Introduction. Vagal nerve stimulation (VNS) is a therapeutical option for the treatment of drug-resistant epileptic patients. The response to VNS varies from patient to patient and is difficult to predict. The proposed study is based on our previous work, identifying relative mean power in pre-implantation EEG as a reliable marker for VNS efficacy prediction in adult patients. Our study has two main tasks. Firstly, to confirm the utility of relative mean power as a feature correlating with VNS efficacy in children. The second is to validate the applicability of our prediction classifier, Pre-X-Stim, in the pediatric population. Material and Methods. We identified a group of children with drug-resistant epilepsy. We included only children in whom EEG contained photic stimulation (Task 1) or was recorded based on the defined acquisition protocol used for development Pre-X-Stim (Task 2). Relative mean powers were calculated. VNS responders and non-responders were compared based on relative mean powers' values. In the next step, we evaluate the utility of our classifier, Pre-X-Stim, in the children population. Results: We identified 57 children treated with VNS - 17 patients were recruited for the Task 1 and 7 patients for the Task 2. When focusing on relative mean powers in EEG spectra, we observed statistically significant differences in theta range. The Pre-X-Stim algorithm was able to predict VNS efficacy correctly in 6 out of 7 patients (the accuracy 83.3%, the sensitivity 75%, the specificity 100%). Conclusions. Based on our results, it seems that children and adults share a similar pattern of EEG relative mean power changes. These changes can be used for pre-implantation prediction of VNS efficacy.
- MeSH
- Child MeSH
- Electroencephalography * methods MeSH
- Epilepsy * therapy physiopathology MeSH
- Humans MeSH
- Adolescent MeSH
- Child, Preschool MeSH
- Drug Resistant Epilepsy * therapy physiopathology MeSH
- Scalp MeSH
- Vagus Nerve Stimulation * methods MeSH
- Treatment Outcome MeSH
- Check Tag
- Child MeSH
- Humans MeSH
- Adolescent MeSH
- Male MeSH
- Child, Preschool MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
BACKGROUND: Various explicit screening tools, developed mostly in central Europe and the USA, assist clinicians in optimizing medication use for older adults. The Turkish Inappropriate Medication use in oldEr adults (TIME) criteria set, primarily based on the STOPP/START criteria set, is a current explicit tool originally developed for Eastern Europe and subsequently validated for broader use in Central European settings. Reviewed every three months to align with the latest scientific literature, it is one of the most up-to-date tools available. The tool is accessible via a free mobile app and website platforms, ensuring convenience for clinicians and timely integration of updates as needed. Healthcare providers often prefer to use their native language in medical practice, highlighting the need for prescribing tools to be translated and adapted into multiple languages to promote optimal medication practices. OBJECTIVE: To describe the protocol for cross-cultural and language validation of the TIME criteria in various commonly used languages and to outline its protocol for clinical validation across different healthcare settings. METHODS: The TIME International Study Group comprised 24 geriatric pharmacotherapy experts from 12 countries. In selecting the framework for the study, we reviewed the steps and outcomes from previous research on cross-cultural adaptations and clinical validations of explicit tools. Assessment tools were selected based on both their validity in accurately addressing the relevant issues and their feasibility for practical implementation. The drafted methodology paper was circulated among the study group members for feedback and revisions leading to a final consensus. RESULTS: The research methodology consists of two phases. Cross-cultural adaptation/language validation phase follows the 8-step approach recommended by World Health Organization. This phase allows regions or countries to make modifications to existing criteria or introduce new adjustments based on local prescribing practices and available medications, as long as these adjustments are supported by current scientific evidence. The second phase involves the clinical validation, where participants will be randomized into two groups. The control group will receive standard care, while the intervention group will have their treatment evaluated by clinicians who will review the TIME criteria and consider its recommendations. A variety of patient outcomes (i.e., number of hospital admissions, quality of life, number of regular medications [including over the counter medications], geriatric syndromes and mortality) in different healthcare settings will be investigated. CONCLUSION: The outputs of this methodological report are expected to promote broader adoption of the TIME criteria. Studies building on this work are anticipated to enhance the identification and management of inappropriate medication use and contribute to improved patient outcomes.
