Use of placebo interventions among Swiss primary care providers

Background  

Placebo interventions can have meaningful effects for patients. However, little is known about the circumstances of their use in clinical practice. We aimed to investigate to what extent and in which way Swiss primary care providers use placebo interventions. Furthermore we explored their ideas about the ethical and legal issues involved.     

Roll-over shapes of the ankle–foot and knee–ankle–foot systems of able-bodied children

BackgroundThe roll-over shape is the effective rocker shape that a lower limb system conforms to during a step. The roll-over shape concept has been explored in detail in adults and has been successfully used in the design, evaluation, and alignment of lower limb prostheses and orthoses. No such analysis exists for the pediatric population. Therefore, the purpose of this study was to investigate the ankle–foot and knee–ankle–foot roll-over shapes in able-bodied children, values that could serve as tools for design and evaluation of lower limb pediatric prostheses and orthoses.MethodsThis study describes a multi-center retrospective review of existing motion analysis data (n = 153 from three centers). Roll-over shapes were calculated by transforming center of pressure data from a laboratory-based coordinate system into two body-based coordinate systems. Roll-over shapes were then characterized using a circular arc model. Best-fit radii of roll-over shapes for children in three age groups (3–7 years, 8–11 years, and 12–17 years) were compared using the Kruskal–Wallis test.FindingsNo significant changes were found in roll-over shape radii between the three age groups (P = 0.54 for ankle–foot roll-over shape radii; P = 0.12 for knee–ankle–foot roll-over shape radii). The weighted mean of median radii for ankle–foot and knee–ankle–foot roll-over shapes from the three centers were approximately 22% and 17% of body stature, values similar to those seen in adults.InterpretationChildren produce nearly circular knee–ankle–foot roll-over shapes at a young age that are similar to those seen in adults when scaled by body stature.     

Serological Crossreactivity Between H-Y (Male) Antigens of Mouse and Man

Antisera to H-Y (male-specific) antigen were prepared by immunizing female mice with spleen cells from males of the same inbred strain. These antisera were used in mixed hemadsorption and cytotoxicity tests with cells of rats, guinea pigs, rabbits, and humans. The results showed that the H-Y components of all four species are antigenically related to H-Y of the mouse.     

Hyperglycemia and Adverse Pregnancy Outcome (HAPO) Study: Common Genetic Variants in GCK and TCF7L2 Are Associated With Fasting and Postchallenge Glucose Levels in Pregnancy and With the New Consensus Definition of Gestational Diabetes Mellitus From the International Association of Diabetes and Pregnancy Study Groups

OBJECTIVE

Common genetic variants in GCK and TCF7L2 are associated with higher fasting glucose and type 2 diabetes in nonpregnant populations. However, their associations with glucose levels from oral glucose tolerance tests (OGTTs) in pregnancy have not been assessed in a large sample. We hypothesized that these variants are associated with quantitative measures of glycemia in pregnancy.

RESEARCH DESIGN AND METHODS

We analyzed the associations between variants rs1799884 (GCK) and rs7903146 (TCF7L2) and OGTT outcomes at 24–32 weeks'' gestation in 3,811 mothers of European (U.K. and Australia) and 1,706 mothers of Asian (Thailand) ancestry from the HAPO cohort. We also tested associations with offspring birth anthropometrics.

RESULTS

The maternal GCK variant was associated with higher fasting glucose in Europeans (P = 0.001) and Thais (P < 0.0001), 1-h glucose in Europeans (P = 0.001), and 2-h glucose in Thais (P = 0.005). It was also associated with higher European offspring birth weight, fat mass, and skinfold thicknesses (P < 0.05). The TCF7L2 variant was associated with all three maternal glucose outcomes (P = 0.03, P < 0.0001, and P < 0.0001 for fasting and 1-h and 2-h glucose, respectively) in the Europeans but not in the Thais (P > 0.05). In both populations, both variants were associated with higher odds of gestational diabetes mellitus according to the new International Association of Diabetes and Pregnancy Study Groups recommendations (P = 0.001–0.08).

