Epidemic of parvovirus B19 and disease severity in pregnant people, Denmark, January to March 2024.

We report an epidemic of parvovirus B19 infections in Denmark during the first quarter of 2024, with a peak incidence 3.5 times higher than during the most recent epidemic in 2017. In total, 20.1% (130/648) of laboratory-confirmed cases were pregnant. Severe adverse outcomes were observed among 12.3% (16/130) of pregnant people and included foetal anaemia, foetal hydrops and miscarriage. Parvovirus B19 infection is not systematically monitored, but a national laboratory-based surveillance system is currently being established in Denmark.

Cost of out-of-hospital cardiac arrest survivors compared with matched control groups.

INTRODUCTION: Societal costs of out-of-hospital cardiac arrest (OHCA) survivors may be extensive due to high health care utilization and sick leave. Knowledge of the costs of OHCA survivors may guide decision-makers to prioritize health resources. AIM: The aims of the study were to evaluate the costs of OHCA survivors from a societal perspective, and to compare these costs to the costs of individuals with non-cardiac arrest myocardial infarction (MI) and individuals with no cardiac disease (non-CD). METHODS: From the Danish OHCA Registers, survivors, with a cardiac arrest between 2005-2018 were identified. Each case was assigned one MI control and one non-CD control, matched on gender and age. Based on register data, costs of healthcare utilization, sick leave, vocational rehabilitation, disability pension and other social benefits one year before event and five years after, were estimated. RESULTS: In total 5,646 OHCA survivors were identified with associated control groups. The mean costs for OHCA survivors during the 6-year period were €119,106 (95%CI: 116,297-121,916), with €83,472 (95%CI: 81,392-85,552) being healthcare costs. Mean costs of OHCA survivors were €49,132 higher than the MI-control group and €100,583 higher than the non-CD control group. CONCLUSIONS: Total costs of OHCA survivors were considerably higher than costs of MI- and non-CD controls. Hospital costs were highest during the first year after event, and work inability during the second to fifth year with sick leave and later disability pension as main burdens.

Mycoplasma pneumoniae epidemic in Denmark, October to December, 2023.

We report a surge of patients, especially children and adolescents, with respiratory disease caused by Mycoplasma pneumoniae in Denmark since October 2023. While the surge has reached an epidemic level, no impact on hospital capacity has been observed; only 14% (446/3,195) of cases, primarily adults, required hospitalisation. Macrolide resistance was detected in less than 2% of samples tested. Timely monitoring of hospitalisations linked to M. pneumoniae infections has been established to inform the healthcare system, decisionmakers and the public.

Feasibility of early digital health rehabilitation after cardiac surgery in the elderly: a qualitative study.

BACKGROUND: Increasing numbers of elderly patients experience prolonged decreased functional capacity and impaired quality of life after seemingly successful cardiac surgery. After discharge from hospital, these patients experience a substantial gap in care until centre-based cardiac rehabilitation commences. They may benefit from immediate coaching by means of mobile health technology to overcome psychological and physiological barriers to physical activity. The aim of this study was to explore the usability, acceptability, and relevance of a mobile health application designed to support remote exercise-based cardiac rehabilitation of elderly patients early after cardiac surgery from the perspective of patients, their relatives, and physiotherapists. METHODS: We adapted a home-based mobile health application for use by elderly patients early after cardiac surgery. Semi-structured dyadic interviews were conducted with a purposive sample of patients (n = 9), their spouses (n = 5), and physiotherapists (n = 2) following two weeks of the intervention. The transcribed interviews were analysed thematically. RESULTS: Three themes were identified: 1) creating an individual fit by tailoring the intervention; 2) prioritizing communication and collaboration; and 3) interacting with the mobile health application. Overall, the findings indicate that the mobile health intervention has the potential to promote engagement, responsibility, and motivation among elderly patients to exercise early after surgery. However, the intervention can also be a burden on patients and their relatives when roles and responsibilities are unclear. CONCLUSION: The mobile health intervention showed potential to bridge the intervention gap after cardiac surgery, as well as in fostering engagement, responsibility, and motivation for physical activity among elderly individuals. Nevertheless, our findings emphasize the necessity of tailoring the intervention to accommodate individual vulnerabilities and capabilities. The intervention may be improved by addressing a number of organizational and communicational issues. Adaptions should be made according to the barriers and facilitators identified in this study prior to testing the effectiveness of the intervention on a larger scale. Future research should focus on the implementation of a hybrid design that supplements or complements face-to-face and centre-based cardiac rehabilitation. TRIAL REGISTRATION: Danish Data Protection Agency, Central Denmark Region (1-16-02-193-22, 11 August 2022).