BACKGROUND: Patients with severe aortic stenosis present frequently (∼50%) with concomitant obstructive coronary artery disease. Current guidelines recommend combined surgical aortic valve replacement (SAVR) and coronary artery bypass grafting (CABG) as the preferred treatment. Transcatheter aortic valve implantation (TAVI) and fractional flow reserve (FFR)-guided percutaneous coronary intervention (PCI) represent a valid treatment alternative. We aimed to test the non-inferiority of FFR-guided PCI plus TAVI versus SAVR plus CABG in patients with severe aortic stenosis and complex coronary artery disease. METHODS: This international, multicentre, prospective, open-label, non-inferiority, randomised controlled trial was conducted at 18 tertiary medical centres across Europe. Patients (aged ≥70 years) with severe aortic stenosis and complex coronary artery disease, deemed feasible for percutaneous or surgical treatment according to the on-site Heart Team, were randomly assigned (1:1) to FFR-guided PCI plus TAVI or SAVR plus CABG according to a computer-generated sequence with random permuted blocks sizes stratified by site. The primary endpoint was a composite of all-cause mortality, myocardial infarction, disabling stroke, clinically driven target-vessel revascularisation, valve reintervention, and life-threatening or disabling bleeding at 1 year post-treatment. The trial was powered for non-inferiority (with a margin of 15%) and if met, for superiority. The primary and safety analyses were done per an intention-to-treat principle. This trial is registered with ClinicalTrials.gov (NCT03424941) and is closed. FINDINGS: Between May 31, 2018, and June 30, 2023, 172 patients were enrolled, of whom 91 were assigned to the FFR-guided PCI plus TAVI group and 81 to the SAVR plus CABG group. The mean age of patients was 76·5 years (SD 3·9). 118 (69%) of 172 patients were male and 54 (31%) patients were female. FFR-guided PCI plus TAVI resulted in favourable outcomes for the primary endpoint (four [4%] of 91 patients) versus SAVR plus CABG (17 [23%] of 77 patients; risk difference -18·5 [90% CI -27·8 to -9·7]), which was below the 15% prespecified non-inferiority margin (pnon-inferiority<0·001). FFR-guided PCI plus TAVI was superior to SAVR plus CABG (hazard ratio 0·17 [95% CI 0·06-0·51]; psuperiority<0·001), which was driven mainly by all-cause mortality (none [0%] of 91 patients vs seven (10%) of 77 patients; p=0·0025) and life-threatening bleeding (two [2%] vs nine [12%]; p=0·010). INTERPRETATION: The TCW trial is the first trial to compare percutaneous treatment versus surgical treatment in patients with severe aortic stenosis and complex coronary artery disease, showing favourable primary endpoint and mortality outcomes with percutaneous treatment. FUNDING: Isala Heart Centre and Medtronic.
