Increased Intracranial Arterial Pulsatility and Microvascular Brain Damage in Pseudoxanthoma Elasticum.

BACKGROUND AND PURPOSE: Carotid siphon calcification might contribute to the high prevalence of cerebrovascular disease in pseudoxanthoma elasticum through increased arterial flow pulsatility. This study aimed to compare intracranial artery flow pulsatility, brain volumes, and small-vessel disease markers between patients with pseudoxanthoma elasticum and controls and the association between arterial calcification and pulsatility in pseudoxanthoma elasticum. MATERIALS AND METHODS: Fifty patients with pseudoxanthoma elasticum and 40 age- and sex-matched controls underwent 3T MR imaging, including 2D phase-contrast acquisitions for flow pulsatility in the assessment of ICA and MCA and FLAIR acquisitions for brain volumes, white matter lesions, and infarctions. All patients with pseudoxanthoma elasticum underwent CT scanning to measure siphon calcification. Flow pulsatility (2D phase-contrast), brain volumes, white matter lesions, and infarctions (3D T1 and 3D T2 FLAIR) were compared between patients and controls. The association between siphon calcification and pulsatility in pseudoxanthoma elasticum was tested with linear regression models. RESULTS: Patients with pseudoxanthoma elasticum (mean age, 57 [SD, 12] years; 24 men) had significantly higher pulsatility indexes (1.05; range, 0.94-1.21 versus 0.94; range, 0.82-1.04; P = .02), lower mean GM volumes (597 [SD, 53] mL versus 632 [SD, 53] mL; P < .01), more white matter lesions (2.6; range, 0.5-7.5 versus 1.1; range, 0.5-2.4) mL; P = .05), and more lacunar infarctions (64 versus 8, P = .04) than controls (mean age, 58 [SD, 11] years; 20 men). Carotid siphon calcification was associated with higher pulsatility indexes in patients with pseudoxanthoma elasticum (ß = 0.10; 95% CI, 0.01-0.18). CONCLUSIONS: Patients with pseudoxanthoma elasticum have increased intracranial artery flow pulsatility and measures of small-vessel disease. Carotid siphon calcification might underlie the high prevalence of cerebrovascular disease in pseudoxanthoma elasticum.

[Fall prevention in older adults: what if the physician's and the patient's risk evaluation vary?] / Valpreventie bij de oudere patiënt.

Falls may lead to functional impairment, fear of falling, decreased quality of life, high health care costs and mortality. A case of an older adult presented in this article, illustrates the multifactorial nature of risk of falling and fall prevention strategies. Recently, meta-analyses were performed to determine the effectiveness of interventions to prevent falls and to explore the effect of intervention components in reducing fear of falling. The single interventions whole body vibration, exercise and quality improvement strategies are associated with a reduction in number of fallers. Common components of multiple interventions significantly associated with a reduction in number of fallers are exercise, assistive technology, environmental modifications, quality improvement strategies and basic falls risk assessment. Interventions with meditation, holistic exercises or body awareness are more effective in reducing fear of falling than interventions without these components. The patient's risk evaluation and personal preferences should be taken into account when developing a treatment plan.

[Treatment of dementia]. / Behandeling van dementie.

- Treatment options for patients with dementia are limited. This article provides an overview of possible interventions, both pharmaceutical and non-pharmaceutical, for Alzheimer's disease, vascular dementia and mixed dementia.- Pharmaceutical treatment options include cholinesterase inhibitors, memantine and experimental medication. Cholinesterase inhibitors are only recommended for Alzheimer's disease and mixed dementia, not for vascular dementia or mild cognitive impairment. There is no proof of effectiveness for the other pharmaceutical options.- Interventions towards cardiovascular risk factors do not slow down cognitive decline.- Evidence is still lacking for other non-pharmaceutical interventions such as memory training and dietary supplements. Physical exercise may have a positive effect on dementia, but research is still ongoing.- Many patients with dementia exhibit behavioural changes such as agitation and depression. We recommend non-pharmaceutical interventions as a first step to lower the burden of this behaviour for both patients and caregivers.

