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Selected AbstractsCarvedilol Produces Sustained Long-Term Benefits: Follow-Up at 12 YearsCONGESTIVE HEART FAILURE, Issue 1 2009John F. MacGregor MD The authors measured long-term outcomes of patients who initiated carvedilol between 1990 and 1992 to test the hypothesis that carvedilol produces sustained benefits in heart failure patients. The study population consisted of 57 patients who completed a carvedilol placebo-controlled phase II trial. Patients were given open-label carvedilol and were titrated to the maximum dose. Patients were assessed by serial multigated acquisition, echocardiography, and symptom scores. Survival was assessed for all patients and censored as of January 1, 2004. Survival for ischemic vs nonischemic patients was compared using the log-rank test and further compared using Cox regression, controlling for covariates. Etiology of heart failure was ischemic in 15 patients and nonischemic in 42 patients. Median follow-up was 12.9 years. Resting left ventricular ejection fraction (LVEF) and heart failure symptom scores improved at 4 months of treatment and were sustained at 24 months. Left ventricular internal diameter in systole (LVIDS) and left ventricular internal diameter in diastole decreased significantly at 4 and 8 months, respectively, and LVIDS continued to improve at 24 months. Overall mortality was 43% in nonischemic patients and 73% in ischemic patients. In a multivariate analysis, ischemic etiology and baseline LVEF were significant predictors of mortality. Carvedilol produces sustained improvements in left ventricular remodeling and symptoms. Long-term survival is good, particularly in nonischemic patients. [source] Effectiveness of antipsychotic polypharmacy for patients with treatment refractory schizophrenia: an open-label trial of olanzapine plus risperidone for those who failed to respond to a sequential treatment with olanzapine, quetiapine and risperidoneHUMAN PSYCHOPHARMACOLOGY: CLINICAL AND EXPERIMENTAL, Issue 6 2008Takefumi Suzuki Abstract Objective To evaluate the effectiveness of antipsychotic polypharmacy in a methodologically sound manner. Methods In this open-label study, 17 patients with treatment-refractory schizophrenia, who failed to respond to a sequential monotherapy with olanzapine, quetiapine and risperidone, were subsequently treated with a combination therapy with olanzapine plus risperidone for at least 8 weeks. Results Seven responded according to the primary endpoint defined as the post-treatment Brief Psychiatric Rating Scale being less than 70% of the pretreatment values, and they were classified as such an average of 10 weeks after the initiation of polypharmacy. Two of them were successful in a later conversion to monotherapy. None dropped out prematurely. Four (out of 13 inpatients) got better enough to be discharged from the hospital, while six patients did not show any response. The Global Assessment of Functioning score improved from 37.1 to 53.0 in responders (mean maximum dose: olanzapine 12.9,mg; risperidone 3.14,mg), while it showed non-significant changes among others (mean maximum dose: olanzapine 14.5,mg; risperidone 5.50,mg). Body weight, prolactin, and total cholesterol increased significantly. Conclusions Antipsychotic polypharmacy might be sometimes helpful for difficult populations but at the cost of adverse effects. More studies of antipsychotic combination therapy versus clozapine, augmentation strategies or tenacious longer- term monotherapy are warranted for refractory schizophrenia. Copyright © 2008 John Wiley & Sons, Ltd. [source] Dosimetric comparison of intensity modulated radiotherapy techniques and standard wedged tangents for whole breast radiotherapy*JOURNAL OF MEDICAL IMAGING AND RADIATION ONCOLOGY, Issue 1 2009Andrew Fong Summary Prior to introducing intensity modulated radiotherapy (IMRT) for whole breast radiotherapy (WBRT) into our department we undertook a comparison of the dose parameters of several IMRT techniques and standard wedged tangents (SWT). Our aim was to improve the dose distribution to the breast and to decrease the dose to organs at risk (OAR): heart, lung and contralateral breast (Contra Br). Treatment plans for 20 women (10 right-sided and 10 left-sided) previously treated with SWT for WBRT were used to compare (a) SWT; (b) electronic compensators IMRT (E-IMRT); (c) tangential beam IMRT (T-IMRT); (d) coplanar multi-field IMRT (CP-IMRT); and (e) non-coplanar multi-field IMRT (NCP-IMRT). Plans for the breast were compared for (i) dose homogeneity (DH); (ii) conformity index (CI); (iii) mean dose; (iv) maximum dose; (v) minimum dose; and dose to OAR were calculated (vi) heart; (vii) lung and (viii) Contra Br. Compared with SWT, all plans except CP-IMRT gave improvement in at least two of the seven parameters evaluated. T-IMRT and NCP-IMRT resulted in significant improvement in all parameters except DH and both gave significant reduction in doses to OAR. As on initial evaluation NCP-IMRT is likely to be too time consuming to introduce on a large scale, T-IMRT is the preferred technique for WBRT for use in our department. [source] Pathological gambling in Parkinson's disease: Risk factors and differences from dopamine dysregulation.MOVEMENT DISORDERS, Issue 12 2007An analysis of published case series Abstract Pathological gambling (PG) has been reported as a complication of the treatment of Parkinson's disease (PD). We examined all published cases of PG for prevalence and risk factors of this complication, the relationship of PG and use of dopamine agonists (DA), and the relationship of PG to the dopamine dysregulation syndrome (DDS). The prevalence of PG in prospective studies of PD patients using DA has been reported between 2.3 and 8%, compared to approximately 1% in the general population. As in the general population, PD patients with this complication are often young, male and have psychiatric co-morbidity. The vast majority are on DA, often at maximum dose or above. Differences between oral DA failed to reach significance. PG associated with levodopa monotherapy is uncommon, but in the majority of cases levodopa is co-prescribed, suggesting possible cross-sensitization of brain systems mediating reward. PG can occur with DDS but often occurs in isolation. In contrast to DDS, escalation and self regulation of anti-parkinsonian medication are not usually seen. PG in patients with PD using DA is higher than PG reported in the general population, but shares similar characteristics and risk factors. PG is predominantly associated with