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Treatments and treatment predictors in patients with substance use disorders and comorbid attention-deficit/hyperactivity disorder: First results from the International Naturalistic Cohort Study of ADHD and SUD (INCAS)
No full textItem does not contain fulltextBackground: Treatment of attention-deficit/ hyperactivity disorder (ADHD) in patients with a substance use disorder (SUD) and comorbid ADHD (SUD +ADHD) may have positive effects on the outcome of both conditions, but controversy exists regarding the preferred ADHD treatment in these patients. Little is known about the treatments that are provided for these patients in routine addiction care practice and the factors that are associated with treatment provision. Objective: To describe the treatments provided in everyday clinical practice and to explore factors associated with ADHD treatment provision in patients with SUD +ADHD. Methods: An international multicenter observational prospective cohort design was employed. Patients with moderate to severe SUD and comorbid ADHD according to DSM-5 were invited to participate at the start of a new SUD treatment episode between June 2017 and May 2021. Clinical and sociodemographic data were collected at 12 study sites in 9 countries through patient interviews, interviews with treatment providers, and patient files. Treatment variation across studies was described, and mixed-effect logistic regression was used to identify factors associated with ADHD treatment provision. Results: A total of 578 treatment-seeking patients with SUD +ADHD (274 inpatients, 303 outpatients, and 1 unknown) were recruited. About two thirds received some kind of ADHD treatment (62.8%), with 54.0% receiving pharmacologic, 34.0% receiving psychological treatment, and 25.1% receiving combined pharmacologic and psychological treatment. The treatment site explained more of the variation in ADHD treatment provision than individual patient factors. In addition, higher ADHD symptom severity and sobriety at intake were associated with receiving ADHD treatment. Conclusion: These findings suggest that treatment of SUD +ADHD patients is suboptimal even in specialized centers with substantial practice variation. Further research is needed to better understand the barriers to implement treatment guidelines for ADHD + SUD and, thus, to improve quality of care. Trial Registration: ISRCTN: 15998989 20/12/2019 (https://doi.org/10.1186/ISRCTN15998989).10 p
Partial renal deletion of Klotho is not sufficient to impact renal electrolyte handling in distal convoluted tubule specific knock-out mice.
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318188.pdf (Publisher’s version ) (Open Access)Klotho controls renal electrolyte handling by modulating tubular reabsorption of calcium and phosphate through the epithelial calcium channel TRPV5 and sodium phosphate co-transporter NPT2A. The Ksp-KL(-/-) mice have a targeted deletion of Klotho in the distal part of the nephron. Considering that the distal convoluted tubule is the most important site for Ca(2+) regulation in the kidney, Ksp-KL(-/-) mice were challenged with a Ca(2+)-deficient diet for determining the Ca(2+) handling and pinpointing the Klotho levels needed for controlling renal Ca(2+) handling. The Ksp-KL(-/-) mice displayed normal weight and showed unaltered calcium and phosphate levels in serum and 24-h urine. Expression of calciotropic (Trpv5, Trpv6) and phosphotropic (Slc34a1, Slc34a2) genes in the kidneys, duodenum, ileum, and colon were not affected by Klotho deletion. In conclusion, our study reports that mice with 18%-93% residual levels of Klotho in the kidney exhibit normal electrolyte homeostasis when placed on a low Ca(2+)-content diet.01 april 202
Clinical Evidence 2030
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318474.pdf (Publisher’s version ) (Open Access
Circulating tryptophan-kynurenine pathway metabolites are associated with all-cause mortality among patients with stage I-III colorectal cancer.
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313188.pdf (Publisher’s version ) (Open Access)Alterations within the tryptophan-kynurenine metabolic pathway have been linked to the etiology of colorectal cancer (CRC), but the relevance of this pathway for prognostic outcomes in CRC patients needs further elucidation. Therefore, we investigated associations between circulating concentrations of tryptophan-kynurenine pathway metabolites and all-cause mortality among CRC patients. This study utilizes data from 2102 stage I-III CRC patients participating in six prospective cohorts involved in the international FOCUS Consortium. Preoperative circulating concentrations of tryptophan, kynurenine, kynurenic acid (KA), 3-hydroxykynurenine (HK), xanthurenic acid (XA), 3-hydroxyanthranilic acid (HAA), anthranilic acid (AA), picolinic acid (PA), and quinolinic acid (QA) were measured by liquid chromatography-tandem mass spectrometry. Using Cox proportional hazards regression, we examined associations of above-mentioned metabolites with all-cause mortality, adjusted for potential confounders. During a median follow-up of 3.2 years (interquartile range: 2.2-4.9), 290 patients (13.8%) deceased. Higher blood concentrations of tryptophan, XA, and PA were associated with a lower risk of all-cause mortality (per doubling in concentrations: tryptophan: HR = 0.56; 95%CI:0.41,0.76, XA: HR = 0.74; 95%CI:0.64,0.85, PA: HR = 0.76; 95%CI:0.64,0.92), while higher concentrations of HK and QA were associated with an increased risk of death (per doubling in concentrations: HK: HR = 1.80; 95%CI:1.47,2.21, QA: HR = 1.31; 95%CI:1.05,1.63). A higher kynurenine-to-tryptophan ratio, a marker of cell-mediated immune activation, was associated with an increased risk of death (per doubling: HR = 2.07; 95%CI:1.52,2.83). In conclusion, tryptophan-kynurenine pathway metabolites may be prognostic markers of survival in CRC patients
Isoniazid preventive therapy modulates Mycobacterium tuberculosis-specific T-cell responses in individuals with latent tuberculosis and type 2 diabetes.