Prognostic factors for high societal costs: a register-based study on 561,665 patients with shoulder disorders.

ABSTRACT: Shoulder disorders are common and associated with high societal costs, especially for a small group of patients. Prognostic factors can help identify high-cost patients, which is crucial to optimize early identification and develop tailored interventions. We aimed to identify prognostic factors for high societal costs, to examine whether the prognostic factors were similar for high healthcare costs and high costs of sick leave, and to investigate the model's robustness across 4 diagnostic categories. Using national Danish registers, potential prognostic factors (age, sex, educational level, long-term sick leave, admission, visits to general practitioner and physiotherapist, comorbidity, diabetes, low back pain, and neck pain) were included in a logistic regression model with high societal costs, defined by the top 10th percentile, as the main outcome. The model's prognostic accuracy was assessed using the Nagelkerke R2 and its discriminative ability using area under the receiver operating curve (AUC). Data on 80% of the patients (n = 449,302) were used to develop the model and 20% (n = 112,363) to validate the model. By far the strongest prognostic factor for high societal costs and high costs of sick leave was sick leave at the time of diagnosis (OR: 20.2, 95% CI: 19.5-20.9). Prognostic factors for high healthcare costs were high age, comorbidity, and hospital admission the year before diagnosis. The model was robust across diagnostic categories and sensitivity analyses. In the validation sample, the primary model's discriminative ability was good (AUC = 0.80) and the model explained 28% of the variation in the outcome (Nagelkerke R2 ).

A 1-year follow-up study in patients with idiopathic pulmonary fibrosis regarding adverse outcomes to unintended weight loss.

OBJECTIVES: Malnutrition in pulmonary fibrosis may influence clinical outcomes negatively. This project aimed to investigate if weight, unintended weight loss (UWL) at baseline and weight development, and signs of sarcopenia measured by the strength, assistance with the walking, rising from a chair, climbing stairs, and falls questionnaire (SARC-F) are associated with hospital admissions and mortality for idiopathic pulmonary fibrosis outpatients in ≤1 y as well as referral to pulmonary rehabilitation. METHODS: At baseline, prevalence of weight and UWL were sought in a cross-sectional questionnaire study, consecutively, including 100 patients in an outpatient clinic. Medical records were sought for time from diagnosis and comorbidities. One year after inclusion weight, UWL and SARC-F were collected by phone interviews, and medical records were revisited for clinical outcomes. RESULTS: Of the 100 patients, two patients died and seven were lost to follow-up. The prevalence of UWL increased within the year (10-13%), and the amount of UWL increased (9.1-11.8 kg). Patients with a UWL at baseline had a significantly higher risk of mortality (odds ratio = 29.8; P = 0.037). UWL at baseline was associated with risk of hospital admissions (odds ratio = 14.7; P = 0.009). Based on the results from SARC-F, 20.9% have signs of sarcopenia. UWL at follow-up was associated with the risk of sarcopenia by SARC-F. Patients with risk of sarcopenia and those with body mass index ≥30 kg/m2 were to a higher degree offered pulmonary rehabilitation; however, participation was low. CONCLUSIONS: UWL at baseline was significantly associated with risk of hospital admissions and mortality in ≤1 y in idiopathic pulmonary fibrosis outpatients. Patients with signs of sarcopenia and body mass index ≥30 kg/m2 were most often referred to pulmonary rehabilitation.

Risk stratification for post-operative pulmonary complications following major cardiothoracic or abdominal surgery: Validation of the PPC Risk Prediction Score for physiotherapist's clinical decision-making.

