Upper Limb Function of Children with Unilateral Cerebral Palsy After a Magic-Themed HABIT: A Pre-Post-Study with 3- and 6-Month Follow-Up.

Aims: To examine changes in upper limb function, and performance in everyday tasks, for children with unilateral cerebral palsy who participated in a magic-themed hand-arm bimanual intensive therapy (HABIT). Methods: Twenty-eight children participated; mean age 10 y 6 mo (SD 2 y 2 mo), n = 15 male and n = 13 female. Using a single group, pre-and post-test design, the magic-themed HABIT was delivered for 60 hours over 10 days. Bimanual and unimanual hand function were measured using the Assisting Hand Assessment (AHA) and Box and Blocks Test (BBT). Occupational performance was rated using the Canadian Occupational Performance Measure (COPM). Two parent questionnaires explored change in bimanual hand use in everyday activities; ABILHAND-Kids and Children's Hand-use Experience Questionnaire (CHEQ). Assessments were completed pre-, immediately post, 3 months and 6 months after the intervention. Results: Friedman's ANOVA revealed a significant improvement for COPM and CHEQ grasp subscale. Repeated measures ANOVA revealed a significant improvement in BBT, and ABILHAND-Kids, and no significant change for AHA. Conclusions: Children who participated in the magic-themed HABIT experienced improved occupational performance, unimanual skills, and parent ratings of performance in challenging everyday tasks.

RAPID COMMUNICATION: Expression of an endogenous retroviral element, during early gestation in beef heifers.

Endogenous retroviral gene elements have been implicated in development and formation of the feto-maternal interface. A variant of the syncytin endogenous retroviral envelope gene family, , was recently found in ruminants. We hypothesized that mRNA would be differentially expressed in utero-placental tissues and would fluctuate during key time points of early gestation in beef heifers. Commercial Angus crossbred heifers ( = 46; ∼15 mo of age; BW = 362.3 ± 34.7kg) housed in 6-animal pens were fed daily with native grass hay and supplemented with cracked corn to gain 0.3 kg/d. The heifers were estrus synchronized, artificially inseminated, (d of breeding= d 0) and ovariohysterectomized on d 16, 22, 28, 34, 40, and 50 ( = 9, 6, 6, 7, 6, and 5, respectively) of gestation and at d 16 of the estrous cycle for non-bred, non-pregnant controls (NP; = 7). Harvested tissues were separated into maternal caruncle (CAR), intercarunclar endometrium (ICAR), and fetal membranes, (FM; chorioallantois, d 22 and later). All tissues were obtained from the ipsilateral uterine horn to the CL. Statistical analyses were conducted via the GLM procedure of SAS. Maternal CAR expression of was greater ( = 0.003) on d 50 by 81.5-fold compared to NP controls. At d 50 expression of in CAR was 190.3-fold greater than ( < 0.0001) ICAR. Fetal membranes had greater ( < 0.002) expression of from d 22 until d 50 of gestation compared to maternal ICAR (d 16 not analyzed). Expression of in FM was greater ( < 0.004) than in CAR until d 40 of gestation. Therefore, we conclude that is differentially expressed in utero-placental tissues and may be involved in the establishment of pregnancy. The expression of in maternal tissues is completely novel and indicates unique functions of syncytin in ruminant pregnancy.

Changing patterns of prescription in vitamin D supplementation in adults: analysis of a regional dataset.