Predictors of functional disability in mild cognitive impairment and dementia.

OBJECTIVE: Knowledge about factors predicting functional disability in mild cognitive impairment (MCI) and dementia would help health care providers to identify those patients who are at high risk of functional disability. Previous research is scarce and focused on only a small number of possible predictors. The aim of this study was to identify predictors of functional disability in patients with MCI and dementia. STUDY DESIGN: Cross-sectional cohort study. MAIN OUTCOME MEASURES: Data from patients who visited a memory clinic between 2011 and 2015 were evaluated. The Disability Assessment for Dementia (DAD) was used to assess functional disability. Patients diagnosed with MCI or dementia and with a DAD score available were included. This led to the inclusion of 474 patients. Univariate analyses with a broad range of variables were performed to detect factors that had a significant relationship to the DAD score. Age, gender and variables with a p-value of 0.1 or lower in the univariate analyses were taken into a multivariable analysis. This multiple linear regression analysis was performed to determine which variables were independently associated with the DAD score. MAIN RESULTS: Our multivariable model explained 42% of the variance in the DAD score. Independent predictors of the DAD score were age (B=0.03, 95%CI=0.002-0.05), gender (B=-0.43, 95%CI=-0.78 to -0.07), score on the Clinical Dementia Rating scale (CDR) (B=1.53, 95%CI=1.07-1.99 for CDR 1, B=2.93, 95%CI=2.28-3.58 for CDR 2, B=3.96, 95%CI=2.65-5.27 for CDR 3) and level of physical activity (B=0.56, 95%CI=0.05-1.07). CONCLUSION: Older age, male gender, higher CDR score and lower levels of physical activity are independent predictors of functional disability in MCI and dementia.

The validity of national hospital discharge register data on dementia: a comparative analysis using clinical data from a university medical centre.

BACKGROUND: Most information on the incidence and prognosis of dementia comes from small studies with limited precision and generalisability. Nationwide registers can be an alternative source of information, but only when the diagnosis is validly recorded. We assessed the validity of the Dutch Hospital Discharge Register (HDR). METHODS: HDR data on dementia diagnoses (ICD-9 codes 290.0; 290.1; 290.3; 290.4; 294.1; 331.0; 331.1; 331.82) in a university medical centre in the Netherlands were collected. Diagnoses were verified by using hospital medical records. Positive predictive values (PPVs) were calculated. Multivariate logistic regression models were used to evaluate determinants of inaccuracy in discharge diagnoses. RESULTS: A sample of the HDR data was used for this study (n = 340). PPV was 93.2% for overall dementia, indicating confirmation of 93.2% of HDR dementia diagnoses by the medical records. The accuracy of the diagnosis of overall dementia in patients aged ≥ 65 years was significantly higher compared with younger patients (PPV 95.5 % vs. 67.9%; p = 0.0001). There was no difference in the accuracy of the diagnosis between men and women and accuracy was not influenced by type of admission, comorbidity and polypharmacy. CONCLUSION: The results of this study show a high validity of the diagnosis of overall dementia in the HDR, making this register of great value for further nationwide research on dementia.

Classification of daily mental status in critically ill patients for research purposes.

