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BACKGROUND: Information about dysarthria and dysphagia in mitochondrial diseases (MD) is scarce. However, this knowledge is needed to identify speech and swallowing problems early, to monitor the disease course, and to develop and offer optimal treatment and support. This study therefore aims to examine the prevalence and severity of dysarthria and dysphagia in patients with MD and its relation to clinical phenotype and disease severity. Secondary aim is to determine clinically relevant outcome measures for natural history studies and clinical trials. METHODS: This retrospective cross-sectional medical record study includes adults (age ≥ 18 years) diagnosed with genetically confirmed MD who participated in a multidisciplinary admission within the Radboud center for mitochondrial medicine between January 2015 and April 2023. Dysarthria and dysphagia were examined by administering the Radboud dysarthria assessment, swallowing speed, dysphagia limit, test of mastication and swallowing solids (TOMASS), and 6-min mastication test (6MMT). The disease severity was assessed using the Newcastle mitochondrial disease scale for adults (NMDAS). RESULTS: The study included 224 patients with MD with a median age of 42 years of whom 37.5% were male. The pooled prevalence of dysarthria was 33.8% and of dysphagia 35%. Patients with MD showed a negative deviation from the norm on swallowing speed, TOMASS (total time) and the 6MMT. Furthermore, a significant moderate relation was found between the presence of dysarthria and the clinical phenotypes. There was a statistically significant difference in total time on the TOMASS between the clinical phenotypes. Finally, disease severity showed a significant moderate relation with the severity of dysarthria and a significant weak relation with the severity of dysphagia. CONCLUSION: Dysarthria and dysphagia occur in about one-third of patients with MD. It is important for treating physicians to pay attention to this subject because of the influence of both disorders on social participation and wellbeing. Referral to a speech and language therapist should therefore be considered, especially in patients with a more severe clinical phenotype. The swallowing speed, TOMASS and 6MMT are the most clinically relevant tests to administer.
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Transtornos de Deglutição , Disartria , Doenças Mitocondriais , Humanos , Transtornos de Deglutição/etiologia , Transtornos de Deglutição/fisiopatologia , Disartria/etiologia , Disartria/fisiopatologia , Masculino , Feminino , Doenças Mitocondriais/complicações , Doenças Mitocondriais/fisiopatologia , Adulto , Pessoa de Meia-Idade , Estudos Retrospectivos , Estudos Transversais , Idoso , Índice de Gravidade de Doença , Prevalência , Deglutição , Adulto Jovem , FenótipoRESUMO
This paper introduces the concept of an operational reference glass database, specifically designed for broken glass fragments from ATM attacks, jewelry store robberies, and ramraids on high-end clothing stores. The database, initiated in 2014, is used to compare glass traces from organized crews involved said criminal activities. Utilizing LA-ICPMS, this study establishes a methodology for collecting reference glass samples from the scenes of the aforementioned crimes, thus creating a comprehensive database containing over 3500 reference glass samples from crime scenes. The operational database is employed to match trace elemental profiles of glass fragments from suspected items to known reference samples, offering specificity and accuracy. Analysis of results, while ongoing due to the nature of active cases, find matches of trace materials in over 50â¯% of case requests since 2019. Challenges such as database scalability and continuous updating are acknowledged, and future directions include technological advancements to enhance precision and the application into other areas of forensic material analysis. The paper emphasizes the efficacy of this specialized approach in chemical profiling, providing a potent tool for linking glass traces to specific criminal contexts and providing intelligence and investigative leads into individuals involved in ATM-related crimes.
