Daniel O. Slosman

NON-INVASIVE DIAGNOSIS OF VENOUS THROMBOEMBOLISM IN OUTPATIENTS

BACKGROUND We designed a simple and integrated diagnostic algorithm for acute venous thromboembolism based on clinical probability assessment of deep-vein thrombosis (DVT) or pulmonary embolism (PE), plasma D-dimer measurement, lower-limb venous compression ultrasonography, and lung scan to reduce the need for phlebography and pulmonary angiography. METHODS 918 consecutive patients presenting at the emergency ward of the Geneva University Hospital, Geneva, Switzerland, and Hôpital Saint-Luc, Montreal, Canada, with clinically suspected venous thromboembolism were entered into a sequential diagnostic protocol. Patients in whom venous thromboembolism was deemed absent were not given anticoagulants and were followed up for 3 months. FINDINGS A normal D-dimer concentration (<500 microg/L by a rapid ELISA) ruled out venous thromboembolism in 286 (31%) members of the study cohort, whereas DVT by ultrasonography established the diagnosis in 157 (17%). Lung scan was diagnostic in 80 (9%) of the remaining patients. Venous thromboembolism was also deemed absent in patients with low to intermediate clinical probability of DVT and a normal venous ultrasonography (236 [26%] patients), and in patients with a low clinical probability of PE and a non-diagnostic result on lung scan (107 [12%] patients). Pulmonary angiography and phlebography were done in only 50 (5%) and 2 (<1%) of the patients, respectively. Hence, a non-invasive diagnosis was possible in 866 (94%) members of the entire cohort. The 3-month thromboembolic risk in patients not given anticoagulants, based on the results of the diagnostic protocol, was 1.8% (95% CI 0.9-3.1). INTERPRETATION A diagnostic strategy combining clinical assessment, D-dimer, ultrasonography, and lung scan gave a non-invasive diagnosis in the vast majority of outpatients with suspected venous thromboembolism, and appeared to be safe.

Single Prediction Equation for Bioelectrical Impedance Analysis in Adults Aged 20 -94 Years

Existing equations for bioelectrical impedance analysis (BIA) are of limited use when subjects age or become overweight because these equations were developed in young, normal-weight subjects and are not valid in elderly or overweight people. The purpose of this study was to validate a single BIA equation in healthy white subjects aged 22--94 y with a body mass index between 17.0 and 33.8 kg/m(2). Healthy subjects (202 men and 141 women) aged 20--94 y were measured by two methods: fat-free mass (FFM) was measured by dual-energy x-ray absorptiometry (Hologic QDR-4500) and by a bioelectrical impedance analyzer (Xitron 4000B). Validity of BIA was assessed by double cross validation. Because correlations were high (r = 0.986--0.987) and prediction errors low, a single equation was developed using all subjects, as follows: FFM = -4.104 + (0.518 x height(2)/resistance) + (0.231 x weight) + (0.130 x reactance) + (4.229 x sex: men = 1, women = 0). FFM predicted with dual-energy x-ray absorptiometry was 54.0 +/- 10.7 kg. BIA-predicted FFM was 54.0 +/- 10.5 kg (r = 0.986, standard error of the estimate = 1.72 kg, technical error = 1.74 kg). In conclusion, the new Geneva BIA equation was valid for prediction of FFM in healthy adults aged 22--94 y with body mass indexes between 17.0 and 33.8 kg/m(2). Inclusion of reactance in the single prediction equation appeared to be essential for use of BIA equations in populations with large variations in age or body mass.

Effects of calcium supplements on femoral bone mineral density and vertebral fracture rate in vitamin-D-replete elderly patients

