Preferences of patients undergoing hemodialysis - results from a questionnaire-based study with 4,518 patients

Janssen IM, Gerhardus A, von Gersdorff G, et al. Preferences of patients undergoing hemodialysis - results from a questionnaire-based study with 4,518 patients. Patient Preference and Adherence. 2015;2015(9):847-855.Background: Chronic kidney disease is an increasing health problem worldwide and in its final stage (stage V) can only be treated by renal replacement therapy, mostly hemodialysis. Hemodialysis has a major influence on the everyday life of patients and many patients report dissatisfaction with treatment. Little is known about which aspects of treatment are considered important by hemodialysis patients. The objective of this study was to rate the relative importance of different outcomes for hemodialysis patients and to analyze whether the relative importance differed among subgroups of patients. Patients and methods: Within the framework of a yearly questionnaire which is distributed among patients receiving hemodialysis by the largest hemodialysis provider in Germany, we assessed the relative importance of 23 outcomes as rated on a discrete visual analog scale. Descriptive statistics were used to rank the outcomes. Subgroup analyses were performed using Mann–Whitney U or Kruskal–Wallis tests. Results: Questionnaires of 4,518 hemodialysis patients were included in the analysis. The three most important outcomes were safety of treatment, health-related quality of life, and satisfaction with care. Further important outcomes were hospital stays, accompanying symptoms, hemodialysis duration, and the improvement or preservation of a good emotional state. Age, profession, and education had the strongest influence on relevant differences of preferences for outcomes; no relevant influence of sex or comorbidity was observed. Conclusion: Outcomes concerning the delivery or provision of care and aspects influencing quality of life are rated by patients to be at least as important as clinical outcomes. Many of the outcomes judged to be important by the patients are not regularly considered in research, evaluation studies, or quality programs

Immunization with lytic polysaccharide monooxygenase CbpD induces protective immunity against Pseudomonas aeruginosa pneumonia

publishedVersio

Association of Mortality and Risk of Epilepsy With Type of Acute Symptomatic Seizure After Ischemic Stroke and an Updated Prognostic Model

IMPORTANCE: Acute symptomatic seizures occurring within 7 days after ischemic stroke may be associated with an increased mortality and risk of epilepsy. It is unknown whether the type of acute symptomatic seizure influences this risk. OBJECTIVE: To compare mortality and risk of epilepsy following different types of acute symptomatic seizures. DESIGN, SETTING, AND PARTICIPANTS: This cohort study analyzed data acquired from 2002 to 2019 from 9 tertiary referral centers. The derivation cohort included adults from 7 cohorts and 2 case-control studies with neuroimaging-confirmed ischemic stroke and without a history of seizures. Replication in 3 separate cohorts included adults with acute symptomatic status epilepticus after neuroimaging-confirmed ischemic stroke. The final data analysis was performed in July 2022. EXPOSURES: Type of acute symptomatic seizure. MAIN OUTCOMES AND MEASURES: All-cause mortality and epilepsy (at least 1 unprovoked seizure presenting >7 days after stroke). RESULTS: A total of 4552 adults were included in the derivation cohort (2547 male participants [56%]; 2005 female [44%]; median age, 73 years [IQR, 62-81]). Acute symptomatic seizures occurred in 226 individuals (5%), of whom 8 (0.2%) presented with status epilepticus. In patients with acute symptomatic status epilepticus, 10-year mortality was 79% compared with 30% in those with short acute symptomatic seizures and 11% in those without seizures. The 10-year risk of epilepsy in stroke survivors with acute symptomatic status epilepticus was 81%, compared with 40% in survivors with short acute symptomatic seizures and 13% in survivors without seizures. In a replication cohort of 39 individuals with acute symptomatic status epilepticus after ischemic stroke (24 female; median age, 78 years), the 10-year risk of mortality and epilepsy was 76% and 88%, respectively. We updated a previously described prognostic model (SeLECT 2.0) with the type of acute symptomatic seizures as a covariate. SeLECT 2.0 successfully captured cases at high risk of poststroke epilepsy. CONCLUSIONS AND RELEVANCE: In this study, individuals with stroke and acute symptomatic seizures presenting as status epilepticus had a higher mortality and risk of epilepsy compared with those with short acute symptomatic seizures or no seizures. The SeLECT 2.0 prognostic model adequately reflected the risk of epilepsy in high-risk cases and may inform decisions on the continuation of antiseizure medication treatment and the methods and frequency of follow-up

