Quantitative Ultrasound of the Mandible as a Novel Screening Approach for Osteoporosis.

This study used an axial transmission quantitative ultrasound (QUS) device to assess mandibular bone strength. The aim of the study was first to establish the precision and repeatability of the axial transmission QUS measurement for a range of mandibular anatomic sites, and second to investigate the ability of the modality to differentiate between osteoporotic subjects and a control group. Three groups of adult Caucasian women were recruited: (1) healthy premenopausal women (n = 26), (2) healthy postmenopausal women (n = 48), and (3) women with osteoporosis (n = 53). Subjects were excluded from groups 1 and 2 if they had any pre-existing bone conditions. Speed of sound (SOS) measurements were taken from the mandible using an OmniSense multisite QUS device. Group 3 had dual-energy X-ray absorptiometry scans of the lumbar spine and femur. The most suitable site on the mandible was determined by repeat SOS measurements in 10 healthy premenopausal subjects, at 5 different sites. The parasymphysis site had the lowest root mean squared coefficient of variation at 0.74%, and was chosen as the most suitable site for mandibular SOS measurements. Group 1 and group 2 had significantly higher mean SOS measurements than the osteoporotic subjects (group 3), with means of 3683 m/s (210), 3514 m/s (221), and 3312 m/s (264), respectively. A 1-way analysis of variance confirmed a statistically significant difference between mean SOS measurements from the 3 groups (p < 0.0001). Axial transmission QUS of the mandible can differentiate between subjects with osteoporosis and a healthy control group, and shows potential for use as a screening tool for osteoporosis.

Effective osteoporosis treatment with teriparatide is associated with enhanced quality of life in postmenopausal women with osteoporosis: the European Forsteo Observational Study.

BACKGROUND: To describe changes in health-related quality of life (HRQoL) of postmenopausal women with osteoporosis treated with teriparatide for up to 18 months and followed-up for a further 18 months, and to assess the influence of recent prior and incident fractures. METHODS: The European Forsteo Observational Study (EFOS) is an observational, prospective, multinational study measuring HRQoL using the EQ-5D. The primary objective was to assess changes in HRQoL during 36 months in the whole study population. A secondary post-hoc analysis examined fracture impact on HRQoL in four subgroups classified based on recent prior fracture 12 months before baseline and incident clinical fractures during the study. Changes from baseline were analysed using a repeated measures model. RESULTS: Of the 1581 patients, 48.4% had a recent prior fracture and 15.6% of these patients had an incident fracture during follow-up. 10.9% of the 816 patients with no recent prior fracture had an incident fracture. Baseline mean EQ-VAS scores were similar across the subgroups. In the total study cohort (n = 1581), HRQoL (EQ-VAS and EQ-5D index scores) improved significantly from baseline to 18 months and this improvement was maintained over the 18-month post-teriparatide period. Improvements were seen across all five EQ-5D domains during teriparatide treatment that were maintained after teriparatide was discontinued. Subjects with incident clinical fractures had significantly less improvement in EQ-VAS than those without incident fractures. Recent prior fracture did not influence the change in EQ-VAS during treatment. CONCLUSIONS: EFOS is the first longitudinal study in women with severe postmenopausal osteoporosis in the real world setting to show a substantial improvement in HRQoL during teriparatide treatment that was sustained during subsequent treatment with other medications. The increase in HRQoL was lower in the subgroups with incident fracture but was not influenced by recent prior fracture. The results should be interpreted in the context of the design of an observational study.

Frailty and quality of life for people with Alzheimer's dementia and mild cognitive impairment.

BACKGROUND: Our aim was to investigate the relationship between frailty and health-related quality of life (HR-QOL) in cognitively impaired elderly individuals. METHODS: A cross-sectional observational study of a convenience sample of 115 patients with a diagnosis of Alzheimer's dementia or mild cognitive impairment. Frailty was measured using the biological syndrome model and HR-QOL was measured using the DEMQOL-Proxy. Regression models were constructed to establish the factors associated with HR-QOL. RESULTS: Frailty and neuropsychiatric symptoms were associated with HR-QOL, with Mini-Mental State Examination (MMSE) scores ≥21 (P = .037, P ≤ .001, and R (2) = .362). Functional limitation was associated with HR-QOL, with MMSE scores ≤20 (P = .017 and R (2) = .377). CONCLUSION: Frailty and neuropsychiatric symptoms were the determinants of HR-QOL in the earlier stages of cognitive impairment. Functional limitation predicted HR-QOL in the later stages of cognitive impairment. Frailty may represent a novel modifiable target in early dementia to improve HR-QOL for patients.

Effectiveness of Teriparatide in women over 75 years of age with severe osteoporosis: 36-month results from the European Forsteo Observational Study (EFOS).

