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Daily Dosage (daily + dosage)

Distribution by Scientific Domains

Medical Sciences	95%

Distribution within Medical Sciences

Pharmacology & Pharmaceutical Medicine	24%
Neurology	14%
Psychiatry	9%
9 Other Subdomains	53%

Selected Abstracts

10-Year trends in the treatment and outcomes of patients with first-episode schizophrenia

ACTA PSYCHIATRICA SCANDINAVICA, Issue 5 2010
J. Nielsen
Nielsen J, le Quach P, Emborg C, Foldager L, Correll CU. 10-Year trends in the treatment and outcomes of patients with first-episode schizophrenia. Objective:, The first episode of schizophrenia is a critical period for illness course and outcomes. We aimed to investigate treatments and outcomes during the first year after the diagnosis of schizophrenia. Method:, Pharmacoepidemiologic inception cohort study of all newly diagnosed patients with schizophrenia in Denmark (n = 13 600) 1996,2005. Results:, From 1996 to 2005, the mean age at first diagnosis decreased significantly (29.2,26.1 years), more patients received antipsychotics (67.2,80.7%, annual OR = 1.07, CI: 1.06,1.09, P < 0.001) and antipsychotic polypharmacy for >4 months (16.7,37.1%, OR = 1.14, CI: 1.12,1.57, P < 0.001). The antipsychotic defined daily dosage (DDD) doubled (150,332 DDD, P < 0.001), use of antidepressants (24.3,40.6%, P < 0.001). Bed days [89.9 days (CI: 81.8,98.8) to 71.8 days, CI: 63.7,80.8, P < 0.0001] decreased, whereas outpatient contacts [10.2 (CI: 9.5,11.0) to 21.4 (CI: 19.9,21.0), P < 0.0001] doubled. Conclusion:, Between 1996 and 2005, there was an earlier recognition of schizophrenia, intensified outpatient treatment, increased use and dosing of antipsychotics and antidepressants, but also more antipsychotic polypharmacy. [source]

Accumulation and DNA damage in fathead minnows (Pimephales promelas) exposed to 2 brominated flame-retardant mixtures, Firemaster® 550 and Firemaster® BZ-54

ENVIRONMENTAL TOXICOLOGY & CHEMISTRY, Issue 3 2010
Jonathan S. Bearr
Abstract Firemaster® 550 and Firemaster® BZ-54 are two brominated formulations that are in use as replacements for polybrominated diphenyl ether (PBDE) flame retardants. Two major components of these mixtures are 2,3,4,5-tetrabromo-ethylhexylbenzoate (TBB) and 2,3,4,5-tetrabromo-bis(2-ethylhexyl) phthalate (TBPH). Both have been measured in environmental matrices; however, scant toxicological information exists. The present study aimed to determine if these brominated flame-retardant formulations are bioavailable and adversely affect DNA integrity in fish. Fathead minnows (Pimephales promelas) were orally exposed to either FM 550, FM BZ54, or the nonbrominated form of TBPH, di-(2-ethylhexyl) phthalate (DEHP) for 56 d and depurated (e.g., fed clean food) for 22 d. At several time points, liver and blood cells were collected and assessed for DNA damage. Homogenized fish tissues were extracted and analyzed on day 0 and day 56 to determine the residue of TBB and TBPH and the appearance of any metabolites using gas chromatography-electron-capture negative ion mass spectrometry (GC/ECNI-MS). Significant increases (p,<,0.05) in DNA strand breaks from liver cells (but not blood cells) were observed during the exposure period compared with controls, although during depuration these levels returned to control. Both parent compounds, TBB and TBPH, were detected in tissues at approximately 1% of daily dosage along with brominated metabolites. The present study provides evidence for accumulation, metabolism, and genotoxicity of these new formulation flame retardants in fish and highlights the potential adverse effects of TBB- and TBPH-formulated fire retardants to aquatic species. Environ. Toxicol. Chem. 2010;29:722,729. © 2009 SETAC [source]

Catechol-O-methyltransferase val108/158met genotype and response to antipsychotic medication in schizophrenia

