Changes in under-treatment after comprehensive geriatric assessment: an observational study.

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 contraindications 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.

Do geriatric outpatients adhere to medication changes advised after assessment? An exploratory pilot study.

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.

Discrepancies in reported drug use in geriatric outpatients: relevance to adverse events and drug-drug interactions.

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.

Serum amyloid beta peptides in patients with dementia and age-matched non-demented controls as detected by surface-enhanced laser desorption ionisation-time of flight mass spectrometry (SELDI-TOF MS).

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.

Amyloid beta protein and tau in cerebrospinal fluid and plasma as biomarkers for dementia: a review of recent literature.

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).

Drug-drug interactions in a geriatric outpatient cohort: prevalence and relevance.

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.

Evaluation of pharmacotherapy in geriatric patients after performing complete geriatric assessment at a diagnostic day clinic.

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 simple and sensitive assay for the quantitative analysis of rivastigmine and its metabolite NAP 226-90 in human EDTA plasma using coupled liquid chromatography and tandem mass spectrometry.

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.

ABCB1 genotypes and haplotypes in patients with dementia and age-matched non-demented control patients.

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.

The effect of admission to a geriatric ward on medication use: 2002 versus 1985.

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.

Discontinuation of rivastigmine in routine clinical practice.

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.

Discrepancies between medical and pharmacy records for patients on anti-HIV drugs.

OBJECTIVE: To compare and evaluate drug notations in outpatient medical records and in pharmacy records in a cohort of HIV-1-infected patients treated with antiretroviral drugs. METHODS: Data on 103 patients were obtained from January 1, 1998, through December 31, 1999, by medical chart review and collection of pharmacy records. Two analyses were performed. First, antiretroviral drugs and comedication in the pharmacy records were documented and compared with their appearance in the outpatient medical records. Second, a detailed comparison was performed at 5 time points during the study period for the antiretroviral drugs. Generic name, formulation, strength, and frequency of dosing as registered in the outpatient medical records were compared with those registered in the pharmacy records. RESULTS: Total drug dispensation was 1607 (366 and 1241 antiretroviral drugs and comedication, respectively). The first screening resulted in a total discrepancy of 55.1% (n = 885), of which 97.1% (n = 859) was attributed to the comedication and 2.9% (n = 26) to the antiretroviral drugs. The discrepancy for the antiretroviral drugs at the specific time points ranged from 5.1% to 12.6% when the generic name only was used, and from 7.1% to 17% when formulation, strength, and frequency of dosing were also taken into account. CONCLUSIONS: The observed discrepancy between outpatient medical records and pharmacy records mainly concerns the comedication. For the antiretroviral drugs fewer, but still substantial, discrepancies were observed. These results indicate that full exchange of information conceming drug use in this population between general practitioners and specialists (infectious disease) is lacking.