oral DA. It often occurs in isolation and may not be associated with DDS, which typically occurs on treatment with levodopa or subcutaneous apomorphine. © 2007 Movement Disorder Society [source] A double blind randomized placebo control trial of levetiracetam in tourette syndromeMOVEMENT DISORDERS, Issue 12 2007Constance L. Smith-Hicks MD Abstract The objective of this study was to investigate the effectiveness of levetiracetam for the treatment of tics in children with Tourette syndrome (TS). Levetiracetam, an atypical anticonvulsant, has been suggested in open-label protocols to be an effective tic-suppressing agent in individuals with TS. A double blind, randomized, placebo-controlled, cross-over trial was performed to investigate this medication in children with moderate to moderately-severe tics. Subjects received, in a randomized sequence, 4-weeks of levetiracetam (maximum dose 30 mg/kg/day) or placebo, with a 2-week intervening washout period between cycles. Primary outcome measures included two separate scales from the Yale Global Tic Severity Scale; the Total Tic score and the Total overall score. Measures were assessed at baseline, prior to randomization, on Day 28 (end of Phase 1), on Day 42 (baseline for second phase) and on Day 70 (end of Phase 2). Twenty-two subjects (21 boys and 1 girl) with TS, mean age 12.2 ± 2.3 years, range 8 to 16 years, participated. A mild reduction in tics occurred during both the levetiracetam and placebo treatment phases. There was no significant difference between treatments and no evidence of sequence or cross-over effects. In conclusion, Levetiracetam is not more beneficial than placebo in suppressing tics in children with TS. © 2007 Movement Disorder Society [source] Analysis of optimal controls for a mathematical model of tumour anti-angiogenesisOPTIMAL CONTROL APPLICATIONS AND METHODS, Issue 1 2008U. Ledzewicz Abstract Anti-angiogenic therapy is a novel treatment approach for cancer that aims at preventing a tumour from developing its own blood supply system that it needs for growth. In this paper we consider a mathematical model where the endogenous stimulation term in the dynamics is taken proportional to the number of endothelial cells. This system is an example from a class of mathematical models for anti-angiogenic treatment that were derived from a biologically validated model by Hahnfeldt, Panigrahy, Folkman and Hlatky. The problem how to schedule a given amount of angiogenic inhibitors to achieve a maximum reduction in the primary cancer volume is considered as an optimal control problem and it is shown that optimal controls are bang-bang of the type 0a0 with 0 denoting a trajectory corresponding to no treatment and a a trajectory with treatment at maximum dose along that all inhibitors are being exhausted. Copyright © 2007 John Wiley & Sons, Ltd. [source] Favorable response of intraommaya topotecan for leptomeningeal metastasis of neuroblastoma after intravenous route failurePEDIATRIC BLOOD & CANCER, Issue 1 2008Nongnuch Sirachainan Abstract A 3-year-old male, diagnosed with stage 4 neuroblastoma, developed recurrent leptomeningeal metastasis after multi-modality treatment including multi-agent chemotherapy, surgery, high dose chemotherapy plus stem cell rescue, cis-retinoic acid and intravenous (IV) topotecan. He then received intraommaya (IO) topotecan three times weekly (maximum dose; 0.4 mg). A complete response was achieved by a resolution of malignant cells in cerebrospinal fluid and resolution leptomeningeal enhancement by brain MRI. Treatment toxicities included low-grade fever and minimal headache. The duration of treatment response from IO topotecan was 18 weeks. The survival time from CNS recurrence in this patient was 13 months. We suggest IO topotecan be considered for neoplastic meningitis of tumors with known sensitivity to topotecan. Pediatr Blood Cancer 2008;50:169,172. © 2006 Wiley-Liss, Inc. [source] Mycophenolate mofetil without antibody induction in cadaver vs. living donor pediatric renal transplantationPEDIATRIC TRANSPLANTATION, Issue 2 2003O. Ojogho Abstract: Mycophenolate mofetil (MMF) is a new immunosuppressive agent that blocks de novo purine synthesis in T and B lymphocytes via a potent selective inhibition of inosine monophosphate dehydrogenase. MMF has been shown to significantly reduce the incidence of acute rejection in both adult and pediatric renal transplantation. The impact of MMF on routine antibody induction therapy in pediatric renal transplantation has not been defined. Remarkably, a recent North American Pediatric Transplant Cooperative Study concluded that T-cell antibody induction therapy was deleterious for patients who received MMF. Our study examines the use of MMF in an evolving immunosuppressive strategy to avoid antibody induction in both living (LD) and cadaver (CAD) donor pediatric renal transplantation. We retrospectively analyzed the records of 43 pediatric renal transplants that received MMF-based triple therapy without antibody induction therapy between November 1996 and April 2000. We compared CAD (n = 17) with LD (n = 26). The two groups were similar demographically except that CAD had significantly younger donors than LD, 26.1 ± 13.7 vs. 36.2 ± 9.2 yr (p = 0.006). All the patients received MMF at 600 mg/m2/b.i.d. (maximum dose of 2 g/d) and prednisone with cyclosporine (86%) or tacrolimus (14%). Mean follow-up was >36 months for each group. Acute rejection rate at 6 months was 11.8% (CAD) vs. 15.4% (LD) (p = 0.999) and at 1 yr was 23.5% (CAD) vs. 26.9% (LD) (p = 0.999). Mean estimated glomerular filtration rate (ml/min/1.73 m2) at 6 months was 73.3 ± 15.3 (CAD) vs. 87.6 ± 24.2 (LD) (p = 0.068). Patient survival at 1, 2, and 3 yr was 100, 100, and 100% for CAD vs. 100, 96, and 96% for LD, respectively. Graft survival at 1, 2, and 3 yr was 100, 100, and 94% for CAD vs. 96, 88, and 71% for LD, respectively. Graft loss in CAD was because of chronic rejection (n = 2) while in LD it was because of non-compliance (n = 6), post-transplant lymphoproliferative disorder (n = 1), and sepsis (n = 1). In conclusion, MMF without antibody induction in both CAD and LD pediatric renal transplantation provides statistically similar and effective prophylaxis against acute rejection at 6 months and 1 yr post-transplant. The short-term patient and graft survival rates are excellent, however, non-compliance remains a serious challenge to long-term graft survival. Additional controlled studies are needed to define the role of MMF without antibody induction therapy in pediatric renal transplantation. [source] Broad-band