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Distribution by Scientific Domains

Medical Sciences	78%
Life Sciences	9%

Selected Abstracts

Phase I/II study of a fine-powder formulation of cisplatin for transcatheter arterial chemoembolization in hepatocellular carcinoma

HEPATOLOGY RESEARCH, Issue 4 2010
Masamichi Moriguchi
Aim:, The clinical feasibility of transcatheter arterial chemoembolization (TACE) with fine-powder cisplatin (CDDP) in patients with hepatocellular carcinoma (HCC) has not been investigated. A phase I/II study was conducted to investigate the safety and tolerability of fine-powder CDDP when it was used with lipiodol and gelatin sponge particles for TACE. Methods:, Fine-powder CDDP emulsified in lipiodol was injected into tumor arteries. Embolization was subsequently performed with gelatin sponge particles. The CDDP dose was started at 45 mg/m2 (level 1) and increased to 65 mg/m2 in 10 mg/m2 increments. Results:, Thirteen patients were enrolled in phase I study since no dose limiting toxicity was observed in any patients, even in seven patients at level 3 (65 mg/m2), the recommended dose was 65 mg/m2. The major adverse event was grade 3 thrombocytopenia, which occurred in 8% of patients. The incidence of hematological toxicities was 15% for leukocytopenia, 84% for thrombocytopenia, and 84% for anemia. Increased serum total bilirubin was observed in 54% and increased aspartate aminotransferase or alanine aminotransferase in all patients. All digestive tract symptoms (nausea 77%, anorexia 84%, vomiting 31%) were grade 2 or lower. Total adverse events were grade 3 or higher in 44%. The response rate in 19 patients who received the recommended dose was 21%. Conclusions:, TACE with a fine-powder formulation of CDDP at a dose of 65 mg/m2 is well tolerated in patients with unresectable HCC. [source]

PDE5 inhibitors in diabetic peripheral neuropathy

INTERNATIONAL JOURNAL OF CLINICAL PRACTICE, Issue 9 2006
G. HACKETT
Summary Peripheral neuropathy is the most common complication of diabetes. This paper reviews the case histories of five patients with diabetic peripheral neuropathy or severe peripheral vascular disease who reported improvement in their symptoms when treated with regular or daily dosing with phosphodiesterase type 5 inhibitors (PDE5Is). These patients had been previously treated with PDE5Is for erectile dysfunction (ED) and not responded to on-demand therapy with a PDE5I at maximal recommended dose. This improvement is likely to be due to the known benefit of these drugs on endothelial dysfunction via an improvement of blood supply to the vasa nervorum. These cases suggest that further research is indicated to evaluate the potential use of PDE5Is in the treatment and prevention of diabetic peripheral neuropathy, particularly as these drugs are already licensed to treat ED, which occurs in around 50% of male diabetics. [source]

Effect of Straw on Yield Components of Rice (Oryza sativa L.) Under Rice-Rice Cropping System

JOURNAL OF AGRONOMY AND CROP SCIENCE, Issue 2 2006
K. Surekha
Abstract Field experiments were conducted at the Directorate of Rice Research experimental farm, ICRISAT campus, Patancheru, Hyderabad, during 1998,2000 for five consecutive seasons (three wet and two dry seasons) with five treatments [T1 , 100 % straw incorporation; T2 , 50 % straw incorporation; T3 , 100 % straw + green manure (GM) incorporation; T4 , 100 % straw burning and T5 , 100 % straw removal (control)] along with the recommended dose of fertilizers to evaluate the effect of different crop residue management (CRM) practices on yield components and yield of rice in rice,rice cropping sequence. The ammonium N measured at active tillering was higher in 100 % straw-added plots over 50 % straw addition and straw removal with maximum values in the straw + GM-incorporated plots. Among the yield components, tillers, panicles and spikelets were influenced from the second season of residue incorporation with significant increase in 100 % straw-added treatments. The increase in tiller and panicle number could be attributed to the increased NH4 -N in these treatments, which is evident from the significant correlation between tiller number and NH4 -N (r = 0.82**) and panicle number and NH4 -N (r = 0.87**). The influence of residue treatments on rice grain yield was observed from the third season onwards where incorporation of straw alone or in combination with GM and burning of straw significantly increased grain and straw yields. Grain yield showed significant positive correlation with the number of tillers (r = 0.74*,0.81**) and panicles (r = 0.74*,0.84**) in three treatments (T1, T3 andT4) where grain yields were significantly higher. The regression analysis showed that 57,66 % and 64,75 % of the variation in yield could be explained by tillers and panicles together in these three treatments during wet and dry seasons respectively. Thus, CRM practices such as addition of 100 % straw either alone or with GM and straw burning influenced the yield components (tillers, panicles and spikelets) positively and thereby increased rice grain yields. [source]

Effects of Nitrogen on Dry Matter Accumulation and Productivity of Three Cropping Systems and Residual Effects on Wheat in Deep Vertisols of Central India

JOURNAL OF AGRONOMY AND CROP SCIENCE, Issue 2 2002
P. Ramesh
A field experiment was conducted on deep vertisols of Bhopal, India to study the effects of three levels of nitrogen (N), namely 0, 75 and 100 % of the recommended dose of nitrogen (RDN), on the dry matter accumulation (DMA) and productivity of three cropping systems (sole soybean, sole sorghum and soybean + sorghum intercropping) during the rainy season and their residual effect on the subsequent wheat crop during the post-rainy season. During the rainy season, sole sorghum was found to have significantly higher DMA and productivity in terms of soybean equivalent yield (SEY) than sole soybean or soybean + sorghum intercropping. Increasing the N dose from 0 to 100 % RDN significantly improved the DMA and SEY. At a low fertility level (N0), soybean + sorghum intercropping was found to be more productive, while at a high fertility level (100 % RDN), sole sorghum was more productive than the other two cropping systems. However, during the post-rainy season, sole soybean as the preceding crop gave the highest DMA and seed yield of wheat, which were similar to those found with soybean + sorghum intercropping. Sorghum followed by wheat gave the lowest DMA and seed yield of wheat. Application of 100 % RDN irrespective of cropping system during the preceding crop improved the DMA of wheat but not its seed yield. However, N applied to the wheat crop significantly increased its DMA and seed yield. Einfluss von Stickstoff auf Trockenmasseakkumulation und Produktivität von drei Anbausystemen und deren Rückstandswirkung auf Weizen in einem tiefen Vertisol Zentralindiens Ein Feldexperiment wurde durchgeführt auf einem tiefen Vertisol bei Bhopal, Indien, um den Einfluss von drei Stickstoffkonzentrationen 0, 75 und 100 % der empfohlenen Stickstoffmenge (RDN) auf die Trockenmasseakkumulation (DMA) und Produktivität von drei Anbausystemen (Reinanbau Sojabohne, Reinanbau Sorghum und Sojabohne + Sorghum Mischanbau) während der Regensaison und deren Nachwirkungen auf den folgenden Anbau von Weizen während der Nachregensaison zu untersuchen. Während der Regensaison war der Reinanbau von Sorghum signifikant höher in DMA und in der Produktivität in Form von Ertragsäquivalenten für Sojabohnen (SEY) im Vergleich zu einem Reinanbau von Sojabohne oder einem Mischanbau von Sojabohne + Sorghum. Eine Erhöhung der N-Anwendung von 0 bis 100 % RDN erhöhte Signifikanz DMA und SEY. Unter der niedrigen Düngung (N0) erwies sich Sojabohne + Sorghum Mischanbau als produktiver im Vergleich zu einer hohen Düngungeranwendung (100 % RDN), Reinanbau war produktiver als die anderen beiden Anbausysteme. Allerdings während der Nachregensaison erwies sich der Reinanbau von Sojabohnen vor Weizen als die höchste DMA und Ertragsmenge, was mit dem Sojabohnen + Sorghum Mischanbau vergleichbar war. Sorghum gefolgt von Weizen ergab den geringsten DMA und niedrigsten Weizenertrag. Die Anwendung von 100 % RDN erhöhte unabhängig von dem Anbausystem der vorhergehenden Kulturpflanzen DMA von Weizen aber nicht den Kornertrag. Allerdings erhöhte N im Weizenanbau signifikant sowohl DMA als auch Kornertrag. [source]

Comparing the Feasibilities of Pearlmillet-Based Intercropping Systems Supplied with Varying Levels of Nitrogen and Phosphorus

