Effects of methylphenidate on executive functioning in attention-deficit/hyperactivity disorder across the lifespan:A meta-regression analysis

Attention-deficit/hyperactivity disorder (ADHD) in childhood and adulthood is often treated with the psychostimulant methylphenidate (MPH). However, it is unknown whether cognitive effects of MPH depend on age in individuals with ADHD, while animal studies have suggested age-related effects. In this meta-analysis, we first determined the effects of MPH on response inhibition, working memory and sustained attention, but our main goal was to examine whether these effects are moderated by age. A systematic literature search using PubMed, PsycINFO, Web of Science and MEDLINE for double-blind, placebo-controlled studies with MPH resulted in 25 studies on response inhibition (n = 775), 13 studies on working memory (n = 559) and 29 studies on sustained attention (n = 956) (mean age range 4.8–50.1 years). The effects of MPH on response inhibition [effect size (ES) = 0.40, p < 0.0001, 95% confidence interval (CI) 0.22–0.58], working memory (ES = 0.24, p = 0.053, 95% CI 0.00–0.48) and sustained attention (ES = 0.42, p < 0.0001, 95% CI 26–0.59) were small to moderate. No linear or quadratic age-dependencies were observed, indicating that effects of MPH on executive functions are independent of age in children and adults with ADHD. However, adolescent studies are lacking and needed to conclude a lack of an age-dependency across the lifespan

Measuring decline in white matter integrity after systemic treatment for breast cancer:Omitting skeletonization enhances sensitivity

Chemotherapy for non-central nervous system cancers is associated with abnormalities in brain structure and function. Diffusion tensor imaging (DTI) allows for studying in vivo microstructural changes in brain white matter. Tract-based spatial statistics (TBSS) is a widely used processing pipeline in which DTI data are typically normalized to a generic DTI template and then ‘skeletonized’ to compensate for misregistration effects. However, this approach greatly reduces the overall white matter volume that is subjected to statistical analysis, leading to information loss. Here, we present a re-analysis of longitudinal data previously analyzed with standard TBSS (Menning et al., BIB 2018, 324–334). For our current approach, we constructed a pipeline with an optimized registration method in Advanced Normalization Tools (ANTs) where DTI data are registered to a study-specific, high-resolution T1 template and the skeletonization step is omitted. In a head to head comparison, we show that with our novel approach breast cancer survivors who had received chemotherapy plus or minus endocrine therapy (BC + SYST, n = 26) showed a global decline in overall FA that was not present in breast cancer survivors who did not receive systemic therapy (BC-SYST, n = 23) or women without a cancer diagnosis (no cancer controls, NC, n = 30). With the standard TBSS approach we did not find any group differences. Moreover, voxel-based analysis for our novel pipeline showed a widespread decline in FA in the BC + SYST compared to the NC group. Interestingly, the BC-SYST group also showed a decline in FA compared to the NC group, although in much less voxels. These results were not found with the standard TBSS approach. We demonstrate that a modified processing pipeline makes DTI data more sensitive to detecting changes in white matter integrity in non-CNS cancer patients after treatment, particularly chemotherapy

Symptom increase following a functional capacity evaluation in patients with chronic low back pain:An explorative study of safety

Introduction: This study was performed to study intensity and duration of symptom increase following an FCE and to explore safety of an FCE. Methods: Included were 92 patients with chronic low back pain (CLBP), mean age 38.5 years, mean self-reported disability 12.5 (Roland Morris Disability Questionnaire). All patients underwent an FCE. Symptom increase was measured with a 2-item questionnaire. Operational definition for safety: no formal complaint filed and symptom increase to occur only temporarily. Results: No formal complaints were filed (n=92). In total, 54 patients returned the questionnaire (59%; 'responders'). Of the responders, 76% reported increased symptom intensity after an FCE, ranging from 'little increase' to 'severe increase'. Symptoms of all responders returned to pre-FCE level. Duration of symptom increase of the responders ranged from 1 day to 3 weeks. Symptom increase resided to pre-FCE level within 1 week in 93% of the responders. Symptom increase was weakly related to self-reported disability (r=0.38, p <0.05). Except for gender, differences between responders and non-responders were non-significant. Conclusion: A temporary increase in symptom intensity following an FCE is common. Within the operational definitions of safety used in this study, assessment of functional capacity of patients with CLBP appears safe

Validation of the work ability index-single item and the pain disability index-work item in patients with chronic low back pain

PURPOSE: A cross-sectional and longitudinal study was conducted to analyse construct validity, responsiveness, and Minimal Clinically Important Change (MCIC) in the Work Ability Score (WAS) and Pain Disability Index Work item (PDI-W) in patients with Chronic Low Back Pain (CLBP). METHOD: Construct validity was assessed by testing predefined hypotheses. Responsiveness and MCIC were measured with an anchor-based method. The area under the receiver Operating Characteristic Curve (AUC) and the optimal cut-off point were calculated. Smallest Detectable Change (SDC) was calculated to determine measurement error. RESULTS: In total, 1502 patients (age 18-65 years) with CLBP were included. For validity of the WAS and PDI-W, respectively, seven and six out of 10 hypotheses were not rejected. The WAS (n = 355) was responsive to change with an AUC of 0.70. MCIC was 1.5 point, SDCindividual 4.9, and SDCgroup 0.3. MCICs were 4.5, 1.5, and - 0.5 points for, respectively, low, middle, and high scoring baseline groups. The PDI-W (n = 297) was responsive to change with an AUC of 0.80. MCIC was - 2.5 points, SDCindividual 5.2, and SDCgroup 0.3. MCICs were - 0.5, - 2.5, and - 4.5 points for, respectively, low, middle, and high scoring baseline groups. CONCLUSION: Construct validity of the WAS and PDI-W was insufficient in this patient sample. The WAS and PDI-W are responsive to change. On average, improvements of 1.5 point (WAS) and  - 2.5 points (PDI-W) were interpreted as clinically important. However, MCICs are also baseline dependent. Due to a risk of measurement error, at the individual level change scores should be interpreted with caution