Prevention and treatment of vitamin D deficiency in Dutch psychogeriatric nursing home residents by weekly half-body UVB exposure after showering: a pilot study.

BACKGROUND: in older people, induction of cutaneous vitamin D production by ultraviolet B (UVB) exposure may be preferable to oral supplementation: it cannot cause toxic levels, it helps to prevent polypharmacy and, moreover, there are indications that UVB exposure has beneficial effects on health and well being by mechanisms other than the vitamin D pathway alone. OBJECTIVE: the aim of this pilot study is to investigate whether weekly, half-body, UVB irradiation after showering can increase serum 25-hydroxyvitamin D (25(OH)D) to sufficient levels, in a Dutch psychogeriatric nursing home population. METHOD: subjects were eight psychogeriatric nursing home patients, mean age: 79 ± 8. Exclusion criteria were going outdoors into the sun more than once a week, the presence of actinic or cancer skin lesions and known resistance to body contact. The intervention consisted of weekly half-body UVB irradiation, after showering, over 8 weeks, with 0.5 minimal erythemal dose (MED). Main outcome measures were change in fasting serum levels of 25(OH)D and parathyroid hormone (PTH) at 0, 2, 4 and 8 weeks. RESULTS: at baseline, mean serum 25(OH)D was 28.5 nmol/l. Mean serum 25(OH)D levels increased to 46.5 nmol/l. Median serum PTH levels decreased by 20% after 8 weeks of treatment. CONCLUSION: an 8 week course of weekly, frontal half-body irradiation with UVB, at 0.5 MED, leads to an significant increase in 25(OH)D serum levels, but this period is too short to reach vitamin D sufficiency.

[Degree of discomfort following the decision to discontinue artificial nutrition and hydration in institutionalised psychogeriatric patients with severe dementia who no longer or scarcely eat or drink]. / Mate van onwelbevinden bij psychogeriatrische patiënten met vergevorderde dementie, die zelf niet of nauwelijks meer eten of drinken, bij wie in het verpleeghuis is besloten afte zien van kunstmatige toediening van voedsel en vocht.

OBJECTIVE: To determine the level and course of discomfort after the decision was made to forgo artificial nutrition and hydration (ANH) in nursing home patients with severe dementia who scarcely or no longer eat and drink. DESIGN: Longitudinal questionnaire investigation. METHOD: In a prospective, longitudinal, observational study conducted in 32 Dutch nursing homes, discomfort was measured in 178 patients using the observational 'Discomfort scale for patients with dementia of the Alzheimer type' (DS-DAT) at various time points: on the day of the decision to discontinue ANH and 2, 5, 9, 14 and 42 days thereafter. Data on factors that may have influenced the degree of discomfort were also collected at all time points. RESULTS: The decision to forgo ANH occurred most often in severely demented female patients with an acute illness. Overall, 134 patients (75%) died within 1-2 weeks after the decision. The mean level ofdiscomfort was highest on the day of the decision and decreased thereafter. However, the degree of discomfort differed substantially among patients. The presence of dyspnoea, restlessness, and physician-observed pain and dehydration were associated with higher levels of discomfort. Patients who were awake had higher levels of observed discomfort than patients who were asleep. CONCLUSION: Discontinuing ANH in patients with severe dementia who scarcely or no longer eat or drink was not generally associated with high levels of discomfort and therefore appears to be an acceptable decision. The individual differences emphasise the need for constant attention to distressful symptoms.

Immunization with human papillomavirus type 16 (HPV16) oncoprotein-loaded dendritic cells as well as protein in adjuvant induces MHC class I-restricted protection to HPV16-induced tumor cells.

Human papillomavirus (HPV) E6 and E7 oncoproteins are attractive targets for T-cell-based immunotherapy of cervical cancer. In this study, we demonstrate that dendritic cells (DCs) pulsed with HPV16 E7 protein are not only recognized in vitro by E7-specific CTLs but also elicit E7-specific CTL responses in vivo, associated with protection against a challenge with syngeneic HPV16-induced tumor cells. Vaccination with soluble E7 protein in incomplete Freund's adjuvant likewise induces E7-specific CTL responses associated with tumor protection. The presence of HPV16 E7-specific CTLs in vivo and the observation that depletion of CD8+ cells completely abolishes tumor protection demonstrate that CTLs are the major effector cells in mediating antitumor activity. The in vivo involvement of DCs in the activation of protective CTLs is suggested by the surface display of E7 peptide-loaded MHC class I molecules on these cells after E7 protein immunization. These data show that HPV16 E7 protein-pulsed DCs, as well as the administration of E7 protein antigen in adjuvant, can effectively stimulate tumor-specific MHC class I-restricted CD8+ T-cell-mediated protective immunity to HPV16-induced cancers.