JOURNAL OF AGRONOMY AND CROP SCIENCE, Issue 2 2001
O. P. Sharma
To compare the feasibilities of pearlmillet-based intercropping systems, field experiments were carried out for 2 years on loamy sand soils in the semi-arid plain zone of Rajasthan, India. Results showed that the pooled yields of pearlmillet from the single crop (1525 kg ha,1) and from the crop intercropped with legumes (1528, 1498 or 1540 kg ha,1) were statistically the same. The yields from intercrop legumes were obtained as a bonus. The highest value of land equivalent ratio (1.21) was recorded for the pearlmillet + clusterbean system, which gave significantly better results than the pearlmillet + cowpea system. It was also found that the dose of nitrogen can be reduced by up to 25 % when pearlmillet is grown with legumes. However, intercrop legumes required the recommended dose of fertilizer to produce their optimal yields. The practice of intercropping without fertilizer proved disadvantageous. Ein Vergleich der Eignung eines auf Perlhirse basierenden Mischanbausystems mit unter- schiedlichen Stickstoff- und Phosphorsäuremengen Um die Eignung der Perlhirse auf der Basis eines Mischanbausystems zu überprüfen, wurden Feldexperimente für zwei Jahre auf einem lehmigen Sandboden in der semiariden Ebene von Rajastan, Indien durchgeführt. Die Ergebnisse zeigten, dass der Gesamtertrag von Perlhirse in einem Reinanbau (1525 kg ha,1) und in einem Mischanbau mit Leguminosen (1528, 1498 bzw. 1540 kg ha,1) statistisch gleich war. Die Erträge der Leguminosen im Mischanbau waren ein zusätzlicher Gewinn. Die höchsten Werte von LER (1,21) wurden im Mischanbau von Perlhirse + Klusterbohnenanbau nachgewiesen, wobei eine signifikante Überlegenheit gegenüber Perlhirse + Kuhbohnenanbausystemen nachzuweisen war. Die Ergebnisse weisen ferner darauf hin, dass bei der Stickstoffanwendung bis zu 25 % eingespart werden können, wenn Perlhirsen zusammen mit Leguminosen angebaut werden. Allerdings, der Mischanbau mit Leguminosen erfordert eine zu empfehlende Anwendungsmenge von Dünger, um optimale Erträge zu produzieren. Die Praxis des Mischanbaus ohne zusätzliche Düngung erwies sich als ungünstig. [source]

A randomised, controlled trial of the effects of an energy-dense supplement on energy intake, appetite and blood lipids in malnourished community-based elderly patients

JOURNAL OF HUMAN NUTRITION & DIETETICS, Issue 4 2008
G.P. Hubbard
Background:, Disease-related malnutrition is common in the elderly and if left untreated may have severe consequences (Stratton & Elia, 2003). One of the strategies used to combat malnutrition is the use of high-energy, low-volume [18.8 kJ mL,1 (4.5 kcal ml,1)] nutritional supplements. This study aimed to investigate the effects of an energy dense supplement on energy intake, appetite and blood lipids in elderly patients at risk of malnutrition. Methods:, In this randomised, controlled, parallel study, 42 community-based patients (mean (SD) age: 84 (7.0) years, mean body mass index (BMI): 20.9 (3.5) kg m,2), identified as being at medium or high risk of malnutrition [Malnutrition Universal Screening Tool (MUST) (Elia, 2003)] were randomised (using standard randomisation methods) to receive either; (i) 1674 kJ day,1 (400 kcal day,1) (in 3 × 30 mL doses) of an energy-dense supplement (Calogen, Nutricia®) (n = 19) or (ii) dietary advice in the form of a standardised dietary advice sheet (n = 23), for 4 weeks. Energy intake, appetite, blood lipids [i.e. total cholesterol, low density lipoprotein (LDL) cholesterol (subset analysis only)], body weight, gastro-intestinal tolerance, product compliance and product acceptability were assessed during the 4 week study. Results are presented as mean (SD). Paired t -test and one way anova statistical analyses were undertaken using SPSS v15. Ethical approval for this study was obtained from the appropriate committee. Results:, Supplementation with the energy dense supplement significantly increased mean total daily energy intake by +1736 kJ (+415 kcal, P = 0.009) from 6456 (2330) kJ [1543 (557) kcal] to 8192 (1477) kJ [1958 (353) kcal], with no significant effect on voluntary food intake or appetite scores (for hunger, fullness and desire to eat). In the dietary advice group, although mean total daily energy intake was also significantly increased by +1105 kJ (+264 kcal, P = 0.026) from 5623 (2107) kJ [1344 (503) kcal] to 6728 (2029) kJ [1608 (485) kcal], it was significantly lower than in the energy dense group [-1464 kJ (-350 kcal), P = 0.012] at week 4. Both energy-dense and dietary advice groups maintained weight during the study. No significant adverse effects on blood lipid concentrations were observed in either group, with a significant decrease in total cholesterol concentrations [from 4.26 (1.0) mM to 3.96 (0.8) mM, P = 0.03] and LDL cholesterol concentrations [from 2.32 (0.6) mM to 2.06 (0.5) mM, P = 0.03] in the energy dense group (subset analysis, n = 9). Both supplementation with energy dense supplement and dietary advice were well tolerated with no gastro-intestinal side effects. The energy dense supplement was well accepted with >80% of patients rating it as pleasant and convenient, with an enjoyable taste. Compliance with the energy dense supplement was high, with 95% of patients consuming the recommended dose of 3 × 30 mL throughout the study. Discussion:, This study in elderly patients with or at risk of malnutrition suggests that the energy dense supplement is effective in significantly improving total intakes of energy with no suppression of appetite or voluntary dietary intake, enabling patients to maintain weight and that the energy dense supplement is well tolerated and accepted, with excellent compliance and no adverse effects on blood lipids. Conclusions:, This randomised controlled trial suggests that an energy-dense supplement is an effective, well tolerated and safe method of providing energy supplementation for the management of elderly patients with or at risk of malnutrition in clinical practice. References, Elia, M. (2003) The "MUST" report. Nutritional screening for adults: a multidisciplinary responsibility. Redditch, UK: BAPEN. Available at http://www.bapen.org.uk (accessed on 15 March 2008). Stratton, R.J., Green, C.J. & Elia, M. (2003) Disease-related malnutrition: an evidence-based approach. Oxford: CABI publishing. [source]

Loperamide and P-glycoprotein inhibition: assessment of the clinical relevance

JOURNAL OF PHARMACY AND PHARMACOLOGY: AN INTERNATI ONAL JOURNAL OF PHARMACEUTICAL SCIENCE, Issue 4 2010
Joris Vandenbossche
Abstract Objectives Loperamide is a peripherally acting , opioid receptor agonist and an avid substrate for P-glycoprotein. This may give rise to drug,drug interactions and increased risk for central adverse effects. The objective of this study was to re-evaluate the predictability of non-clinical data using loperamide as a probe P-glycoprotein substrate. We searched the literature for papers containing data on drug,drug interactions of loperamide-containing products in humans. We also reviewed the internal worldwide safety database of Johnson & Johnson for spontaneous case reports suggestive of a central opioid effect after coadministration of loperamide with a P-glycoprotein inhibitor or substrate. Key findings Only one of the ten studies in our review supported the finding that inhibition of P-glycoprotein is associated with clinically relevant signs or symptoms of central nervous system (CNS) depression/opioid toxicity of loperamide. None of the 25 spontaneous case reports of interest were suggestive of signs or symptoms of CNS depression/opioid toxicity due to coadministration of loperamide and a P-glycoprotein inhibitor or substrate. Summary Based on a review of the literature and a cumulative review of the sponta-neous case reports, there is insufficient evidence that an interaction between loperamide and a P-glycoprotein inhibitor or substrate is associated with clinical symptoms of CNS depression/opioid toxicity when loperamide is taken at the recommended dose. [source]

Effect of combined maternal and infant vitamin D supplementation on vitamin D status of exclusively breastfed infants

MATERNAL & CHILD NUTRITION, Issue 1 2009
Hussein F. Saadi
Abstract Severe vitamin D deficiency in mothers and their breastfed infants is a significant health problem in the Middle East. Supplementation of the breastfed infant alone with the recommended dose of vitamin D may be insufficient in high-risk population. We investigated the effect of combined maternal and infant vitamin D supplementation on vitamin D status of the breastfed infant. We examined also the effect of supplementation on vitamin D antirachitic activity of breast milk in a subset of mothers. Healthy breastfeeding mothers (n = 90) were randomly assigned to 2000 IU daily (group 1) or 60 000 IU monthly (group 2) of vitamin D2, and all their infants (n = 92) received 400 IU daily of vitamin D2 for 3 months. Most infants had vitamin D deficiency , 25-hydroxyvitamin D [25(OH)D] , 37.5 nmol L,1, at study entry. Serum 25(OH)D concentrations at 3 months increased significantly from baseline in infants of mothers in group 1 (13.9 ± 8.6 vs. 49.6 ± 18.5 nmol L,1, P < 0.0001) and group 2 (13.7 ± 12.1 vs. 44.6 ± 15.0 nmol L,1, P < 0.0001). Maternal and infant serum 25(OH)D concentrations correlated positively at baseline (r = 0.36, P = 0.01) and 3 months (r = 0.46, P = 0.002). Milk antirachitic activity increased from undetectable (<20 IU L,1) to a median of 50.9 IU L,1. In conclusion, combined maternal and infant vitamin D supplementation was associated with a threefold increase in infants' serum 25(OH)D concentrations and a 64% reduction in the prevalence of vitamin D deficiency without causing hypervitaminosis D. [source]