ultraviolet B phototherapy in zoster patients may reduce the incidence and severity of postherpetic neuralgiaPHOTODERMATOLOGY, PHOTOIMMUNOLOGY & PHOTOMEDICINE, Issue 5 2006Mir Hadi Aziz Jalali Background: Postherpetic neuralgia (PHN) is one of the common complications of herpes zoster infection, particularly in the elderly. Current therapeutic measures are only partially effective in the affected patients. As inflammatory mediators released by different cells play an important role in the pathogenesis of this neuropathic pain and with regard to the immunomodulatory effects of ultraviolet B (UVB) spectrum, we presumed that UVB phototherapy might be effective in the prevention of PHN. Method: This study was performed in two phases. Phase I was a prospective open controlled trial. Twenty-five patients with severe pain in the first 7 days of zoster rash were divided into two groups: the prevention group (n=12) received oral acyclovir (800 mg five times a day for 10 days) plus broad-band UVB to the affected dermatomes, starting with 20 mJ/cm2 and gradually increasing the dose by 10 mJ/cm2 each session to a maximum dose of 100 mJ/cm2. Treatment sessions were repeated three times a week until pain relief or to a maximum of 15 sessions. The control group (n=13), who had disease characteristics similar to the prevention group, received only oral acyclovir with the same dose. All patients reported their severity of pain on a verbal rating scale (VRS, score 0,4) before treatment and at 1 and 3 months' follow-up. In phase II of the study, five patients with established PHN (more than 3 months after rash onset) received UVB with the above-mentioned protocol. Results: A total of 17 patients older than 40 (10 females, seven males; mean age, 65.5 years; range: 47,82 years) who had intractable pain due to zoster infection received UVB in two phases of the study. In patients who received phototherapy in the first 7 days of rash, 58.33% and 83.33% were completely pain free at 1-and 3-month follow-up, respectively. The corresponding figure in the control group was significantly lower (38.46% at 1 month and 53.85% at 3 months). The severity of pain was also lower in the phototherapy group than the control group (mean VRS 2.50 vs. 3.28 at 3 months). None of the patients who were treated more than 3 months after rash onset (established PHN) experienced significant (more than 50%) pain relief. Conclusion: UVB phototherapy in the acute stage of zoster rash might reduce the incidence and severity of PHN. Treatment after 3 months does not seem to have a significant beneficial effect. [source] Latest news and product developmentsPRESCRIBER, Issue 21 2007Article first published online: 3 DEC 200 NSAIDs and SSRIs increase GI bleeding Taking an NSAID and an SSRI increases the risk of GI bleeding more than six-fold compared with taking neither drug, a meta-analysis shows (Aliment Pharmacol Ther online: 5 Oct 2007; doi:10.1111/j.1365-2036.20 07.03541.x). The analysis included four observational studies involving a total of 153 000 patients, and 101 cases reported in postmarketing surveillance. Compared with nonuse, the odds ratio for upper GI haemorrhage in patients taking an SSRI alone was 2.36; the number needed to harm (NNH) was 411 for one year's treatment in patients aged over 50 with no risk factors. For those taking an SSRI and an NSAID, it was 6.33 (NNH 106). Of 22 cases where treatment duration was known, the median time to onset of bleeding was 25 weeks and five occurred within one month. The MHRA warns of this interaction in its latest issue of Drug Safety Update, noting: ,corticosteroids, antiplatelet agents, and SSRIs may increase the risk of GI ulceration or bleeding. NSAIDs may enhance the effects of anticoagulants, such as warfarin'. MHRA warning on NSAID safety The MHRA reminds prescribers of new restrictions on prescribing piroxicam and the risks associated with ketorolac and ketoprofen in its latest Drug Safety Update (2007;1:Issue 3). Treatment with piroxicam should now only be initiated by a specialist as a second-line drug; patients currently taking it should be reviewed at the next routine appointment. Piroxicam is no longer indicated for any acute indications. These restrictions do not apply to topical piroxicam (Feldene gel). Ketorolac and ketoprofen are associated with a higher risk of adverse GI effects than other NSAIDs. The MHRA advises prescribers to adhere to the licensed indications that limit oral ketorolac therapy to seven days (two days for continuous iv or im use) and the maximum dose of ketoprofen to 100-200mg. Inhaled steroids may increase the risk of pneumonia in patients with COPD. In the TORCH study (N Engl J Med 2007;356:775-89), fluticasone (Flixotide) and fluticasone plus salmeterol (Seretide) were associated with a significantly increased risk compared with salmeterol alone. The MHRA recommends vigilance for signs of pneumonia or bronchitis in patients with COPD who are treated with inhaled steroids; affected patients should have their treatment reconsidered. Other issues reviewed in Drug Safety Update include: a more intense reaction after revaccination with the pneumococcal vaccine, Pneumovax II; exacerbation of osteonecrosis of the jaw by dental surgery in patients taking a bisphosphonate; a lower maximum dose for lorazepam (4mg for severe anxiety, 2mg for severe insomnia) rare reactions with botulinum toxin; and the cardiovascular safety and risk of fractures with the glitazones. Antibiotic resistance GPs who reduce their antibiotic prescribing achieve a significant reduction in bacterial resistance, a study from Wales has shown (Br J Gen Pract 2007;57:785-92). The analysis of 164 225 coliform isolates from urine samples submitted from 240 general practices found a 5.2 per cent decrease in ampicillin resistance in practices with the greatest reductions in total antibiotic prescribing. Overall, ampicillin resistance decreased by 1 per cent for every reduction of 50 amoxicillin prescriptions per 1000 patients. Trimethoprim resistance showed a similar trend. Mortality risk with discontinuing statins Patients who discontinue statin therapy after acute stroke are almost three times more likely to die than those who do not, an Italian study shows (Stroke 2007;38:2652-7). Follow-up of 631 patients discharged after acute stroke revealed that 39 per cent discontinued statin therapy. The hazard ratio for all-cause mortality in the first 12 months was 2.78 compared with those who continued treatment; this compared with a hazard ratio of 1.81 for stopping antiplatelet therapy. The authors