HUMAN PSYCHOPHARMACOLOGY: CLINICAL AND EXPERIMENTAL, Issue 4 2007
Ari Illi
Abstract Catechol-O-methyltransferase (COMT) gene has been investigated as a possible candidate gene in schizophrenia. The most studied polymorphism has been the functional val108/158met polymorphism of this COMT gene. There is also some evidence that this polymorphism could be related to drug response to antipsychotics in schizophrenia. COMT enzyme inactivates dopamine and noradrenaline. Based mainly on the original dopamine theory of schizophrenia, our primary hypothesis was that the maintenance dose of antipsychotics would be higher in patients with the low activity COMT genotype. In this study we evaluated the current daily dosage of antipsychotics in 180 patients with schizophrenia in connection with the COMT genotype. We could not demonstrate any clearly significant effect of this particular COMT genotype in relation to the daily maintenance dosages of antipsychotics in patients with schizophrenia. Copyright © 2007 John Wiley & Sons, Ltd. [source]

Effects of flexible-dose fesoterodine on overactive bladder symptoms and treatment satisfaction: an open-label study

INTERNATIONAL JOURNAL OF CLINICAL PRACTICE, Issue 4 2009
J.-J. Wyndaele
Summary Aims:, To evaluate the efficacy and tolerability of flexible-dose fesoterodine in subjects with overactive bladder (OAB) who were dissatisfied with previous tolterodine treatment. Methods:, This was a 12-week, open-label, flexible-dose study of adults with OAB (, 8 micturitions and , 3 urgency episodes per 24 h) who had been treated with tolterodine (immediate- or extended-release) for OAB within 2 years of screening and reported dissatisfaction with tolterodine treatment. Subjects received fesoterodine 4 mg once daily for 4 weeks; thereafter, daily dosage was maintained at 4 mg or increased to 8 mg based on the subject's and physician's subjective assessment of efficacy and tolerability. Subjects completed 5-day diaries, the Patient Perception of Bladder Condition (PPBC) and the Overactive Bladder Questionnaire (OAB-q) at baseline and week 12 and rated treatment satisfaction at week 12 using the Treatment Satisfaction Question (TSQ). Safety and tolerability were assessed. Results:, Among 516 subjects treated, approximately 50% opted for dose escalation to 8 mg at week 4. Significant improvements from baseline to week 12 were observed in micturitions, urgency urinary incontinence episodes, micturition-related urgency episodes and severe micturition-related urgency episodes per 24 h (all p < 0.0001). Approximately 80% of subjects who responded to the TSQ at week 12 reported satisfaction with treatment; 38% reported being very satisfied. Using the PPBC, 83% of subjects reported improvement at week 12 with 59% reporting improvement , 2 points. Significant improvements from baseline (p < 0.0001) exceeding the minimally important difference (10 points) were observed in OAB-q Symptom Bother and Health-Related Quality of Life (HRQL) scales and all four HRQL domains. Dry mouth (23%) and constipation (5%) were the most common adverse events; no safety issues were identified. Conclusion:, Flexible-dose fesoterodine significantly improved OAB symptoms, HRQL, and rates of treatment satisfaction and was well tolerated in subjects with OAB who were dissatisfied with prior tolterodine therapy. [source]

Nursing management of fever in children: A systematic review

INTERNATIONAL JOURNAL OF NURSING PRACTICE, Issue 1 2003
FRCNA, Robin Watts RN
ABSTRACT Objectives:, The aim of the present review was to determine whether the best available evidence supports the types and timing of the various nursing interventions that are commonly used to reduce fever in non-critically-ill children, and to what extent the outcomes are influenced by these nursing actions. Methods:, Studies included were randomised or quasi-randomised controlled trials that involved non-critically-ill children with a fever aged between 3 months and 16 years. ,,The search strategy sought to identify both published and unpublished research reports in the English language and covered all major databases up to 1998. ,,The methodological quality of each study was assessed by two independent reviewers using a piloted critical appraisal checklist. ,,Despite all studies being randomised, heterogeneity precluded conduction of a meta-analysis; therefore, evidence was synthesised using narrative summaries. Results: Ten studies were assessed as being of sufficient quality to be included in the review. These studies addressed two of the intervention categories identified in the protocol: (i) administration of antipyretics (paracetamol); and (ii) direct cooling measures on the outcome measure (reduction of or prevention of increase in fever). The review found little benefit from sponging in temperate climates and usually at the expense of the child's comfort. There may be situations in high environmental temperatures and high humidity, or where there is a need for immediate temperature reduction, in which sponging may be warranted. Risks were identified when paracetamol was administered on a sustained basis over even a short period of time and above a relatively low total daily dosage. There was a lack of evidence to support the administration of antipyretics to reduce the incidence of febrile convulsions. There is a need for parental education that focuses on knowledge of the body's protective physiological responses and how to support these responses. Conclusion: The primary purpose for intervening when a child has a fever is to increase the child's comfort. This consideration should be weighed against any harm that might result from intervening. There was a lack of evidence to support the routine use of sponging. The administration of paracetamol should be used selectively and with caution. In summary, care needs to be individualised, based on current knowledge of the effectiveness and risks of interventions. [source]

