Assessment of Epithelial Lining Fluid Partitioning of Systemically Administered Monoclonal Antibodies in Rats.

For systemically administered monoclonal antibodies (mAbs) with pharmacological targets in the epithelial lining fluid (ELF), information on the partitioning of mAb between plasma and ELF is instrumental for dose predictions. Bronchoalveolar lavage (BAL) combined with measurements of urea as indicator of sample dilution is often used to estimate ELF concentrations of a drug. However, unbalanced extraction of mAb and urea could potentially lead to a systematic bias in the back-calculated ELF concentration. In the present study 0.5, 1, or 4 mL phosphate-buffered saline was instilled to lungs of rats to obtain lavage samples after systemic dosing of mAb and tool small molecule (n≥4/group). Furthermore, extraction of urea, mAb and the small molecule was assessed by repeatedly lavaging the lung (n = 4). There was no statistically significant difference in the calculated partitioning into ELF between the evaluated instillation volumes. Repeated BAL demonstrated that urea and the small molecule were extracted from other sources than the ELF. In contrast, there was limited to none in-flow of mAb into the lavage fluid. The unbalanced extraction of urea and mAb could theoretically result in underestimated ELF concentrations and the calculated partitioning of 0.17±0.062 might therefore constitute a lower boundary for the true partitioning.

Attendance in a national screening program for diabetic retinopathy: a population-based study of 205,970 patients.

AIMS: A nationwide diabetic retinopathy (DR) screening program has been established in Denmark since 2013. We aimed to perform an evaluation of adherence to DR screenings and to examine whether non-adherence was correlated to DR progression. METHODS: The population consisted of a register-based cohort, who participated in the screening program from 2013 to 2018. We analyzed age, gender, marital status, DR level (International Clinical DR severity scale, none, mild-, moderate-, severe non-proliferative DR (NPDR) and proliferative DR (PDR)), comorbidities and socioeconomic factors. The attendance pattern of patients was grouped as either timely (no delays > 33%), delayed (delays > 33%) or one-time attendance (unexplained). RESULTS: We included 205,970 patients with 591,136 screenings. Rates of timely, delayed and one-time attendance were 53.0%, 35.5% and 11.5%, respectively. DR level at baseline was associated with delays (mild-, moderate-, severe NPDR and PDR) and one-time attendance (moderate-, severe NPDR and PDR) with relative risk ratios (RRR) of 1.68, 2.27, 3.14, 2.44 and 1.18, 2.07, 1.26, respectively (P < 0.05). Delays at previous screenings were associated with progression to severe NPDR or PDR (hazard ratio (HR) 2.27, 6.25 and 12.84 for 1, 2 and 3+ delays, respectively). Any given delay doubled the risk of progression (HR 2.28). CONCLUSIONS: In a national cohort of 205,970 patients, almost half of the patients attended DR screening later than scheduled or dropped out after first screening episode. This was, in particular, true for patients with any levels of DR at baseline. DR progression in patients with delayed attendance, increased with the number of missed appointments.

Baseline bone turnover marker levels can predict change in bone mineral density during antiresorptive treatment in osteoporotic patients: the Copenhagen bone turnover marker study.

Anti-resorptive osteoporosis treatment might be more effective in patients with high bone turnover. In this registry study including clinical data, high pre-treatment bone turnover measured with biochemical markers was correlated with higher bone mineral density increases. Bone turnover markers may be useful tools to identify patients benefitting most from anti-resorptive treatment. INTRODUCTION: In randomized, controlled trials of bisphosphonates, high pre-treatment levels of bone turnover markers (BTM) were associated with a larger increase in bone mineral density (BMD). The purpose of this study was to examine this correlation in a real-world setting. METHODS: In this registry-based cohort study of osteoporosis patients (n = 158) receiving antiresorptive therapy, the association between pre-treatment levels of plasma C-telopeptide of type I Collagen (CTX) and/or N-terminal propeptide of type I procollagen (PINP) and change in bone mineral density (BMD) at lumbar spine, total hip, and femoral neck upon treatment was examined. Patients were grouped according to their pre-treatment BTM levels, defined as values above and below the geometric mean for premenopausal women. RESULTS: Pre-treatment CTX correlated with annual increase in total hip BMD, where patients with CTX above the geometric mean experienced a larger annual increase in BMD (p = 0.008) than patients with CTX below the geometric mean. The numerical pre-treatment level of CTX showed a similar correlation at all three skeletal sites (total hip (p = 0.03), femoral neck (p = 0.04), and lumbar spine (p = 0.0003)). A similar association was found for PINP where pre-treatment levels of PINP above the geometric mean correlated with a larger annual increase in BMD for total hip (p = 0.02) and lumbar spine (p = 0.006). CONCLUSION: Measurement of pre-treatment BTM levels predicts osteoporosis patients' response to antiresorptive treatment. Patients with high pre-treatment levels of CTX and/or PINP benefit more from antiresorptive treatment with larger increases in BMD than patients with lower pre-treatment levels.

