To establish a possible role for the natural environment in the transmission of clinically relevant AMR bacteria to humans, a literature review was conducted to systematically collect and categorize ...evidence for human exposure to extended-spectrum β-lactamase-producing Enterobacteriaceae, methicillin-resistant Staphylococcus aureus, and vancomycin-resistant Enterococcus spp. in the environment. In total, 239 datasets adhered to inclusion criteria. AMR bacteria were detected at exposure-relevant sites (35/38), including recreational areas, drinking water, ambient air, and shellfish, and in fresh produce (8/16). More datasets were available for environmental compartments (139/157), including wildlife, water, soil, and air/dust. Quantitative data from exposure-relevant sites (6/35) and environmental compartments (11/139) were scarce. AMR bacteria were detected in the contamination sources (66/66) wastewater and manure, and molecular data supporting their transmission from wastewater to the environment (1/66) were found. The abundance of AMR bacteria at exposure-relevant sites suggests risk for human exposure. Of publications pertaining to both environmental and human isolates, however, only one compared isolates from samples that had a clear spatial and temporal relationship, and no direct evidence was found for transmission to humans through the environment. To what extent the environment, compared to the clinical and veterinary domains, contributes to human exposure needs to be quantified. AMR bacteria in the environment, including sites relevant for human exposure, originate from contamination sources. Intervention strategies targeted at these sources could therefore limit emission of AMR bacteria to the environment.
Background
Psoriasis is a common inflammatory disease in any age group, but also in older patients (≥ 65 years of age). Since older patients are often excluded from clinical trials, limited data ...specifically on this growing population are available, e.g. regarding the safety and performance of biological treatment.
Aims
We aimed to give insight into this specific population by comparing the drug survival and safety of biologics in older patients with that in younger patients.
Methods
In this real-world observational study, data from 3 academic and 15 non-academic centers in The Netherlands were extracted from the prospective BioCAPTURE registry. Biologics included in this study were tumor necrosis factor (TNF)-α, interleukin (IL)-17, IL-12/23, and IL-23 inhibitors. Patients were divided into two age groups: ≥ 65 years and < 65 years. The Charlson Comorbidity Index (CCI) was used to measure comorbid disease status, and all adverse events (AEs) that led to treatment discontinuation were classified according to the Medical Dictionary for Regulatory Activities (MedDRA) classification. All AEs that led to treatment discontinuation were studied to check whether they could be classified as serious AEs (SAEs). Kaplan–Meier survival curves for overall 5-year drug survival and split according to reasons of discontinuation (ineffectiveness or AEs) were constructed. Cox regression models were used to correct for possible confounders and to investigate associations with drug survival in both age groups separately. Psoriasis Area and Severity Index (PASI) scores during the first 2 years of treatment and at the time of treatment discontinuation were assessed and compared between age groups.
Results
A total of 890 patients were included, of whom 102 (11.4%) were aged ≥ 65 years. Body mass index, sex, and distribution of biologic classes (e.g. TNFα, IL12/23) were not significantly different between the two age groups. A significantly higher CCI score was found in older patients, indicative of more comorbidity (
p
< 0.001). The 5-year ineffectiveness-related drug survival was lower for older patients (44.5% vs. 60.5%;
p
= 0.006), and the 5-year overall (≥ 65 years: 32.4% vs. < 65 years: 42.1%;
p
= 0.144) and AE-related (≥ 65 years: 82.1% vs. < 65 years: 79.5%;
p
= 0.913) drug survival was comparable between age groups. Of all AEs (
n
= 155) that led to discontinuation, 16 (10.3%) were reported as SAEs but these only occurred in younger patients. After correcting for confounders, the same trends were observed in the drug survival outcomes. Linear regression analyses on PASI scores showed no statistical differences at 6, 12, 18, and 24 months of treatment between age groups.
