[Death of an older patient after reactivation of latent tuberculosis]. / Wie denkt er nog aan tuberculose? Overlijden na reactivatie van latente tuberculose bij een oudere patiënt.

Latent tuberculosis has a high prevalence rate among older patients. Latent tuberculosis could be reactivated when patients are treated with immunosuppression. Therefore it is crucial to create awareness of the high prevalence of tuberculosis in the older patient. A thorough assessment of the risk of infection before starting immune modulating treatments contributes to timely recognition and treatment Our patient had an unknown history of latent tuberculosis. He was admitted to the geriatric department because of his deteriorating condition after the start of different immunosuppressing drugs for his arthritis. He developed cavitating pulmonary lesions. The PCR detected Mycobaterium tuberculosis.

Components and Outcomes in Under- and Postgraduate Medical Education to Prepare for the Delivery of Integrated Care for the Elderly: A Scoping Review.

Introduction: The ageing society requires physicians who can deliver integrated care, but it is unclear how they should be prepared for doing so. This scoping review aims to create an overview of educational programmes that prepare (future) physicians to deliver integrated care while addressing components and outcomes of the interventions. Method: We included papers from five databases that contained: (1) integrated care (2) education programme (3) medical students (4) elderly, or synonyms. We divided the WHO definition of integrated care into ten components for the concept of 'integrated care'. Data were collected with a charting template, and template analysis was used to formulate themes. Results: We found 17 educational programmes in different learning settings. All programmes addressed several components of the WHO definition. The programmes primarily focused on care for individual patients (micro-level), and the outcomes suggested that experiencing the complexity of care is key. Conclusion: This review revealed the limited evidence on educational programmes about integrated care for the elderly. Our findings suggest that educational programmes on integrated care should not be limited to the micro-level, and that students should obtain adaptive expertise by experiencing complexity. Future research should contain an explicit description and definition of integrated care.

[Effects of a structured medication review by geriatrician and clinical pharmacologist on appropriateness of pharmacotherapy in frail elderly inpatients]. / Interventies na een gestructureerde medicatie-analyse door klinisch geriater en ziekenhuisapotheker bij klinisch opgenomen kwetsbare oudere patiënten.

OBJECTIVE: To study the results of a structured medication review of geriatric inpatients by both geriatrician and hospital pharmacist/clinical pharmacologist. METHODS: Patients who were present at the geriatric ward were eligible for a review of their medication and medical problems using a screening form. Recommendations and questions following these forms were subsequently discussed in the gerontopharmacologic meeting ('GFO') held every two weeks. RESULTS: In a 30 month-period 44 GFO's were held during which 184 patients were discussed. A total of 206 recommendations were made and 115 questions were asked. Of the recommended interventions,134 (65%) were accepted by the geriatrician. To stop a medication (64/206), to change the dosage of a medication (60/206) and to switch to another medication (44/206) were the types of interventions most accounted for. CONCLUSION: Structured medication review led to a substantial number of medication changes in geriatric inpatients. Nearly two-thirds of the recommended interventions were accepted by the geriatricians. Seventy-two recommendations (35%) were not implemented due to logistic or patient-related reasons.

Interventies na een gestructureerde medicatie-analyse door klinisch geriater en ziekenhuisapotheker bij klinisch opgenomen kwetsbare oudere patiënten.

EFFECTS OF A STRUCTURED MEDICATION REVIEW BY GERIATRICIAN AND CLINICAL PHARMACOLOGIST ON APPROPRIATENESS OF PHARMACOTHERAPY OF FRAIL ELDERLY INPATIENTS: Objective To study the results of a structured medication review of geriatric inpatients by both geriatrician and hospital pharmacist/clinical pharmacologist. Methods Patients who were present at the geriatric ward were eligible for a review of their medication and medical problems using a screening form. Recommendations and questions following these forms were subsequently discussed in the gerontopharmacologic meeting ('GFO') held every two weeks. Results In a 30 month-period 44 GFO's were held during which 184 patients were discussed. A total of 206 recommendations were made and 115 questions were asked. Of the recommended interventions,134 (65%) were accepted by the geriatrician. To stop a medication (64/206), to change the dosage of a medication (60/206) and to switch to another medication (44/206) were the types of interventions most accounted for. Conclusion Structured medication review led to a substantial number of medication changes in geriatric inpatients. Nearly two-thirds of the recommended interventions were accepted by the geriatricians. Seventy-two recommendations (35%) were not implemented due to logistic or patient-related reasons.

