Implementation of osteoporosis guidelines: a survey of five large fracture liaison services in the Netherlands.

SUMMARY: Implementation of case findings according to guidelines for osteoporosis in fracture patients presenting at a Fracture Liaison Service (FLS) was evaluated. Despite one guideline, all FLSs differed in the performance of patient selection and prevalence of clinical risk factors (CRFs) indicating the need for more concrete and standardised guidelines. INTRODUCTION: The aim of the study was to evaluate the implementation of case findings according to guidelines for osteoporosis in fracture patients presenting at FLSs in the Netherlands. METHODS: Five FLSs were contacted to participate in this prospective study. Patients older than 50 years with a recent clinical fracture who were able and were willing to participate in fracture risk evaluation were included. Performance was evaluated by criteria for patient recruitment, patient characteristics, nurse time, evaluated clinical risk factors (CRFs), bone mineral density (BMD) and laboratory testing and results of CRFs and BMD are presented. Differences between FLSs were analysed for performance (by chi-square and Student's t test) and for prevalence of CRFs (by relative risks (RR)). RESULTS: All FLSs had a dedicated nurse spending 0.9 to 1.7 h per patient. During 39 to 58 months follow-up, 7,199 patients were evaluated (15 to 47 patients/centre/month; mean age, 67 years; 77% women). Major differences were found between FLSs in the performance of patient recruitment, evaluation of CRFs, BMD and laboratory testing, varying between 0% and 100%. The prevalence of CRFs and osteoporosis varied significantly between FLSs (RR between 1.7 and 37.0, depending on the risk factor). CONCLUSION: All five participating FLSs with a dedicated fracture nurse differed in the performance of patient selection, CRFs and in the prevalence of CRFs, indicating the need for more concrete and standardised guidelines to organise evaluation of patients at the time of fracture in daily practice.

Percutaneous vertebroplasty is not a risk factor for new osteoporotic compression fractures: results from VERTOS II.

BACKGROUND AND PURPOSE: PV is increasingly used as treatment for osteoporotic VCFs. However, controversy exists as to whether PV increases the risk for new VCFs during follow-up. The purpose of our research was to assess the incidence of new VCFs in patients with acute VCFs randomized to PV and conservative therapy. MATERIALS AND METHODS: VERTOS II is a prospective multicenter randomized controlled trial comparing PV with conservative therapy in 202 patients. Incidence, distribution, and timing of new VCFs during follow-up were assessed from spine radiographs. In addition, further height loss during follow-up of treated VCFs was measured. RESULTS: After a mean follow-up of 11.4 months (median, 12.0; range, 1-24 months), 18 new VCFs occurred in 15 of 91 patients after PV and 30 new VCFs in 21 of 85 patients after conservative therapy. This difference was not significant (P = .44). There was no higher fracture risk for adjacent-versus-distant vertebrae. Mean time to new VCF was 16.2 months after PV and 17.8 months after conservative treatment (logrank, P = .45). The baseline number of VCFs was the only risk factor for occurrence (OR, 1.43; 95% CI, 1.05-1.95) and number (P = .01) of new VCFs. After conservative therapy, further height loss of treated vertebrae occurred more frequently (35 of 85 versus 11 of 91 patients, P < .001) and was more severe (P < .001) than after PV. CONCLUSIONS: Incidence of new VCFs was not different after PV compared with conservative therapy after a mean of 11.4 months' follow-up. The only risk factor for new VCFs was the number of VCFs at baseline. PV contributed to preservation of stature by decreasing both the incidence and severity of further height loss in treated vertebrae.

VERTOS II: percutaneous vertebroplasty versus conservative therapy in patients with painful osteoporotic vertebral compression fractures; rationale, objectives and design of a multicenter randomized controlled trial.

BACKGROUND: The standard care in patients with a painful osteoporotic vertebral compression fracture (VCF) is conservative therapy. Percutaneous vertebroplasty (PV), a minimally invasive technique, is gaining popularity as a new treatment option. Many prospective and retrospective studies have reported on the effectiveness and safety of PV, but no large randomized controlled trial (RCT) has been published. OBJECTIVE: To estimate cost-effectiveness of PV compared to conservative therapy in terms of: pain reduction, quality of life, complications, secondary fractures and mortality. MATERIALS AND METHODS: The VERTOS II study is designed as a prospective, multicenter RCT. Patients with a painful VCF with bone edema on MR imaging, local back pain for 6 weeks or less, osteopenia and aged 50 years or older, after obtaining informed consent are included and randomized for PV or conservative therapy. In total 200 patients will be enrolled. Follow-up is at regular intervals during a 1-year period with standard questionnaires, addressing: clinical symptoms, pain medication, Visual Analogue Scale (VAS) score, quality of life and cost-effectiveness. Secondary fractures, necessary additional therapies and complications are recorded. CONCLUSION: The VERTOS II study is the first methodologically sound RCT designed to assess the cost-effectiveness of PV compared to conservative therapy in patients with an acute osteoporotic VCF. TRIAL REGISTRATION: http://www.clinicaltrials.gov, NCT00232466.