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Bases de Dados Factuais , Explosões , Ciências Forenses , Vidro , Humanos , Ciências Forenses/métodos , Espectrometria de MassasAssuntos
Calcinose , Osteoartrite , Humanos , Calcinose/diagnóstico por imagem , Dedos , Cápsula ArticularRESUMO
Objective: To investigate whether multi-frequency Vestibular Evoked Myogenic Potential (VEMP) testing at 500, 750, 1,000, and 2,000 Hz, would improve the detection of present dynamic otolith responses in patients with bilateral vestibulopathy (BV). Methods: Prospective study in a tertiary referral center. BV patients underwent multi-frequency VEMP testing. Cervical VEMPs and ocular VEMPs were recorded with the Neuro-Audio system (v2010, Neurosoft, Ivanovo, Russia). The stimuli included air-conducted tone bursts of 500, 750, 1,000, and 2,000 Hz, at a stimulation rate of 13 Hz. Outcome measures included the percentage of present and absent VEMP responses, and VEMP thresholds. Outcomes were compared between frequencies and type of VEMPs (cVEMPs, oVEMPs). VEMP outcomes obtained with the 500 Hz stimulus, were also compared to normative values obtained in healthy subjects. Results: Forty-nine BV patients completed VEMP testing: 47 patients completed cVEMP testing and 48 patients completed oVEMP testing. Six to 15 % more present VEMP responses were obtained with multifrequency testing, compared to only testing at 500 Hz. The 2,000 Hz stimulus elicited significantly fewer present cVEMP responses (right and left ears) and oVEMP responses (right ears) compared to the other frequencies (p ≤ 0.044). Using multi-frequency testing, 78% of BV patients demonstrated at least one present VEMP response in at least one ear. In 46% a present VEMP response was found bilaterally. BV patients demonstrated a significantly higher percentage of absent VEMP responses and significantly higher VEMP thresholds than healthy subjects, when corrected for age (p ≤ 0.002). Based on these results, a pragmatic VEMP testing paradigm is proposed, taking into account multi-frequency VEMP testing. Conclusion: Multi-frequency VEMP testing improves the detection rate of present otolith responses in BV patients. Therefore, multi-frequency VEMPs should be considered when evaluation of (residual) otolith function is indicated.
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Adverse outcome pathways (AOPs) were introduced in modern toxicology to provide evidence-based representations of the events and processes involved in the progression of toxicological effects across varying levels of the biological organisation to better facilitate the safety assessment of chemicals. AOPs offer an opportunity to address knowledge gaps and help to identify novel therapeutic targets. They also aid in the selection and development of existing and new in vitro and in silico test methods for hazard identification and risk assessment of chemical compounds. However, many toxicological processes are too intricate to be captured in a single, linear AOP. As a result, AOP networks have been developed to aid in the comprehension and placement of associated events underlying the emergence of related forms of toxicity-where complex exposure scenarios and interactions may influence the ultimate adverse outcome. This study utilised established criteria to develop an AOP network that connects thirteen individual AOPs associated with nephrotoxicity (as sourced from the AOP-Wiki) to identify several key events (KEs) linked to various adverse outcomes, including kidney failure and chronic kidney disease. Analysis of the modelled AOP network and its topological features determined mitochondrial dysfunction, oxidative stress, and tubular necrosis to be the most connected and central KEs. These KEs can provide a logical foundation for guiding the selection and creation of in vitro assays and in silico tools to substitute for animal-based in vivo experiments in the prediction and assessment of chemical-induced nephrotoxicity in human health.
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Rotas de Resultados Adversos , Experimentação Animal , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos , Insuficiência Renal , Animais , Humanos , Medição de Risco/métodosRESUMO
INTRODUCTION: Myasthenia gravis (MG) is a rare neuromuscular disorder marked by a variable combination of weakness of eye, bulbar, respiratory, axial, and limb muscles. This study compared the experience of people with MG regarding breathing, fatigue, sleep, pain/discomfort, mental health, and usual activities with the general population. METHODS: The MyRealWorld-MG digital, multinational study enrolled patients with MG and collected demographics, PROMIS-Dyspnea, PROMIS-Sleep Disturbance, FACIT-Fatigue, EQ-5D-5L, Health Utilities Index (HUI-3), Hospital Anxiety and Depression Scale (HADS), MG-Activities of Daily Living (MG-ADL), and MG-Quality-of-Life (MG-QoL-15r). Comparisons with the general population were based on PROMIS population norms, published literature, or on data from a digital, multinational, observational study which enrolled a representative sample of the general population (POPUP). RESULTS: In MyRealWorld-MG (N = 2074), patients experienced higher intensity, frequency, and duration of PROMIS shortness of breath than a US population (p < 0.0001). Patients with MG had higher PROMIS-Sleep Disturbance scores than POPUP (53.7 vs 50.0, p < 0.0001), and 54.9% of patients had clinically severe FACIT-Fatigue scores vs 6.8% in POPUP (p < 0.0001). Among patients with MG, 69.6% and 18.5% had moderate-to-severe HADS-Anxiety and HADS-Depression compared to 20.3% and 6.9% in POPUP (p < 0.001). Statistically significant and strong associations were found between fatigue, sleep, dyspnea, usual activities, and emotions. All outcomes worsened with more severe disease. CONCLUSION: A considerable burden was observed in this comparison of breathing, sleep, fatigue, mental health, and usual activities between patients with MG and the general population, using data from two international studies and published population norms. Even mildly affected patients had significantly worse outcomes than the general population.
