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Biomedical subjects

M G Olde Rikkert

Publications and source records attributed to M G Olde Rikkert.

At least 19 recordsLinked to original sources

Melatonin in elderly patients with insomnia. A systematic review.

BACKGROUND: Melatonin is a hormone and antioxidant produced by the pineal gland of which four neurobiological roles have been claimed in the aged population: anti-ageing agent; free-radical scavenger; regulator of circadian rhythm; endogeneous sleep-inducer. The "melatonin replacement" hypothesis states that 1) the well-evidenced age-related decline contributes to insomnia and that 2) replacement with physiological doses of melatonin improves sleep. The aim of this review was to determine the evidence for the efficacy of melatonin in elderly insomniacs. METHODS: MEDLINE's database from 1990-2000 was searched with "melatonin", "geriatrics" and "(frail)-elderly" as major sub-headings. This resulted in 78 articles: only studies with empirical treatment data were reviewed (N = 12). RESULTS: Six reports (abstract, research letter, retrospective case study, 3 open label studies) showed a trend towards efficacy of melatonin: sleep quality improved and in patients with Alzheimer's disease sundowning was reduced. In 6 double blind, randomised crossover trials, a total number of 95 patients (mean ages: 65-79 yrs) were treated. Melatonin doses ranged from 0.5 mg to 6 mg; most took a single dose 30-120 min before bedtime. In 3 studies a slow release form was used. Sleep quality was objectively measured by wrist actigraphy (n = 4) and polysomnography (n = 2), and additionally subjective sleep quality was assessed (n = 2). Sleep latency decreased significantly in 4 studies. In 3 studies other measures of sleep quality (sleep efficiency, total sleep time and wake time during sleep) improved. Subjective sleep quality did not improve. No early-morning sleepiness occurred. Comparison of the studies suggests that melatonin is most effective in elderly insomniacs who chronically use benzodiazepines and/or with documented low melatonin levels during sleep. CONCLUSION: There is sufficient evidence that low doses of melatonin improve initial sleep quality in selected elderly insomniacs. However, larger randomized controlled trials, with less strict inclusion criteria are necessary to yield evidence of effectiveness (i.e. clinical and subjective relevance) in geriatric patients who suffer from insomnia, before wide-spread use can be advocated.

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Toward individualized evidence-based medicine: five "N of 1" trials of methylphenidate in geriatric patients.

OBJECTIVES: To investigate the efficacy of methylphenidate in depressed or apathetic geriatric patients. DESIGN: Five "N of 1" trials (individual cross-over, double-blinded, randomized trials). SETTING: Department of Geriatrics, University Medical Center, Nijmegen, and two nursing homes in Nijmegen, the Netherlands. PARTICIPANTS: Patients suffered from depression due to a general medical condition (n = 2); depression resistant to antidepressive drugs (n = 1), chronic apathy due to mild and moderate severe dementia (n = 2). INTERVENTION: Methylphenidate (5 mg bid) and placebo (both for two subsequent days) in 5 weeks of randomized treatment blocks. MEASUREMENTS: Montgomery Asberg Depression Rating Scale (MADRS), Apathy Evaluation Scale (AES)-clinician, the AES-informant, Barthel index and a semiquantitative checklist of adverse effects. RESULTS: Among the three depressed patients, two showed significant improvement on the MADRS (P = .089 and P = .001; alpha = 0.10), one patient's apathy showed significant improvement on AES-clinician and -informant (P = .077 and P = .086). One apathetic patient's trial was stopped because AES could not be completed. None of the patients showed significant changes in the Barthel index. No side effects developed. CONCLUSION: "N of 1" trials are useful in evaluating efficacy of methylphenidate in depressed or apathetic geriatric patients. Single-patient trials can be a useful tool in pharmacotherapeutic decision-making in frail older subjects.

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A new course in age-based medicine at the University Medical Center of Nijmegen.

In 1995 the Medical Faculty of the University Medical Center of Nijmegen revised its curriculum to be more problem-oriented and student-centered. Each of the first four years now consists of ten four-week courses constructed around specific learning objectives. For the new curriculum the authors developed a fourth-year course on age-related health problems in which selected issues of pediatrics, general practice, and geriatrics are integrated. The primary objective of this course is to enable students to understand the differences and similarities in approaches to health problems in different age groups. Moreover, by the end of the course students should be able to analyze the physical, psychological, and social aspects of age-specific medical problems and understand their consequences for prevention and treatment. The course covers age-specific health concerns (e.g., neonatal jaundice, growth problems, sudden infant death syndrome, anorexia nervosa, dementia, multiple pathology, frailty) as well as important age-related differences in pathophysiology, etiology, diagnosis, and treatment (e.g., acute abdomen, constipation, maltreatment, urinary incontinence, pharmacokinetics). Based on assessments and evaluations after the first three implementations, the authors conclude that the enthusiastically received course is an effective introduction to age-specific health problems.