argue that patient care should be improved during the transition from hospital to outpatient primary care. ACEI ± ARB = ADRs Combining an ACE inhibitor and an angiotensin-II receptor blocker increases the risk of adverse effects in patients with symptomatic left ventricular dysfunction, according to a US study (Arch Intern Med 2007;167:1930-6). Meta-analysis of four trials involving a total of 17 337 patients followed up for about two years showed that, compared with therapy including an ACE inhibitor, combined treatment increased the risk of stopping treatment due to adverse events by 38 per cent in patients with heart failure and by 17 per cent in patients with MI. The authors estimate that, for every 1,000 patients treated, 25 will discontinue treatment due to adverse effects and 17 will develop renal dysfunction. WOSCOPS: statin protection continues Pravastatin reduces the risk of death years after treatment has stopped, according to a follow-up of the WOSCOPS study (N Engl J Med 2007;357:1477-86). The West of Scotland Coronary Prevention Study originally randomised men with hypercholesterolaemia but no history of myocardial infarction (MI) to treatment with pravastatin or placebo. After five years, the combined incidence of death from CHD or nonfatal MI was reduced from 7.9 to 5.5 per cent in the treatment group. During the 10 years after completion of the trial, the incidence of the combined end-point was 8.6 per cent in those originally assigned to pravastatin and 10.3 per cent in the placebo group. All- cause mortality was also reduced over the entire 15-year period. The proportions of patients still taking a statin in the middle of this period, ie five years after the trial ended, were 39 per cent of the placebo group. Prescribing policies on HRT need reappraisal Health authorities should reconsider their policy on prescribing HRT, the International Menopause Society (IMS) says. In an open letter, the IMS says current safety concerns over HRT use are founded, but have been misinterpreted in observational studies, such as the Women's Health Initiative, that led to changes in guidelines. The IMS says HRT is the most effective treatment for vasomotor and urogenital symptoms and the risk:benefit profile is favourable until age 60. Low-dose oestrogen or the transdermal route of administration may lead to a more favourable risk profile. Flu vaccine does cut morbidity and mortality Following The Lancet's commentary doubting the effectiveness of flu vaccination (Lancet Infectious Diseases 2007;7:658-66), a US cohort study has found that it does reduce morbidity and mortality (N Engl J Med 2007;357:1373-81). The observational study included 713 872 person-seasons in older people living in the community over a 10year period from 1990 to 2000. Vaccination was associated with a 48 per cent reduction in the risk of death and a 27 per cent reduction in admission for pneumonia or flu. These benefits changed little in subgroups or with age. Copyright © 2007 Wiley Interface Ltd [source] Perospirone in the treatment of patients with deliriumPSYCHIATRY AND CLINICAL NEUROSCIENCES, Issue 1 2007TAKASHI TAKEUCHI phd Abstract, Perospirone is a recently developed atypical antipsychotic with potent serotonin 5-HT2 and dopamine D2 antagonist activity. Other atypical antipsychotics including risperidone, quetiapine and olanzapine have been widely used for treatment, not only for schizophrenia symptoms but also for delirium, because of their low potential to induce extrapyramidal disturbances. In the present study the effectiveness and safety of perospirone in patients with delirium are described. Thirty-eight patients with DSM-IV delirium were given open-label perospirone. To evaluate the usefulness of perospirone, scores from 13 severity items of the Delirium Rating Scale-Revised-98 were assessed. Data were gathered from October 2003 to September 2004. Perospirone was effective in 86.8% (33/38) of patients, and the effect appeared within several days (5.1 ± 4.9 days). The initial dose was 6.5 ± 3.7 mg/day and maximum dose of perospirone was 10.0 ± 5.3 mg/day. There were no serious adverse effects. However, increased fatigue (15.2%), sleepiness (6.1%), akathisia (3.0%) and a decline in blood pressure (3.0%) were observed. It is proposed that perospirone may be another safe and effective atypical antipsychotic drug for the treatment of delirium symptoms in hospitalized patients. This is a preliminary open trial, and further randomized double-blind placebo-controlled tests are needed. [source] Plant extract contact toxicities to various developmental stages of Colorado potato beetles (Coleoptera: Chrysomelidae)ANNALS OF APPLIED BIOLOGY, Issue 2 2006A. Gökçe Abstract The contact toxicities of methanol extracts from the nine plant species Hedera helix, Artemisia vulgaris, Xanthium strumarium, Humulus lupulus, Sambucus nigra, Chenopodium album, Salvia officinalis, Lolium temulentum and Verbascum songaricum were tested on the developmental stages of Colorado potato beetle (CPB) (Leptinotarsa decemlineata). About 2 mL of plant extract, 40% (w/w), was applied to the first instar to fourth instar larvae and adult beetles using a Potter spray tower. Most of the tested plant extracts caused relatively low mortality in all the beetle instars. Among the plant extracts, H. lupulus extract was the most toxic to all stages of the insect, except for the adult beetles. Larval mortality ranged from 40% in the fourth instars to 84% in the third instars. In a second series of experiments, dose,response bioassays using H. lupulus extract produced lethal concentration 50 (LC50) values ranging from 10%, 12%, 17% to 46% (w/w) active ingredient (plant material) for instars 1,4, respectively. This increasing mortality trend, however, did not extend to the adult stage where even the maximum dose of 40% plant material did not provide sufficient mortality to allow estimation of a LC50. These results demonstrated that the extract from H. lupulus has potential as an active ingredient in biological pesticides developed to manage larval instars of the CPB. The potential uses of this plant extract may be in conventional and organic pest management or as part of a mixture of plant extracts or conventional insecticides. Before extracts can be considered as biological control agents, their impact on natural enemies should be assessed. [source] Long-term safety and effectiveness of etanercept in children with selected categories of juvenile idiopathic arthritis,ARTHRITIS & RHEUMATISM, Issue 9 2009E. H. Giannini Objective This study was undertaken to evaluate