Health-Related Quality of Life in Adults with Osteogenesis Imperfecta.

Osteogenesis imperfecta (OI) is a systemic connective tissue disorder most often caused by mutations in collagen type 1 related genes. Patients with OI suffer from multiple fractures and various degrees of growth deficiency and bone deformity. It is unknown whether the systemic effect of defect collagen type 1 influences the quality of life in patients with OI. We therefore aimed to investigate health-related quality of life (HRQoL) in a well-characterized cohort of adult patients with OI. We included 85 adult patients with mild to severe OI (types I, III, and IV) and obtained information about skeletal- and non-skeletal phenotypes and patient demographics. We investigated physical and mental HRQoL using a validated questionnaire, SF-36, and compared the data to values obtained in a population without OI. Patients with mild, moderate, and severe OI all had lower mean scores on domains describing physical HRQoL and a lower mean physical component score compared to the general population, p < 0.001. Patients with severe OI had lower mean scores on physical HRQoL, p < 0.05. The scores on domains reflecting mental HRQoL were more inhomogenously affected, but did not differ significantly from the general population. OI has an impact on physical and some aspects of mental HRQoL. The scores on physical health were correlated to severity of the OI disease. The mental component score in the OI patients was unaffected and comparable with the general population.

Genetic Screening of WNT4 and WNT5B in Two Populations with Deviating Bone Mineral Densities.

A role for WNT4 and WNT5B in bone metabolism was indicated by genome-wide association studies (GWAS) and a Wnt4 knockout mouse model. The aim of this study was therefore to replicate and further investigate the causality between genetic variation in WNT4 and WNT5B and deviating bone mineral density (BMD) values. A WNT4 and WNT5B mutation screening was performed in patients with craniotubular hyperostosis using Sanger sequencing. Here, no putative causal mutations were detected. Moreover, a high and low BMD cohort was selected from the Odense Androgen Study population for re-sequencing. In WNT4 we detected four variants (three rare, one common), while in WNT5B we detected five variants (two rare, three common). For the common variants, no significant difference in genotype frequencies between the high and low BMD cohorts was observed. The SNPs associated with the GWAS were genotyped in these cohorts, but again no significant difference in genotype frequencies was observed. Despite the findings of the GWAS, we were not able to replicate or further verify the genetic association of polymorphisms in WNT4 and WNT5B with BMD. In order to do so, the intronic regions of both genes could be investigated more thoroughly in more extended populations (or extremes) with greater power. Future genetic and functional studies toward adjacent genes of WNT4 and WNT5B can also be interesting to figure out whether the signal from GWAS could possibly be attributed to genetic variation in these genes.

Point-of-Care Phalangeal Bone Mineral Density Measurement Can Reduce the Need of Dual-Energy X-Ray Absorptiometry Scanning in Danish Women at Risk of Fracture.

Identifying persons with a high risk of osteoporotic fractures remains a challenge. DXA uptake in women with elevated risk of osteoporosis seems to be depending on distance to scanning facilities. This study aimed to investigate the ability of a small portable scanner in identifying women with reduced bone mineral density (BMD), and to define triage thresholds for pre-selection. Total hip and lumbar spine BMD was measured by dual-energy X-ray absorptiometry and phalangeal BMD by radiographic absorptiometry in 121 Danish women with intermediate or high 10-year fracture probability (aged 61-81 years). Correlation between the two methods was estimated using correlation coefficient (r) and Bland-Altman plots. A moderate correlation between phalangeal BMD versus total hip (r = 0.47) and lumbar spine (r = 0.51), and an AUC on 0.80 was found. The mean difference between phalangeal T score and total hip T score/lumbar spine T score was low, and ranged from -0.26 SD to -0.31 SD depending on site and reference database used for calculation of T scores, but, large variation was seen at an individual level. When applying a triage approach approx. one-third of all DXA scan could be avoided and only 6 % of women in the low-risk group would be false negatives.

Bone Structural Changes and Estimated Strength After Gastric Bypass Surgery Evaluated by HR-pQCT.

