Comparison of surgical outcomes of Carlevale sutureless scleral fixation and Artisan Aphakia intraocular lens.

PURPOSE: To compare intra- and postoperative results of sutureless scleral fixated Carlevale intraocular lens (IOL) with iris fixated Artisan IOL. METHODS: Monocentre, retrospective analysis of refractive outcomes and intra- and postoperative complications of patients who received a Carlevale or Artisan IOL between January 2019 and March 2022. RESULTS: 178 eyes of 169 patients were included (101 Carlevale and 77 Artisan IOLs). The standard follow-up time was 1 month. Two statistically significant differences were found: in the deviation of the postoperative spherical equivalent of the refraction from the preoperative chosen IOL target (p = 0.019; mean deviation was -0.46 in the Carlevale and 0.08 in the Artisan group), and the number of eyes with complications between the Carlevale and Artisan groups (p = 0.003; 33 in the Carlevale and 42 in the Artisan group). CONCLUSION: The current study is the largest so far comparing both refractive outcomes and complications after implantation of Carlevale and Artisan IOL. The Carlevale IOL does not carry a greater complication risk on the short-term follow-up. This provides additional evidence that the Carlevale IOL has to be added to the armamentarium of the ophthalmic surgeon.

Exploring the choroidal vascular labyrinth and its molecular and structural roles in health and disease.

The choroid is a key player in maintaining ocular homeostasis and plays a role in a variety of chorioretinal diseases, many of which are poorly understood. Recent advances in the field of single-cell RNA sequencing have yielded valuable insights into the properties of choroidal endothelial cells (CECs). Here, we review the role of the choroid in various physiological and pathophysiological mechanisms, focusing on the role of CECs. We also discuss new insights regarding the phenotypic properties of CECs, CEC subpopulations, and the value of measuring transcriptomics in primary CEC cultures derived from post-mortem eyes. In addition, we discuss key phenotypic, structural, and functional differences that distinguish CECs from other endothelial cells such as retinal vascular endothelial cells. Understanding the specific clinical and molecular properties of the choroid will shed new light on the pathogenesis of the broad clinical range of chorioretinal diseases such as age-related macular degeneration, central serous chorioretinopathy and other diseases within the pachychoroid spectrum, uveitis, and diabetic choroidopathy. Although our knowledge is still relatively limited with respect to the clinical features and molecular pathways that underlie these chorioretinal diseases, we summarise new approaches and discuss future directions for gaining new insights into these sight-threatening diseases and highlight new therapeutic strategies such as pluripotent stem cell‒based technologies and gene therapy.

Coronary angiography findings in patients with shock-resistant ventricular fibrillation cardiac arrest.

INTRODUCTION: Shock-resistant ventricular fibrillation (VF) poses a therapeutic challenge during out-of-hospital cardiac arrest (OHCA). For these patients, new treatment strategies are under active investigation, yet underlying trigger(s) and substrate(s) have been poorly characterised, and evidence on coronary angiography (CAG) data is often limited to studies without a control group. METHODS: In our OHCA-registry, we studied CAG-findings in OHCA-patients with VF who underwent CAG after hospital arrival. We compared baseline demographics, arrest characteristics, CAG-findings and outcomes between patients with VF that was shock-resistant (defined as >3 shocks) or not shock-resistant (≤3 shocks). RESULTS: Baseline demographics, arrest location, bystander resuscitation and AED-use did not differ between 105 patients with and 196 patients without shock-resistant VF. Shock-resistant VF-patients required more shocks, with higher proportions endotracheal intubation, mechanical CPR, amiodaron and epinephrine. In both groups, significant coronary artery disease (≥1 stenosis >70%) was highly prevalent (78% vs. 77%, p = 0.76). Acute coronary occlusions (ACOs) were more prevalent in shock-resistant VF-patients (41% vs. 26%, p = 0.006). Chronic total occlusions did not differ between groups (29% vs. 33%, p = 0.47). There was an association between increasing numbers of shocks and a higher likelihood of ACO. Shock-resistant VF-patients had lower proportions 24-h survival (75% vs. 93%, p < 0.001) and survival to discharge (61% vs. 78%, p = 0.002). CONCLUSION: In this cohort of OHCA-patients with VF and CAG after transport, acute coronary occlusions were more prevalent in patients with shock-resistant VF compared to VF that was not shock-resistant, and their clinical outcome was worse. Confirmative studies are warranted for this potentially reversible therapeutic target.

