A Comparison of Patients with Hip Fracture, Ten Years Apart: Morbidity, Malnutrition and Sarcopenia.

OBJECTIVES: To investigate possible differences in morbidity, malnutrition, sarcopenia and specific drug use in patients with hip fracture, ten years apart. To analyse 1-year mortality and possible associations with variables. DESIGN: A prospective, observational study. SETTING: Örebro University Hospital, Sweden. PARTICIPANTS: Two cohorts of patients with hip fracture, included in 2008 (n=78) and 2018 (n=76). MEASUREMENTS: Presence of comorbidity according to the Elixhauser comorbidity measure, multimorbidity defined as ≥3 comorbidities, preoperative American Society of Anaesthesiologists Classification (ASA-class), malnutrition according to the definition by the Global Leadership Initiative on Malnutrition (GLIM), sarcopenia according to the most recently revised definition by the European Working Group on Sarcopenia in Older People (EWGSOP), polypharmacy defined as ≥5 prescribed medications, use of Potentially Inappropriate Medications (PIM) and Fall-Risk-Increasing-Drugs (FRID) and postoperative 1-year mortality. RESULTS: When comparing the cohorts, significant increases over time was seen for mean comorbidity-count (Difference -1; p=0.002), multimorbidity (Difference -15%; 95%CI -27;-2), ASA-class 3-4 (Difference -25%; 95%CI -39;-9) and polypharmacy (Difference -17%; 95%CI -32;-2). Prevalence of malnutrition and sarcopenia coherently decreased with 22% (95%CI 5;37) and 14% (95%CI 1;29) respectively. One-year mortality remained unchanged and a significant association was found for a higher ASA-class in 2008 (OR 3.5, 95%CI 1.1;11.6) when adjusted for age. Results on PIM exposure suggest a decrease while exposure to FRID remained high. CONCLUSION: Our findings support an increasing morbidity within the population over time. However, also presented is a coherent decrease in malnutrition and sarcopenia, suggesting a decrease in frailty as a possible explanation for the observed unaltered mortality, in turn suggesting advances in treatment of comorbidities.

Nutrient density and variation in nutrient intake with changing energy intake in multimorbid nursing home residents.

BACKGROUND: The low energy intake seen in some institutionalised elderly has led to a focus on energy dense diets. The present study aimed to investigate nutrient density in the diet of nursing home residents, and calculate how changes in energy intake affect nutrient intake. METHODS: The investigation comprised a longitudinal observational study analysing the relation between energy and nutrient intake in a general nursing home in Sweden. Food intake was weighed for 5 days every sixth month over 1.5 years and nutrient density was calculated. The 52 multimorbid residents [mean (range) age 84 (67-102) years] with three complete 5-day weighed food records were included in the study. A mixed linear model was used to calculate changes in nutrient intake with changing energy intake. RESULTS: Nutrient density was adequate for vitamins A, B(12), thiamine, riboflavin and niacin, and low for vitamins D and E, folate, potassium, magnesium and iron. The mixed linear model showed that the fat-soluble vitamins, as well as folate and vitamin B(12), increased the most with increasing energy intake, whereas sodium, potassium, thiamine and selenium had the smallest increase. CONCLUSIONS: Nutritional density of the food should be considered when planning diets for elderly patients with poor appetite.

Resting metabolic rate in elderly nursing home patients with multiple diagnoses.

BACKGROUND: In the diseased elderly weight loss and malnutrition are common. It is unclear to what degree this is caused by an elevated resting metabolic rate (RMR), a decreased energy intake or a combination of the two. OBJECTIVE: To measure RMR and nutrient induced thermogenesis (NIT) in chronically diseased elderly living in a nursing home and test for a correlation with fat free mass (FFM), age, energy intake and activities of daily living (ADL). DESIGN: Explorative study performed in the residents' own apartments. RMR was measured by indirect calorimetry, and NIT was tested by giving the subjects an oral fluid test meal, then measuring metabolic rate again one hour later. Body composition was measured anthropometrically and FFM was calculated. Energy intake was calculated from a five-day record of weighed food. BMR was calculated using four different prediction equations and compared with measured RMR. RESULTS: RMR was 1,174 kcal/d (29.3 kcal/kg FFM/d). The variation in RMR was significantly related to FFM (p < 0.0001). Energy intake was 1,474 kcal/d, (36.5 kcal/kg FFM/d). The energy intake/RMR ratio, was 1.27, and NIT was 15% (0-33%). NIT was not correlated to any of the parameters tested. The equation of Harris and Benedict underestimated BMR by 4%; the WHO/FAO overestimated BMR by 7%; Schofield and an estimate of 20 kcal/kg/d did not significantly differ from the measured mean. CONCLUSION: RMR was closely correlated to FFM. Variations in NIT could not be explained by any tested parameters. Predicted BMR differed from measured RMR by less than 8% in all methods, but individual variations were large.