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Miastenia Gravis , Transtornos do Sono-Vigília , Humanos , Saúde Mental , Qualidade de Vida/psicologia , Atividades Cotidianas , Miastenia Gravis/complicações , Miastenia Gravis/diagnóstico , Miastenia Gravis/psicologia , Fadiga/epidemiologia , Fadiga/etiologia , Transtornos do Sono-Vigília/epidemiologia , Transtornos do Sono-Vigília/etiologia , Sono , DispneiaRESUMO
INTRODUCTION: Early-life stress (ES) increases the risk for Alzheimer's disease (AD). We and others have shown that ES aggravates amyloid-beta (Aß) pathology and promotes cognitive dysfunction in APP/PS1 mice, but underlying mechanisms remain unclear. METHODS: We studied how ES affects the hippocampal synaptic proteome in wild-type (WT) and APP/PS1 mice at early and late pathological stages, and validated hits using electron microscopy and immunofluorescence. RESULTS: The hippocampal synaptosomes of both ES-exposed WT and early-stage APP/PS1 mice showed a relative decrease in actin dynamics-related proteins and a relative increase in mitochondrial proteins. ES had minimal effects on older WT mice, while strongly affecting the synaptic proteome of advanced stage APP/PS1 mice, particularly the expression of astrocytic and mitochondrial proteins. DISCUSSION: Our data show that ES and amyloidosis share pathogenic pathways involving synaptic mitochondrial dysfunction and lipid metabolism, which may underlie the observed impact of ES on the trajectory of AD.
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Experiências Adversas da Infância , Doença de Alzheimer , Amiloidose , Camundongos , Animais , Metabolismo dos Lipídeos , Camundongos Transgênicos , Proteoma , Doença de Alzheimer/patologia , Peptídeos beta-Amiloides/metabolismo , Amiloidose/metabolismo , Mitocôndrias , Proteínas Mitocondriais , Modelos Animais de Doenças , Precursor de Proteína beta-Amiloide/genética , Precursor de Proteína beta-Amiloide/metabolismo , Presenilina-1/metabolismoRESUMO
BACKGROUND: Three-dimensional (3D) reconstruction in renal surgery offers significant benefits in planning of the operation itself, in patient education and training fellows. OBJECTIVE: The goal was to study the possible application and use of 3D reconstruction in modern renal surgery. METHODS: A literature search in PubMed using keywords "3D" and "renal surgery" within the last 10 years of publication was performed. RESULTS: The search revealed 655 articles among them 53 reviews. Relevant for this article were 120 articles which included 14 reviews. The publication statistics showed a strong increase in the last 10 years which may reflect the increasing application and demand for 3D technology in the field of renal surgery. Especially in robot-assisted minimally invasive surgery applications, the use of 3D technology was studied more often. The technical standards are not yet uniform and 3D printing in complex renal surgery remains cost- and time-intensive. Nevertheless, the results of the pioneering clinical studies showed positive results, and 3D technology can be used not only in planning the operation, but in patient education and also the training of fellows and staff. A limitation to more complex cases seems to be sensible for this is still a costly tool. To identify complex cases in renal surgery, the established renometric scoring systems should be used more broadly in daily practice to identify patients who would profit most from this technique. CONCLUSION: In complex renal surgery, 3D reconstruction and modelling is rational; furthermore, it can be useful in patient education and in training of fellows.