PURPOSE: The purpose of this study is to develop a reliable tool for daily mental status classification in intensive care unit (ICU) patients for research purposes. Secondly, to identify patients with single, 1-day episodes of delirium and to compare them with patients having more delirium days or episodes. PATIENTS AND METHODS: A 5-step algorithm was designed, which includes Richmond Agitation Sedation Scale and Confusion Assessment Method for the ICU scores from bedside nurses, initiation of delirium treatment, chart review, and the Confusion Assessment Method for the ICU administered by researchers. This algorithm was validated against a reference standard of delirium experts. Subsequently, a cohort study was performed in patients admitted to a mixed ICU. RESULTS: In 65 paired observations, the algorithm had 0.75 sensitivity and 0.85 specificity. Applying the algorithm, interobserver agreement was high with mean Fleiss κ of 0.94 (5 raters) and 0.97 (4 raters). In the cohort study, 1112 patients were included of whom 535 (48%) became delirious. Single, 1-day episodes occurred in 43% of the delirious patients, whom were characterized by lower age compared with those with more delirium days. CONCLUSIONS: The algorithm for daily mental status classification seems to be a valid tool. In a substantial proportion of patients, delirium occurs only once during ICU admission lasting only 1 day.

The association between vitamin D and cognition: a systematic review.

Vitamin D insufficiency and deficiency are a major health care problem. The association between vitamin D levels and cognitive function is still under debate. We conducted a systematic review to assess the association between levels of vitamin D and cognition. Therefore, the databases of Embase and Pubmed were searched through June 2012 for observational studies relating vitamin D levels to cognition. Our initial search yielded 2182 articles. After applying exclusion criteria, there were 28 studies eligible for inclusion: 25 cross-sectional and 6 prospective studies (3 studies show cross-sectional as well as prospective data). The main finding of the 25 cross-sectional studies was a statistically significant worse outcome on one or more cognitive function tests or a higher frequency of dementia with lower vitamin D levels or intake in 18 out of 25 (72%) studies, whereas 7 (28%) studies failed to show an association. Four out of 6 (66.7%) prospective studies showed a higher risk of cognitive decline after a follow-up period of 4-7 years in participants with lower vitamin D levels at baseline. In conclusion, this review supports the hypothesis that hypovitaminosis D is associated with worse outcome on one or more cognitive function tests or a higher frequency of dementia in cross-sectional as well as prospective studies. Further studies should focus on the role of vitamin D supplementation in the prevention of cognitive decline in participants with low vitamin D levels.

Diagnostic accuracy of conventional or age adjusted D-dimer cut-off values in older patients with suspected venous thromboembolism: systematic review and meta-analysis.

OBJECTIVE: To review the diagnostic accuracy of D-dimer testing in older patients (>50 years) with suspected venous thromboembolism, using conventional or age adjusted D-dimer cut-off values. DESIGN: Systematic review and bivariate random effects meta-analysis. DATA SOURCES: We searched Medline and Embase for studies published before 21 June 2012 and we contacted the authors of primary studies. STUDY SELECTION: Primary studies that enrolled older patients with suspected venous thromboembolism in whom D-dimer testing, using both conventional (500 µg/L) and age adjusted (age × 10 µg/L) cut-off values, and reference testing were performed. For patients with a non-high clinical probability, 2 × 2 tables were reconstructed and stratified by age category and applied D-dimer cut-off level. RESULTS: 13 cohorts including 12,497 patients with a non-high clinical probability were included in the meta-analysis. The specificity of the conventional cut-off value decreased with increasing age, from 57.6% (95% confidence interval 51.4% to 63.6%) in patients aged 51-60 years to 39.4% (33.5% to 45.6%) in those aged 61-70, 24.5% (20.0% to 29.7% in those aged 71-80, and 14.7% (11.3% to 18.6%) in those aged >80. Age adjusted cut-off values revealed higher specificities over all age categories: 62.3% (56.2% to 68.0%), 49.5% (43.2% to 55.8%), 44.2% (38.0% to 50.5%), and 35.2% (29.4% to 41.5%), respectively. Sensitivities of the age adjusted cut-off remained above 97% in all age categories. CONCLUSIONS: The application of age adjusted cut-off values for D-dimer tests substantially increases specificity without modifying sensitivity, thereby improving the clinical utility of D-dimer testing in patients aged 50 or more with a non-high clinical probability.

Validation of two age dependent D-dimer cut-off values for exclusion of deep vein thrombosis in suspected elderly patients in primary care: retrospective, cross sectional, diagnostic analysis.