UNLABELLED: Scientific interest in vitamin D has greatly risen during the last 10 years. The analysis of the changes in vitamin D prescriptions and related costs in a regional prescription dataset has revealed a profound increase in the period 2006-2013. Further studies on cost-effectiveness of such increase in vitamin D supplementation are needed. INTRODUCTION: The aim of this study was to analyze the changes in population-based prescription patterns of vitamin D supplements in the general population in an Italian regional setting during an 8-year period (2006-2013). METHODS: Data have been retrieved from the database of reimbursed prescriptions of the Region of Tuscany containing all of the medical reimbursements for the whole regional population (total of 3,619,872 and 3,692,828 inhabitants in 2006 and 2013, respectively). Data referring to adult population (age 20-90+ years) have been considered for this analysis (3,033,530 in 2006 and 3,066,741 in 2013). Two different flows (pharmaceutical distribution dataset and general data flow) were taken into account, using the ATC5 coding system for vitamin D supplements alone or in combination with calcium or alendronate. The number of boxes dispensed was retrieved, the number of patients receiving a specific treatment was calculated, and a cost analysis was performed. RESULTS: An upsurge in the prescriptions of vitamin D compounds was disclosed, mainly sustained by a 75.3-fold increase in cholecalciferol, in all age groups and both sexes. This occurred in parallel to a 4.3-fold rise in prescriptions of oral alendronate in combination with cholecalciferol, a slight decrease in dispensed alendronate alone, and a modest increase in the prescription of the combination of calcium salts and cholecalciferol, and calcium alone. The total cost for reimbursement by the Regional Health System for vitamin D-related compounds rose from €3,242,100 euros in 2006 to €8,155,778 in 2013. CONCLUSION: The huge increase in vitamin D prescriptions and related costs in the last decade, as revealed by the analysis of a regional pharmaceutical dataset, reflects the increased awareness of the possible consequences of a poor vitamin D status. Further studies on cost-effectiveness of such increase in vitamin D supplementation are needed.

Mindfulness-based interventions for obesity-related eating behaviours: a literature review.

Mindfulness-based interventions (MBIs) targeting eating behaviours have gained popularity in recent years. A literature review was conducted to determine the effectiveness of MBIs for treating obesity-related eating behaviours, such as binge eating, emotional eating and external eating. A search protocol was conducted using the online databases Google Scholar, PubMed, PsycINFO and Ovid Healthstar. Papers were required to meet the following criteria to be included in this review: (i) describe a MBI or the use of mindfulness exercises as part of an intervention; (ii) include at least one obesity-related eating behaviour as an outcome; (iii) include quantitative outcomes; and (iv) be published in English in a peer-reviewed journal. A total of N = 21 papers were included in this review. Interventions used a variety of approaches to implement mindfulness training, including combined mindfulness and cognitive behavioural therapies, mindfulness-based stress reduction, acceptance-based therapies, mindful eating programmes, and combinations of mindfulness exercises. Targeted eating behaviour outcomes included binge eating, emotional eating, external eating and dietary intake. Eighteen (86%) of the reviewed studies reported improvements in the targeted eating behaviours. Overall, the results of this first review on the topic support the efficacy of MBIs for changing obesity-related eating behaviours, specifically binge eating, emotional eating and external eating.

In calmodulin-IQ domain complexes, the Ca(2+)-free and Ca(2+)-bound forms of the calmodulin C-lobe direct the N-lobe to different binding sites.

We have investigated the roles played by the calmodulin (CaM) N- and C-lobes in establishing the conformations of CaM-IQ domain complexes in different Ca(2+)-free and Ca(2+)-bound states. Our results indicate a dominant role for the C-lobe in these complexes. When the C-lobe is Ca(2+)-free, it directs the N-lobe to a binding site within the IQ domain consensus sequence. It appears that the N-lobe must be Ca(2+)-free to interact productively with this site. When the C-lobe is Ca(2+)-bound, it directs the N-lobe to a site upstream of the consensus sequence, and it appears that the N-lobe must be Ca(2+)-bound to interact productively with this site. A model for switching in CaM-IQ domain complexes is presented in which the N-lobe adopts bound and extended positions that depend on the status of the Ca(2+)-binding sites in each CaM lobe and the compositions of the two N-lobe binding sites. Ca(2+)-dependent changes in the conformation of the bound C-lobe that appear to be responsible for directed N-lobe binding are also identified. Changes in the equilibria between extended and bound N-lobe positions may control bridging interactions in which the extended N-lobe is bound to another CaM-binding domain. Ca(2+)-dependent control of bridging interactions with CaM has been implicated in the regulation of ion channel and unconventional myosin activities.

