SwePub
Sök i SwePub databas

  Utökad sökning

Träfflista för sökning "L773:2075 4426 "

Sökning: L773:2075 4426

  • Resultat 1-50 av 62
Sortera/gruppera träfflistan
   
NumreringReferensOmslagsbildHitta
1.
  • Abdel-Aziz, MI, et al. (författare)
  • A System Pharmacology Multi-Omics Approach toward Uncontrolled Pediatric Asthma
  • 2021
  • Ingår i: Journal of personalized medicine. - : MDPI AG. - 2075-4426. ; 11:6
  • 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.
  •  
2.
  • Cao, Yang, Associate Professor, 1972-, et al. (författare)
  • Predictive Values of Preoperative Characteristics for 30-Day Mortality in Traumatic Hip Fracture Patients
  • 2021
  • Ingår i: Journal of Personalized Medicine. - : MDPI. - 2075-4426. ; 11:5
  • 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.
  •  
3.
  • Chala, A, et al. (författare)
  • Predictors of Efavirenz Plasma Exposure, Auto-Induction Profile, and Effect of Pharmacogenetic Variations among HIV-Infected Children in Ethiopia: A Prospective Cohort Study
  • 2021
  • Ingår i: Journal of personalized medicine. - : MDPI AG. - 2075-4426. ; 11:12
  • 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.
  •  
4.
  • Chen, Jiaying, et al. (författare)
  • Associations between Multimorbidity Patterns and Subsequent Labor Market Marginalization among Refugees and Swedish-Born Young Adults-A Nationwide Registered-Based Cohort Study
  • 2021
  • Ingår i: Journal of Personalized Medicine. - : MDPI AG. - 2075-4426. ; 11:12
  • 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.
  •  
5.
  • Collin, CB, et al. (författare)
  • Computational Models for Clinical Applications in Personalized Medicine-Guidelines and Recommendations for Data Integration and Model Validation
  • 2022
  • Ingår i: Journal of personalized medicine. - : MDPI AG. - 2075-4426. ; 12:2
  • 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.
  •  
6.
  • de Anta, L, et al. (författare)
  • Areas of Interest and Social Consideration of Antidepressants on English Tweets: A Natural Language Processing Classification Study
  • 2022
  • Ingår i: Journal of personalized medicine. - : MDPI AG. - 2075-4426. ; 12:2
  • 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.
  •  
7.
  • Fares, M, et al. (författare)
  • COL-3-Induced Molecular and Ultrastructural Alterations in K562 Cells
  • 2022
  • Ingår i: Journal of personalized medicine. - : MDPI AG. - 2075-4426. ; 12:1
  • 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.
  •  
8.
  • Forssten, Maximilian Peter, 1996-, et al. (författare)
  • Predicting 1-Year Mortality after Hip Fracture Surgery : An Evaluation of Multiple Machine Learning Approaches
  • 2021
  • Ingår i: Journal of Personalized Medicine. - : MDPI. - 2075-4426. ; 11:8
  • 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.
  •  
9.
  • Giontella, Alice, et al. (författare)
  • Association of thyroid function with blood pressure and cardiovascular disease : A mendelian randomization
  • 2021
  • Ingår i: Journal of Personalized Medicine. - : MDPI AG. - 2075-4426. ; 11:12
  • 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.
  •  
10.
  • Gretarsdottir, Helga Maria, et al. (författare)
  • Personalized Medicine Approach in Treating Parkinson's Disease, Using Oral Administration of Levodopa/Carbidopa Microtablets in Clinical Practice
  • 2021
  • Ingår i: Journal of Personalized Medicine. - : MDPI. - 2075-4426. ; 11:8
  • 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.
  •  
11.
  • Hawranek, Carolina, et al. (författare)
  • A focus group study of perceptions of genetic risk disclosure in members of the public in sweden: "I’ll phone the five closest ones, but what happens to the other ten?"
  • 2021
  • Ingår i: Journal of Personalized Medicine. - : MDPI. - 2075-4426. ; 11:11
  • Tidskriftsartikel (refereegranskat)abstract
    • This study explores perceptions and preferences on receiving genetic risk informationabout hereditary cancer risk in members of the Swedish public. We conducted qualitative contentanalysis of five focus group discussions with participants (n = 18) aged between 24 and 71 years,recruited from various social contexts. Two prominent phenomena surfaced around the interplaybetween the three stakeholders involved in risk disclosure: the individual, healthcare, and therelative at risk. First, there is a genuine will to share risk information that can benefit others, evenif this is difficult and causes discomfort. Second, when the duty to inform becomes overwhelming,compromises are made, such as limiting one’s own responsibility of disclosure or projecting the mainresponsibility onto another party. In conclusion, our results reveal a discrepancy between publicexpectations and the actual services offered by clinical genetics. These expectations paired with desirefor a more personalized process and shared decision-making highlight a missing link in today’s riskcommunication and suggest a need for developed clinical routines with stronger healthcare–patientcollaboration. Future research needs to investigate the views of genetic professionals on how toaddress these expectations to co-create a transparent risk disclosure process which can realize the fullpotential of personalized prevention.
  •  
12.
  • Heier, C. R., et al. (författare)
  • Multi-Omics Identifies Circulating miRNA and Protein Biomarkers for Facioscapulohumeral Dystrophy
  • 2020
  • Ingår i: Journal of Personalized Medicine. - : MDPI AG. - 2075-4426. ; 10:4
  • Tidskriftsartikel (refereegranskat)abstract
    • The development of therapeutics for muscle diseases such as facioscapulohumeral dystrophy (FSHD) is impeded by a lack of objective, minimally invasive biomarkers. Here we identify circulating miRNAs and proteins that are dysregulated in early-onset FSHD patients to develop blood-based molecular biomarkers. Plasma samples from clinically characterized individuals with early-onset FSHD provide a discovery group and are compared to healthy control volunteers. Low-density quantitative polymerase chain reaction (PCR)-based arrays identify 19 candidate miRNAs, while mass spectrometry proteomic analysis identifies 13 candidate proteins. Bioinformatic analysis of chromatin immunoprecipitation (ChIP)-seq data shows that the FSHD-dysregulated DUX4 transcription factor binds to regulatory regions of several candidate miRNAs. This panel of miRNAs also shows ChIP signatures consistent with regulation by additional transcription factors which are up-regulated in FSHD (FOS, EGR1, MYC, and YY1). Validation studies in a separate group of patients with FSHD show consistent up-regulation of miR-100, miR-103, miR-146b, miR-29b, miR-34a, miR-454, miR-505, and miR-576. An increase in the expression of S100A8 protein, an inflammatory regulatory factor and subunit of calprotectin, is validated by Enzyme-Linked Immunosorbent Assay (ELISA). Bioinformatic analyses of proteomics and miRNA data further support a model of calprotectin and toll-like receptor 4 (TLR4) pathway dysregulation in FSHD. Moving forward, this panel of miRNAs, along with S100A8 and calprotectin, merit further investigation as monitoring and pharmacodynamic biomarkers for FSHD.
  •  
13.
  • Hernandez-Pacheco, N, et al. (författare)
  • Identification of ROBO2 as a Potential Locus Associated with Inhaled Corticosteroid Response in Childhood Asthma
  • 2021
  • Ingår i: Journal of personalized medicine. - : MDPI AG. - 2075-4426. ; 11:8
  • Tidskriftsartikel (refereegranskat)abstract
    • Inhaled corticosteroids (ICS) are the most common asthma controller medication. An important contribution of genetic factors in ICS response has been evidenced. Here, we aimed to identify novel genetic markers involved in ICS response in asthma. A genome-wide association study (GWAS) of the change in lung function after 6 weeks of ICS treatment was performed in 166 asthma patients from the SLOVENIA study. Patients with an improvement in lung function ≥8% were considered as ICS responders. Suggestively associated variants (p-value ≤ 5 × 10−6) were evaluated in an independent study (n = 175). Validation of the association with asthma exacerbations despite ICS use was attempted in European (n = 2681) and admixed (n = 1347) populations. Variants previously associated with ICS response were also assessed for replication. As a result, the SNP rs1166980 from the ROBO2 gene was suggestively associated with the change in lung function (OR for G allele: 7.01, 95% CI: 3.29–14.93, p = 4.61 × 10−7), although this was not validated in CAMP. ROBO2 showed gene-level evidence of replication with asthma exacerbations despite ICS use in Europeans (minimum p-value = 1.44 × 10−5), but not in admixed individuals. The association of PDE10A-T with ICS response described by a previous study was validated. This study suggests that ROBO2 could be a potential novel locus for ICS response in Europeans.
  •  
14.