Roux-en-Y gastric bypass surgery (RYGB) is an effective treatment of morbid obesity, with positive effects on obesity-related complications. The treatment is associated with bone loss, which in turn might increase fracture risk. The aim of this study was to evaluate changes in bone mineral density (BMD) and bone architecture assessed using dual-energy X-ray absorptiometry (DXA) and high-resolution peripheral quantitative computed tomography (HR-pQCT), 6 and 12 months after RYGB, and correlate them to changes in selected biochemical markers. A prospective cohort study included 25 morbidly obese patients (10 males, 15 females). Patients were examined with DXA of the hip and spine, HR-pQCT of radius and tibia, and blood sampling before and 6 and 12 months after RYGB. Patients lost in average 33.5 ± 12.1 kg (25.8 ± 8.5 %) in 12 months. In tibia, we found significant loss of total, cortical and trabecular volumetric BMD after 12 months (all p < 0.001). Microarchitectural changes involved lower trabecular number, increased trabecular separation, and network inhomogeneity along with thinning of the cortex. Estimated bone failure load was decreased after 12 months (p = 0.005). We found only minor changes in radius. Results demonstrate significant alterations of bone microarchitecture suggesting an accelerated endosteal resorption along with disintegration of the trabecular structure which resulted in a loss of estimated bone strength in tibia. Such changes may underlie the recently reported increased risk of fracture in bariatric patients after surgery. We only observed bone structural changes in the weight-bearing bone, which indicates that mechanical un-loading is the primary mediator.

Multidisciplinary Management of Mastocytosis: Nordic Expert Group Consensus.

Mastocytosis is a heterogeneous group of diseases defined by an increased number and accumulation of mast cells, and often also by signs and symptoms of mast cell activation. Disease subtypes range from indolent to rare aggressive forms. Mastocytosis affects people of all ages and has been considered rare; however, it is probably underdiagnosed with potential severe implications. Diagnosis can be challenging and symptoms may be complex and involve multiple organ-systems. In general it is advised that patients should be referred to centres with experience in the disease offering an individualized, multidisciplinary approach. We present here consensus recommendations from a Nordic expert group for the diagnosis and general management of patients with mastocytosis.

Fracture risk and zoledronic acid therapy in men with osteoporosis.

BACKGROUND: Fractures in men are a major health issue, and data on the antifracture efficacy of therapies for osteoporosis in men are limited. We studied the effect of zoledronic acid on fracture risk among men with osteoporosis. METHODS: In this multicenter, double-blind, placebo-controlled trial, we randomly assigned 1199 men with primary or hypogonadism-associated osteoporosis who were 50 to 85 years of age to receive an intravenous infusion of zoledronic acid (5 mg) or placebo at baseline and at 12 months. Participants received daily calcium and vitamin D supplementation. The primary end point was the proportion of participants with one or more new morphometric vertebral fractures over a period of 24 months. RESULTS: The rate of any new morphometric vertebral fracture was 1.6% in the zoledronic acid group and 4.9% in the placebo group over the 24-month period, representing a 67% risk reduction with zoledronic acid (relative risk, 0.33; 95% confidence interval, 0.16 to 0.70; P=0.002). As compared with men who received placebo, men who received zoledronic acid had fewer moderate-to-severe vertebral fractures (P=0.03) and less height loss (P=0.002). Fewer participants who received zoledronic acid had clinical vertebral or nonvertebral fractures, although this difference did not reach significance because of the small number of fractures. Bone mineral density was higher and bone-turnover markers were lower in the men who received zoledronic acid (P<0.05 for both comparisons). Results were similar in men with low serum levels of total testosterone. The zoledronic acid and placebo groups did not differ significantly with respect to the incidence of death (2.6% and 2.9%, respectively) or serious adverse events (25.3% and 25.2%). CONCLUSIONS: Zoledronic acid treatment was associated with a significantly reduced risk of vertebral fracture among men with osteoporosis. (Funded by Novartis Pharma; ClinicalTrials.gov number, NCT00439647.).

The risk-stratified osteoporosis strategy evaluation study (ROSE): a randomized prospective population-based study. Design and baseline characteristics.