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

Early role of vascular dysregulation on late-onset Alzheimer's disease based on multifactorial data-driven analysis

Multifactorial mechanisms underlying late-onset Alzheimer's disease (LOAD) are poorly characterized from an integrative perspective. Here spatiotemporal alterations in brain amyloid-β deposition, metabolism, vascular, functional activity at rest, structural properties, cognitive integrity and peripheral proteins levels are characterized in relation to LOAD progression. We analyse over 7,700 brain images and tens of plasma and cerebrospinal fluid biomarkers from the Alzheimer's Disease Neuroimaging Initiative (ADNI). Through a multifactorial data-driven analysis, we obtain dynamic LOAD–abnormality indices for all biomarkers, and a tentative temporal ordering of disease progression. Imaging results suggest that intra-brain vascular dysregulation is an early pathological event during disease development. Cognitive decline is noticeable from initial LOAD stages, suggesting early memory deficit associated with the primary disease factors. High abnormality levels are also observed for specific proteins associated with the vascular system's integrity. Although still subjected to the sensitivity of the algorithms and biomarkers employed, our results might contribute to the development of preventive therapeutic interventions

Conversion Discriminative Analysis on Mild Cognitive Impairment Using Multiple Cortical Features from MR Images

Neuroimaging measurements derived from magnetic resonance imaging provide important information required for detecting changes related to the progression of mild cognitive impairment (MCI). Cortical features and changes play a crucial role in revealing unique anatomical patterns of brain regions, and further differentiate MCI patients from normal states. Four cortical features, namely, gray matter volume, cortical thickness, surface area, and mean curvature, were explored for discriminative analysis among three groups including the stable MCI (sMCI), the converted MCI (cMCI), and the normal control (NC) groups. In this study, 158 subjects (72 NC, 46 sMCI, and 40 cMCI) were selected from the Alzheimer's Disease Neuroimaging Initiative. A sparse-constrained regression model based on the l2-1-norm was introduced to reduce the feature dimensionality and retrieve essential features for the discrimination of the three groups by using a support vector machine (SVM). An optimized strategy of feature addition based on the weight of each feature was adopted for the SVM classifier in order to achieve the best classification performance. The baseline cortical features combined with the longitudinal measurements for 2 years of follow-up data yielded prominent classification results. In particular, the cortical thickness produced a classification with 98.84% accuracy, 97.5% sensitivity, and 100% specificity for the sMCI–cMCI comparison; 92.37% accuracy, 84.78% sensitivity, and 97.22% specificity for the cMCI–NC comparison; and 93.75% accuracy, 92.5% sensitivity, and 94.44% specificity for the sMCI–NC comparison. The best performances obtained by the SVM classifier using the essential features were 5–40% more than those using all of the retained features. The feasibility of the cortical features for the recognition of anatomical patterns was certified; thus, the proposed method has the potential to improve the clinical diagnosis of sub-types of MCI and predict the risk of its conversion to Alzheimer's disease

Quantitative 18F-AV1451 Brain Tau PET Imaging in Cognitively Normal Older Adults, Mild Cognitive Impairment, and Alzheimer's Disease Patients

