Inappropriate prescribing in patients with kidney disease: A rapid review of prevalence, associated clinical outcomes and impact of interventions.

BACKGROUND: The prevalence of patients with chronic kidney disease (CKD) and polypharmacy is increasing and has amplified the importance of examining inappropriate prescribing (IP) in CKD. This review focuses on the latest research regarding the prevalence of IP in CKD and the related adverse clinical effects and explores new interventions against IP. METHOD: A literature search was performed using PubMed, EMBASE and the Cochrane Library searching articles published between June 2016 and March 2022. RESULTS: Twenty-seven studies were included. An IP prevalence of 12.6% to 96% and 0.3% to 66% was reported in hospital and outpatient settings, respectively. In nonhospital settings, the prevalence of IP varied between 3.9% and 60%. IP was associated with higher risk of hospitalisation (HR 1.46, 95% CI 1.17-1.81), higher bleeding rate (HR 2.34, 95% CI 1.32 to 3.37) and higher risk of all-cause mortality (OR 1.07, 95% CI 1.02 to 1.13). Three studies reported the impact of interventions on IP. CONCLUSION: This review highlights widespread IP in CKD patients across healthcare settings, with varying prevalence rates. IP is substantially linked to adverse outcomes in patients. While limited interventions show promise, urgent research is needed to develop effective strategies addressing IP and improving CKD patient care.

Catheter-associated bladder mucosal trauma during intermittent voiding: An experimental study in pigs.

Objective: The objective of this study is to characterize bladder mucosal trauma associated with intermittent catheterization with conventional eyelet catheters (CECs) and to assess if a microhole zone catheter (MHZC) design concept reduces this adverse effect. Materials and Methods: A porcine model was developed to reflect human catheterization and bladder drainage. Nine pigs were randomized for catheterization with CEC (n = 6) or MHZC (n = 3). The bladder was drained repeatedly 20 times through the catheter. Cystoscopy was performed before and after the procedure, and bladders were analysed by histopathology. Two additional pigs were used for cystoscopy visualization of suction events in vivo. Cystoscopy, gross pathology, histopathological score, leucocyte infiltration, and intracatheter pressure at flow stops during voiding were compared for each group. Results: A significant higher pressure gradient was measured inside the CECs compared with MHZCs during flow stop. Consequently, CECs resulted in suction events inflicting bladder trauma characterized by loss of epithelium, oedema, haemorrhage, and neutrophil tissue infiltration. No significant trauma was identified when using MHZC. Conclusions: Considerable mucosal bladder trauma is inflicted by CECs which may be an overlooked risk factor for urinary tract infection. Catheters can be designed to minimize mucosal suction and reduce associated trauma. This may be a solution to reduce infection frequency and increase user comfort. Furthermore, the study demonstrates the potential of pigs as an attractive animal model for investigating urinary catheter performances.

Health-related quality of life and quality-adjusted progression free survival for carfilzomib and dexamethasone maintenance following salvage autologous stem-cell transplantation in patients with multiple myeloma: a randomized phase 2 trial by the Nordic Myeloma Study Group.