Recommended dietary allowance for vitamin C in the United States is also applicable to a population of young Japanese women

JOURNAL OF CLINICAL LABORATORY ANALYSIS, Issue 6 2004
Hiroshi Ihara
Abstract The recommended dietary allowance (RDA) for ascorbic acid (AA) in Canada and the United States has been set for several years at 75 mg/day for women 19,30 years old. Recently this level was questioned, and an increase to 90 mg/day was suggested. For Japanese women in the same age group, we found that the RDA for AA is currently 100 mg/day. Our goal was to determine which RDA is sufficient for maintaining a serum concentration of AA in young Japanese women above the lower reference limit of 7.0 mg/L. We measured serum AA concentrations by an ascorbate oxidase method in 176 healthy Japanese women (19,26 years old). We also performed an ROC analysis to estimate the optimal cutoff value for oral dosage to distinguish individuals with hypovitaminosis-C (<7.0 mg/L) from those with a normal serum AA. We evaluated the Japanese RDA using the 75 or 90 mg/day U.S. RDA and the weight ratio between Japanese and U.S. women, and discovered that the RDA value ranged between 66 and 79 mg/day. From the ROC analysis, we found that the optimal daily dosage of AA is approximately 75 mg/day. This value gave the highest efficiency, sensitivity, negative predictive value, and positive likelihood ratio, and the lowest negative likelihood ratio. Therefore, an RDA of 100 mg/day may be unnecessarily high for young Japanese women. J. Clin. Lab. Anal. 18:305,308, 2004. © 2004 Wiley-Liss, Inc. [source]

Effect of obesity on serum amiodarone concentration in Japanese patients: population pharmacokinetic investigation by multiple trough screen analysis

JOURNAL OF CLINICAL PHARMACY & THERAPEUTICS, Issue 3 2009
H. Fukuchi MS
Summary Objective:, To evaluate the influence of obesity on pharmacokinetics of amiodarone (AMD) using Non-Linear Mixed Effects Modelling (nonmem) in Japanese patients treated with oral therapy. Method:, Serum concentrations of AMD were determined by high performance liquid chromatography. One hundred and fifty-one trough concentrations from 23 patients receiving repetitive oral AMD were collected. Body mass index (BMI) and body fat percentage were measured. Results:, Estimates generated using nonmem indicated that the clearance of AMD was influenced by BMI, age and daily dosage of AMD. The final pharmacokinetic model was CL (L/h) = 0·16 · TBW · 0·53AGE , 65 · 0·78BMI , 25 · DD0·51, Vd (L) = 10·2 · TBW, where CL is total body clearance, TBW is total body weight (kg), DD (mg/kg/day) is daily dosage of AMD, AGE (years) ,65 = 1 for patient was 65 years old or over and 0 otherwise, BMI (kg/m2) ,25 = 1 for patient was 25 kg/m2 or over and 0 otherwise and Vd is apparent volume of distribution. The clearance of AMD decreased significantly by 22·3% with a BMI higher than 25 kg/m2. The clearance of AMD also decreased significantly by 46·9% when patient age was more than 65 years. Conclusion:, Population pharmacokinetic analysis confirms that obesity affects the pharmacokinetics of AMD. [source]

Conversion from mycophenolate mofetil to enteric-coated mycophenolate sodium in liver transplant patients presenting gastrointestinal disorders: A pilot study

