Minifragment plating of the fibula in unstable ankle fractures.

INTRODUCTION: Only 6.4-17% of the load is transmitted through the fibula when weight-bearing. Plate fixation of distal fibular fractures using minifragments (≤ 2.8 mm) could lead to similar reduction with less implant removal (IR) rates, compared to small-fragment plates (3.5 mm). We hypothesized that the use of minifragment plates is at least similar in unscheduled secondary surgery. MATERIALS AND METHODS: In this retrospective cohort study, all patients with surgically treated distal fibular fractures between October 2015 and March 2021 were included. Patients treated with plate fixation using minifragments and patients treated with small-fragment plates were compared regarding the following outcomes: secondary dislocation, malreduction, implant malposition, nonunion, surgical site infections (SSI) and IR. RESULTS: Sixty-five patients (54.2%) received a minifragment implant (≤ 2.8 mm) and 55 patients (45.8%) received a small-fragment implant (3.5 mm). There were no patients needing secondary surgery in the minifragment group compared to 9 patients following fixation using small-fragment implants (3 with secondary dislocation, 5 with malreduction and 1 with malposition, p = 0.001). SSI rates were 3.1% for minifragment and 9.1% for small-fragment implants (p = 0.161). Implant removal was performed significantly less often following use of minifragment implants (17.8% and 53.2%, p < 0.001). CONCLUSIONS: In this cohort, minifragment plate fixation for distal fibular fractures is an adequate fixation method offering stable fixation with significant lower need for implant removal and comparable complications to small-fragment plates, although an adequately powered randomized controlled study is needed for implementation in a clinical setting. LEVEL OF EVIDENCE: Therapeutic, III.

Clinical trials and registries in haemophilia: Opponents or collaborators? Comparison of PUP data derived from different data sources.

INTRODUCTION: The "Guideline on the clinical investigation of recombinant and human plasma-derived factor VIII products" (ClinGL) provides the requirements for the performing of clinical trials (CTs) for marketing authorization in Europe. The number of eligible previously untreated patients (PUPs) for CTs might be difficult to meet because of the concurrent development of FVIII concentrates, and additional data sources must be explored. AIM: The extent to which CTs and the PedNet registry met relevant parameters, identified in the ClinGL, as well as inhibitor incidences were investigated in patients from both sources. METHODS: Anonymized data of eight CTs in 369 PUPs performed from 1987 to 2009 were compared with each other and with 632 PUPs (born 2000-2009) from PedNet. RESULTS: Clinical trials in PUPs performed for marketing authorization were too heterogeneous in their investigated parameters; therefore, a comparison of single factor concentrates was not possible. Data collection in PedNet met relevant parameters required for PUPs in accordance with the ClinGL. The overall inhibitor incidences were comparable (CT = 30.9% vs PedNet = 30.6%) when only severe haemophilia A (HA) patients from both data sources were considered. CONCLUSIONS: Previously performed CTs in PUPs were divergent, which prevented a direct comparison of outcomes. However, this study demonstrated that data from CTs and carefully designed registries may complement each other in the establishing of sufficient safety information for single products to improve clinical insights and support regulatory decisions.

Hypertension as a predictor of advanced colorectal cancer outcome and cetuximab treatment response.

Background: Adrenergic receptor stimulation is involved in the development of hypertension (htn) and has been implicated in cancer progression and dissemination of metastases in various tumours, including colon cancer. Adrenergic antagonists such as beta-blockers (bbs) demonstrate inhibition of invasion and migration in colon cancer cell lines and have been associated with decreased mortality in colorectal cancer (crc). We examined the association of baseline htn and bb use with overall (os) and progression-free survival (pfs) in patients with pretreated, chemotherapy refractory, metastatic crc (mcrc). We also examined baseline htn as a predictor of cetuximab efficacy. Methods: Using data from the Canadian Cancer Trials Group co.17 study [cetuximab vs. best supportive care (bsc)], we coded baseline htn and use of anti-htn medications, including bbs, for 572 patients. The chi-square test was used to assess the associations between those variables and baseline characteristics. Cox regression models were used for univariate and multivariate analyses of os and pfs by htn diagnosis and bb use. Results: Baseline htn, bb use, and anti-htn medication use were not found to be prognostic for improved os. Baseline htn and bb use were not significant predictors of cetuximab benefit. Conclusions: In chemorefractory mcrc, neither baseline htn nor bb use is a significant prognostic factor. Baseline htn and bb use are not predictive of cetuximab benefit. Further investigation to determine whether baseline htn or bb use have a similarly insignificant impact on prognosis in patients receiving earlier lines of treatment remains warranted.

