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Background: Under-treatment is frequently present in geriatric patients. Because this patient group often suffer from multiple diseases, polypharmacy (defined as the concomitant chronic use of five or more drugs) and contra-indications to indicated drugs may also frequently be present. Objective: To describe the prevalence of under-treatment with respect to frequently indicated medications before and after comprehensive geriatric assessment (CGA) and the prevalence of contraindications to these medications. Patients and Methods: The geriatric outpatients evaluated in this study had previously been included in a prospective descriptive study conducted in 2004. Demographic data, medical history, co-morbidity and medication use and changes were documented. The absence of drugs indicated for frequently under-treated conditions before and after CGA was compared. Under-treatment was defined as omission of drug therapy indicated for the treatment or prevention of 13 established diseases or conditions known to be frequently under-treated. Co-morbid conditions were independently classified by two geriatricians, who determined whether or not a condition represented a contraindication to use of these drugs. Results: In 2004, 807 geriatric outpatients were referred for CGA. Of these, 548 patients had at least one of the 13 selected diseases or conditions. Thirty-two of these patients were excluded from the analysis, leaving 516 patients. Before CGA, 170 of these patients were under-treated (32.9%); after CGA, 115 patients (22.3%) were under-treated. Contraindications were present in 102 of the patients (19.8%) and were more frequent in under-treated patients. After CGA, mean drug use and the prevalence of polypharmacy increased. Although 393 drugs were discontinued after CGA, the overall number of drugs used increased from 3177 before CGA to 3424 after CGA. Five times more drugs were initiated for a new diagnosis than for correction of under-treatment. Conclusions: Under-treatment is significantly reduced after CGA. Patients with contraindications to indicated medicines are more frequently under-treated. CGA leads to an increase in polypharmacy, mainly because of new conditions being diagnosed and despite frequent discontinuation of medications. [ABSTRACT FROM AUTHOR]

OBJECTIVES: The main aims of the study were to explore whether oral anticoagulation (OAC) for atrial fibrillation (AF) in geriatric outpatients is prescribed in accordance with international (American College of Cardiology/American Heart Association/European Society of Cardiology [ACC/AHA/ESC]) and Dutch national guidelines for the general practitioner (GP) and to identify whether age and selected co-morbid conditions are associated with undertreatment. As a secondary objective, we wanted to establish how many patients discontinue OAC because of major bleeding. METHODS: In 2004, at the first visit of all patients to the geriatric day clinic of the Slotervaart Hospital in Amsterdam, the Netherlands, demographic data, Mini-Mental State Examination score, medical history, Charlson Comorbidity Index score, and data on medication use and changes were documented. The presence of AF was established by assessment of medical history information obtained by the GP, the history taken from patients and their caregivers, and the results of clinical evaluation, including ECG findings. Associations between the use of OAC, demographic data and co-morbid conditions registered in the Dutch NHG (Nederlands Huisartsen Genootschap [Dutch College of General Practitioners]) standard for GPs as risk factors for stroke or contraindications to the use of OAC were analysed. The reasons for discontinuing OAC were assessed after 4 years by requesting the information from the anticoagulation services or the GP. RESULTS: At the time of the initial visit, 17.5% of the 807 outpatients had chronic AF (n = 135) or were known to have paroxysmal AF (n = 6). The mean age of the 141 patients in this cohort was 84.3 years (SD 6.2 years). Co-morbid conditions increasing the risk of stroke were present in 129 patients (91.5%). Contraindications to the use of OAC were observed in 118 patients (83.7%). Of the 116 patients with AF in their history before their visit, 57.8% were being treated with OAC at the time of their visit. After comprehensive geriatric assessment, 73 (51.8%) of the 141 patients with chronic or paroxysmal AF were continued on OAC. Of the 141 patients with chronic or paroxysmal AF, 110 (78.0%) had both extra stroke risk factors and contraindications to the use of OAC. Only increasing age was significantly and independently associated with not being prescribed anticoagulants (p < 0.001). At the 4-year follow-up, OAC had been discontinued in 5.5% of patients because of major bleeding; three patients (4.1%) taking OAC had died as a result of major bleeding, and one other patient had discontinued treatment because of a major, non-lethal bleeding episode. CONCLUSION: Applying the NHG standard for appropriate prescription, and disregarding age as a risk factor or contraindication, in this population, 14 of 141 patients (9.9%) were inappropriately prescribed OAC, salicylates or no prophylaxis. Since only patient age was associated with not prescribing OAC in this study, higher age still seems to be considered the most important contraindication to anticoagulation therapy. Implementation of better models for stratifying bleeding risk in the frail elderly is needed. After 4 years, the cumulative rate of bleeding causing discontinuation of anticoagulation therapy in this usual-care study of frail older patients was not alarmingly higher than in other usual-care studies. [ABSTRACT FROM AUTHOR]