  • Kilinçalp, G., et al. (författare)
  • Predictive Value of Ambulatory Objective Movement Measurement for Outcomes of Levodopa/Carbidopa Intestinal Gel Infusion
  • 2022
  • Ingår i: Journal of Personalized Medicine. - : MDPI AG. - 2075-4426. ; 12:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Patients with Parkinson’s disease that may benefit from device-assisted therapy can be identified with guidelines like Navigate PD. The decision to offer advanced treatment and the choice of treatment modality are, however, not straightforward, and some patients respond less favorably to a chosen therapy. Measurements with the Parkinson Kinetigraph (PKG) can detect motor fluctuations and could therefore predict patients that respond better or worse to intestinal levodopa/carbidopa gel infusion (LCIG). In a retrospective analysis of 45 patients that had been selected to start LCIG between 2014 and 2020, the effects of baseline PKG and clinical characteristic on the outcome were determined with ordinal regression. Although all patients had been found to have handicapping medication-related symptom fluctuations, patients without clear objective off fluctuations in the baseline PKG had low odds ratio for success. Lower odds for success were also found with increasing age, whereas gender, medication intensity and baseline PKG summary scores (median bradykinesia and dyskinesia scores, fluctuation dyskinesia score and percent time with tremor) had no significant effect. Absence of easily identified off-periods in the PKG has a negative prognostic value for the effect of LCIG and could prompt noninvasive infusion evaluation before surgery. © 2022 by the authors. Licensee MDPI, Basel, Switzerland.
  •  
15.
  • Lazzarino, G., et al. (författare)
  • ILB(R) Attenuates Clinical Symptoms and Serum Biomarkers of Oxidative/Nitrosative Stress and Mitochondrial Dysfunction in Patients with Amyotrophic Lateral Sclerosis
  • 2021
  • Ingår i: Journal of Personalized Medicine. - : MDPI AG. - 2075-4426. ; 11:8
  • Tidskriftsartikel (refereegranskat)abstract
    • Oxidative/nitrosative stress and mitochondrial dysfunction is a hallmark of amyotrophic lateral sclerosis (ALS), an invariably fatal progressive neurodegenerative disease. Here, as an exploratory arm of a phase II clinical trial (EudraCT Number 2017-005065-47), we used high performance liquid chromatography(HPLC) to investigate changes in the metabolic profiles of serum from ALS patients treated weekly for 4 weeks with a repeated sub-cutaneous dose of 1 mg/kg of a proprietary low molecular weight dextran sulphate, called ILB(R). A significant normalization of the serum levels of several key metabolites was observed over the treatment period, including N-acetylaspartate (NAA), oxypurines, biomarkers of oxidative/nitrosative stress and antioxidants. An improved serum metabolic profile was accompanied by significant amelioration of the patients' clinical conditions, indicating a response to ILB(R) treatment that appears to be mediated by improvement of tissue bioenergetics, decrease of oxidative/nitrosative stress and attenuation of (neuro)inflammatory processes.
  •  
16.
  • Leta, Valentina, et al. (författare)
  • Personalised advanced therapies in parkinson’s disease : The role of non-motor symptoms profile
  • 2021
  • Ingår i: Journal of Personalized Medicine. - : MDPI AG. - 2075-4426. ; 11:8
  • Tidskriftsartikel (refereegranskat)abstract
    • Device-aided therapies, including levodopa-carbidopa intestinal gel infusion, apomorphine subcutaneous infusion, and deep brain stimulation, are available in many countries for the management of the advanced stage of Parkinson’s disease (PD). Currently, selection of device-aided therapies is mainly focused on patients’ motor profile while non-motor symptoms play a role limited to being regarded as possible exclusion criteria in the decision-making process for the delivery and sustenance of a successful treatment. Differential beneficial effects on specific non-motor symptoms of the currently available device-aided therapies for PD are emerging and these could hold relevant clinical implications. In this viewpoint, we suggest that specific non-motor symptoms could be used as an additional anchor to motor symptoms and not merely as exclusion criteria to deliver bespoke and patient-specific personalised therapy for advanced PD.
  •  
17.
  • Li, XQ, et al. (författare)
  • Evaluation of 1β-Hydroxylation of Deoxycholic Acid as a Non-Invasive Urinary Biomarker of CYP3A Activity in the Assessment of Inhibition-Based Drug-Drug Interaction in Healthy Volunteers
  • 2021
  • Ingår i: Journal of personalized medicine. - : MDPI AG. - 2075-4426. ; 11:6
  • Tidskriftsartikel (refereegranskat)abstract
    • In this study, we aimed to evaluate the utility of endogenous 1β-hydroxy-deoxycholic acid/total deoxycholic acid ratio (1β-OH-DCA/ToDCA) in spot urine as a surrogate marker of cytochrome P450 3A (CYP3A) activity in the assessment inhibition-based drug–drug interactions in healthy volunteers. This was accomplished through an open-label, three-treatment parallel-arm study in healthy male volunteers from Zimbabwe. Each group received itraconazole (ITZ; 100 mg once daily; n = 10), fluconazole (FKZ; 50 mg once daily; n = 9), or alprazolam (APZ; 1 mg once daily; n = 8) orally. Midazolam (MDZ), dosed orally and intravenously, was used as a comparator to validate the exploratory measures of CYP3A activity and the effects of known inhibitors. Urinary metabolic ratios of 1β-OH-DCA/ToDCA before and after CYP3A inhibitor treatment showed a similar magnitude of inhibitory effects of the three treatments as that measured by oral MDZ clearance. The maximum inhibition effect of a 75% reduction in the 1β-OH-DCA/ToDCA ratio compared to the baseline was achieved in the ITZ group following six once-daily doses of 100 mg. The correlations of the two markers for CYP3A inhibitor treatment were significant (rs = 0.53, p < 0.01). The half-life of urinary endogenous 1β-OH-DCA/ToDCA was estimated as four days. These results suggested that 1β-OH-DCA/ToDCA in spot urine is a promising convenient, non-invasive, sensitive, and relatively quickly responsive endogenous biomarker that can be used for CYP3A inhibition-based drug–drug interaction in clinical studies.
  •  
18.
  • Lin, Yi-Ting, et al. (författare)
  • Differences in the Microbial Composition of Hemodialysis Patients Treated with and without β-Blockers
  • 2021
  • Ingår i: Journal of Personalized Medicine. - : MDPI. - 2075-4426. ; 11:3
  • Tidskriftsartikel (refereegranskat)abstract
    • β-blockers are commonly prescribed to treat cardiovascular disease in hemodialysis patients. Beyond the pharmacological effects, β-blockers have potential impacts on gut microbiota, but no study has investigated the effect in hemodialysis patients. Hence, we aim to investigate the gut microbiota composition difference between β-blocker users and nonusers in hemodialysis patients. Fecal samples collected from hemodialysis patients (83 β-blocker users and 110 nonusers) were determined by 16S ribosomal RNA amplification sequencing. Propensity score (PS) matching was performed to control confounders. The microbial composition differences were analyzed by the linear discriminant analysis effect size, random forest, and zero-inflated Gaussian fit model. The α-diversity (Simpson index) was greater in β-blocker users with a distinct β-diversity (Bray–Curtis Index) compared to nonusers in both full and PS-matched cohorts. There was a significant enrichment in the genus Flavonifractor in β-blocker users compared to nonusers in full and PS-matched cohorts. A similar finding was demonstrated in random forest analysis. In conclusion, hemodialysis patients using β-blockers had a different gut microbiota composition compared to nonusers. In particular, the Flavonifractor genus was increased with β-blocker treatment. Our findings highlight the impact of β-blockers on the gut microbiota in hemodialysis patients.
  •  
19.
  • Lopez-Soley, E, et al. (författare)
  • Dynamics and Predictors of Cognitive Impairment along the Disease Course in Multiple Sclerosis
  • 2021
  • Ingår i: Journal of personalized medicine. - : MDPI AG. - 2075-4426. ; 11:11
  • Tidskriftsartikel (refereegranskat)abstract
    • (1) Background: The evolution and predictors of cognitive impairment (CI) in multiple sclerosis (MS) are poorly understood. We aimed to define the temporal dynamics of cognition throughout the disease course and identify clinical and neuroimaging measures that predict CI. (2) Methods: This paper features a longitudinal study with 212 patients who underwent several cognitive examinations at different time points. Dynamics of cognition were assessed using mixed-effects linear spline models. Machine learning techniques were used to identify which baseline demographic, clinical, and neuroimaging measures best predicted CI. (3) Results: In the first 5 years of MS, we detected an increase in the z-scores of global cognition, verbal memory, and information processing speed, which was followed by a decline in global cognition and memory (p < 0.05) between years 5 and 15. From 15 to 30 years of disease onset, cognitive decline continued, affecting global cognition and verbal memory. The baseline measures that best predicted CI were education, disease severity, lesion burden, and hippocampus and anterior cingulate cortex volume. (4) Conclusions: In MS, cognition deteriorates 5 years after disease onset, declining steadily over the next 25 years and more markedly affecting verbal memory. Education, disease severity, lesion burden, and volume of limbic structures predict future CI and may be helpful when identifying at-risk patients.