INTRODUCTION: Patients undergoing major cardiothoracic or abdominal surgery are at increased risk of developing post-operative pulmonary complications (PPC), but respiratory physiotherapy can prevent PPC. We have previously developed the PPC Risk Prediction Score to allocate physiotherapists' resources and stratify patients into three risk groups. In this study, we performed a temporal external validation of the PPC Risk Prediction Score. Such validation is rare and adds to the originality of this study. METHODS: A cohort of 360 patients, admitted to undergo elective cardiothoracic or abdominal surgery, were included. Performance and clinical usefulness of the PPC Risk Prediction Score were estimated through discrimination, calibration and clinical usefulness, and the score was updated. RESULTS: The score showed c-statistics of 0.62. Related to clinical usefulness, a cut point at 8 gave a sensitivity of 0.49 and a specificity of 0.70, whereas a cut point at 12 gave a sensitivity of 0.13 and a specificity of 0.95. Two predictors included in the development sample score, thoraco-abdominal incision odds ratio (OR) 2.74 (1.12;6.71) and sternotomy OR 2.09 (1.18;3.72), were statistically significantly associated to PPC in the validation sample. CONCLUSIONS: The score was not able to discriminate between patients with and without PPC; neither was the updated score, but the study identified clinically relevant risk factors for developing PPC.

Reliability and responsiveness of the Danish version of The Chelsea Critical Care Physical Assessment tool (CPAx).

INTRODUCTION: Measurement instruments are important in clinical practice and research for assessing physical function in critically ill patients in the intensive care unit (ICU). OBJECTIVE: To investigate inter-rater reliability and responsiveness of the Danish version of the CPAx (CPAx-D). METHOD: Critically ill patients from three Danish ICUs were included. Patients were assessed with CPAx-D by two blinded testers during a regular physiotherapy session. Follow-up tests were performed in patients who stayed in the ICU for more than 24 hours, were not transferred to another hospital or received palliative care. Floor and ceiling effects were examined in all assessments.Results For the reliability analysis 66 patients were included.Results Showed no significant difference between raters. For the total score, intra class correlation coefficient (ICC) was 0.996 (95% CI: 0.993; 0.997), standard error of measurement was 0.72 point and minimal detectable change 2.0 points. Bland-Altman plot revealed no heteroscedacity. The responsiveness results of 24 patients showed that the effect size was 1.2 and the standardized response mean 1.1, which was in accordance with the hypothesis. No ceiling or floor effect was revealed. CONCLUSION: The CPAx-D showed excellent inter-rater reliability and responsiveness.

Risk Stratification for Postoperative Pulmonary Complications following Major Cardiothoracic and Abdominal Surgery - development of the PPC Risk Prediction Score for Physiotherapists Clinical Decision-making.

INTRODUCTION: Major cardiothoracic or abdominal surgery can lead to the development of postoperative pulmonary complications (PPC), associated with increased morbidity and prolonged length of hospital stay. Preventive chest physiotherapy is routinely provided, but optimization of treatment strategies is needed to improve patient outcome and resource utilization. OBJECTIVE: To develop a preoperative risk prediction scorelr to assist clinical decision-making regarding physiotherapy interventions. METHODS: A prospective observational single-center study included 339 of 577 eligible patients admitted for major elective cardiothoracic or abdominal surgery. Primary outcome measure was PPC amendable to chest physiotherapy. RESULTS: A total of 113 patients (33.3%) developed a PPC. Logistic regression modeling identified four independent predictors of PPC presented with odds ratio (OR) and 95% confidence interval. Reduced lung function (FEV1 > 50% to <75% OR 2.4 (1.4; 4.3) and FEV1 ≤ 50% OR 4.7 (1.4;16.0)), Recent unintended weight loss OR 4.5 (1.1; 18.7), Sternotomy OR 3.5 (2.0; 6.0) and Thoraco-abdominal incision OR 4.5 (2.1; 10.1). Based on assigned point values, a score dividing patients into three risk groups was developed. The score had moderate discrimination (c-statistic 0.70). CONCLUSION: By following recommended guidelines (TRIPOD) a preoperative risk prediction score including four predictors of PPC was developed. External validation of the score is currently being investigated.