[The importance of neuropsychological assessment for forensic psychiatric evaluations of defendants]. / De betekenis van neuropsychologisch onderzoek voor de rapportage pro Justitia.

BACKGROUND: In criminal law, increased interest is being shown in brain disorders, cognitive impairment and neuroimaging, particularly in connection with pre-trial reports. In a number of cases the contribution made by neuropsychology to the forensic diagnosis is considerable, and there is a need for further clarification.
AIM: To clarify the relevance of the neuropsychological assessment of suspects and to explore the implications for forensic psychiatry.
METHOD: We discuss recent literature and present a characteristic case selected from the Dutch jurisdiction.
RESULTS: On the basis of neuropsychological assessment it is possible to obtain insight into the relation between brain disorders and criminal behaviour. The case that we present shows that the court may consider the influence of cognitive impairment on behavior to be very important.
CONCLUSION: Neurocognitive disorders can make an important contribution to psychiatric assessments of defendants. In the forensic practice a combined diagnostic approach consisting of psychiatric evaluation, neurological assessment of behaviour, imaging techniques and neuropsychological assessment, is clearly preferable.

Knowledge, attitudes and practices towards blood donation in Barbados.

OBJECTIVE: To obtain information to devise strategies for a voluntary blood donor mobilisation campaign in Barbados. BACKGROUND: The World Health Organization (WHO) recommends that 100% blood should be collected from voluntary non-remunerated donors (VNRD), yet the majority of blood donations (75%) in Barbados are family/replacement donations. Increasing VNRD is paramount to achieving a safe, reliable blood supply, and understanding the population is a strategy suggested by the WHO to inform donor recruitment and education. METHODS: Participants in Barbados (n = 429) completed a self-administered questionnaire in 2014. The questionnaire comprised 31 questions, including demographics (age, gender, highest educational attainment) and blood donation-related knowledge, attitudes and practices. Analysis of variance, t-test and linear regression were used to analyse data. RESULTS: A total of 53% (n = 219) of participants had previously donated blood; almost half were family/replacement donors, and over one-third (36·2%) were lapsed donors and had not donated within the past 2 years. Knowledge deficits included blood donation requirements, deferral factors and maximum yearly donations. Most participants (79%) were willing to donate with more information. Participants with higher educational attainment and previous donors had higher total knowledge and attitude scores (P < 0·01). Single, female and younger participants were less likely to donate blood (P < 0·05). CONCLUSIONS: Barbados can likely increase voluntary blood donation rates by addressing knowledge deficits through education campaigns and increasing awareness of the need for donation.

The influence of glide path preparation on the failure rate of WaveOne reciprocating instruments.

INTRODUCTION: The aim of this study was to determine the influence of two different glide path preparation methods on the fracture rate of the Primary 25/08 WaveOne reciprocating instrument. Preparation times for different glide path methods and total time for root canal preparation, with and without prior glide path preparation, were also calculated. MATERIALS AND METHODS: ISO 15, 0.02 taper Endo-Training-Blocks (n = 300) were selected and randomly divided into three main groups (n = 100): Group 1: no glide path (control); Group 2: glide path preparation with stainless-steel hand files; and Group 3: glide path preparation with rotary PathFiles. The time taken to prepare each glide path was recorded. The specimens in each main group were then randomly assigned into five subgroups (n=20). New Primary 25/08 WaveOne files were used for canal preparation in each subgroup. The outcome was measured by recording how many simulated canals could be shaped with one WaveOne reciprocating file in each subgroup before instrument breakage occurred. The average time it took to prepare each of the simulated canals was calculated and recorded. The data were collected and statistically analysed using the ANOVA / Bonferroni test. RESULTS: Glide path preparation with PathFiles was significantly faster than with hand files (P<0.001). After the glide path preparation had been performed with PathFiles, a greater number of simulated canals could be prepared before failure of the WaveOne file (P<0.001). Root canal preparation time was significantly shorter (P<0.001) when an initial glide path had been prepared with PathFiles.