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Neoplasias Renais , Modelos Anatômicos , Humanos , Rim , Neoplasias Renais/cirurgia , Impressão TridimensionalRESUMO
INTRODUCTION: Myasthenia gravis (MG) is a neuromuscular disease causing extreme muscular fatigue, triggering problems with vision, swallowing, speech, mobility, dexterity, and breathing. This analysis intended to estimate the health-related quality-of-life impact, the medical burden, and the need for caregiver help of people diagnosed with MG. METHODS: MyRealWorld-MG (MRW) is an observational study among adults diagnosed with MG in 9 countries. The General Population Norms (POPUP) observational study enrolled representative members of the general population in 8 countries. In both digital studies, respondents entered personal characteristics and provided data on medical conditions, EQ-5D-5L, HUI3, MG-Activities of Daily Living (MG-ADL), sick leave, caregiver help, and medical care utilization. RESULTS: In MRW (n = 1859), 58.4% of respondents had moderate-to-severe MG. Average utility values were lower in MRW versus POPUP (0.739 vs. 0.843 for EQ-5D-5L; 0.493 vs. 0.746 for HUI3), and declined with more severe disease (0.872, 0.707, 0.511 EQ-5D-5L utilities and 0.695, 0.443, 0.168 HUI3 utilities for mild, moderate, and severe MG, respectively). Taking sick leave in the past month was 2.6 times more frequent among people diagnosed with MG compared to the general population (34.4% vs. 13.2%) and four times more people diagnosed with MG reported needing help from a caregiver (34.8% vs. 8.3%). Use of medical care was twice as likely in MRW in comparison with POPUP (51.9% vs. 24.6%). CONCLUSION: This direct comparison of people diagnosed with MG and the general population using two large international studies revealed significant negative impact of MG. Results were consistent across all outcomes, in all countries.
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Miastenia Gravis , Qualidade de Vida , Adulto , Humanos , Atividades Cotidianas , Cuidadores , Inquéritos e Questionários , Miastenia Gravis/diagnóstico , Miastenia Gravis/terapia , Nível de SaúdeRESUMO
INTRODUCTION/AIMS: Myasthenia gravis (MG) is a neuromuscular disease characterized by abnormal skeletal muscle fatiguability. The MG Activities of Daily Living (MG-ADL) scale assesses eight symptoms and is often used as primary endpoint in MG clinical trials where it is completed by neurologists. However, in observational studies, patients frequently complete the MG-ADL scale independently of their neurologist. In this study we aimed to assess the concordance between self- and physician-reported MG-ADL scores. METHODS: An international observational study was conducted among adult patients with MG scheduled for a routine visit or who entered the hospital via emergency services. Consenting patients and physicians completed the MG-ADL. Concordance between assessments was calculated using Gwet's agreement coefficient (Gwet's AC) for the MG-ADL individual items and the intraclass correlation coefficient (ICC) for the MG-ADL total score. RESULTS: Data were collected from 137 patients (63% female; mean age, 57.7 years). Physicians assessed the patient's symptoms as slightly more severe (8.1 vs 7.5 MG-ADL total score, respectively), corresponding to a difference of 0.6 on a range from 0 to 24. The ICC for the MG-ADL total score between the patient and the physician assessment was 0.94 (95% confidence interval, 0.89 to 0.95), showing excellent concordance. Gwet's AC showed substantial to almost perfect agreement for all items, except eyelid droop, for which the agreement was moderate. DISCUSSION: Our results demonstrate that patients and neurologists have a concordant assessment of the patient's MG symptoms when using the MG-ADL scale. This evidence supports patient self-administration of the MG-ADL in clinical practice and research.