Short-term results of Na131I treatment of hyperthyroidism evaluated using an extended dosimetric method.

OBJECTIVE: To assess and evaluate the short-term results of radio-iodine treatment using an extended dosimetric method. METHODS: Sixty-five patients with Graves disease (GD) and 32 patients with toxic multinodular goitre (TMG) received a pre-therapeutic dosage of Na123I. The overall indicative radiation dose (Dind) and the indicative dosage (Aind) was calculated for the individual patient using the dosimetric results found. In the therapeutic setting dosimetric measurements were performed again. The quotient of the administered dose (A) and the indicative dosage and the quotient of the absorbed radiation dose (Dabs) and the indicative radiation dose were used to evaluate treatment results after 1 year of follow-up. RESULTS: Clinical outcome after 1 year for GD was 26% hyper-, 48% eu- and 26% hypothyroidism and for TMG 32, 59 and 9%, respectively. Within the percentile range P25-P75 of A/Aind these results were 27, 46 and 27% for GD and 36, 64 and 0% for TMG. Within the percentile range P25-P75 of Dabs/Dind these results were 23, 59 and 18% for GD and 33, 67 and 0 for TMG. Correlation coefficients between pre- and therapeutic dosimetric measurements in GD and TMG were 0.76 and 0.38, respectively. CONCLUSIONS: The short-term outcome after 1 year of follow-up is 48 and 59% euthyroidism for GD and TMG, respectively. Clinical outcome within the percentile range P25-P75 of A/Aind did not change these results. Within the percentile range P25-P75 of Dabs/Dind euthyroidism was achieved in 59% and 67% for GD and TMG, respectively. The pre-therapeutic values inaccurately represent the therapeutic values for GD and even more for TMG.

Omega-3 fatty acids in adipose tissue of obese patients with non-insulin-dependent diabetes mellitus reflect long-term dietary intake of eicosapentaenoic and docosahexaenoic acid.

We examined the relationship between long-term dietary intake of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) and the relative content of these fatty acids in adipose tissue triglycerides from 53 obese Dutch subjects--19 men and 34 women--with non-insulin-dependent diabetes mellitus (NIDDM). Adipose tissue fatty acid profiles analyzed in three samples taken from each subject at 1-y intervals showed no within-subject differences for EPA and DHA. Dietary intake was estimated from 12 3-d dietary records made over 2 y at 2-mo intervals. EPA and DHA intakes showed high within-subject variation. Correlation coefficients (Spearman) between the dietary intake of EPA (% of total fat) and EPA in adipose tissue (% of total fatty acids) were 0.76 for men and 0.57 for women. For DHA these coefficients were 0.75 for men and 0.48 for women. We conclude that the analysis of fatty acids in one adipose tissue biopsy provides information on long-term EPA and DHA intakes in obese subjects with NIDDM, and can replace otherwise necessarily frequent diet analyses over a long period.

Influences on weight loss in type 2 diabetic patients: little long-term benefit from group behaviour therapy and exercise training.

The aim of our study was to assess the long-term (24 months) efficacy of a comprehensive weight reduction programme as compared to that of a conventional programme. The Comprehensive Programme comprised, besides the Conventional Programme (diet counselling), behavioural modification and exercise training. The 2-year follow-up period was completed by 53 patients (19M/34F; 88.3%). The differences (95% confidence intervals; CI) between the change in body weight of patients in the Comprehensive Programme compared to the Conventional Programme after 6 and 24 months of treatment were -2.2 (-4.0, -0.3) kg, p = 0.03 and -1.3 (-3.3, 0.7) kg, p = 0.21, respectively. In comparison to the Conventional Programme, the Comprehensive Programme resulted in a greater decrease (95% CI) of HbA1c after 6 months: -0.8 (-1.2, -0.2)%, p = 0.01, but not after 2 years: -0.4 (-1.0, 0.1)%, p = 0.12. The effects on blood pressure and serum lipids of the Comprehensive Programme and the Conventional Programme were comparable. Changes in body weight at 6 months correlated well with changes in HbA1c, fasting plasma insulin, and blood pressure, whereas at 24 months no such correlation was found with HbA1c. Pretreatment variates that were associated with the greatest 2-year weight loss were a high HbA1c value, a low energy per cent carbohydrate intake and a low percentage of obese subjects within the family. In conclusion, the long-term outcome of the Comprehensive Programme was not different from that of the Conventional Programme. The achieved body weight reduction was associated with a sustained fall in blood pressure, but with only a transient beneficial effect on the glycaemic control in the Type 2 diabetic patient.