BACKGROUND: Decisions regarding maintenance therapy in patients with multiple myeloma should be based on both treatment efficacy and health-related quality of life (HRQL) consequences. In the CARFI trial, patients with first relapse of multiple myeloma underwent salvage autologous stem cell transplantation (salvage ASCT) before randomization to carfilzomib-dexamethasone maintenance therapy (Kd) or observation. The primary clinical endpoint was time to progression, which was extended by 8 months by Kd. The aim of this paper is to present the all HRQL endpoints of the CARFI trial including the HRQL effect of Kd maintenance therapy relative to observation. The primary HRQL endpoint was assessed by EORTC QLQ-C30 Summary score (QLQ-C30-sum) at 8 months follow-up. A key secondary HRQL endpoint was quality-adjusted progression-free-survival (QAPFS). METHODS: HRQL was assessed with EORTC QLQ-C30, EORTC QLQ-MY20 and FACT/GOG-Ntx at randomization and every second month during follow-up. HRQL data were analyzed with linear mixed effect models until 8 months follow-up. QAPFS per individual was calculated by multiplying progression-free survival (PFS) by two quality-adjustment metrics, the QLQ-C30-sum and EORTC Quality of Life Utility Measure-Core 10 dimensions (QLU-C10D). The QAPFS per treatment group was estimated with the Kaplan-Meier method. P < 0.05 was used for statistical significance, and a between-group minimal important difference of 10 points was interpreted as clinically relevant for the QLQ-C30-sum. RESULTS: 168 patients were randomized. HRQL questionnaire compliance was 93%. For the QLQ-C30-sum, the difference of 4.62 points (95% confidence interval (CI) -8.9: -0.4, p = 0.032) was not clinically relevant. PFS was 19.3 months for the Kd maintenance group and 16.8 months for the observation group; difference = 2.5 months (95% CI 0.5; 4.5). QAPFS based on the QLQ-C30-sum for the Kd maintenance group was 18.0 months (95% CI 16.4; 19.6) and for the observation group 15.0 months (95% CI 13.5; 16.5); difference = 3.0 months (95% CI 0.8-5.3). QAPFS based on the QLU-C10D for the Kd maintenance group was 17.5 months (95% CI 15.9; 19.2) and 14.0 months (95% CI 12.4; 15.5) for the observation group; difference = 3.5 months (95% CI 1.1-5.9). CONCLUSIONS: Kd maintenance therapy after salvage ASCT did not adversely affect overall HRQL, but adjustment for HRQL reduced the PFS compared to unadjusted PFS. PFS of maintenance therapy should be quality-adjusted to balance the benefits and HRQL impact.

Co-occurring orchid species associated with different low-abundance mycorrhizal fungi from the soil in a high-diversity conservation area in Denmark.

Plant-fungal interactions are ubiquitous across ecosystems and contribute significantly to plant ecology and evolution. All orchids form obligate symbiotic relationships with specific fungi for germination and early growth, and the distribution of terrestrial orchid species has been linked to occurrence and abundance of specific orchid mycorrhizal fungi (OMF) in the soil. The availability of OMF can therefore be a habitat requirement that is relevant to consider when establishing management and conservation strategies for threatened orchid species, but knowledge on the spatial distribution of OMF in soil is limited. We here studied the mycorrhizal associations of three terrestrial orchid species (Anacamptis pyramidalis, Orchis purpurea and Platanthera chlorantha) found in a local orchid diversity hotspot in eastern Denmark, and investigated the abundance of the identified mycorrhizal fungi in the surrounding soil. We applied ITS metabarcoding to samples of orchid roots, rhizosphere soil and bulk soil collected at three localities, supplemented with standard barcoding of root samples with OMF specific primers, and detected 22 Operational Taxonomic Units (OTUs) putatively identified as OMF. The three orchid species displayed different patterns of OMF associations, supporting the theory that association with specific fungi constitutes part of an orchid's ecological niche allowing co-occurrence of many species in orchid-rich habitats. The identified mycorrhizal partners in the basidiomycete families Tulasnellaceae and Ceratobasidiaceae (Cantharallales) were detected in low abundance in rhizosphere soil, and appeared almost absent from bulk soil at the localities. This finding highlights our limited knowledge of the ecology and trophic mode of OMF outside orchid tissues, as well as challenges in the detection of specific OMF with standard methods. Potential implications for management and conservation strategies are discussed.

New micro-hole zone catheter reduces residual urine and mucosal microtrauma in a lower urinary tract model.

Urinary tract infections (UTIs) are the main complication associated with clean intermittent catheterization (CIC) and are facilitated by post-void residual urine and trauma to the mucosa during voiding. The risk of UTI may be diminished by reducing the residual volumes and preventing microtrauma caused by mucosal suction through the eyelets of conventional eyelet catheters (CEC). A new micro-hole zone catheter (MHZC) was developed and tested in an ex vivo porcine lower urinary tract model and in vivo, in pigs, against a CEC. It was shown that, irrespective of the micro-hole diameter, the new catheter ensured increased flowrates and significantly lower residual volumes at the first flow-stop. Furthermore, with a micro-hole diameter of 0.4 mm, mucosal suction was virtually eliminated, regardless of the insertion depth or simulated intra-abdominal pressure mimicking sitting or standing humans. Pressure profile experiments and endoscopy studies indicated that the bladder gradually folds against the drainage tip of the new catheter, without blocking the flow, and, unlike with the CEC, sharp pressure variations and flow-stops did not occur during voiding. The MHZC outperformed the CEC in all tested scenarios and decreased residual volumes, thus potentially decreasing the risk of UTIs.

