DEL-FINE: a new tool for assessing the delirogenic properties of drugs of relevance for European pharmacotherapy.

This article presents a list of potentially delirogenic properties of drugs that are currently of relevance to drug therapy in Europe, which was created through a Delphi process including experts from professions relevant to diagnosis and treatment of delirium. The Diagnostic and Statistical Manual of Mental Disorders 5 (DSM 5) defines delirium as a disturbance in attention, awareness and cognition that develops over a short period of time and fluctuates. Possible causes of delirium are manifold: usually delirium is considered to develop in a multifactorial way, caused by inalterable parameters, such as advanced age and pre-existing cognitive impairment and precipitated by modifiable parameters, such as the use of certain drugs or substance withdrawal. Delirium is a serious condition with a pronounced impact on morbidity, mortality and costs to the healthcare system. Circumstances and drugs that might precipitate or worsen delirium should therefore be avoided whenever possible. A list of drugs that might have a detrimental influence on the emergence and duration of delirium has been created using the terms "delirogenity" and "delirogenic" to describe the potential of a drug or withdrawal to cause or worsen delirium. The results are novel and noteworthy, as their focus is on substances relevant to European pharmacotherapy. Furthermore, they represent a methodical consensus from a group of experts of a wide variety of professions relevant to the prevention, diagnosis and treatment of delirium, such as nursing, pharmacy, pharmacology, surgical and internal medicine, neurology, psychiatry, intensive care and medicine, with working, teaching and scientific experience in several European countries practicing both in primary and secondary care.

Four-wheeled walker related injuries in older adults in the Netherlands.

BACKGROUND: With ageing populations worldwide, mobility devices are used more than ever. In the current literature there is no consensus whether the available mobility devices safely improve the mobility of their users. Also, evidence is lacking concerning the risks and types of injuries sustained while using a four-wheeled walker. OBJECTIVE: To assess injury risks and injury patterns in older adults (≥65 years) who presented at Emergency Departments (ED) in the Netherlands with an injury due to using a four-wheeled walker. DESIGN AND SETTING: In this study, the Dutch Injury Surveillance System was used to obtain a national representative sample of annual ED visits in the Netherlands in the adult population (≥65 years) sustaining an injury while using a four-wheeled walker. The numbers of four-wheeled walker users in the Netherlands were obtained from the national insurance board. The numbers of ED visits were divided by the numbers of four-wheeled walker users to calculate age- and sex-specific injury risks. RESULTS: Annually 1869 older adults visited an ED after sustaining an injury while using a four-wheeled walker. Falls were the main cause of injury (96%). The injury risk was 3.1 per 100 users of four-wheeled walkers. Women (3.5 per 100 users) had a higher risk than men (2.0 per 100 users). Injury risk was the highest in women aged 85 years and older (6.2 per 100 users). The majority of injuries were fractures (60%) with hip fracture (25%) being the most common injury. Nearly half of all four-wheeled walker related injuries required hospitalisation, mostly due to hip fractures. Healthcare costs per injury were approximately €12 000. CONCLUSIONS: This study presents evidence that older adults experiencing a fall while using a four-wheeled walker are at high risk to suffer severe injuries.

Postoperative cognitive dysfunction in geriatric patients.

Postoperative cognitive dysfunction (POCD) is a severe long-term complication after surgical procedures. POCD is mainly seen among geriatric patients. Hospitalization, extent of surgery, and systemic inflammatory response might contribute to POCD. The possible influence of the type of anesthesia is discussed. POCD is often not recognized; thus, incidence rates are likely to be underestimated (19-40%). POCD is associated with major consequences for the individual patient, e.g., delayed long-term recovery, reduced quality of life, and an increased mortality rate. Multiple risk factors have been identified over the last decade. However, the exact etiology is still unknown. This mini-review summarizes the recent developments concerning POCD prevention, diagnosis, and treatment.

Perioperative care of the older patient.

Nearly 60% of the Dutch population undergoing surgery is aged 65 years and over. Older patients are at increased risk of developing perioperative complications (e.g., myocardial infarction, pneumonia, or delirium), which may lead to a prolonged hospital stay or death. Preoperative risk stratification calculates a patient's risk by evaluating the presence and extent of frailty, pathophysiological risk factors, type of surgery, and the results of (additional) testing. Type of anesthesia, fluid management, and pain management affect outcome of surgery. Recent developments focus on multimodal perioperative care of the older patient, using minimally invasive surgery, postoperative anesthesiology rounds, and early geriatric consultation.