Interventions to prevent postoperative delirium in elderly cancer patients should be targeted at those undergoing nonsuperficial surgery with special attention to the cognitive impaired patients.

AIMS: The aim of this study was to determine risk factors for postoperative delirium (POD) in elderly cancer patients. METHODS: This study was an observational multicentre retrospective study performed in the University Medical Center Groningen and Medical Center Leeuwarden, the Netherlands. Patients over 65 years of age undergoing elective surgery for a solid tumour were included. The main outcome was POD. Medical records were screened for POD using a standardized instrument. The risk factors considered were: age, gender, severity of the surgical procedure, comorbidity, American Society of Anaesthesiologists (ASA) score and 15 items suggestive for frailty as measured with the Groningen Frailty Indicator (GFI). To examine an association between the risk factors and the development of POD, univariate and multivariate logistic regression analysis was performed to estimate odds ratios (ORs) and 95% confidence intervals (CIs). RESULTS: We reviewed 251 medical records. Forty-six patients developed POD (18.3%). Preoperative cognitive functioning (as measured by the item cognition of the GFI) (OR: 23.36; 95% CI: 5.33-102.36) and severity of the surgical procedure were identified as independent risk factors for POD; intermediate (OR: 15.44, 95% CI: 1.70-140.18) and major surgical procedures (OR: 45.01, 95% CI: 5.22-387.87) significantly increased the risk for POD as compared to minor surgery. CONCLUSIONS: Preoperative cognitive functioning and the severity of the surgical procedure are independent risk factors for POD in elderly undergoing elective surgery for a solid tumour.

Role of cobalamin intake and atrophic gastritis in mild cobalamin deficiency in older Dutch subjects.

BACKGROUND: The reason for the high prevalence of mild cobalamin (vitamin B-12) deficiency in the elderly is poorly understood. OBJECTIVE: We aimed to determine the reason for this high prevalence. DESIGN: We examined cobalamin intake, the presence and severity of atrophic gastritis, the presence of Helicobacter pylori infection, and plasma cobalamin and methylmalonic acid (MMA) concentrations in 105 healthy, free-living, older subjects aged 74-80 y. RESULTS: Mild cobalamin deficiency, ie, low to low-normal plasma cobalamin concentrations (< 260 pmol/L) and elevated plasma MMA concentrations (> 0.32 micromol/L), were found in 23.8% of subjects; 25.7% of subjects were not cobalamin deficient (plasma cobalamin > or = 260 pmol/L and plasma MMA < or = 0.32 micromol/L). Six subjects (5.8%), including 1 with mild cobalamin deficiency, had dietary cobalamin intakes below the Dutch recommended dietary intake of 2.5 microg/d. Mildly cobalamin-deficient subjects had lower total (diet plus supplements) cobalamin intakes (median: 4.9 microg/d; 25th and 75th percentiles: 3.9, 6.4) than did non-cobalamin-deficient subjects (median: 6.3 microg/d; 25th and 75th percentiles: 5.4, 7.9) (P = 0.0336), mainly because of less frequent use of cobalamin supplements (8% compared with 29.6%; chi2 = 3.9, P = 0.048). Atrophic gastritis was found in 32.4% of the total study group: mild to moderate in 19.6% and severe in 12.7%. The prevalence of severe atrophic gastritis, but not mild-to-moderate atrophic gastritis, was higher in mildly cobalamin-deficient subjects (25%) than in non-cobalamin-deficient subjects (3.7%) (chi2 = 4.6, P = 0.032). The prevalence of immunoglobulin G antibodies to H. pylori was similar in mildly cobalamin-deficient subjects (54.2%) and in non-cobalamin-deficient subjects (44.4%) (chi2 = 0.5, P = 0.5). CONCLUSIONS: The high prevalence of mild cobalamin deficiency in healthy, free-living, older Dutch subjects could be explained by inadequate cobalamin intake or severe atrophic gastritis in only 28% of the study population. Other mechanisms explaining mild cobalamin deficiency in older people must be sought.

Free and protein-bound cobalamin absorption in healthy middle-aged and older subjects.