Attitudes towards deprescribing in geriatric psychiatry: A survey among older psychiatric outpatients.

Understanding the patient perspective is a significant part of the deprescribing process. This study aimed to explore the attitudes of older patients with psychiatric disorders towards deprescribing. A total of 72 of psychiatric outpatients (68% women; median age 76 years) completed the validated Danish version of the revised Patients' Attitudes Towards Deprescribing (rPATD) questionnaire. Patients used a median of eight medications (interquartile range 6-12), with 88%, 49% and 24% using antidepressants, antipsychotics and anxiolytics, respectively. Fifty-one percent of patients reported an intrinsic desire to stop one of their medications, while 92% would be willing to stop one on their physician's advice. Seventy-five percent of patients would be worried about missing out on future benefits following deprescribing and 37% had previous bad deprescribing experiences. Use of ≥8 regular medications was associated with more concerns about stopping medication and greater perceived burden of using medication, while use of antipsychotics was not associated with any differences in rPATD factor scores. It is crucial for health care professionals to be aware of patients' specific concerns and past experiences to promote a patient-centred deprescribing approach that takes into account the needs and preferences of older patients with psychiatric disorders.

Unsupervised item response theory models for assessing sample heterogeneity in patient-reported outcomes measures.

PURPOSE: Unsupervised item-response theory (IRT) models such as polytomous IRT based on recursive partitioning (IRTrees) and mixture IRT (MixIRT) models can be used to assess differential item functioning (DIF) in patient-reported outcome measures (PROMs) when the covariates associated with DIF are unknown a priori. This study examines the consistency of results for IRTrees and MixIRT models. METHODS: Data were from 4478 individuals in the Alberta Provincial Project on Outcome Assessment in Coronary Heart Disease registry who received cardiac angiography in Alberta, Canada, and completed the Hospital Anxiety and Depression Scale (HADS) depression subscale items. The partial credit model (PCM) based on recursive partitioning (PCTree) and mixture PCM (MixPCM) were used to identify covariates associated with differential response patterns to HADS depression subscale items. Model covariates included demographic and clinical characteristics. RESULTS: The median (interquartile range) age was 64.5(15.7) years, and 3522(78.5%) patients were male. The PCTree identified 4 terminal nodes (subgroups) defined by smoking status, age, and body mass index. A 3-class PCM fits the data well. The MixPCM latent classes were defined by age, disease indication, smoking status, comorbid diabetes, congestive heart failure, and chronic obstructive pulmonary disease. CONCLUSION: PCTree and MixPCM were not consistent in detecting covariates associated with differential interpretations of PROM items. Future research will use computer simulations to assess these models' Type I error and statistical power for identifying covariates associated with DIF.

Thrombocytopenia and platelet transfusions in ICU patients: an international inception cohort study (PLOT-ICU).

PURPOSE: Thrombocytopenia (platelet count < 150 × 109/L) is common in intensive care unit (ICU) patients and is likely associated with worse outcomes. In this study we present international contemporary data on thrombocytopenia in ICU patients. METHODS: We conducted a prospective cohort study in adult ICU patients in 52 ICUs across 10 countries. We assessed frequencies of thrombocytopenia, use of platelet transfusions and clinical outcomes including mortality. We evaluated pre-selected potential risk factors for the development of thrombocytopenia during ICU stay and associations between thrombocytopenia at ICU admission and 90-day mortality using pre-specified logistic regression analyses. RESULTS: We analysed 1166 ICU patients; the median age was 63 years and 39.5% were female. Overall, 43.2% (95% confidence interval (CI) 40.4-46.1) had thrombocytopenia; 23.4% (20-26) had thrombocytopenia at ICU admission, and 19.8% (17.6-22.2) developed thrombocytopenia during their ICU stay. Absence of acquired immune deficiency syndrome (AIDS), non-cancer-related immune deficiency, liver failure, male sex, septic shock, and bleeding at ICU admission were associated with the development of thrombocytopenia during ICU stay. Among patients with thrombocytopenia, 22.6% received platelet transfusion(s), and 64.3% of in-ICU transfusions were prophylactic. Patients with thrombocytopenia had higher occurrences of bleeding and death, fewer days alive without the use of life-support, and fewer days alive and out of hospital. Thrombocytopenia at ICU admission was associated with 90-day mortality (adjusted odds ratio 1.7; 95% CI 1.19-2.42). CONCLUSION: Thrombocytopenia occurred in 43% of critically ill patients and was associated with worse outcomes including increased mortality. Platelet transfusions were given to 23% of patients with thrombocytopenia and most were prophylactic.