Cancer prevalence higher in stroke patients than in the general population: the Dutch String-of-Pearls Institute (PSI) Stroke study.

BACKGROUND AND PURPOSE: The aim of this study was to assess the prevalence of cancer and its characteristics in patients with ischemic stroke and to compare this with cancer prevalence in the general population. METHODS: This was a multicenter cohort study with 2736 patients presenting with ischemic stroke or transient ischemic attack. The prevalence of cancer was assessed by interview and verified by reviewing all medical records. In stroke patients with a history of cancer, we studied the subtype of cancer and its treatment characteristics. We used the national database of The Netherlands Cancer Registry to calculate population-based age and sex cancer standardized prevalence ratios (SPRs) for patients with ischemic stroke. RESULTS: Cancer prevalence in ischemic stroke patients was 12%, corresponding to an SPR of 1.2 [95% confidence interval (CI), 1.0-1.3]. Increased SPRs were observed for cancer of the central nervous system (SPR, 18.2; 95% CI, 9.0-27.4), head and neck (SPR, 3.4; 95% CI, 2.3-4.6), lower respiratory tract (SPR, 2.4; 95% CI, 1.5-3.3) and urinary tract (SPR, 2.1; 95% CI, 1.4-2.9), but not for other cancer types. Cardiovascular risk factors, stroke etiology, treatment and outcome were not different between patients with or without a history of cancer. CONCLUSIONS: In stroke patients, the prevalence of cancer, most prominently cancer of the central nervous system, head and neck, lower respiratory and urinary tract, was higher than in the general population. Medical treatment for the prevention of stroke in cancer survivors deserves further study.

Determinants of in-hospital antibiotic prescription behaviour: a systematic review and formation of a comprehensive framework.

BACKGROUND: Knowledge of determinants that influence antibiotic prescription behaviour (APB) is essential for the successful implementation of antimicrobial stewardship interventions. The theory of planned behaviour (TPB) is an established model that describes how cognitions drive human behaviour. OBJECTIVES: The objective of this study was to identify the sociocultural and behavioural determinants that affect APB and to construct a TPB framework of behavioural intent. METHODS: The following online databases were searched: PubMed, Medline, Embase, Web of Science, Cochrane Library and Central. Studies published between July 2010 and July 2017 in European countries, the United States, Canada, New Zealand or Australia were included if they identified one or more determinants of physicians' APB. A systematic review was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. Based on the TPB, determinants were categorized in behavioural, normative and control beliefs, thus shaping a conceptual framework for APB. RESULTS: Nine studies were eligible for inclusion, and 16 determinants were identified. Determinants relating to fear of adverse outcome (5/9), tolerance of risk and uncertainty (5/9), hierarchy (6/9), and determinants concerning normative beliefs-particularly social team dynamics (6/9)-were most frequently reported. Beliefs about antimicrobial resistance and potential negative consequences of antibiotic use were rarely mentioned. CONCLUSIONS: Behavioural, normative and control beliefs are all relevant in APB. There is a need for quantitative studies to assess the weight of the individual determinants to be able to efficiently design and implement future stewardship interventions. The constructed framework enables a comprehensive approach towards understanding and altering APB.

White matter changes and gait decline in cerebral small vessel disease.