Evaluating the performance of the Charlson Comorbidity Index (CCI) in fracture risk prediction and developing a new Charlson Fracture Index (CFI): a register-based cohort study.

The Charlson Comorbidity Index (CCI) may be applicable for predicting fracture risk since several diagnoses from the index are predictors of fracture. Main results were that the CCI was updated to predict risk of hip fracture with fair precision and that the index could be useful in detecting high-risk individuals. PURPOSE: Several of the Charlson Comorbidity Index (CCI) diagnoses are validated predictors of fracture. The purpose of this study was to evaluate the performance of the CCI 1987 by Charlson et al. and of the CCI 2011 by Quan et al. in predicting major osteoporotic fracture (MOF) and hip fracture (HF). Furthermore, it was examined whether the index could be modified to improve fracture risk prediction. METHODS: The study population included the entire Danish population aged 45 + years as per January 1, 2018. The cohort was split randomly 50/50 into a development and a validation cohort. CCI diagnoses and fracture outcomes were identified from hospital diagnoses. The weighting of diagnoses was updated in a new Charlson Fracture Index (CFI) using multivariable logistic regression. Predictive capabilities of the CCI 1987, the updated CCI 2011 and the new Charlson Fracture index were evaluated in the validation cohort by receiver operating characteristics (ROC) curves and area under the curve (AUC). RESULTS: In the validation cohort, the 1987 and 2011 CCIs resulted in AUCs below or around 0.7 in prediction of MOF and HF in both sexes. The CFI resulted in AUCs < 0.7 in prediction of MOF in both sexes. In prediction of HF, the CFI resulted in AUC of 0.755 (95% CI 0.749; 0.761) in women and 0.782 (95% CI 0.772; 0.793) in men. CONCLUSION: The 1987 and 2011 CCIs showed overall poor accuracy in fracture risk prediction. The CFI showed fair accuracy in prediction of HF in women and in men.

The treatment gap after major osteoporotic fractures in Denmark 2005-2014: a combined analysis including both prescription-based and hospital-administered anti-osteoporosis medications.

This study demonstrates a substantial and persistent anti-osteoporosis treatment gap in men and women ≥50 years old who sustained major osteoporotic fracture(s) between 2005 and 2014 in Denmark. This was not substantially reduced by including hospital-administered anti-osteoporosis treatments. Strengthened post-fracture organization of care and secondary fracture prevention is highly needed. INTRODUCTION: The purpose of this study was to evaluate the Danish anti-osteoporosis treatment gap from 2005 to 2014 in patients sustaining a major osteoporotic fracture (MOF), and to assess the impact of including hospital-administered anti-osteoporosis medications (AOM) on the treatment gap among these patients. METHODS: In this retrospective, registry-based study, we included men and women aged 50 years or older and living in Denmark, who sustained at least one MOF between 2005 and 2014. We applied a repeated cross-sectional design to generate cohorts of patients sustaining a first MOF, hip, vertebral, humerus, or forearm fracture, respectively, within each calendar year. We evaluated the treatment gap as the proportion of patients within each cohort not receiving treatment with AOM within 1 year of the fracture. Hospital-administered AOM was identified by SKS code. RESULTS: The treatment gap among MOF patients decreased from 85% in 2005 to 79% in 2014. The gap was smaller among hip and vertebral fracture patients as compared to humerus and forearm fracture patients, and it was smaller in women than in men. The use of hospital-administered AOM was relatively uncommon, with a maximum of 0.9% of MOF patients initiating hospital-administered AOM (in 2012). We observed substantial variations in this proportion between fracture types and gender. Hospital-administered AOM was most commonly used among vertebral fracture patients. CONCLUSION: A significant treatment gap among patients sustaining a major osteoporotic fracture was present throughout our analysis, and including hospital-administered AOM did not significantly improve the treatment gap assessment. Improved secondary fracture prevention is urgently needed.

Reoperation after antireflux surgery: a population-based cohort study.