The efficacy of calcium (Ca) in reducing bone loss is debated. In a randomized placebo-controlled double-masked study, we investigated the effects of oral Ca supplements on femoral shaft (FS), femoral neck (FN) and lumbar spine (LS) bone mineral density (BMD), and on the incidence of vertebral fracture in vitamin-D-replete elderly. Ninety-three healthy subjects (72.1±0.6 years) were randomly allocated to three groups receiving 800 mg/day Ca in two different forms or a placebo for 18 months. Sixty-three patients (78.4±1.0 years) with a recent hip fracture were allocated to two groups receiving the two forms of Ca without placebo. FS BMD changes in Ca-supplemented non-fractured women were significantly different from those in the placebo group (+0.6±0.5% v −1.2±0.7%,p<0.05). There was no difference in effect between the two forms of Ca. The changes of +0.7±0.8% v −1.7±1.6% in FN BMD of Ca-supplemented women and the placebo group did not reach statistical significance. In fractured patients, FS, FN and LS BMD changes were −1.3±0.8, +0.3±1.6 and +3.1±1.2% (p<0.05 for the last). The rate of new vertebral fractures was 74.3 and 106.2 fractures per 1000 patient-years in Ca-supplemented non-fractured subjects and in the placebo group, respectively, and 144.0 in Ca-supplemented fractured patients. Thus, oral Ca supplements prevented a femoral BMD decrease and lowered vertebral fracture rate in the elderly.

Fat-free and fat mass percentiles in 5225 healthy subjects aged 15 to 98 years

OBJECTIVES Fat-free mass (FFM) and fat mass (FM) are important in the evaluation of nutritional status. Bioelectrical impedance analysis (BIA) is a simple, reproducible method used to determine FFM and FM. Because normal values for FFM and FM have not yet been established in adults aged 15 to 98 y, its use is limited in the evaluation of nutritional status. The aims of this study were to determine reference values for FFM, FM, and percentage of FM by BIA in a white population of healthy adults, observe their differences with age, and develop percentile distributions for these parameters between ages 15 and 98 y. METHODS Whole-body resistance and reactance of 2735 healthy white men and 2490 healthy white women, aged 15 to 98 y, was determined by 50-kHz BIA, with four skin electrodes on the right hand and foot. FFM and FM were calculated by a previously validated, single BIA formula and analyzed for age decades. RESULTS Mean FFM peaked in 35- to 44-y-old men and 45- to 54-y-old women and declined thereafter. Mean FFM was 8.9 kg or 14.8% lower in men older than 85 y than in men 35 to 44 y old and 6.2 kg or 14.3% lower in women older than 85 y than in women 45 to 54 y old. Mean FM and percentage of FM increased progressively in men and women between ages 15 and 98 y. The results suggested that the greater weight noted in older subjects is due to larger FM. CONCLUSIONS The percentile data presented serve as reference to evaluate deviations from normal values of FFM and FM in healthy adult men and women at a given age.

Measurement of D-dimer in plasma as diagnostic aid in suspected pulmonary embolism

The potential of plasma measurement of D-dimer (DD), a specific derivative of crosslinked fibrin, for diagnosis or exclusion of pulmonary embolism was investigated in a prospective series of 171 consecutive patients who attended an emergency department with suspected pulmonary embolism. The diagnosis was made or excluded by means of a clinical decision-making process which included clinical evaluation, ventilation-perfusion (VQ) lung scan, and, as indicated, pulmonary angiography, venography, or non-invasive examination of the leg veins. Pulmonary embolism was diagnosed by this process in 55 (32%) of 170 patients with sufficient data. All but 1 of these 55 patients had a DD concentration of 500 micrograms/l or above. The sensitivity and specificity of this cutoff concentration for the presence of pulmonary embolism were 98% and 39%, respectively, which give positive and negative predictive values of 44% and 98%. Among the 115 patients (68%) who had inconclusive VQ scans, 31 were diagnosed as having pulmonary embolism. 29 of the remaining 84 patients without pulmonary embolism had DD concentrations below 500 micrograms/l, which means that further diagnostic procedures could have been avoided in a quarter of the patients with inconclusive VQ scans. The sensitivity of the plasma measurement of DD remained high even 3 and 7 days after presentation (96% and 93%). Plasma measurement of DD therefore has a definite place in the diagnostic procedure for suspected acute pulmonary embolism in attenders at emergency departments: a concentration below 500 micrograms/l rules out the diagnosis.