  •  
20.
  • Luque-Moreno, Carlos, et al. (författare)
  • Virtual reality and physiotherapy in post-stroke functional re-education of the lower extremity : A controlled clinical trial on a new approach
  • 2021
  • Ingår i: Journal of Personalized Medicine. - : MDPI. - 2075-4426. ; 11:11
  • Tidskriftsartikel (refereegranskat)abstract
    • Numerous Virtual Reality (VR) systems address post-stroke functional recovery of the lower extremity (LE), most of them with low early applicability due to the gait autonomy they require. The aim of the present study was to evaluate the feasibility of a specific VR treatment and its clinical effect on LE functionality, gait, balance, and trunk control post-stroke. A controlled, prospective, clinical trial was carried out with 20 stroke patients, who were divided into two groups: the first group (VR + CP; n = 10) received combined therapy of 1 h VR and 1 h of conventional physiotherapy (CP) and the second group (CP; n = 10) received 2 h of CP (5 days/week, for 3 weeks). The following pre-post-intervention measuring scales were used: Functional Ambulatory Scale (FAC), Functional Independence Measure (FIM), Fugl-Meyer Assessment (FM), Berg Balance Scale (BBS), and Trunk Control Test (TCT). Only VR + CP showed a significant improvement in FAC. In FIM, CP presented a tendency to significance, whereas VR + CP showed significance. Both groups improved significantly in FM (especially in amplitude/pain in VR + CP and in sensitivity in CP) and in BBS. In TCT, there was a non-significant improvement in both groups. The results indicate that the intervention with VR is a feasible treatment in the post-stroke functional re-education of the LE, with the potential to be an optimal complement of CP. © 2021 by the authors. Licensee MDPI, Basel, Switzerland.
  •  
21.
  • Nyholm, Dag, et al. (författare)
  • Optimizing Treatment of Parkinson's Disease
  • 2022
  • Ingår i: Journal of Personalized Medicine. - : MDPI. - 2075-4426. ; 12:2
  • Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
    • The holy grail of therapy in Parkinson’s disease (PD) is treatment that would halt the disease process or restore the degenerated neuronal circuits [...]
  •  
22.
  • Paque, PN, et al. (författare)
  • Salivary Biomarkers for Dental Caries Detection and Personalized Monitoring
  • 2021
  • Ingår i: Journal of personalized medicine. - : MDPI AG. - 2075-4426. ; 11:3
  • Tidskriftsartikel (refereegranskat)abstract
    • This study investigated the potential of salivary bacterial and protein markers for evaluating the disease status in healthy individuals or patients with gingivitis or caries. Saliva samples from caries- and gingivitis-free individuals (n = 18), patients with gingivitis (n = 17), or patients with deep caries lesions (n = 38) were collected and analyzed for 44 candidate biomarkers (cytokines, chemokines, growth factors, matrix metalloproteinases, a metallopeptidase inhibitor, proteolytic enzymes, and selected oral bacteria). The resulting data were subjected to principal component analysis and used as a training set for random forest (RF) modeling. This computational analysis revealed four biomarkers (IL-4, IL-13, IL-2-RA, and eotaxin/CCL11) to be of high importance for the correct depiction of caries in 37 of 38 patients. The RF model was then used to classify 10 subjects (five caries-/gingivitis-free and five with caries), who were followed over a period of six months. The results were compared to the clinical assessments of dental specialists, revealing a high correlation between the RF prediction and the clinical classification. Due to the superior sensitivity of the RF model, there was a divergence in the prediction of two caries and four caries-/gingivitis-free subjects. These findings suggest IL-4, IL-13, IL-2-RA, and eotaxin/CCL11 as potential salivary biomarkers for identifying noninvasive caries. Furthermore, we suggest a potential association between JAK/STAT signaling and dental caries onset and progression.
  •  
23.
  • Queckboerner, Suzanna, et al. (författare)
  • Stromal Heterogeneity in the Human Proliferative Endometrium-A Single-Cell RNA Sequencing Study
  • 2021
  • Ingår i: Journal of Personalized Medicine. - : MDPI. - 2075-4426. ; 11:6
  • Tidskriftsartikel (refereegranskat)abstract
    • The endometrium undergoes regular regeneration and stromal proliferation as part of the normal menstrual cycle. To better understand cellular interactions driving the mechanisms in endometrial regeneration we employed single-cell RNA sequencing. Endometrial biopsies were obtained during the proliferative phase of the menstrual cycle from healthy fertile women and processed to single-cell suspensions which were submitted for sequencing. In addition to known endometrial cell types, bioinformatic analysis revealed multiple stromal populations suggestive of specific stromal niches with the ability to control inflammation and extracellular matrix composition. Ten different stromal cells and two pericyte subsets were identified. Applying different R packages (Seurat, SingleR, Velocyto) we established cell cluster diversity and cell lineage/trajectory, while using external data to validate our findings. By understanding healthy regeneration in the described stromal compartments, we aim to identify points of further investigation and possible targets for novel therapy development for benign gynecological disorders affecting endometrial regeneration and proliferation such as endometriosis and Asherman's syndrome.
  •  
24.
  • Shcherbina, Anna, et al. (författare)
  • Accuracy in Wrist-Worn, Sensor-Based Measurements of Heart Rate and Energy Expenditure in a Diverse Cohort.
  • 2017
  • Ingår i: Journal of Personalized Medicine. - : MDPI AG. - 2075-4426. ; 7:2
  • Tidskriftsartikel (refereegranskat)abstract
    • The ability to measure physical activity through wrist-worn devices provides an opportunity for cardiovascular medicine. However, the accuracy of commercial devices is largely unknown. The aim of this work is to assess the accuracy of seven commercially available wrist-worn devices in estimating heart rate (HR) and energy expenditure (EE) and to propose a wearable sensor evaluation framework. We evaluated the Apple Watch, Basis Peak, Fitbit Surge, Microsoft Band, Mio Alpha 2, PulseOn, and Samsung Gear S2. Participants wore devices while being simultaneously assessed with continuous telemetry and indirect calorimetry while sitting, walking, running, and cycling. Sixty volunteers (29 male, 31 female, age 38 ± 11 years) of diverse age, height, weight, skin tone, and fitness level were selected. Error in HR and EE was computed for each subject/device/activity combination. Devices reported the lowest error for cycling and the highest for walking. Device error was higher for males, greater body mass index, darker skin tone, and walking. Six of the devices achieved a median error for HR below 5% during cycling. No device achieved an error in EE below 20 percent. The Apple Watch achieved the lowest overall error in both HR and EE, while the Samsung Gear S2 reported the highest. In conclusion, most wrist-worn devices adequately measure HR in laboratory-based activities, but poorly estimate EE, suggesting caution in the use of EE measurements as part of health improvement programs. We propose reference standards for the validation of consumer health devices (http://precision.stanford.edu/).
  •  
25.
  • Sjögren, Magnus, et al. (författare)
  • Inpatient weight restoration treatment is associated with decrease in post-meal anxiety
  • 2021
  • Ingår i: Journal of Personalized Medicine. - : MDPI. - 2075-4426. ; 11:11
  • Tidskriftsartikel (refereegranskat)abstract
    • Objective: Anorexia nervosa (AN) is characterized by weight loss, distorted body image with fear of becoming fat and associated with anxiety, especially in relation to food intake. Anxiety in relation to meals and weight restoration remains a major challenge in the treatment of AN. We examined the effects of inpatient weight restoration treatment on levels of post-meal anxiety using visual analogue scale (VAS) ratings in patients with AN.Materials: Thirty-two patients with AN, all part of the PROspective Longitudinal all-comer inclusion study on Eating Disorders (PROLED) were followed over eight weeks with baseline psychometric measures and weekly VAS anxiety self-scoring.Methods: Apart from the weekly body mass index (BMI) and VAS, patients were characterized at baseline using the Eating Disorder Examination Questionnaire (EDE-Q), Eating Disorder Inventory (EDI), Symptom Check List 92 (SCL-92), Major Depression Inventory (MDI), and Autism Quotient (AQ).Results: The results showed a significant time effect, Wilks Lambda = 0.523, F = 3.12, p < 0.05 (power of 0.862), indicating a reduction in VAS scores of anxiety from baseline to week 8. There was no effect of baseline medication or scores of MDI on the results. BMI increased from a mean of 15.16 (week 1) to 17.35 (week 8). In comparison, patients dropping out after only three weeks (n = 31) also had a trend toward a reduction in VAS anxiety (ns).Conclusions: Inpatient weight restoration treatment is associated with a decrease in post-meal anxiety in AN, an effect that occurs early and becomes clinically significant in patients who stay in treatment.