Age Factors↗

[Medical-scientific research in the elderly in The Netherlands; historic milestones and methodological problems].

OBJECTIVE: To describe the methodological development of medical research regarding elderly subjects in the Netherlands. DESIGN: Descriptive. SETTING: Nijmegen University, the Netherlands. METHOD: All research on aging published in the Netherlands Tijdschrift voor Geneeskunde (Dutch Journal of Medicine) starting from its first volume in 1857 up to 1983 was studied. Selected were those articles in which new research methods were introduced. Next, six pioneering researchers in geriatrics were interviewed on the methodological development of geriatric research and on the problems they encountered in their own research. RESULTS: Research started with studies on age-associated diseases such as prostatism, presbyacusis and senile dementia. It was only after a considerable delay that new diagnostic instruments such as electrocardiography and new research designs such as randomized trials found their way into research on elderly patients. The development of a questionnaire on the health of the elderly, the introduction of the concept of activities of daily living and of diagnostic instruments in the field of psychogeriatrics were important steps that made possible current geriatric research. From the outset, researchers encountered methodological problems still relevant in current research and caused by characteristics of geriatric patients: frailty, high prevalence of comorbidity, coexistence of physical, psychological and social problems, and large interindividual differences.

Activities of Daily Living↗

[Recruitment and selection of test subjects for scientific research in geriatrics: literature review and experiences of the Nijmegen NESTOR study].

The conduct of research in geriatric medicine differs from that in other medical specialties in a number of ways. In geriatric research it is almost impossible to study a large, homogeneous group of subjects, suffering solely from the problem to be studied. Moreover, measurements and questionnaires should be short, simple and not very troublesome. These differences are due to the heterogeneity of geriatric patients and the high prevalence of multimorbidity, often resulting in impaired physical, psychological and social performance. In this article a number of issues which are important for successful recruitment and selection of subjects for geriatric research are discussed. First, a review of relevant literature is given, and subsequently, experiences concerning recruitment and selection appreciated in the Nijmegen geriatric research programme' are described. This programme was part of the governmental Netherlands Programme for Research on Ageing (NESTOR). According to the literature the efficacy of recruitment may be improved by: personal contact between researcher and subject in view, introduction of the selection criteria already at the time of subjects' recruitment, a balance between research burden and profit, sufficient rewards for participation, both financially and non-financially, maximal effort in the subjects' transport, and also piloting of the recruitment procedure. In the NESTOR-studies the average number of subjects who were recruited and who completed the studies was low (23%), because a lot of the recruited subjects did not meet the selection criteria or considered participation as too troublesome. Subjects who agreed to participate showed high research compliance.

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[Current challenges for scientific research in geriatrics].

Conducting medical research on geriatric patients differs essentially from conducting research on other types of patients. Recruitment and selection of research subjects are difficult, primarily because many geriatric patients will be judged as incapable to consent to participate in scientific research. Moreover, the frailty of geriatric patients requires research instruments that do not trouble subjects too much and research should be aimed at identifying causes of change in functional performances and quality of life. Large randomized controlled clinical trials are very hard to perform in geriatrics, although this research design is considered the most valuable. Therefore, individual treatment decisions generally cannot be evidence based because of a lack of controlled geriatric research or because of uncertainties in individualizing available evidence. In this paper three research designs will be discussed that may be helpful in bridging the gap between evidence and patient care: qualitative research methods, longitudinal research to quantify change in time and interindividual differences in chronic disease, and single patient research aimed at evidencing pharmacotherapeutic decisions in individual elderly patients. These research designs are not new, but they are undervalued and sparsely used. Qualitative research can clarify differences in patients' treatment preferences and motivation and their consequences. Cohort-studies of geriatric patients can show the effects of complex and long lasting medical histories on current treatment options. Single patient research can replace non-systematic trial and error by randomized controlled trials per patient.

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Validation of multifrequency bioelectrical impedance analysis in monitoring fluid balance in healthy elderly subjects.