BACKGROUND: Antireflux surgery for gastro-oesophageal reflux disease (GORD) and/or hiatal hernia is effective. Between 10 and 20 per cent of patients undergo reoperation for recurrent symptoms. Most studies are undertaken in a single centre and possibly underestimate the rate of reoperation. The aim of this nationwide population-based cohort study was to investigate long-term reoperation rates after antireflux surgery. METHODS: This study included patients who underwent antireflux surgery between 2000 and 2017 in Denmark, and were registered in the Danish nationwide health registries. Reoperation rates were calculated for 1, 5, 10 and 15 years after the primary antireflux operation for GORD and/or hiatal hernia. Duration of hospital stay, 30- and 90-day mortality and morbidity, and use of endoscopic pneumatic dilatation were assessed. RESULTS: This study included a total of 4258 antireflux procedures performed in 3717 patients. Some 3252 patients had only primary antireflux surgery and 465 patients underwent reoperation. The 1-, 5-, 10- and 15-year rates of repeat antireflux surgery were 3·1, 9·3, 11·7 and 12·8 per cent respectively. Thirty- and 90-day mortality rates were similar for primary surgery (0·4 and 0·6 per cent respectively) and reoperations. The complication rate was higher for repeat antireflux surgery (7·0 and 8·3 per cent at 30 and 90 days respectively) than primary operation (3·4 and 4·8 per cent). A total of 391 patients (10·5 per cent of all patients) underwent endoscopic dilatation after primary antireflux surgery, of whom 95 (24·3 per cent) had repeat antireflux surgery. CONCLUSION: In this population-based study in Denmark, the reoperation rate 15 years after antireflux surgery was 12·8 per cent. Reoperations were associated with more complications.

ANTECEDENTES: La cirugía antirreflujo es efectiva en el tratamiento de la enfermedad por reflujo gastroesofágico (gastro-oesophageal reflux disease, GORD) y/o de la hernia de hiato. Entre el 10% y el 20% de los pacientes tienen que ser reoperados por recidiva de los síntomas. La mayoría de los estudios son unicéntricos, lo que posiblemente infravalora la tasa de reintervenciones. El objetivo de este estudio de cohortes de base poblacional nacional fue investigar las tasas de reintervenciones a largo plazo tras la cirugía antirreflujo. MÉTODOS: Este estudio incluyó pacientes sometidos a cirugía antirreflujo entre 2000 y 2017 en Dinamarca y que fueron registrados en los registros nacionales de salud daneses. Se calcularon las tasas de reintervención para 1, 5, 10 y 15 años tras la operación antirreflujo primaria por GORD y/o hernia de hiato. Se evaluaron la duración de la estancia hospitalaria, la morbilidad y mortalidad a 30 y 90 días, y el uso de dilatación neumática endoscópica. RESULTADOS: Este estudio incluyó un total de 4.258 procedimientos antirreflujo efectuados en 3.717 pacientes. Unos 3.252 pacientes fueron sometidos únicamente a cirugía antirreflujo primaria y 465 pacientes a una reintervención. Las tasas de cirugía antirreflujo de revisión a 1, 5, 10 y 15 años fueron del 3,1%, 9,3%, 11,7% y 12,9%, respectivamente. La mortalidad a los 30 y 90 días fue similar cuando se comparó cirugía primaria y reintervenciones (mortalidad a 30 días 0,4% y 90 días 0,6% versus 0% y 0,4%, respectivamente). La tasa de complicaciones fue más elevada para la cirugía antirreflujo de revisión en comparación con la cirugía primaria: tasa de complicaciones a los 30 días 7,0%, 90 días 8,3% versus 30 días 3,4% y 90 días 4,8%, respectivamente. Un total de 391 pacientes (10,5% de todos los pacientes) fueron sometidos a dilatación endoscópica tras la cirugía antirreflujo primaria y 95 de 391 pacientes (24,3%) precisaron cirugía antirreflujo de revisión. CONCLUSIÓN: En este estudio de base poblacional en Dinamarca, la tasa de reintervención a los 15 años tras cirugía antirreflujo fue del 12,9%. Las reintervenciones se asociaron con más complicaciones.

The prevalence of type 2 diabetes in people with psychiatric disorders: an umbrella review protocol.