  •  
26.
  • Sundgren, M, et al. (författare)
  • Does Information from the Parkinson KinetiGraph™ (PKG) Influence the Neurologist's Treatment Decisions?-An Observational Study in Routine Clinical Care of People with Parkinson's Disease
  • 2021
  • Ingår i: Journal of personalized medicine. - : MDPI AG. - 2075-4426. ; 11:6
  • Tidskriftsartikel (refereegranskat)abstract
    • Management of Parkinson’s disease traditionally relies solely on clinical assessment. The PKG objectively measures affected persons’ movements in daily life. The present study evaluated how often PKG data changed treatment decisions in routine clinical care and to what extent the clinical assessment and the PKG interpretation differed. PKG recordings were performed before routine visits. The neurologist first made a clinical assessment without reviewing the PKG. Signs and symptoms were recorded, and a treatment plan was documented. Afterward, the PKG was evaluated. Then, the neurologist decided whether to change the initial treatment plan or not. PKG review resulted in a change in the initial treatment plan in 21 of 66 participants (31.8%). The clinical assessment and the PKG review differed frequently, mainly regarding individual overall presence of motor problems (67%), profile of bradykinesia/wearing off (79%), dyskinesia (35%) and sleep (55%). PKG improved the dialogue with the participant in 88% of cases. PKG and clinical variables were stable when they were repeated after 3–6 months. In conclusion, PKG information changes treatment decisions in nearly a third of people with Parkinson’s disease in routine care. Standard clinical assessment and PKG evaluation are often non-identical. Objective measurements in people living with Parkinson’s disease can add therapeutically relevant information.
  •  
27.
  • Vernmark, Karolina, et al. (författare)
  • Mucinous and Non-Mucinous Rectal Adenocarcinoma - Differences in Treatment Response to Preoperative Radiotherapy
  • 2020
  • Ingår i: Journal of Personalized Medicine. - : MDPI. - 2075-4426. ; 10:4
  • Tidskriftsartikel (refereegranskat)abstract
    • There is a need to personalize the treatment for rectal cancer patients. The aim of this study was to analyze therapy response and prognosis after preoperative radiotherapy in rectal cancer patients with mucinous adenocarcinoma compared to those with non-mucinous adenocarcinoma. The study included retrospectively collected data from 433 patients, diagnosed with rectal cancer in the South East health care region in Sweden between 2004 and 2012. Patients with non-mucinous adenocarcinoma that received short-course radiotherapy before surgery had better overall survival, cancer specific survival, and disease-free survival, as well as distant- and local-recurrence-free survival (p = 0.003, p = 0.001, p = 0.002, p = 0.002, and p = 0.033, respectively) compared to the patients that received long-course radiotherapy with concomitant capecitabine. The results were still significant after adjusting for sex, age, stage, differentiation, and chemotherapy in the neoadjuvant and/or adjuvant setting, except for local-recurrence-free survival that was trending towards significance (p = 0.070). In patients with mucinous adenocarcinoma, no difference in survival was seen when comparing patients that had short-course radiotherapy and patients that had long-course radiotherapy. However, none of 18 patients with mucinous adenocarcinoma treated with long-course radiotherapy had local tumor progression, compared to 7% of 67 patients with non-mucinous adenocarcinoma. The results indicate that mucinous adenocarcinoma and non-mucinous adenocarcinoma may respond differently to radiotherapy.
  •  
28.
  • Vinnikov, Volodymyr, et al. (författare)
  • Prediction of the Acute or Late Radiation Toxicity Effects in Radiotherapy Patients Using Ex Vivo Induced Biodosimetric Markers : A Review
  • 2020
  • Ingår i: Journal of Personalized Medicine. - : MDPI AG. - 2075-4426. ; 10:4
  • Forskningsöversikt (refereegranskat)abstract
    • A search for effective methods for the assessment of patients' individual response to radiation is one of the important tasks of clinical radiobiology. This review summarizes available data on the use of ex vivo cytogenetic markers, typically used for biodosimetry, for the prediction of individual clinical radiosensitivity (normal tissue toxicity, NTT) in cells of cancer patients undergoing therapeutic irradiation. In approximately 50% of the relevant reports, selected for the analysis in peer-reviewed international journals, the average ex vivo induced yield of these biodosimetric markers was higher in patients with severe reactions than in patients with a lower grade of NTT. Also, a significant correlation was sometimes found between the biodosimetric marker yield and the severity of acute or late NTT reactions at an individual level, but this observation was not unequivocally proven. A similar controversy of published results was found regarding the attempts to apply G(2)- and gamma H2AX foci assays for NTT prediction. A correlation between ex vivo cytogenetic biomarker yields and NTT occurred most frequently when chromosome aberrations (not micronuclei) were measured in lymphocytes (not fibroblasts) irradiated to relatively high doses (4-6 Gy, not 2 Gy) in patients with various grades of late (not early) radiotherapy (RT) morbidity. The limitations of existing approaches are discussed, and recommendations on the improvement of the ex vivo cytogenetic testing for NTT prediction are provided. However, the efficiency of these methods still needs to be validated in properly organized clinical trials involving large and verified patient cohorts.
  •  
29.
  • Wen, Yugang, et al. (författare)
  • Predictive Role of Biopsy Based Biomarkers for Radiotherapy Treatment in Rectal Cancer
  • 2020
  • Ingår i: Journal of Personalized Medicine. - : MDPI. - 2075-4426. ; 10:4
  • Tidskriftsartikel (refereegranskat)abstract
    • Background and Purpose: Radiation therapy has long been contemplated as an important mode in the treatment of rectal cancer. However, there are few ideal tools available for clinicians to make a radiotherapy decision at the time of diagnosis for rectal cancer. The purpose of this study was to assess whether biomarkers expressed in the biopsy could help to choose the suitable therapy and provide predictive and/or prognostic information. Experimental Design: In total, 30 biomarkers were analyzed in 219 biopsy samples before treatment to discover the possibility of using them as an indicator for radiotherapy selection, diagnosis, survival and recurrence. Results: Twenty-two biomarkers (COX2-RT, COX2-NonRT, etc.; 36.67%) had diagnostic value. For survival, four biomarkers (NFKBP65, p130, PINCH and PPAR) were significant in regulating gene promoter activity and overall survival, while four had a trend (AEG1, LOX, SATB1 and SIRT6). Three biomarkers (COX2, PINCH and WRAP53) correlated with disease-free survival, while eight had a trend (AEG1, COX2, Ki67, LOX, NFKBP65, PPAR and SATB1). Four biomarkers (COX2-RT, NFKBP65cyto-RT, P130cyto-NonRT and PPARcyto-RT) were independent prognostic factors for recurrence. NFKBP65 and SIRT6 were significantly correlated with lymph node metastasis regardless of radiation. Patients with high AEG1, LOX, NFKBP65, PPAR and SATB1 had or showed a positive trend for better survival after radiotherapy, while those with positive PINCH and WRAP53 expression would not benefit from radiotherapy. Conclusions: AEG1, LOX, NFKBP65cyto, PPAR and SATB1 could be used as indicators for choosing radiotherapy. COX2-RT, COX2-NonRT and some other biomarkers may provide additional help for diagnosis.
  •  
30.
  • Wu, YK, et al. (författare)
  • Associations of Stress and Appetite Hormones with Binge Eating in Females with Anorexia Nervosa after Weight Restoration: A Longitudinal Study
  • 2021
  • Ingår i: Journal of personalized medicine. - : MDPI AG. - 2075-4426. ; 11:10
  • Tidskriftsartikel (refereegranskat)abstract
    • Binge eating is a transdiagnostic eating disorder symptom that can occur in patients with anorexia nervosa (AN), persisting after weight restoration, and impeding their recovery. However, little is known about the biological predictors of binge eating after AN weight restoration. The goals of this exploratory study of 73 females with AN were: (1) to examine changes in cortisol, the adrenocorticotropic hormone, norepinephrine, ghrelin (total and active), and leptin levels across the admission, discharge, and 3 months post-discharge from the inpatient AN weight restoration; and (2) to determine whether the target hormones were associated with objective or subjective binge eating (OBE or SBE). The participants completed the self-reported Eating Disorder Examination Questionnaire, Beck Anxiety Inventory, and Beck Depression Inventory-II, and provided fasting whole blood samples for hormone assays. The results showed significant changes in body mass index (BMI), cortisol, total ghrelin, and leptin levels over the three time points. The cortisol levels at admission and discharge were significantly associated with the number of SBE episodes at 3 months post-discharge. Findings suggest the need to replicate and confirm the role of cortisol in predicting the emergence of SBE and uncover the mechanisms underlying SBE and cortisol to prevent SBE and its negative consequences.
  •  
31.