Magnetic resonance imaging-guided attenuation and scatter corrections in three-dimensional brain positron emission tomography

Reliable attenuation correction represents an essential component of the long chain of modules required for the reconstruction of artifact-free, quantitative brain positron emission tomography (PET) images. In this work we demonstrate the proof of principle of segmented magnetic resonance imaging (MRI)-guided attenuation and scatter corrections in three-dimensional (3D) brain PET. We have developed a method for attenuation correction based on registered T1-weighted MRI, eliminating the need of an additional transmission (TX) scan. The MR images were realigned to preliminary reconstructions of PET data using an automatic algorithm and then segmented by means of a fuzzy clustering technique which identifies tissues of significantly different density and composition. The voxels belonging to different regions were classified into air, skull, brain tissue and nasal sinuses. These voxels were then assigned theoretical tissue-dependent attenuation coefficients as reported in the ICRU 44 report followed by Gaussian smoothing and addition of a good statistics bed image. The MRI-derived attenuation map was then forward projected to generate attenuation correction factors (ACFs) to be used for correcting the emission (EM) data. The method was evaluated and validated on 10 patient data where TX and MRI brain images were available. Qualitative and quantitative assessment of differences between TX-guided and segmented MRI-guided 3D reconstructions were performed by visual assessment and by estimating parameters of clinical interest. The results indicated a small but noticeable improvement in image quality as a consequence of the reduction of noise propagation from TX into EM data. Considering the difficulties associated with preinjection TX-based attenuation correction and the limitations of current calculated attenuation correction, MRI-based attenuation correction in 3D brain PET would likely be the method of choice for the foreseeable future as a second best approach in a busy nuclear medicine center and could be applied to other functional brain imaging modalities such as SPECT.

Standardized Uptake Value of 2-[18F] Fluoro-2-Deoxy-d-Glucose in Predicting Outcome in Head and Neck Carcinomas Treated by Radiotherapy With or Without Chemotherapy

PURPOSE In patients with head and neck cancer enrolled onto a prospective study of positron emission tomography (PET), pretreatment 2-[(18)F] fluoro-2- deoxy-D-glucose (FDG) uptake was evaluated as a predictor of local control and disease-free survival (DFS) after treatment by radiotherapy (RT) with or without chemotherapy. PATIENTS AND METHODS We studied 63 patients with carcinomas of the head and neck who had an FDG-PET scan before radical RT. Tumor FDG uptake was measured with the semiquantitative standardized uptake value (SUV). All patients but one were treated with accelerated or hyperfractionated RT schedules. Thirteen patients received concomitant cisplatin-based chemotherapy. RESULTS In 25 patients who presented with any component of treatment failure, the SUV was significantly higher than in the remaining patients without any such failure. Patients having tumors with high FDG uptake had a significantly lower 3-year local control (55% v 86%, P =.01) and DFS (42% v 79%, P =.005) compared with patients having low uptake tumors. In the multivariate analysis, the only factor that retained its significance for DFS was SUV category, whereas T category was of borderline significance. For local control, T category remained a significant factor, whereas a lower local control was observed for tumors with a high SUV compared with those with low SUV. CONCLUSION FDG uptake, as measured by the SUV, has potential value in predicting local control and DFS in head and neck carcinomas treated by RT. High FDG uptake may be a useful parameter for identifying patients requiring more aggressive treatment approaches.

Gain in bone mineral mass in prepubertal girls 3–5 years after discontinuation of calcium supplementation: a follow-up study

BACKGROUND Calcium supplementation during childhood and adolescence increases bone-mass accrual. Whether or not this benefit persists after discontinuation of supplementation is not known. We previously showed a favourable effect of milk-extracted calcium phosphate incorporated in various foods on accumulation of bone mineral mass in 8-year-old girls. We now report the results of a follow-up study undertaken more than 3 years after the end of calcium supplementation. METHODS Anthropometric and bone variables were measured in 116 of the 144 girls whose data had been studied at the end of the supplementation period. The mean time elapsed between the end of the intervention period and this follow-up measurement was 3.5 years. Areal bone mineral density was measured by dual-energy X-ray absorptiometry at the same six skeletal sites as those studied during the intervention phase. FINDINGS We were able to remeasure 62 and 54 girls of the calcium-supplemented and placebo groups, respectively. The increase from baseline in the overall mean bone mineral density of the six skeletal sites was still highly significant (calcium-supplemented group 179 mg/cm(2) [SE 8] vs placebo group 151 mg/cm(2) [7], p=0.012). A significant difference in favour of the supplemented group was also seen with respect to mean bone mineral content (p=0.031) and mean bone area (p=0.04). Difference in pubertal maturation did not seem to account for the recorded differences. INTERPRETATION Our results suggest that this form of milk-extracted calcium phosphate taken during the prepubertal period can modify the trajectory of bone mass growth and cause a long-standing increase in bone mass accrual, which lasts beyond the end of supplementation.