Increased risk of mortality associated with social isolation in older men: only when feeling lonely? Results from the Amsterdam Study of the Elderly (AMSTEL).

BACKGROUND: Loneliness has a significant influence on both physical and mental health. Few studies have investigated the possible associations of loneliness with mortality risk, impact on men and women and whether this impact concerns the situation of being alone (social isolation), experiencing loneliness (feeling lonely) or both. The current study investigated whether social isolation and feelings of loneliness in older men and women were associated with increased mortality risk, controlling for depression and other potentially confounding factors. METHOD: In our prospective cohort study of 4004 older persons aged 65-84 years with a 10-year follow-up of mortality data a Cox proportional hazard regression analysis was used to test whether social isolation factors and feelings of loneliness predicted an increased risk of mortality, controlling for psychiatric disorders and medical conditions, cognitive functioning, functional status and sociodemographic factors. RESULTS: At 10 years follow-up, significantly more men than women with feelings of loneliness at baseline had died. After adjustment for explanatory variables including social isolation, the mortality hazard ratio for feelings of loneliness was 1.30 [95% confidence interval (CI) 1.04-1.63] in men and 1.04 (95% CI 0.90-1.24) in women. No higher risk of mortality was found for social isolation. CONCLUSIONS: Feelings of loneliness rather than social isolation factors were found to be a major risk factor for increasing mortality in older men. Developing a better understanding of the nature of this association may help us to improve quality of life and longevity, especially in older men.

[Two subjects, each with a brain lesion and each prone to criminal behaviour: a plea for the involvement of a behavioural neurologist in the forensic psychiatric evaluation of such cases]. / Twee verdachten met hersenletsel en crimineel gedrag. De bijdrage van de neuroloog aan forensisch psychiatrische diagnostiek.

Interest in the neurobiology of criminal behaviour is increasing. Recent research emphasises the important role played by the frontal lobe in the processing of emotional and social information and in the controlling of behaviour. Damage to specific frontal structures in the brain may therefore lead to antisocial and criminal behaviour. On the basis of the case histories of two suspects with brain lesions, the impact of such damage on the forensic psychiatric diagnosis is discussed. A plea is made for the more frequent involvement of a neurologist in the diagnostic evaluation usually undertaken by the forensic psychiatrist.

[The lived-experiences of early-stage dementia and the feared suffering: an explorative survey]. / De beleving van beginnende dementie en het gevreesde lijden.

This qualitative explorative survey aimed at investigating the personal experiences of elderly people with early-stage dementia with regard to their illness and the extent to which they experience their situation as 'suffering'. In the Netherlands insight in this suffering is relevant with regard to ongoing debate on euthanasia and physician assisted death in early dementia. Participants in the study were 24 elderly (mean age 76.3 years) diagnosed with early-stage Alzheimer's disease. The semi-structured interviews were transcribed verbatim, and qualitatively analyzed. The elderly were found to be very capable of sharing experiences about their disease. They indicated not to experience their situation 'as a whole' as one of dreadful suffering. The gradual progression, which is distinctive of Alzheimer's disease, also allows people to adapt and adjust to their changing situation. As a result, the actual experiences of the disease can, in a positive manner, deviate from their anticipatory beliefs. The experiences of the participants appeared less negative than the ideas 'healthy' elderly often have about a life with dementia. The results from this study emphasize the importance of listening to the voices of people with dementia. Communication with elderly with Alzheimer's disease, is in the early stages quite possible and essential for advance care planning to be adjusted to their actual wishes and needs.

Homocysteine and inflammation: predictors of cognitive decline in older persons?

The aim of the current study was to examine the association between homocysteine and 6-year cognitive decline, and the modifying role of the inflammatory markers Interleukin-6 (IL-6), C-reactive protein (CRP) and alpha-1-antichymotrypsin (ACT). Data were collected within the Longitudinal Aging Study Amsterdam (ages >or=65 years) and analyzed using multiple longitudinal regression models (N=1257 of whom N=1076 had longitudinal data). Cognition was measured with the Mini-Mental State Examination (general cognition), Auditory Verbal Learning Test (memory), Coding Task (information processing speed) and Raven Coloured Progressive Matrices (fluid intelligence). Higher homocysteine at baseline was negatively associated with prolonged lower cognitive functioning and a faster rate of decline in information processing speed and fluid intelligence. The negative association between higher homocysteine and immediate recall was strongest in persons with a high level of IL-6. Only in the highest tertile of CRP, higher homocysteine was negatively associated with retention. In the middle tertile of ACT, higher homocysteine was associated with lower information processing speed and faster decline. Both in the lower and middle tertile of CRP, higher homocysteine was associated with a faster rate of decline in information processing speed. The results implicate that a combination of both risk factors may be used as a marker for cognitive impairment.