A randomized, controlled trial of meditation for work stress, anxiety and depressed mood in full-time workers.

Objective. To assess the effect of meditation on work stress, anxiety and mood in full-time workers. Methods. 178 adult workers participated in an 8-week, 3-arm randomized controlled trial comparing a "mental silence" approach to meditation (n = 59) to a "relaxation" active control (n = 56) and a wait-list control (n = 63). Participants were assessed before and after using Psychological Strain Questionnaire (PSQ), a subscale of the larger Occupational Stress Inventory (OSI), the State component of the State/Trait Anxiety Inventory for Adults (STAI), and the depression-dejection (DD) subscale of the Profile of Mood States (POMS). Results. There was a significant improvement for the meditation group compared to both the relaxation control and the wait-list groups the PSQ (P = .026), and DD (P = .019). Conclusions. Mental silence-orientated meditation, in this case Sahaja Yoga meditation, is a safe and effective strategy for dealing with work stress and depressive feelings. The findings suggest that "thought reduction" or "mental silence" may have specific effects relevant to work stress and hence occupational health.

MR imaging of central nervous system Whipple disease: a 15-year review.

CNS WD is fatal if antibiotics are not begun early, but knowledge regarding the variety of presentations on MR imaging is limited. In order to more effectively recognize this entity on MR imaging, the Mayo Clinic medical records were reviewed for subjects diagnosed with CNS WD from 1992-2006 who had also undergone MR imaging of the neuraxis. Seven subjects were identified and their imaging findings were reviewed by the authors. Four of 7 had head MR imaging findings indicative of WD. Two subjects demonstrated high T2 signal within the corticospinal tracts. CNS WD may demonstrate high T2 signal with minimal enhancement and no restricted diffusion, primarily in the midline of the midbrain, hypothalamus, and mesial temporal lobes and occasionally the corticospinal tracts. MR imaging may also be normal. Radiologists should be aware of these presentations and be prepared to mention CNS WD as a diagnostic possibility since early antibiotic therapy may significantly impact morbidity and mortality.

Effects of three types of trace element supplementation on the fertility of three commercial dairy herds.

The effects on the fertility of three commercial dairy herds of three types of copper- and selenium-containing mineral supplements was investigated. As the cows on each farm were dried off they were allocated to one of three treatment groups, and treated with either subcutaneous injections of copper and selenium, or two matrix intraruminal trace element boluses, or two glass intraruminal trace element boluses. When the data from the 406 cows on the three farms were combined, there was a significant difference between the conception rates of the three groups (P < 0.001). The cows treated with the glass boluses conceived at a rate 1.8 times greater than those treated by injection (P < 0.001), and at a rate 1.5 times greater than those treated with matrix boluses (P = 0.002). These differences were associated with a significantly higher likelihood of service resulting in a conception in the group treated with glass boluses than in the group treated by injection (P = 0.004). After adjusting for time from calving, time from treatment, time of year and farm, there was a significant (P = 0.012) difference in glutathione peroxidase activities between the treatments, with the group treated by injection having a significantly lower activity than the groups treated with boluses.

Regulation of intestinal apolipoprotein A-I synthesis by dietary phosphatidylcholine in newborn swine.

Phospholipid (PL) from both dietary sources and biliary secretions may be important in the regulation of intestinal apolipoprotein (apo) synthesis. We previously demonstrated the up-regulation of apo A-I secretion by phosphatidylcholine (PC) in a newborn piglet intestinal epithelial cell line. We hypothesized that dietary PC increases small intestinal apo A-I synthesis in vivo in the newborn piglet. Two-day-old female swine were fed by gavage for 48 h. Diets consisted of a formula containing 51% of calories as triacylglycerol providing 180 kcal/kg/24 h. The experimental group (+PC, n = 7) received 1 g/L added soybean PC, and the control group (-PC, n = 7) received no added PC. At the end of the study period, jejunal apo A-I, B, and A-IV synthesis was measured, and apo A-I mRNA levels were quantitated. Jejunal mucosal PL content and serum lipids and apo B and A-I levels were measured. Jejunal apo A-I synthesis was almost twice as high in the +PC group as compared to the -PC group with no difference in apo A-I mRNA levels. Jejunal content of PL was higher in the +PC group than in the -PC group. There were no differences in jejunal apo B and A-IV synthesis or serum levels of lipids and apo-lipoproteins between the two groups. Dietary PC supplementation in newborn swine up-regulated jejunal apo A-I synthesis. Apo A-IV synthesis, which is sensitive to fatty acid flux, was not significantly increased, which suggests a specific effect of PC on apo A-I synthesis. Lumenal PC may be important in the regulation of intestinal apo A-I synthesis in the neonate.