Are younger children at highest risk of renal sequelae after pyelonephritis

BACKGROUND The general belief about the relation between risk of renal sequelae after pyelonephritis and age is that infants are at highest risk and children older than 5 years at lower risk. This assumption has led to differences in treatment based on age. The aim of this prospective study was to investigate the occurrence of renal lesions in children aged 0-16 years. METHODS Between May, 1994, and January, 1996, all children aged 0-16 years who were admitted to our department with a diagnosis of probable pyelonephritis and a positive urine culture were included in this prospective study. All patients received antibiotics for 7-21 days. During the acute phase of urinary-tract infection, scintigraphy with technetium-99m-dimercaptosuccinic acid (DMSA) and ultrasonography were done. Voiding cystourethrography was undertaken at least 6 weeks after the end of antibiotic treatment. When scintigraphy showed renal parenchymal lesions, repeat scintigraphy was done after at least 2 months to assess the progression of renal lesions. For the analysis, children were grouped by age according to presumed risk of renal sequelae after pyelonephritis: high risk (< 1 year), moderate risk (1-5 years), low risk (> 5 years). FINDINGS 201 patients were enrolled in the study (119 < 1 year, 47 aged 1-5 years, 35 > 5 years). During the acute phase of urinary-tract infection, renal lesions were found in 66 (55%) infants under 1 year, in 37 (79%) children aged 1-5 years, and in 24 (69%) children older than 5 years. Of these 127 children, 108 underwent repeat scintigraphy after an average of 3 months (50 < 1 year, 36 aged 1-5 years, 22 > 5 years). Overall, renal scars were found on repeat scintigraphy in 20 (40%) infants under 1 year, in 31 (86%) children aged 1-5 years, and in 14 (64%) children older than 5 years. 38 (36%) of these 65 patients had vesicoureteric reflux. Among 88 children who had a first documented urinary-tract infection and underwent repeat scintigraphy, renal scars were found in 20 (43%) under 1 year, in 26 (84%) aged 1-5 years, and in eight (80%) older than 5 years. INTERPRETATION This study did not confirm the conventional view that the risk of renal scars after pyelonephritis diminishes with age. We believe that all children, irrespective of age, will benefit from any measure that prevents the development of renal sequelae.

Relationship between bone mineral density and dietary intakes in the elderly

Dietary protein and/or calorie insufficiencies represent an important problem in elderly patients. The biological and clinical implications, and particularly the influence on bone mass of undernutrition in the elderly, have not been completely defined, although several studies have demonstrated a high prevalence of dietary insufficiencies in patients with a recent fracture of the proximal femur. In the present study the relationship between dietary intakes, physical performance and bone mineral density (BMD) was examined in hospitalized elderly patients. The study comprised 74 patients (48 women, mean age 82 years; and 26 men, mean age 80 years) who were hospitalized for various medical indications. They were divided into two groups according to their dietary protein intakes, evaluated during the first 28 days in hospital while on a regular diet. The first group consisted of 26 patients (14 women and 12 men) whose protein intake was equal to or greater than 1 g per kilogram of ideal body weight. The second group consisted of 48 patients (34 women and 14 men) who consumed less than 1 g of protein per kilogram of ideal body weight. The two groups differed also in their energy, carbohydrate, lipid and calcium intakes. Patients in the group with the higher protein intake displayed higher BMD at the level of the femoral neck as measured by dual-photon absorptiometry. The men in this group also had higher lumbar spine BMD. After 4 weeks in hospital the women with a higher protein intake had significantly enhanced bicipital and quadricipital muscle strength and better performance as indicated by the increased capacity to climb stairs. These results indicate that lower dietary intakes in hospitalized elderly patients without fractures are associated with lower physical performance and lower femoral neck BMD. Thus, the role of dietary factors, including protein, in the risk of proximal femoral fractures deserves further investigation.