  • Öthman, Mezin, et al. (författare)
  • Initial Experience of the Levodopa–Entacapone–Carbidopa Intestinal Gel in Clinical Practice
  • 2021
  • Ingår i: Journal of Personalized Medicine. - : MDPI. - 2075-4426. ; 11:4
  • Tidskriftsartikel (refereegranskat)abstract
    • Patients in fluctuating stages of Parkinson’s disease (PD) require device-aided treatments. Continuous infusion of levodopa–carbidopa intestinal gel (LCIG) is a well-proven option in clinical practice. We now report the first clinical experience of levodopa–entacapone–carbidopa intestinal gel (LECIG) therapy. An observational study of the first patients to start LECIG in our clinic was performed. Twenty-four patients (11 females, 13 males) were included. The median age was 71.5 years, and the median duration since PD diagnosis was 15.5 years. The median treatment duration was 305 days. Median doses were: 6.0 mL as morning dose, 2.5 mL/h as infusion rate, and 1.0 mL as extra dose. Half of the patients were switched directly from LCIG. These patients express improvements in the size and weight of the pump. Furthermore, most of them considered the new pump to be improved regarding user-friendliness. Six patients discontinued LECIG, three due to diarrhea, one due to hallucinations and two deceased (one cardiac arrest and one COVID-19). LECIG has shown to be possible to use in patients with PD, efficacy and safety as expected. Patients are generally happy with the size and usability of the pump, but some technical improvements of the software are warranted, as well as larger, prospective studies.
  •  
32.
  • Augustinsson, Annelie, et al. (författare)
  • Red-Haired People's Altered Responsiveness to Pain, Analgesics, and Hypnotics : Myth or Fact? A Narrative Review
  • 2024
  • Ingår i: Journal of Personalized Medicine. - : MDPI. - 2075-4426. ; 14:6
  • Forskningsöversikt (refereegranskat)abstract
    • Red hair has been linked to altered sensitivity to pain, analgesics, and hypnotics. This alteration may be impacted by variants in the melanocortin-1 receptor (MC1R) gene, which are mainly found in redheads. The aim of this narrative review was to explore and present the current state of knowledge on red hair and its plausible associations with altered responsiveness to pain, analgesics, and hypnotics. Structured searches in the PubMed, CINAHL Complete, and Scopus electronic databases were conducted. Evidence suggests that women with red hair have an increased sensitivity to pain. Conversely, data also indicate a higher pain tolerance in homozygous carriers of MC1R variant alleles. Varied responses to analgesia have been reported, with both increased analgesic responsiveness in homozygous carriers of MC1R variant alleles and less analgesia in redheads. Data indicate an increased need for hypnotics in redheads. However, failed attempts to find statistical associations between red hair and altered responsiveness to hypnotics are also evident. Even though there seems to be an association between red hair and an altered responsiveness to pain, analgesics, and/or hypnotics, the results of this narrative review are inconclusive. Further research studies with larger populations and MC1R testing are needed.
  •  
33.
  •  
34.
  • Barakat, Ruben, et al. (författare)
  • Influence of Physical Activity during Pregnancy on Maternal Hypertensive Disorders: A Systematic Review and Meta-Analysis of Randomized Controlled Trials
  • 2024
  • Ingår i: JOURNAL OF PERSONALIZED MEDICINE. - 2075-4426. ; 14:1
  • Forskningsöversikt (refereegranskat)abstract
    • Gestational hypertension is a notable concern with ramifications for maternal and fetal health. Preemptive measures, including physical activity (PA), are crucial. There is a pressing need for comprehensive investigations into the impact of various forms of PA on hypertensive disorders. A systematic review and meta-analysis (CRD42022372468) following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines was performed. Our review exclusively considered randomized clinical trials (RCTs) between 2010 and 2023, using the following databases: EBSCO, including Academic Search Premier, Education Resources Information Center, PubMed/MEDLINE, SPORTDiscus, and OpenDissertations; Clinicaltrials.gov; Web of Science; Scopus; the Cochrane Database of Systematic Reviews; and the Physiotherapy Evidence Database (PEDro). The primary outcome was hypertensive disorders occurring during pregnancy (14 studies). Diagnosed preeclampsia (15 studies) and blood pressure levels were also examined (17 studies). PA during pregnancy was significantly associated with a reduced risk of hypertensive disorders (RR = 0.44, 95% CI = 0.30, 0.66). The data also indicate a positive correlation between PA during pregnancy and both systolic (MD = -2.64, 95% CI = -4.79, -0.49) and diastolic (MD = -1.99, 95% CI = -3.68, -0.29) blood pressure levels. The relationship between PA and the incidence of diagnosed preeclampsia did not demonstrate a statistically significant association (RR = 0.81, 95% CI = 0.59, 1.11; p = 0.20). Random effects were used for all analyses. PA during pregnancy promises to improve maternal health by reducing the risk of gestational hypertension and positively affecting systolic and diastolic blood pressure.
  •  
35.
  • Barizzone, N, et al. (författare)
  • A Scoping Review on Body Fluid Biomarkers for Prognosis and Disease Activity in Patients with Multiple Sclerosis
  • 2022
  • Ingår i: Journal of personalized medicine. - : MDPI AG. - 2075-4426. ; 12:9
  • Tidskriftsartikel (refereegranskat)abstract
    • Multiple sclerosis (MS) is a complex demyelinating disease of the central nervous system, presenting with different clinical forms, including clinically isolated syndrome (CIS), which is a first clinical episode suggestive of demyelination. Several molecules have been proposed as prognostic biomarkers in MS. We aimed to perform a scoping review of the potential use of prognostic biomarkers in MS clinical practice. We searched MEDLINE up to 25 November 2021 for review articles assessing body fluid biomarkers for prognostic purposes, including any type of biomarkers, cell types and tissues. Original articles were obtained to confirm and detail the data reported by the review authors. We evaluated the reliability of the biomarkers based on the sample size used by various studies. Fifty-two review articles were included. We identified 110 molecules proposed as prognostic biomarkers. Only six studies had an adequate sample size to explore the risk of conversion from CIS to MS. These confirm the role of oligoclonal bands, immunoglobulin free light chain and chitinase CHI3L1 in CSF and of serum vitamin D in the prediction of conversion from CIS to clinically definite MS. Other prognostic markers are not yet explored in adequately powered samples. Serum and CSF levels of neurofilaments represent a promising biomarker.
  •  
36.
  • Cao, Yang, Associate Professor, 1972-, et al. (författare)
  • Development and Validation of an XGBoost-Algorithm-Powered Survival Model for Predicting In-Hospital Mortality Based on 545,388 Isolated Severe Traumatic Brain Injury Patients from the TQIP Database
  • 2023
  • Ingår i: Journal of Personalized Medicine. - : MDPI. - 2075-4426. ; 13:9
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: Traumatic brain injury (TBI) represents a significant global health issue; the traditional tools such as the Glasgow Coma Scale (GCS) and Abbreviated Injury Scale (AIS) which have been used for injury severity grading, struggle to capture outcomes after TBI.AIM AND METHODS: This paper aims to implement extreme gradient boosting (XGBoost), a powerful machine learning algorithm that combines the predictions of multiple weak models to create a strong predictive model with high accuracy and efficiency, in order to develop and validate a predictive model for in-hospital mortality in patients with isolated severe traumatic brain injury and to identify the most influential predictors. In total, 545,388 patients from the 2013-2021 American College of Surgeons Trauma Quality Improvement Program (TQIP) database were included in the current study, with 80% of the patients used for model training and 20% of the patients for the final model test. The primary outcome of the study was in-hospital mortality. Predictors were patients' demographics, admission status, as well as comorbidities, and clinical characteristics. Penalized Cox regression models were used to investigate the associations between the survival outcomes and the predictors and select the best predictors. An extreme gradient boosting (XGBoost)-powered Cox regression model was then used to predict the survival outcome. The performance of the models was evaluated using the Harrell's concordance index (C-index). The time-dependent area under the receiver operating characteristic curve (AUC) was used to evaluate the dynamic cumulative performance of the models. The importance of the predictors in the final prediction model was evaluated using the Shapley additive explanations (SHAP) value.RESULTS: On average, the final XGBoost-powered Cox regression model performed at an acceptable level for patients with a length of stay up to 250 days (mean time-dependent AUC = 0.713) in the test dataset. However, for patients with a length of stay between 20 and 213 days, the performance of the model was relatively poor (time-dependent AUC < 0.7). When limited to patients with a length of stay ≤20 days, which accounts for 95.4% of all the patients, the model achieved an excellent performance (mean time-dependent AUC = 0.813). When further limited to patients with a length of stay ≤5 days, which accounts for two-thirds of all the patients, the model achieved an outstanding performance (mean time-dependent AUC = 0.917).CONCLUSION: The XGBoost-powered Cox regression model can achieve an outstanding predictive ability for in-hospital mortality during the first 5 days, primarily based on the severity of the injury, the GCS on admission, and the patient's age. These variables continue to demonstrate an excellent predictive ability up to 20 days after admission, a period of care that accounts for over 95% of severe TBI patients. Past 20 days of care, other factors appear to be the primary drivers of in-hospital mortality, indicating a potential window of opportunity for improving outcomes.
