Translation, validity and reliability of the persian version of the rapid assessment of physical activity questionnaire.

PURPOSE: The purpose of this study was to produce a valid and reliable Persian version of the Rapid Assessment of Physical Activity (RAPA) questionnaire, which previously has been shown to be valid and reliable for assessing physical activity among older adults. METHODS: Permission was obtained from the scale developer, who provided a copy of the the Linguistic Validation of the RAPA Qestionnaire, which utilizes a forward-backward translation methodology. Content validity, face validity, and construct validity of the questionnaire were then determined. Comparison of known groups (older adults with more or less than 50% balance confidence) was used to assess construct validity and the Leiden-Padua (LEIPAD) quality of life questionnaire were used to assess convergent validity. Three hundred older adults, who were members of the Qom retirement centers, participated in the study. Thirty participants completed the RAPA twice with a one-week interval to determine test-retest reliability. RESULTS: Results of comparisons of known groups showed that the mean RAPA score of the older people with greater balance confidence was significantly higher. Significant correlations between most of the scores obtained from both RAPA and the LEIPAD questionnaires confirmed the convergent validity of the questionnaire. Intraclass Correlation Coefficient (ICC) was as high as 0.94 showing that the test-retest reliability was good. CONCLUSION: This study showed the Persian RAPA is a reliable and valid instrument for measuring physical activity among older individuals in both research and clinical contexts.

Pain and function in patients with chronic low back pain and leg pain after Zhineng Qigong - a quasi-experimental feasibility study.

BACKGROUND: Qigong includes training for body and mind, one method is Zhineng Qigong. Scientific literature on qigong for chronic low back pain (LBP) is sparse. This study aimed to investigate feasibility including evaluation of a Zhineng Qigong intervention for pain and other lumbar spine-related symptoms, disability, and health-related quality of life in patients with chronic LBP and/or leg pain. METHODS: Prospective interventional feasibility study without control group. Fifty-two chronic pain patients (18-75 years) with LBP and/or leg pain (Visual Analogue Scale ≥ 30) were recruited from orthopaedic clinics (spinal stenosis, spondylolisthesis, or segmental pain) and primary healthcare (chronic LBP). Patients from orthopaedic clinics were 1-6 years postoperative after lumbar spine surgery or on lumbar surgery waiting list. Patients received a 12-week training intervention with European Zhineng Qigong. The intervention consisted of face-to-face group activities in non-healthcare setting (4 weekends and 2 evenings per week), and individual Zhineng Qigong training. Main health outcomes were self-reported in a 14-day pain diary, Oswestry Disability Index (ODI), Short Form 36 version 2 (SF-36v2), and EuroQol 5 Dimensions 5 Levels (EQ-5D-5L), once directly before and once directly after the intervention. RESULTS: Recruitment rate was 11% and retention rate was 58%. Dropouts did not report higher pain (baseline), only 3 dropped out because of lumbar spine-related pain. Adherence was median 78 h group attendance (maximum 94 h) and 14 min daily individual training. Ability to collect outcomes was 100%. Thirty patients completed (mean 15 years symptom duration). Twenty-five had degenerative lumbar disorder, and 17 history of lumbar surgery. Results showed statistically significant (within-group) improvements in pain, ODI, all SF-36v2 scales, and EQ-5D-5L. CONCLUSIONS: Despite low recruitment rate, recruitment was sufficient. A multicentre randomized controlled trial is proposed, with efforts to increase recruitment and retention rate. After this Zhineng Qigong intervention patients with chronic LBP and/or leg pain, also patients with considerable remaining LBP/sciatica after lumbar surgery, had significantly improved in pain and function. Results support involvement of postoperative patients in a future study. The results are promising, and this intervention needs to be further evaluated to provide the most reliable evidence. TRIAL REGISTRATION: NCT04520334. Retrospectively registered 20/08/2020.

Exploring a New Application of Construct Specification Equations (CSEs) and Entropy: A Pilot Study with Balance Measurements.

