce in a laboratory setup either caused the well-known exponential increases of BVOC emissions or induced irreversible changes of BVOC emissions. Considering only irreversible changes of BVOC emissions as stress impacts, we found that high temperatures decreased the &lt;i&gt;de novo&lt;/i&gt; emissions of monoterpenes, sesquiterpenes and phenolic BVOC. This behaviour was independent of the tree species and whether the &lt;i&gt;de novo&lt;/i&gt; emissions were constitutive or induced by biotic stress. &lt;br&gt;&lt;br&gt; In contrast, application of thermal stress to conifers amplified the release of monoterpenes stored in resin ducts of conifers and induced emissions of green leaf volatiles. In particular during insect attack on conifers, the plants showed &lt;i&gt;de novo&lt;/i&gt; emissions of sesquiterpenes and phenolic BVOCs, which exceeded constitutive monoterpene emissions from pools. The heat-induced decrease of &lt;i&gt;de novo&lt;/i&gt; emissions was larger than the increased monoterpene release caused by damage of resin ducts. For insect-infested conifers the net effect of thermal stress on BVOC emissions could be an overall decrease. &lt;br&gt;&lt;br&gt; Global change-induced heat waves may put hard thermal stress on plants. If so, we project that BVOC emissions increase is more than predicted by models only in areas predominantly covered with conifers that do not emit high amounts of sesquiterpenes and phenolic BVOCs. Otherwise overall effects of high temperature stress will be lower increases of BVOC emissions than predicted by algorithms that do not consider stress impacts

Von Willebrand factor propeptide as a marker of disease activity in systemic sclerosis (scleroderma)

In 44 consecutive patients with systemic sclerosis (SSc), plasma concentrations of von Willebrand factor (vWf) were higher than those of the vWf propeptide, but the propeptide showed less variability within patient subgroups. Higher values of the propeptide were observed in patients with early pulmonary involvement. A closer correlation of the propeptide than of vWf to biochemical markers of activity was also evident. Our results suggest that the propeptide, despite a shorter circulating half-time and lower plasma concentrations than vWf, is more useful in the assessment of disease activity in SSc

Feasibility of sedation and analgesia interruption following cannulation in neonates on extracorporeal membrane oxygenation

Purpose: In most extracorporeal membrane oxygenation (ECMO) centers patients are heavily sedated to prevent accidental decannulation and bleeding complications. In ventilated adults not on ECMO, daily sedation interruption protocols improve short- and long-term outcome. This study aims to evaluate safety and feasibility of sedation interruption following cannulation in neonates on ECMO. Methods: Prospective observational study in 20 neonates (0.17-5.8 days of age) admitted for ECMO treatment. Midazolam (n = 20) and morphine (n = 18) infusions were discontinued within 30 min after cannulation. Pain and sedation were regularly assessed using COMFORT-B and visual analog scale (VAS) scores. Midazolam and/or morphine were restarted and titrated according to protocolized treatment algorithms. Results: Median (interquartile range, IQR) time without any sedatives was 10.3 h (5.0-24.1 h). Median interruption duration for midazolam was 16.5 h (6.6-29.6 h), and for morphine was 11.2 h (6.7-39.4 h). During this period no accidental extubations, decannulations or bleeding complications occurred. Conclusions: This is the first study to show that interruption of sedatives and analgesics following cannulation in neonates on ECMO is safe and feasible. Interruption times are 2-3 times longer than reported for adult ICU patients not on ECMO. Further trials are needed to substantiate these findings and evaluate short- and long-term outcomes

Gas phase formation of extremely oxidized pinene reaction products in chamber and ambient air