LIVER TRANSPLANTATION, Issue 9 2006
Jérôme Dumortier
Gastrointestinal (GI) disorders are one of the main adverse events in patients treated by mycophenolic acid (MPA). The aim of this prospective study was to evaluate the effect of conversion from mycophenolate mofetil (MMF) to enteric-coated mycophenolate sodium (EC-MPS) in liver transplant patients presenting GI side-effects Since January 2003, stable liver transplant patients receiving MMF and presenting GI disorders, without evidence of other origin than MMF were enrolled. Conversion was performed without a washout period at an equimolar daily dosage. Thirty-six patients were included after a median delay of 45 months after liver transplantation (LT) (16 women and 20 men, median age of 47 years). Diarrhoea was the main clinical symptom (n = 28, 77.7%). At the time of inclusion, patients were treated with MMF since 18 months (range 3-28) and GI disorders were known for 9 months (range 3-12). After a median follow-up of 12 months after conversion, GI disorders were resolved in 20 patients (55%), improved in 6 patients (17%) and not modified or worsened in 10 patients (28%). Our results strongly suggest that conversion from MMF to EC-MPS in liver transplant patients can improve gastrointestinal disorders in a majority of the patients, and therefore might be considered as the best therapeutic option. Liver Transpl 12:1342-1346, 2006. © 2006 AASLD. [source]

Long-term follow-up of impulse control disorders in Parkinson's disease

MOVEMENT DISORDERS, Issue 1 2008
Eugenia Mamikonyan MS
Abstract Recent studies have linked dopamine agonist (DA) usage with the development of impulse control disorders (ICDs) in Parkinson's disease (PD). Little is known about optimal management strategies or the long-term outcomes of affected patients. To report on the clinical interventions and long-term outcomes of PD patients who developed an ICD after DA initiation. Subjects contacted by telephone for a follow-up interview after a mean time period of 29.2 months. They were administered a modified Minnesota Impulse Disorder Interview for compulsive buying, gambling, and sexuality, and also self-rated changes in their ICD symptomatology. Baseline and follow-up dopamine replacement therapy use was recorded and verified by chart review. Of 18 subjects, 15 (83.3%) participated in the follow-up interview. At follow-up, patients were receiving a significantly lower DA levodopa equivalent daily dosage (LEDD) (Z = ,3.1, P = 0.002) and a higher daily levodopa dosage (Z = ,1.9, P = 0.05), but a similar total LEDD dosage (Z = ,0.47, P = 0.64) with no changes in Unified Parkinson's Disease Rating Scale motor score (Z = ,1.3, P = 0.19). As part of ICD management, 12 (80.0%) patients discontinued or significantly decreased DA treatment, all of whom experienced full or partial remission of ICD symptoms by self-report, and 10 (83.3%) of whom no longer met diagnostic criteria for an ICD. For PD patients who develop an ICD in the context of DA treatment, discontinuing or significantly decreasing DA exposure, even when offset by an increase in levodopa treatment, is associated with remission of or significant reduction in ICD behaviors without worsening in motor symptoms. © 2007 Movement Disorder Society [source]

Gender differences in patients with Parkinson's disease treated with subthalamic deep brain stimulation

MOVEMENT DISORDERS, Issue 8 2007
Ettore Accolla MD
Abstract We investigated gender-differences in clinical phenomenology and response to deep brain stimulation (DBS) of the subthalamic nucleus (STN) in a group of patients with advanced Parkinson's disease (PD). Thirty-eight consecutive patients with PD (22 men and 16 women), bilaterally implanted for DBS of the STN, were evaluated 1 month before and 11 to 14 months after surgery. Gender differences in severity of the disease (HY and UPDRS), ability in the activities of daily living (ADL, UPDRS II), tremor and rigidity (UPDRS III), bradykinesia (UPDRS III and hand tapping test), levodopa-induced dyskinesias (LIDs, UPDRS IV), and levodopa equivalent daily dosage (LEDD) were analyzed before and after intervention. We found a predominantly male population, with no gender-related differences in age at onset, disease progression rate, or severity of disease. Nevertheless, women had more severe LIDs than men, only before the intervention. Bradykinesia was significantly less responsive to any kind of treatment (pharmacologic and neurosurgical) in women than in men. Finally, although STN-DBS induced similar total benefits in both genders, postoperative assessment suggested that the ADL improved more in women than in men. Women and men with advanced PD appear to differ in some clinical features and in response to dopaminergic and STN-DBS treatment. © 2007 Movement Disorder Society [source]