- MeSH
- Aortic Valve Stenosis * surgery complications MeSH
- Heart Valve Prosthesis Implantation methods MeSH
- Fractional Flow Reserve, Myocardial * MeSH
- Percutaneous Coronary Intervention * methods MeSH
- Coronary Artery Bypass * methods MeSH
- Humans MeSH
- Coronary Artery Disease * surgery complications therapy MeSH
- Prospective Studies MeSH
- Aged, 80 and over MeSH
- Aged MeSH
- Transcatheter Aortic Valve Replacement * methods MeSH
- Treatment Outcome MeSH
- Check Tag
- Humans MeSH
- Male MeSH
- Aged, 80 and over MeSH
- Aged MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Equivalence Trial MeSH
- Multicenter Study MeSH
- Comparative Study MeSH
BACKGROUND: Spasticity is a common feature in patients with disruptions in corticospinal pathways. However, the term is used ambiguously. Here, spasticity is defined as enhanced velocity-dependent stretch reflexes and placed within the context of deforming spastic paresis encompassing other forms of muscle overactivity. OBJECTIVE: This scoping review aims at evaluating the clinimetric quality of clinical outcome assessments (COAs) for spasticity across different pathologies and to make recommendations for their use. METHODS: A literature search was conducted to identify COAs used to assess spasticity. An international expert panel evaluated the measurement properties in the included COAs. Recommendations were based on the MDS-COA program methodology based on three criteria: if the COA was (1) applied to patients with spastic paresis, (2) used by others beyond the developers, and (3) determined to be reliable, valid, and sensitive to change in patients with spasticity. RESULTS: We identified 72 COAs of which 17 clinician-reported outcomes (ClinROs) and 6 patient-reported outcomes (PROs) were reviewed. The Tardieu Scale was the only ClinRO recommended for assessing spasticity. One ClinRO-Composite Spasticity Index-and two PROs-Spasticity 0-10 Numeric Rating Scale and 88-Item Multiple Sclerosis Spasticity Scale-were recommended with caveats. The Ashworth-derived COAs were excluded after evaluation due to their focus on muscle tone rather than spasticity, as defined in this review. CONCLUSIONS: The Tardieu Scale is recommended for assessing spasticity, and two PROs are recommended with caveats. Consistent terminology about the various types of muscle overactivity is necessary to facilitate their assessment and treatment. © 2024 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.
- MeSH
- Outcome Assessment, Health Care * standards MeSH
- Humans MeSH
- Muscle Spasticity * physiopathology diagnosis etiology MeSH
- Check Tag
- Humans MeSH
- Publication type
- Journal Article MeSH
- Review MeSH
BACKGROUND: Cell cycle progression and leukemia development are tightly regulated processes in which even a small imbalance in the expression of cell cycle regulatory molecules and microRNAs (miRNAs) can lead to an increased risk of cancer/leukemia development. Here, we focus on the study of a ubiquitous, multifunctional, and oncogenic miRNA-hsa-miR-155-5p (miR-155, MIR155HG), which is overexpressed in malignancies including chronic lymphocytic leukemia (CLL). Nonetheless, the precise mechanism of how miR-155 regulates the cell cycle in leukemic cells remains the subject of extensive research. METHODS: We edited the CLL cell line MEC-1 by CRISPR/Cas9 to introduce a short deletion within the MIR155HG gene. To describe changes at the transcriptome and miRNome level in miR-155-deficient cells, we performed mRNA-seq/miRNA-seq and validated changes by qRT-PCR. Flow cytometry was used to measure cell cycle kinetics. A WST-1 assay, hemocytometer, and Annexin V/PI staining assessed cell viability and proliferation. RESULTS: The limited but phenotypically robust miR-155 modification impaired cell proliferation, cell cycle, and cell ploidy. This was accompanied by overexpression of the negative cell cycle regulator p21/CDKN1A and Cyclin D1 (CCND1). We confirmed the overexpression of canonical miR-155 targets such as PU.1, FOS, SHIP-1, TP53INP1 and revealed new potential targets (FCRL5, ISG15, and MX1). CONCLUSIONS: We demonstrate that miR-155 deficiency impairs cell proliferation, cell cycle, transcriptome, and miRNome via deregulation of the MIR155HG/TP53INP1/CDKN1A/CCND1 axis. Our CLL model is valuable for further studies to manipulate miRNA levels to revert highly aggressive leukemic cells to nearly benign or non-leukemic types.