Recent developments of tau Positron Emission Tomography (PET) allows assessment of regional neurofibrillary tangles (NFTs) deposition in human brain. Among the tau PET molecular probes, 18F-AV1451 is characterized by high selectivity for pathologic tau aggregates over amyloid plaques, limited non-specific binding in white and gray matter, and confined off-target binding. The objectives of the study are (1) to quantitatively characterize regional brain tau deposition measured by 18F-AV1451 PET in cognitively normal older adults (CN), mild cognitive impairment (MCI), and AD participants; (2) to evaluate the correlations between cerebrospinal fluid (CSF) biomarkers or Mini-Mental State Examination (MMSE) and 18F-AV1451 PET standardized uptake value ratio (SUVR); and (3) to evaluate the partial volume effects on 18F-AV1451 brain uptake.Methods: The study included total 115 participants (CN = 49, MCI = 58, and AD = 8) from the Alzheimer's Disease Neuroimaging Initiative (ADNI). Preprocessed 18F-AV1451 PET images, structural MRIs, and demographic and clinical assessments were downloaded from the ADNI database. A reblurred Van Cittertiteration method was used for voxelwise partial volume correction (PVC) on PET images. Structural MRIs were used for PET spatial normalization and region of interest (ROI) definition in standard space. The parametric images of 18F-AV1451 SUVR relative to cerebellum were calculated. The ROI SUVR measurements from PVC and non-PVC SUVR images were compared. The correlation between ROI 18F-AV1451 SUVR and the measurements of MMSE, CSF total tau (t-tau), and phosphorylated tau (p-tau) were also assessed.Results:18F-AV1451 prominently specific binding was found in the amygdala, entorhinal cortex, parahippocampus, fusiform, posterior cingulate, temporal, parietal, and frontal brain regions. Most regional SUVRs showed significantly higher uptake of 18F-AV1451 in AD than MCI and CN participants. SUVRs of small regions like amygdala, entorhinal cortex and parahippocampus were statistically improved by PVC in all groups (p < 0.01). Although there was an increasing tendency of 18F-AV-1451 SUVRs in MCI group compared with CN group, no significant difference of 18F-AV1451 deposition was found between CN and MCI brains with or without PVC (p > 0.05). Declined MMSE score was observed with increasing 18F-AV1451 binding in amygdala, entorhinal cortex, parahippocampus, and fusiform. CSF p-tau was positively correlated with 18F-AV1451 deposition. PVC improved the results of 18F-AV-1451 tau deposition and correlation studies in small brain regions.Conclusion: The typical deposition of 18F-AV1451 tau PET imaging in AD brain was found in amygdala, entorhinal cortex, fusiform and parahippocampus, and these regions were strongly associated with cognitive impairment and CSF biomarkers. Although more deposition was observed in MCI group, the 18F-AV-1451 PET imaging could not differentiate the MCI patients from CN population. More tau deposition related to decreased MMSE score and increased level of CSF p-tau, especially in ROIs of amygdala, entorhinal cortex and parahippocampus. PVC did improve the results of tau deposition and correlation studies in small brain regions and suggest to be routinely used in 18F-AV1451 tau PET quantification

Psychophysiologische Effekte von Angewandter Entspannung bei Generalisierter Angststörung