Chronische pijn bij dementie en bij aandoeningen met een verhoogd risico op cognitieve achteruitgang.

Chronic pain in dementia and in disorders with a high risk for cognitive impairment. Ageing increases the risk for the etiology of chronic pain ánd dementia. Hence, the increase in the number of elderly people implies that the number of elderly with dementia suffering from chronic pain will increase as well. A key question relates to if and how patients with dementia perceive pain. The inadequateness of pain assessment, particularly in a more advanced stage, is also reflected in a decreased use of analgesics by elderly people with dementia. Insight into possible changes in pain experience as have been observed in the few available clinical studies, could be enhanced by knowledge about the neuropathology which may differ per subtype of dementia. It is striking that pain has not been examined in degenerative diseases of the central nervous system with a high risk for cognitive impairment such as Parkinson's disease and multiple sclerosis. In these disorders, pain is a prominent clinical symptom and to date it is not known whether the experience of pain will change in a stage in which patients become cognitively impaired. Finally, a number of instruments which are most appropriate to assess pain in communicative and non-communicative patients are discussed.

[Chronic pain in dementia and in disorders with a high risk for congnitive impairment]. / Chronische pijn bij dementie en bij aandoeningen met een verhoogd risico op cognitieve achteruitgang.

Ageing increases the risk for the etiology of chronic pain and dementia. hence, the increase in the number of elderly people implies that the number of elderly with dementia suffering from chronic pain will increase as well. A key question relates to if and how patients with dementia perceive pain. the inadequateness of pain assessment, particularly in a more advanced stage, is also reflected in a decreased use of analgesics by elderly people with dementia. Insight into possible changes in pain experience as have been observed in the few available clinical studies, could be enhanced by knowledge about the neuropathology which may differ per subtype of dementia. It is striking that pain has not been examined in degenerative diseases of the central nervous system with a high risk for cognitive impairment such as Parkinson's disease and multiple sclerosis. In these disorders, pain is a prominent clinical symptom and to date it is not known whether the experience of pain will change in a stage in which patients become cognitively impaired. Finally, a number of instruments which are most appropriate to assess pain in communicative and non-communicative patients are discussed.

Determinants of bone mineral density and risk factors for osteoporosis in healthy elderly women.

Bone mineral density (BMD) and risk factors for osteoporosis were assessed in 348 apparently healthy women over 70 years of age (mean 82.3 years). BMD was measured at both hips and the dominant distal radius. With stepwise multiple regression the best determinants of BMD, selected from anthropometric measurements, age, and years since menopause, were body weight and years since menopause (R2 between 0.07 and 0.20, p < 0.001). Risk and protective factors for osteoporosis were analyzed as indicator variables by multiple regression and corrected for confounding by age, years since menopause, and body weight. Significantly lower BMD at the hip was found in participants with impaired mobility (-5%) and users of loop diuretics (-5%). Use of thiazide(like) diuretics did not influence BMD significantly at any site. Users of oral corticosteroids had a significantly lower BMD at the hip and the distal radius (range -9.1 to -24.3%). Participants with a history of Colles' fracture (n = 56) had a significantly lower BMD at the other radius (-12.9%). The mean calcium intake from dairy products was high (mean 921 mg/day), only 11% having an intake below 500 mg. A relation of calcium intake with BMD could not be detected at any measurement site. We conclude that BMD cannot be adequately predicted in elderly women. Risk factors for low BMD in the elderly are low body weight, high number of years since menopause, impaired mobility, and use of loop diuretics and oral corticosteroids. Calcium intake was not a risk factor in this study, but the number of individuals on a low calcium intake was small.

The effect of vitamin D supplementation on the bone mineral density of the femoral neck is associated with vitamin D receptor genotype.