OBJECTIVE: To study free- and protein-bound cobalamin absorption and the correlation with atrophic gastritis in healthy middle-aged and older subjects. DESIGN: A cross-sectional study. PARTICIPANTS: Fifty-two healthy subjects, aged 26 to 87 years, apparently free from conditions known to influence the cobalamin status. Middle-aged subjects were defined as those younger than 65 years of age (median age 57 years) and older subjects as those 65 years and older (median age 75 years). MEASUREMENTS: Protein-bound cobalamin absorption was assessed by 48-hour urinary excretion method following oral administration of scrambled egg yolk, labeled in vivo with 57 Co-cobalamin by injecting a hen with 57 Co-cyanocobalamin. The percentage of 57 Co-cobalamin bound to protein was 65%. Free cobalamin absorption was assessed by 48-hour urinary excretion method following oral administration of crystalline 57 Co-cyanocobalamin. Plasma cobalamin, folate and fasting plasma gastrin, and pepsinogen A and C concentrations were determined. RESULTS: The median urinary excretion of egg yolk 57 Co-cobalamin in middle-aged subjects was 12.3% (25th and 75th percentiles 10.5%-14.5%) compared with 11.7% (25th and 75th percentiles 9.8%-13.6%) in older subjects (P = .283). The median urinary excretion after administration of free 57 Co-cobalamin in middle-aged subjects was 25.7% (25th and 75th percentiles 20.6%-30.7%) compared with 27.9% (25th and 75th percentiles 21.4%-34.5%) in older subjects (P = .694). Neither egg yolk nor free 57 Co-cobalamin excretion correlated with age. A ratio of pepsinogen A to pepsinogen C less than 1.6, indicating atrophic gastritis, was found in 13 subjects. Within the atrophic gastritis group, 11 subjects had a pepsinogen A concentration greater than or equal to 17 micrograms/L, indicating mild to moderate atrophic gastritis, and two subjects had a pepsinogen A concentration less than 17 micrograms/L, indicating severe atrophic gastritis or gastric atrophy. All subjects had normal fasting plasma gastrin concentrations. Free and egg yolk 57 Co-cobalamin excretions were not reduced in the atrophic gastritis group when compared with the non-atrophic gastritis group. Median plasma cobalamin concentration was not significantly lower in older subjects (P = .205). Nonetheless, plasma cobalamin concentration correlated negatively with age (r = -.36; P = .008). CONCLUSIONS: We demonstrated no significant difference in either free or protein-bound cobalamin absorption between healthy middle-aged and older adults. In addition, no alteration in cobalamin absorption was found in subjects identified as having mild to moderate atrophic gastritis. Therefore, based on our results, the high prevalence of low cobalamin levels in older people cannot be explained by either the aging process or mild to moderate atrophic gastritis.

Cobalamin supplementation improves cognitive and cerebral function in older, cobalamin-deficient persons.

BACKGROUND: Mild cobalamin (Cbl) deficiency is frequently found in older persons and is associated with cognitive and cerebral abnormalities. The effects of Cbl supplementation on these abnormalities are largely unknown. METHODS: In a single-blind, placebo-controlled intervention study, 16 healthy community-dwelling elderly subjects with low plasma Cbl concentration and no cognitive impairments were studied. Subjects underwent 1 month of treatment with placebo, followed by 5 months of treatment with intramuscular injections of hydroxycobalamin. Before and after measurements of plasma cobalamin, total homocysteine (tHcy), methylmalonic acid (MMA), quantitative electroencephalograph (qEEG), and psychometric tests were taken. RESULTS: After Cbl supplementation, plasma Cbl concentrations increased, and plasma MMA and tHcy concentrations decreased. The performance on the Verbal Word Learning Test, Verbal Fluency and Similarities improved. qEEG showed more fast activity and less slow activity. Lower plasma tHcy concentrations were related to increased fast activity on qEEG on the one hand and improved performance on the Verbal Word Learning Test and Similarities on the other. Increased fast or decreased slow activity on qEEG was associated with improved performance on the Verbal Word Learning Test, Similarities and Verbal Fluency. CONCLUSIONS: Electrographic signs of improved cerebral function and improved cognitive function were found after Cbl supplementation in older subjects with low plasma Cbl concentrations who were free of significant cognitive impairment. These improvements were related to a reduction of plasma tHcy concentration.

Clinical significance of low cobalamin levels in older hospital patients.

