Citations

Levodopa is the most widely used medication for the symptomatic treatment of Parkinson’s disease and, despite being an “old” drug, is still considered the gold standard for offering symptomatic relief. The pharmacokinetic and pharmacodynamics of levodopa have been studied extensively. Our review explores the molecular mechanisms that affect the absorption of this drug, focusing on the large intra- and interindividual variability of absorption that is commonly encountered in daily clinical practice, and on the interaction with other medications. In addition, we will explore the clinical implications of levodopa absorption variability and address current and future strategies for researchers and clinicians.

Abstract Background Various studies have revealed that there is a disproportionately low representation of skin of colour (SOC) in medical school dermatologic curriculum and board study resources. Methods First-year and second-year medical students were emailed an 18-question survey regarding (1) identifying correct diagnoses of dermatologic conditions on either White skin or SOC and (2) their confidence in identifying dermatologic conditions on SOC. Results 15% of the images of dermatologic conditions included in the institutional preclinical curriculum show images of patients with SOC. Regarding overall scores for diagnosing dermatologic diseases, students performed similarly on both the White image survey (61.73%) and SOC image survey (66.20%) with no statistically significant differences between surveys (p = 0.14). Second-year medical students performed better than first-year medical students overall (p = 0.01) and on White skin image survey scores (p = 0.02) but not on people of colour image survey scores (p = 0.09). Students largely agreed that they were more comfortable identifying dermatologic diagnoses on White skin and that their school could benefit from increased SOC dermatological resources. Conclusion The overall low scores for the diagnosis of common skin conditions on both the White image and SOC image survey by first- and second-year students are not surprising given the results of a prior study and support the need for re-exposure to dermatology presentations in all skin types during the preclinical curriculum. The low scores support the need for changes in the pre-clinical dermatology curriculum to improve diagnostic ability. Second-year students performed better at diagnosing dermatologic conditions overall and on White skin compared to SOC at the end of their didactic years, possibly due to an underrepresentation of SOC images in institutional and outside educational resources. Attitudes towards school-specific dermatologic SOC education demonstrated a clear desire amongst students for more exposure to dermatologic conditions in various skin colours throughout the curriculum.

Abstract Introduction: Current guidelines state the effectiveness of desmopressin to reduce hematoma expansion in antiplatelet-related intracerebral hemorrhage (ICH) is uncertain. This study sought to determine if desmopressin decreased hematoma expansion in ICH patients on antiplatelet agents. Methods: We conducted a multi-center, retrospective propensity-matched cohort study at 11 US emergency departments (ED) that participate in EMPHARM-NET. Adult patients ≥18 years with a primary diagnosis of spontaneous ICH on antiplatelets prior to admission from January 1, 2017 through May 1, 2021 were included. The primary endpoint was good or excellent hemostatic efficacy within the first 24 hours following ICH between patients that did and did not receive desmopressin. Brain imaging was reviewed using 3D-Slicer by blinded expert physicians. Results: Overall, 1408 patients were evaluated for inclusion. A total of 324 patients were included, of which 13.8% (n=45) received desmopressin and 86.1% (n=279) did not. After propensity matching, 35 patients receive desmopressin compared to 140 controls. Baseline hematoma volume (27.6 mL vs. 2.1 mL) and was significantly higher in the desmopressin group. The primary endpoint of good or excellent hemostatic efficacy was similar between groups (74.3% desmopressin group vs. 85% control group, -10.7% [-28.1% to 6.7%]). There was no difference in secondary outcomes. Conclusion: In this multicenter cohort, patients receiving desmopressin had higher baseline intraparenchymal hematoma volume, and did not appear to result in improved hemostatic efficacy relative to the control group. These results suggest against routine administration of desmopressin for antiplatelet-related ICH, though future study in a randomized trial design is necessary.

AbstractBackgroundAdverse effects of medical treatment (AEMT) pose significant risks to paediatric patients. However, the mortality trends associated with AEMT in this population have been unclear.ObjectiveWe aimed to clarify the trends in the incidence, disability‐adjusted life years (DALYs) and mortality rates of AEMT for children in the US from 2000 to 2019.MethodsData were retrieved from the Global Burden of Disease study 2019. We estimated age‐standardized incidence, DALYs and mortality rates of paediatric AEMT per 100,000 children in the US using a Bayesian meta‐regression model. We also analysed incidence, DALYs and mortality in different age groups, and employed Joinpoint regression models to assess the age‐ and sex‐specific trends.ResultsThe number of deaths due to AEMT in children, the number of cases, and DALYs were 105.1, 551,076 and 145,555 in 2019, decreased by 37.5%, 6% and 28% from those in 2000, respectively. Age‐standardized mortality rates decreased across all age groups, while the incidence increased across all age groups with an average annual percentage change (AAPC) of 2.2% in those children <1 year and 4.5% in 5–9 years of age. The increases in DALYs over time was higher in children aged 1–4 years (AAPC: 0.51, 95% CI: 0.47, 0.62) and 5–9 years (AAPC: 0.33, 95% CI: 0.15, 0.50), with the 1–4 year age group being the highest.ConclusionThe study reveals declining AEMT mortality but rising incidence and DALYs, emphasizing a disproportionate burden in <1, 1–4 and 5–9 years. To develop effective mitigation strategies, future research is warranted to identify the causes of increased AEMT in children, especially young males.