Recent studies suggest that variations of the vitamin D receptor (VDR) gene are related to bone mineral density (BMD). In this study, we examined the effect of vitamin D3 supplementation on BMD at the femoral neck in relation to VDR genotype. We analyzed 81 women, age 70 years and over, who participated in a placebo-controlled clinical trial on the effect of vitamin D3 supplementation (400 IU daily for at least 2 years) on BMD and fracture incidence. VDR genotype was based on the presence (b) or absence (B) of the BsmI restriction site. Mean BMD of the right and left femoral neck was measured at baseline and after 1 and 2 years. Dietary calcium, body mass index, and years since menopause were assessed at baseline while biochemical markers were measured at baseline and after 1 year. There was no difference among the BB, Bb, and bb genotype for baseline measurements of BMD at the femoral neck (mean and SD, g/cm2: 0.70 (0.10), 0.71 (0.12), and 0.69 (0.10), respectively), nor for any of the biochemical indices. The mean increase of BMD in the vitamin D group relative to the placebo group, expressed as percentage of baseline BMD, was significantly higher (p = 0.03) in the BB (delta BMD: 4.4%, p = 0.04) and Bb genotype (delta BMD: 4.2%, p = 0.007) compared with the bb genotype (delta BMD: -0.3%, p = 0.61). No significant changes were found for any of the other measured parameters. The VDR genotype-dependent effect of vitamin D supplementation in these elderly subjects suggest a functional involvement of VDR gene variants in determining BMD.

Ultraviolet irradiation corrects vitamin D deficiency and suppresses secondary hyperparathyroidism in the elderly.

The objective of this study was to compare the effect of ultraviolet radiation (UV) and oral vitamin D3 on the vitamin D status and parathyroid hormone (PTH) concentration in elderly nursing home patients. The design of the study was a randomized clinical trial. The setting was a psychogeriatric nursing home. Subjects included 45 female psychogeriatric patients with a mean age of 85 years. Exclusion criteria were going outdoors more than once a week and the presence of actinic or cancer skin lesions. Intervention was random allocation of UV-B irradiation at half the minimal erythemal dose of the lower back, three times per week during 12 weeks (UV-B), or oral vitamin D3 400 IU/day during 12 weeks (VIT-D), or no treatment (CONTR). Main outcome measures were change in fasting serum levels of vitamin D metabolites at 0, 2, 4, 8, and 12 weeks in the treatment groups, compared with the control group. PTH(1-84) was measured at 0 and 12 weeks. Baseline serum 25-hydroxyvitamin D (25(OH)D) was lower than 30 nmol/l in 95% of the participants. It increased to a median value of around 60 nmol/l after 12 weeks both in the UV-B and VIT-D groups, whereas there was no change in the CONTR group. Serum 1,25-dihydroxyvitamin D increased significantly in the UV-B group. Serum calcium increased significantly in both treatment groups. Serum PTH decreased more than 30% in both treatment groups (p < 0.001), whereas there was no significant change in the control group. Irradiation with UV-B in the very elderly for a few minutes per day leads to adequate improvement of the vitamin D status. It is as effective as oral vitamin D3 in increasing serum 25(OH)D and suppressing secondary hyperparathyroidism.

Vitamin D status and sex hormone binding globulin: determinants of bone turnover and bone mineral density in elderly women.

To examine the relation of the vitamin D status and the remaining estrogen activity with bone turnover and bone mineral density (BMD) in elderly women, BMD was measured at both hips using dual-energy X-ray absorptiometry and at the distal radius using single photon absorptiometry, in 330 healthy women aged 70 and over. Vitamin D metabolites, sex hormone binding globulin (SHBG), PTH(1-84), osteocalcin, alkaline phosphatase, and hydroxyproline and calcium excretion in 2 h fasting urine were measured. Multiple linear regression was used to adjust for potential confounders. In 65% of the women, serum 25(OH)D was below 30 nmol/l. Only values below a threshold for 25(OH)D were negatively related to serum PTH(1-84) (p = 0.02, threshold at 25 nmol/l) and to osteocalcin levels (p = 0.04, threshold at 30 nmol/l). BMD of the femoral neck and trochanter was positively related to serum 25(OH)D (left neck p = 0.001) with thresholds at 30 nmol/l whereas the distal radius was not (p = 0.32). Serum PTH was negatively related to BMD at all measurement sites (all p < 0.001). Serum SHBG, an inverse measure of estrogen activity, was positively related to osteocalcin levels (p = 0.004) and the urinary hydroxyproline/creatinine ratio (p = 0.002) and negatively related to the BMD of the trochanter (left trochanter p = 0.02) and the distal radius (p = 0.001). We conclude that in elderly women, serum 25(OH)D levels below 30 nmol/l are associated with secondary hyperparathyroidism and increased bone turnover. SHBG is positively related to bone turnover.(ABSTRACT TRUNCATED AT 250 WORDS)