This predefined analysis of the European Forsteo Observational Study (EFOS) aimed to describe clinical fracture incidence, back pain, and health-related quality of life (HRQoL) during 18 months of teriparatide treatment and 18 months post-teriparatide in the subgroup of 589 postmenopausal women with osteoporosis aged ≥75 years. Data on clinical fractures, back pain (visual analogue scale, VAS), and HRQoL (EQ-5D) were collected over 36 months. Fracture data were summarized in 6-month intervals and analyzed using logistic regression with repeated measures. A repeated-measures model analyzed changes from baseline in back pain VAS and EQ-VAS. During the 36-month observation period, 87 (14.8 %) women aged ≥75 years sustained a total of 111 new fractures: 37 (33.3 %) vertebral fractures and 74 (66.7 %) nonvertebral fractures. Adjusted odds of fracture was decreased by 80 % in the 30 to <36-month interval compared with the first 6-month interval (P < 0.009). Although the older subgroup had higher back pain scores and poorer HRQoL at baseline than the younger subgroup, both age groups showed significant reductions in back pain and improvements in HRQoL postbaseline. In conclusion, women aged ≥75 years with severe postmenopausal osteoporosis treated with teriparatide in normal clinical practice showed a reduced clinical fracture incidence by 30 months compared with baseline. An improvement in HRQoL and, possibly, an early and significant reduction in back pain were also observed, which lasted for at least 18 months after teriparatide discontinuation when patients were taking other osteoporosis medication. The results should be interpreted in the context of an uncontrolled observational study.

Effectiveness of teriparatide in postmenopausal women with osteoporosis and glucocorticoid use: 3-year results from the EFOS study.

OBJECTIVE: To describe clinical fracture rates, back pain, and health-related quality of life (HRQOL) in postmenopausal women with osteoporosis who are receiving glucocorticoids (GC), during a 36-month study of teriparatide treatment for up to 18 months, with an additional 18-month followup period when patients were receiving other osteoporosis medications. METHODS: A prospective, multinational, observational study. Data for clinical fractures, back pain (by visual analog scale; VAS) and HRQOL (by EQ-5D) were collected over 36 months. Fracture data were summarized in 6-month segments and analyzed using logistic regression with repeated measures. Changes from baseline in back pain VAS and EQ-VAS were analyzed. RESULTS: Of 1581 enrolled women with followup data, 294 (18.6%) had antecedents of GC use. Of these, 49 (16.7%) patients sustained a total of 69 fractures during the 36-month study period. Adjusted odds of fracture were significantly decreased during the last year of followup compared with the first 6 months of teriparatide treatment: an 81% decrease in the 24 to < 30-month period (p < 0.05), and an 89% decrease in the 30 to < 36-month period (p < 0.05). There were significant reductions in back pain and improvements in HRQOL in both groups of GC users and nonusers. CONCLUSION: Postmenopausal women with severe osteoporosis receiving GC, who were treated with teriparatide for up to 18 months, showed a reduced incidence of clinical fractures during the third year while receiving sequential osteoporosis treatments compared with the first 6 months, together with reduced back pain and improved HRQOL. Our results should be interpreted in the context of an uncontrolled observational study in a routine clinical setting.

Self-efficacy for managing dementia may protect against burden and depression in Alzheimer's caregivers.

BACKGROUND: Self-efficacy is the belief that one can perform a specific task or behaviour and is a modifiable attribute which has been shown to influence health behaviours. Few studies have examined the relationship between self-efficacy for dementia-related tasks and symptoms of burden and depression in caregivers. METHODS: Eighty four patient/caregiver dyads with Alzheimer's disease were recruited through a memory clinic. Patient function, cognition and neuropsychiatric symptoms were assessed together with caregiver burden, personality, depressive symptoms, coping strategies and self-efficacy for completing tasks related to dementia care. RESULTS: 33% (28) of caregivers reported significant depressive symptoms (CES-D ≥ 10). In multivariate analyses, caregiver burden was predicted by self-efficacy for symptom management, neuroticism, patient function and neuropsychiatric symptoms while caregiver depression was predicted by self-efficacy for symptom management, caregiver educational level, neuroticism, emotion-focused coping, dysfunctional coping and patient function. In patients with moderate to severe impairment (MMSE ≤ 20), self-efficacy for symptom management behaved as a mediator between patient neuropsychiatric symptoms and symptoms of burden and depression in caregivers. CONCLUSIONS: Further longitudinal investigation is warranted to determine if self-efficacy might be usefully considered a target in future interventional studies to alleviate symptoms of burden and depression in Alzheimer's caregivers.

Determinants of the desire to institutionalize in Alzheimer's caregivers.