Both construct specification equations (CSEs) and entropy can be used to provide a specific, causal, and rigorously mathematical conceptualization of item attributes in order to provide fit-for-purpose measurements of person abilities. This has been previously demonstrated for memory measurements. It can also be reasonably expected to be applicable to other kinds of measures of human abilities and task difficulty in health care, but further exploration is needed about how to incorporate qualitative explanatory variables in the CSE formulation. In this paper we report two case studies exploring the possibilities of advancing CSE and entropy to include human functional balance measurements. In case study I, physiotherapists have formulated a CSE for balance task difficulty by principal component regression of empirical balance task difficulty values from Berg's Balance Scale transformed using the Rasch model. In case study II, four balance tasks of increasing difficulty due to diminishing bases of support and vision were briefly investigated in relation to entropy as a measure of the amount of information and order as well as physical thermodynamics. The pilot study has explored both methodological and conceptual possibilities and concerns to be considered in further work. The results should not be considered as fully comprehensive or absolute, but rather open up for further discussion and investigations to advance measurements of person balance ability in clinical practice, research, and trials.

Maternal and fetal haemopexin and α1-microglobulin concentrations in pre-eclamptic IVF pregnancies according to presence of corpus luteum at embryo transfer.

RESEARCH QUESTION: Do pregnancies with corpus luteum show different maternal and fetal plasma concentrations of the scavenger proteins haemopexin and α1-microglobulin compared with pregnancies without corpus luteum in preeclampsia? DESIGN: Case-control study of 160 singleton pregnancies: 54 naturally conceived, 50 by IVF after fresh embryo transfer or frozen embryo transfer (FET) in natural cycle (presence of corpus luteum) and 56 after fresh oocyte donation or FET in programmed cycles (absence of corpus luteum). Pregnancies were subclassified into normotensive, preeclampsia and severe preeclampsia cases. Heme-scavenger concentrations were measured by ELISA in maternal and cord plasma collected at delivery. RESULTS: After adjustment, maternal haemopexin was higher in IVF with corpus luteum than in naturally conceived pregnancies in normotensive (P = 0.038) and preeclampsia (P = 0.011) populations, and lower in preeclampsia for IVF pregnancies lacking corpus luteum compared with IVF with corpus luteum (P = 0.002). Maternal α1-microglobulin levels were higher in the absence of corpus luteum only in severe cases of preeclampsia compared with naturally conceived pregnancies (P = 0.014) and IVF with corpus luteum pregnancies (P = 0.041). In cord blood, haemopexin was higher in IVF with corpus luteum compared with naturally conceived pregnancies in preeclampsia (P = 0.039) and α1-microglobulin was higher in the group lacking corpus luteum compared with IVF with corpus luteum in the normotensive population (P < 0.001). CONCLUSIONS: The physiological differences shown for these heme-scavengers between pregnancies after embryo transfer in the presence or absence of corpus luteum support the hypothesis that corpus luteum activity could influence perinatal outcomes. Future research is needed on whether applying potential strategies to develop a corpus luteum might reduce the perinatal complications associated with programmed cycles of IVF.

Experiences of activity monitoring and perceptions of digital support among working individuals with hip and knee osteoarthritis - a focus group study.

BACKGROUND: Mobile health (mHealth), wearable activity trackers (WATs) and other digital solutions could support physical activity (PA) in individuals with hip and knee osteoarthritis (OA), but little is described regarding experiences and perceptions of digital support and the use of WAT to self-monitor PA. Thus, the aim of this study was to explore the experiences of using a WAT to monitor PA and the general perceptions of mHealth and digital support in OA care among individuals of working age with hip and knee OA. METHODS: We conducted a focus group study where individuals with hip and knee OA (n = 18) were recruited from the intervention group in a cluster-randomized controlled trial (C-RCT). The intervention in the C-RCT comprised of 12-weeks use of a WAT with a mobile application to monitor PA in addition to participating in a supported OA self-management program. In this study, three focus group discussions were conducted. The discussions were transcribed and qualitative content analysis with an inductive approach was applied. RESULTS: The analysis resulted in two main categories: A WAT may aid in optimization of PA, but is not a panacea with subcategories WATs facilitate PA; Increased awareness of one's limitations and WATs are not always encouraging, and the second main category was Digital support is an appreciated part of OA care with subcategories Individualized, early and continuous support; PT is essential but needs to be modernized and Easy, comprehensive, and reliable digital support. CONCLUSION: WATs may facilitate PA but also aid individuals with OA to find the optimal level of activity to avoid increased pain. Digital support in OA care was appreciated, particularly as a part of traditional care with physical visits. The participants expressed that the digital support should be easy, comprehensive, early, and continuous.

