| 1. |
- Abdel-Aziz, MI, et al.
(författare)
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A System Pharmacology Multi-Omics Approach toward Uncontrolled Pediatric Asthma
- 2021
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Ingår i: Journal of personalized medicine. - : MDPI AG. - 2075-4426. ; 11:6
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Tidskriftsartikel (refereegranskat)abstract
- There is a clinical need to identify children with poor asthma control as early as possible, to optimize treatment and/or to find therapeutic alternatives. Here, we present the “Systems Pharmacology Approach to Uncontrolled Pediatric Asthma” (SysPharmPediA) study, which aims to establish a pediatric cohort of moderate-to-severe uncontrolled and controlled patients with asthma, to investigate pathophysiological mechanisms underlying uncontrolled moderate-to-severe asthma in children on maintenance treatment, using a multi-omics systems medicine approach. In this multicenter observational case–control study, moderate-to-severe asthmatic children (age; 6–17 years) were included from four European countries (Netherlands, Germany, Spain, and Slovenia). Subjects were classified based on asthma control and number of exacerbations. Demographics, current and past patient/family history, and clinical characteristics were collected. In addition, systems-wide omics layers, including epi(genomics), transcriptomics, microbiome, proteomics, and metabolomics were evaluated from multiple samples. In all, 145 children were included in this cohort, 91 with uncontrolled (median age = 12 years, 43% females) and 54 with controlled asthma (median age = 11.7 years, 37% females). The two groups did not show statistically significant differences in age, sex, and body mass index z-score distribution. Comprehensive information and diverse noninvasive biosampling procedures for various omics analyses will provide the opportunity to delineate underlying pathophysiological mechanisms of moderate-to-severe uncontrolled pediatric asthma. This eventually might reveal novel biomarkers, which could potentially be used for noninvasive personalized diagnostics and/or treatment.
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| 2. |
- Cao, Yang, Associate Professor, 1972-, et al.
(författare)
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Predictive Values of Preoperative Characteristics for 30-Day Mortality in Traumatic Hip Fracture Patients
- 2021
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Ingår i: Journal of Personalized Medicine. - : MDPI. - 2075-4426. ; 11:5
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Tidskriftsartikel (refereegranskat)abstract
- Hip fracture patients have a high risk of mortality after surgery, with 30-day postoperative rates as high as 10%. This study aimed to explore the predictive ability of preoperative characteristics in traumatic hip fracture patients as they relate to 30-day postoperative mortality using readily available variables in clinical practice. All adult patients who underwent primary emergency hip fracture surgery in Sweden between 2008 and 2017 were included in the analysis. Associations between the possible predictors and 30-day mortality was performed using a multivariate logistic regression (LR) model; the bidirectional stepwise method was used for variable selection. An LR model and convolutional neural network (CNN) were then fitted for prediction. The relative importance of individual predictors was evaluated using the permutation importance and Gini importance. A total of 134,915 traumatic hip fracture patients were included in the study. The CNN and LR models displayed an acceptable predictive ability for predicting 30-day postoperative mortality using a test dataset, displaying an area under the ROC curve (AUC) of as high as 0.76. The variables with the highest importance in prediction were age, sex, hypertension, dementia, American Society of Anesthesiologists (ASA) classification, and the Revised Cardiac Risk Index (RCRI). Both the CNN and LR models achieved an acceptable performance in identifying patients at risk of mortality 30 days after hip fracture surgery. The most important variables for prediction, based on the variables used in the current study are age, hypertension, dementia, sex, ASA classification, and RCRI.
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| 3. |
- Chala, A, et al.