BACKGROUND: The desire to institutionalize is an important predictor of future institutionalization. Few studies have examined potentially modifiable caregiver characteristics which might be the focus of future interventional strategies. METHODS: A total of 102 patient/caregiver dyads with Alzheimer's disease (n = 84) or mild cognitive impairment were recruited through a memory clinic. Cross-sectional analyses of a range of patients, caregivers, and context of care-related characteristics were conducted. RESULTS: Caregiver desire to institutionalize was significantly associated with a number of potentially modifiable variables including caregiver coping style, self-efficacy, depression, burden, and the presence of an unmet service need. In a multivariate analysis, caregiver burden, depression, and nonspousal status were the only significant independent predictors of caregiver desire to institutionalize in a model which correctly classified 80.4% of caregivers. CONCLUSIONS: Interventions which seek to reduce caregiver desire to institutionalize should adopt a multifactorial approach to reduce symptoms of burden and depression in caregivers.

Dependence and caregiver burden in Alzheimer's disease and mild cognitive impairment.

The dependence scale has been designed to be sensitive to the overall care needs of the patient and is considered distinct from standard measures of functional ability in this regard. Little is known regarding the relationship between patient dependence and caregiver burden. We recruited 100 patients with Alzheimer's disease or mild cognitive impairment and their caregivers through a memory clinic. Patient function, dependence, hours of care, cognition, neuropsychiatric symptoms, and caregiver burden were assessed. Dependence was significantly correlated with caregiver burden. Functional decline and dependence were most predictive of caregiver burden in patients with mild impairment while behavioral symptoms were most predictive in patients with moderate to severe disease. The dependence scale demonstrated good utility as a predictor of caregiver burden. Interventions to reduce caregiver burden should address patient dependence, functional decline, and behavioral symptoms while successful management of the latter becomes more critical with disease progression.

Reduction in fracture rate and back pain and increased quality of life in postmenopausal women treated with teriparatide: 18-month data from the European Forsteo Observational Study (EFOS).

The European Forsteo Observational Study was designed to examine the effectiveness of teriparatide in postmenopausal women with osteoporosis treated for up to 18 months in normal clinical practice in eight European countries. The incidence of clinical vertebral and nonvertebral fragility fractures, back pain, and health-related quality of life (HRQoL, EQ-5D) were assessed. Spontaneous reports of adverse events were collected. All 1,648 enrolled women were teriparatide treatment-naive, 91.0% of them had previously received other anti-osteoporosis drugs, and 72.8% completed the 18-month study. A total of 168 incident clinical fractures were sustained by 138 (8.8%) women (821 fractures/10,000 patient-years). A 47% decrease in the odds of fracture in the last 6-month period compared to the first 6-month period was observed (P < 0.005). Mean back pain VAS was reduced by 25.8 mm at end point (P < 0.001). Mean change from baseline in EQ-VAS was 13 mm by 18 months. The largest improvements were reported in the EQ-5D subdomains of usual activities and pain/discomfort. There were 365 adverse events spontaneously reported, of which 48.0% were considered related to teriparatide; adverse events were the reason for discontinuation for 79 (5.8%) patients. In conclusion, postmenopausal women with severe osteoporosis who were prescribed teriparatide in standard clinical practice had a significant reduction in the incidence of fragility fractures and a reduction in back pain over an 18-month treatment period. This was associated with a clinically significant improvement in HRQoL. Safety was consistent with current prescribing information. These results should be interpreted in the context of the open-label, noncontrolled design of the study.

Characterization of patients in the European Forsteo Observational Study (EFOS): postmenopausal women entering teriparatide treatment in a community setting.

OBJECTIVE: The European Forsteo Observational Study (EFOS) study was primarily designed to assess fracture incidence, degree of pain, health-related quality of life (HRQoL) and compliance in women prescribed teriparatide in a community setting. This report describes the design of the study and characteristics of the patients at entry. METHODS: At entry, 1645 postmenopausal women with a diagnosis of osteoporosis and about to initiate teriparatide treatment were enrolled in eight European countries. Baseline data were collected on demographic characteristics, medical and osteoporosis history, disease status, prior use of medications and HRQoL. RESULTS: The mean (standard deviation [SD]) age of patients was 71.5 (8.4) years, lumbar spine bone mineral density (BMD) T-score was -3.3 (1.2), the mean number of previous fractures reported after 40 years of age was 2.9 (2.0), 70% had two or more vertebral deformities and 91.7% were pre-treated with bisphosphonates. HRQoL, evaluated by the health state value (HSV) (median: 0.59, Q1; Q3: 0.08; 0.71) and visual analogue scale (VAS) (median 50.0, Q1; Q3: 35.0; 69.0) status of the European quality of life questionnaire (EQ-5D) was poor. Extreme problems were reported by 31% of patients for the pain/discomfort dimension, mobility was limited in 69% and anxiety/depression was reported by 57% of patients. Chronic or intermittent back pain was reported by 91% of patients, which occurred every day or almost every day within the last month in 66% of patients. CONCLUSIONS: The post-menopausal women prescribed teriparatide were severely osteoporotic, with a high fracture risk and poor HRQoL, despite previous therapy for osteoporosis. Moderate to severe back pain was very common.