Conclusions
This study in a substantial, well-defined, prospective cohort provides further support that the use of biologics in older patients seems well-tolerated and effective. Biologic discontinuation due to AEs did not occur more frequently in older patients. Older patients discontinued biologic treatment more often due to ineffectiveness, although no clear difference in PASI scores was observed. More real-world studies on physician- and patient-related factors in older patients are warranted.
Ex situ normothermic machine perfusion (NMP) is increasingly used for viability assessment of high‐risk donor livers, whereas dual hypothermic oxygenated machine perfusion (DHOPE) reduces ...ischemia‐reperfusion injury. We aimed to resuscitate and test the viability of initially‐discarded, high‐risk donor livers using sequential DHOPE and NMP with two different oxygen carriers: an artificial hemoglobin‐based oxygen carrier (HBOC) or red blood cells (RBC). In a prospective observational cohort study of 54 livers that underwent DHOPE‐NMP, the first 18 procedures were performed with a HBOC‐based perfusion solution and the subsequent 36 procedures were performed with an RBC‐based perfusion solution for the NMP phase. All but one livers were derived from extended criteria donation after circulatory death donors, with a median donor risk index of 2.84 (IQR 2.52–3.11). After functional assessment during NMP, 34 livers (63% utilization), met the viability criteria and were transplanted. One‐year graft and patient survival were 94% and 100%, respectively. Post‐transplant cholangiopathy occurred in 1 patient (3%). There were no significant differences in utilization rate and post‐transplant outcomes between the HBOC and RBC group. Ex situ machine perfusion using sequential DHOPE‐NMP for resuscitation and viability assessment of high‐risk donor livers results in excellent transplant outcomes, irrespective of the oxygen carrier used.
Sequential end‐ischemic hypothermic and normothermic machine perfusion results in safe transplantation of previously discarded, high‐risk, human donor livers, irrespective of the oxygen carrier used for normothermic perfusion.
Summary
Background
Drug survival is a marker for treatment success. To date, no analyses relating dermatological quality‐of‐life measures to drug survival have been published.
Objectives
(i) To ...describe 1‐year drug survival for adalimumab, etanercept and ustekinumab in a daily practice psoriasis cohort, and (ii) to introduce the concept of ‘happy’ drug survival, defined as Dermatology Life Quality Index (DLQI) ≤ 5 combined with being ‘on drug’ at a specific time point.
Methods
Data were extracted from a prospective registry. Drug survival was analysed using Kaplan–Meier estimates. ‘Happy’ drug survival was calculated, with data split into ‘happy’ (DLQI ≤ 5) vs. ‘unhappy’ (DLQI > 5) at baseline and months 3, 6, 9 and 12.
Results
249 treatment episodes were included (101 adalimumab, 82 etanercept, 66 ustekinumab). The 1‐year drug survival rates for ustekinumab, adalimumab and etanercept were 85%, 74% and 68%, respectively. Ustekinumab showed a better confounder‐corrected drug survival vs. etanercept hazard ratio (HR) 3·8, P = 0·02 and a trend towards better survival vs. adalimumab (HR 2·3, P = 0·1). At baseline, the majority (n = 115, 73%) was considered ‘unhappy’ and a minority ‘happy’ (n = 42, 27%) (ratio ‘happy’:‘unhappy’ was 1 : 2.7). The percentage of treatment episodes with ‘happy’ on‐drug patients increased to 79% after 1 year.
Conclusions
Ustekinumab showed a better overall drug survival than etanercept, and a trend towards a better overall drug survival than adalimumab. After 1 year, patients reported to be ‘happy’ in 79% of episodes and ‘unhappy’ in 21%. We introduced the new concept of ‘happy’ drug survival because the proportion of on‐drug patients with good quality of life is an important indicator for treatment success.
What's already known about this topic?
The Dermatology Life Quality Index is a validated score for dermatology‐specific quality‐of‐life measurements.
Drug survival studies of biologics for psoriasis show varying results and differ in study design and population.