The risk-stratified osteoporosis strategy evaluation study (ROSE) is a randomized prospective population-based study investigating the effectiveness of a two-step screening program for osteoporosis in women. This paper reports the study design and baseline characteristics of the study population. 35,000 women aged 65-80 years were selected at random from the population in the Region of Southern Denmark and-before inclusion-randomized to either a screening group or a control group. As first step, a self-administered questionnaire regarding risk factors for osteoporosis based on FRAX(®) was issued to both groups. As second step, subjects in the screening group with a 10-year probability of major osteoporotic fractures ≥15% were offered a DXA scan. Patients diagnosed with osteoporosis from the DXA scan were advised to see their GP and discuss pharmaceutical treatment according to Danish National guidelines. The primary outcome is incident clinical fractures as evaluated through annual follow-up using the Danish National Patient Registry. The secondary outcomes are cost-effectiveness, participation rate, and patient preferences. 20,904 (60%) women participated and included in the baseline analyses (10,411 in screening and 10,949 in control group). The mean age was 71 years. As expected by randomization, the screening and control groups had similar baseline characteristics. Screening for osteoporosis is at present not evidence based according to the WHO screening criteria. The ROSE study is expected to provide knowledge of the effectiveness of a screening strategy that may be implemented in health care systems to prevent fractures.

Use of Relative vs Fixed Offset Distance to Define Region of Interest at the Distal Radius and Tibia in High-Resolution Peripheral Quantitative Computed Tomography.

Although the region of interest in high-resolution peripheral quantitative computed tomography, defined based on the manufacturer's protocol for in vivo scanning, provides consistency and is practically convenient, it does not take into account possible variation in morphology in the regions adjacent to the measurement site. This study aimed at compare the morphologic variation in measurements using the standard fixed offset distance to define the distal starting slice against those obtained by using a relative measurement position scaled to the individual bone length at the distal radius and tibia in normal healthy adult subjects. A total of 40 healthy adult subjects (median height, 175.3 cm; range: 150.0-196.0 cm) were included in the study. High-resolution peripheral quantitative computed tomography at the distal radius and tibia was performed in all subjects, the region of interest defined by, first, the standard measurement protocol, where the most distal CT slice was 9.5 mm and 22.5 mm from the end plate of the radius and tibia, respectively, and second, the relative measurement method, where the most distal CT slice was at 4% and 7% of the radial and tibial lengths, respectively. Volumetric densities and microarchitectural parameters were compared between the 2 methods. Measurements of the total and cortical volumetric density and cortical thickness at the radius and tibia and cortical porosity, trabecular volumetric density, and trabecular number at the tibia were significantly different between the 2 methods (all p < 0.001). The predicted morphologic variation with varying measurement position was substantial at both the radius (up to 34%) and the tibia (up to 36%). A lack of consideration to height (and in turn the bone lengths) in the standard patient protocol could lead to the introduction of systematic errors in radial and tibial measurements. Although this may not be of particular significance in longitudinal studies in the same individual, it potentially assumes critical importance in cross-sectional studies.

Differential effects of strength training and testosterone treatment on soluble CD36 in aging men: Possible relation to changes in body composition.

PURPOSE: We measured soluble CD36 (sCD36) and body composition to determine the effects of testosterone treatment (TT) and/or strength training (ST) on cardiovascular risk in men with low normal testosterone levels. METHODS: Double-blinded, placebo-controlled study in 54 men aged 60-78 years with bioavailable testosterone < 7.3 nmol/L and waist > 94 cm randomized to TT (gel, 50-100 mg/day, n = 20), placebo (n = 18) or ST (n = 16) for 6 months. Moreover, the ST group was randomized to TT (ST + TT, n = 7) or placebo (ST + placebo, n = 9) after 3 months. OUTCOMES: sCD36, total and regional fat mass were established by Dual X-ray absorptiometry and magnetic resonance imaging. Data are presented as median (quartiles). Kruskal-Wallis and Mann-Whitney tests were performed on delta values at 0, 3 and 6 months. RESULTS: ST + placebo decreased sCD36 levels by 21% [from 0.80 (0.68-1.22) to 0.63 (0.51-0.73) rel. units] vs. TT and vs. placebo (p < 0.05). ST + placebo did not change bioavailable testosterone and lean body mass. Fat mass measures significantly improved during ST + placebo, ST + TT, and TT vs. placebo. During ST + placebo, delta sCD36 was associated with delta total fat mass (r = 0.81) and delta central fat mass (r = 0.84). CONCLUSIONS: Compared to testosterone treatment, six months of strength training reduced sCD36 levels suggesting decreased cardiovascular risk, possibly due to a reduction in central fat mass.

Bone microarchitecture and estimated strength in 499 adult Danish women and men: a cross-sectional, population-based high-resolution peripheral quantitative computed tomographic study on peak bone structure.