Transcriptome profiling of Fraxinus excelsior genotypes infested by emerald ash borer.

European ash, Fraxinus excelsior is facing the double threat of ongoing devastation by the invasive fungal pathogen, Hymenoscyphus fraxineus and the imminent arrival of the non-native emerald ash borer (EAB), Agrilus planipennis. The spread of EAB which is currently moving westwards from European Russia and Ukraine into central Europe, poses an additional substantial threat to European ash, F. excelsior. While the molecular basis for resistance or variation in resistance among European ash genotypes is heavily investigated, comparatively little is known about the molecular ash traits involved in resistance against EAB. In this study we have gathered transcriptomic data from EAB inoculated genotypes of F. excelsior that have previously shown different levels of susceptibility to EAB. Resultant datasets show differential gene expression in susceptible and resistant genotypes in response to EAB infestation. This data will provide important information on the molecular basis of resistance to the EAB and allow the development of management plans to combat a pending threat of a culturally and ecologically important European tree species.

First cases of SARS-CoV-2 BA.2.86 in Denmark, 2023.

We describe 10 cases of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variant BA.2.86 detected in Denmark, including molecular characteristics and results from wastewater surveillance that indicate that the variant is circulating in the country at a low level. This new variant with many spike gene mutations was classified as a variant under monitoring by the World Health Organization on 17 August 2023. Further global monitoring of COVID-19, BA.2.86 and other SARS-CoV-2 variants is highly warranted.

Changes in Health-Related Quality of Life During Multiple Myeloma Treatment: A Qualitative Interview Study.

PURPOSE: To explore whether patients with multiple myeloma changed their construct of health-related quality of life during treatment. PARTICIPANTS & SETTING: 14 participants were selected from 10 hematology-oncology departments in Denmark. METHODOLOGIC APPROACH: This interview study used a prospective, longitudinal, exploratory design. Semistructured interviews were conducted while participants were undergoing active treatment for multiple myeloma and six months after the baseline interview. Interviews were analyzed using systematic text condensation. FINDINGS: The overall theme at baseline was insecurity, and the overall theme at six months was coping. The following subthemes were also identified based on participants' description of their health-related quality of life: concerns about having a meaningful life, dealing with everyday limitations, and maintaining social networks; adjusting expectations to abilities; expanding social networks; and exploring a meaningful life. IMPLICATIONS FOR NURSING: Patients' ability to use coping strategies should be considered when screening for rehabilitation needs. During systematic in-depth symptom screening, unmet rehabilitation needs (e.g., physical functioning, fatigue, pain) may become apparent.

Intensifying treatment in PET-positive multiple myeloma patients after upfront autologous stem cell transplantation.

18F-Fluorodeoxyglucose positron emission tomography/computed tomography (PET) positivity after first-line treatment with autologous stem cell transplantation (ASCT) in multiple myeloma is strongly correlated with reduced progression-free and overall survival. However, PET-positive patients who achieve PET negativity after treatment seem to have comparable outcomes to patients who were PET negative at diagnosis. Hence, giving PET-positive patients additional treatment may improve their outcome. In this phase II study, we screened first-line patients with very good partial response (VGPR) or better after ASCT with PET. PET-positive patients received four 28-day cycles of carfilzomib-lenalidomide-dexamethasone (KRd). Flow cytometry-based minimal residual disease (MRD) analysis was performed before and after treatment for correlation with PET. Overall, 159 patients were screened with PET. A total of 53 patients (33%) were PET positive and 57% of PET-positive patients were MRD negative, demonstrating that these response assessments are complementary. KRd consolidation converted 33% of PET-positive patients into PET negativity. MRD-negative patients were more likely to convert than MRD-positive patients. In summary, PET after ASCT detected residual disease in a substantial proportion of patients in VGPR or better, even in patients who were MRD negative, and KRd consolidation treatment changed PET status in 33% of patients.