Promoting work ability with a wearable activity tracker in working age individuals with hip and/or knee osteoarthritis: a randomized controlled trial.

BACKGROUND: Physical activity (PA) may improve work ability and health in individuals with hip and/or knee osteoarthritis (OA). The use of wearable activity trackers (WATs) has been shown to increase PA and improve other health outcomes but little is known concerning their effect on work ability. The objectives of this study were to examine the effect of self-monitoring PA with a WAT on work ability, PA and work productivity among individuals of working age with hip and/or knee OA. METHODS: Individuals (n = 160) were included and cluster-randomized to a Supported Osteoarthritis Self-management Program (SOASP) with the addition of self-monitoring PA using a commercial WAT for 12 weeks (n = 86), or only the SOASP (n = 74). Primary outcome was self-reported work ability measured with the Work Ability Index (WAI) and secondary outcomes were self-reported PA measured with the International Physical Activity Questionnaire - Short Form (IPAQ-SF) and work productivity, measured with the Work Productivity and Activity Impairment scale: Osteoarthritis (WPAI:OA) at baseline and after 3, 6 and 12 months. Data was primarily analysed with linear mixed models. RESULTS: Participants with data from baseline and at least one follow-up were included in the analyses (n = 124). Linear mixed models showed no statistically significant difference between groups regarding pattern of change in work ability or PA, from baseline to follow-ups. Also, neither group had a statistically significant difference in work ability between baseline and each follow-up. CONCLUSION: The SOASP together with self-monitoring PA with a WAT did not have any effect on the primary outcome variable work ability. Participants already at baseline had good work ability and were physically active, which could have reduced the possibility for improvements. Future interventions should target a population with lower work ability and PA-level. TRIAL REGISTRATION: ClinicalTrials.gov, NCT03354091 . Registered 15/11/2017.

Enablement and empowerment among patients participating in a supported osteoarthritis self-management programme - a prospective observational study.

BACKGROUND: In Sweden, core treatment for osteoarthritis is offered through a Supported Osteoarthritis Self-Management Programme (SOASP), combining education and exercise to provide patients with coping strategies in self-managing the disease. The aim was to study enablement and empowerment among patients with osteoarthritis in the hip and/or knee participating in a SOASP. An additional aim was to study the relation between the Swedish version of the Patient Enablement Instrument (PEI) and the Swedish Rheumatic Disease Empowerment Scale (SWE-RES-23). METHODS: Patients with osteoarthritis participating in a SOASP in primary health care were recruited consecutively from 2016 to 2018. The PEI (score range 0-12) was used to measure enablement and the SWE-RES-23 (score range 1-5) to measure empowerment. The instruments were answered before (SWE-RES-23) and after the SOASP (PEI, SWE-RES-23). A patient partner was incorporated in the study. Descriptive statistics, the Wilcoxon's signed rank test, effect size (r), and the Spearman's rho (rs) were used in the analysis. RESULTS: In total, 143 patients were included in the study, 111 (78%) were women (mean age 66, SD 9.3 years). At baseline the reported median value for the SWE-RES-23 (n = 142) was 3.6 (IQR 3.3-4.0). After the educational part of the SOASP, the reported median value was 6 (IQR 3-6.5) for the PEI (n = 109) and 3.8 (IQR 3.6-4.1) for the SWE-RES-23 (n = 108). At three months follow-up (n = 116), the reported median value was 6 (IQR 4-7) for the PEI and 3.9 (IQR 3.6-4.2) for the SWE-RES-23. The SWE-RES-23 score increased between baseline and three months (p ≤ 0.000). The analysis showed a positive correlation between PEI and SWE-RES-23 after the educational part of the SOASP (rs = 0.493, p < 0.00, n = 108) and at follow-up at three months (rs = 0.507, p < 0.00, n = 116). CONCLUSIONS: Patients reported moderate to high enablement and empowerment and an increase in empowerment after participating in a SOASP, which might indicate that the SOASP is useful to enable and empower patients at least in the short term. Since our results showed that the PEI and the SWE-RES-23 are only partly related both instruments can be of use in evaluating interventions such as the SOASP. TRIAL REGISTRATION: ClinicalTrials.gov. NCT02974036 . First registration 28/11/2016, retrospectively registered.