Regulation of apolipoprotein secretion by long-chain polyunsaturated fatty acids in newborn swine enterocytes.

Long-chain polyunsaturated fatty acids (LC-PUFA) are important in the development of the immature nervous system, and adding these fatty acids to infant formula has been proposed. To determine the effect of n-3 LC-PUFA on apolipoprotein secretion and lipid synthesis in newborn swine enterocytes, differentiated IPEC-1 cells were incubated for 24 h with docosahexaenoic acid (DHA; 22:6) or eicosapentaenoic acid (EPA; 20:5) complexed with albumin at a fatty acid concentration of 0.8 mM or albumin alone (control) added to the apical medium. Oleic acid (OA; 18:1) was used a control for lipid-labeling studies. Both DHA and EPA reduced apolipoprotein (apo) B secretion by one-half, whereas EPA increased apo A-I secretion. The increased apo A-I secretion occurred primarily in the high-density lipoprotein fraction. These changes in apoprotein secretion were not accompanied by significant changes in synthesis. Modest decreases in apo B mRNA levels were observed for DHA and EPA, whereas there were no changes in apo A-I mRNA abundance. EPA reduced cellular triacylglycerol labeling by one-half, and DHA and EPA decreased cellular phospholipid labeling compared with OA. Labeled triacylglycerol secretion was decreased 75% by EPA, and DHA doubled labeled phospholipid secretion. If present in vivo, these effects should be considered before supplementing infant formula with these fatty acids.

The Iowa follow-up of chemically sensitive persons.

Clinical symptoms and self-reported health status in persons reporting multiple chemical sensitivities (MCS) are presented from a 9-year follow-up study. Eighteen (69%) subjects from a sample of 26 persons originally interviewed in 1988 were followed up in 1997 and given structured interviews and self-report questionnaires. In terms of psychiatric diagnosis, 15 (83%) met DSM-IV criteria for a lifetime mood disorder, 10 (56%) for a lifetime anxiety disorder, and 10 (56%) for a lifetime somatoform disorder. Seven (39%) of subjects met criteria for a personality disorder using the Personality Diagnostic Questionnaire-IV. Self-report data from the Illness Behavior Questionnaire and Symptom Checklist-90-Revised show little change from 1988. The 10 most frequent complaints attributed to MCS were headache, memory loss, forgetfulness, sore throat, joint aches, trouble thinking, shortness of breath, back pain, muscle aches, and nausea. Global assessment showed that 2 (11%) had "remitted", 8 (45%) were "much" or "very much" improved, 6 (33%) were "improved", and 2 (11%) were "unchanged/worse". Mean scores on the SF-36 health survey showed that, compared to U.S. population means, subjects reported worse physical functioning, more bodily pain, worse general health, worse social functioning, and more emotional-role impairment; self-reported mental health was better than the U.S. population mean. All subjects maintained a belief that they had MCS; 16 (89%) acknowledged that the diagnosis was controversial. It is concluded that the subjects remain strongly committed to their diagnosis of MCS. Most have improved since their original interview, but many remain symptomatic and continue to report ongoing lifestyle changes.

Lipid and apolipoprotein levels and distribution in patients with hypertriglyceridemia: effect of triglyceride reductions with atorvastatin.