To date, studies including drug survival rates for ustekinumab are scarce.
What does this study add?
The introduction of a concept named ‘happy’ drug survival, which combines drug survival rates with dermatology‐specific quality‐of‐life measures to evaluate treatments for psoriasis.
Analysis of ‘happy’ drug survival showed that the proportion of ‘on‐drug’ biologic users with a good quality of life increased from 27% to 79% after 1 year of treatment.
Ustekinumab showed a better overall drug survival vs. etanercept and a trend towards a better survival vs. adalimumab.
Patients vary in their preferences regarding involvement in medical decision-making. Current research does not provide complete explanation for this observed variation. Patient involvement in medical ...decision-making has been found to be influenced by various mechanisms, one of which could be patients' trust in physicians. The aim of this study was to examine whether trust in physicians fosters or impairs patient involvement in medical decision-making. This study also aimed to determine to what extent the relationship between trust and preferences regarding decision-making roles was influenced by the sociodemographic characteristics of the patients. We hypothesised that trust can both foster and impair patient involvement in medical decision-making.
A survey was sent out to members of the Nivel Dutch Health Care Consumer Panel in February 2016 (response rate = 47%, N = 703). The Wake Forest Physician Trust Scale was used to measure trust. Patient involvement was measured using two items based on the study published by Flynn and colleagues in 2006. Multiple regression analysis was used to analyse the relationship between trust and patient involvement.
We found a negative relationship between trust and patient involvement in medical decision-making in men. Women with high trust reported to be more involved in medical decision-making compared to men with high trust.
The results suggest that trust impairs involvement in medical decision-making for men but not for women. Further research could provide a more comprehensive explanation of the variation in patient preferences regarding involvement in medical decision-making to further elucidate which underlying mechanisms could enhance patient participation.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Summary
Background
The physical appearance of psoriasis can be cosmetically disfiguring, resulting in a substantial social burden for patients. An important aspect of this burden is the experience of ...stigmatization. While stigmatization is known to be disabling and stressful for patients, little is known about its correlates, and effective interventions are lacking.
Objectives
To examine predictor variables for perceived stigmatization in psoriasis.
Methods
Questionnaires were administered to 514 patients with psoriasis in a cross‐sectional study. Zero‐order correlation and multiple‐regression analyses were conducted including sociodemographic, disease‐related, personality, illness cognitions and social support predictor variables.
Results
Stigmatization was experienced by 73% of patients to some degree, and correlated with all five categories of predictor variables. In multiple‐regression analyses, stigmatization was associated with higher impact on daily life; lower education; higher disease visibility, severity and duration; higher levels of social inhibition; having a type D personality; and not having a partner.
Conclusions
The results indicate that perceived stigmatization is common in psoriasis, and can be predicted by sociodemographic, disease‐related and personality variables. These predictor variables provide indications of which patients are especially vulnerable regarding perceived stigmatization, which might be used in treatment.
What's already known about this topic?
Perceived stigmatization is common and distressing in patients with psoriasis.
Some of its predictors have been examined in small samples.
What does this study add?
This large study of 514 patients with psoriasis examined a combination of potential predictor variables, both previously examined and never before studied.
Sociodemographic, disease‐related and previously unstudied type D personality variables were found to be predictive of perceived stigmatization.
What are the clinical implications of this work?
These results provide an understanding of which patients may be especially vulnerable to stigmatization‐related problems, which may warrant special attention during treatment.
