An anti-aging vaccine: BCG turns back the clock on remyelination failure.

Aging leads to alterations that precipitate or aggravate several diseases that occur across our lifespan. In the CNS, aging affects the capacity to maintain and repair the myelin sheaths that protect axons and facilitate neuronal signaling. Tiwari et al. report aging-associated transcriptional responses in microglia after demyelination, which could be reversed by epigenetic remodeling after BCG vaccination.

Dysarthria and dysphagia in patients with mitochondrial diseases.

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.

Development of an adverse outcome pathway network for nephrotoxicity.

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.

Early-life stress and amyloidosis in mice share pathogenic pathways involving synaptic mitochondria and lipid metabolism.

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.

Concordance between patient- and physician-reported Myasthenia Gravis Activities of Daily Living (MG-ADL) scores.

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.

What is measured by the composite, single-item pain/discomfort dimension of the EQ-5D-5L? An exploratory analysis.

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.

Explainable artificial intelligence (XAI): closing the gap between image analysis and navigation in complex invasive diagnostic procedures.

LITERATURE REVIEW: Cystoscopy is the gold standard for initial macroscopic assessments of the human urinary bladder to rule out (or diagnose) bladder cancer (BCa). Despite having guidelines, cystoscopic findings are diverse and often challenging to classify. The extent of the false negatives and false positives in cystoscopic diagnosis is currently unknown. We suspect that there is a certain degree of under-diagnosis (like the failure to detect malignant tumours) and over-diagnosis (e.g. sending the patient for unnecessary transurethral resection of bladder tumors with anesthesia) that put the patient at risk. CONCLUSIONS: XAI robot-assisted cystoscopes would help to overcome the risks/flaws of conventional cystoscopy. Cystoscopy is considered a less life-threatening starting point for automation than open surgical procedures. Semi-autonomous cystoscopy requires standards and cystoscopy is a good procedure to establish a model that can then be exported/copied to other procedures of endoscopy and surgery. Standards also define the automation levels-an issue for medical product law. These cystoscopy skills do not give full autonomy to the machine, and represent a surgical parallel to 'Autonomous Driving' (where a standard requires a human supervisor to remain in the 'vehicle'). Here in robotic cystoscopy, a human supervisor remains bedside in the 'operating room' as a 'human-in-the-loop' in order to safeguard patients. The urologists will be able to delegate personal- and time-consuming cystoscopy to a specialised nurse. The result of automated diagnostic cystoscopy is a short video (with pre-processed photos from the video), which are then reviewed by the urologists at a more convenient time.

Age is the main determinant of COVID-19 related in-hospital mortality with minimal impact of pre-existing comorbidities, a retrospective cohort study.

BACKGROUND: Age and comorbidities increase COVID-19 related in-hospital mortality risk, but the extent by which comorbidities mediate the impact of age remains unknown. METHODS: In this multicenter retrospective cohort study with data from 45 Dutch hospitals, 4806 proven COVID-19 patients hospitalized in Dutch hospitals (between February and July 2020) from the CAPACITY-COVID registry were included (age 69[58-77]years, 64% men). The primary outcome was defined as a combination of in-hospital mortality or discharge with palliative care. Logistic regression analysis was performed to analyze the associations between sex, age, and comorbidities with the primary outcome. The effect of comorbidities on the relation of age with the primary outcome was evaluated using mediation analysis. RESULTS: In-hospital COVID-19 related mortality occurred in 1108 (23%) patients, 836 (76%) were aged ≥70 years (70+). Both age 70+ and female sex were univariably associated with outcome (odds ratio [OR]4.68, 95%confidence interval [4.02-5.45], OR0.68[0.59-0.79], respectively;both p<  0.001). All comorbidities were univariably associated with outcome (p<0.001), and all but dyslipidemia remained significant after adjustment for age70+ and sex. The impact of comorbidities was attenuated after age-spline adjustment, only leaving female sex, diabetes mellitus (DM), chronic kidney disease (CKD), and chronic pulmonary obstructive disease (COPD) significantly associated (female OR0.65[0.55-0.75], DM OR1.47[1.26-1.72], CKD OR1.61[1.32-1.97], COPD OR1.30[1.07-1.59]). Pre-existing comorbidities in older patients negligibly (<6% in all comorbidities) mediated the association between higher age and outcome. CONCLUSIONS: Age is the main determinant of COVID-19 related in-hospital mortality, with negligible mediation effect of pre-existing comorbidities. TRIAL REGISTRATION: CAPACITY-COVID ( NCT04325412 ).