Preventing and treating dehydration in the elderly during periods of illness and warm weather.

OBJECTIVE: Translate the available knowledge on ageing and dehydration into main messages for clinical practice. MAIN POINTS: Older people are more susceptible to dehydration than younger people. This is partly due to lack of thirst sensation and changes in the water and sodium balance that naturally occur as people age. It is also, to some degree, attributable to the fact that elderly people, both those living at home and those living in institutions, often have various impairments, disabilities and/or handicaps (comorbidity). They also tend to use numerous drugs and medication for these illnesses (polypharmacy). Multimorbidity and polypharmacy often overstress the normal age-related physiological changes in the water and sodium balance and therefore increase elderly people's risk of dehydration,especially during intercurrent infections or warm weather. Elderly people, whether they are living on their own or in an institution, and especially elderly people that can no longer take care of themselves because of cognitive, sensory, motor and/or ADL impairments, need extra help to stay hydrated. The most important strategy is simply a matter of ensuring that elderly people consume a sufficient amount of fluids (at least 1.7 liters every 24 hours). Additional strategies include making healthy drinks and water easily available and accessible at all times and reminding and encouraging the elderly to consume these fluids. Elderly people should not be encouraged to consume large amounts of fluids at once but rather small amounts throughout the day. When the recommended fluid intake cannot, for whatever reason, be realized, fluids can be administered via catheter or by hypodermoclysis. In more specific and severe cases, fluids can be administered intravenously. CONCLUSION: The prevention, signaling and treatment of dehydration in the elderly is an important multidisciplinary endeavor. Formal and informal care providers need to continuously be aware of the risk factors and signs of dehydration in the elderly, especially during periods of very warm weather and when older people are ill. Standard professional care for high risk patients is imperative.

Improvement of spontaneous speech in early stage Alzheimer's with rivastigmine.

OBJECTIVES: Placebo-controlled trials have shown that rivastigmine can delay cognitive deterioration in patients with mild to moderate Alzheimer's disease (AD). Benefits on cognitive functioning, as measured with the ADAS-Cog, occur on a daily dose of 6-12 mg when used for at least 6 months. The effect of rivastigmine on the adequacy of spontaneous speech is unknown. This study aimed to (i) compare the spontaneous speech of AD patients with the spontaneous speech of persons with normal cognition, (ii) compare the spontaneous speech of the same group of AD patients before and after treatment with rivastigmine. METHODS: Spontaneous speech of AD patients (n=9) was compared with that of healthy elderly volunteers (n=8). In the patient group, spontaneous speech was analysed before and after treatment with rivastigmine. RESULTS: Before treatment, 100% discrimination was found between the spontaneous speech of AD patients and of healthy volunteers based on two linguistic parameters: empty words and compound sentences. After treatment with rivastigmine the spontaneous speech of the AD patients improved on these two variables, while the ADAS-Cog scores decreased. Mean interval between the two spontaneous speech samples was 8.89 months. CONCLUSION: Assessment of spontaneous speech might be a valid parameter to discriminate between normal cognition and AD, and to evaluate the effects of anti-AD medication.

Higher serum vitamin D3 levels are associated with better cognitive test performance in patients with Alzheimer's disease.

BACKGROUND/AIMS: Recent studies suggest that vitamin D metabolites may be important for preserving cognitive function via specific neuroprotective effects. No large studies have examined the association between vitamin D status and cognition. METHODS: In this cross-sectional study, we analyzed the serum 25-hydroxyvitamin D(3) levels and Mini-Mental State Examination (MMSE) test scores of 225 older outpatients who were diagnosed as having probable Alzheimer's disease (AD). In addition to the 25-hydroxyvitamin D(3) levels, we analyzed the serum vitamin B(1), B(6) and B(12) levels. RESULTS: An association was found between MMSE test scores and serum 25-hydroxyvitamin D(3) levels, with a beta-coefficient of 0.05 (p = 0.01). Vitamin-D-sufficient patients had significantly higher MMSE scores as compared to vitamin-D-insufficient ones. No association was found with the other serum vitamin levels. CONCLUSIONS: These data support the idea that a relationship exists between vitamin D status and cognition in patients with probable AD. However, given the cross-sectional design of this study, no causality can be concluded. Further prospective studies are needed to specify the contribution of vitamin D status to the onset and course of cognitive decline and AD.