Prevention of bone loss by vitamin D supplementation in elderly women: a randomized double-blind trial.

The purpose of the study was to determine the effect of vitamin D supplementation on bone turnover and bone loss in elderly women. Three hundred forty-eight women, ages 70 yr and older, were randomized to receive 400 IU vitamin D3 per day (n = 177) or placebo (n = 171), double-blind, for a period of 2 yr. Main outcome measures were bone mineral density of both hips (femoral neck and trochanter) and the distal radius, as well as biochemical markers of bone turnover. The effect of vitamin D supplementation was expressed as the difference in mean (percentage) change between the placebo group and the vitamin D group. The measurements were repeated in 283 women after 1 yr and in 248 women after 2 yr. Vitamin D supplementation significantly increased serum 25-hydroxyvitamin D (250HD) (+35 nmol/L) and 1,25-dehydroxyvitamin D [1,25-(OH)2D] (+7.0 pmol/L) levels and urinary calcium/creatinine ratios (+0.5%) and significantly decreased PTH(1-84) secretion (-0.74 pmol/L) after 1 yr. No effect was found for the parameters of bone turnover. The effect on the bone mineral density of the left femoral neck was +1.8% in the first yr, +0.2% in the second yr, and +1.9% during the whole period (95% confidence interval 0.4, 3.4%). At the right femoral neck the effects were +1.5%, +1.1%, and +2.6% (confidence interval 1.1, 4.0%), respectively. No effect was found at the femoral trochanter and the distal radius. Supplementation with 400 IU vitamin D3 daily in elderly women slightly decreases PTH secretion and increases bone mineral density at the femoral neck.

Ultrasound measurements in the calcaneus: precision and its relation with bone mineral density of the heel, hip, and lumbar spine.

Broadband ultrasound attenuation (BUA) and speed of sound (SOS) in the heel are suggested to measure bone density and structure and to predict fracture risk. Short-term precision (five consecutive measurements in 1 h) and long-term precision (six within 3 months) of ultrasound parameters were studied in 20 healthy subjects. The coefficient of variation (CV) did not change over a 3-month period for SOS (1.3%). Short-term precision of BUA was 3.4% (CV) and long-term precision was 4.9% (CV) (not significantly different: p = 0.09). Relationships between ultrasound parameters and BMD at various sites were examined in 42 subjects. BMD at the heel was assessed at the location corresponding to that of the ultrasound measurements (BMDheel). Correlation coefficients, corrected for imprecision in the measurements, for BUA and SOS vs. BMDheel, were 0.81 and 0.76, respectively. The correlation coefficients between heel measurements (BUA, SOS, and BMDheel) and BMD in the hip and lumbar spine ranged from 0.37 to 0.57. The relationships between BUA, SOS, and BMDheel vs. BMD of the hip were modified by physical activity and body weight. Higher physical activity and body weight were associated with higher BMD values at the hip. BUA values < 60 dB/MHz predicted BMD at the femoral neck < 0.70 g/cm2 with a sensitivity and specificity of 80% and 93%, respectively. After the age of 30, 11 participants had sustained vertebral fractures and 12 participants nonvertebral osteoporotic fractures. BUA and SOS values were significantly lower in fracture patients than in participants without fractures. It can be concluded that ultrasound measurements at the heel correlate well to BMD at the same site. BUA can predict BMD at the hip and is lower when the subject has sustained fractures.

Stimulation of cartilage differentiation by osteogenic protein-1 in cultures of human perichondrium.