BACKGROUND: It is still a commonly held belief that many of the frequently found low cobalamin (Cbl, vitamin B12) levels in older people do not represent deficiency and are therefore without clinical significance and should not be treated. In this study this notion will be challenged. METHODS: In this prospective observational cohort design we studied 28 patients aged 65 years and older with low plasma Cbl (< or =150 pmol/l). A number of haematological (Hb, MCV, five- and six-lobed granulocytes), metabolic (plasma levels of methylmalonic acid and homocysteine), and gastrointestinal (plasma pepsinogen A and C and protein-bound and free Cbl absorption) parameters, and the response to Cbl treatment, were measured. Cbl deficiency was considered to be present when at least one of the following three criteria was fulfilled: (1) haematological or metabolic abnormalities compatible with Cbl deficiency; (2) Cbl malabsorption or atrophic gastritis; (3) a response to Cbl supplementation. RESULTS: Haematological or metabolic abnormalities were identified in 27 patients. Atrophic gastritis and Cbl malabsorption were identified in, respectively, 15 and 23 patients. Each treated patient showed a haematological or metabolic response to Cbl supplementation. All patients were considered Cbl deficient: 18 patients (64%) fulfilled three criteria of Cbl deficiency, eight (29%) fulfilled two criteria and two (7%) fulfilled one criterion. CONCLUSIONS: According to the generally accepted and a wide variety of criteria, we found that older patients with low Cbl levels were cobalamin deficient. Therefore, these patients should receive Cbl supplementation.

[Digoxin poisoning in patients of 2 geriatric departments in London: prevalence and mortality]. / Digoxine-intoxicatie bij patiënten van twee Londense geriatrische afdelingen: prevalentie en mortalitiet.

Digoxin is a toxic drug with a narrow therapeutic index that is mostly used by the elderly. Although it is accepted that toxicity of digoxin occurs more frequently in elderly than in younger patients, there is dispute about its prevalence and associated mortality. A study was therefore set up to, on the one hand, find the prevalence and associated mortality of digoxin toxicity in patients admitted onto two geriatric wards in London and, on the other hand, to study the relationship between serum digoxin level and age, serum urea, serum potassium and serum calcium in geriatric patients with digoxin toxicity. Over a period of three years 1438 patients (age 75-93) were admitted of whom 452 (31%) were on digoxin. Thirty-five patients (7.7%) were diagnosed as having digoxin toxicity. Eight patients (22.9%) with digoxin toxicity died during admission. Mortality was higher although not statistically significant for the patients with toxicity than for the patients who were on digoxin without toxicity. The fatal outcome was not predicted by age, serum urea, serum potassium or serum calcium. The serum digoxin level of the eight patients who died was lower than the level of those (n = 23) who survived. Four patients (11%) had a normal serum digoxin level and clinical features of digoxin toxicity that disappeared on stopping digoxin. A hypothesis is put foreward to explain the weak association between serum digoxin level and digoxin toxicity in geriatric patients.

[Recruitment and selection of test subjects for scientific research in geriatrics: literature review and experiences of the Nijmegen NESTOR study]. / Werving en selectie van proefpersonen voor wetenschappelijk onderzoek in de geriatrie: literatuurgegevens en ervaringen uit het Nijmeegse NESTOR-onderzoek.

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.

Effect of long-term treatment with galantamine on weight of patients with Alzheimer's dementia.

OBJECTIVES: There is discussion about the effect of cholinesterase inhibitors (CERs) on weight of patients with Alzheimer's disease (AD). Given the adverse outcomes of weight loss in AD patients, it is important to establish the effect of CERs on weight. This study aimed tot assess the long-term effect of galantamine on weight of AD patients. DESIGN, SETTING AND PARTICIPANTS: This longitudinal study was performed at a large memory clinic in the North of the Netherlands. During the period 2002 to 2010, 303 community-dwelling AD patients, aged 65 years or older who started using a cholinesterase inhibitor (CER), were included. MEASUREMENTS: Socio-demographic characteristics and data on comorbidity, number of medications, type and dosage of CER, use of care, cognitive function, behaviour and nutritional status (weight, Body Mass Index (BMI)) were recorded at the time the diagnosis AD was made and at subsequent outpatient clinic visits. The Generalized Estimating Equations (GEE) model was used to determine the effect of galantamine of 16 mg and 24 mg on weight. The effect of galantamine in a dose of 16 and 24 mg was investigated because the other groups (rivastigmine, galantamine 8 mg) were too small to determine the effect on weight by GEE analysis. Donepezil is not available in the Netherlands. RESULTS: The median follow-up time between the moment patients started using a CER (T0) and the 1st visit was 6 months (n=300); between T0 and the 2nd visit 13 months (n=212); between T0 and the 3rd visit 25 months (n=117) and between T0 and the 4th visit 37 months (n=58). Galantamine 16 mg and 24 mg, corrected for age, gender, social status, informal care, professional care, comorbidity, number of medications, cognition, behaviour and appetite, had no effect on weight (p > 0.05). Male patients had a higher average weight compared to female patients (p=0.000, B=8.333). Patients without an informal caregiver (p=0.01, B=-3.697) or partner (p=0.042, B=-3.197) had a lower average weight compared to patients with an informal caregiver or partner. CONCLUSION: Weight loss in AD patients should not be attributed to long-term treatment with galantamine. This is in accordance with the French guideline. If AD patients are losing weight, other causes, including insufficient care, should be investigated.