  •  
37.
  • Castela Forte, José, et al. (författare)
  • Development and Validation of Decision Rules Models to Stratify Coronary Artery Disease, Diabetes, and Hypertension Risk in Preventive Care : Cohort Study of Returning UK Biobank Participants
  • 2021
  • Ingår i: Journal of Personalized Medicine. - : MDPI AG. - 2075-4426. ; 11:12
  • Tidskriftsartikel (refereegranskat)abstract
    • Many predictive models exist that predict risk of common cardiometabolic conditions. However, a vast majority of these models do not include genetic risk scores and do not distinguish between clinical risk requiring medical or pharmacological interventions and pre-clinical risk, where lifestyle interventions could be first-choice therapy. In this study, we developed, validated, and compared the performance of three decision rule algorithms including biomarkers, physical measurements, and genetic risk scores for incident coronary artery disease (CAD), diabetes (T2D), and hypertension against commonly used clinical risk scores in 60,782 UK Biobank participants. The rules models were tested for an association with incident CAD, T2D, and hypertension, and hazard ratios (with 95% confidence interval) were calculated from survival models. Model performance was assessed using the area under the receiver operating characteristic curve (AUROC), and Net Reclassification Index (NRI). The higher risk group in the decision rules model had a 40-, 40.9-, and 21.6-fold increased risk of CAD, T2D, and hypertension, respectively (p < 0.001 for all). Risk increased significantly between the three strata for all three conditions (p < 0.05). Based on genetic risk alone, we identified not only a high-risk group, but also a group at elevated risk for all health conditions. These decision rule models comprising blood biomarkers, physical measurements, and polygenic risk scores moderately improve commonly used clinical risk scores at identifying individuals likely to benefit from lifestyle intervention for three of the most common lifestyle-related chronic health conditions. Their utility as part of digital data or digital therapeutics platforms to support the implementation of lifestyle interventions in preventive and primary care should be further validated.
  •  
38.
  • Del Cura-González, Isabel, et al. (författare)
  • How to Improve Healthcare for Patients with Multimorbidity and Polypharmacy in Primary Care : A Pragmatic Cluster-Randomized Clinical Trial of the MULTIPAP Intervention
  • 2022
  • Ingår i: Journal of Personalized Medicine. - : MDPI AG. - 2075-4426. ; 12:5
  • Tidskriftsartikel (refereegranskat)abstract
    • (1) Purpose: To investigate a complex MULTIPAP intervention that implements the Ariadne principles in a primary care population of young-elderly patients with multimorbidity and polypharmacy and to evaluate its effectiveness for improving the appropriateness of prescriptions. (2) Methods: A pragmatic cluster-randomized clinical trial was conducted involving 38 family practices in Spain. Patients aged 65-74 years with multimorbidity and polypharmacy were recruited. Family physicians (FPs) were randomly allocated to continue usual care or to provide the MULTIPAP intervention based on the Ariadne principles with two components: FP training (eMULTIPAP) and FP patient interviews. The primary outcome was the appropriateness of prescribing, measured as the between-group difference in the mean Medication Appropriateness Index (MAI) score change from the baseline to the 6-month follow-up. The secondary outcomes were quality of life (EQ-5D-5L), patient perceptions of shared decision making (collaboRATE), use of health services, treatment adherence, and incidence of drug adverse events (all at 1 year), using multi-level regression models, with FP as a random effect. (3) Results: We recruited 117 FPs and 593 of their patients. In the intention-to-treat analysis, the between-group difference for the mean MAI score change after a 6-month follow-up was -2.42 (95% CI from -4.27 to -0.59) and, between baseline and a 12-month follow-up was -3.40 (95% CI from -5.45 to -1.34). There were no significant differences in any other secondary outcomes. (4) Conclusions: The MULTIPAP intervention improved medication appropriateness sustainably over the follow-up time. The small magnitude of the effect, however, advises caution in the interpretation of the results given the paucity of evidence for the clinical benefit of the observed change in the MAI.
  •  
39.
  • Eriksson, Victoria, et al. (författare)
  • A retrospective analysis of the de ritis ratio in muscle invasive bladder cancer, with focus on tumor response and long-term survival in patients receiving neoadjuvant chemotherapy and in chemo naïve cystectomy patients : a study of a clinical multicentre database
  • 2022
  • Ingår i: Journal of Personalized Medicine. - : MDPI. - 2075-4426. ; 12:11
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: A high pre-treatment De Ritis ratio, the aspartate transaminase/alanine aminotransferase ratio, has been suggested to be of prognostic value for mortality in muscle-invasive bladder cancer (MIBC). Our purpose was to evaluate if a high ratio was associated with mortality and downstaging. Methods: A total of 347 Swedish patients with clinically staged T2-T4aN0M0, with administered neoadjuvant chemotherapy (NAC) or eligible for NAC and undergoing radical cystectomy (RC) 2009–2021, were retrospectively evaluated with a low ratio < 1.3 vs. high ratio > 1.3, by Log Rank test, Cox regression and Mann–Whitney U-test (MWU), SPSS 27. Results: Patients with a high ratio had a decrease of up to 3 years in disease-free survival (DFS), cancer-specific survival (CSS) and overall survival (OS) (p = 0.009, p = 0.004 and p = 0.009) and 5 years in CSS and OS (p = 0.019 and p = 0.046). A high ratio was associated with increased risk of mortality, highest in DFS (HR, 1.909; 95% CI, 1.265–2.880; p = 0.002). No significant relationship between downstaging and a high ratio existed (p = 0.564 MWU). Conclusion: A high pre-treatment De Ritis ratio is on a population level, associated with increased mortality post-RC in endpoints DFS, CSS and OS. Associations decrease over time and require further investigations to determine how strong the associations are as meaningful prognostic markers for long-term mortality in MIBC. The ratio is not suitable for downstaging-prediction.
  •  
40.
  • Fetahi, Egzona, et al. (författare)
  • Estimating the Effect of Motivational Interventions in Patients with Eating Disorders : A Systematic Review and Meta-Analysis
  • 2022
  • Ingår i: Journal of Personalized Medicine. - : MDPI. - 2075-4426. ; 12:4
  • Forskningsöversikt (refereegranskat)abstract
    • Motivation to change behavior is seen as an important factor in achieving a better treatment effect in patients with eating disorders (ED). The aim of this systematic review was to assess whether motivational interviewing (MI) and motivational enhancement therapy (MET) might (1) increase motivation to change behavior and (2) improve eating disorder psychopathology (EDP) and body mass index (BMI) in patients with ED. To investigate this, a literature search was conducted on 9 March 2021 on four scientific databases: Cochrane, Embase (Ovid), MEDLINE (PubMed), and PsycInfo (EBSCO). A total of 2647 publications were identified and following a rigorous stepwise procedure to assess titles and abstracts and, thereafter, full texts of relevant publications, 13 studies were included in the data extraction and analyses. A few individual studies (n = 5) found a significant increase in motivation, two a decrease in ED symptoms (n = 2), while none found an effect on BMI. However, the meta-analysis of each outcome found effect sizes near zero, thereby confirming the results of previous narrative reviews that have described a lack of effect of MET/MI on motivation in ED. Since the individual studies differ substantially in design, and the outcomes were inconsistently assessed with regards to instruments and duration, the effect of MET/MI on motivation for behavioral change, ED psychopathology, and BMI is still unclear.
  •  
41.
  • Forssten, Maximilian Peter, 1996-, et al. (författare)
  • Comparative Analysis of Frailty Scores for Predicting Adverse Outcomes in Hip Fracture Patients : Insights from the United States National Inpatient Sample
  • 2024
  • Ingår i: Journal of Personalized Medicine. - : MDPI. - 2075-4426. ; 14:6
  • Tidskriftsartikel (refereegranskat)abstract
    • The aim of the current investigation was to compare the ability of several frailty scores to predict adverse outcomes in hip fracture patients. All adult patients (18 years or older) who suffered a hip fracture due to a fall and underwent surgical fixation were extracted from the 2019 National Inpatient Sample (NIS) Database. A combination of logistic regression and bootstrapping was used to compare the predictive ability of the Orthopedic Frailty Score (OFS), the Nottingham Hip Fracture Score (NHFS), the 11-factor modified Frailty Index (11-mFI) and 5-factor (5-mFI) modified Frailty Index, as well as the Johns Hopkins Frailty Indicator. A total of 227,850 patients were extracted from the NIS. In the prediction of in-hospital mortality and failure-to-rescue (FTR), the OFS surpassed all other frailty measures, approaching an acceptable predictive ability for mortality [AUC (95% CI): 0.69 (0.67-0.72)] and achieving an acceptable predictive ability for FTR [AUC (95% CI): 0.70 (0.67-0.72)]. The NHFS demonstrated the highest predictive ability for predicting any complication [AUC (95% CI): 0.62 (0.62-0.63)]. The 11-mFI exhibited the highest predictive ability for cardiovascular complications [AUC (95% CI): 0.66 (0.64-0.67)] and the NHFS achieved the highest predictive ability for delirium [AUC (95% CI): 0.69 (0.68-0.70)]. No score succeeded in effectively predicting venous thromboembolism or infections. In summary, the investigated frailty scores were most effective in predicting in-hospital mortality and failure-to-rescue; however, they struggled to predict complications.