Physiotherapists' experiences of osteoarthritis guidelines in primary health care - an interview study.

BACKGROUND: Osteoarthritis is a common joint disease, globally. Guidelines recommend information, exercise and, if needed, weight reduction as core treatment. There is a gap between evidence-based recommended care for osteoarthritis and clinical practice. To increase compliance to guidelines, implementation was conducted. The aim of the study was to explore physiotherapists' experiences of osteoarthritis guidelines and their experiences of implementation of the guidelines in primary health care in a region in southern Sweden. METHODS: Eighteen individual, semi-structured interviews with physiotherapists in primary health care were analysed with inductive qualitative content analysis. RESULTS: The analysis resulted in two categories and four subcategories. The physiotherapists were confident in their role as primary assessors for patients with osteoarthritis and the guidelines were aligned with their professional beliefs. The Supported Osteoarthritis Self-Management Programme, that is part of the guidelines, was found to be efficient for the patients. Even though the physiotherapists followed the guidelines they saw room for improvement since all patients with hip and/or knee osteoarthritis did not receive treatment according to the guidelines. Furthermore, the physiotherapists emphasised the need for management's support and that guidelines should be easy to follow. CONCLUSION: The physiotherapists believed in the guidelines and were confident in providing first line treatment to patients with osteoarthritis. However, information about the guidelines probably needs to be repeated to all health care providers and management. Data from a national quality register on osteoarthritis could be used to a greater extent in daily clinical work in primary health care to improve quality of care for patients with osteoarthritis.

Physical activity patterns, adherence to using a wearable activity tracker during a 12-week period and correlation between self-reported function and physical activity in working age individuals with hip and/or knee osteoarthritis.

BACKGROUND: A majority of individuals with osteoarthritis (OA) are insufficiently physically active. Self-monitoring with wearable activity trackers (WAT) could promote physical activity (PA), and increased knowledge of PA patterns and adherence to using a WAT is needed. The aim of this study was to describe PA patterns and adherence to WAT-use during an intervention among participants of working age with hip and/or knee OA. The study further explores the correlation between self-reported joint function and PA. METHODS: Individuals of working age with hip and/or knee OA who used a WAT, Fitbit Flex 2, for 12 weeks were included. Participants monitored their PA in the Fitbit-app. An activity goal of 7,000 steps/day was set. Steps and minutes in light (L), moderate and vigorous (MV) PA were collected from the Fitbit. Self-reported joint function (HOOS/KOOS) was completed. Data was analyzed with linear mixed models and Spearman's rank correlation. RESULTS: Seventy-five participants (45-66 years) walked on average 10 593 (SD 3431) steps/day, spent 248.5 (SD 42.2) minutes in LPA/day, 48.1 (SD 35.5) minutes in MVPA/day, 336.0 (SD 249.9) minutes in MVPA/week and used the Fitbit for an average of 88.4 % (SD 11.6) of the 12-week period. 86.7 % took > 7,000 steps/day and 77.3 % spent > 150 min in MVPA/week. Mean daily steps/week decreased significantly over the 12 weeks (ß-coefficient - 117, 95 % CI -166 to -68, p = < 0.001) as well as mean daily minutes in LPA/week (ß-coefficient - 2.3, 95 % CI -3.3 to -1.4, p = < 0.001), mean daily minutes in MVPA/week (ß-coefficient - 0.58, 95 % CI -1.01 to -0.16, p = 0.008) and mean adherence to Fitbit-use per week (ß-coefficient - 1.3, 95 % CI -1.8 to -0.8, p = < 0.001). There were no significant correlations between function (HOOS/KOOS) and PA. CONCLUSIONS: The majority of participants reached 7,000 steps/day and the recommended 150 min in MVPA per week. However, PA decreased slightly but gradually over time. Adherence to using the Fitbit was high but also decreased during the intervention. Understanding PA patterns and the use of a Fitbit to promote PA could be beneficial in tailoring interventions for individuals with hip and/or knee OA.

Hypoxia-Induced Alpha-Globin Expression in Syncytiotrophoblasts Mimics the Pattern Observed in Preeclamptic Placentas.