High-resolution peripheral quantitative computed tomography (HR-pQCT) allows in vivo assessment of cortical and trabecular bone mineral density (BMD), geometry, and microarchitecture at the distal radius and tibia in unprecedented detail. In this cross-sectional study, we provide normative and descriptive HR-pQCT data from a large population-based sample of Danish Caucasian women and men (n = 499) aged 20-80 years. In young adults (<35 years), women (n = 100) compared to men (n = 64) had smaller total and cortical areas, inferior metric trabecular indices, higher network inhomogeneity, lower cortical porosity, and lower finite element estimated bone strength. The changes in parameters with age were estimated from multiple regression analyses. In men, with age the greatest changes (from parameter minimum or maximum) until 80 years were found for cortical porosity (1.91 IQR), BV/TV (-1.09 IQR), and trabecular thickness (-0.87 IQR) in the radius and BV/TV (-1.55 IQR), cortical BMD (-1.25 IQR), and cortical porosity (1.25 IQR) in the tibia. In women changes were most pronounced for cortical porosity (4.76 IQR), trabecular inhomogeneity (3.84 IQR), and cortical BMD (-2.86 IQR) in the radius and cortical BMD (-5.06 IQR), cortical porosity (3.86 IQR), and cortical area (-1.64 IQR) in the tibia. These findings emphasize the age- and sex-related differences in bone morphology, with men having a structural advantage over women from early adult life translating into superior indices of bone strength. With age women are further disadvantaged compared to men by greater decrements in cortical and trabecular architecture in the radius and cortical architecture in the tibia.

Bone geometry, volumetric bone mineral density, microarchitecture and estimated bone strength in Caucasian females with systemic lupus erythematosus. A cross-sectional study using HR-pQCT.

Patients with systemic lupus erythematosus (SLE) have an increased risk of fracture. We used high resolution peripheral quantitative computed tomography (HR-pQCT) to measure bone geometry, volumetric bone mineral density (vBMD), cortical and trabecular microarchitecture and estimated bone strength by finite element analysis (FEA) at the distal radius and tibia to assess bone characteristics beyond BMD that may contribute to the increased risk of fracture. Thirty-three Caucasian women with SLE (median age 48, range 21-64 years) and 99 controls (median age 45, range 21-64 years) were studied. Groups were comparable in radius regarding geometry and vBMD, but SLE patients had lower trabecular number (-7%, p < 0.05), higher trabecular separation (13%, p < 0.05) and lower FEA-estimated failure load compared to controls (-10%, p < 0.05). In tibia, SLE patients had lower total vBMD (-11%, p < 0.01), cortical area (-14%, p < 0.001) and cortical thickness (-16%, p < 0.001) and higher trabecular area (8%, p < 0.05). In subgroup analyses of the premenopausal participants (SLE n = 21, controls n = 63), SLE patients had significantly lower trabecular bone volume fraction [(BV/TV); -17%, p < 0.01], trabecular number (-9%, p < 0.01), trabecular thickness (-9%, p < 0.05) and higher trabecular separation (13%, p < 0.01) and trabecular network inhomogeneity (14%, p < 0.05) in radius along with lower BV/TV (-15%, p < 0.01) and higher trabecular separation (11%, p < 0.05) in tibia. FEA-estimated bone strength was lower in both radius (-11%, p < 0.01) and tibia (-10%, p < 0.05). In conclusion, Caucasian women with SLE compared to controls had fewer and more widely separated trabeculae and lower estimated bone strength in radius and lower total vBMD, cortical area and thickness in tibia.

Bone structure and estimated bone strength in obese patients evaluated by high-resolution peripheral quantitative computed tomography.