Repeated assessment of energy and nutrient intake in 52 nursing home residents.

UNLABELLED: Studies in Swedish nursing-home patients have shown a high prevalence of protein-energy malnutrition. One potential cause for this may be low food intake. OBJECTIVE: To examine the intake of energy and nutrients in the residents of a nursing home; to investigate changes in dietary intake and body-weight over time and to analyze two-year-mortality. DESIGN: Explorative study. Five-day weighed assessment of food intake repeated three times during 1.5 years. Analysis of body composition at baseline and recording of body weight every third month. Analysis of two-year mortality. RESULTS: Fifty-two residents had three complete dietary assessments. Mean age 84 +/- 7 years, 79% were female. Mean body weight was stable at 61 kg. Mean energy intake at baseline was 1501 kcal/d (25 kcal/kg/d) and mean protein intake was 53 g/d (0.9 g/kg/d). Mean intake of vitamin D, vitamin E, folic acid, selenium and dietary fibre was less than 60% of recommended. At the second assessment intake of energy and many nutrients was higher than at baseline, but at the third assessment intake had decreased. There was no correlation between energy intake and body weight over time. Two-year mortality was 52%. Male gender and low body-weight constituted an increased risk of mortality. Comparing survivors and non-survivors showed that the mean body weight was 9 kg higher in the survivors throughout the study (p=0.02). This group had a relatively lower fat free mass and higher fat mass than the non-survivors. The difference in body composition was only seen in females, possibly due to the low number of males. The survivors had higher intakes of most nutrients but this reached significance only for a few of them. The non-survivors had significantly higher intakes of sucrose. CONCLUSION: Intake of energy and many nutrients was low in these nursing-home patients, and decreased further after one year, without any change in body weight. The significant positive relation between energy intake and body weight at group level disappeared when analyzing data at an individual level. Male gender and low body weight were associated with increased risk of mortality.

Elderly peoples' meals. A comparative study between elderly living in a nursing home and frail, self-managing elderly.

BACKGROUND: Sweden is one of few countries that have specific recommendations regarding mealtime habits. The importance of mealtime habits for health outcome is inadequately studied in elderly subjects. OBJECTIVE: The aim of this study was to investigate the distribution of the daily meals/energy intake; the number of eating episodes per day and subjectively estimated meal-dependent variables (appetite, motivation to eat, sense of taste and sense of smell) and compare the results of elderly living in a nursing home with frail, self-managing elderly living at home. DESIGN: Explorative study. All analyses of energy intake were based on food records; weighed in the nursing home and estimated in the frail, self-managing elderly. Participants or contact persons estimated the subjective variables using a 10-point VAS scale. RESULTS: On average there were 4-5 daily eating episodes in both groups. The eating episodes were much more widespread over the day in the self-managing elderly, and their length of fasting at night was significantly shorter. The subjects estimated appetite and sense of smell was reduced in about 30-40% in both groups. Sense of taste was reduced in 40 % of the males and 10-20 % of the females. Energy intake was similar in both groups, 25 kcal/kg body weight/day, with more than a threefold variation among individual subjects. Energy intake/kg body weight correlated with a shorter length of fasting at night in the nursing home residents, however, did not correlate with ADL, number of eating episodes per day, appetite, motivation to eat, or senses of taste or smell. CONCLUSION: The self-managing elderly had more widespread eating episodes than the elderly in the nursing home, indicating that self-managing elderly exhibit larger variations in food intake preferences, however, without affecting mean energy intake. The lack of correlation between energy intake and estimated appetite, taste and smell is in line with previous findings in elderly.

Dietary intake of energy, nutrients and water in elderly people living at home or in nursing home.