Differences in medication reconciliation interventions between six hospitals: a mixed method study.

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.

The effect of emergency department pharmacists on drug overuse and drug underuse in patients with an ADE-related hospitalisation: a controlled intervention study.

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.

URGENT 1.5: diagnostic accuracy of the modified HEART score, with fingerstick point-of-care troponin testing, in ruling out acute coronary syndrome.

BACKGROUND: The HEART score is a validated risk stratification tool for chest pain patients presenting to the emergency department and was recently investigated for implementation in a pre-hospital setting. Fingerstick (capillary blood) point-of-care (POC) troponin testing enables quick measurements outside the hospital and seems easier to implement than the current venous blood sampling techniques. This study investigates the diagnostic accuracy of the modified HEART score, integrating fingerstick POC troponin testing, in ruling out acute coronary syndrome (ACS). METHODS: The data of 96 patients with chest pain, included in a study investigating a novel POC troponin device under development at the cardiac emergency department, were analysed retrospectively. Based on the patients' admission data and capillary POC high-sensitivity troponin I (hs-cTnI) results, the modified HEART score was determined. The outcome measure, for evaluating the diagnostic accuracy of the modified HEART score, was the occurrence of ACS. RESULTS: Of the total study population, 33 patients (34%) were diagnosed with ACS. Seventeen patients (18%) were classified as low risk (0-3 points) and one patient (6%) in this group was diagnosed with ACS. The sensitivity and negative predictive value of the modified HEART score was 97.0 and 97.6%, respectively. CONCLUSION: The modified HEART score, integrating capillary POC hs-cTnI results, is a promising tool for ruling out ACS in patients with chest pain presenting to the cardiac emergency department. These results encourage prospective investigation into the integration of fingerstick POC troponin testing in the modified HEART score in a pre-hospital setting.

The relation between EQ-5D and fatigue in a Dutch general population sample: an explorative study.

BACKGROUND: Fatigue negatively influences health-related quality of life. It is questionable whether fatigue is sufficiently covered by the EQ-5D. This study investigated whether fatigue is covered by the existing domains of the EQ-5D. METHODS: A Dutch general population sample completed the EQ-5D (3L and 5L version) and the Rivermead Post-Concussion Symptoms Questionnaire (RPQ), of which the fatigue item was used. Outcomes were compared between participants with and without a chronic health condition. Convergent validity was assessed, and multivariate regression analyses was used to predict the RPQ fatigue item from the EQ-5D-3L and EQ-5D-5L domains separately. RESULTS: 3027 people completed the survey, of whom 52% had ≥ 1 chronic health condition. Fatigue was reported by 48% of the participants. Fatigue was moderately correlated to the EQ-5D domains 'pain/discomfort', 'usual activities', and 'anxiety/depression' for the 3L (r = 0.379-0.426) and 5L version (r = 0.411-0.469). For the 5L, also a moderate correlation with 'mobility' (r = 0.335) was observed. The remaining correlations were weak. All EQ-5D-3L and 5L domains except for 'mobility' were significantly associated with the RPQ fatigue item (unstandardized Beta = - 0.20-0.67; p < 0.01 to p = 0.04). Comparable outcomes were found for participants with and without ≥ 1 chronic health condition. CONCLUSIONS: The extent to which fatigue is covered by the EQ-5D domains is small to moderate, with the EQ-5D-5L being slightly more sensitive to capture fatigue compared to the EQ-5D-3L. An extra fatigue item for the EQ-5D may add value, as fatigue is not fully captured by the existing domains, both in people with and without a chronic health condition.

US population norms for the EQ-5D-5L and comparison of norms from face-to-face and online samples.