Obesity is associated with high bone mineral density (BMD), but whether obesity-related higher bone mass increases bone strength and thereby protect against fractures is uncertain. We estimated effects of obesity on bone microarchitecture and estimated strength in 36 patients (12 males and 24 females, age 25-56 years and BMI 33.2-57.6 kg/m(2)) matched with healthy controls (age 25-54 years and BMI 19.5-24.8 kg/m(2)) in regard to gender, menopausal status, age (±6 years) and height (±6 cm) using high resolution peripheral quantitative computed tomography and dual energy X-ray absorptiometry. In radius, total bone area and trabecular area were significantly higher in obese patients (both p < 0.04). In tibia, cortical area was larger in obese patients (p < 0.001) compared with controls. Total BMD was higher in tibia (p = 0.03) but not in radius. Trabecular integrity was strengthened in obese patients compared with controls in radius and tibia with higher trabecular number (p = 0.002 and p < 0.001) and lower trabecular spacing (p = 0.01 and p < 0.001). Finite element analysis estimated failure load (FL) was higher in tibia (p < 0.001), but not in radius in obese patients. FL was significantly lower per kg body weight in radius and tibia in obese patients compared with controls (p = 0.007 and p < 0.001). Furthermore, the ratios of FLs between groups were comparable in both sites. These findings suggest that mechanical loading is not the primary mediator of the effects of obesity on estimated FL, and suggest that bone strength adaptations in morbid obesity may be inadequate with respect to the increased mechanical demands.

The relationship between health-related quality of life, obesity and testosterone levels in older men.

BACKGROUND: quality of life evaluated by Short-Form 36 (SF-36) is decreased in obesity and hypogonadism, but the importance of regional fat mass is unknown. In the present study, we evaluated associations between SF-36, regional fat deposits and bioavailable testosterone (BioT) in ageing men. METHODS: a population-based cross-sectional study in older men. Data included SF-36 questionnaires with the dimensions such as physical function, role limitations physical, bodily pain, general health, vitality, social function, role limitations emotional and mental health. Furthermore, waist, lean body mass (measured by dual X-ray absorptiometry), visceral adipose tissue and subcutaneous adipose tissue (SAT) (measured by magnetic resonance imaging) and BioT were established. RESULTS: five hundred and ninety-eight men aged 60-74 years were included. The SF-36 dimensions such as physical function, general health, vitality and role limitations functional were inversely associated with waist and SAT and positively associated with BioT. In multiple regression analysis, waist was the body composition measure with the strongest association with SF-36 dimension scores. CONCLUSION: SF-36 dimension scores were more closely associated with central obesity than with BioT. CLINICAL TRIAL REGISTRATION NUMBER: www.clinicaltrials.gov, NCT00155961.

Fracture risk prediction using phalangeal bone mineral density or FRAX(®)?-A Danish cohort study on men and women.

In this prospective study, we investigated the ability of Fracture Risk Assessment Tool (FRAX), phalangeal bone mineral density (BMD), and age alone to predict fractures using data from a Danish cohort study, Danish Health Examination Survey 2007-2008, including men (n = 5206) and women (n = 7552) aged 40-90 yr. Data were collected using a self-administered questionnaire and by phalangeal BMD measurement. Information on incident and prevalent fractures, rheumatoid arthritis, and secondary osteoporosis was retrieved from the Danish National Patient Registry. Survival analyses were used to examine the association between low, intermediate, and high risk by phalangeal T-score or FRAX and incident fractures, and receiver operating characteristic curves were obtained. Mean follow-up time was 4.3 yr, and a total of 395 persons (3.1%) experienced a fracture during follow-up. The highest rate of major osteoporotic fractures was observed in persons with a high combined risk (FRAX ≥20% and T-score ≤-2.5; women: 32.7 and men: 27.6 per 1000 person-yr). This group also had the highest risk of hip fractures (women: 8.1 and men: 7.2 per 1000 person-yr). FRAX and T-score in combination analyzed as continuous variables performed overall best in the prediction of major osteoporotic fractures. In predicting hip fractures, there was a tendency of T-score performing worse than the other methods.

Does adding an appended oncology module to the Global Trigger Tool increase its value?

OBJECTIVE: To determine any additional value in the evaluation of safety levels by adding an appended oncology module to the Institute for Healthcare Improvement's Global Trigger Tool (GTT). DESIGN: Comparison of two independent retrospective chart reviews: one review team using the general GTT method and one using the general GTT method plus the appended oncology module on the same inpatient charts. SETTING: The Department of Clinical Oncology at a Danish University Hospital (1000 beds). PARTICIPANTS: All inpatients admitted to the hospital in 2010, n = 3692, biweekly sample of 10 admission charts resulting in a double review of 240 charts. MAIN OUTCOME MEASURES: Total number of identified adverse events (AEs), distribution of identified AEs in the harm categories of the National Coordinating Council for Medication Error Reporting and Prevention (NCC MERP), AEs per 100 admissions and AEs per 1000 admission days. RESULTS: No significant (95% confidence interval) difference was found between review teams using the general GTT versus the general GTT plus the appended oncology module on the total number of identified AEs, AEs per 100 admissions, AEs per 1000 admission days or in the overall distribution of identified AEs in the five NCC MERP harm categories. CONCLUSIONS: The study showed that adding the appended oncology module to the GTT did not increase its value regarding the evaluation of safety levels. This finding could be due to the measurement error of the GTT. Further studies evaluating the measurement properties and the specific additional modules to the general GTT are needed.