- MeSH
- Leukemia, Lymphocytic, Chronic, B-Cell * genetics pathology MeSH
- Cyclin D1 genetics metabolism MeSH
- Cyclin-Dependent Kinase Inhibitor p21 * genetics metabolism MeSH
- Cell Cycle Checkpoints * genetics MeSH
- Humans MeSH
- MicroRNAs * genetics metabolism MeSH
- Cell Line, Tumor MeSH
- Cell Proliferation genetics MeSH
- Heat-Shock Proteins MeSH
- Gene Expression Regulation, Leukemic MeSH
- Carrier Proteins genetics metabolism MeSH
- Check Tag
- Humans MeSH
- Publication type
- Journal Article MeSH
OBJECTIVES: To prospectively validate the diagnostic performance of a non-invasive point-of-care tool (Rapid IAI System), including vaginal alpha-fetoprotein and interleukin-6, to predict the occurrence of intra-amniotic inflammation in a Spanish cohort of patients admitted with a diagnosis of preterm labor and intact membranes. METHODS: From 2017 to 2022, we prospectively evaluated a cohort of pregnant women diagnosed with preterm labor and intact membranes admitted below 34+0 weeks who underwent amniocentesis to rule-in/out intra-amniotic infection and/or inflammation. Vaginal sampling was performed at the time of amniocentesis or within 24-48 h. Amniotic fluid IL-6, vaginal alpha-fetoprotein and vaginal IL-6 concentrations were measured using a point-of-care tool provided by Hologic Inc., "Rapid IAI System". We defined intra-amniotic inflammation when amniotic fluid IL-6 values were greater than 11.3 ng/mL. During recruitment, clinicians were blinded to the results of the point-of-care tool. The original prediction model proposed by Hologic Inc. to predict intra-amniotic inflammation was validated in this cohort of patients. RESULTS: We included 151 patients diagnosed with preterm labor and intact membranes. Among these, 29 (19.2 %) had intra-amniotic inflammation. The algorithm including vaginal IL-6 and alpha-fetoprotein showed an area under curve to predict intra-amniotic inflammation of 80.3 % (±5.3 %) with a sensitivity of 72.4 %, specificity of 84.6 %, positive predictive valuve (PPV) of 52.5 %, negative predictive value (NPV) of 92.9 %, and a positive likelihood ratio (LR+) of 4.6 and negative likelihood ratio (LR-) of 0.33. CONCLUSIONS: External validation of a non-invasive rapid point-of-care tool, including vaginal alpha-fetoprotein and IL-6, showed very good diagnostic performance for predicting the absence of intra-amniotic inflammation in women with preterm labor and intact membranes.
- MeSH
- alpha-Fetoproteins * analysis metabolism MeSH
- Amniocentesis methods MeSH
- Chorioamnionitis * diagnosis MeSH
- Adult MeSH
- Risk Assessment methods MeSH
- Interleukin-6 * analysis blood metabolism MeSH
- Humans MeSH
- Amniotic Fluid * metabolism chemistry MeSH
- Point-of-Care Testing MeSH
- Obstetric Labor, Premature * diagnosis MeSH
- Predictive Value of Tests MeSH
- Prospective Studies MeSH
- Pregnancy MeSH
- Vagina metabolism MeSH
- Point-of-Care Systems MeSH
- Check Tag
- Adult MeSH
- Humans MeSH
- Pregnancy MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Validation Study MeSH
OBJECTIVE AND BACKGROUND: The 10-item Edinburgh Postnatal Depression Scale (EPDS) is a widely-used screening measure for postnatal depression. Factor analysis studies have suggested an embedded sub-scale could be used for screening for anxiety disorders. The current investigation sought to replicate and extend a recent study supporting this assertion. METHODS: A cross-sectional design. EPDS data were collected at up to two years postpartum. Confirmatory factor analysis, correlational and distributional characteristics of the measure were examined. Participants were a large sample (N = 985) of postpartum women in the Czech Republic. RESULTS: Factor structure findings substantially replicated the models evaluated by Della Vedova et al. (2022). Bifactor models, however, offered a better fit to data. A general factor of depression explained most of the variance in data in most models compared to embedded sub-scales across models. CONCLUSION: The model proposed by Della Vedova et al. (2022) offered an excellent fit to data. However, the findings from the bifactor modelling suggest the dominance of a general factor of depression which indicates the potential application of an embedded anxiety sub-scale for screening may be overstated.