PURPOSE: Normative scores (norms) allow for comparisons between population(s) of interest and the general population, which is useful for burden of disease studies and cost-effectiveness analysis. The primary aim of this study was to estimate US visual analogue scale (EQ VAS) and utility-based norms for the EQ-5D-5L using the face-to-face sample. The secondary aim was to compare norms estimated in the face-to-face and online populations. METHODS: This study estimated population norms from two general population surveys: (a) face-to-face and (b) online. In these surveys, respondents provided their health state using the EQ-5D-5L health classifier and the EQ VAS. Descriptive statistics, including mean, standard deviation (SD), 95% confidence interval, and median for the 5L utility and EQ VAS were estimated for each sample and across relevant respondent characteristics to serve as the basis for US EQ-5D-5L norms RESULTS: Face-to-face sample respondents (n = 1134) were representative of the US adult general population. In this sample, mean (SD) utility decreased with increasing age until age 45 or greater (age 45-54: 0.816 (0.249) age 55-64: 0.815 (0.243) age 65-74: 0.824 (0.217) age 75 + : 0.811 (0.218)). With increasing age, more problems were reported on all dimensions except anxiety/depression; a smaller proportion of respondents age 65 and older reported problems with anxiety/depression (23.8%) as compared to the youngest respondents (42.1%). Online (n = 2018) mean utility and EQ VAS values were consistently lower than the face-to-face sample. CONCLUSIONS: The availability of US EQ-5D-5L norms facilitates interpretation and understanding of general population and patient health.

Characterization of astrocytes throughout life in wildtype and APP/PS1 mice after early-life stress exposure.

BACKGROUND: Early-life stress (ES) is an emerging risk factor for later life development of Alzheimer's disease (AD). We have previously shown that ES modulates amyloid-beta pathology and the microglial response to it in the APPswe/PS1dE9 mouse model. Because astrocytes are key players in the pathogenesis of AD, we studied here if and how ES affects astrocytes in wildtype (WT) and APP/PS1 mice and how these relate to the previously reported amyloid pathology and microglial profile. METHODS: We induced ES by limiting nesting and bedding material from postnatal days (P) 2-9. We studied in WT mice (at P9, P30, and 6 months) and in APP/PS1 mice (at 4 and 10 months) (i) GFAP coverage, cell density, and complexity in hippocampus (HPC) and entorhinal cortex (EC); (ii) hippocampal gene expression of astrocyte markers; and (iii) the relationship between astrocyte, microglia, and amyloid markers. RESULTS: In WT mice, ES increased GFAP coverage in HPC subregions at P9 and decreased it at 10 months. APP/PS1 mice at 10 months exhibited both individual cell as well as clustered GFAP signals. APP/PS1 mice when compared to WT exhibited reduced total GFAP coverage in HPC, which is increased in the EC, while coverage of the clustered GFAP signal in the HPC was increased and accompanied by increased expression of several astrocytic genes. While measured astrocytic parameters in APP/PS1 mice appear not be further modulated by ES, analyzing these in the context of ES-induced alterations to amyloid pathology and microglial shows alterations at both 4 and 10 months of age. CONCLUSIONS: Our data suggest that ES leads to alterations to the astrocytic response to amyloid-ß pathology.

Exploring the relation between the EQ-5D-5L pain/discomfort and pain and itching in a sample of burn patients.

BACKGROUND: The EQ-5D domain pain/discomfort (PD) uses one item to capture pain and other aspects of discomfort, like itching. This study explored how pain, itching and the EQ-5D-5L PD domain relate to each other in a sample of burn patients. METHODS: Adult burn patients completed the EQ-5D-5L and the Patient and Observer Scar Assessment Scale (POSAS) 5-7 years after sustaining their injury. The POSAS includes a separate pain and an itching item. Spearman's correlation coefficient established the association between the EQ-5D-5L PD and the POSAS pain and itching item. With multivariable regression analysis the linear association between the POSAS pain and itching item and EQ-5D-5L PD domain was tested. RESULTS: Data from 245 patients were included. Mean EQ-5D-5L index value was 0.87 and 39.2% reported at least slight problems on the EQ-5D-5L PD domain. Most patients gave corresponding answers on the EQ-5D-5L PD domain and on the POSAS pain (73%) and itching (70%) item. Spearman correlation coefficients of the EQ-5D-5L PD domain with the POSAS pain and itching were 0.468 (p < 0.001) and 0.473 (p < 0.001), respectively. Among respondents with pain and without itching and respondents with itching and without pain, Spearman correlation coefficients were 0.585 (p = 0.076) and 0.408 (p = 0.001), respectively. POSAS pain (unstandardized Beta = 0.14) and POSAS itching (unstandardized Beta = 0.08) were significantly associated with EQ-5D-5L PD domain (p < 0.001). CONCLUSIONS: Our findings indicate that, in a sample of burn patients, pain and itching are captured by the broader EQ-5D-5L PD domain. The EQ-5D-5L PD domain can thus be used to assess pain and itching in relation to HRQL, but the POSAS pain and itching items are more sensitive. The EQ-5D-5L is, however, no replacement of the POSAS when the POSAS is used for its primary aim; assessment of scar quality. TRIAL REGISTRATION: Netherlands Trial Register (NTR6407).