OBJECTIVES: There is a lack of detailed information on dietary intake in elderly people at an individual level, which is crucial for improvement of nutritional support. The aim of this study was to investigate the dietary intake in elderly people in two types of living situations. DESIGN: Observational study, analysing prospective data. SETTING: The dietary intake was studied in elderly people living at home or in nursing home, in different cities of Sweden. PARTICIPANTS: A total of 264 elderly people (mean age 84) participated in the observational study. MEASUREMENTS: Dietary intake was measured using weighed food records and food diaries, comparing females and males. The observed dietary intake was related to Recommended intake and Lower intake level. RESULTS: All dietary intake and patient characteristic variables showed large individual differences (ranges). We found no significant differences (p>0.05) between those living at home and nursing home residents regarding the average intake of energy, protein and water when expressed as total intake per kg of body weight. A very low daily intake of energy (<20 kcal/kg body weight/day) was observed in 16% of the participants. For vitamin D and iron, 19% and 15%, respectively, had intakes below the Lower intake level. There was no correlation between intake of energy, protein or water and resident characteristics such as age, autonomy, morbidity, nutritional state or cognition. CONCLUSIONS: The large individual differences (ranges) in energy, nutrients and water show that the use of mean values when analysing dietary intake data from elderly people is misleading. From a clinical perspective it is more important to consider the individual intake of energy, nutrients and water. Ageism is intrinsic in the realm of 'averageology'.

Evidence for reversible, non-microtubule and non-microfilament-dependent nuclear translocation of hsp90 after heat shock in human fibroblasts.

A monoclonal antibody (29A) directed against rat liver heat shock protein M(r) 90,000 (hsp90) was produced. By Western immunoblotting of cytosols prepared from several different tissues and species, 29A was shown to specifically recognize only one band with M(r) approximately 90,000. Localization of hsp90 in human gingival fibroblasts was studied using the 29A antibody by indirect mono- and double-staining immunofluorescence and confocal laser scanning microscopy. The distribution was compared to that of the glucocorticoid receptor (GR) and various cytoskeletal structures. Cells were analyzed in interphase and mitosis under basal culture conditions, after heat shock and after microtubule and microfilament depolymerization, sometimes combined with heat shock. A major part of hsp90 immunoreactivity was diffusely distributed throughout the interphase cytoplasm, but a weak nuclear staining with non-stained nucleoli was also present, however, only detectable after methanol and not after formaldehyde/Triton X-100 fixation. Heat shock induced a time-dependent translocation of hsp90 from the cytoplasm to the cell nucleus reaching a plateau after 15 h. This compartment shift was reversible and also occurred in the absence of intact microtubules or intact microfilaments.

Immunocytochemical localization of glucocorticoid receptor in human gingival fibroblasts and evidence for a colocalization of glucocorticoid receptor with cytoplasmic microtubules.

The cellular distribution of the glucocorticoid receptor (GR) in relation to various intracellular and plasma membrane structures in human fibroblasts was studied using indirect immunofluorescence techniques with monoclonal and polyclonal antibodies. During interphase, GR was located predominantly in the cytoplasm, showing a similar pattern as tubulin. In mitotic cells, GR and tubulin were localized in mitotic spindles and in telophase midbodies. Colchicine and vinblastine induced a similar redistribution of GR and tubulin to the cell periphery. This redistribution was reversible for colchicine but not for vinblastine. Vinblastine also induced paracrystals containing GR and tubulin. These results support the hypothesis that GR interacts in vivo with cytoplasmic microtubules.

Glucocorticoid receptor messenger ribonucleic acid in different regions of human adipose tissue.

The expression of glucocorticoid receptor (GR) messenger RNA (mRNA) was investigated in sc adipose tissue and isolated adipocytes from the abdominal and gluteal regions in men and women using a human GR complementary RNA probe. GR mRNA levels were 2-fold higher in female than in male abdominal tissue or adipocytes, whereas in gluteal tissue or adipocytes no sex differences were observed. GR mRNA levels in female abdominal adipocytes were 50% higher than in corresponding female gluteal adipocytes; the opposite was observed corresponding in males. Northern blot analysis of total cellular RNA isolated from abdominal and gluteal adipocytes showed hybridization of the human GR probe to an RNA species of approximately 7.1 kilobases in both regions. No sex or regional differences in GR mRNA stability were observed. The human metallothionein II (hMTII) mRNA, which is regulated by glucocorticoids at the transcriptional level, showed an opposite sex and regional pattern as GR mRNA. However, in gluteal adipose tissue no sex differences were observed in hMTII mRNA levels. The expression of beta-actin mRNA, which is not regulated by glucocorticoids, showed no sex or regional variation. By immunocytochemistry, using an anti-GR-monoclonal antibody, cytoplasmic as well as nuclear staining for GR was demonstrated in both sexes and both regions. In conclusion, variations in GR mRNA levels between sexes and body regions may explain the well known sex and tissue differences in effects of glucocorticoids on human adipose tissue.

Treatment of protein-energy malnutrition in chronic nonmalignant disorders.