Background: To evaluate the effects of a shared decision making (SDM) intervention for older adults with multiple chronic conditions (MCCs)., Methods: A pragmatic trial evaluated the effects of the SDM MCC intervention, existing of SDM training for nine geriatricians in two hospitals and a preparatory tool for patients. A prospective pre-intervention post-intervention multi-center clinical study was conducted in which an usual care group of older patients with MCC and their informal caregivers was included before the implementation of the intervention and a new cohort of patients and informal caregivers after the implementation of the intervention. SDM was observed using the OPTION MCC during video-recorded consultations. Patient- and caregivers reported outcomes regarding their role in SDM, involvement, perceived SDM and decisional conflict were measured. The differences between groups regarding the level of observed SDM (OPTION MCC ) were analyzed with a mixed model analysis. Dichotomous patient-reported outcomes were analyzed with a logistic mixed model., Results: From two outpatient geriatric clinics 216 patients with MCCs participated. The mean age was 77.3 years, and 56.3% of patients were female. No significant difference was found in the overall level of SDM as measured with the OPTION MCC or in patient-reported outcomes. However, at item level the items discussing 'goals', 'options', and 'decision making' significantly improved after the intervention. The items discussing 'partnership' and 'evaluating the decision-making process' showed a significant decrease. Fifty-two percent of the patients completed the preparatory tool, but the results were only discussed in 12% of the consultations., Conclusion: This study provides scope for improvement of SDM in geriatrics. Engaging older adults with MCCs and informal caregivers in the decision making process should be an essential part of SDM training for geriatricians, beyond the SDM steps of explaining options, benefits and harms. More attention should be paid to the integration of preparatory work in the consultation., (© 2023. The Author(s).)

Objective: To develop a valid and reliable tool to measure triadic decision making between older adults with multiple chronic conditions (MCC), their informal caregivers and geriatricians., Methods: Video observational study with cross-sectional assessment of interaction during medical consultations between geriatricians (n = 10), patients (n = 108) and informal caregivers (68) by three calibrated raters at the geriatric outpatient department of two Dutch hospitals. The Observer OPTION MCC instrument was developed, based on the 'Dynamic model of SDM in frail older patients' and the 'Observing Patient Involvement in Decision Making - 5 item scale' (Observer OPTION-5)., Results: Factor analysis confirms that it is acceptable to regard the new scale as a single construct. The 7-item single factor solution explained 62.76% of the variability for geriatricians, 61.60% of the variability for patients and 54.32% of the variability for informal caregivers. The inter-rater ICC for the total Observer OPTION MCC score was .96, .96, and .95 (resp. geriatricians, patients, informal caregivers), with values ranging from .60 to .95 for individual items, showing good levels of agreement., Conclusion and Practice Implications: We conclude that Observer OPTION MCC is sufficiently valid and reliable to be used for the assessment of triadic SDM in populations of older patients with MCC., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Background: The prevalence of sleep disorders increases with age. Sleep disorders may have serious health implications and may be related to serious underlying diseases. Many older people use hypnotics, like benzodiazepines, although these medications have serious side effects and often lead to habituation. Acetaminophen is one of the most frequently used off-label drugs for sleep disorders, although little is known about its effects. Our objective is to investigate whether acetaminophen is effective in treating self-reported sleep disorders in older people., Methods/design: Participants, aged 65 years or older (n=150), who have sleep disorders will be randomized for treatment with either acetaminophen 1000 mg or placebo, once daily at bedtime in a double-blind design. Eligible patients should be able to give informed consent, should not be cognitively impaired (Minimal Mental State Examination (MMSE) score≥20), should not have pain, and should not use acetaminophen on a regular basis because of pain complaints. The study will take three weeks to complete. During these three weeks, the participants register their sleep behavior in a sleep diary. The participants will use the study medication during the second and third week. The primary endpoint will be the self-reported sleep disorders at the end of week three, as measured by means of the Insomnia Severity Index (ISI). To validate these subjective sleep parameters against objectively measured indices of the sleep-wake pattern, we will measure the periods of wakefulness and sleep in a subgroup of participants, using an actigraph worn on the wrist during the entire study period., Discussion: The proposed study will contribute to our knowledge about the treatment of sleep disorders in an older population. There is a need for treatments for sleep disorders without serious adverse effects. Acetaminophen might be a simple and inexpensive alternative for the regimes that are currently used with older people., Trial Registration: The Netherlands National Trial Register NTR2747.