Incidence of side-effects associated with high-dose ferric gluconate in patients with severe chronic renal failure

NEPHROLOGY, Issue 1 2003
BAHAR BASTANI
SUMMARY: Ferric gluconate complex in sucrose (FerrlecitÔ) has been associated with less side-effects than iron dextran; however, the recommended dose of 62.5,125 mg per treatment is only suitable for haemodialysis (HD) patients. We retrospectively analysed the incidence of the side-effects associated with a high dose of FerrlecitÔ infusion (20 treatments in 13 patients; 10 treatments of 250 mg/3,4 h, and 10 treatments of 500 mg/5 h infusion). The patients were in the age range of 32,75 years old, seven with chronic renal failure (CRF), and six on dialysis treatment. One (10%) of the 10 treatments using a 250 mg dose was complicated with severe nausea/vomiting, diarrhoea and a burning sensation in the feet. Three (30%) of the 10 treatments using a 500 mg dose were complicated with: chills, severe nausea/vomiting, hypotension and syncope in one; severe nausea/vomiting, diarrhoea and hypotension in one; and an episode of vomiting in one patient. A single treatment with a 250 mg dose resulted in no significant change in haematological parameters. A single treatment with a 500 mg dose resulted in a significant increase in haemoglobin (Hgb) and haematocrit (Hct), but only a rising trend in serum iron,% transferrin saturation and ferritin pre versus 1,2 months postinfusion. In conclusion, FerrlecitÔ doses of 250 or 500 mg are complicated with significant untoward reactions in 10,30% of patients, in a dose-dependent fashion. [source]

Oral therapy for migraine: Comparisons between rizatriptan and sumatriptan.

PAIN PRACTICE, Issue 2 2001
A review of 4 randomized, Denmark) Neurology 2000;55:S1, Glostrup, double-blinded clinical trials. (University of Copenhagen
Four comparative, placebo-controlled, randomized clinical trials of oral rizatriptan versus oral sumatriptan including one Phase II trial and three Phase III trials were reported in this study. Forty mg rizatriptan was found to be more effective than 100 mg sumatriptan, but was associated with a high incidence of adverse effects. Five mg rizatriptan was comparable to 50 mg sumatriptan. In two trials, rizatriptan 10 mg, the recommended dose in most countries, had a more rapid onset of action than 50 mg and 100 mg of sumatriptan. In addition, 10 mg of rizatriptan resulted in more patients being pain-free after 2 h than 100 mg of sumatriptan, and resulted in fewer drug-related adverse events than sumatriptan. [source]

Death after re-exposure to propofol in a 3-year-old child: a case report

PEDIATRIC ANESTHESIA, Issue 3 2004
Josef Holzki MD
Summary This case report discusses the cause of death in a 3-year-old child who survived a high dose (20 mg·kg,1·h,1) of propofol, infused over a period of 15 h, following which the patient developed a combined respiratory and metabolic acidosis, the oxygenation remaining normal. Bronchospasm was assumed to be the cause of hypercapnia. At this time the doctors in charge did not think of a possible side-effect of propofol. The administration of propofol was interrupted, the patient recovered within 13 h from the acidosis, woke up and required further sedation. A supposedly entirely safe infusion of 4 mg·kg,1·h,1 propofol, as recommended in the literature for up to 48 h, was administered. After only 8 h intractable bradycardic dysrhythmias occurred. Although pharmacokinetic studies have pointed to a possible accumulation of propofol during continuous infusions, an interruption of an infusion for several hours has been considered sufficient for practically total clearance of the drug from the body. In this case re-exposure with a recommended dose of propofol was accompanied by bradycardia and dysrythmias that proved to be resistant to therapy and led to fatal cardiac insufficiency with a functioning artificial pacemaker in place. This case raises concerns about the safety of long-term infusions of propofol for sedation in children and possibly also in adults. [source]

Predicting effective fungicide doses through observation of leaf emergence

PLANT PATHOLOGY, Issue 6 2000
N. D. Paveley
Experimental data were used to test the hypothesis that the effective fungicide dose (ED) , the dose required to achieve a given level of disease suppression , varies in a predictable manner according to the pattern of development of the wheat canopy. Replicated and randomized field plots received a single systemic fungicide spray at either zero (control), 0·25, 0·5, 0·75 or 1·0 dose (the recommended dose), at one of eight timings from April to June. Wheat cultivars and locations for experiments were selected to promote epidemics of septoria tritici spot and yellow rust caused by Septoria tritici (anamorph of Mycosphaerella graminicola) and Puccinia striiformis, respectively. Logistic or exponential disease progress curves were fitted to disease severity data and used to estimate the date of disease onset (t0) and relative epidemic growth rate (r) on each leaf layer for each treatment. Area under the disease progress curve (AUDPC) values were used to construct fungicide dose by spray timing response surfaces for each of the upper four leaves. A parsimonious function, with an exponential form in the dose,response dimension and a normal distribution in the timing dimension described a high proportion of the variation in AUDPC (R2 values ranging from 0·73 to 0·97). Consistent patterns of treatment effect were noted across pathogen species, leaf layers, sites and seasons. Fungicide applications that coincided with full leaf emergence delayed t0 on that leaf layer. Treatments applied after full leaf emergence did not delay t0, but reduced r. Progressively earlier or later treatments, or lower doses, had decreasing effects. AUDPC was affected more by t0 than r. AUDPC response surface parameter estimates showed that curvature of the dose,response was not affected by spray timing, but appeared to be a characteristic of the fungicide,pathogen combination. However, the lower asymptote of the dose,response curve, and hence the ED, varied substantially with spray timing. The pattern of change in ED with spray timing was consistent across a range of leaf layers, pathosystems and seasons, and the spray timing at which the ED was minimized varied only within a small range, around the time of leaf emergence. In contrast, variation in untreated disease severity, resulting from variation in initial inoculum and weather, was large. It was concluded that the main value of disease forecasting schemes may be in their capacity to predict the level of untreated disease, to which the economic optimum, or ,appropriate', dose relates. Spray timing determines the part of the canopy where disease will be efficiently controlled and hence the green leaf area saved. Timing decisions should relate to observations of emergence of those leaf layers important to yield. [source]

Latest news and product developments

PRESCRIBER, Issue 21 2008
Article first published online: 2 DEC 200
Osteoporosis guideline A new guideline on the management of osteoporosis in men over 50 and post-menopausal women has been published by the National Osteoporosis Guideline Group (www.shef.ac.uk/NOGG), a group of organisations representing health professionals and patients, with funding from several pharmaceutical companies. The guideline recommends using the FRAX tool (www.shef.ac.uk/FRAX) to assess the 10-year fracture risk in individuals with risk factors to facilitate targeting DXA scans to measure bone mineral density. Patients who have already sustained a fragility fracture should be treated without risk assessment. Treatment recommendations are similar to those published in draft NICE guidance on primary and secondary prevention, selecting alendronate as the drug of first choice for most patients. Efalizumab efficacy A multicentred postapproval trial has demonstrated long-term efficacy and a favourable safety profile for efalizumab (Raptiva) in moderate to severe chronic plaque psoriasis. The CONTROL II study, presented in September at the 17th EADV congress in Paris, was conducted at 170 sites in 18 European countries and involved 1255 patients who had failed to respond to traditional systemic therapies. In this non-blinded study, 68 per cent of participants achieved the primary efficacy end-point and showed improvement within the first 12 weeks; control was maintained in responding patients who continued treatment. Adverse effects were graded as mild or moderate and similar to those reported in earlier studies. There was no evidence of an increase in malignancies or infections. New oral anticoagulant Rivaroxaban (Xarelto), an oral factor Xa inhibitor, has been introduced for the prevention of venous thrombo-embolism in patients undergoing elective hip or knee replacement surgery. Compared with the low molecular weight heparin enoxaparin (Clexane), rivaroxaban has been shown to reduce the risk of venous thrombosis by 70 per cent after hip replacement and by 49 per cent after knee replacement; the risk of bleeding was similar. At the recommended dose of 10mg once daily, prophylaxis after hip surgery lasts five weeks and costs £157; prophylaxis after knee surgery lasts two weeks and costs £63. New products UCB Pharma has introduced lacosamide (Vimpat) as adjunctive treatment of partial-onset epilepsy with or without secondary generalisation in patients aged 16 and over. A month's treatment at the recommended maintenance dose of 100-200mg twice daily costs approximately £73-£140. A new non-nucleoside reverse transcriptase inhibitor (NNRI) is available for the treatment of HIV-1 infection in combination with a boosted protease inhibitor (PI) and other antiretrovirals in treatment-experienced adults. Etravirine (Intelence) costs approximately £320 for one month's treatment at the recommended dose of 200mg twice daily. Voltarol Pain-Eze (diclofenac) 12.5mg tablets are now available without prescription; a pack of 18 tablets costs £5.99. Atypicals and EPS risk Atypical antipsychotics are not associated with a significantly lower risk of extra-pyramidal symptoms than first-generation agents such as perphenazine (Fentazin), a new analysis of the CATIE study has shown (Br J Psychiatry 2008;193:279,88). CATIE was a large trial comparing the efficacy and safety of antipsychotics in the treatment of schizophrenia in which perphenazine was a representative first-generation agent (Am J Psychiatry 2006;163:611,22). This analysis found no differences in the risk of parkinsonism, dystonia, akathisia or tardive dyskinesia between perphenazine and the newer antipsychotics; use of antiparkinsonian medication was higher with risperidone and lower with quetiapine (Seroquel). Mental health website A new website offering information about mental illnesses and drug treatment has been launched by the United Kingdom Psychiatric Pharmacy Group (UKPPG), the College of Mental Health Pharmacists (CMHP), the Pharmaceutical Schizo-phrenia Initiative (PSI) and the National Institute for Mental Health in England (NIMHE). www.choiceandmedication.org.uk includes information about 17 mental illnesses and a large number of drug treatments. It offers links to other sites offering information and downloadable leaflets, help to identify the local mental health trust and downloadable charts comparing treatments for each indication. [source]