Protein-energy malnutrition (PEM) is common in connection with chronic disease and is associated with increased morbidity and mortality. Because the risk of PEM is related to the degree of illness, the causal connections between malnutrition and a poorer prognosis are complex. It cannot automatically be inferred that nutritional support will improve the clinical course of patients with wasting disorders. We reviewed studies of the treatment of PEM in cases of chronic obstructive pulmonary disease, chronic heart failure, stroke, dementia, rehabilitation after hip fracture, chronic renal failure, rheumatoid arthritis, and multiple disorders in the elderly. Several methodologic problems are associated with nutrition treatment studies in chronically ill patients. These problems include no generally accepted definition of PEM, uncertain patient compliance with supplementation, and a wide range of outcome variables. Avail-able treatment studies indicate that dietary supplements, either alone or in combination with hormonal treatment, may have positive effects when given to patients with manifest PEM or to patients at risk of developing PEM. In chronic obstructive pulmonary disease, nutritional treatment may improve respiratory function. Nutritional therapy of elderly women after hip fractures may speed up the rehabilitation process. When administered to elderly patients with multiple disorders, diet therapy may improve functional capacity. The data regarding nutritional treatment of the conditions mentioned above is still inconclusive. There is still a great need for randomized controlled long-term studies of the effects of defined nutritional intervention programs in chronically ill and frail elderly with a focus on determining clinically relevant outcomes.

Morphometric studies of the localization of the glucocorticoid receptor in mammalian cells and of glucocorticoid hormone-induced effects.

We studied the subcellular distribution of the glucocorticoid receptor (GR) by light microscopy (LM) and confocal laser scanning microscopy (CLSM) in different mammalian cell types. The effect of added glucocorticoid hormones on GR distribution was investigated by photometric quantitation on optical sections obtained by CLSM followed by statistical analysis. In the control interphase cytoplasm, the distribution of GR was fibrillar in some and diffuse in other cell types. Fibrillar GR was distributed along cytoplasmic microtubules (MTs) with predilection for a subset of MTs. GR was also observed in the centrosomes. Nuclear GR was both diffuse and granular in distribution. During cell division, GR appeared in the mitotic apparatus at all stages of mitosis. These findings were not fixation-dependent. Glucocorticoid treatment increased both the nuclear and cytoplasmic GR signal. However, this was detectable only after precipitating but not cross-linking fixation. There was both intra- and intercellular GR heterogeneity in the absence and presence of hormone but no indication of a hormone-induced nuclear translocation of GR. We present a hypothetical model of two independent GR populations in the nucleus and cytoplasm, respectively, without any discernible ligand-induced nuclear translocation of GR. The extranuclear GR population may exert effect(s) on site in the cytoplasm without involving nuclear genomic transcription.

Glucocorticoid receptor inhibits microtubule assembly in vitro.

The effect of glucocorticoid hormones, purified glucocorticoid receptor (GR) and purified heat shock protein M(r) 90,000 (hsp90) on microtubule (MT) assembly in vitro was tested by a spectrophotometric MT assembly assay and electron microscopy. GR significantly prolonged the nucleation phase, slowed down the assembly rate and reduced the maximal amplitude of MT assembly compared with control. The effects were partially reversed by the addition of glucocorticoid hormone. GR associated with MTs. These results indicate that GR affects MT assembly in vitro, which may be a functional correlate to the structural association of GR with MTs. This implies that factors affecting GR may affect MT assembly in vivo.

Subcellular distribution of the glucocorticoid receptor and evidence for its association with microtubules.

The cellular distribution of the glucocorticoid receptor (GR) has not yet been firmly established. The extensive literature indicates that GR is present both in the cytoplasm and the cell nucleus, however, some studies have failed to detect cytoplasmic GR. It is still controversial as to whether GR is randomly diffusing in the cytoplasm and nucleus, or if the GR-distribution is organized or controlled in some way, which may be of importance for the transduction of glucocorticoid effects to cells. There is evidence that both non-activated and activated GR is associated with the plasma membrane, a number of cytoplasmic organelles and the nucleus. Both morphological and biochemical evidence show that GR is associated with microtubules during different stages of the cell cycle, i.e. GR co-localizes, co-purifies and co-polymerizes with tubulin. This indicates that GR is structurally linked to the intracellular MT-network which may be of importance in the mechanism of action of glucocorticoid hormones. The literature in this field is reviewed including the reported data on subcellular GR-localization.

Evidence for colocalization of glucocorticoid receptor with cytoplasmic microtubules in human gingival fibroblasts, using two different monoclonal anti-GR antibodies, confocal laser scanning microscopy and image analysis.