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Blefaroptose , Miastenia Gravis , Médicos , Adulto , Humanos , Feminino , Pessoa de Meia-Idade , Masculino , Atividades Cotidianas , Miastenia Gravis/diagnóstico , Miastenia Gravis/tratamento farmacológico , NeurologistasRESUMO
OBJECTIVES: Myasthenia gravis (MG) is a rare, chronic, autoimmune neuromuscular disease which can affect functional and mental aspects of health and health-related quality of life (HRQoL). This study aims to obtain detailed knowledge of the impact of MG on HRQoL in a broad population from the perspective of the patient. DESIGN: Prospective, observational, digital, longitudinal real-world study. SETTING: Adult patients with MG from seven countries (USA, Japan, Germany, UK, Italy, Spain and Canada) downloaded a mobile application onto their phones and entered data about themselves and their MG. OUTCOME MEASURES: Data was collected using the following general and disease-specific patient-reported outcome measurements: EuroQol 5 Domains Health-Related Quality of Life Questionnaire (EQ-5D-5L), Myasthenia Gravis Activities of Daily Living (MG-ADL), Myasthenia Gravis Quality of Life 15-item revised scale (MG-QoL-15r), Hospital Anxiety and Depression Scale (HADS) and Health Utilities Index III (HUI3). Patients were categorised by their self-assessed Myasthenia Gravis Foundation of America (MGFA) class (I-V). RESULTS: Baseline results of 841 participants (mean age 47 years, 70% women) are reported . The distribution across the MGFA classes was: 13.9%, 31.0%, 38.1%, 15.5% and 1.6% for classes I-V. The MGFA class was a strong predictor of all aspects of HRQoL, measured with disease-specific and with generic instruments. The domains in which patients with MG most frequently mentioned problems were usual activities, anxiety and depression, tiredness, breathing and vision. The mean total MG-ADL Score was positively associated with increasing MGFA classes: 2.7, 4.4, 6.3 and 8.4 for MGFA classes I-IV. Mean baseline EQ-5D-5L utility was also associated with MGFA classes and was 0.817, 0.766, 0.648 and 0.530 for MGFA class I-IV. CONCLUSIONS: MG has a large impact on key aspects of health and HRQoL. The impact of this disease increases substantially with increasing disease severity.
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Miastenia Gravis , Qualidade de Vida , Adulto , Humanos , Feminino , Pessoa de Meia-Idade , Masculino , Atividades Cotidianas , Estudos Prospectivos , Medidas de Resultados Relatados pelo PacienteRESUMO
PURPOSE: This study examines the EQ-5D-5L pain/discomfort dimension by drawing comparisons with five other pain and discomfort items (pain severity, discomfort severity, pain frequency, discomfort frequency and pain interference) collected in the Australian psychometric study for the EQ Health and Wellbeing instrument. METHODS: Participants, recruited via a market research company, completed an online survey. Methods of analyses included the assessment of descriptive statistics, variation in reporting patterns using chi-square tests and cross-tabulations, correlation analyses, ordered univariate logistic regression, and discriminatory power analyses (Shannon index (H') and Shannon Evenness index (J')). RESULTS: Survey data from 514 participants were used. Compared with EQ-5D-5L pain/discomfort, there was a higher proportion of respondents reporting some level of impairment on at least one of the pain severity and discomfort severity items (74% versus 81%). Correlation with EQ-5D-5L pain/discomfort was strongest for pain severity (r = 0.83) and weakest for discomfort frequency (r = 0.41); the same inferences were drawn for predictive ability. Adding any additional pain or discomfort items to the EQ-5D-5L increased the absolute informativity (H') but not the relative informativity (J'). When replacing EQ-5D-5L pain/discomfort with separate pain and/or discomfort items - i.e., adding items to a modified 'EQ-4D-5L'-absolute informativity increased, while relative informativity increased only when pain interference and frequency-related items (independently or in combination) were added. CONCLUSION: The EQ-5D-5L pain/discomfort dimension captures aspects of pain more than aspects of discomfort. Potential reasons include the absence of descriptors or because pain is mentioned first in the composite item.
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Dor , Qualidade de Vida , Humanos , Qualidade de Vida/psicologia , Austrália , Inquéritos e Questionários , Psicometria/métodos , Reprodutibilidade dos Testes , Nível de SaúdeRESUMO
Early-life stress (ELS) leads to increased vulnerability to psychiatric disorders including depression later in life. Neuroinflammatory processes have been implicated in ELS-induced negative health outcomes, but how ELS impacts microglia, the main tissue-resident macrophages of the central nervous system, is unknown. Here, we determined the effects of ELS-induced by limited bedding and nesting material during the first week of life (postnatal days [P]2-9) on microglial (i) morphology; (ii) hippocampal gene expression; and (iii) synaptosome phagocytic capacity in male pups (P9) and adult (P200) mice. The hippocampus of ELS-exposed adult mice displayed altered proportions of morphological subtypes of microglia, as well as microglial transcriptomic changes related to the tumor necrosis factor response and protein ubiquitination. ELS exposure leads to distinct gene expression profiles during microglial development from P9 to P200 and in response to an LPS challenge at P200. Functionally, synaptosomes from ELS-exposed mice were phagocytosed less by age-matched microglia. At P200, but not P9, ELS microglia showed reduced synaptosome phagocytic capacity when compared to control microglia. Lastly, we confirmed the ELS-induced increased expression of the phagocytosis-related gene GAS6 that we observed in mice, in the dentate gyrus of individuals with a history of child abuse using in situ hybridization. These findings reveal persistent effects of ELS on microglial function and suggest that altered microglial phagocytic capacity is a key contributor to ELS-induced phenotypes.