Meta-analyses showed that psychotropic drugs (antidepressants, neuroleptics, benzodiazepines, antiepileptic drugs) and some cardiac drugs (digoxin, type IA anti-arrhythmics, diuretics) are associated with increased fall risk. Because balance and gait disorders are the most consistent predictors of future falls, falls due to use of these so-called fall-risk-increasing drugs (FRIDs) might be partly caused by impairments of postural control that these drugs can induce. Therefore, the effects of FRIDs on postural control were examined by reviewing literature. Electronic databases and reference lists of identified papers were searched until June 2013. Only controlled research papers examining the effects of FRIDs on postural control were included. FRIDs were defined according to meta-analyses as antidepressants, neuroleptics, benzodiazepines, antiepileptic drugs, digoxin, type IA anti-arrhythmics, and diuretics. Ninety-four papers were included, of which study methods for quantifying postural control, and the effects of FRIDs on postural control were abstracted. Postural control was assessed with a variety of instruments, mainly evaluating aspects of body sway during quiet standing. In general, postural control was impaired, indicated by an increase in parameters quantifying body sway, when using psychotropic FRIDs. The effects were more pronounced when people were of a higher age, used psychotropics at higher daily doses, with longer half-lives, and administered for a longer period. From the present literature review, it can be concluded that psychotropic drugs cause impairments in postural control, which is probably one of the mediating factors for the increased fall risk these FRIDs are associated with. The sedative effects of these drugs on postural control are reversible, as was proven in intervention studies where FRIDs were withdrawn. The findings of the present literature review highlight the importance of using psychotropic drugs in the older population only at the lowest effective dose and for a limited period of time.

Objectives: to determine the prevalence of vertebral fractures and their risk factors in geriatric patients., Design: prospective cohort study., Setting: teaching hospital in Amsterdam, The Netherlands., Subjects: three hundred and three geriatric patients, who had their first visit at a diagnostic day hospital between April and August 2007., Measurements: lateral X-rays of the lumbar spine and chest were performed; vertebral fractures were scored according to the semi-quantitative method of Genant by trained observers and compared with the official report of radiologists. Co-morbidity, reported falls, mobility and cognitive function were scored., Results: vertebral fractures were observed in 51% (156/303) of geriatric patients. Sixty-nine per cent (107/156) of these fractures were moderate to severe. In 21% (33/156) of the patients with a fracture, vertebral fractures were diagnosed on the lumbar spine X-ray alone. Patients with vertebral fractures had more previous non-vertebral fractures (odds ratio: 2.40 95% CI: 1.40-4.10), had lower serum albumin levels (OR: 0.92 95% CI: 0.87-0.97) and more current prednisone use (OR: 8.94 95% CI: 1.12-71.45). Co-morbidity and cognitive decline were not identified as risk factors. Radiologists reported vertebral fractures in 53% (82/156) of the cases., Conclusion: this study showed a very high prevalence of vertebral fractures in geriatric patients; particularly the high prevalence of moderate and severe fractures is remarkable. Because of this high prevalence, the routinely performed lateral X-ray of the chest should be used to look for vertebral fractures. An additional X-ray of the lumbar spine might be useful in patients without vertebral fractures on the chest X-ray.

Background: Oral anticoagulation (OAC) is the most effective treatment to prevent strokes in patients with atrial fibrillation (AF). Many older patients are not prescribed OAC., Objective: To explore which co-morbid conditions in older patients with AF have been associated with under-treatment with OAC, or were used as exclusion criteria for trials, or have been associated with increased risk of bleeding., Methods: A Pubmed search was conducted with the terms elderly, atrial fibrillation, stroke risk, bleeding risk, intracranial haemorrhage, cognition, fall risk, renal dysfunction, alcohol abuse, malignancy, polypharmacy, NSAID, under-treatment, under-use and under-prescription., Results: Higher age is associated with under-treatment. Patients with a higher risk of stroke show higher rates of bleeding complications. The associations of bleeding rates with possible contraindications are inconsistent., Discussion: Published bleeding rates reflect selection bias, describing mainly relatively healthy older patients. The use of stratification schemes for stroke risk and for bleeding risk will have to be implemented., Conclusion: The decision to prescribe OAC in older patients with AF remains a challenging task since bleeding risk is difficult to estimate reliably. Stratification schemes may be helpful.