Nutritional status of community-dwelling elderly with newly diagnosed Alzheimer's disease: prevalence of malnutrition and the relation of various factors to nutritional status.

OBJECTIVES: To determine the prevalence of malnutrition and its relation to various factors in community-dwelling elderly with newly diagnosed Alzheimer's disease (AD). DESIGN: Retrospective cross-sectional study. SETTING: Memory clinic in a rural part of the Netherlands. PARTICIPANTS: 312 Community-dwelling AD patients, aged 65 years or older, were included. MEASUREMENTS: At the time the diagnosis AD was made, socio-demographic characteristics and data on nutritional status (Mini Nutritional Assessment (MNA)), cognitive function (Mini Mental State Examination (MMSE), Cambridge Cognitive Examination (Camcog)), functional status (Interview for Deterioration in Daily Living Activities in Dementia (IDDD), Barthel Index (BI)) and behaviour (Revised Memory and Behaviour Problems Checklist (RMBPC)) were assessed. Characteristics of well-nourished patients (MNA score >23.5) were compared to characteristics of patients at risk of malnutrition (MNA score 17-23.5). Linear regression analysis was performed to assess the effect of various factors on nutritional status. RESULTS: The prevalence of malnutrition was 0% and 14.1% was at risk of malnutrition. AD patients at risk of malnutrition were more impaired in basic and complex daily functioning than well-nourished AD patients (median IDDD score 41.5 [25th -75th percentile 38.8-48.0] versus median IDDD score 40.0 [25th -75th percentile 37.0-43.0], p = 0.028). The degree of impairment in basic and complex daily functioning (IDDD) was independently related to nutritional status (MNA) (p = 0.001, B = -0.062). CONCLUSION: One in seven community-dwelling elderly with newly diagnosed AD is at risk of malnutrition. The degree of impairment in daily functioning is independently related to nutritional status. Therefore, assessment of the nutritional status should be included in the comprehensive assessment of AD patients. The relation between daily functioning, nutritional status and AD warrants further investigation.

Nasal absorption of hydroxocobalamin in healthy elderly adults.

AIMS: To investigate the nasal absorption of hydroxocobalamin in 10 healthy elderly adults. METHODS: In a cross-over study, blood samples were collected before administration of the drug and after 10, 20, 30, 40, 60, 120, 180 and 240 min. The plasma cobalamin concentration was determined by competitive radioisotope binding technique. RESULTS: The maximal plasma cobalamin concentration (Cmax) after nasal administration of 750 microg hydroxocobalamin was 1900 +/- 900 pmol l(-1) (mean +/- s.d.). The maximal plasma cobalamin concentration was reached in 35 +/- 13 min (t[max]). The Cmax after nasal administration of 1500 microg hydroxocobalamin was 3500 +/- 2500 pmol l(-1) with a t(max) of 28 +/- 16 min. Both the AUC(0,240 min) and AUC(0,00) increased significantly with an increase of the dose from 750 microg to 1500 microg (P = 0.037 and P = 0.028, respectively). The nasal spray was well tolerated. No signs of irritation or local sensitivity were noted. CONCLUSIONS: The nasal absorption of hydroxocobalamin in healthy elderly adults is rapid, high and well tolerated.

Cerebrospinal fluid methylmalonic acid concentrations in neurological patients with low and normal serum cobalamin concentrations.

OBJECTIVE: To determine whether cerebrospinal fluid (CSF) methylmalonic acid (MMA) is increased in neurological patients with low serum cobalamin (Cbl, vitamin B12) concentrations as opposed to neurological patients with normal serum Cbl concentrations. MATERIAL AND METHODS: We measured MMA concentrations in serum and CSF of neurological patients with low serum cobalamin concentrations, but without overt cobalamin related manifestations such as anemia or combined disease of the cord, and neurological patients with normal serum cobalamin concentrations (controls). RESULTS: Serum and CSF MMA concentrations were significantly higher in patients than in controls. Serum MMA was elevated in 4 patients of whom 3 had clearly elevated CSF MMA concentrations. CONCLUSION: Strong indications for cobalamin deficiency can be found not only in serum but also in CSF of patients with seemingly asymptomatic low serum cobalamin concentrations.