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Experiências Adversas da Infância , Maus-Tratos Infantis , Microglia , Animais , Criança , Masculino , Camundongos , Transcriptoma , Humanos , Microglia/patologia , Fagocitose , Sinaptossomos , Hipocampo/fisiopatologia , Giro Denteado/fisiopatologiaRESUMO
BACKGROUND: Drug overuse or drug underuse are the most common causes of adverse drug events and can lead to hospital admissions. Using clinical pharmacists in the emergency department may improve patient safety as they are specialised in recognising of adverse drug events and tackling drug overuse and drug underuse. This study tested the effect of an emergency department pharmacist on the number of medication changes for drug overuse and drug underuse taking place in patients with an adverse drug event-related hospitalisation following an emergency department visit. METHODS: A multicenter prospective non-randomized controlled intervention study was conducted in a university hospital and a general teaching hospital. Trained emergency department pharmacists included patients in the intervention group with a hospital admission related to an adverse drug event. The interdisciplinary intervention consisted of a pharmacist-led medication review, patient counselling regarding medication, and information transmission to general practitioners and community pharmacies after discharge. The control patients were also admitted after an emergency department visit and received the usual care. The primary outcome was the number of medication changes for drug overuse and drug underuse that took place during hospital admission and persisted 6 months thereafter. Poisson regression analysis was used to estimate the difference in these medication changes between the intervention group and the control group. RESULTS: A total of 216 patients were included (intervention group 104, control group 112). In the intervention group, 156 medication changes for drug overuse and drug underuse persisted 6 months after admission compared to 59 in the control group (adjusted rate ratio 1.22 [95%CI 1.01-1.49] p = 0.039). CONCLUSION: Emergency department pharmacists do contribute to reduction of drug overuse and drug underuse of medication in patients with a hospitalisation related to adverse drug events after an emergency department visit.
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Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos , Farmacêuticos , Uso Excessivo de Medicamentos Prescritos , Humanos , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/epidemiologia , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/prevenção & controle , Serviço Hospitalar de Emergência , Hospitalização , Hospitais Universitários , Erros de Medicação/prevenção & controle , Estudos ProspectivosRESUMO
BACKGROUND: Of all hospital admissions in older patients, 10-30% seem to be medication-related. However, medication-related admissions are often unidentified in clinical practice. To increase the identification of medication-related hospital admissions in older patients a triggerlist is published in the Dutch guideline for polypharmacy. AIM: To assess whether the triggerlist has value as selection criterion to identify patients at high risk of medication-related hospital admissions. METHOD: This retrospective cohort study was carried out in 100 older (≥ 60 years) patients with polypharmacy and having two triggers from the triggerlist. The admissions were assessed as either possibly or unlikely medication-related according to the Assessment Tool for identifying Hospital Admissions Related to Medications. RESULTS: Of all the admissions 48% were classified as possibly medication-related. Patients with a possible medication-related hospital admission were more likely to have an impaired renal function (p = 0.015), but no differences with regard to age, sex, comorbidity or number of medicines were found. CONCLUSION: The high prevalence of medication-related hospital admissions, suggests the triggerlist may have added value as selection criterion in a cohort of older patients with polypharmacy and can be used to improve the identification of a population at high risk of medication-related hospital admissions.