the long-term safety and effectiveness of etanercept alone or in combination with methotrexate (MTX) in children with selected categories of juvenile idiopathic arthritis (JIA). Methods Patients ages 2,18 years with rheumatoid factor (RF),positive or RF-negative polyarthritis, systemic JIA, or extended oligoarthritis were eligible for the study. Patients received MTX alone (,10 mg/m2/week [,0.3 mg/kg/week], maximum dosage 1 mg/kg/week), etanercept alone (0.8 mg/kg/week, maximum dose 50 mg), or etanercept plus MTX for 3 years in an open-label, nonrandomized study. Safety was assessed by measuring rates of adverse events, and effectiveness was assessed using the physician's global assessment of disease activity and the pediatric total joint assessment. Results A total of 197, 103, and 294 patients were enrolled in the MTX, etanercept, and etanercept plus MTX groups, respectively. Exposure-adjusted rates of adverse events were similar among the 3 treatment groups (18.3, 18.7, and 21.6 per 100 patient-years in the MTX, etanercept, and etanercept plus MTX groups, respectively). Respective rates per 100 patient-years of serious adverse events (4.6, 7.1, and 6.0) and medically important infections (1.3, 1.8, and 2.1) were also similar among the 3 treatment groups. Scores for physician's global assessment and total active joints improved from baseline, and improvement was maintained for the duration of the study. Conclusion These data confirm the findings of other long-term studies and suggest that etanercept or etanercept plus MTX has an acceptable safety and effectiveness profile in children with selected categories of JIA. Improvement was maintained for 3 years in those continuing to receive medication. [source] Determining the Optimal Dose of Intravenous Fat Emulsion for the Treatment of Severe Verapamil Toxicity in a Rodent ModelACADEMIC EMERGENCY MEDICINE, Issue 12 2008Eric Perez MD Abstract Objectives:, Recent animal studies have shown that intravenous fat emulsion (IFE) increases survival and hemodynamics in severe verapamil toxicity. However, the optimal dose of IFE is unknown. The primary objective was to determine the optimal dose of IFE based on survival in severe verapamil toxicity. Secondary objectives were to determine the effects on hemodynamic and metabolic parameters. The hypothesis was that there is a dose-dependent effect of IFE on survival until a maximum dose is reached. Methods:, This was a controlled dose-escalation study. Thirty male rats were anesthetized, ventilated, and instrumented to record mean arterial pressure (MAP) and heart rate (HR). Verapamil toxicity was achieved by a constant infusion of 15 mg/kg/hr. After 5 minutes, a bolus of 20% IFE was given. Animals were divided into six groups based on differing doses of IFE. Arterial base excess (ABE) was measured every 30 minutes. Data were analyzed with analysis of variance. Results:, The mean survival time for each dose of IFE was 0 mL/kg = 34 minutes, 6.2 mL/kg = 58 minutes, 12.4 mL/kg = 63 minutes, 18.6 mL/kg = 143.8 minutes, 24.8 mL/kg = 125.6 minutes, and 37.6 mL/kg = 130 minutes. Post hoc testing determined that the 18.6 mL/kg dose resulted in the greatest survival when compared to other doses. It increased survival 107.2 minutes (p = 0.004), 91.2 minutes (p = 0.001), and 80.8 minutes (p = 0.023) when compared to the lower doses of 0, 6.2, and 12.4 mL/kg, respectively. There was no added benefit to survival for doses greater than 18.6 mL/kg. The secondary outcomes of HR, MAP, and ABE showed the most benefit with 24.8 mL/kg of IFE at both 30 and 60 minutes. Conclusions:, The greatest benefit to survival occurs with 18.6 mL/kg IFE, while the greatest benefit to HR, MAP, and BE occurs at 24.8 mL/kg IFE. The optimal dose for the treatment of severe verapamil toxicity in this murine model was 18.6 mL/kg. [source] Effects of lamotrigine in patients with bipolar disorder and alcohol dependenceBIPOLAR DISORDERS, Issue 3 2006Gabriel Rubio Background:, Bipolar disorder is significantly associated with alcohol use disorders. Anticonvulsant drugs are used in the treatment of bipolar disorder and they have also been used to treat alcohol dependence. The purpose of the present study was to evaluate tolerance and safety of lamotrigine in a dual-diagnosis population presenting bipolar disorder and alcohol dependence. Open-label lamotrigine was examined in 28 outpatients with DSM-IV bipolar disorder and alcohol dependence. Lamotrigine was added to existing medication regimens. Method:, Lamotrigine was started at a dose of 25 mg/day and titrated to a maximum dose of 300 mg/day. Subjects received a baseline evaluation which included a Structured Clinical Interview for DSM-IV (SCID) and weekly assessments for 12 weeks with the Hamilton Rating Scale for Depression (HAM-D), Young Mania Rating Scale (YMRS), Brief Psychiatric Rating Scale (BPRS), Severity of Alcohol Dependence Scale (SADS), a Visual Analogue Scale for Craving severity (VASC), and alcohol consumption. The concentration of carbohydrate-deficient transferrin (CDT) was used as an indirect measure of alcohol consumption. The sample consisted of 18 men and 10 women diagnosed with alcohol dependence and bipolar disorder I (n = 21) or bipolar disorder II (n = 7), with a mean age of 36.5 ± 7.7 years. Results:, Significant improvement was observed in HAM-D, YMRS, and BPRS scores (p < 0.01). Craving and CDT also significantly decreased (p < 0.001). Lamotrigine was well tolerated with no dropout subjects due to adverse events. Conclusion:, Lamotrigine is safe and well tolerated in this sample and associated with improvement in mood, alcohol craving and alcohol consumption. A placebo-controlled study would be of interest. [source] A lower dose of thalidomide is better than a high dose in metastatic renal cell carcinomaBJU INTERNATIONAL, Issue 4 2005Sandy Srinivas OBJECTIVE To conduct a dose-finding trial using a single low dose and dose escalation of a higher dose of thalidomide in patients with metastatic renal cell carcinoma (RCC), and to evaluate the antineoplastic effectiveness of thalidomide as an anti-angiogenic agent on RCC. PATIENTS AND METHODS The 14 patients enrolled in the study had progressive measurable metastatic RCC and consented to participate. Patients were randomized to either a fixed low dose of 200 mg of thalidomide or to a high dose of 800 mg that was increased to a maximum dose of 1200 mg daily. Patients were evaluated for response after 8 weeks of therapy. RESULTS Stable disease was achieved in six patients and was seen in both the low-dose and high-dose thalidomide