Does the EQ-5D-5L benefit from extension with a cognitive domain: Testing a multi-criteria psychometric strategy in trauma patients.

PURPOSE: This study investigated the psychometric yield of extension of the EQ-5D-5L with a cognitive domain (EQ-5D+C) in a mixed cohort of trauma patients with repeated data. METHODS: A stratified sample of patients that presented at the emergency department filled out a follow-up survey 6 and 12 months after trauma. The surveys included the EQ-5D-5L+C, EQ-VAS, and the impact of events scale-revised (IES-R), a validated post-traumatic stress disorder (PTSD) self-assessment scale. Generally, results of the EQ-5D and EQ-5D+C were compared. Psychometrics included the following: distributional features (ceiling/floor effects), discriminatory performance, convergent validity with the EQ-VAS as reference, and responsiveness to change. Psychometric properties were compared between predefined subgroups based on conditions with cognitive impact (Traumatic Brain Injury (TBI)/PTSD). RESULTS: In total, 1799 trauma patients responded 6 and 12 months after trauma, including 107 respondents with PTSD, and 273 with TBI. Six months post-trauma, ceiling of the EQ-5D (26.3%) was reduced with 2.2% with the additional cognitive domain. Using EQ-VAS as reference, convergent validity increased slightly with the addition of the cognitive domain: correlation increasing from 0.651 to 0.664. Cognitive level was found to slightly improve over time in TBI (delta: 0.04) and PTSD patients (delta: 0.05), while (almost) no change was found in patients without TBI and PTSD. CONCLUSION: Adding a cognitive domain to the EQ-5D-5L slightly improved measurement properties and better captured change in health status for trauma patients with TBI and PTSD. Inclusion of the cognitive domain in the EQ-5D-5L when measuring in populations with cognitive problems should be considered.

Swallowing dysfunction in patients with nephropathic cystinosis.

INTRODUCTION: Nephropathic cystinosis is a rare autosomal recessive lysosomal storage disorder caused by mutations in the CTNS gene. Patients with nephropathic cystinosis suffer not only from renal disease but have also other systemic complications like myopathy and swallowing dysfunction. Dysphagia for solid food is mentioned in patients with cystinosis, but in clinical practice swallowing investigations are only performed when the patient has complaints. The aim of this study was to explore the swallowing function in patients with cystinosis by use of the Test of Mastication and Swallowing Solids (TOMASS), and to compare their performance with patients with myotonic dystrophy type 1 - a neuromuscular disease in which dysphagia for solid food is a known problem. METHODS: Twenty adult patients with cystinosis (11 men and 9 women, range 19-51 years) and 10 patients with myotonic dystrophy type 1 (5 men and 5 women, range 20-60 years) were included. All cystinosis patients were treated with cysteamine. Data of the two groups were compared with normative data using independent-samples t-tests. In case the variables were not normally distributed, the non-parametric Mann-Whitney U test was used. RESULTS: There was a significant difference in the number of bites, masticatory cycles, swallows and total time between the normal values and cystinosis patients. The results of the cystinosis patients were comparable to those of the patients with myotonic dystrophy. DISCUSSION AND CONCLUSION: Adult patients with cystinosis have significant dysphagia for solid food. Clinicians treating these patients should be aware of this fact. The TOMASS can be performed easily in clinical practice to investigate whether patients with cystinosis have swallowing dysfunction. The swallowing dysfunction can now be diagnosed by use of a non-invasive, very simple, non-harmful test. It can be discussed whether this should be added to the regular care scheme of cystinosis patients in order to regularly follow-up swallowing function.

Telemonitoring with an implantable loop recorder in outpatient heart failure care : One year follow-up report from a prospective observational Dutch multicentre study.