BACKGROUND: Many epidemiological studies have investigated the prevalence of type 2 diabetes in individuals with a psychiatric disorder. In an umbrella review, we aim to systematically summarize existing systematic reviews examining the prevalence of type 2 diabetes in people with a psychiatric disorder. When information is available in the identified systematic reviews, comparisons with control groups without a psychiatric disorder will be made. Furthermore, we aim to assess the quality of the included systematic reviews. METHODS: The umbrella review will be based on a comprehensive systematic search of systematic reviews of observational (cross-sectional or longitudinal) studies investigating the prevalence of type 2 diabetes in people with a psychiatric disorder. Four electronic databases (Embase, PsycINFO, PubMed, and the Cochrane Database of Systematic Reviews) will be searched. Retrieved papers will be screened for eligibility by two independent reviewers. Furthermore, the reference lists of all included publications will be screened. Data will be extracted by using an a priori developed data extraction form and two independent reviewers will assess the risk of bias in the included systematic reviews using with the Risk of Bias in Systematic Reviews (ROBIS) tool. A narrative data-synthesis and a subsequent meta-analysis based on the primary studies will be made. DISCUSSION: For each psychiatric disorder, the data regarding the prevalence of type 2 diabetes will be summarized and discussed. When possible, comparisons with control groups will be reported and discussed. Finally, future implications and recommendations for clinical care will be presented. SYSTEMATIC REVIEW REGISTRATION: This protocol was submitted for registration with the International Prospective Register of Systematic Reviews (PROSPERO) on December 9, 2019 (registration number: pending).

Secular trends in the initiation of therapy in secondary fracture prevention in Europe: a multi-national cohort study including data from Denmark, Catalonia, and the United Kingdom.

This paper demonstrates a large post-fracture anti-osteoporosis treatment gap in the period 2005 to 2015. The gap was stable in Denmark at around 88-90%, increased in Catalonia from 80 to 88%, and started to increase in the UK towards the end of our study. Improved post-fracture care is needed. INTRODUCTION: Patients experiencing a fragility fracture are at high risk of subsequent fractures, particularly within the first 2 years after the fracture. Previous studies have demonstrated that only a small proportion of fracture patients initiate therapy with an anti-osteoporotic medication (AOM), despite the proven fracture risk reduction of such therapies. The aim of this paper is to evaluate the changes in this post-fracture treatment gap across three different countries from 2005 to 2015. METHODS: This analysis, which is part of a multinational cohort study, included men and women, aged 50 years or older, sustaining a first incident fragility fracture. Using routinely collected patient data from three administrative health databases covering Catalonia, Denmark, and the United Kingdom, we estimated the treatment gap as the proportion of patients not treated with AOM within 1 year of their first incident fracture. RESULTS: A total of 648,369 fracture patients were included. Mean age 70.2-78.9 years; 22.2-31.7% were men. In Denmark, the treatment gap was stable at approximately 88-90% throughout the 2005 to 2015 time period. In Catalonia, the treatment gap increased from 80 to 88%. In the UK, an initially decreasing treatment gap-though never smaller than 63%-was replaced by an increasing gap towards the end of our study. The gap was more pronounced in men than in women. CONCLUSION: Despite repeated calls for improved secondary fracture prevention, an unacceptably large treatment gap remains, with time trends indicating that the problem may be getting worse in recent years.

Predictive values of anti-cyclic citrullinated peptide antibodies and rheumatoid factor in relation to serological aspects of the ACR/EULAR 2010 classification criteria for rheumatoid arthritis.

Objective: In this retrospective population-based register study, we wanted to determine the positive predictive values (PPVs) of immunoglobulin M rheumatoid factor (IgM RF) and anti-citrullinated protein antibodies (ACPAs) at 3 × upper normal limit (UNL), since they are weighted equally in the American College of Rheumatology (ACR)/ European League Against Rheumatism (EULAR) 2010 criteria for rheumatoid arthritis (RA).Methods: Test results, ordering unit, test date, and patient social security number were collected from the Department of Clinical Immunology at Odense University Hospital from 2007 to 2016 and merged with patient diagnosis from the Danish National Patient Registry.Results: The PPV of IgM RF at 3 × UNL was 14%, compared to a PPV of 43% for ACPAs at 3 × UNL.Conclusion: The PPV of ACPAs is higher than the PPV of IgM RF at 3 × UNL. These findings are not reflected in the ACR/EULAR 2010 classification criteria for RA.

Use of antiosteoporotic medication in the Danish ROSE population-based screening study.