Preeclampsia (PE) is a pregnancy disorder associated with placental dysfunction and elevated fetal hemoglobin (HbF). Early in pregnancy the placenta harbors hematopoietic stem and progenitor cells (HSPCs) and is an extramedullary source of erythropoiesis. However, globin expression is not unique to erythroid cells and can be triggered by hypoxia. To investigate the role of the placenta in increasing globin levels previously reported in PE, flow cytometry, histological and immunostaining and in situ analyses were used on placenta samples and ex vivo explant cultures. Our results indicated that in PE pregnancies, placental HSPC homing and erythropoiesis were not affected. Non-erythroid alpha-globin mRNA and protein, but not gamma-globin, were detected in syncytiotrophoblasts and stroma of PE placenta samples. Similarly, alpha-globin protein and mRNA were upregulated in normal placenta explants cultured in hypoxia. The upregulation was independent of HIF1 and NRF2, the two main candidates of globin transcription in non-erythroid cells. Our study is the first to demonstrate alpha-globin mRNA expression in syncytiotrophoblasts in PE, induced by hypoxia. However, gamma-globin was only expressed in erythrocytes. We conclude that alpha-globin, but not HbF, is expressed in placental syncytiotrophoblasts in PE and may contribute to the pathology of the disease.

Dyskinesia and FAB score predict future falling in Parkinson's disease.

A growing body of research highlights the importance of cognition for prediction of falls in Parkinson's disease (PD). However, a previously proposed prediction model for future near falls and falls in PD, which includes history of near falls, tandem gait, and retropulsion, was developed without considering cognitive impairment. Therefore, by using a sample of 64 individuals with relatively mild PD and not excluding those with impaired cognition we aimed to externally validate the previously proposed model as well as to explore the value of additional predictors that also consider cognitive impairment. Since this validation study failed to support the proposed model in a PD sample including individuals with impaired global cognition, extended analyses generated a new model including dyskinesia (item 32 of Unified PD Rating Scale) and frontal lobe impairment (Frontal Assessment Battery-FAB) as significant independent predictors for future near falls and falls in PD. The discriminant ability of this new model was acceptable (AUC, 0. 80; 95% CI 0.68-0.91). Replacing the continuous FAB scores by a dichotomized version of FAB with a cut-off score ≤14 yielded slightly lower but still acceptable discriminant ability (AUC, 0. 79; 95% CI 0.68-0.91). Further studies are needed to test our new model and the proposed cut-off score of FAB in additional samples. Taken together, our observations suggest potentially important additions to the evidence base for clinical fall prediction in PD with concomitant cognitive impairment.

Fractures among patients with dizziness - a ten-year follow-up.

BACKGROUND: The number of elderly people persons suffering from dizziness is substantial, and dizziness is a risk factor for falls and fractures. Fall-related fractures represent a major public health issue. Longitudinal studies can help find ways of predicting fall-related fractures among frail elderly persons with multisensory dizziness. The aim of the present study was therefore to investigate whether different measures of balance, being male/female or admission to hospital, could predict fracture at a ten-year follow-up in patients suffering from multisensory dizziness. METHODS: Patients who had participated in two earlier (ten years previous) dizziness studies were sought in the local health authority's patient administrative system. Information was extracted regarding patient hospitalization, for fractures or for any other reason, during the ten-year period. Logistic regression was used to analyse the relations between clinical balance measures, vestibular rehabilitation, admission to hospital, sex, and fracture. RESULTS: There was no difference between the group of patients with fracture and the group of patients without fracture, regarding balance measures at baseline or admission to hospital for reasons other than fracture. There was no difference between men and women in any of the measures. CONCLUSIONS: This study did not identify any predictors of fracture. Thus, among frail elderly, attention to fall risk should be equally high regardless of patient history.

The effect of education and supervised exercise on physical activity, pain, quality of life and self-efficacy - an intervention study with a reference group.

