Are osteoporotic fractures being adequately investigated?: A questionnaire of GP & orthopaedic surgeons

BACKGROUND: To investigate the current practice of Orthopaedic Surgeons & General Practitioners (GP) when presented with patients who have a fracture, with possible underlying Osteoporosis. METHODS: Questionnaires were sent to 140 GPs and 140 Orthopaedic Surgeons. The participants were asked their routine clinical practice with regard to investigation of underlying osteoporosis in 3 clinical scenarios. 55 year old lady with a low trauma Colles fracture 60 year old lady with a vertebral wedge fracture 70 year old lady with a low trauma neck of femur fracture. RESULTS: Most doctors agreed that patients over 50 years old with low trauma fractures required investigation for osteoporosis, however, most surgeons (56%, n = 66) would discharge patients with low trauma Colles fracture without requesting or initiating investigation for osteoporosis. Most GPs (67%, n = 76) would not investigate a similar patient for osteoporosis, unless prompted by the Orthopaedic Surgeon or patient. More surgeons (71%, n= 83) and GPs (64%, n = 72) would initiate investigations for osteoporosis in a vertebral wedge fracture, but few surgeons (35%, n = 23) would investigate a neck of femur fracture patient after orthopaedic treatment. CONCLUSION: Most doctors know that fragility fractures in patients over 50 years old require investigation for Osteoporosis; however, a large population of patients with osteoporotic fractures are not being given the advantages of secondary prevention

Alcohol Use Disorders (AUD) among Tuberculosis Patients: A Study from Chennai, South India

BACKGROUND: Alcohol Use Disorders (AUDs) among tuberculosis (TB) patients are associated with nonadherence and poor treatment outcomes. Studies from Tuberculosis Research Centre (TRC), Chennai have reported that alcoholism has been one of the major reasons for default and mortality in under the DOTS programme in South India. Hence, it is planned to conduct a study to estimate prevalence of alcohol use and AUDs among TB patients attending the corporation health centres in Chennai, India. METHODOLOGY: This is a cross-sectional cohort study covering 10 corporation zones at Chennai and it included situational assessment followed by screening of TB patients by a WHO developed Alcohol Use Disorders Identification Test AUDIT scale. Four zones were randomly selected and all TB patients treated during July to September 2009 were screened with AUDIT scale for alcohol consumption. RESULTS: Out of 490 patients, 66% were males, 66% were 35 years and above, 57% were married, 58% were from the low monthly income group of <Rs 5000 per month. No females reported alcohol use. Overall, out of 490 TB pts, 29% (141) were found to consume alcohol. Among 141 current drinkers 52% (73) had an AUDIT score of >8. Age (>35 years), education (less educated), income (<Rs 5000 per month), marital status (separated/divorced) and treatment category (Category 2) were statistically significant for TB patients with alcohol use than those TB patients without alcohol use. CONCLUSIONS: AUD among TB patients needs to be addressed urgently and the findings suggest the importance of integrating alcohol treatment into TB care

Oral cancer treatment costs in Greece and the effect of advanced disease

BACKGROUND: The main purpose of the study was to quantify the direct costs of oral cancer treatment to the healthcare system of Greece. Another aim was to identify factors that affect costs and potential cost reduction items. More specifically, we examined the relationship between stage of disease, modality of treatment and total direct costs. METHODS: The medical records and clinic files of the Oral and Maxillofacial Clinic of the Athens General Hospital "Genimatas" were abstracted to investigate clinical treatment characteristics, including length of hospitalization, modes of treatment, stage of disease etc. Records of 95 patients with oral squamous cell carcinoma (OSSC), with at least six months of follow-up, were examined. The clinical data was then used to calculate actual direct costs, based on 2001 market values. RESULTS: The mean total direct costs for OSSC treatment estimated at euro 8,450 or approximately US$ 7,450. Costs depended on the stage of the disease, with significant increases in stages III and IV, as compared with stages I and II (p < 0.05). Multi-modality treatment applied mainly to patients in stages III and IV was the factor that affected the cost. Disease stage was also associated with the total duration of hospitalization (p < 0.05). CONCLUSIONS: The clinical management of advanced oral cancer is strongly associated with higher costs. Although the ideal would be to prevent cancer, the combination of high-risk screening, early diagnosis and early treatment seems the most efficient way to reduce costs, and most importantly, prolong life