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Hospitalização , Polimedicação , Humanos , Idoso , Estudos Retrospectivos , Estudos de Coortes , HospitaisRESUMO
Background: Little is known about pyridoxine-dependent epilepsy due to α-aminoadipic semialdehyde dehydrogenase deficiency (PDE-ALDH7A1) in adulthood, as the genetic basis of the disorder has only been elucidated 15 years ago. This creates a knowledge gap for physicians, pediatric patients and their parents, which was aimed to address in this study using clinical data as well as patient-reported outcome measures (PROMs) for the patient's perspective. Methods: Dutch, genetically confirmed PDE-ALDH7A1 patients ≥18 years were eligible for inclusion. Clinical data were collected as well as PROMs (PROMIS item banks Anxiety, Depression, Anger, Physical Functioning, Cognitive Functioning, Cognitive Abilities, Ability to Participate and Satisfaction with Social Roles). Results: Ten out of 11 patients agreed to participate (91% response rate). Seizure control at last follow up (median age 25.2 years, range 17.8-29.8 years) was achieved with pyridoxine monotherapy in 70%, 20% with adjunct common-anti epileptic drugs and 10% did not obtain complete seizure control. Neurologic symptoms were present in all but one patient (90%) and included tremors, noted in 40%. Neuro-imaging abnormalities were present in 80%. Intellectual disability was present in 70%. One patient (10%) attended university, three maintained a job without assistance, five maintained a job with assistance or attended social daycare, and one patient never followed regular education. The cohort scored significantly lower on the PROMIS Cognitive Functioning compared to the general (age-related) population. Distribution of scores was wide on all PROMIS item banks. Discussion & conclusion: Outcomes of this young adult cohort are heterogeneous and individualized approaches are therefore needed. Long-term seizure control with pyridoxine was achieved for almost all patients. Neurologic symptoms were noted in the majority, including tremors, as well as neuro-imaging abnormalities and intellectual disability, additionally reflected by the PROMIS Cognitive Functioning. PDE-ALDH7A1 patients scored comparable to the general population on all other PROMs, especially regarding Ability to Participate and Satisfaction with Social Roles this may indicate a positive interpretation of their functioning. The aim is to expand this pilot study to larger populations to obtain more solid data, and to advance the use of PROMs to engage patients in research and provide the opportunity for personalized care.
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BACKGROUND: Although medication reconciliation (MedRec) is mandated and effective in decreasing preventable medication errors during transition of care, hospitals implement MedRec differently. OBJECTIVE: Quantitatively compare the number and type of MedRec interventions between hospitals upon admission and discharge, followed by a qualitative analysis on potential reasons for differences. METHODS: This explanatory retrospective mixed-method study consisted of a quantitative and a qualitative part. Patients from six hospitals and six different wards i.e. orthopaedics, surgery, pulmonary diseases, internal medicine, cardiology and gastroenterology were included. At these wards, MedRec was implemented both on hospital admission and discharge. The number of pharmacy interventions was collected and classified in two subcategories. First, the number of interventions to resolve unintended discrepancies (elimination of differences between listed medication and the patient's actual medication use). And second, the number of medication optimizations (optimization of pharmacotherapy e.g. eliminating double medication). Based on these quantitative results and interviews, a focus group was performed to give insight in local MedRec processes to address differences in context between hospitals. Descriptive analysis (quantitative) and content analysis (qualitative) was used. RESULTS: On admission 765 (85%) patients from six hospitals, received MedRec by trained nurses, pharmacy technicians, pharmaceutical consultants or pharmacists. Of those, 36-95% (mean per patient 2.2 (SD ± 2.4)) had at least one discrepancy. Upon discharge, these numbers were among 632 (70%) of patients, 5-28% (mean per patient 0.7 (SD 1.2)). Optimizations in pharmacotherapy were implemented for 2% (0.4-3.7 interventions per patient upon admission) to 95% (0.1-1.7 interventions per patient upon discharge) of patients. The main themes explaining differences in numbers of interventions were patient-mix, the type of healthcare professionals involved, where and when patient interviews for MedRec were performed and finally, embedding and extent of medication optimization. CONCLUSIONS: Hospitals differed greatly in the number of interventions performed during MedRec. Differences in execution of MedRec and local context determines the number of interventions. This study can support hospitals who want to optimize MedRec processes.