Latest news and product developments

PRESCRIBER, Issue 19 2007
Article first published online: 22 NOV 200
UK data suggest OCs may reduce cancer risk The latest analysis of the RCGP oral contraception (OC) study suggests that oral contraceptives may be associated with an overall reduction in the risk of cancer (Br Med J online: 11 September 2007; doi:10.1136/bmj.39289. 649410.55). The cohort of 46 000 women provided 744 000 woman-years for ever use of an oral contraceptive and 339 000 woman-years of never use. Longer use was associated with increasing risks of cervical (RR 2.73), and pituitary or CNS (RR 5.51) cancers, but decreasing risks of uterine (RR 0.57) and ovarian (RR 0.38) cancers. OC use was also associated with a lower overall risk of colorectal cancers. The overall risk of any cancer was reduced by 12 per cent (RR 0.88). CombAT two-year data Two-year data revealed at the 29th Congress of the Société Internationale d'Urologie in Paris in September show that dutasteride (Avodart) and tamsulosin combination therapy provides significantly improved symptom control in BPH compared with either therapy alone. The Combination therapy with Avodart (dutasteride) and tamsulosin (CombAT) study took over 4800 eligible men (age ,50 years with a prostate volume ,30cc, serum PSA level ,1.5-10ng per ml and IPSS ,12) who received placebo for four weeks before being randomised in a 1:1:1 ratio to either dutasteride monotherapy (0.5mg per day), tamsulosin monotherapy (0.4mg per day) or a combination of both drugs. At two years the primary efficacy end-point was achieved: combination therapy was significantly more effective than either monotherapy, and continuous improvement could be observed throughout the two years. The combination therapy was also well tolerated, although drug-related adverse events were more common with combination therapy (24 per cent) than either monotherapy (dutasteride 18 per cent, tamsulosin 14 per cent). Dutasteride, a 5-, reductase inhibitor, has been shown to be more effective for long-term use in men than tamsulosin, while tamsulosin, an alpha blocker, has been shown to be effective in the short term. CombAT is the first study to demonstrate that the combination therapy of both drugs could lead to greater symptom improvement over time than an alpha blocker alone. Aliskiren - new class of antihypertensive Novartis has introduced aliskiren (Rasilez), the first direct renin inhibitor for the treatment of hypertension. It is likely to be used in combination with other agents but is also licensed as monotherapy. The commonest adverse effect is diarrhoea. At the recommended dose of 150-300mg per day, a month's treatment costs £19.80-£23.80. MHRA updates drug safety advice The balance of benefit and risks from HRT may be more favourable for younger women, the MHRA says in its monthly bulletin, Drug Update (September 2007). GPs considering prescribing HRT should evaluate the potential risks and benefits for each individual, the MHRA says. The bulletin summarises the risks of cardiovascular events and cancers associated with HRT. Cardiovascular risk is a particular concern for women over 60, whose baseline risk is high; although evidence for the safety of HRT in younger women is limited, their baseline risk is lower. Overall, the lowest dose of HRT should be used for the shortest possible time, and HRT should be prescribed to prevent osteoporosis only when alternatives are not suitable. The MHRA also advises in the bulletin that: Individual risk of stroke, breast cancer and endometrial cancer should be considered before prescribing tibolone (Livial). Nasal formulations of desmopressin are no longer indicated for primary nocturnal enuresis; prescribers are reminded to adhere to product guidance on fluid intake. Patients and carers should be warned of the risk of psychiatric effects associated with corticosteroids; symptoms may develop within a few days or weeks in children and adults, and may be more common at higher doses. Patients taking steroids for more than three weeks are reminded not to stop treatment abruptly. A list of questions and answers for patients is available at www.mhra.gov.uk. The use of parenteral B vitamins plus ascorbic acid (Pabrinex) may rarely be associated with severe allergic reactions, but this should not preclude its use for patients who need it. Study claims statin switch may increase CV morbidity Switching patients from atorvastatin (Lipitor) to simvastatin may increase the risk of cardiovascular events, according to a UK study presented at the European Society of Cardiology Congress in Vienna. The analysis, from The Health Improvement Network database, included 11 520 patients taking atorvastatin for at least six months, of whom 2511 were switched to simvastatin. Switching was associated with a 30 per cent increase in the relative risk of cardiovascular events, though absolute figures have not been reported. Patients who were switched were also more likely to discontinue treatment (21 vs 8 per cent of those continuing atorvastatin). Details of the conduct of the study, which will be published in the British Journal of Cardiology, are not available. Glitazones controversy rumbles on New systematic reviews have fuelled the controversy over the cardiac safety of rosiglitazone and pioglitazone. A meta-analysis of four trials involving 14 291 patients and lasting one to four years found that rosiglitazone was associated with a significantly increased risk of myocardial infarction (relative risk, RR, 1.42) and heart failure (RR 2.09) but not cardiovascular mortality (RR 0.90) (J Am Med Assoc 2007;298:1189-95). The second review included 19 trials of pioglitazone involving 16 390 patients, with follow-up from four months to 3.5 years. Pioglitazone was associated with a lower risk of composite events (death, myocardial infarction, stroke; hazard ratio, HR, 0.82) but an increased risk of serious heart failure (HR 1.41) (J Am Med Assoc 2007;298: 1180-8). Neither review reported significant heterogeneity between the included studies. Another systematic review of eight controlled and cohort studies concluded that metformin is the only antidiabetic drug not associated with an increased risk of harm in patients with diabetes and heart failure (Br Med J Online First 30 August; doi:10.1136/bmj.39314. 620174.80). The Canadian authors found methodological problems with all studies, and concluded that results for sulphonylureas were conflicting due to differences between the studies. Asthma prescribing education Health professionals need more education about rational prescribing for children with asthma, say researchers from Australia (Arch Dis Child online: 4 September 2007; doi: 10. 1136/adc.2007.119834). Analysing trends in asthma medication prescriptions for children in the UK between 2000 and 2006, they found the proportion of steroid inhalers prescribed as combinations increased from 2.7 per cent in 2000 to 25 per cent in 2006. The authors say this excessive increase is inconsistent with guidance that steroid-only inhalers should be the mainstay for most people with asthma. Copyright © 2007 Wiley Interface Ltd [source]