Sleep-Disordered Breathing and Chronic Opioid Therapy

PAIN MEDICINE, Issue 4 2008
Lynn R. Webster MD
ABSTRACT Objective., To assess the relation between medications prescribed for chronic pain and sleep apnea. Design., An observational study of chronic pain patients on opioid therapy who received overnight polysomnographies. Generalized linear models determined whether a dose relation exists between methadone, nonmethadone opioids, and benzodiazepines and the indices measuring sleep apnea. Setting., A private clinic specializing in the treatment of chronic pain. Patients., Polysomnography was sought for all consecutive (392) patients on around-the-clock opioid therapy for at least 6 months with a stable dose for at least 4 weeks. Of these, 147 polysomnographies were completed (189 patients declined, 56 were directed to other sleep laboratories by insurance companies, and data were incomplete for seven patients). Available data were analyzed on 140 patients. Outcome Measures., The apnea,hypopnea index to assess overall severity of sleep apnea and the central apnea index to assess central sleep apnea. Results., The apnea,hypopnea index was abnormal (,5 per hour) in 75% of patients (39% had obstructive sleep apnea, 4% had sleep apnea of indeterminate type, 24% had central sleep apnea, and 8% had both central and obstructive sleep apnea); 25% had no sleep apnea. We found a direct relation between the apnea,hypopnea index and the daily dosage of methadone (P = 0.002) but not to other around-the-clock opioids. We found a direct relation between the central apnea index and the daily dosage of methadone (P = 0.008) and also with benzodiazepines (P = 0.004). Conclusions., Sleep-disordered breathing was common in chronic pain patients on opioids. The dose,response relation of sleep apnea to methadone and benzodiazepines calls for increased vigilance. [source]

Evidence of effectiveness of herbal antiinflammatory drugs in the treatment of painful osteoarthritis and chronic low back pain

PHYTOTHERAPY RESEARCH, Issue 7 2007
J. E. Chrubasik
Abstract Treatment with herbal medicines is very popular in Europe. In order to get information on the evidence of effectiveness of oral herbal medicines in the treatment of pain in the joints or lower back, OVID(MEDLINE), PUBMED and COCHRANE COLLABORATION LIBRARY were searched back to 1985 for systematic reviews. The level of evidence of effectiveness was defined as strong , at least two confirmatory studies demonstrating a clinical relevant effect, moderate , one confirmatory study with a clinical relevant effect and/or multiple exploratory studies of good quality; otherwise the evidence was insufficient or conflicting in the case of inconsistent findings. Fifteen systematic reviews were identified. The evidence of effectiveness was strong for a proprietary unsaponifiable avocado soybean fraction and Harpagophytum preparations containing >50 mg harpagoside in the daily dosage, moderate for ginger and a proprietary rose hip and seed powder, insufficient for Boswellia serrata gum resin and other herbal preparations and inconsistent for a proprietary willow bark extract. Further rigorous studies are required to confirm the usefulness of herbal medicines in the treatment of osteoarthritic complaints and chronic low back pain in order to enable acceptance of the herbal medicines into the treatment guidelines. Copyright © 2007 John Wiley & Sons, Ltd. [source]

Glucocorticoids and cardiovascular events in rheumatoid arthritis: A population-based cohort study

ARTHRITIS & RHEUMATISM, Issue 3 2007
John M. Davis III
Objective To determine the relationship between glucocorticoid exposure and cardiovascular (CV) events in patients with rheumatoid arthritis (RA). Methods A total of 603 adult residents of Rochester, Minnesota with incident RA between 1955 and 1995 were followed up through their medical records for a median of 13 years (total of 9,066 person-years). Glucocorticoid exposure was defined 3 ways: tertiles of cumulative exposure; recent use (,3 months) versus past use (>3 months); and average daily dosage (,7.5 mg/day or >7.5 mg/day). CV events, including myocardial infarction, heart failure, and death from CV causes, were defined according to validated criteria. Cox regression models were adjusted for demographic features, CV risk factors, and RA characteristics. Results Rheumatoid factor (RF),negative patients with exposure to glucocorticoids were not at increased risk of CV events, irrespective of the glucocorticoid dosage or timing of use, as compared with the reference group of RF-negative patients who had never been exposed to glucocorticoids. In contrast, RF-positive patients were at increased risk of CV events, particularly with higher cumulative exposure, higher average daily dosage, and recent use of glucocorticoids. RF-positive patients with high cumulative exposure to glucocorticoids had a 3-fold increased risk of CV events (hazard ratio 3.06 [95% confidence interval 1.81,5.18]), whereas RF-negative patients with high cumulative exposure were not at increased risk (hazard ratio 0.85 [95% confidence interval 0.39,1.87]). Conclusion RF-positive but not RF-negative patients were at increased risk of CV events following exposure to glucocorticoids. These findings suggest that glucocorticoids interact with RF status to modulate the occurrence of CV events in patients with RA. The mechanisms underlying this interaction are unknown and should be the subject of further research. [source]