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Hospitais , Reconciliação de Medicamentos , Humanos , Erros de Medicação/prevenção & controle , Reconciliação de Medicamentos/métodos , Farmacêuticos , Estudos RetrospectivosRESUMO
Despite the increasing incidence of kidney-related diseases, we are still far from understanding the underlying mechanisms of these diseases and their progression. This lack of understanding is partly because of a poor replication of the diseasesin vitro,limited to planar culture. Advancing towards three-dimensional models, hereby we propose coaxial printing to obtain microfibers containing a helical hollow microchannel. These recapitulate the architecture of the proximal tubule (PT), an important nephron segment often affected in kidney disorders. A stable gelatin/alginate-based ink was formulated to allow printability while maintaining structural properties. Fine-tuning of the composition, printing temperature and extrusion rate allowed for optimal ink viscosity that led to coiling of the microfiber's inner channel. The printed microfibers exhibited prolonged structural stability (42 days) and cytocompatibility in culture. Healthy conditionally immortalized PT epithelial cells and a knockout cell model for cystinosis (CTNS-/-) were seeded to mimic two genotypes of PT. Upon culturing for 14 days, engineered PT showed homogenous cytoskeleton organization as indicated by staining for filamentous actin, barrier-formation and polarization with apical markerα-tubulin and basolateral marker Na+/K+-ATPase. Cell viability was slightly decreased upon prolonged culturing for 14 days, which was more pronounced inCTNS-/-microfibers. Finally,CTNS-/-cells showed reduced apical transport activity in the microfibers compared to healthy PT epithelial cells when looking at breast cancer resistance protein and multidrug resistance-associated protein 4. Engineered PT incorporated in a custom-designed microfluidic chip allowed to assess leak-tightness of the epithelium, which appeared less tight inCTNS-/-PT compared to healthy PT, in agreement with itsin vivophenotype. While we are still on the verge of patient-oriented medicine, this system holds great promise for further research in establishing advancedin vitrodisease models.
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Nefropatias , Proteínas de Neoplasias , Membro 2 da Subfamília G de Transportadores de Cassetes de Ligação de ATP/metabolismo , Humanos , Nefropatias/metabolismo , Túbulos Renais Proximais/metabolismo , Proteínas de Neoplasias/metabolismo , Impressão TridimensionalRESUMO
Early-life adversity (ELA) is a major risk factor for developing later-life mental and metabolic disorders. However, if and to what extent ELA contributes to the comorbidity and sex-dependent prevalence/presentation of these disorders remains unclear. We here comprehensively review and integrate human and rodent ELA (pre- and postnatal) studies examining mental or metabolic health in both sexes and discuss the role of the placenta and maternal milk, key in transferring maternal effects to the offspring. We conclude that ELA impacts mental and metabolic health with sex-specific presentations that depend on timing of exposure, and that human and rodent studies largely converge in their findings. ELA is more often reported to impact cognitive and externalizing domains in males, internalizing behaviors in both sexes and concerning the metabolic dimension, adiposity in females and insulin sensitivity in males. Thus, ELA seems to be involved in the origin of the comorbidity and sex-specific prevalence/presentation of some of the most common disorders in our society. Therefore, ELA-induced disease states deserve specific preventive and intervention strategies.
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Experiências Adversas da Infância , Doenças Metabólicas , Animais , Comorbidade , Feminino , Humanos , Masculino , Doenças Metabólicas/epidemiologia , Doenças Metabólicas/etiologia , Gravidez , Fatores de Risco , RoedoresRESUMO
BACKGROUND/OBJECTIVE: Different testing paradigms have been proposed to investigate perceptual self-motion thresholds. They can differ regarding the amount of possible motions that patients have to choose from. Objective of this study was to compare the two-option paradigm and twelve-option paradigm, to investigate whether reducing the choice options significantly influences the reported thresholds of self-motion perception of healthy subjects. METHODS: Thirty-three volunteers with no prior vestibular complaints were included and sequentially tested with both paradigms at a random sequence. Perceptual self-motion thresholds were measured using a hydraulic motion platform in the absence of external visual and auditory cues. The platform delivered twelve different movements: six translations and six rotations. Each subject had to report the correct type and direction of movements. Thresholds were determined by a double confirmation of the lowest threshold, in combination with a double rejection of the one-step lower stimulus. Perceptual self-motion thresholds of both paradigms were compared using the mixed model analysis. RESULTS: The twelve-option paradigm showed significantly higher reported thresholds for yaw rotations and translations left, right and down (p < 0.001), compared to the two-option paradigm. No statistical difference was found for rolls and translations up. No significant gender effect, learning effect and carry-over effect were present in any of the applied motion directions. CONCLUSION: Reported thresholds of self-motion perception of healthy subjects are influenced by the testing paradigm. The twelve-option paradigm showed significantly higher thresholds than the two-option paradigm. Results obtained with each testing paradigm should, therefore, be compared to paradigm-specific normative data.