groups. The median overall survival was 9 months. The low-dose thalidomide regimen was better tolerated and patients survived longer than those on the high-dose regimen (16 vs 6 months, P = 0.04) CONCLUSION The use of low-dose thalidomide in patients with metastatic RCC was well tolerated and they survived for longer than those on the high-dose regimen. [source] Results from different patient populations using combined therapy with alprostadil and sildenafil: predictors of satisfactionBJU INTERNATIONAL, Issue 4 2000J.H. Mydlo Objective To evaluate the outcome of combined therapy (using intraurethral alprostadil and oral sildenafil) in private and clinic patients with erectile dysfunction, and thus assess predictors of satisfaction. Patients and methods In all, 360 men were treated for erectile dysfunction using single and/or combined therapy, comprising 214 private-practice and 166 clinic patients. Responses were evaluated using the International Index for Erectile Function (IIEF) questionnaire before and after treatment. Serum testosterone levels, education and socio-economic status were also assessed. Group 1a consisted of 33 private patients and Group 1b of 24 clinic patients who tried the maximum dose of intraurethral alprostadil monotherapy initially, followed by the maximum dose of sildenafil monotherapy, and remained dissatisfied. Group 2a consisted of 32 private patients and group 2b of 31 clinic patients who tried the maximum dose of sildenafil monotherapy initially, followed by the maximum dose of alprostadil monotherapy, and were also dissatisfied. These two groups of 65 private and 55 clinic patients then underwent combined therapy. Results The mean ( sd) score for erectile function was 24.1 (2) for combined therapy (a 123% improvement), and 19.8 (1.8) (83% improvement) and 15.2 (1.6) (41% improvement) for sildenafil and alprostadil monotherapies (P < 0.05 for both patient groups). The men also reported an improvement in their satisfaction with intercourse. However, at 18 months, 60 of the 65 private patients but only 40 of the 55 clinic patients continued with combined therapy; thus, the discontinuation rate was three times greater among clinic than among private patients. Furthermore, the private patients had an overall improvement in the satisfaction score of 128%, compared with 51% for the clinic patients. Conclusion Although there were no significant differences in erectile function improvement within the two satisfied combined therapy groups, the differences in overall satisfaction and long-term withdrawal rates suggests that other factors beside motivation must be involved for success, e.g. education, persistence, realistic expectations, and certain psychological factors. Combined therapy should be considered for those patients who have a suboptimal response to monotherapy and refuse or are not candidates for surgical options. Generally, those patients with a higher education, greater persistence and more realistic expectations were more satisfied with combined therapy. [source] Methaemoglobinaemia risk factors with inhaled nitric oxide therapy in newborn infantsACTA PAEDIATRICA, Issue 10 2010I Hamon Abstract Background:, Inhaled nitric oxide (iNO), commonly used for hypoxic neonates, may react with haemoglobin to form methaemoglobin (MetHb). MetHb monitoring during iNO therapy has been questioned since low doses of iNO are used. Aim:, To evaluate the incidence of and identify risk factors associated with elevated MetHb in neonates treated with iNO. Methods:, Neonates who were treated with iNO and had at least one MetHb measurement were included. Demographic characteristics and methods of iNO administration (dosage, duration) at the time of each MetHb measurement were analysed. Results:, Four hundred and fifty-two MetHb measurements from 81 premature and 82 term and near-term infants were analysed. MetHb was above 5% in one-term infant, and between 2.5,5% in 16 infants. A higher maximum dose of iNO (22.7 vs 17.7 p.p.m.), but not gestational age, was a significant risk factor for elevated MetHb. Significantly higher oxygen levels (75.5% vs 51.7%) were associated with higher MetHb in term infants. Preterm infants had no risk for high MetHb when iNO was kept below 8 p.p.m. These data suggest the possibility of limiting blood withdrawal when low doses iNO are used. Conclusion:, High MetHb is exceptional in neonates treated with low dose iNO. Associated risk factors are related to high iNO dose and the simultaneous use of high concentrations of oxygen. [source] Potential medication dosing errors in outpatient pediatricsCHILD: CARE, HEALTH AND DEVELOPMENT, Issue 3 2006Robert M. Jacobson md Potential medication dosing errors in outpatient pediatrics . McPhillipsH.A., StilleC.J., SmithD., HechtJ., PearsonJ., StullJ., DebellisK.P., AndradeS., MillerM., KaushalR., GurwitzJ. & DavisR.L. ( 2005 ) Journal of Pediatrics , 147 , 761 , 767 . Objective To determine the prevalence of potential dosing errors of medication dispensed to children for 22 common medications. Study design The investigators used automated pharmacy data from three health maintenance organizations. Children were eligible if they were less than 17 years old at the time of dispensing. The investigators randomly selected up to 120 children with a new dispensing prescription for each drug of interest, giving 1933 study subjects. Errors were defined as potential overdoses or potential under-doses. The error rate in two health maintenance organizations that use paper prescriptions was compared with one health maintenance organization that uses an electronic prescription writer. Results Approximately 15% of children were dispensed a medication with a potential dosing error: 8% were potential overdoses and 7% were potential under-doses. Among children weighing less than 35 kg, only 67% of doses were dispensed within recommended dosing ranges, and more than 1% were dispensed at more than twice the recommended maximum dose. Analgesics were most likely to be potentially overdosed (15%), whereas anti-epileptics were most likely potentially under-dosed (20%). Potential error rates were not lower at the site with an electronic prescription writer. Conclusions Potential medication dosing errors occur frequently in outpatient paediatrics. Studies on the clinical impact of these potential errors and effective error prevention strategies are needed. [source] Rosiglitazone RECORD study: glucose control outcomes at 18 monthsDIABETIC MEDICINE, Issue 6 2007P. D. Home Abstract Aims To compare glucose control over 18 months between rosiglitazone oral