Several authors have reported greater muscle tension in Generalized Anxiety Disorder (GAD) patients than in non-anxious controls, and muscle relaxation therapy (MRT) is as clinically effective in the treatment of GAD as Cognitive-Behavior Therapy. MRT assumes that GAD patients lack the ability to relax, but can learn this in therapy. We tested these assumptions by recruiting 49 GAD patients and randomizing them to individualized 12-week Applied Relaxation (AR) treatment (Öst, 1987) or to a waiting list control (WLC) condition. Before, during, and after treatment participants underwent a Relaxation Test, in which for 5 min, in randomized order, they (a) just sat quietly (QS) and (b) sat quietly and tried to relax (R). The tests were preceded by a 2 min speaking period. Before treatment, GAD patients were more anxious and worried during the laboratory assessment than non-anxious controls (n = 21), had higher heart rates and lower end-tidal pCO2, but did not differ in multi-channel electromyographic recordings. QS and R did not differ in most psychological and physiological measures: Thus, before training the intention to relax did not speed relaxation. AR patients showed greater improvement than the WLC group at the end of treatment (Cohen’s d = 0.24 - 1.13), and 53% of AR patients were considered significantly improved after treatment in the completer analysis. However, dropout rate was 28% for AR during treatment, and participants’ improvement wore off at 6-week follow-up, leaving only 29% and 24% clinically improved in the completer and intention-to-treat analyses, respectively. Before treatment, anxiety was not associated with electromyographic or autonomic measures within the GAD group, and there was little evidence in the psychometric and physiological data of the Relaxation Test suggesting that AR patients learned to relax in therapy or that a reduction in anxiety and worry was associated with a decrease in activation. We conclude that GAD is not necessarily characterized by chronic muscle tension. AR is at most moderately effective in reducing anxiety and worry in GAD patients but does not affect muscle tension or autonomic functioning. Since effective cognitive-behavioral and pharmacological treatments are available, MRT may not be the best option for patients meeting DSM-IV GAD criteria, which have evolved to deemphasize hyperarousal symptoms and to emphasize intrusive worry.Verschiedene Studien dokumentieren erhöhte Muskelspannung bei Patienten mit der Diagnose Generalisierte Angststörung (GAS) und die Wirksamkeit der Progressiven Muskelentspannung (PME) bei GAS ist vergleichbar mit der der kognitiven Verhaltenstherapie. Annahmen der PME sind, dass GAS Patienten nicht die Fähigkeit besitzen, sich entspannen zu können, und diese in der Therapie erlernen. In der vorliegenden Studie wurden diese Thesen untersucht. Wir randomisierten 49 GAS Patienten zu 12 wöchentlichen Stunden ambulanter Einzeltherapie (Angewandte Entspannung, AE, Öst, 1987) oder zu einer unbehandelten Kontrollgruppe. Wir testeten die Teilnehmer vor, während, und nach der Therapie mit einem Entspannungstest, bei dem die Teilnehmer instruiert wurden, in zufälliger Reihenfolge für 5 min (a) ruhig zu sitzen (RS) und (b) ruhig zu sitzen und sich zu entspannen (E). Vor jeder Bedingung wurden die Teilnehmer aufgefordert, einen 2 min langen Vortrag zu halten. Während des Entspannungstests vor Beginn der Therapie beschrieben sich die GAS Patienten als ängstlicher und sorgenvoller als eine nicht-ängstliche Kontrollgruppe (n = 21) und wiesen eine erhöhte Herzfrequenz und einen reduzierten end-expiratorischen CO2 Partialdruck auf. Die Gruppen unterschieden sich nicht in elektrischer Muskelaktivität, die in multiplen Kanälen gemessen wurde. Es zeigten sich keine Unterschiede zwischen RS und E in den meisten psychometrischen und physiologischen Kennwerten. Dies belegt, dass die Intention sich zu entspannen, Entspannung nicht schneller herbeiführt. AE führte zu einer bedeutsamen Verbesserung gegenüber der unbehandelten Kontrollgruppe (Cohen’s d = 0.24 - 1.13) und die Symptome von 53% der AE Patienten galten als klinisch relevant verbessert in der Completer Analyse. Allerdings brachen 28% der AE Patienten die Therapie ab und die erzielten Verbesserungen erwiesen sich in der Katamnese 6 Wochen nach Behandlungsende als nicht stabil. In der Nachuntersuchung galten die Verbesserungen von 29% in der Completer Analyse und 24% in der Intention-to-treat Analyse als klinisch relevant. Vor Beginn der Therapie waren Angstzustände innerhalb der GAS Patientengruppe nicht mit skelettmuskulärer Aktivität oder Kennwerten des autonomen Nervensystems assoziiert. Zudem fanden wir in den psychophysiologischen Daten des Relaxationstests nur wenige Indizien dafür, dass AE Patienten lernten sich zu entspannen, oder dass die Angstreduktion mit einer Reduktion der Aktivierung korrespondierte. Zusammenfassend lässt sich sagen, dass die GAS nicht notwendigerweise durch chronisch erhöhte Muskelanspannung gekennzeichnet ist. Die Wirksamkeit der AE bei GAS kann höchstens als moderat beschrieben werden und hat keinen Einfluss auf die Skelettmuskulatur oder das autonome Nervensystem. Da es effektive kognitiv-behaviorale und pharmakologische Behandlungsalternativen gibt, sollte reevaluiert werden, ob AE für Patienten, die anhand von DSM-IV mit GAS diagnostiziert wurden, geeignet ist, besonders, da die gegenwärtigen Kriterien Symptome der Hyperaktivation weniger beachten und unkontrollierbare Sorgen stärker in den Vordergrund stellen als vorherige Auflagen

Muscle tension in generalized anxiety disorder : a critical review of the literature

BACKGROUND: Generalized anxiety disorder (GAD) is a prevalent, disabling, and often chronic disorder. With a typical recovery rate of only about 40% with current psychological treatments a better understanding of potential psychophysiological mechanisms is vital. METHODS: Since the most discriminative somatic symptom of GAD compared to other anxiety disorders is muscle tension this review qualitatively examines the literature on muscle tension as it relates to GAD and muscle relaxation therapy for GAD patients. RESULTS: Muscle tension in GAD is poorly understood. Experimental studies refute the often-assumed direct relationship between anxiety and muscle tension. However, muscle relaxation therapies have been as effective as cognitive interventions directly addressing the defining symptom worry. CONCLUSIONS: Muscle tension in its objective and subjective representations may play a role in GAD through various pathways that are testable. Future research needs to better examine the different aspects and functions of muscle tension in GAD