Background: The treatment of older patients with hypertension has been controversial-in addition to uncertainty regarding appropriate blood pressure (BP) targets in the very old, there are concerns that excessive BP lowering could result in adverse events such as falls, stroke, and cognitive problems. The Hypertension in the Very Elderly Trial (HYVET), however, found that lowering BP in patients aged > or =80 years was associated with decreased morbidity and mortality., Objective: This study compared the findings of HYVET with data from a population of elderly outpatients with hypertension in a clinical practice setting., Methods: This was a retrospective study of prospectively collected data from patients aged > or =80 years with a history of hypertension who visited a geriatric diagnostic day clinic in the Netherlands in 2004. The data were analyzed to determine how many patients were being prescribed antihypertensive medication, how many would have been eligible for HYVET, how many achieved adequate BP control, and whether reaching BP goals was associated with the number and type of antihypertensive medications received or with eligibility for HYVET., Results: During 2004, 518 patients aged > or =80 years visited the geriatric diagnostic day clinic, of whom 147 met the criteria for inclusion in this study. One hundred forty-one patients (95.9%) were receiving antihypertensive medication, although only 52 (35.4%) would have been eligible for HYVET. Dementia, which was an exclusion criterion in HYVET, was the major reason for ineligibility (70 [47.6%]). Greater proportions of patients in this study had comorbidities compared with the HYVET population (stroke: 22.4% vs 6.7%, respectively; myocardial infarction: 7.5% vs 3.1%; heart failure: 11.6% vs 2.9%; diabetes mellitus: 21.1% vs 6.8%). At the time of the clinic visit, 50.3% of patients had adequate BP control, as defined in HYVET (systolic BP <150 mm Hg and diastolic BP <80 mm Hg). Levels of BP control were similar in patients who would and would not have been ineligible for HYVET. Only the mean (SD) number of antihypertensive medications received was significantly associated with the achievement of BP control compared with failure to achieve adequate BP control (2.2 [1.0] vs 1.8 [1.1], respectively; P < 0.05)., Conclusions: Based on the findings of this study, the benefits of treating elderly patients with hypertension in clinical practice may be lower than those reported by HYVET. The study results support the current recommendation that all patients with hypertension should be treated with >1 antihypertensive medication if adequate control is not achieved at low doses of a single medication.

Background: The most frequent intervention after Comprehensive Geriatric Assessment (CGA) is adjustment of medications. Adherence to recommendations is often incomplete. Patients at high risk of non-adherence should be identified., Objective: To explore if changes in drug-use after CGA are carried out by the patient. To identify factors influencing non-adherence., Methods: Co-morbidity and medication use were recorded. Patients, and when cognitively impaired, a caregiver, were questioned about advised changes. Drug-use before and after CGA was assessed. Patients were asked whether they would discontinue their drugs either with or without consulting their physician. Univariate logistic regression analysis to identify factors influencing non-adherence, was performed with SPSS., Results: Forty patients were included. Of the changes in medication advised, 90 % were reported to be carried out. 65 % of the patients were compliant. Only the presence of a caregiver was associated with reported complete adherence to drug therapy. Most patients can't describe for how long they will have to continue taking the drugs that are prescribed to them., Conclusion: Most geriatric patients carry out changes in medication made after CGA. Supervision by caregivers may explain a high rate of reported adherence despite the presence of polypharmacy and cognitive decline., Practice Implications: In the absence of caregivers special attention should be paid to adherence to medication changes. Information about intended duration of drug therapy should be improved.