Insertion/deletion gene polymorphism of the angiotensin-converting enzyme and blood pressure changes in older adults. The Rotterdam study.

The insertion/deletion (I/D) polymorphism of the angiotensin converting enzyme (ACE) gene may be involved in determining blood pressure changes. The aim of the present study was to assess the relationship between the ACE I/D gene and the change of blood pressure levels during follow-up. We calculated the difference between mean levels of SBP, DBP and PP obtained during the two observations as follows: BP mean levels obtained at third phase minus the BP mean levels at baseline and subsequently we investigated the association of the ACE I/D polymorphism and the mean changes of SBP, DBP and PP levels. The study was conducted within the Rotterdam Study, a population-based cohort study including subjects aged 55 years and older. Information on the II, ID and DD genotypes of the ACE gene and mean change of blood pressure levels were available in 3966 subjects. In adjusted models, subjects with the D allele had higher mean changes of systolic and pulse pressure (PP) than subjects with the I allele. The mean changes of systolic blood pressure were 6.1 (4.7-7.5), 8.2 (7.5-9.3) and 7.4 (5.9-8.5) mm Hg in subjects with the II, ID and DD genotype, respectively. The corresponding mean changes of PP through genotypes were 4.3 (3.3-5.4), 6.0 (5.3-6.7) and 5.9 (4.9-6.9) mm Hg, respectively. No difference was found for mean change of diastolic blood pressure among genotypes. In conclusion, the results of this population-based study show that the ACE ID/DD genotypes are associated with increased mean changes of systolic and PP.

Association of Proton Pump Inhibitor Use with Recurrent Falls and Risk of Fractures in Older Women: A Study of Medication Use in Older Fallers.

OBJECTIVES: To examine the association between Proton pump inhibitors (PPIs) use and falls and fractures. DESIGN: A cross-sectional study. SETTING AND PARTICIPANTS: 400 female patients aged 70 years or older who were consecutively admitted to the Trauma Center Meidling, Vienna, after a fall and who required hospital admission. METHODS: We quantified the strength of the associations between PPI use and falls, and between PPI use and fractures, using a logistic regression. RESULTS: use of PPIs was significantly associated with risk of recurrent falls (OR 1.92, 95% CI = 1.05 - 3.50, p = 0.04) as well as with risk of a fracture (OR 2.15, 95% CI 1.10 - 4.21, p = 0.03). CONCLUSIONS: In conclusion, our results provide further evidence that PPI use may increase risk of falls and fractures in older women and highlight the need for clinicians to reassess the original indication and the need for continuation of PPIs on a regular basis.

[Adverse drug reactions in three older patients, even without changes in medication]. / Bijwerkingen van geneesmiddelen bij 3 oudere patiënten: ook bij ongewijzigd medicatiegebruik.

Two women, aged 77 and 73 years, and one man, aged 71 years, were admitted because of a serious adverse drug reaction (ADR). The first woman had a probable adverse drug reaction caused by digoxin after the addition of a NSAID (diclofenac) to a combination of digoxin and other drugs (furosemide and hydroquinine). The ADR due to digoxin is an example of a pharmacokinetic interaction. The second woman had serious orthostatic hypotension because of a pharmacodynamic interaction between three different antihypertensives. In the man, the ADR was hypoglycaemia while taking glibenclamide, a second generation sulfonylurea derivative. This was probably caused by declining renal function of a transplanted kidney because of bladder cancer. Doctors should be aware of ADRs in older patients, which also can occur when no changes in medication have taken place. In old age, any decline in vitality or function can be due to an ADR.

The association between plasma homocysteine levels and bone quality and bone mineral density parameters in older persons.