A mobile observatory powered by sun and wind for near real time measurements of atmospheric, glacial, terrestrial, limnic and coastal oceanic conditions in remote off-grid areas.

Climate change is rapidly altering the Arctic environment. Although long-term environmental observations have been made at a few locations in the Arctic, the incomplete coverage from ground stations is a main limitation to observations in these remote areas. Here we present a wind and sun powered multi-purpose mobile observatory (ARC-MO) that enables near real time measurements of air, ice, land, rivers, and marine parameters in remote off-grid areas. Two test units were constructed and placed in Northeast Greenland where they have collected data from cabled and wireless instruments deployed in the environment since late summer 2021. The two units can communicate locally via WiFi (units placed 25 km apart) and transmit near-real time data globally over satellite. Data are streamed live and accessible from (https://gios.org). The cost of one mobile observatory unit is c. 304.000€. These test units demonstrate the possibility for integrative and automated environmental data collection in remote coastal areas and could serve as models for a proposed global observatory system.

Change in exercise capacity measured by Cardio-pulmonary Exercise Testing (CPET) in Danish people with cystic fibrosis after initiation of treatment with Lumacaftor/Ivacaftor and Tezacaftor/Ivacaftor.

BACKGROUND: Since 2015, when the first cystic fibrosis transmembrane conductance regulator (CFTR) modulators were approved for people with cystic fibrosis (CF) homozygous for F508del-CFTR, studies have shown improved lung function after initiation of the treatment and patients experience improved physical capacity. The aim of this study was to investigate change in exercise capacity after initiation of Lumacaftor/Ivacaftor and Tezacaftor/Ivacaftor treatment (LUM/IVA, TEZ/IVA). METHODS: We performed a single group prospective observational cohort study with follow-up at six and 12 months. The study examined change in exercise capacity in people with CF initiating treatment with LUM/IVA and TEZ/IVA, measured by cardio-pulmonary exercise testing (CPET). Inclusion criteria were people with CF homozygous for F508del-CFTR aged 12 years or older eligible for LUM/IVA and TEZ/IVA treatment from June 2017 until June 2019. Primary outcomes were change in VO2peak and maximal workload. Secondary outcomes were change in muscle strength, muscle power and body composition in a subgroup of the study population. RESULTS: A total of 91 patients were included in the analysis. The mean change in VO2peak and VO2peak divided by body weight from baseline to 12-months follow-up was 145.7 (91.2;200.2) ml/min and 1.07 (95% CI 0.19;1.95) ml/min/kg, respectively. The mean change in maximal workload between baseline and 12 months was 14.2 Watt (95% CI 9.1;19.2). All improvements in exercise capacity were statistically significant. CONCLUSIONS: Patients in this study improved their exercise capacity by a statistically significant increase in VO2peak and maximal workload 12 months after initiation of treatment with LUM/IVA and TEZ/IVA.

Costs of shoulder disorders in Denmark: a nationwide cost-of-illness study investigating 617,334 patients and matched controls.

ABSTRACT: Shoulder disorders are very common musculoskeletal conditions. Few studies have focused on the costs associated with shoulder disorders, and the economic burden has never been established in a nationwide cost-of-illness study. We aimed to evaluate the healthcare costs and costs of productivity loss (sick leave) and to evaluate if costs were higher for specific subgroups. Using national Danish registers, we identified individuals with shoulder disorders (subacromial pain, stiffness, fracture, or dislocation) diagnosed between 2005 and 2017 and controls matched on age and gender without shoulder disorders. Health care usage, sick leave, and related costs were estimated. During the 13-year inclusion period, 617,334 unique individuals were identified and the incidence rate was 1215 per 100,000 person-years in 2017. The expected additional societal costs were €1.21 billion annually. The mean additional total costs for the 6-year period were €11,334 (11,014-11,654) for individuals aged ≥65 years and €25,771 (25,531-26,012) for individuals aged <65 years. For individuals in the working age, the costs of sick leave accounted for approximately 70% of the total costs. Individuals aged ≥65 years had healthcare costs that were twice as high as individuals aged <65 years. Additionally, the 20% of cases accruing the highest costs accounted for 66% of the total costs. In conclusion, incidence rates of shoulder disorders were high and costs of sick leave accounted for a large proportion of total costs associated with illness in working age people. Furthermore, a minority of patients accounted for a substantial share of the total costs.