The CYP2D6 polymorphism in relation to the metabolism of amitriptyline and nortriptyline in the Faroese population

BRITISH JOURNAL OF CLINICAL PHARMACOLOGY, Issue 1 2008
Jónrit Halling
WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT ,,The metabolisms of amitriptyline (AT) to (E)-10-hydroxyamitriptyline and of nortripyline (NT) to (E)-10-hydroxynortriptyline are catalysed by CYP2D6. ,,A correlation between the sparteine metabolic ratio and the NT/(E)-10-hydroxynortriptyline and the AT/(E)-10-hydroxyamitriptyline ratios, respectively, has been observed in patients in treatment with the same dose of AT or NT. ,,The frequency of CYP2D6 poor metabolizers (PMs) is 15% (twofold compared with other Whites) among healthy Faroese. ,,This frequency has not been investigated in Faroese patients in AT treatment and the consequences of the CYP2D6 PM phenotype for dose and plasma concentrations of AT and metabolites are not known in these patients. WHAT THIS STUDY ADDS ,,In patients treated with different daily dosages (5,100 mg) of AT a correlation between the sparteine metabolic ratio and the NT/(E)-10-hydroxynortriptyline and AT/(E)-10-hydroxyamitriptyline ratios was observed. ,,A high proportion (22%) of CYP2D6 PMs in a Faroese patient group medicated with AT was observed. ,,However, similar doses of AT and concentrations of AT and NT were noted in extensive metabolizers and in PMs. AIM To determine the frequency of CYP2D6 poor metabolizers (PMs) in a Faroese patient group medicated with amitriptyline (AT) and to investigate plasma concentrations of AT and metabolites in relation to CYP2D6. METHODS CYP2D6 phenotype and genotype were determined in 23 Faroese patients treated with AT. Plasma concentrations of AT and metabolites were determined by high-performance liquid chromatography and investigated in relation to CYP2D6 activity. RESULTS Of the 23 patients phenotyped and genotyped, five (22%) (95% confidence interval 7.5, 43.7) were CYP2D6 PMs. No difference was found in AT daily dosage between PMs (median 25 mg day,1; range 5,80) and extensive metabolizers (EMs) (median 27.5 mg day,1; range 10,100). The (E)-10-OH-nortriptyline (NT)/dose concentrations were higher in EMs than in PMs and the NT/(E)-10-OH-NT and AT/(E) -10-OH-AT ratios were higher in PMs compared with EMs. The log sparteine metabolic ratio correlated positively with the NT/(E)- 10-OH-NT ratio (rs = 0.821; P < 0.0005) and the AT/(E)- 10-OH-AT ratio (rs = 0.605; P < 0.006). CONCLUSION A high proportion of CYP2D6 PMs was found in a Faroese patient group medicated with AT. However, similar doses of AT and concentrations of AT and NT were noted in EMs and PMs, probably due to varying doses and indications for AT treatment. [source]

The impact of zonisamide on weight.

ACTA NEUROLOGICA SCANDINAVICA, Issue 4 2009
A clinical study in 103 patients with epilepsy
Objective,,, To investigate the impact of zonisamide (ZNS) on body weight in patients with epilepsy. Methods,,, A retrospective chart analysis of weight changes after initiation of ZNS (103 patients; 54 female; age 17,68 years). For 31 patients follow-up data after ZNS-withdrawal were available. Patients were categorized according to body-mass-index (BMI) <20, 20,25, and >25 kg/m2. Results,,, Body weight before ZNS was 78.6 ± 16.0 kg (range 45,120 kg), BMI 26.5 ± 5.2 kg/m2 (range17.6,41.3 kg/m2). Within 13 ± 7.2 months of treatment, mean body weight decreased by ,3.7% ± 9.1%, showing high interindividual variability (,36% to +32%). Weight loss >5% was documented in 35%, weight gain >5% in 14% of patients. Weight loss was more prominent in patients being overweight prior to treatment onset. At the end of follow-up, patients with overweight had decreased by number. Weight changes under ZNS were not correlated to ZNS daily dosage. Following discontinuation of ZNS treatment weight loss proved to be reversible. Conclusion,,, Zonisamide reduced weight in 35% of patients, especially in patients with overweight prior to treatment. Weight loss is reversible following discontinuation of treatment with ZNS. [source]