Efficacy and tolerability of intravenous methylergonovine in migraine female patients attending the emergency department: a pilot open-label study

<p>Abstract</p> <p>Background</p> <p>Methylergonovine is an ergot alkaloid widely used in postpartum women. It is also an active metabolite of methysergide and previous studies suggest that it could be effective against refractory headache and cluster headache. The purpose of the present study was to assess the potential therapeutic effectiveness of methylergonovine in the emergency treatment of severe migraine.</p> <p>Methods</p> <p>One hundred and twenty five female patients with migraine attending the emergency department received 0.15 mg of methylergonovine intravenously. Pain intensity, heart rate, blood pressure, and methylergonovine side effects were checked 5, 10, 15, 30 and 60 minutes after drug administration. An additional 0.075 mg dose of methylergonovine was administered to those patients who did not experienced relevant pain relief 15 minutes after dosing. </p> <p>Results</p> <p>Pain intensity decreased markedly from the first minutes after dosing, the 74.4% of patients being pain free at 60 minutes. Only seven patients required an additional dose of methylergonovine. Nausea and vomiting were the most relevant side effects related with methylergonovine administration (84% of patients). A substantial decrease (10 to 25 mmHg) in systolic blood pressure values was observed in 56% of the patients. A significant correlation (p < 0.0001) was found between the decrease in pain intensity and the reduction of systolic blood pressure.</p> <p>Conclusion</p> <p>Although limited by the non-controlled design of the study, our data suggest that intravenous methylergonovine can be an effective and safe drug in the management of severe migraine attacks in the emergency room.</p

Differences between the real and the desired worlds in the results of clinical trials

OBJECTIVE:We refer to the effectiveness (known as pragmatic or real world) and efficacy (known as explanatory or desired or ideal world) of interventions. However, these terms seem to be randomly chosen by investigators who design clinical trials and do not always reflect the true purpose of the study. A pragmatic-explanatory continuum indicator summary tool was thus developed with the aim of identifying the characteristics of clinical trials that distinguish between effectiveness and efficacy issues. We verified whether clinical trials used the criteria proposed by the indicator summary tool, and we categorized these clinical trials according to a new classification.METHOD:A systematic survey of randomized clinical trials was performed. We added a score ranging from 0 (more efficacious) to 10 (more effective) to each domain of the indicator summary tool and proposed the following classifications: high efficacy

A Small Genomic Region Containing Several Loci Required for Gastrulation in Drosophila

Genetic screens in Drosophila designed to search for loci involved in gastrulation have identified four regions of the genome that are required zygotically for the formation of the ventral furrow. For three of these, the genes responsible for the mutant phenotypes have been found. We now describe a genetic characterization of the fourth region, which encompasses the cytogenetic interval 24C3-25B, and the mapping of genes involved in gastrulation in this region. We have determined the precise breakpoints of several existing deficiencies and have generated new deficiencies. Our results show that the region contains at least three different loci associated with gastrulation effects. One maternal effect gene involved in ventral furrow formation maps at 24F but could not be identified. For a second maternal effect gene which is required for germ band extension, we identify a candidate gene, CG31660, which encodes a G protein coupled receptor. Finally, one gene acts zygotically in ventral furrow formation and we identify it as Traf4

Explaining the Atypical Reaction Profiles of Heme Enzymes with a Novel Mechanistic Hypothesis and Kinetic Treatment

Many heme enzymes show remarkable versatility and atypical kinetics. The fungal extracellular enzyme chloroperoxidase (CPO) characterizes a variety of one and two electron redox reactions in the presence of hydroperoxides. A structural counterpart, found in mammalian microsomal cytochrome P450 (CYP), uses molecular oxygen plus NADPH for the oxidative metabolism (predominantly hydroxylation) of substrate in conjunction with a redox partner enzyme, cytochrome P450 reductase. In this study, we employ the two above-mentioned heme-thiolate proteins to probe the reaction kinetics and mechanism of heme enzymes. Hitherto, a substrate inhibition model based upon non-productive binding of substrate (two-site model) was used to account for the inhibition of reaction at higher substrate concentrations for the CYP reaction systems. Herein, the observation of substrate inhibition is shown for both peroxide and final substrate in CPO catalyzed peroxidations. Further, analogy is drawn in the “steady state kinetics” of CPO and CYP reaction systems. New experimental observations and analyses indicate that a scheme of competing reactions (involving primary product with enzyme or other reaction components/intermediates) is relevant in such complex reaction mixtures. The presence of non-selective reactive intermediate(s) affords alternate reaction routes at various substrate/product concentrations, thereby leading to a lowered detectable concentration of “the product of interest” in the reaction milieu. Occam's razor favors the new hypothesis. With the new hypothesis as foundation, a new biphasic treatment to analyze the kinetics is put forth. We also introduce a key concept of “substrate concentration at maximum observed rate”. The new treatment affords a more acceptable fit for observable experimental kinetic data of heme redox enzymes