AbstractBackgroundIrritable bowel syndrome (IBS) is a disorder of gut–brain interaction characterized by abdominal pain and altered bowel habits, with patient‐perceived dissatisfaction of treatment symptom control. We assessed disease burden, satisfaction with medication use, and impact on activities, in participants with IBS with constipation (IBS‐C) and diarrhea (IBS‐D).MethodsThis study assessed data from a large, United States survey of adults querying demographics, comorbid conditions, quality of life, medication use, satisfaction with symptom control, and work productivity. Participants were grouped into the IBS‐C or IBS‐D cohort if they met Rome IV criteria, with controls matched 1:1 according to age, sex, race, region, and Charlson Comorbidity Index score. All data were self‐reported.Key ResultsNine hundred and ten participants with IBS‐C and 669 with IBS‐D were matched to controls. The most reported symptoms were abdominal discomfort for IBS‐C and abdominal pain and abdominal discomfort for IBS‐D. Among the IBS‐C and IBS‐D cohorts, 74.2% and 65.9%, respectively, took prescription and/or over‐the‐counter medication for their symptoms. Respondents were more dissatisfied than satisfied with control of their symptoms. Respondents taking prescription medication(s) with or without over‐the‐counter medication(s) reported better symptom control than respondents only taking over‐the‐counter medications (p < 0.001). There was significantly higher mean presenteeism, work productivity loss, and daily activity impairment (p < 0.001 for all) in respondents with IBS compared with controls.Conclusions and InferencesThis study provides insight into respondents' experiences of IBS symptoms, including the impact on daily activity, as well as satisfaction with control of symptoms and prescription and over‐the‐counter medications.

AbstractTransitive inference (TI) has a long history in the study of human development. There have, however, few pediatric studies that report clinical diagnoses have tested trial‐and‐error TI learning, in which participants infer item relations, rather than evaluate them explicitly from verbal descriptions. Children aged 8–10 underwent a battery of clinical assessments and received a range of diagnoses, potentially including autism spectrum disorder (ASD), attention‐deficit hyperactive disorder (ADHD), anxiety disorders (AD), specific learning disorders (SLD), and/or communication disorders (CD). Participants also performed a trial‐and‐error learning task that tested for TI. Response accuracy and reaction time were assessed using a statistical model that controlled for diagnostic comorbidity at the group level. Participants in all diagnostic categories showed evidence of TI. However, a model comparison analysis suggested that those diagnosed with ASD succeeded in a qualitatively different way, responding more slowly to each choice and improving faster across trials than their non‐ASD counterparts. Additionally, TI performance was not associated with IQ. Overall, our data suggest that superficially similar performance levels between ASD and non‐ASD participants may have resulted from a difference in the speed‐accuracy tradeoff made by each group. Our work provides a preliminary profile of the impact of various clinical diagnoses on TI performance in young children. Of these, an ASD diagnosis resulted in the largest difference in task strategy.

LINKED CONTENTThis article is linked to Idalsoaga et al papers. To view these articles, visithttps://doi.org/10.1111/apt.18193andhttps://doi.org/10.1111/apt.18220

Abstract Binary encoding of features has proven to be a versatile tool for optimizing data processing and memory efficiency in various machine learning applications. This includes deep barcoding of images for retrieval of similar cases among millions of indexed images. Despite the recent advancement in barcode generation methods, converting hyperdimensional feature vectors (e.g., deep features) to compact and discriminative binary barcodes is still an urgent necessity and widely an unresolved problem. MinMax barcoding of features is one of the efficient binarization methods, where the accuracy of the generated barcodes is inherently dependent on the feature order due to its computation process. In this paper, we propose a combinatorial evolutionary framework for optimizing barcodes. The primary goal is to determine an optimal permutation of extracted deep features, leading to more accurate barcodes. The performance of the proposed model has been assessed in downstream image retrieval tasks using a variety of datasets. This evaluation includes medical images from The Cancer Genome Atlas (TCGA), a comprehensive publicly available dataset, as well as images from a COVID-19 dataset. In addition, the model's performance was tested on diverse non-medical image collections, such as CIFAR-10 and Fashion-MNIST. Our findings demonstrate that optimizing barcodes significantly enhances retrieval accuracy across a wide range of applications, highlighting the applicability and potential of barcodes in various domains.

AbstractBackgroundPost‐infectious disorders of gut‐brain interaction (PI‐DGBI) have significant impact on children and adolescents. The effect of COVID‐19 on PI‐DGBI‐associated symptoms in this population, however, is unknown.MethodsWe performed electronic medical record searches to identify patients 8–17 years old with a SARS‐CoV2 PCR test at Lurie Children's Hospital between November 2020 and March 2021 (cohort 1) and April–October 2021 (cohort 2). Questionnaires were administered to assess symptoms prior to and 3 months following the test. This included the Pediatric Eosinophilic Esophagitis Symptom Score (PEESS), questionnaire of pediatric gastrointestinal symptoms—Rome IV, Nausea Profile (NP), dyspepsia symptom survey (DSS), nausea severity profile (NSP), and Pediatric Quality of Life Inventory (PedsQL). We grouped patients based on the presence of symptoms prior to COVID‐19 test or the test result.ResultsOne hundred and ninety‐six parent(s) or guardian(s) in cohort 1 and 274 in cohort 2 completed surveys and self‐reported their child's COVID‐19 result. Cohort 1 had increased PEESS and DSS scores, lower PedsQL scores, and increased frequency of abdominal pain disorders among patients with symptoms prior to COVID‐19 testing. Both cohorts had increased NP and NSP scores among patients with symptoms prior to COVID‐19 testing that was highest among patients with a positive COVID‐19 test. Abdominal pain and diarrhea prior to COVID‐19 testing predicted higher NP scores.ConclusionsAmong symptomatic COVID‐19 tested children, we found increased severity of nausea‐associated somatic, emotional, and gastrointestinal symptoms in the 3 months following the test that was most increased among patients with a positive COVID‐19 test.