Objective In Sweden, Consultation Liaison-psychiatry (CLP) has hitherto largely been practiced by enthusiasts with a lack of exchange and consensus on clinical practice. Hence, an important impetus ...for development has been lacking. In 2014, the Swedish Psychiatric Society initiated a work on clinical guidelines in CLP. Since 2019, a working group within the national CL Association has been responsible for this work. Methods To start with, clinical guidelines from other countries/languages were identified, and central issues and themes for practicing CL-psychiatrists were collected. After the formulation of a preliminary list of content, 21 authors for 25 chapters were identified. In the following process, a smaller editorial committee stayed in close touch with authors and presented drafts for external reviewers and for selected chapters. A Delphy-like process was initiated with participation from active CL-psychiatrists in Sweden (and partially Norway). Final drafts were then presented to the board of the Swedish Psychiatric Society and after minor modifications as result of their reviews a final version was agreed upon. Results The Swedish clinical guidelines on consultation-liaison psychiatry will encompass ca 280 pages in print, and will also be published online, in March 2022. Conclusions The development of clinical guidelines is feasible as a process within professional bodies outside of the official governmental institutions. It is anticipated that the guidelines will promote and accelerate the development of CL-psychiatry in countries were Swedish is understood, such as the Nordic countries.
Mental health disorders are prevalent among individuals with intellectual disabilities (ID). However, there is a lack of research on the impact of concomitant autism spectrum disorders (ASD) or ...attention deficit hyperactivity disorder (ADHD) on the mental health within this population. We aimed to investigate the prevalence of mental health disorders and registered healthcare visits due to self-harm among individuals with ID.
We used administrative data for all healthcare with at least one recorded diagnosis of mental health disorder or self-harm during 2007-2017 among people with a diagnosis of Down syndrome (DS; n = 1298) and with ID without DS (IDnonDS; n = 10,671) using the rest of the population in Stockholm Region (n = 2,048,488) for comparison.
The highest odds ratios for a mental health disorder were present in females with IDnonDS (9.01) followed by males with IDnonDS (8.50), compared to the general population. The ORs for self-harm among individuals with IDnonDS were high (8.00 for females and 6.60 for males). There were no registered cases of self-harm among individuals with DS. The prevalence of an anxiety or affective disorder was higher among individuals with ID including DS with concomitant ASD or ADHD. Neighbourhood socio-economic status was associated with a lower occurrence of mental health disorders and self-harm in wealthier areas for all outcomes and for all groups.
Self-harm and psychiatric comorbidities were common among individuals with ID without DS with an attenuated difference among those with concomitant ASD or ADHD, which calls for attention.
The accurate prediction of pharmacokinetics (PK) is fundamental to underwriting safety and efficacy in pediatric clinical trials; age-dependent PK may be observed with pediatrics because of the ...growth and maturation processes that occur during development. Understanding the ontogeny of drug-metabolizing enzymes is a critical enabler for pediatric PK prediction, as enzyme expression or activity may change with age. Although ontogeny functions for the cytochrome P450s (CYPs) have been developed, disconnects between ontogeny functions for the same CYP may exist, depending on whether the functions were derived from in vitro or in vivo data. This report describes the development of ontogeny functions for all the major hepatic CYPs based on in vitro or in vivo data; these ontogeny functions were subsequently incorporated into a physiologically based pharmacokinetic model and evaluated. Pediatric PK predictions based on in vivo-derived ontogeny functions performed markedly better than those developed from in vitro data for intravenous (100% versus 51% within 2-fold, respectively) and oral (98% versus 67%, respectively) dosing. The verified models were then applied to complex pediatric scenarios involving active metabolites, CYP polymorphisms and physiological changes because of critical illness; the models reasonably explained the observed age-dependent changes in pediatric PK.
An assay for quantification of riboflavin (Rf) in milk-based products has been developed using the principle of surface plasmon resonance with on-chip measurement. The quantification was done ...indirectly by measuring excess of Rf binding protein (RBP) that remains free after complexation with Rf molecules originally present in the sample solution. The chip was modified with covalently immobilized Rf in order to bind the RBP in excess. A chemical modification was performed to introduce a reactive ester group at the N-3 position of the natural Rf to bind amino groups present on the chip surface. Calibration solutions were prepared by mixing a range of Rf standard solutions with an optimized concentration of RBP. The Rf content in the milk-based products was then measured by comparison of the response against the calibration. Results obtained were very close to those from an official HPLC-fluorescence procedure. The limit of quantification was determined to 234 μg/L and the limit of detection to 70 μg/L by an injection volume of 160 μL.
Abstract Objectives The objectives were 2-fold: (1) to examine how high school start times relate to adolescent sleep duration, and (2) to test associations between sleep duration and mental health– ...and substance use–related issues and behaviors in teens. Design This study examines selected questions from survey data collected between 2010 and 2013 high school students. Setting Respondents included more than 9000 students in grades 9 to 12 in 8 high schools in 5 school districts across the United States. Measurements The survey instrument is the 97-item Teen Sleep Habits Survey. Logistic regression models were used to calculate adjusted odds ratios and 95% confidence intervals. Because of clustering within schools and the use of repeated measures, generalized estimating equations were used to account for variance inflation. Results Greater sleep duration was associated with fewer reports of various mental health– and substance use–related issues and behaviors (all P values <.01). For instance, for each additional hour of sleep reported, there was a 28% reduction in the adjusted odds of a participant reporting that he or she felt “unhappy, sad, or depressed.” Later wake-up times were associated with a reduction in risk for some, but not all factors. Later start times were significantly associated with greater sleep duration. Conclusions Given that later start times allow for greater sleep duration and that adequate sleep duration is associated with more favorable mental health– and substance use–related issues and behaviors, it is important that school districts prioritize exploring and implementing policies, such as delayed start times, that may increase the amount of sleep of adolescent students, which is needed for their optimal development.