The incidence of hip fractures in Norway -accuracy of the national Norwegian patient registry.

BACKGROUND: Hip fractures incur the greatest medical costs of any fracture. Valid epidemiological data are important to monitor for time-dependent changes. In Norway, hip fractures are registered in the Norwegian Patient Registry (NPR), but no published national validation exists. The aim of the present study was a national validation of NPR as a register for hip fractures using diagnostic codes (ICD-10 S 72.0-2) and/or procedure codes (NOMESCO version 1.14 NFBxy (x=0-9, y=0-2) or NFJxy (x=0-9, y=0-2). METHOD: A nationwide, population-based cohort comprising a random sub-sample of 1,000 hip fracture-related entries for the years 2008-09 was drawn from the NPR. 200 entries were defined by a combination of diagnostic and procedure codes (subsample 1), 400 entries were defined by diagnostic codes only (subsample 2) and 400 entries were defined by procedure codes only (subsample 3). Accuracy was ascertained through comparison with discharge summaries, procedure notes and X-ray reports requested from 40 health institutions. Comparisons between groups were done by chi2 for categorical and t-test for continuous variables. RESULTS: 792 health records from 32 institutions were reviewed. High accuracy (98.2%, 95% C.I. 96.5-99.9%) was found for subsample 1, a combination of diagnostic and procedure codes. Coding errors were prominent in other subsamples. Defining fractures by a combination of diagnostic and procedure codes, annual average hip fracture incidence in Norway was 9,092 (95% C.I. 8,934 -9,249), excluding only 6.5% of all hip fractures defined by wider definitions. CONCLUSIONS: Based on current coding practice in Norway, a reliable national estimate of hip fracture incidences is found by a combination of relevant ICD-10 and NOMESCO codes in the NPR. This method may be used for monitoring epidemiological changes.

KIT D816V mutation burden does not correlate to clinical manifestations of indolent systemic mastocytosis.

BACKGROUND: Clinical manifestations of indolent systemic mastocytosis (ISM) comprise mediator-related symptoms, anaphylaxis, and osteoporosis. A new sensitive method for KIT D816V mutation detection allows quantification of the level of mutation-positive cells. OBJECTIVE: To investigate whether the fraction of KIT D816V positive cells in peripheral blood (PB) or bone marrow (BM) aspirate in adult patients with ISM correlates with clinical manifestations of the disease. METHODS: We included 48 adult patients with ISM (28 females/20 males) from our center in whom the KIT D816V mutation level in both BM aspirate and PB was analyzed. For each patient, the severity of mediator-related symptoms (skin, gastrointestinal, musculoskeletal, and neuropsychiatric) and episodes of anaphylaxis were evaluated by interview and medical record files. Bone mineral density was determined by using dual-energy x-ray absorptiometry. RESULTS: Median fraction (range) of KIT D816V positive cells was 0.6 (0.01%-90%) in BM and 0.3 (0.003%-49%) in PB. Mutation level did not differ between patients with none/mild symptoms and patients with moderate/severe symptoms, patients with and without anaphylaxis, or patients with osteoporosis/osteopenia and normal bone mineral density. No significant differences in clinical profile were detected in patients with different levels of mutation except for an indication of longer disease duration and age in patients with highest mutation levels. CONCLUSION: To our knowledge, this is the first report on the clinical impact of the fraction of KIT D816V mutation positive cells in ISM, which in the present study does not seem to correlate with clinical manifestations of the disease.

The use and application of Lean Management methods to research processes-a scoping review protocol.

