Author: Dols, Annemieke ; Jimenez, Esther ; Vieta, Eduard ; Nunes, Paula V ; Forester, Brent P ; Calkin, Cynthia ; Lavin, Paola ; Teixeira, Antonio L ; Eyler, Lisa T ; Montejo, Laura ; Briggs, Farren B S ; Gildengers, Ariel G ; Korten, Nicole ; Levin, Jennifer B ; Patrick, Regan E ; Oudega, Mardien L ; Barbosa, Izabela G ; Almeida, Osvaldo P ; Hajek, Tomas ; Olagunju, Andrew T ; Soares, Jair C ; Forlenza, Orestes V ; Chen, Peijun ; Oluwaniyi, Stephen ; Balanzá-Martínez, Vicent ; Rej, Soham ; Schouws, Sigfried ; Sutherland, Ashley N ; Radua, Joaquim ; Yala, Joy ; Alda, Martin ; Lafer, Beny ; Haarman, Benno ; Altinbas, Kursat ; Sajatovic, Martha

OBJECTIVESTo compare the prevalence of physical morbidities between older aged patients with bipolar disorder (OABD) and non-psychiatric comparisons (NC), and to analyze sex differences in prevalence.METHODSOABD was defined as bipolar disorder among adults aged ≥50 years. Outcomes analyzed were the prevalence of diseases affecting the cardiovascular, respiratory, gastrointestinal, genitourinary, renal, musculoskeletal, and endocrine systems. The analysis used cross-sectional data of OABD participants (n = 878; mean age 60.9 ± 8.0 years, n = 496 (56%) women) from the collaborative Global Aging & Geriatric Experiments in Bipolar Disorder (GAGE-BD) dataset and NC participants recruited at the same sites (n = 355; mean age 64.4 ± 9.7 years, n = 215 (61%) women).RESULTSAfter controlling for sex, age, education, and smoking history, the OABD group had more cardiovascular (odds ratio [95% confidence interval]: 2.12 [1.38-3.30]), renal (5.97 [1.31-43.16]), musculoskeletal (2.09 [1.30-3.43]) and endocrine (1.90 [1.20-3.05]) diseases than NC. Women with OABD had more gastrointestinal (1.56 [0.99-2.49]), genitourinary (1.72 [1.02-2.92]), musculoskeletal (2.64 [1.66-4.37]) and endocrine (1.71 [1.08-2.73]) comorbidities than men with OABD, when age, education, smoking history, and study site were controlled.CONCLUSIONSThis replication GAGE-BD study confirms previous findings indicating that OABD present more physical morbidities than matched comparison participants, and that this health burden is significantly greater among women.

01 Jun 2024·European Journal of Immunology

Predominance of M2 macrophages in organized thrombi in chronic thromboembolic pulmonary hypertension patients

Article

Author: Bresser, Paul ; Koudstaal, Thomas ; Bergen, Ingrid ; Lila, Karishma ; von der Thüsen, Jan ; Bogaard, Harm Jan ; van den Bosch, Thierry ; Hendriks, Rudi ; Boomars, Karin

AbstractChronic thromboembolic pulmonary hypertension (CTEPH) is a debilitating disease characterized by thrombotic occlusion of pulmonary arteries and vasculopathy, leading to increased pulmonary vascular resistance and progressive right‐sided heart failure. Thrombotic lesions in CTEPH contain CD68+ macrophages, and increasing evidence supports their role in disease pathogenesis. Macrophages are classically divided into pro‐inflammatory M1 macrophages and anti‐inflammatory M2 macrophages, which are involved in wound healing and tissue repair. Currently, the phenotype of macrophages and their localization within thrombotic lesions of CTEPH are largely unknown. In our study, we subclassified thrombotic lesions of CTEPH patients into developing fresh thrombi (FT) and organized thrombi (OT), based on the degree of fibrosis and remodeling. We used multiplex immunofluorescence histology to identify immune cell infiltrates in thrombotic lesions of CPTEH patients. Utilizing software‐assisted cell detection and quantification, increased proportions of macrophages were observed in immune cell infiltrates of OT lesions, compared with FT. Strikingly, the proportions with a CD206+INOS− M2 phenotype were significantly higher in OT than in FT, which mainly contained unpolarized macrophages. Taken together, we observed a shift from unpolarized macrophages in FT toward an expanded population of M2 macrophages in OT, indicating a dynamic role of macrophages during CTEPH pathogenesis.

01 May 2024·Pediatric Drugs

Improving Methylphenidate Titration in Children with Attention-Deficit/Hyperactivity Disorder (ADHD): A Randomized Controlled Trial Using Placebo-Controlled Titration Implemented in Clinical Practice

Article

Author: Vertessen, Karen ; Bottelier, Marco ; Bet, Pierre ; Bergwerff, Catharina E ; Swanson, James M ; Wisse, Annemiek ; Luman, Marjolein ; Stoffelsen, Reino ; Twisk, Jos ; Oosterlaan, Jaap

BACKGROUND AND OBJECTIVESConcerns exist regarding the rising use of methylphenidate. A double-blind, placebo-controlled methylphenidate titration (PCT) for children with attention-deficit/hyperactivity disorder (ADHD) has shown potential to improve titration (i.e., detection of placebo responders and larger ADHD symptom improvement) in experimental settings. This study aims to determine if these advantages can be transferred to clinical settings.METHODChildren (aged 5-13 years) with an ADHD diagnosis and an indication to start methylphenidate (MPH) treatment were recruited. Participants were randomized to PCT or care as usual (CAU) in a 1:1 ratio followed by a 7-week randomized controlled trial (T1) and 6-month, naturalistic, open-label follow-up (T2). Parents, teachers, and physicians rated ADHD symptoms, ADHD medication use, MPH dosing, and treatment satisfaction using questionnaires.RESULTSA total of 100 children were enrolled and randomized to PCT (n = 49) or CAU (n = 51). In the PCT group, we found 8.2% placebo responders, 16.3% non-responders, and 65.3% responders to MPH. With PCT compared with CAU, a significantly larger number of children discontinued MPH (T1: 24.5 vs 5.9%, p = 0.009; T2: 41.7 vs 10.4%, p < 0.001) and refrained from using other pharmacological treatment (T1: 20.4 vs 3.9%, p = 0.013; T2: 20.83 vs 6.25%, p = 0.002). At both timepoints, there were no significant differences between the groups in the average dose of MPH, ADHD symptoms, or treatment satisfaction.CONCLUSIONSPCT can be used to improve detection of children who do not benefit from MPH, and may therefore potentially reduce overtreatment of ADHD with MPH.

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