Background: Increased age is associated with polypharmacy. Polypharmacy is a risk factor for severe adverse drug reactions (ADRs) and is associated with an increased risk of mortality., Objectives: The main goal of the current study was to describe the frequency and relevancy of discrepancies in drug use in Dutch geriatric outpatients as reported by the patients and their caregivers, documented by the referring general practitioner (GP), and registered by the public pharmacy. The frequency of medication discrepancy adverse patient events (MDAPEs) was also recorded. In addition, possible contributing factors-such as increasing age, cognitive status and depressive symptoms, the number of medications used, the number of physicians visited by the patient, and the presence of a caregiver to supervise medication use-were studied., Methods: This was a prospective descriptive study conducted at the geriatric outpatient clinic of a teaching hospital. Between January 1 and May 1, 2005, consecutive patients were included if they were aged >65 years, reported use of > or =1 medication, and if they could understand the goals and consequences of participating in the study. The medications described by geriatric patients and their caregivers were compared with the drugs listed by their GP. The pharmacies of the referred patients were asked to send a description of the drugs distributed in the 6 months preceding the patient's visit to the geriatric outpatient clinic. The classification of ADRs and undertreatment as clinically relevant was done by study investigators who were blinded for the presence of discrepancy., Results: A total of 120 outpatients were included. The mean (SD) age of the study patients was 82.3 (6.8) years; 71.7% were women. Of the 120 patients, 113 patients (94.2%) reported taking >1 drug and 88 (73.3%) were prescribed > or =4 drugs. At least 1 discrepancy between the medication lists of the patients, GP, or pharmacy was present in 104 of the 120 patients (86.7%). In 90 patients (75.0%), there was > or =1 discrepancy between the medication reported by the patient and the GP. Patients with > or =1 discrepancy reported taking a higher mean number of drugs and had more prescribing physicians in addition to their GP. Twenty-nine patients (24.2%) experienced an MDAPE involving the use of drugs the GP had not correctly described in the letter of referral. The pharmacy was unaware of the use of medication involved in an MDAPE in 2 patients., Conclusions: Geriatricians should assume that the medication lists supplied by GPs are incomplete or incorrect, and be aware that in approximately 25% of patients, symptoms may be caused by medication use inaccurately described in the referral. Reports by the community pharmacy may supply valuable additional information. Because there are also discrepancies between patients and pharmacies, medication use from a database-with data from prescribing physicians and pharmacy systems-will still have to be confirmed by the patient.

Background: By using surface enhanced laser desorption/ionisation- time of flight mass spectrometry (SELDI-TOF MS) an amyloid beta (Abeta) profile was shown in cerebrospinal fluid (CSF) of patients with dementia., Objective: To investigate the Abeta-profile in serum with SELDI-TOF MS, to evaluate if this profile resembles CSF profiles and to investigate the correlation between intensity of Abeta-peptide-peaks in serum and clinical, demographical and genetic variables., Methods: Duplicate profiling of Abeta by an SELDI-TOF MS immunocapture assay was performed in 106 patients, suffering from Alzheimer's Disease or Vascular Dementia and age-matched non-demented control patients. Linear regression analyses were performed to investigate the intensities of four selected Abeta peaks as dependent variables in relation to the independent clinical, demographic or genetic variables., Results: Abeta37, Abeta38 and Abeta40 were found among additional unidentified Abeta peptides, with the most pronounced Abeta peak at a molecular mass of 7752. This profile partly resembled the CSF profile. The clinical diagnosis was not a predictive independent variable, however ABCB1 genotypes C1236T, G2677T/A, age and creatinine level showed to be related to Abeta peak intensities in multivariate analyses., Conclusions: We found an Abeta profile in serum that partly resembled the CSF profile in demented patients. Age, creatinine levels, presence of the APOE epsilon4 allele and ABCB1 genotypes (C1236T and G2677T/A) were correlated with the Abeta serum profile. The role of P-gp as an Abeta transporter and the role of ABCB1 genotypes deserves further research. The investigated serum Abeta profile is probably not useful in the diagnosis of dementia.

This review addresses recent developments in amyloid beta (Abeta), total tau (t-tau), and phosporylated tau (p-tau) protein analysis, in cerebrospinal fluid (CSF) and plasma as biomarkers for dementia. Recent research focused on the protection of patients with mild cognitive impairment (MCI) into dementia and the differential diagnosis of Alzheimer's Disease (AD). A combination of Abeta42 and t-tau in CSF can discriminate between patients with stable MCI and patients with progressive MCI into AD or other types of dementia with a sufficient sensitivity and specificity. Regression analyses demonstrated that pathological CSF (with decreased Abeta42 and and increased tau levels) is a very strong predictor for the progression of MCI into AD. Furthermore, CSF measurements of p-tau and Abeta42 can assist in diagnosing vascular dementia or frontotemporal dementia in the differential diagnosis of AD indicated by a reasonable sensitivity and specificity. Whether tau in combination with Abeta42 or in combination with the Abeta37/Abeta42 or Abeta38/Abeta42 ratio aids in the discrimination between AD and Lewy Body dementia remains to be elucidated. Cross-sectional research could not demonstrate significant differences for Abeta40 and Abeta42 in plasma between AD and controls. However, a recently published longitudinal study showed high baseline Abeta40 levels, especially when combined with low baseline Abeta 42 levels, are a strong risk factor for the development of dementia. This emphasizes the importance of performing longitudinal studies in addition to cross-sectional ones. The origin of plasma Abeta and its transport between CSF and plasma, however, needs further clarification. In conclusion, progress has been made regarding Abeta and tau as biomarkers for dementia, both for differentiation between stable MCI and progressive MCI patients and for the differential diagnosis of AD. Future research should aim to validate these recently published results, preferably in pathologically confirmed AD patients. In addition, it is important to standardise research in terms of study design (longitudinal, minimal follow-up period of 5 years), type of researched parameters ( total or p-tau, type of Abeta peptides), type of matrix (CSF and plasma) and data analysis (establishment of predefined cut-off values, type of ratio, type of marker combination).