(författare)
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Predictors of Efavirenz Plasma Exposure, Auto-Induction Profile, and Effect of Pharmacogenetic Variations among HIV-Infected Children in Ethiopia: A Prospective Cohort Study
- 2021
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Ingår i: Journal of personalized medicine. - : MDPI AG. - 2075-4426. ; 11:12
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Tidskriftsartikel (refereegranskat)abstract
- (1) Background: Efavirenz plasma concentration displays wide between-patient variability partly due to pharmacogenetic variation and autoinduction. Pediatric data on efavirenz pharmacokinetics and the relevance of pharmacogenetic variation are scarce, particularly from sub-Saharan Africa, where >90% of HIV-infected children live and population genetic diversity is extensive. We prospectively investigated the short- and long-term effects of efavirenz auto-induction on plasma drug exposure and the influence of pharmacogenetics among HIV-infected Ethiopian children. (2) Method: Treatment-naïve HIV-infected children aged 3–16 years old (n = 111) were enrolled prospectively to initiate efavirenz-based combination antiretroviral therapy (cART). Plasma efavirenz concentrations were quantified at 4, 8, 12, 24, and 48 weeks of cART. Genotyping for CYP2B6, CYP3A5, UGT2B7, ABCB1, and SLCO1B1 common functional variant alleles was performed. (3) Results: The efavirenz plasma concentration reached a peak at two months, declined by the 3rd month, and stabilized thereafter, with no significant difference in geometric mean over time. On average, one-fourth of the children had plasma efavirenz concentrations ≥4 µg/mL. On multivariate analysis, CYP2B6*6 and ABCB1c.3435 C > T genotypes and low pre-treatment low-density lipoprotein (LDL) were significantly associated with higher plasma efavirenz concentration regardless of treatment duration. Duration of cART, sex, age, nutritional status, weight, and SLCO1B, CYP3A5, UGT2B7, and ABCB1 rs3842 genotypes were not significant predictors of efavirenz plasma exposure. (4) Conclusion: Pre-treatment LDL cholesterol and CYP2B6*6 and ABCB1c.3435 C > T genotypes predict efavirenz plasma exposure among HIV-infected children, but treatment-duration-dependent changes in plasma efavirenz exposure due to auto-induction are not statistically significant.
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| 4. |
- Chen, Jiaying, et al.
(författare)
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Associations between Multimorbidity Patterns and Subsequent Labor Market Marginalization among Refugees and Swedish-Born Young Adults-A Nationwide Registered-Based Cohort Study
- 2021
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Ingår i: Journal of Personalized Medicine. - : MDPI AG. - 2075-4426. ; 11:12
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Tidskriftsartikel (refereegranskat)abstract
- Background: Young refugees are at increased risk of labor market marginalization (LMM). We sought to examine whether the association of multimorbidity patterns and LMM differs in refugee youth compared to Swedish-born youth and identify the diagnostic groups driving this association. Methodology: We analyzed 249,245 individuals between 20–25 years, on 31 December 2011, from a combined Swedish registry. Refugees were matched 1:5 to Swedish-born youth. A multimorbidity score was computed from a network of disease co-occurrences in 2009–2011. LMM was defined as disability pension (DP) or >180 days of unemployment during 2012–2016. Relative risks (RR) of LMM were calculated for 114 diagnostic groups (2009–2011). The odds of LMM as a function of multimorbidity score were estimated using logistic regression. Results: 2841 (1.1%) individuals received DP and 16,323 (6.5%) experienced >180 annual days of unemployment during follow-up. Refugee youth had a marginally higher risk of DP (OR (95% CI): 1.59 (1.52, 1.67)) depending on their multimorbidity score compared to Swedish-born youth (OR (95% CI): 1.51 (1.48, 1.54)); no differences were found for unemployment (OR (95% CI): 1.15 (1.12, 1.17), 1.12 (1.10, 1.14), respectively). Diabetes mellitus and influenza/pneumonia elevated RR of DP in refugees (RRs (95% CI) 2.4 (1.02, 5.6) and 1.75 (0.88, 3.45), respectively); most diagnostic groups were associated with a higher risk for unemployment in refugees. Conclusion: Multimorbidity related similarly to LMM in refugees and Swedish-born youth, but different diagnoses drove these associations. Targeted prevention, screening, and early intervention strategies towards specific diagnoses may effectively reduce LMM in young adult refugees.
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| 5. |
- Collin, CB, et al.
(författare)
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Computational Models for Clinical Applications in Personalized Medicine-Guidelines and Recommendations for Data Integration and Model Validation
- 2022
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Ingår i: Journal of personalized medicine. - : MDPI AG. - 2075-4426. ; 12:2
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Tidskriftsartikel (refereegranskat)abstract
- The future development of personalized medicine depends on a vast exchange of data from different sources, as well as harmonized integrative analysis of large-scale clinical health and sample data. Computational-modelling approaches play a key role in the analysis of the underlying molecular processes and pathways that characterize human biology, but they also lead to a more profound understanding of the mechanisms and factors that drive diseases; hence, they allow personalized treatment strategies that are guided by central clinical questions. However, despite the growing popularity of computational-modelling approaches in different stakeholder communities, there are still many hurdles to overcome for their clinical routine implementation in the future. Especially the integration of heterogeneous data from multiple sources and types are challenging tasks that require clear guidelines that also have to comply with high ethical and legal standards. Here, we discuss the most relevant computational models for personalized medicine in detail that can be considered as best-practice guidelines for application in clinical care. We define specific challenges and provide applicable guidelines and recommendations for study design, data acquisition, and operation as well as for model validation and clinical translation and other research areas.
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| 6. |
- de Anta, L, et al.