The cellular distribution of the glucocorticoid receptor (GR) in relation to the microtubule protein tubulin was studied in human gingival fibroblasts, using two different anti-GR antibodies of different Ig-classes, by indirect immunofluorescence immunocytology. Further studies were performed by confocal laser scanning microscopy and digital image analysis. The study focused on fluorochrome separation, optical sectioning, digital subtraction techniques and reconstruction of projections obtained using stacks of recorded transversal sections. The data presented further strengthens the notion of a structural colocalization between GR and cytoplasmic microtubules in human fibroblasts.

Individual assessment of intake of energy, nutrients and water in 54 elderly multidiseased nursing-home residents.

PURPOSE: Examination of the individual intake of energy, nutrients and water in clinically stable multidiseased nursing-home residents. METHODS: Comprehensive clinical assessment of 54 elderly nursing-home residents (80 +/- 10 years, mean +/- SD). The intake of food and beverages was measured by the weighed food intake method during five consecutive week days followed by computerized transformation to energy, 21 different nutrients, dietary fiber, alcohol and water. The resting energy expenditure was determined by indirect calorimetry. RESULTS: There was at least 2-3-fold, variation in intake of energy, nutrients and water, present also when expressed per kg body weight. For some micronutrients the relative intake variation was more than 8-fold. The results are compared with the present swedish recommended dietary allowances as well as with seven other studies of dietary intake in elderly using the weighed food intake method. The residents had on average 14.1 (range 6-31) different current clinical problems and were treated with a mean of 9.5 different drugs. The nursing staff spent 40 % of the total daytime working hours (7 am to 7 pm) on nutrition related issues. CONCLUSIONS: The nursing-home residents exhibited a large interindividual heterogeneity regarding intake of energy, nutrients and water. More emphasis should be given to individualized nutrition assessment in clinical geriatric care as a more solid base for nutrition treatment programmes integrated with the regular medical management and evaluation.

[Diagnostic test in clinical nutrition for medical students. Test results show that training in clinical nutrition must be improved]. / Diagnostiskt prov i klinisk nutrition för läkarstuderande. Provresultat visar att utbildningen i klinisk nutrition måste förbättras.

A national core curriculum in clinical nutrition was approved by the Section for Nutrition in the Swedish Society of Medicine in 1995. Here we report on the results of an anonymous diagnostic test based on this core curriculum in clinical nutrition, administered to medical students at the end of medical school. The test was the same for students in Linköping, Lund and Stockholm. Only 42% of the participants obtained an acceptable test result, with the score in Lund being significantly lower than those in Linköping and Stockholm. We compare the results with a similar test administered in Stockholm in 1996, and discuss current developmental work in clinical nutrition being done in all the medical faculties in Sweden.

Effects of nutritional intervention and physical training on energy intake, resting metabolic rate and body composition in frail elderly. a randomised, controlled pilot study.

OBJECTIVES: To analyse the effect of nutritional intervention and physical training on energy intake, resting metabolic rate (RMR) and body composition in the frail elderly. DESIGN: Open, randomised, controlled pilot treatment study. SETTING: Community-based research centre. PARTICIPANTS: Ninety-six community-dwelling frail elderly people aged 75 and older, 40% men. INTERVENTION: Four treatment arms: i) individual nutritional advice and group sessions on nutrition for the elderly, ii) physical training 2 x 45 minutes per week for 3 months, iii) combined nutritional and physical intervention and iv) control group. MEASUREMENTS: The outcomes were energy intake (4-day food diary); resting metabolic rate (indirect calorimetry) and body composition (anthropometry) performed at baseline, after 3 months' intervention (completed by 79 individuals), and as a follow-up at 9 months (completed by 64 individuals). RESULTS: The training group showed a significantly increased RMR at 3 months. Otherwise, there were no observed differences within or between the four groups. There was no correlation over time between energy intake, RMR and fat free mass. The participants with a low energy intake who managed to increase their energy intake during the study ('responders') had a statistically significantly lower BMI (21 vs. 24) and a lower fat percentage (23 vs. 30) at baseline than the 'non-responders'. The 'non-responders' showed a small but statistically significant decrease in body fat percentage at F1, and in body weight, BMI and FFM at 9 months (F3). CONCLUSION: Individual nutrition counselling and physical exercise had no effect on energy intake, RMR or fat free mass in community-dwelling frail elderly people aged 75 and older. Interventions in frail elderly people should be targeted according to the needs of the individual patients. The issues of randomisation, targeting and responders in are problematised and discussed.