Atorvastatin is a new hepatic hydroxymethyl glutaryl coenzyme A (HMG-CoA) reductase inhibitor that has been demonstrated to be efficacious in reducing both triglyceride (TG) and cholesterol (CHOL) levels in humans. Twenty-seven (N = 27) patients with primary hypertriglyceridemia (TG > 350 mg/dL) were studied before and after 4 weeks on atorvastatin treatment at a dosage of either 20 (n = 16) or 80 (n = 11) mg/d. The present report examines changes in the plasma levels of several apolipoproteins, including apolipoprotein C-II (apoC-II), apoC-III, and apoE, after atorvastatin. Dose-dependent reductions in both CHOL (20.3% v 43.1%) and TG (26.5% v 45.8%) for the low and high dose, respectively, have been reported in these individuals. In addition to the reductions in apoB commonly associated with the use of HMG-CoA reductase inhibitors, significant reductions in apoE (37% and 49%), apoC-II (28% and 42%), and apoC-III (18% and 30%) were observed with this agent at the 20- and 80-mg/d dosage, respectively. Using fast protein liquid chromatography (FPLC) to fractionate whole plasma according to particle size, the effect of atorvastatin on lipid and apolipoprotein distribution in 20 lipoprotein fractions was also determined. Our results indicate that after 4 weeks on atorvastatin, (1) there was a 2-fold increase in the CHOL content as assessed by the CHOL/apoB ratio for 13 subfractions from very-low-density lipoprotein (VLDL) to small low-density lipoprotein (LDL); (2) there was a statistically significant reduction in the percentage of plasma apoB associated with VLDL-sized particles (30.5% v 26.8%); (3) there was a preferential reduction in plasma apoE from non-apoB-containing lipoproteins with treatment; (4) the losses of apoC-II and apoC-III, on the other hand, were comparable for all lipoprotein fractions; and (5) the fraction of plasma TG associated with HDL was increased after treatment. These changes in lipids and apolipoproteins did not depend on the dose of atorvastatin. There was, on the other hand, a dose-dependent reduction in cholesteryl ester transfer protein (CETP) activity, defined as the percentage of 3H-cholesteryl oleate transferred from high-density lipoprotein (HDL) to LDL. CETP activity was reduced by 10.3% and 26.4% with the low and high dose of atorvastatin. Together, these composition data would be consistent with a net reduction in the number of TG-rich lipoproteins that may be explained by (1) a reduction in VLDL synthesis, (2) a preferential removal of VLDL without conversion to LDL, and (3) a preferential accelerated removal of a subpopulation of LDL.

Reduction of vertebral fracture risk in postmenopausal women with osteoporosis treated with raloxifene: results from a 3-year randomized clinical trial. Multiple Outcomes of Raloxifene Evaluation (MORE) Investigators.

CONTEXT: Raloxifene hydrochloride, a selective estrogen receptor modulator, prevents bone loss in postmenopausal women, but whether it reduces fracture risk in these women is not known. OBJECTIVE: To determine the effect of raloxifene therapy on risk of vertebral and nonvertebral fractures. DESIGN: The Multiple Outcomes of Raloxifene Evaluation (MORE) study, a multicenter, randomized, blinded, placebo-controlled trial. SETTING AND PARTICIPANTS: A total of 7705 women aged 31 to 80 years in 25 countries who had been postmenopausal for at least 2 years and who met World Health Organization criteria for having osteoporosis. The study began in 1994 and had up to 36 months of follow-up for primary efficacy measurements and nonserious adverse events and up to 40 months of follow-up for serious adverse events. INTERVENTIONS: Participants were randomized to 60 mg/d or 120 mg/d of raloxifene or to identically appearing placebo pills; in addition, all women received supplemental calcium and cholecalciferol. MAIN OUTCOME MEASURES: Incident vertebral fracture was determined radiographically at baseline and at scheduled 24- and 36-month visits. Nonvertebral fracture was ascertained by interview at 6-month-interim visits. Bone mineral density was determined annually by dual-energy x-ray absorptiometry. RESULTS: At 36 months of the evaluable radiographs in 6828 women, 503 (7.4%) had at least 1 new vertebral fracture, including 10.1% of women receiving placebo, 6.6% of those receiving 60 mg/d of raloxifene, and 5.4% of those receiving 120 mg/d of raloxifene. Risk of vertebral fracture was reduced in both study groups receiving raloxifene (for 60-mg/d group: relative risk [RR], 0.7; 95% confidence interval [CI], 0.5-0.8; for 120-mg/d group: RR, 0.5; 95% CI, 0.4-0.7). Frequency of vertebral fracture was reduced both in women who did and did not have prevalent fracture. Risk of nonvertebral fracture for raloxifene vs placebo did not differ significantly (RR, 0.9; 95% CI, 0.8-1.1 for both raloxifene groups combined). Compared with placebo, raloxifene increased bone mineral density in the femoral neck by 2.1 % (60 mg) and 2.4% (120 mg) and in the spine by 2.6% (60 mg) and 2.7% (120 mg) P<0.001 for all comparisons). Women receiving raloxifene had increased risk of venous thromboembolus vs placebo (RR, 3.1; 95% CI, 1.5-6.2). Raloxifene did not cause vaginal bleeding or breast pain and was associated with a lower incidence of breast cancer. CONCLUSIONS: In postmenopausal women with osteoporosis, raloxifene increases bone mineral density in the spine and femoral neck and reduces risk of vertebral fracture.