INTRODUCTION: In the care of heart failure patients, telemonitoring is receiving growing attention. The main purpose of this study was to determine the effect of continuous telemonitoring with an implantable loop recorder (ILR, Reveal XT), a novel strategy in the management of stable heart failure patients without a cardiac implantable device. Furthermore, little is known about the incidence of subclinical arrhythmias in this specific group of patients. MATERIALS AND METHODS: Stable heart failure patients, New York Heart Association Class II and III, without recent hospitalisation or upcoming intervention, were included. After implantation of the ILR there was regular contact with the research nurse on a pre-specified basis. Clinic visits and telephonic interviews were alternated for a minimum of 1 year. Parallel visits to their treating physician continued according to standard care. The treating physician was blinded for the ILR findings, accept for pre-specified, significant arrhythmic events. RESULTS: Thirty patients were included and followed for a median duration of 12 months. In 13 patients, data from the loop recorder led to therapeutic changes. One patient received a pacemaker. Eight patients developed atrial fibrillation, all subclinical, with a mean burden of 65.8 ± 173.2 min/day. CONCLUSION: The use of an ILR could potentially impact patient management. Additional study is needed in different patient populations (e. g. higher risk groups) to assess if an ILR could also impact on endpoints such as heart failure hospitalisation.

Direct costs of transfusion reactions - an expert judgement approach.

BACKGROUND AND OBJECTIVES: Despite increasingly meticulous haemovigilance reporting throughout the world, a systematic assessment of the cost of transfusion reactions is still lacking. This is partly caused by the fact that such an assessment requires a subjective expert assessment of the additional costs linked to the adverse reaction. Data on the cost of transfusion reactions could support decision-making regarding blood transfusion safety measures. MATERIALS AND METHODS: Thirteen experts from nine hospitals were asked to estimate the additional care required following various types of transfusion reactions. Additional care was quantified as the proportion of reactions requiring care, and the amount of care required (e.g. hospitalization days, additional physician's time). Experts were also asked to provide, per type of transfusion reaction, an estimate of the proportion of transfusion reactions preventable. Structured quantitative expert elicitation methods were applied to obtain and combine expert estimates. RESULTS: The estimated annual in-hospital cost of transfusion reactions in the Netherlands is €933 356 per year (€1.52 per transfusion). Two-thirds (64%) of these are incurred by non-serious transfusion reactions. Circulatory overload, TRALI and anaphylaxis clearly dominate the costs of serious adverse transfusion reactions (66% in total); non-haemolytic transfusion reactions incur 46% of the cost of non-serious transfusion reactions. Additional safety measures targeting circulatory overload and new antibody formation potentially offer the highest cost reduction. CONCLUSION: In-hospital costs of transfusion reactions are substantial but contribute to less than 1% of the total cost of transfusion in the Netherlands. A considerable part of these costs (24%) might be preventable.

Patients with gout have short telomeres compared with healthy participants: association of telomere length with flare frequency and cardiovascular disease in gout.

AIM AND BACKGROUND: Chronic inflammation associates with increased senescence, which is a strong predictor for cardiovascular disease. We hypothesised that inflammation accelerates senescence and thereby enhances the risk of cardiovascular disease in gout. METHODS: We assessed replicative senescence by quantifying telomere length (TL) in a discovery cohort of 145 Dutch patients with gout and 273 healthy individuals and validated our results in 474 patients with gout and 293 healthy participants from New Zealand. Subsequently, we investigated the effect of cardiovascular disease on TL of all participants. Also, we measured TL of CD4+ and CD8+ T lymphocytes, B lymphocytes, monocytes, natural killer cells and plasmacytoid dendritic cells. Additionally, we assessed the potential temporal difference in TL and telomerase activity. RESULTS: TL in PBMCs of healthy donors decreased over time, reflecting normal ageing. Patients with gout demonstrated shorter telomeres (p=0.001, R2=0.01873). In fact, the extent of telomere erosion in patients with gout was higher at any age compared with healthy counterparts at any age (p<0.0001, R2=0.02847). Patients with gout with cardiovascular disease had the shortest telomeres and TL was an independent risk factor for cardiovascular disease in patients with gout (p=0.001). TL was inversely associated with the number of gouty flares (p=0.005). CONCLUSIONS: Patients with gout have shorter telomeres than healthy participants, reflecting increased cellular senescence. Telomere shortening was associated with the number of flares and with cardiovascular disease in people with gout.