OBJECTIVE: To determine whether the use of age adapted D-dimer cut-off values can be translated to primary care patients who are suspected of deep vein thrombosis. DESIGN: Retrospective, cross sectional diagnostic study. SETTING: 110 primary care doctors affiliated with three hospitals in the Netherlands. PARTICIPANTS: 1374 consecutive patients (936 (68.1%) aged >50 years) with clinically suspected deep vein thrombosis. MAIN OUTCOME MEASURES: Proportion of patients with D-dimer values below two proposed age adapted cut-off levels (age in years × 10 µg/L in patients aged >50 years, or 750 µg/L in patients aged ≥ 60 years), in whom deep vein thrombosis could be excluded; and the number of false negative results. RESULTS: Using the Wells score, 647 patients had an unlikely clinical probability of deep vein thrombosis. In these patients (at all ages), deep vein thrombosis could be excluded in 309 (47.8%) using the age dependent cut-off value compared with 272 (42.0%) using the conventional cut-off value of 500 µg/L (increase 5.7%, 95% confidence interval 4.1% to 7.8%). This exclusion rate resulted in 0.5% and 0.3% false negative cases, respectively (increase 0.2%, 0.004% to 8.6%).The increase in exclusion rate by using the age dependent cut-off value was highest in the oldest patients. In patients older than 80 years, deep vein thrombosis could be safely excluded in 22 (35.5%) patients using the age dependent cut-off value compared with 13 (21.0%) using the conventional cut-off value (increase 14.5%, 6.8% to 25.8%). Compared with the age dependent cut-off value, the cut-off value of 750 µg/L had a similar exclusion rate (307 (47.4%) patients) and false negative rate (0.3%). CONCLUSIONS: Combined with a low clinical probability of deep vein thrombosis, use of the age dependent D-dimer cut-off value for patients older than 50 years or the cut-off value of 750 µg/L for patients aged 60 years and older resulted in a considerable increase in the proportion of patients in primary care in whom deep vein thrombosis could be safely excluded, compared with the conventional cut-off value of 500 µg/L.

Non-diagnosis decisions and non-treatment decisions in elderly patients with cardiovascular diseases, do they differ?--A systematic review.

The growth in the number of possible medical interventions in the past decennia necessitates physicians to consider whether to use them. Contrary to decisions to withhold treatment, little is known about "non-diagnosis decisions" (NDD) although their consequences seem to be more uncertain. Hence, we hypothesized that "determinants" and "reasons" for NDD are different from those that are associated with non-treatment decisions (NTD). We performed a systematic review on research on physicians' decisions to withhold or withdraw diagnostic or therapeutic interventions. A total of 11,773 unique citations published either in Medline, Embase, or the Cochrane databases were screened, of which 45 articles,--including 4 articles describing NDD in elderly patients suspected of cardiovascular diseases, were considered relevant and analysed in detail. "Determinants" and "reasons" for NDD and NTD were extracted, categorized into predefined categories, and compared with each other. Besides several similarities, we found various differences between NDD and NTD. The proportionality of an intervention (ie, the risk or burden of an intervention opposed to that of no intervention) was associated with NTD but not with NDD. Physician and care institution related characteristics, such as age of the physician or the employment of physician extenders, were more frequently associated with NDD than with NTD. Furthermore, the presence of non-resuscitate directives was correlated with NDD but not with NTD. This systematic review shows that there is little information on NDD in the current literature. Yet, there is not enough evidence to conclude whether NDD can be seen as a separate entity distinct from NTD. More research focusing on NDD seems needed.

Therapeutic challenges in elderly patients with symptomatic hypercalcaemia caused by primary hyperparathyroidism.