  •  
42.
  • Forster-Ruhrmann, U, et al. (författare)
  • Chemokine Expression-Based Endotype Clustering of Chronic Rhinosinusitis
  • 2022
  • Ingår i: Journal of personalized medicine. - : MDPI AG. - 2075-4426. ; 12:4
  • Tidskriftsartikel (refereegranskat)abstract
    • Chronic rhinosinusitis (CRS) with (CRSwNP) or without nasal polyps (CRSsNP) is a persistent, heterogeneous inflammatory condition affecting the upper respiratory tract. The present study aimed to improve the characterization of CRS endotypes based on the chemokine and cytokine expression pattern in the CRS tissues. Concentrations of chemokines and cytokines were measured in tissues from nasal biopsies obtained from 66 CRS patients and 25 control subjects using multiplexing or single analyte technologies. Cluster analysis based on the concentration of type-1 (MCP-3/CCL7, MIP-1 α/CCL3), type-2 (IL-5, MCP-3/CCL7, MIP-1 α/CCL3, TARC/CCL17, PARC/CCL18, IP-10/CXCL10, ECP), and type-3 (IL-22) chemokines and cytokines identified six CRS endotypes (clusters). Cluster 1 (type-3) and 2 (type-1) were associated with a low prevalence of nasal polyps, Cluster 3 (type-1, -2, -3) and Cluster 4 (type-2, -3, medium IL-22) with medium, and Cluster 5 (type-2, -3, high Il-22) and Cluster 6 (type-2) with high prevalence of nasal polyps. Asthma was highly prevalent in Cluster-6. Our findings add to the existing knowledge of CRS endotypes and may be useful for the clinical decision-making process. The advancement of biologics therapy for upper respiratory tract disorders rationalizes the personalized diagnostic approach to warrant a successful treatment and monitoring of CRS.
  •  
43.
  • Frostad, Stein, et al. (författare)
  • BMI at Discharge from Treatment Predicts Relapse in Anorexia Nervosa : A Systematic Scoping Review
  • 2022
  • Ingår i: Journal of Personalized Medicine. - : MDPI AG. - 2075-4426. ; 12:5
  • Forskningsöversikt (refereegranskat)abstract
    • Background: Anorexia nervosa (AN) has high rates of enduring disease and mortality. Currently, there is insufficient knowledge on the predictors of relapse after weight normalization and this is why a systematic literature review was performed. Methods: PubMed, EMBASE, PsychInfo, and Cochrane databases were searched for literature published until 13 July 2021. All study designs were eligible for inclusion if they focused on predictors of relapse after weight normalization in AN. Individual study definitions of relapse were used, and in general, this was either a drop in BMI and/or reccurrence of AN symptoms. Results: The database search identified 11,507 publications, leaving 9511 publications after the removal of duplicates and after a review of abstracts and titles; 191 were selected for full-text review. Nineteen publications met the criteria and included 1398 AN patients and 39 healthy controls (HC) from adults and adolescents (ages range 11–73 years). The majority used a prospective observational study design (12 studies), a few used a retrospective observational design (6 studies), and only one was a non-randomized control trial (NRCT). Sample sizes ranged from 16 to 191 participants. BMI or measures of body fat and leptin levels at discharge were the strongest predictors of relapse with an approximate relapse rate of 50% at 12 months. Other predictors included signs of eating disorder psychopathology at discharge. Conclusions: BMI at the end of treatment is a predictor of relapse in AN, which is why treatment should target a BMI well above 20. Together with the time to relapse, these outcomes are important to include in the evaluation of current and novel treatments in AN and for benchmarking.
  •  
44.
  • Grandieri, Andrea, et al. (författare)
  • Relationship between People's Interest in Medication Adherence, Health Literacy, and Self-Care : An Infodemiological Analysis in the Pre- and Post-COVID-19 Era
  • 2023
  • Ingår i: Journal of Personalized Medicine. - 2075-4426. ; 13:7
  • Tidskriftsartikel (refereegranskat)abstract
    • The prevalence of non-communicable diseases has risen sharply in recent years, particularly among older individuals who require complex drug regimens. Patients are increasingly required to manage their health through medication adherence and self-care, but about 50% of patients struggle to adhere to prescribed treatments. This study explored the relationship between interest in medication adherence, health literacy, and self-care and how it changed during the COVID-19 pandemic. We used Google Trends to measure relative search volumes (RSVs) for these three topics from 2012 to 2022. We found that interest in self-care increased the most over time, followed by health literacy and medication adherence. Direct correlations emerged between RSVs for medication adherence and health literacy (r = 0.674, p < 0.0001), medication adherence and self-care (r = 0.466, p < 0.0001), and health literacy and self-care (r = 0.545, p < 0.0001). After the COVID-19 pandemic outbreak, interest in self-care significantly increased, and Latin countries showed a greater interest in self-care than other geographical areas. This study suggests that people are increasingly interested in managing their health, especially in the context of the recent pandemic, and that infodemiology may provide interesting information about the attitudes of the population toward chronic disease management.
  •  
45.
  • Hemmingsen, Simone Daugaard, et al. (författare)
  • Cognitive flexibility in hospitalized patients with severe or extreme Anorexia nervosa : a case-control study
  • 2023
  • Ingår i: Journal of Personalized Medicine. - : MDPI. - 2075-4426. ; 13:6
  • Tidskriftsartikel (refereegranskat)abstract
    • Objective: To investigate whether cognitive inflexibility could be identified using the Wisconsin Card Sorting Test (WCST) in patients with severe and extreme anorexia nervosa (AN) compared to healthy control participants (HCs). Method: We used the WCST to assess 34 patients with AN (mean age: 25.9 years, mean body mass index (BMI): 13.2 kg/m2) 3–7 days after admission to a specialized nutrition unit and 34 HCs. The Beck Depression Inventory II and the Eating Disorder Inventory 3 were distributed.Results: The patients displayed more perseveration than HCs controlled for age and years of education, with moderate effect sizes (perseverative responses (%): adjusted difference = −7.74, 95% CI: −14.29–(−1.20), p-value: 0.021; perseverative errors (%): adjusted difference = −6.01, 95% CI: −11.06–(−0.96), p-value: 0.020). There were no significant relationships between perseveration and depression, eating disorder symptoms, illness duration, or BMI.Discussion: Patients with severe and extreme AN demonstrated lower cognitive flexibility compared to HCs. Performance was not related to psychopathology or BMI. Patients with severe and extreme anorexia nervosa may not differ from less severe patients in cognitive flexibility performance. As this study exclusively focused on patients suffering from severe and extreme AN, potential correlations might be masked by a floor effect.
  •  
46.
  • Ivanov, HY, et al. (författare)
  • CYP2C19 and CYP2D6 Genotypes and Metabolizer Status Distribution in a Bulgarian Psychiatric Cohort
  • 2022
  • Ingår i: Journal of personalized medicine. - : MDPI AG. - 2075-4426. ; 12:7
  • Tidskriftsartikel (refereegranskat)abstract
    • CYP2D6 and CYP2C19 are enzymes of essential significance for the pharmacokinetics of a multitude of commonly used antidepressants, antipsychotics, antiemetics, β-blockers, opioids, antiestrogen, antacids, etc. Polymorphisms in the respective genes are well established as resulting in functional differences, which in turn can impact safety and efficacy. Importantly, the prevalence of genetic CYP2D6 and CYP2C19 variability differs drastically between populations. Drawing on the limited information concerning genotype frequencies in Bulgaria, we here analyzed 742 Bulgarian psychiatric patients predominantly diagnosed with depression and/or anxiety. Specifically, we analyzed frequencies of CYPC19*2, *4 and *17, as well as of CYP2D6*2, *3, *4, *5, *6, *10 and *41. In total, 571 out of 742 patients (77%) carried at least one variant which impacts metabolizer status. Overall, 48.6% of the studied individuals were classified as non-normal metabolizers of CYP2D6 with most exhibiting reduced function (38.2% intermediate metabolizers and 6.6% poor metabolizers). In contrast, for CYP2C19, the majority of non-normal metabolizers showed increased functionality (28.9% rapid and 5.5% ultrarapid metabolizers), while reduced activity metabolizer status accounted for 25.6% (23.8% intermediate and 1.8% poor metabolizers). These results provide an important resource to assess the genetically encoded functional variability of CYP2D6 and CYP2C19 which may have significant implications for precision medicine in Bulgarian psychiatry practice.