Skin and Artificial Skin Models in Electrical Sensing Applications.

Skin electrical properties play a significant role in recording biopotentials by using electrophysiological sensors. To test and evaluate sensor systems, it is commonly accepted to employ artificial skin models due to complications associated with testing on living tissues. The first goal of this Review is to provide a systematic understanding of the relation between skin structure and skin electrochemical behavior at an appropriate depth for electrophysiological sensing applications through a focus on skin structure, electrochemical properties of skin, and theoretical models (equivalent circuits) representing skin electrochemical behavior. The second goal is to review artificial skin models mimicking the electrochemical properties of skin and to give suggestions for future studies on relevant skin models based on a comparison between the behavior of skin and that of artificial skin models. The Review aims to help the reader to analyze the relation between the structure, elements of the equivalent circuits, and the resulting impedance data for both skin and artificial skin models.

A glimmer of hope - ash genotypes with increased resistance to ash dieback pathogen show cross-resistance to emerald ash borer.

Plants rely on cross-resistance traits to defend against multiple, phylogenetically distinct enemies. These traits are often the result of long co-evolutionary histories. Biological invasions can force naïve plants to cope with novel, coincident pests, and pathogens. For example, European ash (Fraxinus excelsior) is substantially threatened by the emerald ash borer (EAB), Agrilus planipennis, a wood-boring beetle, and the ash dieback (ADB) pathogen, Hymenoscyphus fraxineus. Yet, plant cross-resistance traits against novel enemies are poorly explored and it is unknown whether naïve ash trees can defend against novel enemy complexes via cross-resistance mechanisms. To gain mechanistic insights, we quantified EAB performance on grafted replicates of ash genotypes varying in ADB resistance and characterized ash phloem chemistry with targeted and untargeted metabolomics. Emerald ash borer performed better on ADB-susceptible than on ADB-resistant genotypes. Moreover, changes in EAB performance aligned with differences in phloem chemical profiles between ADB-susceptible and ADB-resistant genotypes. We show that intraspecific variation in phloem chemistry in European ash can confer increased cross-resistance to invasive antagonists from different taxonomic kingdoms. Our study suggests that promotion of ADB-resistant ash genotypes may simultaneously help to control the ADB disease and reduce EAB-caused ash losses, which may be critical for the long-term stability of this keystone tree species.

Endophytic fungi related to the ash dieback causal agent encode signatures of pathogenicity on European ash.

Tree diseases constitute a significant threat to biodiversity worldwide. Pathogen discovery in natural habitats is of vital importance to understanding current and future threats and prioritising efforts towards developing disease management strategies. Ash dieback is a fungal disease of major conservational concern that is infecting common ash trees, Fraxinus excelsior, in Europe. The disease is caused by a non-native fungal pathogen, Hymenoscyphus fraxineus. Other dieback causing-species have not previously been identified in the genus Hymenoscyphus. Here, we discover the pathogenicity potential of two newly identified related species of Asian origin, H. koreanus and H. occultus, and one Europe-native related species, H. albidus. We sequence the genomes of all three Hymenoscyphus species and compare them to that of H. fraxineus. Phylogenetic analysis of core eukaryotic genes identified H. albidus and H. koreanus as sister species, whilst H. occultus diverged prior to these and H. fraxineus. All four Hymenoscyphus genomes are of comparable size (55-62 Mbp) and GC contents (42-44%) and encode for polymorphic secretomes. Surprisingly, 1133 predicted secreted proteins are shared between the ash dieback pathogen H. fraxineus and the three related Hymenoscyphus endophytes. Amongst shared secreted proteins are cell death-inducing effector candidates, such as necrosis, and ethylene-inducing peptide 1-like proteins, Nep1-like proteins, that are upregulated during in planta growth of all Hymenoscyphus species. Indeed, pathogenicity tests showed that all four related Hymenoscyphus species develop pathogenic growth on European ash stems, with native H. albidus being the least virulent. Our results identify the threat Hymenoscypohus species pose to the survival of European ash trees, and highlight the importance of promoting pathogen surveillance in environmental landscapes. Identifying new pathogens and including them in the screening for durable immunity of common ash trees is key to the long-term survival of ash in Europe.