Distinct brain systems underlie the processing of valence and arousal of affective pictures.

Valence and arousal are thought to be the primary dimensions of human emotion. However, the degree to which valence and arousal interact in determining brain responses to emotional pictures is still elusive. This functional MRI study aimed to delineate neural systems responding to valence and arousal, and their interaction. We measured neural activation in healthy females (N=23) to affective pictures using a 2 (Valence) x 2 (Arousal) design. Results show that arousal was preferentially processed by middle temporal gyrus, hippocampus and ventrolateral prefrontal cortex. Regions responding to negative valence included visual and lateral prefrontal regions, positive valence activated middle temporal and orbitofrontal areas. Importantly, distinct arousal-by-valence interactions were present in anterior insula (negative pictures), and in occipital cortex, parahippocampal gyrus and posterior cingulate (positive pictures). These data demonstrate that the brain not only differentiates between valence and arousal but also responds to specific combinations of these two, thereby highlighting the sophisticated nature of emotion processing in (female) human subjects.

The effect of anxiety and depression on decline of memory function in Alzheimer's disease.

BACKGROUND: Patients with Alzheimer's disease (AD) and concomitant atrophy of the hippocampus may be extra vulnerable to the consequences of psychological distress, leading to greater decline in memory function. The present study investigated whether symptoms of anxiety and depression predict decline of memory function in elderly people diagnosed with early stage AD. METHODS: A sample of 44 elderly people diagnosed with early stage AD was tested on their memory function, anxiety and depression and confounding variables with one year follow-up. Episodic memory was measured with a modified Dutch version of the Auditory Verbal Learning Test (AVLT) which measures learning and recall abilities. Linear regression analyses were used to investigate the association between anxiety and depressive symptoms and decline of memory function. RESULTS: Anxiety symptoms predicted a smaller decline in learning on the AVLT. Anxiety symptoms did not predict decline on the recall of the AVLT. No association was found between depressive symptoms and decline in either learning or recall of the AVLT. CONCLUSIONS: In early AD, symptoms of anxiety and depression generally seem to be mild, and do not accelerate decline of memory function over time. On the contrary, anxiety symptoms were found to predict a smaller decline in memory function.

Depression and excess mortality: evidence for a dose response relation in community living elderly.

CONTEXT: Depression is associated with an increased mortality risk. It is not known to what extent depression characteristics such as severity and length of exposure to depression contribute to the association with excess mortality. OBJECTIVES: To investigate the association between depression severity and duration with mortality in community-living elderly. DESIGN: Two-wave prospective cohort study with 10-year follow-up of vital status. Assessment of depression at baseline and at three year follow-up (GMS-AGECAT). Cox proportional hazards analyses of mortality with depression according to severity and length of exposure, adjusted for demographic variables, physical illnesses, cognitive decline and functional disabilities. SETTING AND PARTICIPANTS: Randomly selected cohort of 3 746 non-demented older community-living persons in the city of Amsterdam. MAIN OUTCOME MEASURES: Excess mortality of both the baseline cohort, and of non-demented subjects participating in both assessments (n = 1989). RESULTS: Both moderate (MHR 1.29, 95% CI 1.03-1.61) and severe depression (MHR 1.34, 95% CI 1.07-1.68) predicted 10-year mortality after multivariate adjustment. Chronic depression was associated with a 41% higher mortality risk in 6-year follow-up compared to subjects without depression. CONCLUSIONS: Severity and chronicity of depression are associated with a higher mortality risk. In combination with other findings this is suggestive of a causal relationship and may have implications for both preventive and treatment strategies of late-life depression.

Total cholesterol and oxysterols: early markers for cognitive decline in elderly?