High molecular weight (300–650 Da) naturally charged negative ions have previously been observed at a boreal forest site in Hyytiälä, Finland. The long-term measurements conducted in this work showed that these ions are observed practically every night between spring and autumn in Hyytiälä. The ambient mass spectral patterns could be reproduced in striking detail during additional measurements of α-pinene (C&lt;sub&gt;10&lt;/sub&gt;H&lt;sub&gt;16&lt;/sub&gt;) oxidation at low-OH conditions in the Jülich Plant Atmosphere Chamber (JPAC). The ions were identified as clusters of the nitrate ion (NO&lt;sub&gt;3&lt;/sub&gt;&lt;sup&gt;&amp;minus;&lt;/sup&gt;) and α-pinene oxidation products reaching oxygen to carbon ratios of 0.7–1.3, while retaining most of the initial ten carbon atoms. Attributing the ions to clusters instead of single molecules was based on additional observations of the same extremely oxidized organics in clusters with HSO&lt;sub&gt;4&lt;/sub&gt;&lt;sup&gt;&amp;minus;&lt;/sup&gt; (Hyytiälä) and C&lt;sub&gt;3&lt;/sub&gt;F&lt;sub&gt;5&lt;/sub&gt;O&lt;sub&gt;2&lt;/sub&gt;&lt;sup&gt;&amp;minus;&lt;/sup&gt; (JPAC). The most abundant products in the ion spectra were identified as C&lt;sub&gt;10&lt;/sub&gt;H&lt;sub&gt;14&lt;/sub&gt;O&lt;sub&gt;7&lt;/sub&gt;, C&lt;sub&gt;10&lt;/sub&gt;H&lt;sub&gt;14&lt;/sub&gt;O&lt;sub&gt;9&lt;/sub&gt;, C&lt;sub&gt;10&lt;/sub&gt;H&lt;sub&gt;16&lt;/sub&gt;O&lt;sub&gt;9&lt;/sub&gt;, and C&lt;sub&gt;10&lt;/sub&gt;H&lt;sub&gt;14&lt;/sub&gt;O&lt;sub&gt;11&lt;/sub&gt;. The mechanism responsible for forming these molecules is still not clear, but the initial reaction is most likely ozone attack at the double bond, as the ions are mainly observed under dark conditions. β-pinene also formed highly oxidized products under the same conditions, but less efficiently, and mainly C&lt;sub&gt;9&lt;/sub&gt; compounds which were not observed in Hyytiälä, where β-pinene on average is 4–5 times less abundant than α-pinene. Further, to explain the high O/C together with the relatively high H/C, we propose that geminal diols and/or hydroperoxide groups may be important. We estimate that the night-time concentration of the sum of the neutral extremely oxidized products is on the order of 0.1–1 ppt (~10&lt;sup&gt;6&lt;/sup&gt;–10&lt;sup&gt;7&lt;/sup&gt; molec cm&lt;sup&gt;−3&lt;/sup&gt;). This is in a similar range as the amount of gaseous H&lt;sub&gt;2&lt;/sub&gt;SO&lt;sub&gt;4&lt;/sub&gt; in Hyytiälä during day-time. As these highly oxidized organics are roughly 3 times heavier, likely with extremely low vapor pressures, their role in the initial steps of new aerosol particle formation and growth may be important and needs to be explored in more detail in the future

Pragmatic physiologically-based pharmacokinetic modeling to support clinical implementation of optimized gentamicin dosing in term neonates and infants: proof-of-concept

IntroductionModeling and simulation can support dosing recommendations for clinical practice, but a simple framework is missing. In this proof-of-concept study, we aimed to develop neonatal and infant gentamicin dosing guidelines, supported by a pragmatic physiologically-based pharmacokinetic (PBPK) modeling approach and a decision framework for implementation.MethodsAn already existing PBPK model was verified with data of 87 adults, 485 children and 912 neonates, based on visual predictive checks and predicted-to-observed pharmacokinetic (PK) parameter ratios. After acceptance of the model, dosages now recommended by the Dutch Pediatric Formulary (DPF) were simulated, along with several alternative dosing scenarios, aiming for recommended peak (i.e., 8–12 mg/L for neonates and 15–20 mg/L for infants) and trough (i.e., &lt;1 mg/L) levels. We then used a decision framework to weigh benefits and risks for implementation.ResultsThe PBPK model adequately described gentamicin PK. Simulations of current DPF dosages showed that the dosing interval for term neonates up to 6 weeks of age should be extended to 36–48 h to reach trough levels &lt;1 mg/L. For infants, a 7.5 mg/kg/24 h dose will reach adequate peak levels. The benefits of these dose adaptations outweigh remaining uncertainties which can be minimized by routine drug monitoring.ConclusionWe used a PBPK model to show that current DPF dosages for gentamicin in term neonates and infants needed to be optimized. In the context of potential uncertainties, the risk-benefit analysis proved positive; the model-informed dose is ready for clinical implementation