'Personality and bipolar disorder: personality profiles of patients with remitted bipolar disorder and matched controls in a Danish sample'.

BACKGROUND: The aim of the study was to investigate whether patients with bipolar disorder (BD) in remission differ in personality traits compared with a healthy control group. METHODS: A sample of patients with BD (n = 44) was compared with an individually matched control group (n = 44) using the Danish version of the Revised NEO Personality Inventory (NEO PI-R). Paired t-tests were used to analyze differences between the two groups and multiple regression models to evaluate predictors of NEO scores in the patient group. RESULTS: Patients with BD reported significantly higher scores on both Neuroticism and Openness to Experience and lower scores on Conscientiousness. No differences were found on Extraversion and Agreeableness. The effect size for Neuroticism and its facets had a range from 0.77 to 1.45 SD.Statistically significant group differences were seen on 15 of 30 lower-level traits within all five high-order dimensions. There were large effect sizes for Trust (0.77) and Self-discipline (0.85), while the other statistically significant group differences were smaller with effect sizes in the range from 0.43 to 0.74 SD.However, patients with BD showed a profile with high-order dimensions and lower-level traits within one standard deviation from the mean score except for the lower-level trait Depression. CONCLUSIONS: Our findings suggest that patients with BD differ from healthy control persons with respect to higher levels of Neuroticism, Openness to Experience and lower scores on Agreeableness and on Conscientiousness, but prospective studies are needed to evaluate the implications of this finding.

Fungal succession in decomposing ash leaves colonized by the ash dieback pathogen Hymenoscyphus fraxineus or its harmless relative Hymenoscyphus albidus.

Introduction: The ascomycete Hymenoscyphus fraxineus, originating from Asia, is currently threatening common ash (Fraxinus excelsior) in Europe, massive ascospore production from the saprotrophic phase being a key determinant of its invasiveness. Methods: To consider whether fungal diversity and succession in decomposing leaf litter are affected by this invader, we used ITS-1 metabarcoding to profile changes in fungal community composition during overwintering. The subjected ash leaf petioles, collected from a diseased forest and a healthy ash stand hosting the harmless ash endophyte Hymenoscyphus albidus, were incubated in the forest floor of the diseased stand between October 2017 and June 2018 and harvested at 2-3-month intervals. Results: Total fungal DNA level showed a 3-fold increase during overwintering as estimated by FungiQuant qPCR. Petioles from the healthy site showed pronounced changes during overwintering; ascomycetes of the class Dothideomycetes were predominant after leaf shed, but the basidiomycete genus Mycena (class Agaricomycetes) became predominant by April, whereas H. albidus showed low prevalence. Petioles from the diseased site showed little change during overwintering; H. fraxineus was predominant, while Mycena spp. showed increased read proportion by June. Discussion: The low species richness and evenness in petioles from the diseased site in comparison to petioles from the healthy site were obviously related to tremendous infection pressure of H. fraxineus in diseased forests. Changes in leaf litter quality, owing to accumulation of host defense phenolics in the pathogen challenged leaves, and strong saprophytic competence of H. fraxineus are other factors that probably influence fungal succession. For additional comparison, we examined fungal community structure in petioles collected in the healthy stand in August 2013 and showing H. albidus ascomata. This species was similarly predominant in these petioles as H. fraxineus was in petioles from the diseased site, suggesting that both fungi have similar suppressive effects on fungal richness in petiole/rachis segments they have secured for completion of their life cycle. However, the ability of H. fraxineus to secure the entire leaf nerve system in diseased forests, in opposite to H. albidus, impacts the general diversity and successional trajectory of fungi in decomposing ash petioles.