Atrophy is regarded a sensitive marker of neurodegenerative pathology. In addition to confirming the well-known presence of decreased global grey matter and hippocampal volumes in Alzheimer's ...disease, this study investigated whether deep grey matter structure also suffer degeneration in Alzheimer's disease, and whether such degeneration is associated with cognitive deterioration. In this cross-sectional correlation study, two groups were compared on volumes of seven subcortical regions: 70 memory complainers (MCs) and 69 subjects diagnosed with probable Alzheimer's disease. Using 3T 3D T1 MR images, volumes of nucleus accumbens, amygdala, caudate nucleus, hippocampus, pallidum, putamen and thalamus were automatically calculated by the FMRIB's Integrated Registration and Segmentation Tool (FIRST)—algorithm FMRIB's Software Library (FSL). Subsequently, the volumes of the different regions were correlated with cognitive test results. In addition to finding the expected association between hippocampal atrophy and cognitive decline in Alzheimer's disease, volumes of putamen and thalamus were significantly reduced in patients diagnosed with probable Alzheimer's disease. We also found that the decrease in volume correlated linearly with impaired global cognitive performance. These findings strongly suggest that, beside neo-cortical atrophy, deep grey matter structures in Alzheimer's disease suffer atrophy as well and that degenerative processes in the putamen and thalamus, like the hippocampus, may contribute to cognitive decline in Alzheimer's disease.
Retinal vessels provide a unique opportunity to study both systemic and cerebrovascular disease. Smaller retinal arteriolar calibers are strongly related to hypertension, whereas larger retinal ...venular calibers are more related to inflammation, cerebral hypoperfusion, and cerebrovascular disease. Whether retinal vessel calibers are related to dementia remains unclear.
We investigated whether retinal arteriolar and venular calibers are associated with risk of dementia, and its subtypes Alzheimer disease (AD) and vascular dementia, in the prospective population-based Rotterdam Study. Digitized retinal images were available in 5,553 participants aged 55 years or over and dementia-free at baseline (1990-1993). Participants were re-examined in 1993-1994, 1997-1999, and 2002-2004 and were continuously monitored for development of dementia.
During a mean follow-up of 11.6 years, 655 participants developed dementia. AD was diagnosed in 519 and vascular dementia in 73 participants. Larger venular calibers were associated with an increased risk of dementia, in particular vascular dementia (age- and sex-adjusted hazard ratio per SD increase: 1.31; 95% confidence interval 1.06-1.64), but not AD. The association remained significant after adjustment for stroke and cardiovascular risk factors. Smaller arteriolar calibers were also associated with an increased risk of vascular dementia, yet only when adjusted for venular calibers.
Retinal venular widening is associated with an increased risk of vascular dementia. Our findings are in line with previous observations in stroke and cerebral small-vessel disease and suggest that the association between larger retinal venular calibers and dementia may reflect cerebral hypoperfusion and subsequent ischemia.
Article Note: Funding sources: this investigator-initiated study was conducted with financial support from Almirall. The funding source had no influence on study design, data collection and analysis, ...or the content of the manuscript. Conflicts of interest: M.E.C.v.W. has carried out investigator-initiated research with financial support from Almirall and has conducted clinical trials for AbbVie, Celgene, Janssen, Leo Pharma, Lilly and Novartis. E.L.M.t.H. has carried out investigator-initiated research with financial support from Almirall and has conducted clinical trials for Novartis. P.C.M.v.d.K. served as the chief medical officer of the International Psoriasis Council and received fees for lectures and consultancies from Bristol Mayer Squib, UCB, Leo Pharma, Eli Lilly and Company, Dermavant, Almirall, Celgene Novartis, Janssen and AbbVie. E.M.G.J.d.J. has received research grants for the independent research fund of the Department of Dermatology, Radboud University Medical Centre, Nijmegen from AbbVie, Pfizer, Novartis, Janssen Pharmaceutica and Leo Pharma, has acted as consultant and/or paid speaker for and/or participated in research sponsored by companies that manufacture drugs used for the treatment of psoriasis including AbbVie, Janssen Pharmaceutica, Novartis, Lily, Celgene, Leo Pharma, UCB and Almirall. All funding is not personal but goes to the independent research fund of the Department of Dermatology at Radboud University Medical Centre Nijmegen, the Netherlands. S.F.K.L. has received research grants for investigator-initiated research by Almirall.
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