combination therapy and combination metformin and sulphonylurea in people with Type 2 diabetes. Methods RECORD, a multicentre, parallel-group study of cardiovascular outcomes, enrolled people with an HbA1c of 7.1,9.0% on maximum doses of metformin or sulphonylurea. If on metformin they were randomized to add-on rosiglitazone or sulphonylurea (open label) and if on sulphonylurea to rosiglitazone or metformin. HbA1c was managed to , 7.0% by dose titration. A prospectively defined analysis of glycaemic control on the first 1122 participants is reported here, with a primary outcome assessed against a non-inferiority margin for HbA1c of 0.4%. Results At 18 months, HbA1c reduction on background metformin was similar with rosiglitazone and sulphonylurea [difference 0.07 (95% CI ,0.09, 0.23)%], as was the change when rosiglitazone or metformin was added to sulphonylurea [0.06 (,0.09, 0.20)%]. At 6 months, the effect on HbA1c was greater with add-on sulphonylurea, but was similar whether sulphonylurea was added to rosiglitazone or metformin. Differences in fasting plasma glucose were not statistically significant at 18 months [rosiglitazone vs. sulphonylurea ,0.36 (,0.74, 0.02) mmol/l, rosiglitazone vs. metformin ,0.34 (,0.73, 0.05) mmol/l]. Increased homeostasis model assessment insulin sensitivity and reduced C-reactive protein were greater with rosiglitazone than metformin or sulphonylurea (all P , 0.001). Body weight was significantly increased with rosiglitazone compared with sulphonylurea [difference 1.2 (0.4, 2.0) kg, P = 0.003] and metformin [difference 4.3 (3.6, 5.1) kg, P < 0.001]. Conclusions In people with diabetes, rosiglitazone in combination with metformin or sulphonylurea was demonstrated to be non-inferior to the standard combination of metformin + sulphonylurea in lowering HbA1c over 18 months, and produces greater improvements in C-reactive protein and basal insulin sensitivity but is also associated with greater weight gain. [source] Beta-cell function evaluated by HOMA as a predictor of secondary sulphonylurea failure in Type 2 diabetesDIABETIC MEDICINE, Issue 7 2001M. J Taverna Abstract Background and aims Secondary failure to oral hypoglycaemic agents, a common evolution of long-standing Type 2 diabetes, is usually assessed by non-standardized indices requiring fine clinical assessment, including hyperglycaemia resistant to maximum doses of sulphonylureas despite appropriate diet and follow-up. The goal of this study was to evaluate if HOMA, a modelized plasma insulin/glucose ratio allowing simple evaluation of residual insulin secretion and sensitivity, is a better predictor of the insulin requiring stage than clinical indices. Materials and methods HOMA was measured in 84 Type 2 diabetic patients aged 58 ± sd 6 years, with diabetes duration 11 ± 4 years, hospitalized because of hyperglycaemia resistant to maximal doses of sulphonylureas (e.g. glibenclamide ,,15 mg/day), with no apparent external reason for hyperglycaemia. Despite reinforced appropriate diet recommendations, 62 of these patients remained hyperglycaemic (insulin-requiring group). Results Age, duration of diabetes, body mass index (BMI) and HOMA value for insulin sensitivity (71 ± 6% vs. 76 ± 7%, normal values 59,161%) were comparable in the two groups. HbA1c was higher (10.0 ± 0.2% vs. 8.3 ± 0.3%, P < 0.001) and HOMA insulin secretion values lower (25 ± 2% vs. 43 ± 6%, normal values 70,150%, P < 0.01) in the insulin-requiring group. Of the following potential predictors: HbA1c >,8%, duration of diabetes ,,10 years, HbA1c combined with diabetes duration, insulin sensitivity ,,40%, insulin secretion ,,20%, the latter showed the best positive predictivity (86% patients with low insulin secretion were insulin-requiring). Conclusions (i) HOMA is a simple and good predictor of the insulin-requiring stage in Type 2 diabetes mellitus; (ii) this stage of diabetes is characterized by a further decline of insulin secretion rather than of insulin sensitivity. Diabet. Med. 18, 584,588 (2001) [source] Pregabalin, tiapride and lorazepam in alcohol withdrawal syndrome: a multi-centre, randomized, single-blind comparison trialADDICTION, Issue 2 2010Giovanni Martinotti ABSTRACT Introduction The aim of this trial was to compare lorazepam with non-benzodiazepine medications such as pregabalin and tiapride in the treatment of alcohol withdrawal syndrome (AWS). These drugs were chosen for their inhibitorial effects on the hypersecretion of neurotransmitters usually observed in AWS. Craving reduction and improvement of psychiatric symptoms were the secondary end-points. Methods One hundred and ninety subjects affected by current alcohol dependence were considered consecutively: 111 were enrolled and divided into three groups of 37 subjects each. Within a treatment duration of 14 days, medication was given up to the following maximum doses (pregabalin 450 mg/day; tiapride 800 mg/day; lorazepam 10 mg/day). Withdrawal (CIWA-Ar), craving [visual analogue scale (VAS); Obsessive and Compulsive Drinking Scale (OCDS)], psychiatric symptoms [Symptom Check List 90 Revised (SCL-90-R)] and quality of life (QL-index) rating scales were applied. Results On the CIWA-Ar score, all the groups showed a significant reduction between times (P < 0.001) with a higher reduction for the pregabalin group (P < 0.01) on items regarding headache and orientation. Retention in treatment was lower in the tiapride group (P < 0.05), while the number of subjects remaining alcohol free was higher in the pregabalin group (P < 0.05). Significant reduction between baseline and the end of the treatment was found in all the groups at the OCDS and the VAS for craving, at the SCL-90-R and QL-index (P < 0.001). Discussion All the medications in the trial showed evidence of safety and efficacy in the treatment of uncomplicated forms of AWS, with some particular differences. The efficacy of pregabalin was superior to that of tiapride, used largely in research trials and, for some measures, to that of the ,gold standard', lorazepam. Accordingly, pregabalin may be considered as a potentially useful new drug for treatment of AWS, deserving further investigation. [source] Interictal Psychoses in Comparison with Schizophrenia,A Prospective StudyEPILEPSIA, Issue 12 2007Yukari Tadokoro Summary Purpose: To prospectively investigate the incidence of interictal psychoses of epilepsy patients, and make a comparison between those with interictal psychoses and patients with schizophrenia in respect to their responses to antipsychotic drugs, as well as psychotic states. Methods: We undertook a two-part