Determinants of insulin sensitivity and consequences for lipoproteins and blood pressure in subjects with non-insulin-dependent diabetes mellitus.

The aim of the present study was to investigate the possible determinants of insulin sensitivity and the relationships of these determinants and insulin sensitivity to lipoprotein levels and blood pressure in patients with non-insulin-dependent diabetes mellitus (NIDDM). We studied 46 patients with NIDDM (26 women, 20 men) treated either with diet alone or in combination with sulfonylureas. Insulin sensitivity was assessed as the insulin-mediated glucose uptake rate (M value) with the hyperinsulinemic euglycemic clamp technique. In a multiple regression model, only percent body fat, waist to hip ratio (WHR), and resting energy expenditure (REE) emerged as significant independent determinants of the M value, with a multiple R2 for the model of 44%, whereas age, hemoglobin A1c (HbA1c) level, thyroid function, fitness level, smoking status, alcohol consumption, and dietary habits did not contribute significantly. The M value was independently and negatively associated with the concentrations of triglyceride (TG) and very-low-density lipoprotein (VLDL) cholesterol and positively associated with high-density lipoprotein (HDL) cholesterol subfractions and apolipoprotein A1. In our predominantly normotensive subjects, we found no association between the M value and blood pressure. Moreover, fasting insulin contributed directly, ie, independent of the M value, to the variation of TG, but not to the other lipoproteins and not to blood pressure. The results suggest that in NIDDM (1) insulin sensitivity is determined mainly by percentage body fat and REE, (2) the insulin level determines the TG level directly, whereas the lipoproteins are influenced indirectly as a reflection of the degree of insulin resistance, and (3) insulin sensitivity is not related to blood pressure in a normotensive population.

Sequential development of peripheral T-cell lymphoma in the course of chronic myelogenous leukemia.

A patient is described with chronic myelogenous leukemia (CML) and an unusual karyotype 46XY,t(Y;12) (q11;p12), whose clinical course was complicated by T-cell lymphoma 5 years later. At that time bone marrow cells showed an additional karyotypic abnormality 46XY,t(Y;12) (q11;p12) del(7) (pter-p21), which remained unchanged until blastic transformation of the CML 8 months later. The bone marrow biopsy specimen, which revealed the blastic transformation of the CML, also showed evidence for localization of T-cell lymphoma. This case, added to two previously reported cases of the concurrence of CML and T-cell lymphoma, suggests a relationship between the two diseases, which is discussed.

Dose-response effects of fish-oil supplementation in healthy volunteers.

We performed a randomized, controlled study on the dose-response effects of daily supplementation of 1.5, 3, and 6 g of the marine fatty acids eicosapentaenoic acid (EPA, 20:5n-3) and docosahexaenoic acid (DHA, 22:6n-3) as their ethyl esters for 12 wk in 45 healthy normotriglyceridemic male volunteers. Significant dose-related increases of the n-3 fatty acids 20:5, 22:5, and 22:6 in plasma phospholipids (p less than 0.0001) were found, corresponding roughly to decreases of the n-6 fatty acids 18:2 and 20:4 (p less than 0.001). Serum triglycerides and HDL3-cholesterol concentrations showed a dose-dependent reduction (p less than 0.05) and HDL2 cholesterol increased (p less than 0.05). Results for 3 and 6 g n-3 fatty acids were similar. No dose-dependent effects were observed in the VLDL-, LDL-, and total HDL-cholesterol subfractions; blood pressure; bleeding time; erythrocyte deformability; or capacity of polymorphonuclear leukocytes to kill Staphylococcus aureus. This study indicates that 3 g n-3 ethyl ester fatty acids appears to be the appropriate supplementation dose in humans, at least regarding lipid-profile changes and the ability to incorporate such fatty acids in the plasma phospholipids.

Functional pneumectomy by a saccular aneurysm of the aortic root.

This case report describes a patient with severe stenosis of the right pulmonary artery due to an expanding arteriosclerotic aneurysm of the ascending aorta. The clinical data and the lung perfusion ventilation scintigrams supported the diagnosis of pulmonary embolism, and initially the patient was treated accordingly.