Understanding the potential for cytochrome P450-mediated drug-drug interactions (DDIs) is a critical step in the drug discovery process. DDIs of CYP3A4 are of particular importance because of the ...number of marketed drugs that are cleared by this enzyme. In response to studies that suggested the presence of several binding regions within the CYP3A4 active site, multiple probe substrates are often used for in vitro CYP3A4 DDI studies, including midazolam (the clinical standard), felodipine/nifedipine, and testosterone. However, the design of clinical CYP3A4 DDI studies may be confounded for cases such as 1-(2-hydroxy-2-methylpropyl)-N-5-(7-methoxyquinolin-4-yloxy)pyridin-2-yl-5-methyl-3-oxo-2-phenyl-2,3-dihydro-1H-pyrazole-4-carboxamide (AMG 458), with which testosterone is predicted to exhibit a clinically relevant DDI whereas midazolam and felodipine/nifedipine are not. To develop an appropriate path forward for such clinical DDI studies, the inhibition potency of 20 known inhibitors of CYP3A4 were measured in vitro using 8 clinically relevant CYP3A4 probe substrates and testosterone. Hierarchical clustering suggested four probe substrate clusters: testosterone; felodipine; midazolam, buspirone, quinidine, and sildenafil; and simvastatin, budesonide, and fluticasone. The in vivo sensitivities of six clinically relevant CYP3A4 probe substrates (buspirone, cyclosporine, nifedipine, quinidine, sildenafil, and simvastatin) were determined in relation to midazolam from literature DDI data. Buspirone, sildenafil, and simvastatin exhibited similar or greater sensitivity than midazolam to CYP3A4 inhibition in vivo. Finally, Simcyp was used to predict the in vivo magnitude of CYP3A4 DDIs caused by AMG 458 using midazolam, sildenafil, simvastatin, and testosterone as probe substrates.
Remote ischemic preconditioning (RIPC) prior to surgery has recently been shown to reduce the risk of myocardial injury and myocardial infarction after hip fracture surgery. This study investigated ...whether RIPC initiated antithrombotic mechanisms in patients undergoing hip fracture surgery. This trial was a predefined sub-study of a multicentre randomized clinical trial. Adult patients with cardiovascular risk factors undergoing hip fracture surgery between September 2015 and September 2017 were randomized 1 : 1 to RIPC or control. RIPC was initiated before surgery with a tourniquet applied to the upper arm and it consisted of four cycles of 5 min of forearm ischemia followed by five minutes of reperfusion. The outcomes such as surgery-induced changes in thrombin generation, fibrinogen/fibrin turnover, tissue plasminogen activator, plasminogen activator inhibitor-1 and fibrin structure measurements were determined preoperatively (prior to RIPC) and 2 h postoperatively. One hundred and thirty-seven patients were randomized to RIPC (n = 65) or control (n = 72). There were no significant changes in thrombin generation, fibrinogen/fibrin turnover or fibrin structure measurements determined pre and postoperatively between patients in the RIPC and control groups. Subgroup analyses on patients not on anticoagulant therapy (n = 103), patients receiving warfarin (n = 17) and patients receiving direct oral anticoagulant therapy (n = 18) showed no significant changes between the RIPC-patients and controls. RIPC did not affect changes in thrombin generation, fibrin turnover or fibrin structure in adult patients undergoing hip fracture surgery suggesting that the cardiovascular effect of RIPC in hip fracture surgery is not related to alterations in fibrinogen/fibrin metabolism.
Endothelial dysfunction result from inflammation and excessive production of reactive oxygen species as part of the surgical stress response. Remote ischemic preconditioning (RIPC) potentially exerts ...anti-oxidative and anti-inflammatory properties, which might stabilise the endothelial function after non-cardiac surgery. This was a single centre randomised clinical trial including 60 patients undergoing sub-acute laparoscopic cholecystectomy due to acute cholecystitis. Patients were randomised to RIPC or control. The RIPC procedure consisted of four cycles of five minutes of ischaemia and reperfusion of one upper extremity. Endothelial function was assessed as the reactive hyperaemia index (RHI) and circulating biomarkers of nitric oxide (NO) bioavailability (L-arginine, asymmetric dimethylarginine (ADMA), L-arginine/ADMA ratio, tetra- and dihydrobiopterin (BH
and BH
), and total plasma biopterin) preoperative, 2-4 h after surgery and 24 h after surgery. RHI did not differ between the groups (
= 0.07). Neither did levels of circulating biomarkers of NO bioavailability change in response to RIPC. L-arginine and L-arginine/ADMA ratio was suppressed preoperatively and increased 24 h after surgery (
< 0.001). The BH
/BH
-ratio had a high preoperative level, decreased 2-4 h after surgery and remained low 24 h after surgery (
= 0.01). RIPC did not influence endothelial function or markers of NO bioavailability until 24 h after sub-acute laparoscopic cholecystectomy. In response to surgery, markers of NO bioavailability increased, and oxidative stress decreased. These findings support that a minimally invasive removal of the inflamed gallbladder countereffects reduced markers of NO bioavailability and increased oxidative stress caused by acute cholecystitis.
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