Background: The prevalence of drug-drug interactions (DDIs) in a geriatric population may be high because of polypharmacy. However, wide variance in the clinical relevance of these interactions has been shown., Objectives: To explore whether adverse drug reactions (ADRs) as a result of DDIs can be identified by clinical evaluation, to describe the prevalence of ADRs and diminished drug effectiveness as a result of DDIs and to verify whether the top ten most frequent potential DDIs known to public pharmacies are of primary importance in geriatric outpatients in the Netherlands., Method: All adverse events classified by the Naranjo algorithm as being a possible ADR and drug combinations resulting in diminished drug effectiveness were identified prospectively in 807 geriatric outpatients (mean age 81 years) at their first visit. The setting was a diagnostic day clinic. The Medication Appropriateness Index (MAI) and Beers criteria were used to evaluate drug use and identify possible DDIs. The ten most frequent potential interactions, according to a 1997 national database of public pharmacies ('Top Ten') in the Netherlands, and possible adverse events as a result of other interactions, were described. The effects of changes in medication regimen were recorded by checking the medical records., Results: In 300 patients (44.5% of the 674 patients taking more than one drug), 398 potential DDIs were identified. In 172 (25.5%) of patients taking more than one drug, drug combinations were identified that were responsible for at least one ADR or which possibly resulted in reduced effectiveness of therapy. Eighty-four of the 158 possible ADRs resulting from enhanced action of drugs forming combinations listed in the 'Top Ten' were seen in 73 patients. Only four DDIs resulting in less effective therapy that involved drug combinations in the 'Top Ten' were identified. Changes in drug regimens pertaining to possible interactions were proposed or put into effect in 111 of the 172 (65%) patients with possible DDIs. Sixty-one (55%) of these patients returned for follow-up. Of these, 49 (80%) were shown to have improved after changes were made to their medication regimen., Conclusion: In this study, nearly half of the geriatric outpatients attending a diagnostic day clinic who were taking more than one drug were candidates for DDIs. One-quarter of these patients were found to have possible adverse events or diminished treatment effectiveness that may have been at least partly caused by these DDIs. These potential interactions can be identified through clinical evaluation. In the majority of patients (99 of 172) the potential interactions resulting in possible ADRs or diminished effectiveness were not present in the 'Top Ten' interactions described by a national database of public pharmacies, a finding that emphasizes that the particular characteristics of geriatric patients (e.g. frequent psychiatric co-morbidities) need to be considered when evaluating their drug use. At least 7% of all patients taking more than one drug, and 80% of those with possible drug interactions whose drug regimen was adjusted, benefited from changes made to their drug regimens.

Purpose: Presently, it is unclear which patients suffering from Alzheimer's Disease (AD) respond to rivastigmine and if rivastigmine acts on specific cognitive domains. The aims of this study are thus to investigate treatment effects of rivastigmine on specific cognitive domains and to find possible responsive subpopulations to rivastigmine cognitive effects., Methods: Mini Mental State Examination (MMSE) and Cambridge Cognitive Examination (CAMCOG) were administered at baseline and after 6 months in 83 rivastigmine users and 96 historical controls, representing natural decline. Treatment effects on different subsections of the CAMCOG and in different subpopulations were investigated by linear regression analyses., Results: Rivastigmine showed effectiveness on total CAMCOG (p < 0.001), CAMCOG non-memory subsection (p < 0.001) and subscales of language (p = 0.002), attention/calculation (p = 0.043), abstract thinking (p < 0.001) and perception (p = 0.031). In patients with baseline MMSE < or =19 rivastigmine showed significant and favourable effects compared to historical controls on total CAMCOG (p < 0.001) and both non-memory (p < 0.001) and memory subsections (p = 0.002)., Conclusion: Rivastigmine showed primarily effectiveness on the non-memory section of the CAMCOG and patients with a baseline MMSE < or = 19 appeared to show greater responses to rivastigmine compared to patients with baseline MMSE > or = 20., (Copyright 2006 John Wiley & Sons, Ltd.)