Latest news and product developments

PRESCRIBER, Issue 10 2007
Article first published online: 13 SEP 200
Sitagliptin: novel drug for type 2 diabetes Sitagliptin (Januvia), the first dipeptidyl peptidase-4 (DPP-4) inhibitor, has been introduced for the treatment of type 2 diabetes in combination with metformin or a glitazone when either agent plus exercise and diet fail to control blood glucose. Inhibition of DPP-4 prevents the breakdown of incretin hormones that promote insulin release from pancreatic beta cells. In trials lasting up to 24 weeks, adding sitagliptin to established therapy reduced HbA1C by 0.67-0.90 per cent. It is contraindicated in patients with moderate or more severe renal impairment. At the recommended dose of 100mg per day, a month's treatment with sitagliptin costs £33.36. Guide to treating mentalillness in primary care A new guide from the Centre for Clinical and Academic Workforce Innovation aims to help health professionals and others treating people with mental illness. A Complete Guide to Primary Care Mental Health, a toolkit presented as a reference book and CD, covers aspects of treatment, the law and working with the voluntary sector and includes training materials compatible with evidence-based guidance. Copies are available from amazon.co.uk. Follow-up improves statin adherence Patients may take long holidays from statin treatment but a visit to the doctor is among the most effective ways to improve adherence, a US study shows (Arch Intern Med 2007;167:847,52). Observation of 239 911 patients who began statin treatment during a seven-year period showed that 54 per cent stopped their treatment for at least 90 days. Of these, 48 per cent restarted within one year and 60 per cent within two years. Factors associated with restarting treatment were a visit to the doctor who prescribed the statin (odds ratio, OR, 6.1) or a visit to a different doctor (OR 2.9). A cholesterol test and hospital admission for a cardiovascular event were also significant factors. Pharmacist MUR does not reduce heart failure deaths Medication review by trained community pharmacists does not reduce admissions or deaths among patients with heart failure, according to a study from East Anglia (BMJ online: 23 April 2007; doi:10.1136/bmj.39164.568183.AE). Patients admitted as emergencies with heart failure were randomised to usual care or two home visits by a community pharmacist within two and eight weeks after discharge. Pharmacists reviewed medication and advised on self-management of symptoms and lifestyle. There were no significant differences in hospital admissions over the next six months (rate ratio 1.15 for pharmacist vs control) or deaths (rate ratio 1.18); quality of life scores were similar in the two groups. The authors speculate that the interventions may have been too brief or too late (lifestyle changes having been made already), or disadvantaged by not adjusting beta-blocker doses. A Cardiff study of pharmacist medication reviews for elderly patients (BMJ online: 20 April 2007; doi:10.1136/bmj.39171. 577106.55), found that their advice had the potential to undermine patients' ,confidence, integrity and self-governanc'. The study found that pharmacists gave advice unnecessarily and uninvited. CHD targets met early The national programme to tackle heart disease has made substantial progress towards it targets, the Department of Health says in a 10-year report, and a 40 per cent cut in mortality will be achieved ahead of the deadline of 2010. Coronary Heart Disease Ten Years On: Improving Heart Care, a report by Professor Roger Boyle, National Director for Heart Disease and Stroke, states that 7 per cent of the population is now taking statins, resulting in 9700 deaths avoided annually. The prevalence of untreated hypertension fell from 32 to 24 per cent between 1998 and 2003. The report also summarises changes in service delivery, nutrition and smoking cessation. HRT: ovarian cancer risk The MHRA has not altered its advice on the use of HRT following news that five years' use increases ovarian cancer risk in women over 50. The Million Women Study revealed an approximately 20 per cent increased risk of ovarian cancer or death among women still using HRT after five or more years. There was no difference in risk between oestrogen-only and combined formulations. The MHRA says HRT is still indicated for relieving symptoms of the menopause for short-term use; as an alternative for women over 50 who cannot take other treatments to prevent osteoporosis, or when such options fail; and in women under 50 who experience a premature menopause. Poor angina treatment Over half of patients with angina continue to experience attacks despite treatment, according to a survey by the British Cardiac Patients Association. The survey of 600 patients with angina also found that twot-hirds of respondents reported that angina had a moderate to severe impact on their lives. Half said that the adverse effects of their treatment negatively affected their work, two-thirds reported an adverse impact on sex, and almost three-quarters of patients taking beta-blockers reported fatigue. A second survey of 2000 adults revealed widespread ignorance about the prevalence and symptoms of angina. The surveys were sponsored by Servier Laboratories Limited and conducted in collaboration with Research Quorum. Cabergoline restriction Indications for the dopamine agonist cabergoline (Cabaser) are being restricted to match those of pergolide (Celance), the MHRA has announced. Pergolide was recently withdrawn in the United States and its use in the EU is limited because of the risk of cardiac valvular damage. Similar toxicity has been reported with cabergolide, which is now restricted to second-line use when a nonergot treatment for Parkinson's disease has failed. It is contraindicated in patients with valvular damage or a history of fibrotic disorders and requires patient monitoring. Sodium reduction cuts CV events Long-term reduction in dietary sodium may reduce cardiovascular events by 25 per cent, US epidemiologists say (BMJ online: 20 April 2007; doi:10.1136/bmj.39147.604896.55). Participants in the two Trials of Hypertension Prevention (TOHP I and II) reduced their sodium intake by 44 and 33mmol per 24hr. After 10,15 years' follow-up of 2415 participants, the adjusted relative risk of cardiovascular events was 0.75 compared with controls. There was a nonsignificant 20 per cent reduction in mortality. Copyright © 2007 Wiley Interface Ltd [source]

Latest news and product developments

PRESCRIBER, Issue 7 2007
Article first published online: 11 JUL 200
Poor asthma control with off-licence prescribing Children who are prescribed off-licence medications are more likely to have poor asthma control, according to an analysis from Dundee (Br J Gen Practice 2007;57:220-2). The review of 17 163 consultations identified 1050 (6.1 per cent) who received a prescription for an unlicensed use (defined as not licensed for children or the particular age group, or dose not licensed). High doses (4.5 per cent) were more frequent than unlicensed indications (1.9 per cent). Children who received off-label prescriptions reported statistically significantly more symptoms in the day or night, symptoms during activity, and increased use of daily short-acting beta2-agonists. The authors note that off-label prescribing appears to be increasing. Atkins diet most effective over one year? The ultra low-carbohydrate, high-protein Atkins diet achieved greater weight loss than other popular diets in overweight women over one year, say US investigators (J Am Med Assoc 2007;297:969-77). The study compared the Atkins diet with three diets designed as low- or very high-carbohydrate, or based on USA nutritional guidance, in 311 women with body mass index 27-40. After one year, mean weight loss was 4.7kg with the Atkins diet , significantly greater than with the low- carbohydrate diet (1.6kg) but not compared with very high-carbohydrate (2.2kg) or the nutrition-based diet (2.6kg). Metabolic endpoints were comparable or more favourable in women using the Atkins diet. Androgen therapy linked to gum disease The majority of men treated with androgen deprivation therapy for prostate cancer are more likely to have periodontal disease (J Urol 2007;177:921-4). After controlling for risk factors, the prevalence of periodontal disease was 80.5 per cent among treated men compared with 3.7 per cent in matched controls not receiving treatment. There was no difference in bone mineral density between the groups but plaque scores were significantly higher among treated men. Food Commission rebuts MHRA on additives An independent watchdog has not accepted the MHRA's justification for including certain additives in medicines for children. The Food Commission (www.foodcomm.org.uk) found that most medicines for children contained additives, some of which , including azo dyes and benzoates , are not permitted in food. The Commission called on the pharmaceutical industry to stop using ,questionable additives'. The MHRA stated that the licensing process takes into account the likely exposure to excipients that are considered essential to make medicines palatable to children. Colouring helps children to identify the correct medicine, and preservatives ensure a reasonable shelf-life. A list of additives is included in the product's summary of product characteristics and patient information leaflet. In response, the Commission states: , , it is quite possible to flavour medicines with natural oils or extracts, and natural colourings such as beetroot and beta-carotene can be used instead of azo dyes. If parents were advised to give these medicinal products at mealtimes the manufacturers could also add a little sugar to sweeten their products, rather than relying on artificial sweeteners.' All triptans the same? There is no economic case for choosing one triptan over another and no evidence for preferring a particular triptan for adults, a systematic review has concluded. The Canadian Agency for Drugs and Technologies in Health (www.cadth.ca) found that published trials had compared most triptans with sumatriptan but not with one another, and most economic evaluations were flawed. New drug for HIV Janssen-Cilag has introduced darunavir (Prezista), a new protease inhibitor for the treatment of HIV infection. Licensed for highly pre- treated patients in whom more than one other pro- tease inhibitor regimen has failed, darunavir must be co-administered with ritonavir (Norvir). A month's treatment at the recommended dose of 600mg twice daily costs £446.70. Variation in liquid captopril for children The NHS uses a wide range of liquid formulations of captopril to treat children with heart failure , with no assurance of their bioequivalence (Arch Dis Child 2007; published online 15 March. doi: 10.1136/adc.2006.109389). Specialists in Leicester surveyed 13 tertiary paediatric cardiac centres and 13 hospitals that referred patients to them. Only three tertiary centres supplied the same liquid for-mulation of captopril as their referring hospitals. Four hospitals supplied tablets for crushing and dissolving in water; the other hospitals and centres used a total of nine different formulations. The authors say the formulations had widely varying shelf-lives, determined empirically in all but one case, and were used interchangeably despite a lack of quality control data to establish their bioequivalence. QOF CVD targets not good enough for GPs Two-thirds of GPs want Quality Outcome Framework (QOF) targets for cardiovascular disease brought into line with those of the Joint British Societies latest guidance (JBS2), according to a survey by doctor.net.uk. The survey of 1000 GPs showed that 88 per cent were aware of the JBS2 guidelines and most were already implementing the targets for lipids, blood pressure and blood glucose in some form; however, only 55 per cent were implementing the JBS2 obesity target and 14 per cent were implementing screening for the over-40s. The JBS2 target for lipids in at-risk patients is <4mmol per litre total cholesterol and <2 mmol per litre LDL-cholesterol, compared with <5 and <3mmol per litre respectively in QOF and the NSF. The survey was commissioned by Merck Sharp & Dohme and Schering- Plough. Fracture warning Following warnings in the US that rosiglitazone (Avandia) is associated with an increased risk of fractures in women, Takeda has advised prescribers that pioglitazone (Actos) carries a similar risk. An analysis of the company's clinical trials database has revealed an excess risk of fractures of bones below the elbow and knee. The incidence was similar to the excess risk associated with rosiglitazone and also confined to women. Scottish approvals The Scottish Medicines Consortium (www.scottish medicines.org.uk) has approved for use within NHS Scotland the sublingual tablet formulation buprenorphine/naloxone (Suboxone) for the treatment of opioid dependence. It has also approved the combined formulation of valsartan and amlodipine (Exforge) and the restricted use of the If inhibitor ivabradine (Procoralan). [source]