(författare)
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Areas of Interest and Social Consideration of Antidepressants on English Tweets: A Natural Language Processing Classification Study
- 2022
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Ingår i: Journal of personalized medicine. - : MDPI AG. - 2075-4426. ; 12:2
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Tidskriftsartikel (refereegranskat)abstract
- Background: Antidepressants are the foundation of the treatment of major depressive disorders. Despite the scientific evidence, there is still a sustained debate and concern about the efficacy of antidepressants, with widely differing opinions among the population about their positive and negative effects, which may condition people’s attitudes towards such treatments. Our aim is to investigate Twitter posts about antidepressants in order to have a better understanding of the social consideration of antidepressants. Methods: We gathered public tweets mentioning antidepressants written in English, published throughout a 22-month period, between 1 January 2019 and 31 October 2020. We analysed the content of each tweet, determining in the first place whether they included medical aspects or not. Those with medical content were classified into four categories: general aspects, such as quality of life or mood, sleep-related conditions, appetite/weight issues and aspects around somatic alterations. In non-medical tweets, we distinguished three categories: commercial nature (including all economic activity, drug promotion, education or outreach), help request/offer, and drug trivialization. In addition, users were arranged into three categories according to their nature: patients and relatives, caregivers, and interactions between Twitter users. Finally, we identified the most mentioned antidepressants, including the number of retweets and likes, which allowed us to measure the impact among Twitter users. Results: The activity in Twitter concerning antidepressants is mainly focused on the effects these drugs may have on certain health-related areas, specifically sleep (20.87%) and appetite/weight (8.95%). Patients and relatives are the type of user that most frequently posts tweets with medical content (65.2%, specifically 80% when referencing sleep and 78.6% in the case of appetite/weight), whereas they are responsible for only 2.9% of tweets with non-medical content. Among tweets classified as non-medical in this study, the most common subject was drug trivialization (66.86%). Caregivers barely have any presence in conversations in Twitter about antidepressants (3.5%). However, their tweets rose more interest among other users, with a ratio 11.93 times higher than those posted by patients and their friends and family. Mirtazapine is the most mentioned antidepressant in Twitter (45.43%), with a significant difference with the rest, agomelatine (11.11%). Conclusions: This study shows that Twitter users that take antidepressants, or their friends and family, use social media to share medical information about antidepressants. However, other users that do not talk about antidepressants from a personal or close experience, frequently do so in a stigmatizing manner, by trivializing them. Our study also brings to light the scarce presence of caregivers in Twitter.
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| 7. |
- Fares, M, et al.
(författare)
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COL-3-Induced Molecular and Ultrastructural Alterations in K562 Cells
- 2022
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Ingår i: Journal of personalized medicine. - : MDPI AG. - 2075-4426. ; 12:1
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Tidskriftsartikel (refereegranskat)abstract
- Tetracycline-3 (4-dedimethylamino sancycline, COL-3) is a non-antibiotic tetracycline derivative. COL-3 exerts potent anti-metalloproteinase activity and its antitumor effects have been reported both in vitro and in vivo. In this study, we investigated the mechanisms of COL-3-induced cytotoxicity in a chronic myeloid leukemia cell line, K562, characterized by the BCR–ABL fusion protein. COL-3 induced K562 cell death in a concentration-dependent manner with an IC50 of 10.8 µg/mL and exhibited features of both apoptosis and necrosis. However, flow cytometry analysis revealed that necrotic cells dominated over the early and late apoptotic cells upon treatment with COL-3. Transmission electron microscopy analysis in combination with Western blotting (WB) analysis revealed early mitochondrial swelling accompanied by the early release of cytochrome c and truncated apoptosis inducing factor (tAIF). In addition, ultrastructural changes were detected in the endoplasmic reticulum (ER). COL-3 affected the levels of glucose-regulated protein-94 (GRP94) and resulted in m-calpain activation. DNA double strand breaks as a signature for DNA damage was also confirmed using an antibody against γH2AX. WB analyses did not demonstrate caspase activation, while Bcl-xL protein remained unaffected. In conclusion, COL-3-induced cell death involves DNA damage as well as mitochondrial and ER perturbation with features of paraptosis and programmed necrosis.
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| 8. |
- Forssten, Maximilian Peter, 1996-, et al.