Amyloid beta is an in vitro substrate for P-glycoprotein (P-gp), an efflux pump at the blood brain barrier (BBB). The Multi Drug Resistance (ABCB1) gene, encoding for P-gp, is highly polymorphic and this may result in a changed function of P-gp and may possibly interfere with the pathogenesis of Alzheimer's disease. This study investigates to what extent ABCB1 Single Nucleotide Polymorphisms (SNPs; C1236T in exon 12, G2677T/A in exon 21 and C3435T in exon 26) and inferred haplotypes exist in an elderly population and if these SNPs and haplotypes differ between patients with dementia and age-matched non-demented control patients. ABCB1 genotype, allele and haplotype frequencies were neither significantly different between patients with dementia and age-matched controls, nor between subgroups of different types of dementia nor age-matched controls. This study shows ABCB1 genotype frequencies to be comparable with described younger populations. To our knowledge this is the first study on ABCB1 genotypes in dementia. ABCB1 genotypes are presently not useful as a biomarker for dementia, as they were not significantly different between demented patients and age-matched control subjects.

Purpose: To investigate the changes in pharmacotherapy of patients during and after admission to a geriatric ward in 2002 and to investigate if this goes along with reduction of drugs. To describe the differences of the admitted patients and their medication in 2002 compared to 1985., Methods: Included patients were admitted to the geriatric ward of a general hospital in the Netherlands during 2002 (n = 258, mean age 84.2 years). Medication at admission, during admission and at discharge were described after retrospective reviewing of medical charts. A comparable study was performed at the same ward in 1985., Results: In 2002, most frequently used medication at admission was acetylsalicylic acid (30.2%). Pantoprazole was during admission used in 38.8% of patients and at discharge in 31.8%. Folic acid that was at admission used by 11.6% of patients was at discharge increased to 23.4%. At discharge, vitamin D was used in 21.5% of patients, whereas lisinopril was used in 17.8% of patients. Both in 1985 and 2002 vitamins were added and use of antibiotics was increased during admission. A mean addition of 1.0 drug in 1985 and of 0.7 drugs in 2002 was observed., Conclusions: Geriatric hospital admission resulted both in 1985 and 2002 in addition of medication. In both periods reductions in medication were nullified by addition of medication for reason of therapy optimisation. Compared to 1985 admitted patients receive more medication resulting from new insights into pharmacotherapy and more use of preventive medicine., (Copyright 2006 John Wiley & Sons, Ltd.)

We investigated rivastigmine effectiveness in 84 Alzheimer outpatients, with a special focus on behavioural problems. Cognition, activities in daily living (ADL) and behaviour were assessed during 30 months. Changes in test results between 6 months and baseline were compared with a historical control cohort of Alzheimer patients (n = 69) by performing t-tests and calculation of Cohen's d and standardised response mean (SRM). During 6 months, rivastigmine showed effect on cognition (p < 0.001, Cohen's d = 0.33, SRM = 0.78), ADL (p < 0.001, Cohen's d = -0.43, SRM = -0.54) and memory-related behaviour (p = 0.006, Cohen's d = -0.28, SRM = -0.28). Depressive behaviour worsened (p = 0.001, Cohen's d = 0.30, SRM = 0.37) and disruptive behaviour (p = 0.369, Cohen's d = -0.07, SRM = -0.09) was not effected by rivastigmine. During 30 months, a gradual decline was shown in most domains. Most RMBPC items showed stabilization during 30 months. Improvement on disruptive behaviour items and depression items was shown after 6 months of treatment in a large proportion of patients in whom behavioural problems were present at baseline. In conclusion, a huge discontinuation rate is experienced within the first half year of treatment. In the subpopulation of patients who continued rivastigmine for 6 months, it shows modest effectiveness on cognition, functionality and memory-associated behaviour compared with historical control patients. Unfortunately, disruptive behaviour is not altered by rivastigmine therapy, and depressive behaviour worsened slightly after initial treatment. During 30 months, rivastigmine showed stabilization on numerous behaviour items as measured by the RMBPC.