Use of antiosteoporotic medication in the population-based, risk-stratified osteoporosis strategy evaluation (ROSE) screening study, comparing the use of FRAX followed by DXA with usual care, was examined. Screening increased the overall use of medication. Being recommended treatment by the hospital and higher age increased the likelihood of starting medication, but, nevertheless, a large percentage opted not to start treatment. INTRODUCTION: The aim of the study was to examine the impact on medication prescription, adherence, and persistence of osteoporotic medicine in the randomized population-based ROSE screening study for osteoporosis. METHODS: The Danish ROSE study included a population-based random sample of women aged 65-81 years randomized to either a two-step screening program consisting of FRAX followed by DXA for high-risk participants or opportunistic screening for osteoporosis (usual care). This sub-study on the intention-to-treat population examined the impact of the screening program on antiosteoporotic medication redemption rates, adherence, and persistence using Danish registers. RESULTS: A total of 30,719 of 34,229 women were treatment-naïve. Significantly more participants in the screening group started on antiosteoporotic medication, but no differences in adherence and persistence rates were found. Higher age was associated with a higher likelihood of starting medication. A low Charlson comorbidity score (= 1) was associated with higher treatment initiation but lower adherence and persistence of antiosteoporotic treatment. A total of 31.7% of participants advised to initiate treatment did not follow the advice. CONCLUSIONS: Screening for osteoporosis using FRAX followed by DXA increased the overall use of antiosteoporotic medication in the screening group without differences in adherence and persistence rates. A large percentage of participants advised to initiate treatment did nevertheless fail to do so.

Socioeconomic status and risk of osteoporotic fractures and the use of DXA scans: data from the Danish population-based ROSE study.

There is a need of studies exploring the link between socioeconomic status and DXA scans and osteoporotic fracture, which was the aim of the present study. No differences in socioeconomic status and risk of osteoporotic fractures were found. However, women with further/higher education and higher income are more often DXA-scanned. INTRODUCTION: Lower socioeconomic status is known to be associated with a range of chronic conditions and with access to health care services. The link between socioeconomic status and the use of DXA scans and osteoporotic fracture, however, needs to be explored more closely. Therefore, the aim of this study was to examine the relationship between socioeconomic status and both DXA scan utilization and major osteoporotic fractures (MOF) using a population-based cohort of Danish women and national registers. METHODS: The study included 17,155 women (65-81 years) sampled from the Risk-stratified Osteoporosis Strategy Evaluation study (ROSE). Information on socioeconomic background, DXA scans, and MOFs was retrieved from national registers. Competing-risk regression analyses were performed. Mean follow-up was 4.8 years. RESULTS: A total of 4245 women had a DXA scan (24.7%) and 1719 (10.0%) had an incident MOF during follow-up. Analyses showed that women with basic education had a lower probability of undergoing DXA scans than women with further or higher education (greater than upper secondary education and vocational training education) (subhazard ratio (SHR) = 0.82; 95% CI 0.75-0.89, adjusted for age and comorbidity). Moreover, women with disposable income in the low and medium tertiles had a lower probability of undergoing DXA scans than women in the high-income tertile (SHR = 0.90; 95% CI 0.84-0.97 and SHR = 0.88, 95% CI 0.82-0.95, respectively, adjusted for age and comorbidity). No association between socioeconomic background and probability of DXA was found in adjusted analyses. CONCLUSION: The study found no differences in risk of osteoporotic fractures depending on socioeconomic status. However, women with further or higher education as well as higher income are more often DXA-scanned.

Pediatric endocrine society survey of diabetes practices in the United States: What is the current state?

BACKGROUND: The Practice Management Committee (PMC) of the Pediatric Endocrine Society (PES) conducted a survey of its membership in February/March, 2016 to assess the current state of pediatric diabetes care delivery across multiple practice types in the United States. METHODS: The PES distributed an anonymous electronic survey (Survey Monkey) via email to its membership and requested that only one survey be completed for each practice. RESULTS: Ninety-three unique entries from the US were entered into analysis. Care is predominantly delivered by multidisciplinary teams, based at academic institutions (65.6%), with >85% of the provider types being physicians. Each 1.0 full time equivalent certified diabetes educators serves on average 367 diabetic youth. Fee-for-service remains the standard method of reimbursement with 57% of practices reporting financial loss. Survey respondents identified under-reimbursement as a major barrier to improving patient outcomes and lack of behavioral health (BH) providers as a key gap in services provided. CONCLUSIONS: Our survey reveals wide variation in all aspects of pediatric diabetes care delivery in the United States. Pediatric Endocrinologists responding to the survey identified a lack of resources and the current fee for service payment model as a major impediment to practice and the lack of integrated BH staff as a key gap in service. The respondents strongly support its organizations' involvement in the dissemination of standards for care delivery and advocacy for a national payment model aligned with chronic diabetes care in the context of our emerging value-based healthcare system.