Investigating the enhancing effect of music on autobiographical memory in mild Alzheimer's disease.

The enhancing effect of music on autobiographical memory recall in mild Alzheimer's disease individuals (n = 10; Mini-Mental State Examination score >17/30) and healthy elderly matched individuals (n = 10; Mini-Mental State Examination score 25-30) was investigated. Using a repeated-measures design, each participant was seen on two occasions: once in music condition (Vivaldi's 'Spring' movement from 'The Four Seasons') and once in silence condition, with order counterbalanced. Considerable improvement was found for Alzheimer individuals' recall on the Autobiographical Memory Interview in the music condition, with an interaction for condition by group (p < 0.005). There were no differences in terms of overall arousal using galvanic skin response recordings or attentional errors during the Sustained Attention to Response Task. A significant reduction in state anxiety was found on the State Trait Anxiety Inventory in the music condition (p < 0.001), suggesting anxiety reduction as a potential mechanism underlying the enhancing effect of music on autobiographical memory recall.

Sequence and phylogenetic analysis of the gene for surface layer protein, slpA, from 14 PCR ribotypes of Clostridium difficile.

Clostridium difficile is the commonest cause of antibiotic-associated diarrhoea, with the hospitalized elderly being at particular risk. The organism makes a crystalline surface protein layer (S-layer), encoded by the slpA gene, the product of which is cleaved to give two mature peptides which associate to form the layer. The larger peptide (high molecular weight; HMW), derived from the C-terminal portion of the precursor, is relatively conserved, whereas the smaller peptide (low molecular weight; LMW), derived from the N-terminal portion of the precursor, is a dominant antigen which substantially forms the basis for serotyping of isolates. PCR ribotyping is a more discriminatory typing method, based on the intergenic rRNA. We obtained the sequence for slpA and some flanking DNA from a collection of C. difficile strains of 14 ribotypes isolated from elderly patients. Sequences from different ribotypes were compared with one another and with published sequences. Sequences from C. difficile ribotypes 046 and 092 were identical. Sequences from ribotype pairs 005 and 054, 012 and 046/092, 014 and 066 and 031 and 094 differed by 1-3 nt in the slpA gene. There were ultimately nine ribotypes or groups of ribotypes with very different slpA sequences, particularly in the region encoding the LMW peptide. The sequence from ribotype 002 was very different from previously published sequences. The DNA segment sequenced included the 5' 315 bp of a secA homologue, encoding a putative transport protein required for peptide secretion across the plasma membrane. The amino acid sequences of the predicted HMW peptides were aligned and a neighbour-joining tree was produced using 10,000 bootstrap replicates. The predicted SecA N-terminal region was similarly analysed. For both SlpA and SecA, a strong association was found between ribotypes 012, 046/092, 017, 031 and 094. Ribotypes 001 and 078 formed part of this clade for SlpA but not SecA, indicating independent evolution for slpA and secA, presumably because they come under different selection pressures.

Screening for dementia in an Irish community sample using MMSE: a comparison of norm-adjusted versus fixed cut-points.

BACKGROUND: The MMSE is a widely-used instrument in screening for dementia in the community. The traditional cut-point of <24/30 may be unsuitable for use in some settings, due to biases in age and education. OBJECTIVES: This study aimed to investigate whether cut-points derived from age- and education-specific norms would improve the performance of the MMSE as a screening tool for dementia and cognitive impairment in an Irish community setting, potentially reducing the number of onward referrals. A secondary aim was to obtain score norms in an Irish sample. METHODS: One thousand one hundred and fifteen people aged over 65 (mean age 74.8+/-6.8 years; 68% female) were assessed in their own homes, using MMSE (world) and the AGECAT computerised diagnostic system for mental illness in the elderly. The performance of the MMSE in identifying case- and sub-case-level dementia was investigated using cut-points of <24 and <23, as well as adjusted cut-points based on published norms and norms derived from the Irish sample. RESULTS: Published norms did not prove useful in improving screening accuracy. Cut-points based on 10th percentile Irish norms and the <23 cut-point performed comparably well, both yielding 93% specificity, with overall accuracy of 90% and 91% respectively (as sensitivity was higher for the <23 cut-point). CONCLUSIONS: Locally-derived norms yielded better screening accuracy than did published norms or the traditional <24 cut-point. The importance of selecting an appropriate percentile cut-off when using norms is discussed. The best results were obtained with a simple <23 cut-point, and this may be optimal when screening for dementia in an Irish community setting.