Effect of feeding diets of varying fatty acid composition on apolipoprotein expression in newborn swine.

The purpose of this study was to determine the effect of chronic (1 wk) feeding of dietary triacylglycerol (TG) of varying fatty acid composition on small intestinal and hepatic apolipoprotein expression, as well as serum lipid and apolipoprotein concentrations, in newborn swine. Two-day-old female swine were fed one of three diets by gavage with the following lipid composition: medium-chain TG (MCT; MCT oil), intermediate-chain saturated TG (ICST; coconut oil), and long-chain polyunsaturated TG (LCPUT; safflower oil) at 753 kJ . kg-1 . day-1 with 51% of energy from fat. After 1 wk, serum lipids and apolipoprotein concentrations were measured, and jejunal apolipoprotein B (apo B) and apo A-I mass and apo B, apo A-I, apo A-IV, and apo C-III synthesis were measured. Liver was processed for determination of apo B and apo A-I mass and apo B, apo A-I, apo C-III, and beta-actin mRNA abundance by slot blot hybridization. Compared with the MCT and LCPUT groups, the ICST group had higher total serum cholesterol, TG, high-density lipoprotein (HDL)-cholesterol, and apo A-I concentrations. There were no differences among the three groups for intestinal apolipoprotein mass or synthesis. In liver, apo A-I mass was highest in the ICST group. Liver apo A-I and apo C-III mRNA abundance was highest in the ICST group. Among all three groups, hepatic apo A-I mass correlated significantly with plasma HDL-cholesterol concentrations, and serum TG concentrations correlated with hepatic apo C-III mRNA abundance. In conclusion, we found that in the newborn piglet, chronic feeding of ICST increases serum total cholesterol, TG, HDL-cholesterol, and apo A-I concentrations and hepatic expression of apo A-I and apo C-III mRNA, compared with feeding of MCT or LCPUT. We speculate that increased hepatic apo A-I expression may contribute to the higher serum HDL and apo A-I concentrations in the ICST animals. Increased hepatic expression of apo C-III with ICST feeding may contribute to the higher serum TG concentrations by apo C-III-mediated inhibition of the catabolism of triacylglycerol-rich lipoproteins.