Effectiveness of a two-step population-based osteoporosis screening program using FRAX: the randomized Risk-stratified Osteoporosis Strategy Evaluation (ROSE) study.

The Risk-stratified Osteoporosis Strategy Evaluation (ROSE) study investigated the effectiveness of a two-step screening program for osteoporosis in women. We found no overall reduction in fractures from systematic screening compared to the current case-finding strategy. The group of moderate- to high-risk women, who accepted the invitation to DXA, seemed to benefit from the program. INTRODUCTION: The purpose of the ROSE study was to investigate the effectiveness of a two-step population-based osteoporosis screening program using the Fracture Risk Assessment Tool (FRAX) derived from a self-administered questionnaire to select women for DXA scan. After the scanning, standard osteoporosis management according to Danish national guidelines was followed. METHODS: Participants were randomized to either screening or control group, and randomization was stratified according to age and area of residence. Inclusion took place from February 2010 to November 2011. Participants received a self-administered questionnaire, and women in the screening group with a FRAX score ≥ 15% (major osteoporotic fractures) were invited to a DXA scan. Primary outcome was incident clinical fractures. Intention-to-treat analysis and two per-protocol analyses were performed. RESULTS: A total of 3416 fractures were observed during a median follow-up of 5 years. No significant differences were found in the intention-to-treat analyses with 34,229 women included aged 65-80 years. The per-protocol analyses showed a risk reduction in the group that underwent DXA scanning compared to women in the control group with a FRAX ≥ 15%, in regard to major osteoporotic fractures, hip fractures, and all fractures. The risk reduction was most pronounced for hip fractures (adjusted SHR 0.741, p = 0.007). CONCLUSIONS: Compared to an office-based case-finding strategy, the two-step systematic screening strategy had no overall effect on fracture incidence. The two-step strategy seemed, however, to be beneficial in the group of women who were identified by FRAX as moderate- or high-risk patients and complied with DXA.

Non-participation in systematic screening for osteoporosis-the ROSE trial.

Population-based screening for osteoporosis is still controversial and has not been implemented. Non-participation in systematic screening was evaluated in 34,229 women age 65-81 years. Although participation rate was high, non-participation was associated with comorbidity, aging other risk factors for fractures, and markers of low social status, e.g., low income, pension, and living alone. A range of strategies is needed to increase participation, including development of targeted information and further research to better understand the barriers and enablers in screening for osteoporosis. INTRODUCTION: Participation is crucial to the success of a screening program. The objective of this study was to analyze non-participation in Risk-stratified Osteoporosis Strategy Evaluation, a two-step population-based screening program for osteoporosis. METHODS: Thirty-four thousand two hundred twenty-nine women aged 65 to 81 years were randomly selected from the background population and randomized to either a screening group (intervention) or a control group. All women received a self-administered questionnaire designed to allow calculation of future risk of fracture based on FRAX. In the intervention group, women with an estimated high risk of future fracture were invited to DXA scanning. Information on individual socioeconomic status and comorbidity was obtained from national registers. RESULTS: A completed questionnaire was returned by 20,905 (61%) women. Non-completion was associated with older age, living alone, lower education, lower income, and higher comorbidity. In the intervention group, ticking "not interested in DXA" in the questionnaire was associated with older age, living alone, and low self-perceived fracture risk. Women with previous fracture or history of parental hip fracture were more likely to accept screening by DXA. Dropping out when offered DXA, was associated with older age, current smoking, higher alcohol consumption, and physical impairment. CONCLUSIONS: Barriers to population-based screening for osteoporosis appear to be both psychosocial and physical in nature. Women who decline are older, have lower self-perceived fracture risk, and more often live alone compared to women who accept the program. Dropping out after primary acceptance is associated not only with aging and physical impairment but also with current smoking and alcohol consumption. Measures to increase program participation could include targeted information and reducing physical barriers for attending screening procedures.

Diagnostic devices for osteoporosis in the general population: A systematic review.