Background: Elderly patients often take multiple drugs. It is known that polypharmacy, i.e. use of five or more drugs, may lead to drug interactions and adverse events. However, undertreatment of conditions or illnesses is also a concern in geriatric patients. A centralised review of both diagnoses and medication may play a key role in optimising pharmacotherapy in geriatric patients. The aims of this study were to evaluate the quality and appropriateness of medication after performing a complete geriatric assessment (CGA) and medication review at a diagnostic geriatric day clinic, to investigate reasons for drug changes, and to determine whether medication review leads to a reduction in the number of drugs used., Methods: A chart review was performed in 702 patients (mean age 82.0 years, range 57.1-104.1 years) who underwent a CGA at a diagnostic geriatric day clinic. Medication at admission, changes in medication and reasons for changes were noted., Results: Vitamins, for example folic acid and vitamin B(12) (cyanocobalamin), and trimethoprim for urinary tract infections were the most frequently started medications after CGA and medication review. The number of drugs used was reduced in only a minority of patients (11.7%); reasons for discontinuation were a diagnosis that was no longer relevant (38.8%), adverse events (33.2%) and identification of better pharmacotherapeutic options (22.0%). In 69.2% of the cases a new diagnosis was the reason for starting a new medication, followed by osteoporosis prophylaxis (15.0%) and improvement in pharmacotherapy (10.6%). At admission, patients were taking a mean number of 4.6 drugs (range 0-17). A mean of 0.8 drugs (range from reduction of 5 to addition of 7) had been added per patient, resulting in a mean number of 5.4 (range 0-18) prescribed drugs at discharge., Conclusion: Evaluation of medication in patients after performing CGA at the geriatric day clinic investigated resulted in relevant medication changes. The main reason for prescribing new drugs was a new diagnosis. Absence of a relevant medical indication was the main reason for stopping drugs. CGA and medication review resulted in a mean net addition of 0.8 drugs per patient.

A sensitive and specific high-performance liquid chromatography/tandem mass spectrometry (HPLC/MS/MS) assay for the determination of rivastigmine and its major metabolite NAP 226-90 is presented. A 100 microL plasma aliquot was spiked with a structural analogue of rivastigmine as internal standard (PKF214-976-AE-1) and proteins were precipitated by adding 200 microL of methanol. After centrifugation a volume of 100 microL of the clear supernatant was mixed with 100 microL of methanol/water (30:70, v/v) and volumes of 25 microL were injected onto the HPLC system. Separation was acquired on a 150 x 2.0 mm i.d. Gemini C18 column using a gradient system with 10 mM ammonium hydroxide and methanol. Detection was performed by using a turboionspray interface and positive ion multiple reaction monitoring by tandem mass spectrometry. The assay quantifies rivastigmine from 0.25 to 50 ng/mL and its metabolite NAP 226-90 from 0.50 to 25 ng/mL, using human plasma samples of 100 microL. Validation results demonstrate that rivastigmine and metabolite concentrations can be accurately and precisely quantified in human EDTA plasma. This assay is now used to support clinical pharmacologic studies with rivastigmine., (Copyright 2006 John Wiley & Sons, Ltd.)

Background: Rivastigmine is used for symptomatic treatment of mild-to-moderately severe Alzheimer's Dementia (AD). We investigated the frequency of and reasons for rivastigmine discontinuation in clinical practice and possible predictive factors for discontinuation within the first six months after starting therapy., Methods: A retrospective cohort study was performed in rivastigmine users, who started therapy in a naturalistic setting. A nurse supported a part of the studied cohort, as this was introduced during the study period. Reasons for discontinuation were investigated, including therapy discontinuation if the Maximum Achieved Dose (MAD) was below 6 mg daily. Predictors of discontinuation within the first half year were investigated by logistic regression analysis., Results: Baseline Mini-Mental-State-Examination (MMSE) of included patients (n = 154) was 20.1, mean age was 78.4 years and 70% was female. Within 6 months, 61 users (39.6%) discontinued therapy, primarily (59.0%) for adverse events. Thereafter, the main reason for discontinuation was non-response according to clinimetrics. A MAD during the titration phase of 1.5-4.5 mg/day and absence of nurse support are significantly related to discontinuation within 6 months., Conclusions: Rivastigmine is primarily discontinued within the first six months for intolerable adverse events and thereafter mainly for ongoing deterioration. A MAD of 1.5-4.5 mg/day and the absence of nurse support are independently related to discontinuation of rivastigmine within the initial 6 months., (Copyright (c) 2005 John Wiley & Sons, Ltd.)

Immunosenescence refers to the influence of aging on the immune system. Numerous problems are encountered in studying this topic, the main one being the influence of concomitant disease. Despite the great efforts that have been devoted to research in this field, the results of studies performed to date have not been convincing and, until now, no sound scientific evidence has emerged to show that immunosenescence is clinically significant. The only possible exceptions to this are the discovery of a selective defect in cell-mediated immunity and the reactivation of varicella zoster virus. Therefore, many more, and better designed, studies will have to be conducted before the full clinical impact of immunosenescence can be delineated.