Comparison of the Heart and Estrogen/Progestin Replacement Study (HERS) cohort with women with coronary disease from the National Health and Nutrition Examination Survey III (NHANES III)

BACKGROUND: The Heart and Estrogen/Progestin Replacement Study (HERS) is the first large clinical trial designed to test the efficacy of postmenopausal estrogen/progestin therapy for secondary prevention of coronary heart disease (CHD). To examine the representativeness of the HERS cohort to the general population of postmenopausal women with CHD, we compared the baseline cardiovascular risk factor data from HERS with similar data from women presumed to have CHD from the National Health and Nutrition Examination Survey (NHANES) III. METHODS: Age, race, and cardiovascular disease risk factors were compared in the 2763 postmenopausal women younger than 80 years old, with a uterus, and with documented CHD in HERS versus 145 similarly aged women with clinical or electrocardiographic evidence of CHD from phase I of NHANES III. RESULTS: There were fewer current smokers in HERS (13%) than in the NHANES cohort (21.7%, p = 0.05). Similarly, a history of hypertension was less prevalent in HERS (58.6%) than in the NHANES cohort (69.3%, p = 0.03). Women with fasting triglyceride levels >3.39 mmol/L or fasting glucose levels >16.6 mmol/L were excluded from HERS, resulting in fewer diabetics (22.9% vs 29.5%, p = 0.26) and lower serum triglyceride levels (1.88 mmol/L vs 2.25 mmol/L, p = 0.19) in HERS versus the NHANES cohort. Systolic and diastolic blood pressure, body mass index, physical activity, and total LDL and HDL cholesterol were not significantly different between the two groups. CONCLUSIONS: The HERS cohort had fewer CHD risk factors than women with myocardial infarction or angina in NHANES III, although comparison is hindered by differences in selection criteria. The many women with diabetes and hypertriglyceridemia in the NHANES cohort emphasizes the importance of testing strategies for secondary prevention of CHD in this high-risk subgroup.

The cost of reaching National Cholesterol Education Program (NCEP) goals in hypercholesterolaemic patients. A comparison of atorvastatin, simvastatin, lovastatin and fluvastatin.

OBJECTIVE: Recognising the importance of treating hyperlipidaemia, the National Cholesterol Education Program (NCEP) has established widely accepted treatment goals for low density lipoprotein cholesterol (LDL-C). Medications used most commonly to achieve these LDL-C goals are HMG-CoA reductase inhibitors. The relative resource utilisation and cost associated with the use of reductase inhibitors of different LDL-C lowering efficacy are unknown, but are major health and economic concerns. The objective of this study was to determine the mean total cost of care to reach NCEP goals with various reductase inhibitors. DESIGN: In a randomised, 54-week, 30-centre controlled trial we compared resources used and costs associated with treating patients to achieve NCEP goals using 4 reductase inhibitors: atorvastatin, simvastatin, lovastatin and fluvastatin. PATIENTS AND PARTICIPANTS: The trial studied 662 patients; 318 had known atherosclerotic disease. INTERVENTIONS: Reductase inhibitor therapy was initiated at recommended starting doses and increased according to NCEP guidelines and package insert information. For patients who did not reach the goal at the highest recommended dose of each reductase inhibitor, the resin colestipol was added. MAIN OUTCOME MEASURES AND RESULTS: Patients treated with atorvastatin, compared-with other reductase inhibitors, were more likely to reach NCEP goals during treatment (p < 0.05), required fewer office visits (p < 0.001) and less adjuvant colestipol therapy (p = 0.001). Consequently, the mean total cost of care (1996 values) to reach NCEP goals was lower with atorvastatin [$US1064; 95% confidence interval (CI): $US953 to $US1176] compared with simvastatin ($US1471, 95% CI: $US1304 to $US1648), lovastatin ($US1972; 95% CI: $US1758 to $US2186) and fluvastatin ($US1542; 95% CI: $US1384 to $US1710). Results were similar for patients with or without known atherosclerotic disease. CONCLUSIONS: In patients requiring drug therapy for hypercholesterolaemia, NCEP LDL-C goals are achieved significantly more often using fewer resources with atorvastatin compared with simvastatin, lovastatin or fluvastatin.

Effect of alendronate on risk of fracture in women with low bone density but without vertebral fractures: results from the Fracture Intervention Trial.