Autocrine Activation of the MET Receptor Tyrosine Kinase in Acute Myeloid Leukemia

Although the treatment of acute myeloid leukemia (AML) has improved significantly, more than half of all patients develop disease that is refractory to intensive chemotherapy. Functional genomics approaches offer a means to discover specific molecules mediating aberrant growth and survival of cancer cells. Thus, using a loss-of-function RNA interference genomic screen, we identified aberrant expression of the hepatocyte growth factor (HGF) as a critical factor in AML pathogenesis. We found HGF expression leading to autocrine activation of its receptor tyrosine kinase, MET, in nearly half of the AML cell lines and clinical samples studied. Genetic depletion of HGF or MET potently inhibited the growth and survival of HGF-expressing AML cells. However, leukemic cells treated with the specific MET kinase inhibitor crizotinib developed resistance due to compensatory upregulation of HGF expression, leading to restoration of MET signaling. In cases of AML where MET is coactivated with other tyrosine kinases, such as fibroblast growth factor receptor 1 (FGFR1), concomitant inhibition of FGFR1 and MET blocked compensatory HGF upregulation, resulting in sustained logarithmic cell kill both in vitro and in xenograft models in vivo. Our results demonstrate widespread dependence of AML cells on autocrine activation of MET, as well as the importance of compensatory upregulation of HGF expression in maintaining leukemogenic signaling by this receptor. We anticipate that these findings will lead to the design of additional strategies to block adaptive cellular responses that drive compensatory ligand expression as an essential component of the targeted inhibition of oncogenic receptors in human cancers

Vitamin D Deficiency and Exogenous Vitamin D Excess Similarly Increase Diffuse Atherosclerotic Calcification in Apolipoprotein E Knockout Mice

Background: Observational data associate lower levels of serum vitamin D with coronary artery calcification, cardiovascular events and mortality. However, there is little interventional evidence demonstrating that moderate vitamin D deficiency plays a causative role in cardiovascular disease. This study examined the cardiovascular effects of dietary vitamin D deficiency and of vitamin D receptor agonist (paricalcitol) administration in apolipoprotein E knockout mice. Methods: Mice were fed atherogenic diets with normal vitamin D content (1.5IU/kg) or without vitamin D. Paricalcitol, or matched vehicle, was administered 3× weekly by intraperitoneal injection. Following 20 weeks of these interventions cardiovascular phenotype was characterized by histological assessment of aortic sinus atheroma, soluble markers, blood pressure and echocardiography. To place the cardiovascular assessments in the context of intervention effects on bone, structural changes at the tibia were assessed by microtomography. Results: Vitamin D deficient diet induced significant reductions in plasma vitamin D (p<0.001), trabecular bone volume (p<0.01) and bone mineral density (p<0.005). These changes were accompanied by an increase in calcification density (number of calcifications per mm2) of von Kossa-stained aortic sinus atheroma (461 versus 200, p<0.01). Paricalcitol administration suppressed parathyroid hormone (p<0.001), elevated plasma calcium phosphate product (p<0.005) and induced an increase in calcification density (472 versus 200, p<0.005) similar to that seen with vitamin D deficiency. Atheroma burden, blood pressure, metabolic profile and measures of left ventricular hypertrophy were unaffected by the interventions. Conclusion: Vitamin D deficiency, as well as excess, increases atherosclerotic calcification. This phenotype is induced before other measures of cardiovascular pathology associated clinically with vitamin D deficiency. Thus, maintenance of an optimal range of vitamin D signalling may be important for prevention of atherosclerotic calcification