INTRODUCTION: A diagnostic gap exists in the current dual photon X-ray absorptiometry (DXA) based diagnostic approach to osteoporosis. Other diagnostic devices have been developed, but no comprehensive review concerning the applicability of these diagnostic devices for population-based screening have been performed. MATERIAL AND METHODS: A systematic review of Embase, Medline and the Cochrane Central Register for Controlled Trials was performed for population-based studies that focused on technical methods that could either indicate bone mineral density (BMD) by DXA, substitute for DXA in prediction of fracture risk, or that could have an incremental value in fracture prediction in addition to DXA. Quality of included studies was rated by QUADAS 2. RESULTS: Many other technical devices have been tested in a population-based setting. Five studies aiming to indicate BMD and 17 studies aiming to predict fractures were found. Overall, the latter studies had higher methodological quality. The highest number of studies was found for quantitative ultrasound (QUS). The ability to indicate BMD or predict fractures was moderate to minor for all examined devices, using reported area under the curve (AUC) of Receiver Operating Characteristic curves values as standard. CONCLUSIONS: Of the methods assessed, only QUS appears capable of perhaps replacing DXA as standalone examination in the future whilst radiographic absorptiometry could provide important information in areas with scarcity of DXA. QUS may be of added value even after DXA has been performed. Evaluation of proposed cutoff-values from population-based studies in separate population-based cohorts is still lacking for most examination devices.

Relação entre práticas parentais e problemas de externalização e internalização: papel mediador do vínculo de apego / Relationship between parenting and internalizing and externalizing problems: the mediating role of attachment

Os problemas emocionais e comportamentais infantis têm sido alvo de crescente investigação devido a sua alta estabilidade e por precederem os transtornos psicopatológicos na vida adulta. Esse estudo objetivou investigar o papel mediador do vínculo de apego na relação entre práticas parentais e problemas externalizantes (agressividade/delinquência) e internalizantes (retraimento social/ansiedade/depres-são). Um total de 289 crianças (M = 10,5 anos, DP = 0,77) responderam à Security Scale e 181 mães responderam ao Child Rearing Practices Report–Q e, também, ao ChildBehavior Checklist. Os resultados revelaram o papel mediador do vínculo de apego materno nosproblemas externalizantes, mas não nos internalizantes, e salientam a importância de se considerar aqualidade do apego nas relações entre práticas parentais e problemas emocionais e comportamentaisna infância(AU)

Risk factors for osteoporosis and factors related to the use of DXA in Norway.

UNLABELLED: To evaluate the case-finding strategy for osteoporosis in Norway, a questionnaire concerning risk factors for osteoporosis and history of osteodensitometry was mailed to a population-based cohort of 6000 men and 6000 women. Suboptimal examination rates among high risk and reallocation of scanning capacity to seemingly low-risk individuals was found. PURPOSE: In Norway, a case-finding strategy for osteoporosis has been used. No data exist regarding the efficacy of this approach. The aim was to examine the prevalence of risk factors for osteoporosis and factors related to the use of dual X-ray absorptiometry (DXA) in Norway. METHODS: Questionnaires regarding previous history of DXA, risk factors for osteoporosis and fracture were sent to an age-stratified, nationwide cross-sectional sample of 6000 men and 6000 women aged 40-90 years, drawn from the Norwegian Civil Registration System. RESULTS: Valid responses (6029) were included. Twenty-two point three percent of women and 3.8 % of men had been examined by DXA. Suboptimal examination rates among high risk (e.g., current/previous glucocorticoid treatment or previous low-energy fracture) and reallocation of scanning capacity to seemingly low-risk individuals was found. Of all DXA, 19.5 % were reported by women without any risk factor for osteoporosis, similarly by 16.2 % of men. Distance to DXA facilities and current smoking were inversely related to probability of reporting a DXA. CONCLUSIONS: Suboptimal examination rates among high risk and reallocation of scanning capacity to seemingly low-risk individuals were found. Distance to DXA, current smoking, and male sex constituted possible barriers to the case-finding strategy employed. Cheap and more available diagnostic tools for osteoporosis are needed, and risk stratification tools should be employed more extensively.

Characteristics of patients who suffer major osteoporotic fractures despite adhering to alendronate treatment: a National Prescription registry study.