INTRODUCTION: Waste in medical research is a relatively well-known issue. However, only a few initiatives exist to address this issue. Lean Management methods (Lean) were developed in industrial manufacturing and later applied within healthcare improvement. Overall, the results from studies of the application of Lean to healthcare appear to be positive in terms of greater efficiency regarding treatment outcomes and patient care. Nevertheless, the application of Lean to improve research processes is not well studied and, given that research alongside clinical practice and experiential knowledge provides the foundation for the treatment and care of patients, it is paramount to identify approaches and review the degree to which they increase efficiency within research procedures. Therefore, this review will scope the landscape of studies that investigated Lean and how to implement Lean in research processes, particularly regarding healthcare research. METHODS AND ANALYSIS: Our approach follows the methodological framework of Arksey and O'Malley for conducting scoping reviews (PRISMA-ScR). The search strategy for this scoping review was developed using the PCC model. We will identify the relevant literature by searching four search databases: Scopus, Web of Science, Academic Search Premier and Business Source Complete. Next, we will use citation pearl growing to identify all relevant published literature. The data charting process will follow the PRISMA-ScR checklist and will be organised using NVivo. We will generate qualitative and quantitative assessments of the extracted data by using NVivo, RStudio and Excel. We will follow the PRISMA-ScR guideline when reporting the results. ETHICS AND DISSEMINATION: The review will comprise existing published studies and no primary data will be collected. Our findings will be shared through open access peer-reviewed journals, national and international conferences and emails to all relevant collaborative relationships. We plan to disseminate our findings via academic social media platforms, newspaper articles and blogposts.

Resistin polymorphisms show associations with obesity, but not with bone parameters in men: results from the Odense Androgen Study.

Resistin is an obesity-related adipokine which has also been implicated in bone metabolism. Therefore, we designed a study to investigate the possible role of resistin gene variation in both obesity and bone mineral density. We included 1,155 individuals from the Odense Androgen Study (663 young subjects and 492 older subjects), a population-based, prospective, observational study on the inter-relationship between endocrine status, body composition, muscle function, and bone metabolism in men, in an association study with resistin (RETN) polymorphisms. Three RETN variants (rs1862513, rs3745367 and rs3745369) were genotyped with TaqMan Pre-Designed Genotyping assays. Linear regression was performed to investigate the possible association of these variants with several obesity- and bone-related parameters. After genotyping 1,155 Danish men, 663 young subjects and 492 older subjects, we found that rs3745367 was associated with several obesity-related measures in both the young and elderly cohort. Rs3745369 was only associated with obesity-phenotypes in the elderly cohort. When studying the combined cohorts, we could confirm the associations of rs3745367 with several obesity-related parameters. We were unable to identify any association between RETN polymorphisms and bone-related measurements. Together, these results illustrate resistin's role in the development of obesity. Rs3745367 gives the most consistent results in the current study and these should be confirmed in other populations. Research into its possible functional effect might also be required. A role for RETN variants in determining bone mineral density seems unlikely from our results.

Central nervous system medications and falls risk in men aged 60-75 years: the Study on Male Osteoporosis and Aging (SOMA).

INTRODUCTION: drugs acting on the central nervous system (CNS) increase falls risk. Most data on CNS drugs and falls are in women/mixed-sex populations. This study assessed the relationship between CNS drugs and falls in men aged 60-75 years. METHODS: a questionnaire was sent to randomly selected Danish men aged 60-75 years. Cross-sectional data on CNS drugs and falls in the previous year were available for 4,696 men. Logistic regression investigated the relationship between falls and CNS drugs. RESULTS: the median age was 66.3 (IQR = 63.1-70.0) years; 21.7% were fallers. The following were associated with fallers (OR; 95% CI): opiates (2.4; 1.5-3.7), other analgesics (1.7; 1.4-2.1), antiepileptics (2.8; 1.5-5.1), antidepressants (2.8; 1.9-4.1) and anxiolytics/hypnotics (1.5; 0.9-2.6). Effects of opiates interacted strongly and significantly with age, with a marked association with falls in the older half of the subjects only. No significant associations were found between antipsychotics and fallers. Selective serotonin reuptake inhibitors and tricyclics were significantly associated with fallers (3.1; 2.0-5.0 and 2.2; 1.0-4.7, respectively). CONCLUSION: several CNS drug classes are associated with an approximately 2-3-fold increase risk of falls in men aged 60-75 years randomly selected from the population. Further longitudinal data are now required to confirm and further investigate the role of CNS drugs in falls causation in men.