- MeSH
- Adult MeSH
- Factor Analysis, Statistical MeSH
- Humans MeSH
- Young Adult MeSH
- Depression, Postpartum * diagnosis psychology MeSH
- Cross-Sectional Studies MeSH
- Psychiatric Status Rating Scales * standards MeSH
- Psychometrics MeSH
- Reproducibility of Results MeSH
- Check Tag
- Adult MeSH
- Humans MeSH
- Young Adult MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Geographicals
- Czech Republic MeSH
OBJECTIVES: Mindfulness-based interventions (MBIs) for persons with dementia (PwD) have yielded mixed results, possibly attributable to the fact that little is known about the validity and reliability of trait mindfulness self-report measures in PwD. This narrative review sought to identify studies involving self-reported trait mindfulness and other clinical measures that may hold information on the convergent validity and reliability of these measures in PwD. METHODS: Scientific databases were searched for studies involving PwD and mindfulness assessments. RESULTS: N = 426 studies from PubMed and N = 156 from PsychInfo databases were reviewed. Four cross-sectional studies were identified that allowed inferences about the validity of mindfulness measures. A qualitative review indicated that convergent validity with other measures varied with sample heterogeneity and cognitive impairment. Merely one MBI included self-reported trait mindfulness, however without reporting sample-specific validity or reliability. CONCLUSIONS: Despite efforts to implement MBIs in PwD, information on basic methodological psychometric issues is minimal. Future studies ought to address the validity and reliability of self-reported mindfulness in detail across different stages of dementia. CLINICAL IMPLICATIONS: Results of MBIs need to be considered cautiously. Basic information about psychometric properties of mindfulness self-report measures is required and these measures need to be included systematically in MBIs.
- MeSH
- Dementia * psychology therapy MeSH
- Humans MeSH
- Psychometrics methods MeSH
- Reproducibility of Results MeSH
- Aged MeSH
- Mindfulness * methods MeSH
- Self Report * standards MeSH
- Check Tag
- Humans MeSH
- Aged MeSH
- Publication type
- Journal Article MeSH
- Review MeSH
PURPOSE: While anal cancer is a very rare oncological diagnosis representing less than 2% of lower gastrointestinal tract cancers, the incidence has doubled in the past 20 years. Radical radiochemotherapy with sequential or simultaneous boost is now the standard treatment modality. Interstitial HDR brachytherapy is one of the boost application options. Implementation of new radiotherapy techniques has resulted in improved therapeutic outcomes; however, it is still associated with acute and especially late toxicity. Gastrointestinal disorders and sexual dysfunction are the most frequent factors affecting the long-term quality of cured patients' lives. METHODS: A total of 96 patients consecutively treated between 2000 and 2022 with external beam radio-/chemotherapy and an interstitial brachytherapy boost for histologically verified nonmetastatic anal squamous cell carcinoma were evaluated. The median follow-up time was 15.4 years (range 13.4-17.3 years). The primary objective of the study was to assess local control (LC) and quality of life (QoL). The Czech versions of internationally validated EORTC questionnaires were used to evaluate life quality-the basic EORTC QOL-C30 v.3 and the specific QOL-ANL 27 questionnaire. RESULTS: Local control was 85.5% at 5 years, 83.4% at 10 years, 83.4% at 15 years, and 83.4% at 20 years, and there was no dependence on clinical stage. The most common forms of acute toxicity were cutaneous and hematological but were gastrointestinal for late toxicities. In the evaluation of quality of life, 80.5% of patients alive at the time participated. In the EORTC quality of life questionnaire C30 v.3, patients rated the functional scale score as 86.2 points (standard deviation [SD] = 12.6) and the symptom score as 15.5 points (SD = 12.5). The global health score achieved 68.4 points (SD = 23.6). The most common symptoms were fatigue with 25.6 points (SD = 20.2) and diarrhea with 19.0 points (SD = 27.8). In the QOL-ANL 27 questionnaire, symptom scales assessing bowel symptoms were scored 27.5 points (SD = 19) in non-stoma patients and 11.9 points (SD = 17.2) in stoma patients. In the single-item symptom scales, the highest scores were rated for frequency of urination with 26.4 points (SD = 30.8), need to be close to a toilet with 22.4 points (SD = 27.3), and self-cleaning more often with 25.3 points (SD = 31.8). In the functional scales assessing sex life and interest, men and women reported scores of 45.2 (SD = 23) and 45.5 points (SD = 19), respectively. CONCLUSION: Boost with interstitial HDR brachytherapy is an established safe method of anal cancer treatment, with excellent results and limited late toxicity. Functioning scales were rated relatively highly in QoL questionnaires, and the overall global health score was comparable to published data. Gastrointestinal difficulties, fatigue, and sexual dysfunction dominated the symptom scales in our cohort.