CONTEXT: Alendronate sodium reduces fracture risk in postmenopausal women who have vertebral fractures, but its effects on fracture risk have not been studied for women without vertebral fractures. OBJECTIVE: To test the hypothesis that 4 years of alendronate would decrease the risk of clinical and vertebral fractures in women who have low bone mineral density (BMD) but no vertebral fractures. DESIGN: Randomized, blinded, placebo-controlled trial. SETTING: Eleven community-based clinical research centers. SUBJECTS: Women aged 54 to 81 years with a femoral neck BMD of 0.68 g/cm2 or less (Hologic Inc, Waltham, Mass) but no vertebral fracture; 4432 were randomized to alendronate or placebo and 4272 (96%) completed outcome measurements at the final visit (an average of 4.2 years later). INTERVENTION: All participants reporting calcium intakes of 1000 mg/d or less received a supplement containing 500 mg of calcium and 250 IU of cholecalciferol. Subjects were randomly assigned to either placebo or 5 mg/d of alendronate sodium for 2 years followed by 10 mg/d for the remainder of the trial. MAIN OUTCOME MEASURES: Clinical fractures confirmed by x-ray reports, new vertebral deformities detected by morphometric measurements on radiographs, and BMD measured by dual x-ray absorptiometry. RESULTS: Alendronate increased BMD at all sites studied (P<.001) and reduced clinical fractures from 312 in the placebo group to 272 in the intervention group, but not significantly so (14% reduction; relative hazard [RH], 0.86; 95% confidence interval [CI], 0.73-1.01). Alendronate reduced clinical fractures by 36% in women with baseline osteoporosis at the femoral neck (>2.5 SDs below the normal young adult mean; RH, 0.64; 95% CI, 0.50-0.82; treatment-control difference, 6.5%; number needed to treat [NNT], 15), but there was no significant reduction among those with higher BMD (RH, 1.08; 95% CI, 0.87-1.35). Alendronate decreased the risk of radiographic vertebral fractures by 44% overall (relative risk, 0.56; 95% CI, 0.39-0.80; treatment-control difference, 1.7%; NNT, 60). Alendronate did not increase the risk of gastrointestinal or other adverse effects. CONCLUSIONS: In women with low BMD but without vertebral fractures, 4 years of alendronate safely increased BMD and decreased the risk of first vertebral deformity. Alendronate significantly reduced the risk of clinical fractures among women with osteoporosis but not among women with higher BMD.

Factors associated with appendicular bone mass in older women. The Study of Osteoporotic Fractures Research Group.

OBJECTIVE: To determine the factors associated with appendicular bone mass in older women. DESIGN: Cross-sectional analysis of baseline data collected for a multicenter, prospective study of osteoporotic fractures. SETTING: Four clinical centers in Baltimore, Maryland; Minneapolis, Minnesota; Portland, Oregon; and the Monongahela valley, Pennsylvania. PATIENTS: A total of 9704 ambulatory, nonblack women, ages 65 years or older, recruited from population-based listings. MEASUREMENTS: Demographic and historical information and anthropometric measurements were obtained from a baseline questionnaire, interview, and examination. Single-photon absorptiometry scans were obtained at three sites: the distal radius, midradius, and calcaneus. Multivariate associations with bone mass were first examined in a randomly selected half of the cohort (training group) and were then tested on the other half of the cohort (validation group). RESULTS: In order of decreasing strength of association, estrogen use, non-insulin-dependent diabetes, thiazide use, increased weight, greater muscle strength, later age at menopause, and greater height were independently associated with higher bone mass. Gastric surgery, age, history of maternal fracture, smoking, and caffeine intake were associated with lower bone mass (all P < 0.05). For example, we found that 2 or more years of estrogen use was associated with a 7.2% increase in distal radius bone mass, whereas gastrectomy was associated with an 8.2% decrease in bone mass. The associations between bone mass and dietary calcium intake and rheumatoid arthritis were inconsistent. Alcohol use, physical activity, use of calcium supplements, pregnancy, breast-feeding, parental nationality, and hair color were among the many variables not associated with bone mass. Multivariate models accounted for 20% to 35% of the total variance of bone mass. CONCLUSIONS: A large number of factors influence the bone mass of elderly women; however, age, weight, muscle strength, and estrogen use are the most important factors.