INTRODUCTION: High plasma homocysteine levels have been associated with incident osteoporotic fractures, but the mechanisms underlying this association are still unknown. It has been hypothesized that homocysteine might interfere with collagen cross-linking in bone, thereby weakening bone structure. Therefore, we wanted to investigate whether plasma homocysteine levels are associated with bone quality parameters, rather than with bone mineral density. METHODS: Cross-sectional data of the B-PROOF study (n=1227) and of two cohorts of the Rotterdam Study (RS-I (n=2850) and RS-II (n=2023)) were used. Data on bone mineral density of the femoral neck and lumbar spine were obtained in these participants using dual-energy X-ray assessment (DXA). In addition, participants of B-PROOF and RS-I underwent quantitative ultrasound measurement of the calcaneus, as a marker for bone quality. Multiple linear regression analysis was used to investigate the associations between natural-log transformed plasma levels of homocysteine and bone mineral density or ultrasound parameters. RESULTS: Natural-log transformed homocysteine levels were inversely associated with femoral neck bone mineral density in the two cohorts of the Rotterdam Study (B=-0.025, p=0.004 and B=-0.024, p=0.024). In B-PROOF, no association was found. Pooled data analysis showed significant associations between homocysteine and bone mineral density at both femoral neck (B=-0.032, p=0.010) and lumbar spine (B=-0.098, p=0.021). Higher natural-log transformed homocysteine levels associated significantly with lower bone ultrasound attenuation in B-PROOF (B=-3.7, p=0.009) and speed of sound in both B-PROOF (B=-8.9, p=0.001) and RS-I (B=-14.5, p=0.003), indicating lower bone quality. Pooled analysis confirmed the association between homocysteine and SOS (B=-13.1, p=0.016). Results from ANCOVA-analysis indicate that differences in SOS and BUA between participants having a plasma homocysteine level above or below median correspond to 0.14 and 0.09 SD, respectively. DISCUSSION: In this study, plasma levels of homocysteine were significantly inversely associated with both bone ultrasound parameters and with bone mineral density. However, the size of the associations seems to be of limited clinical relevance and may therefore not explain the previously observed association between plasma homocysteine and osteoporotic fracture incidence.

Better drug knowledge with fewer drugs, both in the young and the old.

Little is known about drug knowledge of patients, which is relevant for both the compliance and quality of pharmacotherapy. Drug knowledge was quantified in 160 patients in the outpatient clinics of the departments of Internal and Geriatric Medicine. Medication knowledge was generally poor, especially among older patients. Better knowledge was associated with the use of fewer drugs. Caregivers of dementia patients performed as well as younger patients, indicating that older people can perform well, if well-instructed.

Polypharmacy and falls in the middle age and elderly population.

AIM: Falls in the elderly are common and often serious. We studied the association between multiple drug use (polypharmacy) and falls in the elderly. METHODS: This was a population-based cross-sectional study, part of the Rotterdam Study. The participants were 6928 individuals aged > or = 55 years. The prevalence of falls in the previous year was assessed. Medication use was determined with an interviewer-administered questionnaire with verification of use. Polypharmacy was defined as the use of four or more drugs per day. RESULTS: The prevalence of falls strongly increased with age. Falls were more common in women than in men. Fall risk increased with increasing disability, presence of joint complaints, use of a walking aid and fracture history. The risk of falling increased significantly with the number of drugs used per day (P for trend < 0.0001). After adjustment for a large number of comorbid conditions and disability, polypharmacy remained a significant risk factor for falling. Stratification for polypharmacy with or without at least one drug which is known to increase fall risk (notably CNS drugs and diuretics) disclosed that only polypharmacy with at least one risk drug was associated with an increased risk of falling. CONCLUSIONS: Fall risk is associated with the use of polypharmacy, but only when at least one established fall risk-increasing drug was part of the daily regimen.

Predictors of falls in elderly people during rehabilitation after hip fracture--who is at risk of a second one?

BACKGROUND: A fall in old age is known as a common consequence of frailty and decline as well as a risk factor for further falls. Studies identifying hip fracture patients who are at risk of a further fall are lacking. Therefore it was of interest to evaluate the risk factors for falling in a high-risk population, i.e., patients during rehabilitation after recent proximal femur fracture. METHODS: 935 consecutive patients who had surgical intervention after acute fracture of the proximal femur underwent a multidimensional assessment within the first two days after admission to the rehabilitation ward. Falls during the stay on the rehabilitation ward were registered. The baseline data were compared between fallers and non-fallers. FINDINGS: 11.8% of the patients fell during rehabilitation. Risk factors associated with a fall were increasing age, male gender, type of surgery, the use of a rollator and nocturnal urinary incontinence. The risk of falling increased in the middle of the second week of rehabilitation, when frailer patients gained mobility and ability to walk by themselves, while they were not yet safe enough. INTERPRETATION: It was possible to compose a risk profile for future falls. Those identified as 'at risk of a further fall' should be selectively offered protective devices and special training programs in order to prevent future fractures. As for the surgical intervention, the type of surgery in relation to age and long-term outcome is of particular interest since the use of the more expensive total hip arthroplasty procedure may be more cost effective in the long term.