Beta-carotene in multivitamins and the possible risk of lung cancer among smokers versus former smokers

CANCER, Issue 1 2008
A meta-analysis, evaluation of national brands
Abstract BACKGROUND Some studies have suggested that beta-carotene supplementation may increase the risk of lung cancer, particularly among smokers or former smokers. Beta-carotene, a provitamin A, is available in multivitamins. In the current study, the authors investigated the risk of lung cancer associated with beta-carotene in smokers or former smokers and surveyed the beta-carotene content in national brand multivitamins. METHODS The authors systemically reviewed the published literature using a search of the MEDLINE database and performed a meta-analysis of large randomized trials that reported on the effect of beta-carotene supplementation on the incidence of lung cancer among smokers or former smokers. A sample of multivitamins was evaluated for their beta-carotene content and the suggested daily dosage. RESULTS Four studies contributing 109,394 subjects were available for analysis. The average daily beta-carotene dosage in these trials ranged from 20 to 30 mg daily. Among current smokers, beta-carotene supplementation was found to be significantly associated with an increased risk of lung cancer (odds ratio [OR], 1.24; 95% confidence interval [95% CI], 1.10,1.39). Among former smokers, there was no significant increase noted (OR, 1.10; 95% CI, 0.84,1.45). In a sample of 47 common multivitamins, beta-carotene was present in 70% of the identified formulas. The median dosage of beta-carotene was 0.3 mg (range, 0,17.2 mg) daily. The beta-carotene content was found to be significantly higher among multivitamins sold to improve visual health than among other multivitamins, with a median daily dosage of 3 mg (range, 0,24 mg). CONCLUSIONS High-dose beta-carotene supplementation appears to increase the risk of lung cancer among current smokers. Although beta-carotene was prevalent in multivitamins, high-dose beta-carotene was observed among multivitamin formulas sold to promote visual health. Cancer 2008. © 2008 American Cancer Society. [source]

Pharmacokinetics of dipeptidylpeptidase-4 inhibitors

DIABETES OBESITY & METABOLISM, Issue 8 2010
A. J. Scheen
Type 2 diabetes (T2DM) is a complex disease combining defects in insulin secretion and insulin action. New compounds have been developed for improving glucose-induced insulin secretion and glucose control, without inducing hypoglycaemia or weight gain. Dipeptidylpeptidase-4 (DPP-4) inhibitors are new oral glucose-lowering agents, so-called incretin enhancers, which may be used as monotherapy or in combination with other antidiabetic compounds. Sitagliptin, vildaglipin and saxagliptin are already on the market in many countries, either as single agents or in fixed-dose combined formulations with metformin. Other DPP-4 inhibitors, such as alogliptin and linagliptin, are currently in late phase of development. The present paper summarizes and compares the main pharmacokinetics (PK) properties, that is, absorption, distribution, metabolism and elimination, of these five DPP-4 inhibitors. Available data were obtained in clinical trials performed in healthy young male subjects, patients with T2DM, and patients with either renal insufficiency or hepatic impairment. PK characteristics were generally similar in young healthy subjects and in middle-aged overweight patients with diabetes. All together gliptins have a good oral bioavailability which is not significantly influenced by food intake. PK/pharmacodynamics characteristics, that is, sufficiently prolonged half-life and sustained DPP-4 enzyme inactivation, generally allow one single oral administration per day for the management of T2DM; the only exception is vildagliptin for which a twice-daily administration is recommended because of a shorter half-life. DPP-4 inhibitors are in general not substrates for cytochrome P450 (except saxagliptin that is metabolized via CYP 3A4/A5) and do not act as inducers or inhibitors of this system. Several metabolites have been documented but most of them are inactive; however, the main metabolite of saxagliptin also exerts a significant DPP-4 inhibition and is half as potent as the parent compound. Renal excretion is the most important elimination pathway, except for linagliptin whose metabolism in the liver appears to be predominant. PK properties of gliptins, combined with their good safety profile, explain why no dose adjustment is necessary in elderly patients or in patients with mild to moderate hepatic impairment. As far as patients with renal impairment are concerned, significant increases in drug exposure for sitagliptin and saxagliptin have been reported so that appropriate reductions in daily dosages are recommended according to estimated glomerular filtration rate. The PK characteristics of DPP-4 inhibitors suggest that these compounds are not exposed to a high risk of drug,drug interactions. However, the daily dose of saxagliptin should be reduced when coadministered with potent CYP 3A4 inhibitors. In conclusion, besides their pharmacodynamic properties leading to effective glucose-lowering effect without inducing hypoglycaemia or weight gain, DPP-4 inhibitors show favourable PK properties, which contribute to a good efficacy/safety ratio for the management of T2DM in clinical practice. [source]