CONCLUSIONS

Maternal GCK and TCF7L2 variants are associated with glucose levels known to carry an increased risk of adverse pregnancy outcome in women without overt diabetes. Further studies will be important to determine the variance in maternal glucose explained by all known genetic variants.Maternal glycemia in pregnancy is associated with adverse pregnancy outcomes including birth weight >90th percentile, delivery by cesarean section, neonatal hypoglycemia, and fetal hyperinsulinemia (1). These associations occur across the full range of maternal glucose levels below those classified as overt diabetes.In healthy, nondiabetic, nonpregnant populations, approximately one-third of the variation in fasting glucose is genetic (2), and common genetic variants at multiple loci are now robustly associated with fasting glucose (3–10) and with type 2 diabetes and related glycemic traits (11–18). Thus, genetic factors are likely to contribute to variation in glucose levels in pregnancy. However, these variants have not been examined extensively in large studies of pregnant women.Studies of birth weight in Europeans have provided indirect evidence that two common genetic variants influence maternal glycemia in pregnancy. The T-allele of the rs1799884 variant in the GCK gene is associated with higher fasting glucose in the general population (4) and with type 2 diabetes (10). Pregnant women who carry this allele give birth to babies that are, on average, 32 g (95% CI 11–53) heavier at birth (4). Similarly, each additional T-allele of rs7903146 in the TCF7L2 gene—which is associated with reduced β-cell function, raised fasting glucose, and type 2 diabetes (10,13,19)—is also associated with a 30-g (95% CI 15–45) higher offspring birth weight when carried by the mother (20). We hypothesize that these associations with birth weight reflect higher levels of maternal glucose, which result in greater fetal insulin secretion and a consequent increase in fetal size at birth (21).There is some evidence from small studies that the GCK and TCF7L2 variants are associated with fasting glucose in pregnancy or gestational diabetes mellitus. The GCK variant was associated with higher fasting glucose in 755 European pregnant women from the U.K. (22) and with gestational diabetes mellitus in a Scandinavian sample (23). Variation at the TCF7L2 locus was not associated with fasting glucose in 921 European pregnant women (20) but was associated with gestational diabetes mellitus in Scandinavian (24,25), Korean (26), and Mexican-American (27) samples.The large sample size and detailed pregnancy and birth phenotype data available in the Hyperglycemia and Adverse Pregnancy Outcome (HAPO) study provide a unique opportunity to investigate more thoroughly the associations of the GCK and TCF7L2 variants with maternal glycemia, as measured in an oral glucose tolerance test (OGTT), during pregnancy as well as fetal size at birth and body composition. We used OGTT results from 5,517 pregnant women of European and South East Asian ancestry to assess associations both with quantitative measures of maternal glucose and with the new International Association of Diabetes and Pregnancy Study Groups (IADPSG) recommendations for the diagnosis of gestational diabetes mellitus (28).     

A phase II evaluation of goserelin and bicalutamide in patients with ovarian cancer in second or higher complete clinical disease remission

BACKGROUND: The current study was conducted to determine the effect of goserelin and bicalutamide on progression-free survival (PFS) in patients with epithelial ovarian cancer who were in second or greater complete disease remission. METHODS: Patients received bicalutamide at a dose of 50 mg orally daily and goserelin at a dose of 3.6 mg subcutaneously every 4 weeks. CA 125 was obtained monthly, with computed tomography performed every 3 months. Correlative studies included serum luteinizing hormone, follicle-stimulating hormone, vascular endothelial growth factor, free testosterone, and androstenedione and the germline polymorphisms CYP19A1 and androgen receptor. RESULTS: Between October of 2000 and October of 2002, 35 patients were enrolled. Three patients (9%) received therapy at the time of first disease remission and were removed from the study, and 1 patient (3%) was removed for liver function test abnormalities. The most frequent toxicities were grade 1 alkaline phosphatase (54%), fatigue (57%), and hot flashes (42%) based on the National Cancer Institute common toxicity scale, version 2.0. The PFS for patients receiving protocol therapy in second disease remission (21 patients) was 11.4 months (95% confidence interval [95% CI], 10.2-12.6 months). The PFS for patients receiving protocol therapy in third or fourth disease remission (11 patients) was 11.9 months (95% CI, 10.8-14.1 months). The percentage of patients remaining in second disease remission at given times are: 100% at 3 months, 100% at 6 months, 72% at 9 months, 47% at 12 months, 28% at 15 months, 22% at 18 months, 19% at 21 months, and 13% at 24 months. There were no associations noted between androgen receptor repeat number, genotype, allelotype, or haplotypes and PFS. CONCLUSIONS: The use of goserelin and bicalutamide did not appear to prolong PFS in patients with epithelial ovarian cancer in second or greater complete disease remission. The number of patients in disease remission at given time points may serve as a clinical trial endpoint for future studies of consolidation therapy.     

Immunological studies of mouse decidual cells. II. Studies of cells in artificially induced decidua

Cells from artificially induced decidual tissue (deciduoma) in the mouse were examined for Thy-1 surface antigen and receptors for the Fc portion of immunoglobulin G (FcR) and compared with cells of the normal decidua from day 6 to day 9 of pregnancy. It was shown that (1) Thy-1 antigen is present on the same proportion of cells in decidua and deciduoma on day 6 and day 7, (2) FcR-bearing cells can be detected in similar numbers on day 6 and day 7 but this does not increase on day 8 in deciduoma as it does in decidua, and (3) progesterone treatment after induction of decidualization allowed further increase of FcR-bearing cells in deciduoma. These results present further evidence of the similarity between deciduoma and decidua in the mouse. They indicate that these two membrane markers are present in the early decidua, regardless of the presence of an embryo, and suggest that progesterone may play a part in the increase of FcR-bearing cells in the decidua during pregnancy.     