BACKGROUND: Hypercalcaemia resulting from primary hyperparathyroidism (PHPT) can cause a wide range of symptoms, including cognitive disorders, psychiatric symptoms and muscle weakness. Parathyroid surgery is the only definite cure for PHPT. When surgery is contraindicated or patients decide against it, several non-surgical treatment options are available. OBJECTIVE: To illustrate the treatment options of symptomatic hypercalcaemia caused by PHPT in the elderly and discuss these options in consideration of the available evidence. DESIGN: Consecutive case series. SETTING: University hospital. PATIENTS: Four older patients aged 79-87 years with symptomatic hypercalcaemia resulting from PHPT. RESULTS: Three patients had a parathyroid adenoma shown on a sestamibi scan. Normocalcaemia and resolution of symptoms was achieved by different treatment scenarios encompassing forced saline hydration, forced diuresis, intravenous pamidronate and cinacalcet, a calcimimetic drug. In one patient, no parathyroid abnormalities were revealed with imaging. Treatment with cinacalcet resulted in normocalcaemia and a strong improvement of symptoms. CONCLUSION: In clinical practice, different treatment scenarios are chosen for the treatment of elderly patients with symptomatic hypercalcaemia caused by PHPT. The introduction of cinacalcet offers a new treatment paradigm. We propose to apply cinacalcet preceding elective surgery as an alternative option to standard therapy or as maintenance dose when surgery is not possible.

Incidence of first acute myocardial infarction in the Netherlands.

OBJECTIVES: To study the incidence of first acute myocardial infarction (AMi) in the Netherlands. BACKGROUND: We recently showed that AMi patients can be followed longitudinally within dutch national medical registrations in a valid way. This makes it possible to provide nationwide incidence estimates of first AMi in the Netherlands. METHODS: New cases of first AMi in the dutch population in 2000 were identified through linkage of the national hospital discharge register, the population register and the cause of death statistics and included hospitalised first Ami patients and out-of-hospital deaths from first AMi. RESULTS: 31,777 patients with a first AMi were identified. The incidence (per 100,000 persons per year) increased from 2 in men aged <30 years to 2996 in men aged > or = 90 years. Corresponding figures for women ranged from 1 to 2226. The incidence was higher in men than in women in all age groups, but the male-to-female ratio decreased after the age of 50-59 year. Of all first AMI patients, 40% died before being admitted to a hospital. The proportion of non-hospitalised AMI patients increased with age in men after the age of 50-59 years. Within the age groups the proportion of out-of-hospital deaths was similar for men and women. CONCLUSION: Our study provides the first nationwide incidence estimates of first AMI in the Netherlands. Expected differences in incidence with regard to age and gender were shown. The large proportion of out-of-hospital deaths reinforces the importance of primary prevention AMI.

Short- and long-term mortality after acute myocardial infarction: comparison of patients with and without diabetes mellitus.

Aims To compare short- and long-term mortality after a first acute myocardial infarction (AMI) in patients with and without diabetes mellitus. Methods and results A nationwide cohort of 2,018 diabetic and 19,547 nondiabetic patients with a first hospitalized AMI in 1995 was identified through linkage of the national hospital discharge register and the population register. Follow-up for mortality lasted until the end of 2000. At 28 days and 5 years respectively, absolute mortality risks were 18 and 53% in diabetic men, 12 and 31% in nondiabetic men, 22 and 58% in diabetic women, and 19 and 42% in nondiabetic women. Crude mortality was significantly higher in diabetic patients than in nondiabetic patients in both men (28-day hazard ratio (HR) 1.55; 95% confidence interval (CI) 1.32-1.81, 5-year HR 2.01; 95% CI 1.84-2.21) and women (28-day HR 1.19; 95% CI 1.03-1.37, 5-year HR 1.53; 95% CI 1.40-1.67). After multivariate adjustment, risk differences became nonsignificant at 28 days, but diabetes was still associated with a significantly higher long-term mortality in both men (28-day HR 1.16; 95% CI 0.99-1.36, 5-year HR 1.49; 95% CI 1.36-1.64) and women (28-day HR 1.12; 95% CI 0.97-1.28, 5-year HR 1.39; 95% CI 1.27-1.52). The interaction between diabetes mellitus and gender did not reach significance in the analyses. Conclusion Our findings in an unselected cohort covering a complete nation show a significantly higher long-term mortality after a first acute myocardial infarction in diabetic patients. Yet, short-term mortality is not significantly higher in diabetic patients. Risks appear to be equally elevated in men and women.