BACKGROUND: Individuals with knee and hip osteoarthritis (OA) are less physically active than people in general, and many of these individuals have adopted a sedentary lifestyle. In this study we evaluate the outcome of education and supervised exercise on the level of physical activity in individuals with knee or hip OA. We also evaluate the effect on pain, quality of life and self-efficacy. METHODS: Of the 264 included individuals with knee or hip OA, 195 were allocated to the intervention group. The intervention group received education and supervised exercise that comprised information delivered by a physiotherapist and individually adapted exercises. The reference group consisted of 69 individuals with knee or hip OA awaiting joint replacement and receiving standard care. The primary outcome was physical activity (as measured with an accelerometer). The secondary outcomes were pain (Visual Analog Scale), quality of life (EQ-5D), and self-efficacy (Arthritis Self-Efficacy Scale, pain and other symptoms subscales). Participants in both groups were evaluated at baseline and after 3 months. The intervention group was also evaluated after 12 months. RESULTS: No differences were found in the number of minutes spent in sedentary or in physical activity between the intervention and reference groups when comparing the baseline and 3 month follow-up. However, there was a significant difference in mean change (mean diff; 95% CI; significance) between the intervention group and reference group favoring the intervention group with regard to pain (13; 7 to 19; p < 0.001), quality of life (- 0.17; - 0.24 to - 0.10; p < 0.001), self-efficacy/other symptoms (- 5; - 10 to - 0.3; p < 0.04), and self-efficacy/pain (- 7; - 13 to - 2; p < 0.01). Improvements in pain and quality of life in the intervention group persisted at the 12-month follow-up. CONCLUSIONS: Participation in an education and exercise program following the Swedish BOA program neither decreased the average amount of sedentary time nor increased the level of physical activity. However, participation in such a program resulted in decreased pain, increased quality of life, and increased self-efficacy. TRIAL REGISTRATION: The trial is registered with ClinicalTrials.gov. Registration number: NCT02022566 . Retrospectively registered 12/18/2013.

Kinesiophobia and its relation to pain characteristics and cognitive affective variables in older adults with chronic pain.

BACKGROUND: The contribution of kinesiophobia (fear of movement) to the pain experience among older adults has been poorly evaluated. The aim of this study was to study prevalence at baseline, development over a 12-month period and cognitive-affective variables of kinesiophobia in a population-based sample of older adults with chronic pain. METHODS: The study included 433 older adults (+65 years) with chronic pain (mean age 74.8 years) randomly selected using a Swedish register of inhabitants. Kinesiophobia was measured at baseline and 12-month follow-up with the 11-item version of the Tampa Scale of Kinesiophobia (TSK-11). Associations of demographic-, cognitive affective - and pain-related variables to kinesiophobia were analysed with linear regression analyses. RESULTS: The mean level of kinesiophobia was low. Worsening and recovering from kinesiophobia occurred over time, but the mean level of kinesiophobia remained unchanged (p = 0.972). High levels of kinesiophobia (TSK ≥35) were found among frailer and older adults predominately living in care homes, but not dependent on sex. Poor self-perceived health (OR = 8.84) and high pain intensity (OR = 1.22) were significantly associated with kinesiophobia. CONCLUSION: Results indicate that potential interventions regarding kinesiophobia among older adults should aim to decrease pain intensity and strengthen health beliefs.

Impact of pain characteristics and fear-avoidance beliefs on physical activity levels among older adults with chronic pain: a population-based, longitudinal study.

BACKGROUND: To explore the level of physical activity in a population based sample of older adults; to analyze the influence of pain characteristics and fear-avoidance beliefs as predictors of physical activity among older adults reporting chronic pain. METHODS: Demographics, pain characteristics (duration, intensity), physical activity, kinesiophobia (excessive fear of movement/(re) injury), self-efficacy and self-rated health were measured with questionnaires at baseline and 12-months later. Logistic regression analyses were done to identify associations at baseline and predictors of physical activity 12-months later during follow-up. RESULTS: Of the 1141 older adults (mean age 74.4 range 65-103 years, 53.5% women) included in the study, 31.1% of those with chronic pain were sufficiently active (scoring ≥ 4 on Grimby's physical activity scale) compared to 56.9% of those without chronic pain. Lower age (OR = 0.93, 95% CI = 0.88-0.99), low kinesiophobia OR = 0.95, 95% CI = 0.91-0.99), and higher activity level at baseline (OR = 10.0, 95% CI = 4.98-20.67) significantly predicted higher levels of physical activity in individuals with chronic pain. CONCLUSION: The level of physical activity was significantly lower among those with chronic pain and was significantly associated with kinesiophobia. Our findings suggest that fear- avoidance believes plays a more important role in predicting future physical activity levels than pain characteristics. Thus our findings are important to consider when aiming to increase physical activity in older adults that have chronic pain.