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318051.pdf (Publisher’s version ) (Open Access)Diabetes mellitus (DM) is a significant contributor to tuberculosis (TB) incidence and poor treatment outcomes. This study explored the impact of isoniazid preventive therapy (IPT) on Mycobacterium tuberculosis (Mtb)-specific T-cell memory phenotypes and function among participants with latent TB infection and DM (LTBI-DM) at baseline and after 6 months of IPT; and compared the responses to healthy controls (HC). Peripheral blood mononuclear cells were stimulated with ESAT-6 and CFP-10 peptide pools to analyse CD4(+) and CD8(+) T-cell responses using flow cytometry. In LTBI-DM participants, effector memory CD4(+) and CD8(+) T cells were decreased post-IPT, suggesting a shift towards a less-activated state or differentiation into other subsets. CXCR5 expression on both CD4(+) and CD8(+) T cells was upregulated, while PD-1 expression was downregulated post-IPT, indicating reduced T-cell exhaustion and improved homing capabilities. Lastly, IL-17 A and IL-13 production in CD4(+) and CD8(+) T cells was increased post-IPT, respectively, which play a role in enhanced Mtb infection control. The post-IPT T-cell alterations were similar to normal HC levels. These findings suggest that IPT modulates and normalises specific T-cell memory phenotypes and functional responses in LTBI-DM participants, potentially contributing to improved long-term immunity and protection against TB. This study highlights the importance of preventive therapy in high-risk populations, and larger studies with more extended follow-up are needed to assess long-lasting IPT effects
Effects of a guideline for children with cerebral visual impairment on the daily practices of vision habilitation and rehabilitation workers
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304291.pdf (Publisher’s version ) (Open Access)To support vision rehabilitation workers, an intervention guideline for the rehabilitation of children with cerebral visual impairment (CVI) was developed. It combines currently available theoretical and practice-based knowledge in the domains of academic performance and mobility. The aim of this study was to evaluate the perceived value of the guideline by professionals. Two studies were performed. First, a process analysis of the guideline was performed to evaluate its strengths and weaknesses. Eleven therapists used a concept of the guideline for 3 months and were interviewed about their expectations (before) and experiences (afterwards). In a second study, the guideline was introduced to 24 professionals working with school-aged children with CVI. The participants filled in a short survey with five questions about their perceived knowledge of and skills in dealing with CVI. The guideline complied with the expectations of the professionals, and the professionals improved in knowledge of CVI and the ability to explain what CVI is. The survey results indicated improvement in self-confidence to perform CVI-specific interventions, and the interviews also showed professionals had expected to learn more options for intervention. After training, the professionals felt more secure about their interventions while using the guideline. This was probably caused by an improvement in their knowledge about CVI and about available interventions. However, the improvement was small and still not perfect and could be enlarged by adding more concrete intervention suggestions to the guideline. The intervention guideline for CVI offers an overview of available theoretical and practice-based knowledge. Improvement in knowledge on CVI can be used directly in rehabilitation practices. A great advantage of the guideline is that therapists are now better prepared to explain the nature and consequences of CVI to a client.14 p
Attachment is in the eye of the beholder: A pupillometry study on emotion processing
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317385.pdf (Publisher’s version ) (Open Access)Early attachment relationships exert lasting effects on psychophysical health across the lifespan. Limited behavioral evidence suggests that these effects stem from how individuals perceive, interpret, and respond to their environment. This study investigated whether adults’ attachment representations modulate autonomic responses to happy and sad facial expressions, evidenced by changes in pupil size. We utilized a sample of healthy adults (N = 100; 68% females, 18–35 years, prevalently White European). In an eye-tracking experiment, we assessed pupil dilation to happy and sad facial expressions (n = 152 trials). Dismissing and preoccupied attachment orientations were assessed as continuous dimensions via self-report. Linear mixed models revealed that individuals with higher scores on dismissing orientations exhibited a significant increase in pupil dilation in response to sad and not happy expressions. No significant effects were observed for preoccupied orientations, age, or sex. These findings suggest that individuals with increased scores on dismissing attachment show heightened arousal to negative emotions.9 p
Should we be careful with exercise in post-exertional malaise after long COVID?
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317492.pdf (Publisher’s version ) (Open Access
Pinpointing the CN Stretch Frequency of Neutral Cyano-Polycyclic Aromatic Hydrocarbons: A Laboratory and Quantum Chemical Spectroscopic Study of 9-Cyanoanthracene
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317170.pdf (Publisher’s version ) (Open Access