The relation between progression of cerebral small vessel disease (SVD) and gait decline is uncertain, and diffusion tensor imaging (DTI) studies on gait decline are lacking. We therefore investigated the longitudinal associations between (micro) structural brain changes and gait decline in SVD using DTI. 275 participants were included from the Radboud University Nijmegen Diffusion tensor and Magnetic resonance imaging Cohort (RUN DMC), a prospective cohort of participants with cerebral small vessel disease aged 50-85 years. Gait (using GAITRite) and magnetic resonance imaging measures were assessed during baseline (2006-2007) and follow-up (2011 - 2012). Linear regression analysis was used to investigate the association between changes in conventional magnetic resonance and diffusion tensor imaging measures and gait decline. Tract-based spatial statistics analysis was used to investigate region-specific associations between changes in white matter integrity and gait decline. 56.2% were male, mean age was 62.9 years (SD8.2), mean follow-up duration was 5.4 years (SD0.2) and mean gait speed decline was 0.2 m/s (SD0.2). Stride length decline was associated with white matter atrophy (ß = 0.16, p = 0.007), and increase in mean white matter radial diffusivity and mean diffusivity, and decrease in mean fractional anisotropy (respectively, ß = - 0.14, p = 0.009; ß = - 0.12, p = 0.018; ß = 0.10, p = 0.049), independent of age, sex, height, follow-up duration and baseline stride length. Tract-based spatial statistics analysis showed significant associations between stride length decline and fractional anisotropy decrease and mean diffusivity increase (primarily explained by radial diffusivity increase) in multiple white matter tracts, with the strongest associations found in the corpus callosum and corona radiata, independent of traditional small vessel disease markers. White matter atrophy and loss of white matter integrity are associated with gait decline in older adults with small vessel disease after 5 years of follow-up. These findings suggest that progression of SVD might play an important role in gait decline.

Willingness to accept chemotherapy and attitudes towards costs of cancer treatment; A multisite survey study in the Netherlands.

BACKGROUND: In the past years, interest in patient treatment preferences is growing. Our objectives were: (1) to assess and compare the minimal required benefit for patients with cancer, patients without cancer and healthcare professionals to make chemotherapy acceptable and (2) to obtain insight into attitudes towards societal costs of cancer treatment. PATIENTS AND METHODS: We performed a prospective survey consisting of hypothetical scenarios among patients with cancer, patients without cancer and healthcare professionals. Participants were asked to indicate the minimal desired benefit in terms of chance of cure, life prolongation and symptom relief which would make intensive and mild chemotherapy regimens acceptable. In two other scenarios, attitudes towards monthly costs for chemotherapy treatment were examined. RESULTS: The minimal benefit required to make chemotherapy acceptable did not differ between cancer and non-cancer patients, with respect to chance of cure (mean 57%), life prolongation (median 24 months) and symptom relief (mean 50%); healthcare providers were likely to accept the same chemotherapy regimen at lower thresholds (p < 0.01). Education level was an important explanatory variable and the differences between patients and healthcare professionals disappeared when corrected for education level. Opinions about the maximum acceptable costs for chemotherapy displayed a large spread between the groups. CONCLUSIONS: Minimal benefits to accept chemotherapy were not different between cancer and non-cancer patients, but are beyond what can generally can be achieved. Healthcare professionals were willing to accept chemotherapy for less benefit. This difference may be attributed to a difference in education level between the groups. Healthcare professionals rated the maximum acceptable societal cost for chemotherapy lower than patients.

Long-term depressive symptoms and anxiety after transient ischaemic attack or ischaemic stroke in young adults.

BACKGROUND AND PURPOSE: Few studies exist on long-term post-stroke depressive symptoms and anxiety in young adults, although these young patients have a particular interest in their long-term prognosis, given their usually long life expectancy and being in the midst of an active social, working and family life. The aims of this study were to investigate the prevalence of depressive symptoms and anxiety and their association with clinical and demographic variables and with functional outcome after stroke in young adults. METHODS AND RESULTS: Long-term prevalence of depressive symptoms and anxiety was calculated in 511 patients with a transient ischaemic attack or ischaemic stroke, aged 18-50 years, using the Hospital Anxiety and Depression scale, compared with 147 controls. Functional outcome was assessed with the modified Rankin Score (mRS) and the Instrumental Activities of Daily Living scale (IADL). 16.8% of patients had depressive symptoms and 23.0% had anxiety, versus 6.1% (P = 0.001) and 12.2% (P < 0.001) in controls. In ischaemic stroke patients, depressive symptoms and anxiety were associated with poor functional outcome (mRS > 2 or IADL < 8). CONCLUSION: Even a decade after stroke at young age, depressive symptoms and anxiety were prevalent and associated with poor functional outcome. Therefore, even in the long term, treating physicians should be aware of the long-term presence of these symptoms as their recognition may be the first step in improving long-term functional independence.