A combination of clinical balance measures and FRAX® to improve identification of high-risk fallers.

BACKGROUND: The FRAX® algorithm quantifies a patient's 10-year probability of a hip or major osteoporotic fracture without taking an individual's balance into account. Balance measures assess the functional ability of an individual and the FRAX® algorithm is a model that integrates the individual patients clinical risk factors [not balance] and bone mineral density. Thus, clinical balance measures capture aspects that the FRAX® algorithm does not, and vice versa. It is therefore possible that combining FRAX® and clinical balance measures can improve the identification of patients at high fall risk and thereby high fracture risk. Our study aim was to explore whether there is an association between clinical balance measures and fracture prediction obtained from FRAX®. METHOD: A cross-sectional study design was used where post hoc was performed on a dataset of 82 participants (54 to 89 years of age, mean age 71.4, 77 female), with a fall-related wrist-fracture between 2008 and 2012. Balance was measured by tandem stance, standing one leg, walking in the figure of eight, walking heel to toe on a line, walking as fast as possible for 30 m and five times sit to stand balance measures [tandem stance and standing one leg measured first with open and then with closed eyes] and each one analyzed for bivariate relations with the 10-year probability values for hip and major osteoporotic fractures as calculated by FRAX® using Spearman's rank correlation test. RESULTS: Individuals with high FRAX® values had poor outcome in balance measures; however the significance level of the correlation differed between tests. Standing one leg eyes closed had strongest correlation to FRAX® (0.610 p = < 0.01) and Five times sit to stand was the only test that did not correlate with FRAX® (0.013). CONCLUSION: This study showed that there is an association between clinical balance measures and FRAX®. Hence, the use of clinical balance measures and FRAX® in combination, might improve the identification of individuals with high risk of falls and thereby following fractures. Results enable healthcare providers to optimize treatment and prevention of fall-related fractures. TRIAL REGISTRATION: The study has been registered in Clinical Trials.gov, registration number NCT00988572 .

Effect of High-Carbohydrate Diet on Plasma Metabolome in Mice with Mitochondrial Respiratory Chain Complex III Deficiency.

Mitochondrial disorders cause energy failure and metabolic derangements. Metabolome profiling in patients and animal models may identify affected metabolic pathways and reveal new biomarkers of disease progression. Using liver metabolomics we have shown a starvation-like condition in a knock-in (Bcs1lc.232A>G) mouse model of GRACILE syndrome, a neonatal lethal respiratory chain complex III dysfunction with hepatopathy. Here, we hypothesized that a high-carbohydrate diet (HCD, 60% dextrose) will alleviate the hypoglycemia and promote survival of the sick mice. However, when fed HCD the homozygotes had shorter survival (mean ± SD, 29 ± 2.5 days, n = 21) than those on standard diet (33 ± 3.8 days, n = 30), and no improvement in hypoglycemia or liver glycogen depletion. We investigated the plasma metabolome of the HCD- and control diet-fed mice and found that several amino acids and urea cycle intermediates were increased, and arginine, carnitines, succinate, and purine catabolites decreased in the homozygotes. Despite reduced survival the increase in aromatic amino acids, an indicator of liver mitochondrial dysfunction, was normalized on HCD. Quantitative enrichment analysis revealed that glycine, serine and threonine metabolism, phenylalanine and tyrosine metabolism, and urea cycle were also partly normalized on HCD. This dietary intervention revealed an unexpected adverse effect of high-glucose diet in complex III deficiency, and suggests that plasma metabolomics is a valuable tool in evaluation of therapies in mitochondrial disorders.

Predicting the relative binding affinity of mineralocorticoid receptor antagonists by density functional methods.

In drug discovery, prediction of binding affinity ahead of synthesis to aid compound prioritization is still hampered by the low throughput of the more accurate methods and the lack of general pertinence of one method that fits all systems. Here we show the applicability of a method based on density functional theory using core fragments and a protein model with only the first shell residues surrounding the core, to predict relative binding affinity of a matched series of mineralocorticoid receptor (MR) antagonists. Antagonists of MR are used for treatment of chronic heart failure and hypertension. Marketed MR antagonists, spironolactone and eplerenone, are also believed to be highly efficacious in treatment of chronic kidney disease in diabetes patients, but is contra-indicated due to the increased risk for hyperkalemia. These findings and a significant unmet medical need among patients with chronic kidney disease continues to stimulate efforts in the discovery of new MR antagonist with maintained efficacy but low or no risk for hyperkalemia. Applied on a matched series of MR antagonists the quantum mechanical based method gave an R(2) = 0.76 for the experimental lipophilic ligand efficiency versus relative predicted binding affinity calculated with the M06-2X functional in gas phase and an R(2) = 0.64 for experimental binding affinity versus relative predicted binding affinity calculated with the M06-2X functional including an implicit solvation model. The quantum mechanical approach using core fragments was compared to free energy perturbation calculations using the full sized compound structures.