Exposure of progenitor cells with chondrogenic potential to recombinant human osteogenic protein-1 [rhOP-1, or bone morphogenetic protein-7 (BMP-7] may be of therapeutic interest in the regeneration of articular cartilage. Therefore, in this study, we examined the influence of rhOP-1 on cartilage formation by human perichondrium tissue containing progenitor cells with chondrogenic potential in vitro. Fragments of outer ear perichondrium tissue were embedded in clotting autologous blood to which rhOP-1 had been added or not (controls), and the resulting explant was cultured for 3 weeks without further addition of rhOP-1. Cartilage formation was monitored biochemically by measuring [³5;S]sulfate incorporation into proteoglycans and histologically by monitoring the presence of metachromatic matrix with cells in nests. The presence of rhOP-1 in the explant at the beginning of culture stimulated [³5;S]sulfate incorporation into proteoglycans in a dose-dependent manner after 3 weeks of culture. Maximal stimulation was reached at 40 microgram/ml. Histology revealed that explants treated with 20-200 microgram/ml rhOP-1, but not untreated control explants, contained areas of metachromatic-staining matrix with chondrocytes in cell nests. These results suggest that rhOP-1 stimulates differentiation of cartilage from perichondrium tissue. The direct actions of rhOP-1 on perichondrium cells to stimulate chondrocytic differentiation and production of cartilage matrix in vitro provide a cellular mechanism for the induction of cartilage formation by rhOP-1 in vivo. Thus, rhOP-1 may promote early steps in the cascade of events leading to cartilage formation. Therefore, rhOP-1 could be an interesting factor for regeneration of cartilage in articular cartilage defects.

Relationship between internal risk factors for development of decubitus ulcers and the blood flow response following pressure load.

The objective of this study was to investigate the extent to which internal risk factors for the development of decubitus ulcers are related to the blood flow response following the relief of a pressure load. There were 122 nursing home patients (43 men, 69 women, mean age: 81 +/- 8 years; range: 60-97). The following potential, internal risk factors for the development of decubitus ulcers were assessed: chronic disorders (diabetes mellitus, cardiovascular disease [congestive heart failure, history of myocardial infarct or angina pectoris] and cerebrovascular accident), fever, blood pressure, nutritional status, serum hemoglobin concentration, and serum urea and serum creatinine concentrations. Skin temperature response (latency time and total response time) was measured following relief of a 100 kPa test pressure. The presence of cardiovascular disease, cerebrovascular accident, poor nutritional condition, high serum urea and male gender showed a significant relationship with an impaired blood flow response. The delayed latency found showed a similarity to the so-called "no-reflow phenomenon." The association of cardiovascular disease and a cerebrovascular accident with a delay in the blood flow response may result from endothelial damage. A poor nutritional condition may be associated with a deficit of scavengers of oxygen-derived free radicals. The presence of free radicals may damage endothelium during reperfusion, thus influencing the blood flow response. The association of high serum urea with delayed vasodilatation may theoretically be explained by the association of serum urea and impaired kidney functioning, since the kidney is an important organ in the production of vasoactive substances. Serum urea can also be considered a measure for nutritional condition. Gender may function as a substitute for other, unmeasured factors that are related to blood flow response.

Effects of the implementation of the Resident Assessment Instrument on gaps between perceived needs and nursing care supply for nursing home residents in the Netherlands.

This study evaluated the effects of the implementation of the Resident Assessment Instrument (RAI) on gaps perceived between residents' needs and nursing care received in Dutch nursing homes. In a controlled group design residents were interviewed before and after the implementation. Most gaps were perceived in the psycho-social area rather than physical or needs with aids and facilities. In general, perceived gaps decreased more strongly in the experimental group. The results give an indication that assessment using RAI leads to a better meeting of the residents' perceived needs. More research is needed to investigate the quality of the assessment using RAI in more detail.

[Short version of the Dutch Behavioral Rating Scale for Psychogeriatric Inpatients (GIP-28)]. / Verkorte Gedragsobservatieschaal voor de Intramurale Psychogeriatrie (GIP-28).