Responsiveness and minimal important change of the Oxford Shoulder Score, EQ-5D, and the Fear-Avoidance Belief Questionnaire Physical Activity subscale in patients undergoing arthroscopic subacromial decompression.

INTRODUCTION: Adequate responsiveness and knowledge of the minimal important change (MIC) is essential when using patient-reported outcome measures to assess treatment efficacy. OBJECTIVE: The objective of this study was to evaluate the responsiveness and MIC of common outcomes in patients with subacromial impingement syndrome undergoing arthroscopic subacromial decompression. METHODS: At baseline and 6 months after surgery, patients completed the Oxford Shoulder Score (OSS), EQ-5D 5-level utility index, EQ visual analogue scale, Fear-Avoidance Belief Questionnaire Physical Activity subscale (FABQ-PA), assessed pain (pain visual analogue scale), and Subjective Shoulder Value. Furthermore, at the 6-month follow-up, patients assessed the overall change with a Global Rating of Change Scale. Responsiveness was examined by analyzing the area under the receiver operating characteristics curve and correlations between the change scores. MIC was assessed using the optimal cutoff point at the receiver operating characteristics curve. RESULTS: Area under the receiver operating characteristics curve estimates were 0.96 (95% confidence interval [CI] 0.91,1.00) for OSS, 0.82 (95% CI 0.66,0.99) for EQ-5D 5-level utility index, 0.73 (95% CI 0.58,0.87) for EQ visual analogue scale, and 0.74 (95% CI 0.58,0.90) for FABQ-PA. MIC were 6.0 points for OSS, 0.024 points for EQ-5D 5-level utility index, 10.0 points for EQ visual analogue scale, and -5.0 points for FABQ-PA. CONCLUSION: Responsiveness of the OSS, EQ-5D, and FABQ-PA was sufficient to measure improvement after arthroscopic decompression surgery.

Establishment of a Danish endodontic practice-based research network: baseline data.

OBJECTIVE: Clinical studies in endodontics are primarily performed in highly controlled environments using strict treatment protocols, inclusion and exclusion criteria, and high success rates have been reported. Most endodontic treatments are, however, performed in private practice, where is has been difficult to obtain similar high success rates. The aim of this pilot project was to evaluate the feasibility of performing practice-based research and to describe baseline information on endodontic procedures used in general practice in Denmark. MATERIALS AND METHODS: The baseline data included information from dental practitioners, collected during 2017-2018. The dentists used the procedures and materials they normally would use. Data were systematized and analysed at Aarhus University. RESULTS: Seventeen dentists provided information on 581 endodontic treatments. Half of the teeth had initially a necrotic pulp, 20% had a vital pulp and 28% were previously root-filled. Adaptation of contemporary technology such as mechanized instrumentation, use of magnification, seems to be well integrated among the participating dentists. CONCLUSIONS: Overall, the endodontic treatments performed by the participating dentists follow international guidelines for good quality endodontic treatments. It is anticipated, that among Danish dentist there is basis for further practice-based research, but logistic issues need to be addressed.

Measurement Properties of Isokinetic Dynamometry for Assessment of Shoulder Muscle Strength: A Systematic Review.