Vestibular Rehabilitation Affects Vestibular Asymmetry among Patients with Fall-Related Wrist Fractures - A Randomized Controlled Trial.

BACKGROUND: Fall-related fractures are an increasing problem for society. Dizziness is identified as a risk factor for falls and vestibular asymmetry is often found among patients with fall-related fractures. An option to prevent fall-related fractures may be to identify patients with vestibular asymmetry and to improve their balance and asymmetry by exercise. OBJECTIVE: To examine whether vestibular rehabilitation improves vestibular function, balance and self-rated health among patients with fall-related wrist fractures. METHODS: Sixty-eight persons (65 women) with fall-related wrist fractures, mean age 72 years (54-89) participated in this randomized controlled trial. The following tests and measurements were performed: head shake test to evaluate vestibular asymmetry as primary outcome measure, five clinical balance measures, a force plate to measure postural sway, a tuning fork to measure vibration and the EQ5D questionnaire to measure self-rated health. The intervention comprised group-based vestibular rehabilitation sessions conducted twice a week for 9 weeks. RESULTS: Nystagmus occurred in the head shake test in 65% (44 of 68) of the patients, indicating vestibular asymmetry. More patients in the intervention group (6 of 21) than in the control group (0 of 23) changed from having nystagmus in the head shake test at baseline (indicating vestibular asymmetry) to not having nystagmus at follow-up, and more patients in the control group (3 of 9) than in the intervention group (0 of 3) changed from not having nystagmus at baseline to have nystagmus at follow-up (p < 0.00). No other changes occurred between the two groups between baseline and follow-up. At baseline, patients with vestibular asymmetry had more balance deficits and increased postural sway compared to patients without (p = 0.00-0.05). CONCLUSION: Group sessions with vestibular rehabilitation twice a week for 9 weeks affected the occurrence of vestibular asymmetry positively among patients having vestibular asymmetry. Patients with vestibular asymmetry had more balance deficits and increased postural sway than patients without vestibular asymmetry. Vestibular assessment is important, and, in patients with diagnosed vestibular asymmetry, vestibular rehabilitation may prove beneficial on balance and possibly reduce the risk of future falls.

Validation of a competitive ELISA assay for the quantification of human serum hepcidin.

BACKGROUND: Hepcidin-25 is a potential marker for iron disorders with a demand for accessible assays. This study aimed to evaluate a commercial competitive enzyme-linked immunosorbent assay (cELISA) for hepcidin quantitation. METHODS: Serum samples; 95 healthy subjects (HS), six patients with iron deficiency (ID), 84 patients with liver disorders (LD) and 220 hemodialysis patients (HD), were analyzed. Controls were used for imprecision, while accuracy was evaluated by quantitating hepcidin-25 with LC-MS/MS in 149 samples. Cross-reactivity for hepcidin-20 and hepcidin-22 was tested. Hepcidin-mRNA expression in 37 liver biopsies was measured. RESULTS: S-hepcidin ranged from 8-76 and 2-31 µg/L in healthy men and women. Levels in ID, LD and HD significantly differed from HS. Total coefficients of variation (CV) for controls were 24% and 22%. Within-sample CV was 10%. Despite a good correlation with LC-MS/MS (r = 0.89), the cELISA showed higher values and detected hepcidin-20 and hepcidin-22. Hepcidin-mRNA correlated well with S-hepcidin using cELISA and LC-MS/MS (r = 0.69 and 0.64). CONCLUSIONS: The correlation with LC-MS/MS is good and the examined kit can differentiate between patient groups although it is not specific for hepcidin-25. Considering ELISA's capacity to readily be set up, the investigated kit can be applied. Specific reference ranges are required.