Latest news and product developments

PRESCRIBER, Issue 6 2007
Article first published online: 8 JUN 200
Initial macrolide better for pneumonia? An observational study has suggested that initial treatment with a macrolide antibiotic (such as erythromycin) may be more effective than a fluoroquinolone (like ciprofloxacin) or tetracycline as initial treatment for community acquired pneumonia and bacteraemia (Chest 2007;131:466-73). The US review of 2209 hospital episodes found that macrolide therapy was associated with a 40 per cent lower risk of death during hospital stay or within 30 days and of hospital readmission within 30 days of discharge. By contrast, no such benefit was apparent with fluoroquinolones or tetracycline. Two-year safety data for inhaled insulin Compared with sc insulin, inhaled insulin (Exubera) is associated with a small early decrease in lung function in the first three months of therapy but no further difference for up to two years (Diabetes Care 2007;30: 579-85). The comparative trial found that FEV1 declined at a mean rate of 0.051 litres per year with inhaled insulin and 0.034 litres per year with sc insulin, but there was no significant difference in the rates of decline after three months. Inhaled insulin was associated with a higher incidence of cough (37.6 vs 13.1 per cent) but a lower incidence of severe hypoglycaemic events (2.8 vs 4.1 events per 100 subject- months) and mean weight gain was 1.25kg less. Fracture risk warning with rosiglitazone GlaxoSmithKline has warned US prescribers that rosiglitazone may be associated with an increased risk of fractures. The company says information for prescribers in Europe will follow shortly. The warning comes from the ADOPT study (N Engl J Med 2006;355:2427-43), which found a significantly higher incidence of fractures of the humerus, hand and foot among women taking rosiglitazone (9.3 per cent) than with metformin (5.1 per cent) or glibenclamide (3.5 per cent). There was no difference in fracture incidence among men. The company recommends that fracture risk should be considered for women taking or about to take rosiglitazone. Oral treatment for grass pollen allergy A new treatment for allergic rhinitis due to grass pollen allergy has been introduced by ALK-Abelló. Grazax is a sublingual tablet containing a stan-dardised dose of allergen from the pollen of timothy grass. Treatment should be initiated by a specialist four months before the onset of the allergy season and continued throughout the season. Adverse effects include oral and ear pruritus, nasopharyngitis and mouth oedema. A month's treatment at the recommended dose of one tablet daily costs £67.50. Frequent analgesics linked with hypertension Men who take analgesics regularly have an increased frequency of hypertension, a US study has shown (Arch Intern Med 2007;167:394-9). The US Health Professionals Follow-Up study evaluated the use of NSAIDs, paracetamol and aspirin in 16 031 men with normal blood pressure and followed them up for four years. Compared with those who did not report analgesic use, the risk of hypertension was increased by 38 per cent for NSAID use, 34 per cent for paracetamol and 26 per cent for aspirin, all for for six or seven days a week. Similar risks were found when anal- gesic use was determined according to the number of tablets taken. The authors acknowledge the increased risk is modest, but point out that the implications may nonetheless be important because analgesics are widely used. Multiples do most pharmacist MURs Uptake of medicines use reviews (MURs) by pharmacists was modest in 2005 and most reviews were carried out by pharmacy chains rather than independent contractors, a new study has shown (Pharm J 2007;278:218-23). The survey of PCTs and SHAs in England and Wales found that, although 38 per cent of community pharmacies claimed payments for the service, 84 per cent of MURs were carried out by pharmacy chains. Uptake was low, amounting to only 7 per cent of the maximum possible number of MURs. Patients see information needs differently There is a mismatch in the perceptions of patients and health professionals about the purpose of written information about medicines, a systematic review has concluded (Health Technol Assess 2007;11:1-178). Some health professionals believe the main purpose of information is to promote compliance, whereas patients want information to help them make decisions about their treatment, including not taking it. In particular, patients want information on adverse effects, but health professionals have reservations about providing it. Aspirin for all women over 65? All women over 65 should take low-dose aspirin if the benefits are likely to outweigh the risk of adverse effects, according to new guidelines from the American Heart Association on preventing cardiovascular disease in women (published online 19 Feb 2007;doi: 10.1161/circulationaha.107.181546). The guidelines have moved away from the long-established Framingham model of risk assessment to categorising three levels of risk: high (heart disease or other relevant disease present), at risk (at least one risk factor) and optimal (healthy lifestyle, no risk factors). Low-dose aspirin is recommended for all women at high risk, for women aged 65 or over when reducing the risk of MI or ischaemic stroke outweighs the risk of adverse effects, and for younger women when reducing the risk of ischaemic stroke outweighs that of toxicity. Combination inhaler therapy Combining an inhaled long-acting bronchodilator with a steroid reduces COPD exacerbations but not all-cause mortality, a three-year trial has shown (N Engl J Med 2007;356:775-89). However, inhaled steroids appear to increase the risk of pneumonia. The TORCH trial randomised 6112 patients (FEV1<60 per cent predicted) to treatment with salmeterol 50µg plus fluticasone 500µg (Seretide) twice daily, salmeterol (Serevent) or fluticasone (Flixotide) as monotherapy, or placebo. All-cause mortality rates were 12.6, 13.5, 16.0 and 15.2 per cent respectively; the risk of death was 17 per cent lower with combined therapy, but the difference did not reach statistical significance. The combination reduced the incidence of exacerbations by 25 per cent and improved health status and FEV1. Use of fluticasone was not associated with more ocular or bone disorders, but there was an increased incidence of pneumonia among users (19.6 per cent with combined therapy and 18.3 per cent with fluticasone vs 12.3 per cent with placebo). Seretide is currently licensed in the UK for use in patients with FEV1 <50 per cent predicted. Tamoxifen long- term benefits Women with breast cancer who take tamoxifen for five to eight years continue to have a lower risk of recurrence for 10-20 years, long-term follow-up of two blinded trials has shown (J Nat Cancer Inst 2007; 99:258-60, 272-90). The frequency of adverse effects was markedly reduced when treatment ended, changing the balance of risk and benefit. Copyright © 2007 Wiley Interface Ltd [source]

Treatment of canine leproid granuloma syndrome: preliminary findings in seven dogs

AUSTRALIAN VETERINARY JOURNAL, Issue 1 2001
R MALIK
Objective To determine effective treatment strategies for patients with refractory canine leproid granuloma syndrome. Design Multi-institutional retrospective/prospective case series using client-owned dogs. Procedure Seven dogs (four Boxers, one Dobermann, one Bullmastiff and one Bullmastiff cross-bred; ages 3 to 11 years) with leproid granulomas were treated successfully using a variety of treatment regimens. These cases were recruited because: lesions were either widely distributed over the dog; progressive, despite routine therapy, or were associated with particularly disfiguring lesions. The treatment regimen evolved during the course of the clinical study. Results Combination therapy using rifampicin (5 to 15 mg/kg PO, every 24 h) and clarithromycin (8 to 24 mg/kg PO daily; dose divided every 8 or every 12 h) was used most frequently and proved to be effective and free from side effects. Total daily doses of clarithromycin in excess of 14 mg/kg were considered optimal and long treatment courses, in the order of 1 to 3 months, were used. Combination therapy using rifampicin (25 mg/kg; that is, higher than the recommended dose) and clofazimine was effective in one case, but resulted in hepatotoxicity. A topical formulation of clofazimine in petroleum jelly was used as an adjunct to oral rifampicin and doxycycline in another patient treated successfully. Conclusion Based on our evolving clinical experience, a combination of rifampicin (10 to 15 mg/kg PO, every 24 h) and clarithromycin (15 to 25 mg/kg PO total daily dose; given divided every 8 to 12 h) is currently recommended for treating severe or refractory cases of canine leproid granuloma syndrome. Treatment should be continued (typically for 4 to 8 weeks) until lesions are substantially reduced in size and ideally until lesions have resolved completely. A topical formulation, containing clofazimine in petroleum jelly may be used as an adjunct to systemic drug therapy. Further work is required to determine the most cost effective treatment regimen for this condition. [source]

Evaluating Decision Rules for Nitrogen Fertilization

BIOMETRICS, Issue 2 2000
T. Antoniadou
Summary. It is important, both for farmer profit and for the environment, to correctly dose nitrogen fertilizer for crop growth. Fertilizer recommendations are embodied in decision rules, which give a recommended dose of nitrogen (N) as a function of information available at the time the decision is made. In this paper, we first propose a criterion for evaluating decision rules. The proposed criterion is the expectation of the objective function when the decision rule is implemented. The major problem here is the estimation of this criterion. Two estimators are considered, a model-based and a nonparametric estimator. A simulation study shows that, in essentially all cases, the nonparametric estimator is better or no worse than the model-based estimator. The bias in the nonparametric estimator is always very small. [source]