Формування світогляду О. Кониського

Crime victimisation is a serious problem in psychiatric patients. However, research has focused on patients with severe mental illness and few studies exist that address victimisation in other outpatient groups, such as patients with depression. Due to large differences in methodology of the studies that address crime victimisation, a comparison of prevalence between psychiatric diagnostic groups is hard to make. Objectives of this study were to determine and compare one-year prevalence of violent and non-violent criminal victimisation among outpatients from different diagnostic psychiatric groups and to examine prevalence differences with the general population.Criminal victimisation prevalence was measured in 300 outpatients living in Amsterdam, The Netherlands. Face-to-face interviews were conducted with outpatients with depressive disorder (n = 102), substance use disorder (SUD, n = 106) and severe mental illness (SMI, n = 92) using a National Crime Victimisation Survey, and compared with a matched general population sample (n = 10865).Of all outpatients, 61% reported experiencing some kind of victimisation over the past year; 33% reported violent victimisation (3.5 times more than the general population) and 36% reported property crimes (1.2 times more than the general population). Outpatients with depression (67%) and SUD (76%) were victimised more often than SMI outpatients (39%). Younger age and hostile behaviour were associated with violent victimisation, while being male and living alone were associated with non-violent victimisation. Moreover, SUD was associated with both violent and non-violent victimisation.Outpatients with depression, SUD, and SMI are at increased risk of victimisation compared to the general population. Furthermore, our results indicate that victimisation of violent and non-violent crimes is more common in outpatients with depression and SUD than in outpatients with SMI living independently in the community

Impact of pretreatment dihydropyrimidine dehydrogenase genotype-guided fluoropyrimidine dosing on chemotherapy associated adverse events

Consensus guidelines exist for genotype-guided fluoropyrimidine dosing based on variation in the gene dihydropyrimidine dehydrogenase (DPYD). However, these guidelines have not been widely implemented in North America and most studies of pretreatment DPYD screening have been conducted in Europe. Given regional differences in treatment practices and rates of adverse events (AEs), we investigated the impact of pretreatment DPYD genotyping on AEs in a Canadian context. Patients referred for DPYD genotyping prior to fluoropyrimidine treatment were enrolled from December 2013 through November 2019 and followed until completion of fluoropyrimidine treatment. Patients were genotyped for DPYD c.1905+1G\u3eA, c.2846A\u3eT, c.1679T\u3eG, and c.1236G\u3eA. Genotype-guided dosing recommendations were informed by Clinical Pharmacogenetics Implementation Consortium guidelines. The primary outcome was the proportion of patients who experienced a severe fluoropyrimidine-related AE (grade ≥3, Common Terminology Criteria for Adverse Events version 5.0). Secondary outcomes included early severe AEs, severe AEs by toxicity category, discontinuation of fluoropyrimidine treatment due to AEs, and fluoropyrimidine-related death. Among 1394 patients, mean (SD) age was 64 (12) years, 764 (54.8%) were men, and 47 (3.4%) were DPYD variant carriers treated with dose reduction. Eleven variant carriers (23%) and 418 (31.0%) noncarriers experienced a severe fluoropyrimidine-related AE (p = 0.265). Six carriers (15%) and 284 noncarriers (21.1%) experienced early severe fluoropyrimidine-related AEs (p = 0.167). DPYD variant carriers treated with genotype-guided dosing did not experience an increased risk for severe AEs. Our data support a role for DPYD genotyping in the use of fluoropyrimidines in North America