Modelling the temperature evolution of bone under high intensity focused ultrasound.

Magnetic resonance-guided high intensity focused ultrasound (MR-HIFU) has been clinically shown to be effective for palliative pain management in patients suffering from skeletal metastasis. The underlying mechanism is supposed to be periosteal denervation caused by ablative temperatures reached through ultrasound heating of the cortex. The challenge is exact temperature control during sonication as MR-based thermometry approaches for bone tissue are currently not available. Thus, in contrast to the MR-HIFU ablation of soft tissue, a thermometry feedback to the HIFU is lacking, and the treatment of bone metastasis is entirely based on temperature information acquired in the soft tissue adjacent to the bone surface. However, heating of the adjacent tissue depends on the exact sonication protocol and requires extensive modelling to estimate the actual temperature of the cortex. Here we develop a computational model to calculate the spatial temperature evolution in bone and the adjacent tissue during sonication. First, a ray-tracing technique is used to compute the heat production in each spatial point serving as a source term for the second part, where the actual temperature is calculated as a function of space and time by solving the Pennes bio-heat equation. Importantly, our model includes shear waves that arise at the bone interface as well as all geometrical considerations of transducer and bone geometry. The model was compared with a theoretical approach based on the far field approximation and an MR-HIFU experiment using a bone phantom. Furthermore, we investigated the contribution of shear waves to the heat production and resulting temperatures in bone. The temperature evolution predicted by our model was in accordance with the far field approximation and agreed well with the experimental data obtained in phantoms. Our model allows the simulation of the HIFU treatments of bone metastasis in patients and can be extended to a planning tool prior to MR-HIFU treatments.

Diffusion tensor imaging of the hippocampus predicts the risk of dementia; the RUN DMC study.

INTRODUCTION: Cerebral small vessel disease is one of the most important risk factors for dementia, and has been related to hippocampal atrophy, which is among the first observed changes on conventional MRI in patients with dementia. However, these volumetric changes might be preceded by loss of microstructural integrity of the hippocampus for which conventional MRI is not sensitive enough. Therefore, we investigated the relation between the hippocampal diffusion parameters and the risk of incident dementia, using diffusion tensor imaging, independent of hippocampal volume. METHODS: The RUNDMC study is a prospective study among 503 elderly with small vessel disease, without dementia, with 5 years follow-up in 2012 (99.6% response-rate). Cox regression analysis was performed to calculate hazard ratios for dementia, of fractional anisotropy and mean diffusivity within the hippocampus, adjusted for demographics, hippocampal volume, and white matter. This was repeated in participants without evident hippocampal volume loss, because in these participants the visible damage might not yet have already started, whereas damage might have started on a microstructural level. RESULTS: 43 participants developed dementia (8.6%), resulting in a 5.5-year cumulative risk of 11.1% (95%CI 7.7-14.6). Higher mean diffusivity was associated with an increased 5-year risk of dementia. In the subgroup of participants with the upper half hippocampal volume, higher hippocampal mean diffusivity, more than doubled the 5-year risk of dementia. CONCLUSION: This is the first prospective study showing a relation between a higher baseline hippocampal mean diffusivity and the risk of incident dementia in elderly with small vessel disease at 5-year follow-up, independent of hippocampal volume and white matter volume.

Behçet's disease, hospital-based prevalence and manifestations in the Rotterdam area.