UNLABELLED: Antiresorptive treatment reduces the risk of fractures, but most patients remain at elevated risk. We used health registers to identify predictors of new major osteoporotic fractures in patients adhering to alendronate. Risk factors showed a different pattern than in the general population and included dementia, ulcer disease, and Parkinson's disease. INTRODUCTION: Antiresorptives reduce the excess risk of fractures in patients with osteoporosis, but most patients remain at elevated risk. In some countries, patients must sustain fractures while on bisphosphonate (BP) treatment to qualify for more expensive treatment. It is unclear if patients who fracture on BP can be viewed as a distinct subgroup. METHODS: The National Prescription registry was used to identify 38,088 new alendronate users. The outcome was major osteoporotic fractures 6+ months after filling the first prescription in patients with a medication possession ratio > 80 %. RESULTS: One thousand and seventy-two (5.5 %) patients sustained major osteoporotic fractures. The risk increased with age and was lower in men. The most important risk factor was the number of comedications (hazard ratio (HR) 1.04, 95 % CI 1.03-1.06, for each drug). Dementia (HR 1.81, 95 % CI 1.18-2.78), prior fracture (one: HR 1.17, 95 % CI 1.02-1.34; multiple: HR 1.34, 95 % CI 1.08-1.67), and ulcer disease (HR 1.45, 95 % CI 1.04-2.03) also increased the risk. Diabetes did not influence fracture risk, nor did rheumatic disorders. The risk was lower in glucocorticoid users (HR 0.78, 95 % CI 0.65-0.93). CONCLUSION: Risk factors while adhering to BP show a somewhat different pattern than that of the general population and FRAX. Ulcer disease and dementia may impair the ability to use the medications correctly. Though this is an observational study and associations may not be causal, it may be prudent to include dementia, ulcer disease, and Parkinson's disease to capture the risk of fractures on treatment. Lower risk in patients treated with glucocorticoids and in men probably reflects a lower treatment threshold related to guidelines.

Pattern of use of DXA scans in men: a cross-sectional, population-based study.

UNLABELLED: Osteoporosis in men is underdiagnosed. The use of dual-emission X-ray absorptiometry (DXA) was evaluated in almost 5,000 men aged 60-74 years. DXA was infrequent, despite the presence of multiple risk factors for osteoporosis and a high FRAX score. There is a need for improved targeting of DXA scans for men at high risk. INTRODUCTION: Clinical and socioeconomic factors associated with bone mass assessment (DXA) in men have seldom been evaluated. This study aimed to evaluate factors associated with the use of DXA in men. METHODS: Self-report information on prior DXA and osteoporosis risk factors were obtained from the baseline data of a study investigating the health perspectives of men aged 60-75 years. Socioeconomic and comorbidity data were retrieved from national registers. The FRAX algorithm was used to calculate the absolute fracture risk. Regression analysis was used to identify factors significantly associated with previous DXA scan. RESULTS: Of the 4,696 men returning questionnaires (50% response rate), 2.7% had prior DXA but 48% had at least one osteoporosis risk factor. Previous DXA was associated with oral glucocorticoid treatment, secondary osteoporosis, rheumatoid arthritis, fracture after age 50, falls within the previous year, smoking, and higher age. Twenty-one percent of men with prior DXA and 10% of men without prior DXA had greater than 20% risk of a major osteoporotic fracture within the next 10 years. One third of those with previous DXA had none of the FRAX osteoporosis risk factors. When family history of osteoporosis and falls were included as risk factors, 18% with previous DXA had no clinical risk factors for osteoporosis. CONCLUSIONS: DXA was infrequent in this group of elderly men, despite the presence of risk factors for osteoporosis. DXA was also used despite a low fracture risk. There is a need for improved targeting of DXA scans for men at high risk.

Ovum pick up, in vitro embryo production, and pregnancy rates from a large-scale commercial program using Nelore cattle (Bos indicus) donors.

The objective was to clarify in vitro production of bovine embryos in Brazil. Data from 656 ovum pick-up/in vitro production (OPU/IVP) procedures, performed on 317 Nelore (Bos indicus) donors, without hormone stimulation or control of ovarian follicular waves, were analysed. Donors were subjected to OPU from one to nine times (no specific schedule), with < 15 d between consecutive procedures. There were 20,848 oocytes, of which 15,747 (75.53%) were considered viable, 5,446 embryos were obtained, 5,398 embryos were immediately transferred, resulting in 1,974 pregnancies (36.57%) at Day 30 and 1,788 (33.12%) pregnancies at Day 60. The average number of total and viable oocytes produced per OPU session was (mean ± SEM) 30.84 ± 0.88 and 23.35 ± 0.7 (average of 8.1 ± 0.3 embryos and 3.0 ± 0.1 pregnancies per OPU-IVP procedure). Since oocyte production varied widely among donor, they were designated as very high, high, intermediate, and low, with 58.94 ± 2.04, 32.61 ± 0.50, 22.13 ± 0.50, and 10.26 ± 0.57 oocytes, respectively, produced by 78, 80, 79, and 80 donors. The number of viable oocytes recovered ranged from 0 to 128; since donors with numerous viable oocytes produced many viable embryos and pregnancies, oocyte production was useful for donor selection. However, there was no significant effect of the number of OPU sessions per donor on mean numbers of oocytes produced. In conclusion, we confirmed field reports of high oocyte production by some Nelore donors and demonstrated individual variation in oocyte yield, which was associated with embryo production and pregnancy rates.