Intravenous and subcutaneous desferrioxamine therapy in children with severe iron overload

Ten children with transfusion dependent anemias (thalassemia, sideroblastic anemia, congenital pure red cell aplasia) received either intravenous desferrioxamine (DF) in increasing doses up to 450 mg/kg at the time of transfusion or daily subcutaneous DF up to 110 mg/kg on an outpatient basis. No patient on intravenous DF reached a negative iron balance. All children with a subcutaneous DF dose of more than 60 mg/kg obtained a negative iron balance with a net iron excretion (transfusion iron already substracted) between 206 to 810 mg (mean 496 mg) monthly. The effectiveness of regular subcutaneous DF on liver storage iron could be confirmed in 4 patients by liver biopsy, showing a decrease between 40–60% iron after 12–14 months of chelation therapy. So far the daily iron excretion has remained constant with a given dose of DF over a period up to 15 months. Even if poor compliance in some patients is taken into account, it is possible with this method of treatment to prevent further accumulation of iron in chronically transfused children.     

Selective pretreatment diagnostic imaging for detecting remote metastases in patients with endometrial cancer

OBJECTIVES: Various diagnostic tests are available to rule out metastases. However, not all of these tests provide significant information. Based on data collected at our institution, we have analyzed the significance of various imaging methods. PATIENTS AND METHODS: In 337 patients with fully staged endometrial carcinoma, the results of chest X-rays, bone scintigraphy, computed tomography (CT), magnetic resonance imaging (MRI) and ultrasonography of the liver, kidneys and abdomen were analyzed. RESULTS: In the 7 patients who showed metastases, the liver was the most frequently affected organ. Hepatic CT is associated with a likelihood ratio (LR) of 9.0, hence representing a valuable technique. In cases with a pretest probability of 1.19% (independent of the disease stage), CT results in a post-test probability of 9.78%, putting into question the usefulness of the method for confirming metastases. With all other analyzed diagnostic modalities, even less information is gained. CONCLUSION: The routine use of the above diagnostic methods, indiscriminate of the disease stage, is not justified. LRs provide an estimate of the information gained by a diagnostic procedure.     

Expression of LRP1 in retinal pigment epithelial cells and its regulation by growth factors

PURPOSE: The retinal pigment epithelial (RPE) cells are mitotically inactive under normal conditions, but play a pivotal role in the pathogenesis of proliferative vitreoretinopathy (PVR). Triggered by changes in the concentrations of growth factors, RPE cells reenter the cell cycle, proliferate, and migrate onto the retinal surface, into the subretinal space, and into the vitreous. The receptor for alpha(2)-macroglobulin (low-density lipoprotein receptor-related protein [LRP1], or CD91) is known to be involved in the processes of cell migration and invasion, as well as in the regulation of growth factor homeostasis. The purpose of this study was to investigate the expression of this receptor and its regulation, at the protein and mRNA levels, in human (h)RPE cells. METHODS: The cell surface expression of the receptor was studied by immunocytochemistry and flow cytometry. The endocytosis-related activity of LRP1 in hRPE cells was examined by assessing the uptake of FITC-labeled, methylamine (MA)-treated alpha(2)-M (alpha(2)-M-MA). LRP1 mRNA expression was analyzed by means of the RNase protection assay (RPA) after the hRPE cells were stimulated with the growth factors TGF-beta1, TGF-beta2, PDGF, VEGF (each 10 ng/mL), or bFGF (5 ng/mL). RESULTS: hRPE cells expressed LRP1 on their cell surface. The receptor mediated rapid binding and endocytosis of FITC-labeled alpha(2)-M-MA. The expression of LRP1 mRNA strongly increased on stimulation of the cells with TGF-beta1, TGF-beta2, or VEGF, whereas PDGF or bFGF elicited only minor effects. CONCLUSIONS: The expression of functionally active LRP1 in hRPE cells suggests that the receptor may be involved in cell migration and invasion, as reported for other LRP1-expressing cells. Thus, certain growth factors may control RPE cell migration and invasion in vivo through a regulation of LRP1 expression. As LRP1 mediates the clearance of alpha(2)-M, known to regulate the homeostasis of many cytokines and growth factors, this receptor may be a promising target for therapeutic intervention in PVR.