[Delirium after a fractured hip in more than one-third of the patients]. / Delier na een heupfractuur bij ruim een derde van de patiënten.

OBJECTIVE: Inventarisation and evaluation of the incidence, risk factors, and prognosis of postoperative delirium in patients with a fractured hip admitted to a surgical ward. DESIGN: Descriptive study of patient records. METHOD: All patients with a fractured hip admitted to the surgical ward of the Jeroen Bosch Hospital, Den Bosch, the Netherlands, in 2004 were included and evaluated. Active multidisciplinary interventions for the recognition and treatment of delirium by non-pharmacological and pharmacological means take place in this surgical ward. The records of all patients from the surgical and geriatric wards were evaluated and the data were analysed statistically by means of univariate and multivariate logistic 'step-forward' regression analysis. RESULTS: 114 patients were included. The incidence of postoperative delirium was 37%. Older age was a significant risk factor for the development of delirium in both the univariate and the multivariate analysis after correcting for overestimation (p < 0.01). Several other factors, including sex, type of surgery, and medical history, had no effect on the risk of delirium. CONCLUSION: Delirium after a hip fracture is not rare; the most important risk factor is older age.

Decline in incidence of hospitalisation for acute myocardial infarction in the Netherlands from 1995 to 2000.

OBJECTIVE: To study the change in incidence of hospitalisation for a first acute myocardial infarction (AMI) in the Netherlands from 1995 to 2000. METHODS: Patients hospitalised with their first AMI in the Netherlands in 1995 and 2000 were identified through linkage of the national hospital discharge register and the population register. RESULTS: 21,565 patients hospitalised for their first AMI in 1995 and 19,058 patients hospitalised for their first AMI in 2000 were identified. In both years, the age specific incidence of hospitalisation for a first AMI was higher in men than in women and increased with age (up to 90 years). In both men and women, the age standardised incidence was lower in 2000 than in 1995, a decline of 19% (95% confidence interval 17% to 21%) and 17% (95% confidence interval 14% to 19%), respectively. CONCLUSIONS: Our study provides the first nationwide incidence estimates of first AMI in the Netherlands. From 1995 to 2000, the risk of AMI declined considerably.

[Trends in cardiovascular morbidity and mortality in the Netherlands, 1980-2000]. / Trends in cardiovasculaire ziekte en sterfte in Nederland, 1980-2000.

OBJECTIVE: To describe and interpret trends in cardiovascular morbidity and mortality among the Dutch population from 1980 to 2000, in particular the decline in hospital admissions for cardiovascular disease during the second half of the 1990s. DESIGN: Descriptive. METHOD: An analysis of trends in hospital admissions and cardiovascular mortality for the period 1980 to 2000 was performed using Dutch hospital admissions and mortality data, specified according to age and sex. These data were taken from the National Medical Register of hospital admissions maintained by Prismant and from the national statistics on the causes of mortality maintained by Statistics Netherlands. RESULTS: Since the 1970s, the mortality due to cardiovascular diseases has gradually declined. The age-adjusted mortality has declined by 36% for men and 33% for women. The decline is evident for both acute and chronic diseases. After an initial increase, hospital admission rates for cardiovascular disease showed a marked decline during the second half of the 1990s. The age-adjusted hospital admission rate has declined by 15% for men and 13% for women. This decline was seen in all age groups and for both acute and chronic diseases. CONCLUSION: The recent decrease in hospital admissions for cardiovascular disease during the second half of the 1990s appears mainly to be the consequence of a shift from hospital admissions to day care and outpatients' clinics.