In this prospective study we examined whether total cholesterol and the oxysterols 24S- and 27-hydroxycholesterol were related to cognitive performance and rate of cognitive decline in elderly, and whether these associations were modified by ApoE epsilon 4. Data were collected during 6 years of follow-up as part of the Longitudinal Aging Study Amsterdam (N=1181, age >or=65 years), and analyzed using generalized estimating equations. Cognitive performance was measured with the mini-mental state examination (general cognition), the auditory verbal learning test (memory) and the coding task (information processing speed). Lower cholesterol at baseline was negatively associated with both general cognition (p=.012) and information processing speed (p=.045). ApoE modified the association between cholesterol and cognitive decline, and the association between the ratio of 27-hydroxycholesterol to cholesterol and cognitive functioning. In ApoE epsilon 4 carriers, lower cholesterol was related to a higher rate of decline on information processing speed (p=.006), and a higher ratio of 27-hydroxycholesterol to cholesterol was related to a lower level of general performance (p=.002) and memory functioning (p=.045). The results implicate that lower total cholesterol may be considered as a frailty marker, predictive of lower cognitive functioning in elderly.

Development of classification models for early identification of persons at risk for persistent cognitive decline.

OBJECTIVE: To develop two classification models for use in primary care to aid early identification of persons at risk for persistent cognitive decline. METHODS: Data were used from the Longitudinal Aging Study Amsterdam (LASA), an ongoing populationbased study. The study sample consisted of 2,021 non-demented men and women aged 58-88 years. Data on relevant predictors of persistent cognitive decline were collected at baseline. RESULTS: The incidence of persistent cognitive decline after three years of follow-up was 4.0 %. In the first model, in which predictors already known or otherwise easily assessed (first set) were included, age was the strongest predictor of persistent cognitive decline, with an increased risk for persons > 75. In addition, having memory problems, low education, and a MMSE score of < or = 24, resulted in a predictive value for persistent cognitive decline of 43.5 %. In the second classification model, in addition to the first set, predictors requiring additional measurement (e.g. markers determined in blood) were included in the analyses. Age was again the strongest predictor of persistent cognitive decline. In persons > 75 years, having a low total cholesterol level (< 5.0 mmol/L) and a MMSE score of < or = 24 resulted in a predictive value of 30.0 %. CONCLUSIONS: Both models lead to a substantial increase of the predictive value for persistent cognitive decline, that is from 4.0 % to 43.5 % and 30.0 %, and may identify to a large extent a different subsample of persons who are at risk for persistent cognitive decline. The developed classification trees could be useful for case-finding of persons at risk for future persistent cognitive decline who are therefore at risk for dementia, in a feasible and cost-effective manner.

Finding the service you need: human centered design of a Digital Interactive Social Chart in DEMentia care (DEM-DISC).

Community dwelling people with dementia and their informal carers experience a lot of problems. In the course of the disease process people with dementia become more dependent on others and professional help is often necessary. Many informal carers and people with dementia experience unmet needs with regard to information on the disease and on the available care and welfare offer, therefore they tend not to utilize the broad spectrum of available care and welfare services. This can have very negative consequences like unsafe situations, social isolation of the person with dementia and overburden of informal carers with consequent increased risk of illness for them. The development of a DEMentia specific Digital Interactive Social Chart (DEM-DISC) may counteract these problems. DEM-DISC is a demand oriented website for people with dementia and their carers, which is easy, accessible and provides users with customized information on healthcare and welfare services. DEM-DISC is developed according to the human centered design principles, this means that people with dementia, informal carers and healthcare professionals were involved throughout the development process. This paper describes the development of DEM-DISC from four perspectives, a domain specific content perspective, an ICT perspective, a user perspective and an organizational perspective. The aims and most important results from each perspective will be discussed. It is concluded that the human centered design was a valuable method for the development of the DEM-DISC.

BDI-modelling of complex intracellular dynamics.

A BDI-based continuous-time modelling approach for intracellular dynamics is presented. It is shown how temporalized BDI-models make it possible to model intracellular biochemical processes as decision processes. By abstracting from some of the details of the biochemical pathways, the model achieves understanding in nearly intuitive terms, without losing veracity: classical intentional state properties such as beliefs, desires and intentions are founded in reality through precise biochemical relations. In an extensive example, the complex regulation of Escherichia coli vis-à-vis lactose, glucose and oxygen is simulated as a discrete-state, continuous-time temporal decision manager. Thus a bridge is introduced between two different scientific areas: the area of BDI-modelling and the area of intracellular dynamics.