prospective investigation. In Part I, the psychotic episodes of 619 epilepsy patients were investigated, while 182 patients with psychotic syndromes were followed in Part II, of whom 59 were diagnosed with schizophrenia and 13 with epilepsy with interictal psychoses. The Positive and Negative Syndrome Scale was used for efficacy assessment. Results: The average annual incidence of interictal psychosis was 0.42% during the 56-month study period. A significant difference was found between patients with schizophrenia and epilepsy patients with interictal psychoses in respect to results on the negative subscale of the PANSS at the initial examination (mean scores of 18.1 and 13.2, respectively, p = 0.004). The response rates one year later for these groups were 27.1% and 53.8%, respectively, which showed a trend of better response to the antipsychotic medication by the epilepsy group (p = 0.098). Initial and maximum doses of antipsychotic drugs used for epilepsy patients with interictal psychoses were significantly lower than those used for patients with schizophrenia (p = 0.008 and p = 0.006, respectively). Conclusions: Schizophrenia and epileptic psychosis showed different symptom profiles. On average, epilepsy patients with interictal psychoses achieved higher remission rates with lower doses of antipsychotic drugs as compared to patients with schizophrenia in the present 1-year follow-up study. [source] A safety and tolerability laboratory study of the combination of aripiprazole and topiramate in volunteers who drink alcoholHUMAN PSYCHOPHARMACOLOGY: CLINICAL AND EXPERIMENTAL, Issue 6 2009George A. Kenna Abstract Objective There are no reports examining the safety of taking both topiramate and aripiprazole together with alcohol. The ultimate aim for this research is to determine whether this combination is safe and is superior to either drug taken alone in reducing alcohol use in alcohol dependent patients. Method This was an open-label trial. Thirteen heavy drinking participants not seeking treatment for alcoholism were randomized. Participants were titrated up to 300,mg of topiramate and 30,mg of aripiprazole a day over 35 days. Participants reported adverse events (AEs) daily alcohol use and participated in an alcohol challenge session (ACS). Results The eight participants who completed the study achieved the maximum doses of drugs. The AEs of the drugs would suggest that the AEs profile is broader but not additive. Alcohol use from the 28 days before screening to the seven days before the ACS was reduced (p,=,0.08). Conclusion There was no evidence that AEs of aripiprazole and topiramate are additive and can, therefore, be administered safely together with a modest amount of alcohol. There was also a trend for a reduction of alcohol use by participants. This finding has implications for further investigation of this combination of drugs for alcohol dependence. Copyright © 2009 John Wiley & Sons, Ltd. [source] CNSB004 (Leconotide) Causes Antihyperalgesia Without Side Effects When Given Intravenously: A Comparison with Ziconotide in a Rat Model of Diabetic Neuropathic PainPAIN MEDICINE, Issue 2 2010Anton Kolosov BSci Abstract Objective., Leconotide is an ,-conotoxin that blocks neuronal voltage sensitive calcium channels. This study compared the antihyperalgesic potencies of leconotide and ziconotide given intravenously alone and in combinations with a potassium channel modulator flupirtine, given intraperitoneally, in a rat model of diabetic neuropathic pain. Design., Rats were given streptozotocin (150 mg/kg ip) to induce diabetic neuropathy and hyperalgesia. Experiments were performed on diabetic rats with ,30% hyperalgesia to noxious heat. Rats were given each conopeptide alone and with flupirtine. Open field activity monitoring and non-invasive blood pressure measurements were used to define the maximum doses and combinations that caused no side effects. Doses in a range up to maximum no side effect doses were tested for antihyperalgesic effects in rats with hyperalgesia. Results., The maximum no side effect dose of leconotide (2 mg/kg intravenously) caused 51.7% reversal of hyperalgesia compared with 0.4% for the highest no side effect dose of ziconotide (0.02 mg/kg; P < 0.001, one-way anova). Leconotide caused dose-related antihyperalgesic effects that were potentiated by coadministration with flupirtine at doses that were ineffective when given alone. Leconotide (0.02 mg/kg) and flupirtine (5 mg/kg) caused 25.3 ± 7.6 and ,6 ± 9.5% reversal of hyperalgesia, respectively when given alone but in combination they caused 84.1 ± 7.2% reversal of hyperalgesia (P < 0.01; one-way anova). No such interaction occurred with ziconotide. Conclusion., Leconotide could have wider clinical applications than ziconotide. Unlike ziconotide, powerful antihyperalgesia without side effects can be achieved by intravenous administration of leconotide thus avoiding the need for an intrathecal injection. [source] Dermatosurgery Using Subcutaneous Infusion Anesthesia with Prilocaine and Ropivacaine in ChildrenPEDIATRIC DERMATOLOGY, Issue 6 2001Matthias Moehrle MD Pediatric surgical procedures under local anesthesia have been limited by the pain of injections and, because of low body weight, rapidly reached maximum doses. In subcutaneous infusion anesthesia (SIA) highly diluted local anesthetics are administered by flow- and volume-controlled infusion pumps. This article presents a retrospective review of the use of SIA in children undergoing excision of dermatologic problem lesions. A total of 354 surgical procedures, predominantly excisions of nevi in 271 children (3 months,16 years) were performed in 1999: 67 children were operated on under general anesthesia and 204 children with local anesthesia. For local anesthesia we used SIA with diluted prilocaine and ropivacaine (equivalent mixtures of 0.3%, 0.15%, 0.08%). The 67 children operated on under general anesthesia were younger (mean age 3.05 ± 2.93 years, median age 2.00 years) than the 204 children who had surgery with SIA (mean age 9.00 ± 4.2 years, median age 9.00 years). The sizes of excisions under general anesthesia were larger (maximum 1060 cm2, mean 76 ± 225 cm2, median 7 cm2) than those under SIA (maximum 628 cm2, mean 22 ± 100 cm2, median 3 cm2). No side effects of local anesthesia were observed in these pediatric procedures. The additional use of ropivacaine resulted in prolonged postoperative analgesia. SIA in children is a well-accepted, safe anesthesia that in some cases offers an alternative to general anesthesia. [source] | ||||||||||||||||||||||||||||