BACKGROUND: Multifrequency Bioelectrical Impedance Analysis (MFBIA) is a novel method to assess body composition in elderly subjects. However, it is unclear whether MFBIA can detect changes in body water compartments in elders. We aimed to determine the within-subject variability of MFBIA and the responsiveness to a diuretic intervention in aged subjects with a stable fluid balance. METHODS: We selected 12 healthy active elderly subjects (5 male, 7 female) with a mean age of 75 years. Total body water and extracellular fluid (ECF) were measured by deuterium oxide- and potassium bromide-dilution techniques. Within-subject variability in total body MFBIA was assessed by performing four measurements at 1, 5, 50, and 100 kHz within a 2-month period. Subsequently, responsiveness of MFBIA to the ECF loss caused by oral administration of 40 mg of furosemide was determined. RESULTS: Within-subject variability in MFBIA at 1, 5, 50, and 100 kHz expressed as standard deviations was 21, 19, 14, and 14 Ohm (omega), respectively. Furosemide caused a mean weight loss of 1.8 +/- 0.6 kg, which resulted in significant increases in impedance of 57 +/- 24 omega at 1 kHz and 37 +/- 12 omega at 100 kHz (p < .001). The responsiveness of MFBIA for the diuretic intervention was best at 5 kHz (responsiveness index = 1.98). CONCLUSIONS: Within-subject variability of MFBIA was small in healthy elderly subjects with stable fluid balance. Responsiveness of MFBIA to 9% furosemide-induced ECF loss was excellent. These data support the necessity for further clinical assessment of the value of MFBIA in monitoring fluid balance in geriatric patients.

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Validation of multi-frequency bioelectrical impedance analysis in detecting changes in fluid balance of geriatric patients.

OBJECTIVES: Multi-Frequency Bioelectrical Impedance Analysis (MFBIA) is a quick, simple, and inexpensive method to assess body fluid compartments. This study aimed at determining the validity of MFBIA in detecting clinically relevant changes of fluid balance in geriatric patients. DESIGN: A prospective, observational study. SETTING: The 22-bed Geriatric Department of the University Hospital Nijmegen. PARTICIPANTS: Hospitalized patients were eligible if they did not have a pacemaker, were not suffering from terminal illnesses, and did not have psychogeriatric diseases likely to interfere with capacity to consent or comply. During a 16-months period, 218 patients were admitted, of whom 78 patients were eligible and 53 consented to participate. MEASUREMENTS: Each subject's fluid balance was diagnosed twice a week as dehydrated, overhydrated, or euvolemic, based on standardized physical examination, laboratory tests, and weight evaluation. Changes in fluid balance were quantified by measuring total body water (TBW) and extracellular fluid (ECF) applying deuterium- and bromide-dilution techniques. Impedance at 1, 5, 50, and 100 kHz and body weight were measured daily. Sensitivity and Guyatt's responsiveness indexes of MFBIA in detecting dehydration and overhydration were determined. RESULTS: In total, 1071 MFBIA measurements were performed, during which 14 transitions from dehydration to euvolemia and 13 transitions from overhydration to euvolemia were monitored. Rehydration of dehydrated patients caused an increase in TBW and ECF of 3.4 +/- 1.8 L and 1.9 +/- 1.9 L, respectively, which resulted in significant decreases in impedance of 133 +/- 67 omega at 1 kHz and 93 +/- 61 omega at 100 kHz (P = .001). Treatment of overhydrated patients caused a TBW and ECF loss of 3.8 +/- 4.2 L and 3.1 +/- 3.8 L, respectively, which resulted in significant increases in impedance of 104 +/- 72 omega at 1 kHz and 81 +/- 68 omega at 100 kHz (P < .001). Sensitivity of a single MFBIA in diagnosing dehydration and overhydration was 14% and 17%, respectively. Responsiveness indexes of weighing and MFBIA for dehydration and overhydration were similar at all frequencies and greater than one. CONCLUSION: The sensitivity of a single impedance measurement in detecting dehydration and overhydration was low. However, responsiveness of serial measurements to intra-individual changes in fluid balance was good. Therefore, this noninvasive technique may be used in clinical practice to improve monitoring fluid balance in geriatric patients, especially when daily weighing is difficult.

Activities of Daily Living↗

[Informed consent and mental competence of the elderly in medical-scientific studies].

The decision whether a potential subject is competent or incompetent is a necessary and crucial part of conducting medical research in the elderly. The assessment of competency is required by the legal and ethical frameworks in which this research has to take place. The state of play in the national and international discussions of bills for legislation of this topic will be summarized. Especially the practical consequences of this forthcoming legislation for researchers will be explained. The ethical framework for medical research with elderly subjects will be described from a historical point of view. By means of a review of relevant literature the legal definition of competency will be operationalized and tests for its assessment will be discussed. Competency of consent is assessed by asking several questions about the essential elements of the study. The introduction of a try out of the study for a subject before asking consent ('experienced consent') is propagated as a method to optimize this consent of elderly subjects. Special conditions for giving the required information to elderly subjects, for the informed consent by proxy and for the inclusion of nursing-home residents, are discussed.

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