Vancomycin dosing assessment in intensive care unit patients based on a population pharmacokinetic/pharmacodynamic simulation

BRITISH JOURNAL OF CLINICAL PHARMACOLOGY, Issue 2 2010
Natalia Revilla
WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT , Despite the frequent use of vancomycin in intensive care unit (ICU) patients, few studies aimed at characterizing vancomycin population pharmacokinetics have been performed in this critical population. , Population pharmacokinetics coupled with pharmacodynamic analysis, in order to optimize drug exposure and hence antibacterial effectiveness, has been little applied in these specific patients. WHAT THIS STUDY ADDS , Our population model characterized the pharmacokinetic profile of vancomycin in adult ICU patients, higher distribution volume values (V) being observed when the patient's serum creatinine (CrSe) was greater than 1 mg dl,1. , Age and creatinine clearance (CLcr) were identified as the main covariates explaining the pharmacokinetic variability in vancomycin CL. , Our pharmacokinetic/pharmacodynamic (PK/PD) simulation should aid clinicians to select initial vancomycin doses that will maximize the rate of response in the ICU setting, taking into account the patient's age and renal function as well as the susceptibility of Staphylococcus aureus. AIM To estimate the vancomycin pharmacokinetic profile in adult ICU patients and to assess vancomycin dosages for increasing the likelihood of optimal exposure. METHODS Five hundred and sixty-nine concentration,time data from 191 patients were analysed using a population pharmacokinetic approach (NONMENÔ). External model evaluation was made in 46 additional patients. The 24 h area under the concentration,time curve (AUC(0,24 h)) was derived from the final model. Minimum inhibitory concentration (MIC) values for S. aureus were obtained from the EUCAST database. AUC(0,24 h) : MIC , 400 was considered as PK/PD efficacy index. The probability of different dosages attaining the target considering different strains of S. aureus and patient subgroups was estimated with Monte Carlo simulation. RESULTS Vancomycin CL showed a significant dependence on patient age and renal function whereas CrSe > 1 mg dl,1 increased V more than twofold. For our representative ICU patient, 61 years, 73 kg, CrSe= 1.4 mg dl,1, measured CLCr= 74.7 ml min,1, the estimated values were CL = 1.06 ml min,1 kg,1 and V= 2.04 l kg,1. The cumulative fraction of response for a standard vancomycin dose (2 g day,1) was less than 25% for VISA strains, and 33% to 95% for susceptible S. aureus, depending on patient characteristics. CONCLUSIONS Simulations provide useful information regarding the initial assessment of vancomycin dosing, the conventional dosing regimen probably being suboptimal in adult ICU patients. A graphic approach provides the recommended dose for any selected probability of attaining the PK/PD efficacy target or to evaluate the cumulative fraction of response for any dosing regimen in this population. [source]

Population pharmacokinetic analysis of varenicline in adult smokers

BRITISH JOURNAL OF CLINICAL PHARMACOLOGY, Issue 5 2009
Patanjali Ravva
WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT? , Several clinical pharmacology studies have characterized the pharmacokinetics of varenicline in young adult and elderly smokers and subjects with impaired renal function. , Varenicline pharmacokinetics is linear over the recommended dose range. , Varenicline total clearance is linearly related to its renal clearance. , Both are progressively reduced as renal function declines, which results in a progressive increase in varenicline systemic exposure and prolonged half-life. WHAT THIS STUDY ADDS? , This work provides an integrated model-based analysis of varenicline pharmacokinetics across multiple studies in the target patient population. , The model describes the impact of patient-specific covariates, such as renal function, and provides a rationale for dose adjustment. , The resulting model also provides a means to predict individual-specific drug exposures to clinical responses in subsequent analyses. AIMS To characterize the population pharmacokinetics of varenicline and identify factors leading to its exposure variability in adult smokers. METHODS Data were pooled from nine clinical studies consisting of 1878 subjects. Models were developed to describe concentration,time profiles across individuals. Covariates were assessed using a full model approach; parameters and bootstrap 95% confidence intervals (CI) were estimated using nonlinear mixed effects modelling. RESULTS A two-compartment model with first-order absorption and elimination best described varenicline pharmacokinetics. The final population parameter estimates (95% CI) were: CL/F, 10.4 l h,1 (10.2, 10.6); V2/F, 337 l (309, 364); V3/F, 78.1 l (61.9, 98.9); Q/F, 2.08 l h,1 (1.39, 3.79); Ka, 1.69 h,1 (1.27, 2.00); and Alag, 0.43 h (0.37, 0.46). Random interindividual variances were estimated for Ka[70% coefficient of variation (CV)], CL/F (25% CV), and V2/F (50% CV) using a block covariance matrix. Fixed effect parameters were precisely estimated [most with % relative standard error < 10 and all with % relative standard error < 25], and a visual predictive check indicated adequate model performance. CL/F decreased from 10.4 l h,1 for a typical subject with normal renal function (CLcr = 100 ml min,1) to 4.4 l h,1 for a typical subject with severe renal impairment (CLcr = 20 ml min,1), which corresponds to a 2.4-fold increase in daily steady-state exposure. Bodyweight was the primary predictor of variability in volume of distribution. After accounting for renal function, there was no apparent effect of age, gender or race on varenicline pharmacokinetics. CONCLUSIONS Renal function is the clinically important factor leading to interindividual variability in varenicline exposure. A dose reduction to 1 mg day,1, which is half the recommended dose, is indicated for subjects with severe renal impairment. [source]

Emergency Department Management of Acute Pain Episodes in Sickle Cell Disease

ACADEMIC EMERGENCY MEDICINE, Issue 5 2007
Paula Tanabe PhD
ObjectivesTo characterize the initial management of patients with sickle cell disease and an acute pain episode, to compare these practices with the American Pain Society Guideline for the Management of Acute and Chronic Pain in Sickle-Cell Disease in the emergency department, and to identify factors associated with a delay in receiving an initial analgesic. MethodsThis was a multicenter retrospective design. Consecutive patients with an emergency department visit in 2004 for an acute pain episode related to sickle cell disease were included. Exclusion criteria included age younger than 18 years. A structured medical record review was used to abstract data, including the following outcome variables: analgesic agent and dose, route, and time to administration of initial analgesic. Additional variables included demographics, triage level, intravenous access, and study site. Mann,Whitney U test or Kruskal,Wallis test and multivariate regression were used to identify differences in time to receiving an initial analgesic between groups. ResultsThere were 612 patient visits, with 159 unique patients. Median time to administration of an initial analgesic was 90 minutes (25th to 75th interquartile range, 54,159 minutes). During 87% of visits, patients received the recommended agent (morphine or hydromorphone); 92% received the recommended dose, and 55% received the drug by the recommended route (intravenously or subcutaneously). Longer times to administration occurred in female patients (mean difference, 21 minutes; 95% confidence interval = 7 to 36 minutes; p = 0.003) and patients assigned triage level 3, 4, or 5 versus 1 or 2 (mean difference, 45 minutes; 95% confidence interval = 29 to 61 minutes; p = 0.00). Patients from study sites 1 and 2 also experienced longer delays. ConclusionsPatients with an acute painful episode related to sickle cell disease experienced significant delays to administration of an initial analgesic. [source]

Renal function with delayed or immediate cyclosporine microemulsion in combination with enteric-coated mycophenolate sodium and steroids: results of follow up to 30 months post-transplant

CLINICAL TRANSPLANTATION, Issue 3 2007
Georges Mourad
Abstract:, Background:, In the multicenter, open-label Myriade study, renal transplant patients were randomized to early cyclosporine microemulsion (CsA-ME, day 0) or delayed CsA-ME (day 6) with enteric-coated mycophenolate sodium (EC-MPS), steroids and interleukin-2 receptor induction. One-yr results have been published previously. We now report the results of an extension study in which patients were followed up for a period of three yr post-transplant. Methods:, All patients completing the one-yr core study on-treatment were eligible to enter the extension study. Results:, Of the 203 patients, 153 completed the core trial on-treatment; 144 (94%) entered the extension study with a minimum follow-up of one yr (73 early CsA-ME, 71 delayed CsA-ME). In 75% of patients receiving EC-MPS during the extension, the recommended dose was administered (1440 mg/d). Median creatinine clearance remained constant (57 mL/min) at 12, 24 and 30 months post-transplant and was similar in the early and delayed CsA-ME groups as well as in subpopulations with or without delayed graft function. One patient in the early CsA-ME group died. No grafts were lost. The incidence of BPAR from time of transplant to the end of the extension study was 17% (24/139). Seven patients (5%) discontinued the extension study prematurely because of adverse events. Conclusion:, These results suggest that a regimen of CsA-ME, EC-MPS and steroids results in excellent survival rates with stable renal function over a mean follow-up of 30 months. Immediate introduction of CsA-ME has no deleterious effect on long-term renal function, even among patients with delayed graft function. [source]