This study reports on a new rating scale, the short version (GIP-28) of the Dutch Behavioral Rating Scale for Geriatric Inpatients (GIP). Only a limited number of items was needed to adequately describe GIP variance in two patient samples (n = 2196 and n = 126). Based on previous results factor analysis produced three factors: 'apathy', 'cognitive' and 'affective' symptoms. This led to the construction of new subscales which showed significant differences between persons in different patient settings. Elderly patients with a cognitive disorder or schizophrenia/mood disorder according to DSM-IV criteria, were correctly classified in almost 80% of the cases. We conclude that the GIP-28 is equivalent to the GIP and describes aspects of apathy and cognitive and affective symptoms in elderly patients. A compact rating scale like this might best be used in (routine) screening of cognitive and noncognitive behavioral problems. It may also prove useful for outpatient purposes.

[Abbreviated form of the Informant Questionnaire on cognitive decline in the elderly]. / Verkorte Informantvragenlijst over cognitieve achteruitgang bij ouderen.

This study evaluated some psychometric qualities of the Dutch short form Informant Questionnaire on Cognitive Decline in the Elderly (IQCODE-N). The score profile on the short form IQCODE-N was comparable in two outpatient populations. Short form and regular IQCODE-N are equivalent, as they were highly correlated (r = 0.97). However, using IQCODE-N cut-off scores the short form appeared to be more strict in defining 'decline'. A moderately high correlation was found between informant ratings and dementia screening tests CST (r = -0.47) and ADS (r = -0.46). Informant ratings were not influenced by patient's age or level of education. The short form IQCODE-N describes cognitive change in everyday activities of elderly patients and can be an efficient rating scale for clinical assessment of dementia.

[The role of observer for the reliability of Dutch version of the Discomfort Scale-Dementia of Alzheimer Type (DS-DAT)]. / De rol van de observator in de betrouwbaarheid van de Nederlandse versie van de Discomfort Scale-Dementia of Alzheimer Type (DS-DAT).

The role of the observer in the reliability of the Dutch Discomfort Scale-Dementia of Alzheimer Type (DS-DAT). The Discomfort Scale of Dementia of the Alzheimer Type (DS-DAT) is an instrument to assess discomfort in severely demented patients. No data on the reliability of assessment using a Dutch translation were available. In this paper, we analyse the role of the observer in the reliability of rating. This is of importance for studies in which many physicians perform multiple assessments. Twenty-eight nursing home physicians in training rated the DS-DAT in five nursing home patients with dementia presented on videotape. This was repeated after five months. All the physicians were previously trained in the use of the instrument. The results were statistically analysed using random effects analysis of variance. The Intra-class Correlation Coefficient (ICC) was 0.74 for inter-observer reliability and 0.97 for intra-observer reliability. Variance between subsequent assessments was small, but physicians appeared to differ somewhat among themselves in the way they rated the videotaped patients. A future complete reliability assessment of rating the DS-DAT in clinical practice would involve patient variation as well, scoring patients in clinical practice.

[Vitamin D supplementation in the elderly: guidelines and practice]. / Vitamine D-suppletie bij ouderen: advies en praktijk.

OBJECTIVE: In 2008, the Health Council of the Netherlands published an advice on vitamin D supplementation for the elderly. Nevertheless, suspicion arose at the Ministry of Health, Welfare and Sport and the Netherlands Nutrition Centre that vitamin D supplementation in the elderly is still insufficient. We aimed to determine the extent to which general practitioners and elderly care physicians actually followed the advice of the Health Council. DESIGN: Questionnaire study. METHOD: Brief questionnaires were sent to all elderly care physicians in the Netherlands. Some questions were also posed to general practitioners at a network meeting of the Academic Network of GP Practices of the VU University Medical Center in Amsterdam. RESULTS: More than two-thirds of the respondents, both elderly care physicians and general practitioners, are familiar with the guidelines of the Health Council of the Netherlands on vitamin D supplementation in the elderly, but about half do not prescribe vitamin D when the guideline advises to do so. When supplementation is prescribed, about half of the elderly care physicians and a fifth of the general practitioners uses an insufficient dose. CONCLUSION: The guidelines of the Health Council of the Netherlands on vitamin D supplementation in the elderly are not sufficiently followed by elderly care physicians and general practitioners. Awareness of and support for the vitamin D supplementation guidelines among health care providers is still limited.