INTRODUCTION: Behçet's disease is most prevalent in countries along the former Silk Road. Prevalence varies from 70-420 per 100,000 in Turkey, and 13.5-20 and 1-2 per 100,000 in Asia and Western Europe, respectively. Additionally, disease severity and morbidity might be correlated with ethnicity. We studied demography and morbidity in the Dutch cohort of patients with Behçet's disease and compared those with known figures. PATIENTS AND METHODS: The prevalence of Behçet's patients in the Rotterdam area was determined by comparing the total number of patients within the ethnic population with the number of patients diagnosed with Behçet's disease. Patient files of the Erasmus University Medical Centre (Erasmus MC) were reviewed for morbidity figures and compared with existing data. RESULTS: In total 84 Behçet's patients of Dutch, Turkish or Moroccan descent were identified in the Rotterdam area. Prevalence of Behçet's disease differed per ethnicity: 1, 71 and 39 per 100,000 for Dutch-Caucasians, Turks, and Moroccans, respectively. These figures are comparable with occurrence in West Turkey and Morocco. Within the studied Erasmus MC cohort no significant differences in morbidity appeared between the ethnic groups. However, uveitis and pustules were significantly more common in the Erasmus MC cohort as compared with UK, German, Turkish and Moroccan cohorts. DISCUSSION AND CONCLUSIONS: We present the first epidemiological study of Behçet's disease in the Netherlands. The prevalence of Behçet's disease in the studied Dutch region and in countries of ancestry is similar. Morbidity is equally spread, compared with other countries, but uveitis and pustules seem to be more common in the Netherlands.

[Prevention and control of infectious diseases from a disciplinary-law perspective]. / Preventie en bestrijding van infectieziekten in tuchtrechtelijk perspectief.

OBJECTIVE: To gain insight into the importance for medical disciplinary courts of the collective health interest in the prevention and control of infectious diseases. DESIGN: Descriptive retrospective study. METHOD: The electronic databases of the Dutch government gazette (Staatscourant) and the Netherlands' medical disciplinary courts were searched for disciplinary court rulings on actions and negligence in the prevention and control of infectious diseases. RESULTS: We found 67 verdicts relevant to our subject in the period 1995-2013. Of these 67 disciplinary hearings, 12 were filed by the Netherlands' health inspectorate, 29 by the patient and 26 by a representative or next of kin. The defendants included 31 medical specialists, 12 dentists and 11 general practitioners. The disciplinary tribunal imposed measures in 23 cases, including 5 suspensions. CONCLUSION: In the case of serious infectious diseases the disciplinary courts decide that the caregiver also has to take into account the interests of other parties than caregiver and the patient. Medical microbiologists in hospitals should even go so far as to surrender their responsibility for general patient safety, if they are unable to comply with the applicable medical guideline. It is also striking that in questions of vaccination the disciplinary court judge is inclined to put a child's health interests before parental authority. One final striking point is that the health inspectorate plays an important role as complainant in disciplinary cases concerning prevention of infection.

Beyond TGFß--novel ways to target airway and parenchymal fibrosis.

Within the lungs, fibrosis can affect both the parenchyma and the airways. Fibrosis is a hallmark pathological change in the parenchyma in patients with idiopathic pulmonary fibrosis (IPF), whilst in asthma or chronic obstructive pulmonary disease (COPD) fibrosis is a component of the remodelling of the airways. In the past decade, significant advances have been made in understanding the disease behaviour and pathogenesis of parenchymal and airway fibrosis and as a result a variety of novel therapeutic targets for slowing or preventing progression of these fibrotic changes have been identified. This review highlights a number of these targets and discusses the potential for treating parenchymal or airway fibrosis through these mediators/pathways in the future.

Comparing modelling techniques for analysing urban pluvial flooding.