  •  
47.
  • Jandura, Jiri, et al. (författare)
  • Previous lumbar spine surgery decreases the therapeutic efficacy of dorsal root ganglion pulsed radiofrequency in patients with chronic lumbosacral radicular pain
  • 2023
  • Ingår i: Journal of Personalized Medicine. - : MDPI. - 2075-4426. ; 13:7
  • Tidskriftsartikel (refereegranskat)abstract
    • Chronic lumbosacral radicular pain (CLRP) as a possible adverse consequence of lumbar spine surgery represents a serious medical challenge. Pulsed radiofrequency of dorsal root ganglion (PRF-DRG) treatment is known to be effective in alleviating CLRP. This retrospective study compares the efficacy of a single CT-guided PRF-DRG procedure in the treatment of unilateral CLRP between patients without (non-PSS) and with (PSS) previous lumbar spine surgery. Non-PSS and PSS groups included 30 and 20 patients, respectively. Outcomes (pain intensity and disability) were evaluated by means of the visual analog scale (VAS) and Oswestry disability index (ODI) immediately after the procedure (VAS), as well as three and six months after the procedure, respectively. Non-PSS group showed a significant (p < 0.001) decrease of VAS (median) at all follow-up intervals (from 6 to 4; 4; 4.5 points, respectively). The PSS group showed a significant yet transient VAS (median) decrease (from 6 to 5 points) immediately after the procedure only (p < 0.001). The decrease of VAS was more pronounced in the non-PSS group after three and six months (p = 0.0054 and 0.011, respectively) in intergroup comparison. A relative decrease of VAS & GE; 50% during follow-up was achieved in 40%; 43.3%; 26.7% (non-PSS), and 25%; 5%; 0% (PSS) of patients. ODI (median) significantly decreased in the non-PSS group (from 21.5 to 18 points) at three and six months (p = 0.014 and 0.021, respectively). In conclusion, previous lumbar spine surgery decreases the therapeutic efficacy of PRF-DRG procedure in CLRP patients.
  •  
48.
  •  
49.
  • Medrzycka-Dabrowska, W, et al. (författare)
  • Delirium in ICU Patients after Cardiac Arrest: A Scoping Review
  • 2022
  • Ingår i: Journal of personalized medicine. - : MDPI AG. - 2075-4426. ; 12:7
  • Tidskriftsartikel (refereegranskat)abstract
    • Introduction: The incidence of delirium in the intensive care unit is high, although it may differ according to the specific characteristics of the unit. Despite the rapid development of research on delirium in recent years, the pathophysiological mechanisms leading to the clinical presentation of delirium are still subject to hypotheses. The aim of this review was to describe the incidence of delirium in cardiac arrest survivors and the clinical impact of delirium on patient outcomes. Methods: A scoping review was conducted in the second quarter of 2022. The number of articles retrieved during each search test was limited to studies conducted between 2010 and 2020. Strict inclusion and exclusion criteria were applied. The last search was conducted in May 2022. Results: A total of 537 records was initially obtained from the databases. After discarding duplicates, selecting titles and abstracts, and then analyzing full-text articles, 7 studies met the inclusion criteria. The incidence of delirium in the cardiac arrest survivor population ranged from 8% to as high as 100%. The length of stay in ICU and hospital was significantly longer in patients with delirium than those without. Ninety-eight percent of patients had cognitive or perceptual impairment and psychomotor impairment. Of the seven studies included in the analysis, the RASS, CAM, and NuDesc scales were used to diagnose delirium. Potential risk factors that may influence the duration of delirium include age and time since resuscitation; propofol use shortened the duration of delirium. Conclusion: the incidence of delirium in ICU patients who survived CA is high. Cardiac arrest is an additional predisposing factor for delirium. In cardiac arrest survivors, the occurrence of delirium prolongs the duration of ICU and hospital stay and adversely affects functional outcomes. The most common type of delirium among this population was hypoactive delirium. A large percentage of patients manifested symptoms such as cognitive or perception impairment, psychomotor impairment, and impaired concentration and attention.
  •  
50.
  • Ottestad, AL, et al. (författare)
  • Assessment of Two Commercial Comprehensive Gene Panels for Personalized Cancer Treatment
  • 2023
  • Ingår i: Journal of personalized medicine. - : MDPI AG. - 2075-4426. ; 13:1
  • Tidskriftsartikel (refereegranskat)abstract
    • (1) Background: Analysis of tumor DNA by next-generation sequencing (NGS) plays various roles in the classification and management of cancer. This study aimed to assess the performance of two similar and large, comprehensive gene panels with a focus on clinically relevant variant detection and tumor mutation burden (TMB) assessment; (2) Methods: DNA from 19 diagnostic small cell lung cancer biopsies and an AcroMetrix™ assessment sample with >500 mutations were sequenced using Oncomine™ Comprehensive Assay Plus (OCAP) on the Ion Torrent platform and TruSight Oncology 500 Assay (TSO500) on the Illumina platform; (3) Results: OCAP and TSO500 achieved comparable NGS quality, such as mean read coverage and mean coverage uniformity. A total of 100% of the variants in the diagnostic samples and 80% of the variants in the AcroMetrix™ assessment sample were detected by both panels, and the panels reported highly similar variant allele frequency. A proportion of 14/19 (74%) samples were classified in the same TMB category; (4) Conclusions: Comparable results were obtained using OCAP and TSO500, suggesting that both panels could be applied to screen patients for enrolment in personalized cancer treatment trials.
  •  
Skapa referenser, mejla, bekava och länka
  • Resultat 1-50 av 62
Typ av publikation
tidskriftsartikel (54)
forskningsöversikt (8)
Typ av innehåll
refereegranskat (61)
övrigt vetenskapligt/konstnärligt (1)
Författare/redaktör
Sherif, Amir (4)
Pino-Yanes, M (3)
Zhao, Y. (2)
Gorenjak, M (2)
Potocnik, U (2)
Kabesch, M (2)
visa fler...
Hassan, M (2)
Li, J. (1)
Huang, M. (1)
Svenningsson, P (1)
Vosough, M (1)
Vetrano, Davide L. (1)
Calderón-Larrañaga, ... (1)
Mukhopadhyay, S (1)
Alvarez-Mon, MA (1)
Donat-Vargas, C (1)
Ortega, MA (1)
Alvarez-Mon, M (1)
Bulik, CM (1)
Hultenby, K (1)
Warrén Stomberg, Mar ... (1)
Abdel-Aziz, MI (1)
Neerincx, AH (1)
Vijverberg, SJH (1)
Hashimoto, S (1)
Brinkman, P (1)
Toncheva, AA (1)
Harner, S (1)
Brandstetter, S (1)
Wolff, C (1)
Perez-Garcia, J (1)
Hedman, AM (1)
Almqvist, C (1)
Corcuera-Elosegui, P (1)
Korta-Murua, J (1)
Sardon-Prado, O (1)
Kraneveld, AD (1)
van der Zee, AMH (1)
Maitland-van Der Zee ... (1)
Gallitto, Enrico (1)
Gargiulo, Mauro (1)
Mani, Kevin, 1975- (1)
Wanhainen, Anders (1)
Sullivan, PF (1)
Kockum, I. (1)
Martinelli-Boneschi, ... (1)
Johansson, A (1)
Jahnson, Staffan (1)
Bachert, C (1)
Abedi-Valugerdi, M (1)
visa färre...
Lärosäte
Karolinska Institutet (30)
Umeå universitet (12)
Uppsala universitet (7)
Linköpings universitet (6)
Göteborgs universitet (5)
Örebro universitet (5)
visa fler...
Lunds universitet (5)
Stockholms universitet (4)
Gymnastik- och idrottshögskolan (1)
VTI - Statens väg- och transportforskningsinstitut (1)
visa färre...
Språk
Engelska (62)
Forskningsämne (UKÄ/SCB)
Medicin och hälsovetenskap (41)

År

Kungliga biblioteket hanterar dina personuppgifter i enlighet med EU:s dataskyddsförordning (2018), GDPR. Läs mer om hur det funkar här.
Så här hanterar KB dina uppgifter vid användning av denna tjänst.

 
pil uppåt Stäng

Kopiera och spara länken för att återkomma till aktuell vy