(författare)
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Predicting 1-Year Mortality after Hip Fracture Surgery : An Evaluation of Multiple Machine Learning Approaches
- 2021
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Ingår i: Journal of Personalized Medicine. - : MDPI. - 2075-4426. ; 11:8
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Tidskriftsartikel (refereegranskat)abstract
- Postoperative death within 1 year following hip fracture surgery is reported to be up to 27%. In the current study, we benchmarked the predictive precision and accuracy of the algorithms support vector machine (SVM), naïve Bayes classifier (NB), and random forest classifier (RF) against logistic regression (LR) in predicting 1-year postoperative mortality in hip fracture patients as well as assessed the relative importance of the variables included in the LR model. All adult patients who underwent primary emergency hip fracture surgery in Sweden, between 1 January 2008 and 31 December 2017 were included in the study. Patients with pathological fractures and non-operatively managed hip fractures, as well as those who died within 30 days after surgery, were excluded from the analysis. A LR model with an elastic net regularization were fitted and compared to NB, SVM, and RF. The relative importance of the variables in the LR model was then evaluated using the permutation importance. The LR model including all the variables demonstrated an acceptable predictive ability on both the training and test datasets for predicting one-year postoperative mortality (Area under the curve (AUC) = 0.74 and 0.74 respectively). NB, SVM, and RF tended to over-predict the mortality, particularly NB and SVM algorithms. In contrast, LR only over-predicted mortality when the predicted probability of mortality was larger than 0.7. The LR algorithm outperformed the other three algorithms in predicting 1-year postoperative mortality in hip fracture patients. The most important predictors of 1-year mortality were the presence of a metastatic carcinoma, American Society of Anesthesiologists(ASA) classification, sex, Charlson Comorbidity Index (CCI) ≤ 4, age, dementia, congestive heart failure, hypertension, surgery using pins/screws, and chronic kidney disease.
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| 9. |
- Giontella, Alice, et al.
(författare)
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Association of thyroid function with blood pressure and cardiovascular disease : A mendelian randomization
- 2021
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Ingår i: Journal of Personalized Medicine. - : MDPI AG. - 2075-4426. ; 11:12
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Tidskriftsartikel (refereegranskat)abstract
- Thyroid function has a widespread effect on the cardiometabolic system. However, the causal association between either subclinical hyper-or hypothyroidism and the thyroid hormones with blood pressure (BP) and cardiovascular diseases (CVD) is not clear. We aim to investigate this in a two-sample Mendelian randomization (MR) study. Single nucleotide polymorphisms (SNPs) associated with thyroid-stimulating hormone (TSH), free tetraiodothyronine (FT4), hyper-and hypothyroidism, and anti-thyroid peroxidase antibodies (TPOAb), from genome-wide association studies (GWAS), were selected as MR instrumental variables. SNPs–outcome (BP, CVD) associations were evaluated in a large-scale cohort, the Malmö Diet and Cancer Study (n = 29,298). Causal estimates were computed by inverse-variance weighted (IVW), weighted median, and MR-Egger approaches. Genetically increased levels of TSH were associated with decreased systolic BP and with a lower risk of atrial fibrillation. Hyperthyroidism and TPOAb were associated with a lower risk of atrial fibrillation. Our data support a causal association between genetically decreased levels of TSH and both atrial fibrillation and systolic BP. The lack of significance after Bonferroni correction and the sensitivity analyses suggesting pleiotropy, should prompt us to be cautious in their interpretation. Nevertheless, these findings offer mechanistic insight into the etiology of CVD. Further work into the genes involved in thyroid functions and their relation to cardiovascular outcomes may highlight pathways for targeted intervention.
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| 10. |
- Gretarsdottir, Helga Maria, et al.
(författare)
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Personalized Medicine Approach in Treating Parkinson's Disease, Using Oral Administration of Levodopa/Carbidopa Microtablets in Clinical Practice
- 2021
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Ingår i: Journal of Personalized Medicine. - : MDPI. - 2075-4426. ; 11:8
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Tidskriftsartikel (refereegranskat)abstract
- Background: The most effective symptomatic treatment in Parkinson's disease (PD) is levodopa in standard doses. However, as the disease progresses, there may be a need for a more personalized approach and fine tuning, in accordance with the patients' needs. This study aims to evaluate the individual experience of levodopa/carbidopa 5/1.25 mg microtablets (LC-5) in clinical practice with respect to efficacy, tolerability, and usability. The method used was as follows: patients answered a questionnaire concerning the effect and usability of LC-5, and their medical records were reviewed. Regarding results, thirty-five survey responses were obtained, and 29 patients' medical records were reviewed. The LC-5 dose dispenser usability was generally rated positively and facilitated medication adherence. The majority (85%) of patients reported symptom improvement while using LC-5, compared with previous standard treatments. These results suggest that LC-5 therapy is generally well-tolerated, with favorable patient-reported efficacy and user friendliness, as well as the possibility for an individualized, fine-tuned PD treatment. Further studies with a prospective design and larger study population are needed to confirm the results.
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