Underdosing of Midazolam in Emergency Endotracheal Intubation

ACADEMIC EMERGENCY MEDICINE, Issue 4 2003
Mark J. Sagarin MD
Objectives: To determine whether midazolam, when used as an induction agent for emergency department (ED) rapid-sequence intubation (RSI), is used in adequate and recommended induction doses (0.1 to 0.3 mg/kg), and to compare the accuracy of the dosing of midazolam for ED RSI with the accuracy of dosing of other agents. Methods: The authors conducted a systematic query of a prospectively collected database of ED intubations using the National Emergency Airway Registry data, gathered in 11 participating EDs over a 16-month period. A data form completed at the time of emergency department intubation (EDI) enabled analysis of patients' ages, weights, and indications for EDI, as well as the techniques and drugs used to facilitate EDI. Data were analyzed to determine whether midazolam is used in recommended doses during RSI. Patients intubated with midazolam alone were compared with patients who received other induction agents for RSI. Results: Of 1,288 patients entered in the study, 1,023 (79%) underwent RSI. Of the 888 RSI patients with an age recorded, midazolam was used as the sole induction agent in 140 (16%). The mean (±SD) dosages of midazolam used in RSI were 2.6 (±1.7) mg in children (age , 18) and 3.7 (±2.5) mg in adults (age ,19); the mean (±SD) dosages by weight were 0.08 (±0.04) mg/kg in children and 0.05 (±0.03) mg/kg in adults. More than half (56%) of the children, and nearly all (92%) of the adults, received dosages lower than the minimum recommended dosage (0.1 mg/kg). Of patients who received barbiturates, only 21% of children and 21% of adults received a dose lower than the minimum recommended. When combined with another induction agent, midazolam was dosed similarly to when it was used alone: mean adult doses were 3.1 (±1.2) mg and 0.04 (±0.02) mg/kg. Conclusions: Underdosing of midazolam during ED RSI is frequent, and appears to be related to incorrect dosage selection, rather than to a deliberate intention to reduce the dose used. [source]

Alcohol exposure and paracetamol-induced hepatotoxicity

ADDICTION BIOLOGY, Issue 2 2002
STEPHEN M. RIORDAN
In contrast, serious hepatotoxicity at recommended or near-recommended doses for therapeutic purposes has been reported, mainly from the United States and in association with chronic alcohol use, leading to the widely held belief that chronic alcoholics are predisposed to paracetamol-related toxicity at relatively low doses. Yet the effects of alcohol on paracetamol metabolism are complex. Studies performed in both experimental animals and humans indicate that chronic alcohol use leads to a short-term, two- to threefold increase in hepatic content of cytochrome P4502E1, the major isoform responsible for the generation of the toxic metabolite from paracetamol, although increased oxidative metabolism of paracetamol at recommended doses has not been demonstrated clinically. A reduced hepatic content of glutathione, required to detoxify the reactive metabolite, has been documented in chronic alcoholics, due probably to associated fasting and malnutrition, providing a metabolic basis for any possible predisposition of this group to hepatotoxicity at relatively low paracetamol doses. Simultaneous alcohol and paracetamol ingestion reduces oxidative metabolism of paracetamol in both rodents and humans, predominantly as a consequence of depletion in cytosol of free NADPH. The possibilities that chronic alcohol use may predispose to paracetamol-related hepatotoxicity and that alcohol taken with paracetamol may protect against it, based on these metabolic observations, are examined in this review. [source]

The efficacy and safety of QVAR (hydrofluoroalkane-beclometasone diproprionate extrafine aerosol) in asthma (part 2): clinical experience in children

INTERNATIONAL JOURNAL OF CLINICAL PRACTICE, Issue 8 2004
C. P. Van Schayck
Summary QVAR [hydrofluoroalkane-134a beclometasone dipropionate (BDP)] produces equivalent asthma control to chlorofluorocarbon-based BDP inhalers, at approximately half the daily dose in adults, a probable consequence of the increased lung deposition of QVAR that results from its greater fine particle fraction. Recent studies have relied on the clinical experience with QVAR in adults as a basis for investigations in childhood asthma. Design considerations, such as the use of the breath-actuated AutohalerÔ delivery device and measurement of direct health benefits, account for problems of variation in inspiratory flow, handling difficulties and low airways resistance that are associated with children. QVAR appears to be well tolerated in children with no clinically relevant adverse effects on adrenal function, bone metabolism or growth at recommended doses. [source]

Comparative insecticidal power of three pyrethroids on netting

MEDICAL AND VETERINARY ENTOMOLOGY, Issue 1 2002
K. J. Adams
Abstract Adult mosquitoes, Anopheles gambiae Giles and Culex quinquefasciatus Say (Diptera: Culicidae), were exposed for 3 min to replicate samples of polyester netting cut from replicate bednets treated with pyrethroid insecticide formulations at the recommended concentration (alphacypermethrin SC at 40 mg ai/m2; cyfluthrin EW at 50 mg ai/m2; deltamethrin WT at 25 mg ai/m2), or treated with only a quarter of those dosages. After 4 months domestic use of the bednets in Malawi, chemical assays showed that pyrethroid deposits on the netting were somewhat less than the target concentrations. Comparing the pyrethroid bioassay results with Anopheles at both treatment concentrations, deltamethrin gave significantly higher mortality (99.7,100%) than the other compounds (alphacypermethrin 94,96%, cyfluthrin 80,89%). Culex bioassay mortality was lower (alphacypermethrin 56,74%; cyfluthrin 63,65%; deltamethrin 50,81%) and results with the three pyrethroid insecticides at their recommended doses did not differ significantly. [source]

Pyridoxine Hydrochloride Treatment of Carpal Tunnel Syndrome: A Review

NUTRITION REVIEWS, Issue 3 2004
Elaine Aufiero M.D.
It has been hypothesized that idiopathic carpal tunnel syndrome (CTS) is a manifestation of vitamin B6 deficiency. Some claim that B6 supplementation can alleviate symptoms. Others argue that pain relief occurs because of vitamin B6's anti-nociceptive properties or because B6 supplementation addresses an unrecognized peripheral neuropathy. Few studies on CTS and B6 employed electrodiagnostic techniques in diagnosis, and few showed a correlation between symptoms and improved electrodiagnostic parameters with supplementation. Other studies failed to measure or estimate B6 levels. Nevertheless, it appears reasonable to recommend vitamin B6 supplementation to people with CTS. Some patients will improve symptomatically with low risks of toxicity in recommended doses. [source]

Underutilization of gastroprotective measures in patients receiving nonsteroidal antiinflammatory drugs

ARTHRITIS & RHEUMATISM, Issue 8 2002
Walter Smalley
Objective To determine the frequency of use of recommended gastroprotective strategies in a cohort of patients receiving recurrent treatment with nonsteroidal antiinflammatory drugs (NSAIDs). Methods A cross-sectional study was performed using administrative data from the Tennessee Medicaid (TennCare) program. The study population consisted of 76,765 recurrent recipients of NSAIDs (NSAID users), comprising 24% of the 319,402 persons ages 50 years or older enrolled in the TennCare program from January 1999 through June 2000. Frequency of use of either of 2 recommended gastroprotective strategies, involving either traditional NSAIDs combined with recommended anti-ulcer cotherapy or use of a selective cyclooxygenase 2,inhibiting drug (coxib), was measured and categorized by risk for ulcer complication. Results Among this cohort of recurrent NSAID users, 16% received 1 of the 2 recommended gastroprotective therapies: 10% received traditional NSAIDs along with antiulcer drugs at the recommended doses and 6% received coxibs. Among those patients with ,2 risk factors for ulcer complications (age 75 years or older, peptic ulcer or gastrointestinal bleeding in the past year, or concurrent use of oral anticoagulants or corticosteroids), 30% received such gastroprotective therapy. Conclusion Use of recommended strategies to decrease ulcer complications in vulnerable populations is relatively uncommon. [source]

CANCER INPATIENTS MORPHINE USAGE: A NEW ENGLAND AREA SURVEY

AUSTRALIAN JOURNAL OF RURAL HEALTH, Issue 4 2003
John Trollor
ABSTRACT:,This is a one year study of the use of morphine in cancer patients in 10 inpatient facilities in the New England Area Health Service in the north-west of New South Wales. The study explored 170 admissions relating to 122 patients, most of whom were cared for by their general practitioners. The use of morphine in these cancer patients was compared with the recommendations made by the expert working group of the European Association of Palliative Care.1 Those items which matched the recommendations included the initial doses for new users of morphine and the subcutaneous route being the preferred parenteral route. The data in this study differed from the recommendations in that only half of the patients received the immediate release morphine when first given oral morphine, only 43% had orders for immediate release oral morphine for breakthrough pain (with a variable frequency) and a significant number of orders for parenteral and immediate release oral morphine for breakthrough pain were outside the recommended doses (100% and 86.2%, respectively). Written orders for immediate release oral and parenteral morphine involved a dose range in significant numbers while only 30% of patients had orders for parenteral morphine for breakthrough pain. There was a low use of fixed interval variable dose (FIVD) morphine charts despite these being available in most facilities. (See summary Appendix A.) [source]