OBJECTIVE: To investigate the evidence of measurement properties of isokinetic dynamometry (ID) for assessment of shoulder muscle strength in healthy individuals and patients with nonneurologic shoulder pathology. DATA SOURCES: Cochrane Central Register of Controlled Trials, PubMed, EMBASE, and Physiotherapy Evidence Database were searched up to February 2020 without restrictions. Reference lists and citations were hand-searched. STUDY SELECTION: Two review authors independently included studies that met the following criteria: (1) evaluated measurement properties of ID when used on the glenohumeral joint and (2) included individuals 18 years and older. Studies including patients with neurologic, neuromuscular, or systemic diseases or critical illness were excluded. DATA EXTRACTION: The quality assessment and data synthesis were performed according to the COnsensus-based Standards for the selection of health Measurement INstruments methodology. DATA SYNTHESIS: Twenty-one studies with a total of 597 participants were included. The results were combined separately for isometric, concentric, and eccentric test mode; for the velocities 30°/s-60°/s, 90°/s, 120°/s, and 240°/s; for the seated, supine, and standing position; and for internal rotation (IR), external rotation (ER), and the ER/IR ratio. The reliability of ID was overall sufficient with the majority of intraclass correlation coefficients ≥0.70. The quality of evidence was moderate or low for 20 of 30 strata examined. The measurement error results were rated as insufficient for all strata. The SEM ranged from 4%-28%. The quality of evidence varied depending of strata examined. CONCLUSIONS: The reliability of ID for measurement of shoulder strength was overall sufficient for all positions, velocities, and modes of strength. The measurement error was not sufficient. Because most studies used the seated position, the velocities 30°/s-60°/s or 120°/s, and the concentric test mode, the quality of evidence was highest for these conditions.

Validity of the Talk Test as a Method to Estimate Ventilatory Threshold and Guide Exercise Intensity in Cardiac Patients.

PURPOSE: To determine the relationship between the Talk Test (TT) and ventilatory threshold (VT) in patients with cardiac disease and to compare the TT with exercise intensity guidelines. METHODS: Twenty cardiac patients, aged 65 ± 8.5 yr, performed 2 exercise tests with identical ramp protocols on a cycle ergometer on the same day. One test was a submaximal effort to assess exercise intensity using the TT. The other was a cardiopulmonary exercise test using breath-by-breath gas analysis to identify VT and cardiorespiratory fitness. RESULTS: Oxygen uptake and workload at the last positive stage (TTpos) was significantly lower than at VT. and workload at the equivocal stage (TTeq) and the first negative stage (TTneg) were not significantly different from VT, but limits of agreement (LoA) were wide. There was no significant difference in heart rate (HR) at TTpos and TTeq compared with VT, but HR at Tneg was significantly higher. The correlations between the TT and VT ranged from 0.37 to 0.60. Intensity at the different TT stages ranged from 58-77% of . All TT stages were within intensity guidelines of 40-80% of . CONCLUSION: Although no significant differences were found in and workload for TTeq and TTneg when compared with VT, LoA demonstrated wide ranges, suggesting poor individual correspondence. The different stages of the TT can be used as a practical method to guide exercise intensity in patients with cardiac disease.

Measurement properties of handheld dynamometry for assessment of shoulder muscle strength: A systematic review.

Like any assessment tool, handheld dynamometry (HHD) must be valid and reliable in order to be meaningful in clinical practice and research. To summarize the evidence of measurement properties of HHD for the assessment of shoulder muscle strength. Cochrane Central Register of Controlled Trials (CENTRAL), PubMed, EMBASE, and PEDro were searched up to February 2020. Inclusion criteria were studies (a) evaluating HHD used on the glenohumeral joint, (b) evaluating measurement properties, and (c) included individuals ≥ 18 years old with or without shoulder symptoms. Exclusion criteria were studies (a) including patients with neurologic, neuromuscular, systemic diseases, or critical illness or bed-side patients and (b) that did not report the results separately for each movement. In total, 28 studies with 963 participants were included. The reliability results showed that 98% of the intraclass correlation coefficient (ICC) values were ≥0.70. The measurement error showed that the minimal detectable change in percent varied from 0% to 51.0%. The quality of evidence was high or moderate for the majority of movements and type of reliability examined. Based on the evidence of low or very low quality of evidence, the convergent validity and discriminative validity of HHD were either sufficient, indeterminate, or insufficient. The reliability of HHD was overall sufficient, and HHD can be used to distinguish between individuals on the group level. The measurement error was not sufficient, and evaluation of treatment effect on the individual level should be interpreted with caution.

Reliability of the Danish version of the short questionnaire to assess health-enhancing physical activity (SQUASH).