- MeSH
- Brachytherapy * methods MeSH
- Radiotherapy Dosage MeSH
- Adult MeSH
- Quality of Life * psychology MeSH
- Middle Aged MeSH
- Humans MeSH
- Anus Neoplasms * radiotherapy psychology pathology MeSH
- Follow-Up Studies MeSH
- Surveys and Questionnaires MeSH
- Radiation Injuries * psychology etiology MeSH
- Aged, 80 and over MeSH
- Aged MeSH
- Carcinoma, Squamous Cell * radiotherapy pathology MeSH
- Treatment Outcome MeSH
- Check Tag
- Adult MeSH
- Middle Aged MeSH
- Humans MeSH
- Male MeSH
- Aged, 80 and over MeSH
- Aged MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
INTRODUCTION: The objective of this study was to assess the relationship between longitudinal changes in the uterine Doppler velocimetry and the maternal profile of angiogenic factors in the third trimester and to assess their ability to predict term preeclampsia (PE). METHODS: A cohort of low-risk pregnant women was scheduled for a uterine Doppler evaluation and measurement of the circulating levels of angiogenic factors at ∼30 and ∼36 weeks. The performance of both parameters and their change over time in predicting term PE was evaluated. RESULTS: A total of 1,191 women were analyzed, of which 28 (2.4%) women developed term PE. At ∼30 weeks, a model including the sFlt-1/PlGF (fms-like tyrosine kinase-1/placental growth factor) ratio and the uterine Doppler explained 16.2% of the uncertainty of developing term PE, while at ∼36 weeks, the same variables explained 25.2% [p < 0.001]. The longitudinal changes of both predictors had an R2 of 26.8%, which was not different from that of the ∼36 weeks evaluation [p = 0.45]. The area under the curve (AUC) of the ∼36 weeks ratio was significantly higher than at ∼30 weeks (0.86 [0.77-0.94] vs. 0.81 [0.73-0.9]; p = 0.043). The AUC of the longitudinal change of the ratio (0.85 [0.77-0.94]) did not differ from that of at ∼36 weeks (p = 0.82). At ∼36 weeks, for a 10% of false positives, the ratio had a detection rate of 71.4%. CONCLUSION: A cross-sectional measurement of the sFlt-1/PlGF ratio outperforms uterine Doppler in predicting term PE. The combination of both markers does not improve such prediction, nor the evaluation of the longitudinal changes between weeks.
- MeSH
- Adult MeSH
- Humans MeSH
- Placental Circulation physiology MeSH
- Placenta Growth Factor * blood MeSH
- Area Under Curve MeSH
- Predictive Value of Tests MeSH
- Pre-Eclampsia * blood diagnostic imaging MeSH
- Vascular Endothelial Growth Factor Receptor-1 * blood MeSH
- Rheology * methods statistics & numerical data MeSH
- Reproducibility of Results MeSH
- Blood Flow Velocity physiology MeSH
- Pregnancy MeSH
- Pregnancy Trimester, Third * blood physiology MeSH
- Ultrasonography, Doppler methods statistics & numerical data MeSH
- Ultrasonography, Prenatal * methods statistics & numerical data MeSH
- Check Tag
- Adult MeSH
- Humans MeSH
- Pregnancy MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Multicenter Study MeSH
- Randomized Controlled Trial MeSH
- Comparative Study MeSH