Short peak rainfall intensities cause sewer systems to overflow leading to flooding of streets and houses. Due to climate change and densification of urban areas, this is expected to occur more often in the future. Hence, next to their minor (i.e. sewer) system, municipalities have to analyse their major (i.e. surface) system in order to anticipate urban flooding during extreme rainfall. Urban flood modelling techniques are powerful tools in both public and internal communications and transparently support design processes. To provide more insight into the (im)possibilities of different urban flood modelling techniques, simulation results have been compared for an extreme rainfall event. The results show that, although modelling software is tending to evolve towards coupled one-dimensional (1D)-two-dimensional (2D) simulation models, surface flow models, using an accurate digital elevation model, prove to be an easy and fast alternative to identify vulnerable locations in hilly and flat areas. In areas at the transition between hilly and flat, however, coupled 1D-2D simulation models give better results since catchments of major and minor systems can differ strongly in these areas. During the decision making process, surface flow models can provide a first insight that can be complemented with complex simulation models for critical locations.

Etiology of first-ever ischaemic stroke in European young adults: the 15 cities young stroke study.

BACKGROUND AND PURPOSE: Risk factors for IS in young adults differ between genders and evolve with age, but data on the age- and gender-specific differences by stroke etiology are scare. These features were compared based on individual patient data from 15 European stroke centers. METHODS: Stroke etiology was reported in detail for 3331 patients aged 15-49 years with first-ever IS according to Trial of Org in Acute Stroke Treatment (TOAST) criteria: large-artery atherosclerosis (LAA), cardioembolism (CE), small-vessel occlusion (SVO), other determined etiology, or undetermined etiology. CE was categorized into low- and high-risk sources. Other determined group was divided into dissection and other non-dissection causes. Comparisons were done using logistic regression, adjusting for age, gender, and center heterogeneity. RESULTS: Etiology remained undetermined in 39.6%. Other determined etiology was found in 21.6%, CE in 17.3%, SVO in 12.2%, and LAA in 9.3%. Other determined etiology was more common in females and younger patients, with cervical artery dissection being the single most common etiology (12.8%). CE was more common in younger patients. Within CE, the most frequent high-risk sources were atrial fibrillation/flutter (15.1%) and cardiomyopathy (11.5%). LAA, high-risk sources of CE, and SVO were more common in males. LAA and SVO showed an increasing frequency with age. No significant etiologic distribution differences were found amongst southern, central, or northern Europe. CONCLUSIONS: The etiology of IS in young adults has clear gender-specific patterns that change with age. A notable portion of these patients remains without an evident stroke mechanism according to TOAST criteria.

Exploring the use of actigraphy to investigate sleep problems in older people with intellectual disability.

BACKGROUND: The aim of this study was to explore the use of actigraphy to investigate sleep problems in a convenience sample of clients of Dutch intellectual disability (ID) care providers. Based on data obtained in a large multi-centre study on healthy ageing in people with ID, research questions were: 'To what degree are actigraphic measurements successful in this population?' and 'What is the influence of different sensitivity settings of the Actiwatch Sleep Analysis software on the distribution of sleep variables in this group?' METHODS: Data were collected in a cross-sectional descriptive study design. We included 563 participants, aged 50 years or older, with borderline to profound ID. Sleep-wake data were measured continuously during 14 days and nights using the Actiwatch AW7. A complete measurement of at least 7 days and nights, including at least one weekend day, was considered successful. Objective variables of sleep were analysed using different sensitivity settings of the Actiwatch AW7 Sleep Analysis software. RESULTS: In 200 participants (35.5%), a successful measurement was obtained. Unsuccessful measurements were caused primarily by problems with wearing the device and incomplete information on bed time and get up time. Of 382 participants who started wearing the Actiwatch, 354 (92.3%) wore it for at least 7 days. Application of different sensitivity settings of the Sleep Analysis software resulted in clear differences of all sleep parameters. CONCLUSIONS: Further research is needed into the validity of objective sleep parameters, as measured with the Actiwatch, for screening and epidemiological research in older people with ID. It needs to be investigated which sensitivity setting of the Actiwatch gives most valid results in this specific group, whereas reference data on sleep parameters and cut-off values are to be obtained.