OBJECTIVE: To translate and cross-cultural adapt the short questionnaire to assess health-enhancing physical activity (SQUASH) to Danish, and to investigate the Danish version's reliability. METHODS: The study was conducted according to the COSMIN guidelines. The reliability was evaluated in 53 healthy subjects, mean age 47.1 ± 12.4 years and mean period 37.8 ± 14.8 days between test and retest. RESULTS: For the total activity score ICC was 0.73 (0.57 to 0.83), SEM was 2316 (24% of the grand mean), and SDC was 6419 (67% of the grand mean). CONCLUSION: The relative reliability was acceptable and indicates that the Danish version of SQUASH can be used to distinguish between individuals; however, the absolute reliability was poor and SQUASH is not considered suitable for measuring physical activity on an individual level.

Resveratrol Increases Osteoblast Differentiation In Vitro Independently of Inflammation.

Low-grade inflammation negatively affects bone. Resveratrol is a natural compound proven to possess both anti-inflammatory and bone protective properties. However, it is uncertain if the bone effects are mediated though anti-inflammatory effects. Firstly, we investigated if resveratrol affects proliferation and differentiation of human bone marrow-derived mesenchymal stem cells. Secondly, we investigated if inflammation negatively affects proliferation and differentiation, and if resveratrol counteracts this through anti-inflammatory effects. Mesenchymal stem cells were obtained from bone marrow aspiration in 13 healthy individuals and cultured towards the osteoblast cell lineage. The cells were stimulated with resveratrol, lipopolysaccharide (LPS), LPS + resveratrol, or vehicle (control) for 21 days. Compared to control, resveratrol decreased cell number by 35 % (p < 0.05) and induced differentiation (a 3-fold increase in alkaline phosphatase (p < 0.002), while P1NP and OPG showed similar trends). LPS induced inflammation with a 44-fold increase in interleukin-6 (p < 0.05) and an extremely prominent increase in interleukin-8 production (p < 0.05) relative to control. In addition, LPS increased cell count (p < 0.05) and decreased differentiation (a reduction in P1NP production (p < 0.02)). Co-stimulation with LPS + resveratrol did not reduce interleukin-6 or interleukin-8, but nonetheless, cell count was reduced (p < 0.05) and alkaline phosphatase, P1NP, and OPG increased (p < 0.05 for all). Thus, resveratrol stimulates osteoblast differentiation independently of inflammation.

The Effect of Treatment With PTH on Undercarboxylated Osteocalcin and Energy Metabolism in Hypoparathyroidism.

CONTEXT: Undercarboxylated osteocalcin (ucOC) has been shown to affect glucose metabolism in mice. We recently randomized patients with hypoparathyroidism to treatment with PTH or placebo and demonstrated a marked increase in total osteocalcin. OBJECTIVE: To investigate whether there was a similar increase in ucOC and whether that increase affected glucose metabolism. DESIGN: A 24-week randomized, placebo-controlled trial. SETTING: Ambulatory patients in a research facility. PATIENTS: Sixty-two patients aged 31-78 years with hypoparathyroidism, of which 58 completed the trial. INTERVENTION: 100 µg/d of PTH (1-84). MAIN OUTCOME MEASURE: Change in ucOC. RESULTS: ucOC increased by 1185.0 ± 814.4% (mean ± SD) in the PTH-treated group and by 69.3 ± 79.4% in the placebo group (P < 10(-50)). In addition, body weight decreased by 1.1 ± 4.0% in the treatment group and increased 0.8 ± 2.5% in the placebo group (P = .04). Glucose, adiponectin, leptin, homeostasis model of assessment for insulin resistance, total body fat mass, or truncal fat did not change significantly. In addition, the number of hypercalcemic episodes per patient was 3.7 ± 2.9 (mean ± SD) in the PTH-treated group but only 0.2 ± 0.6 in the placebo group (P < .001). Moreover, there was a significant and negative correlation between the change in ucOC and change in body weight (P = .004) or change in total body fat mass (P = .03), and a negative but nonsignificant correlation between the number of hypercalcemic episodes and percentage change in body weight (r = -0.32; P = .1). Change in ucOC did not significantly correlate with changes in other parameters. CONCLUSIONS: An explanation for the weight loss may be subtle hypercalcemia in PTH treatment inhibiting appetite. Our data do not support a role for ucOC in energy metabolism in humans.