Randomized controlled trial of a brief intervention for problematic prescription drug use in non-treatment-seeking patients

ADDICTION, Issue 1 2009
Anne Zahradnik
ABSTRACT Aims Dependence on or problematic use of prescription drugs (PD) is estimated to be between 1 and 2% in the general population. In contrast, the proportion of substance-specific treatment in PD use disorders at 0.5% is comparatively low. With an estimated prevalence of 4.7%, PD-specific disorders are widespread in general hospitals compared to the general population. Brief intervention delivered in general hospitals might be useful to promote discontinuation or reduction of problematic prescription drug use. Design A randomized, controlled clinical trial. Setting Internal, surgical and gynaecological wards of a general and a university hospital. Participants One hundred and twenty-six patients fulfilling criteria for either regular use of PD (more than 60 days within the last 3 months) or dependence on or abuse of PD, respectively, were allocated randomly to two conditions. Intervention Subjects received two counselling sessions based on Motivational Interviewing plus an individualized written feedback (intervention group, IG) or a booklet on health behaviour (control group, CG). Measurements The outcome was measured as reduction (>25%) and discontinuation of PD intake in terms of defined daily dosages (DDD). Findings After 3 months, more participants in the IG reduced their DDD compared to the participants in the CG (51.8% versus 30%; ,2 = 6.17; P = 0.017). In the IG 17.9%, in the CG 8.6% discontinued use of PD (,2 = 2.42; P = 0.17). Conclusions Brief intervention based on Motivational Interviewing is effective in reducing PD intake in non-treatment-seeking patients. [source]

Women with Pain due to Osteoarthritis: The Efficacy and Safety of a Once-Daily Formulation of Tramadol

PAIN MEDICINE, Issue 6 2009
FRCP, Walter F. Kean MB ChB
ABSTRACT Objective., This analysis assesses the efficacy and safety of treatment with a once-daily oral formulation of tramadol for up to 12 weeks compared with placebo in women with moderate-to-severe pain due to osteoarthritis of the knee. Design., Two parallel, placebo-controlled phase III clinical trials were analyzed; patients were randomized to a fixed dosage of Tramadol Contramid® once a day (OAD) 100, 200, and 300 mg daily, or placebo. Outcome Measures., The primary efficacy end points were the percentage difference from baseline of the Western Ontario and McMaster University Osteoarthritis Index (WOMAC) subscale scores for pain and physical function, and the patient global rating of pain relief after 12 weeks of maintenance therapy. Results., The analysis included 405 women receiving tramadol and 280 receiving placebo. At week 12, 179 of 204 women (87.7%) receiving tramadol rated their overall pain relief as effective or very effective compared with 134 of 177 (75.7%) receiving placebo. A time-weighted analysis revealed statistically significant improvements over placebo for all the WOMAC subscale scores across all three dosages. The percentage improvements from baseline of the WOMAC pain scores were significantly better than placebo for the 100-mg (58.8 ± 37.1%, P = 0.018) and 300-mg (58.9 ± 38.8%, P = 0.023) treatment arms; however, the 200-mg dosage was not significant (53.0 ± 38.5%, P = 0.175). The WOMAC physical function scores showed significant improvement for the 100 (56.9 ± 36.4%, P = 0.009), 200 (54.0 ± 33.8%, P = 0.034), and 300 mg (53.4 ± 41.4%, P = 0.043) daily dosages. Conclusion., For moderate-to-severe pain due to osteoarthritis of the knee, women experience significant analgesia and improvement of physical function over time with treatment with Tramadol Contramid® OAD. [source]

Use of beta-2 agonists and risk of hip/femur fracture: a population-based case-control study,

PHARMACOEPIDEMIOLOGY AND DRUG SAFETY, Issue 6 2007
Frank de Vries Pharm D
Abstract Introduction Administration of beta-2 agonists decreased bone mineral density in rats. But the association between bronchodilators and fracture risk has not been studied in humans. Objectives To examine the association between use of beta-2 agonists and risk of hip/femur fracture. Methods We conducted a population-based case-control study (6763 cases) in the Dutch PHARMO database. Current beta-2 agonist use was compared to never use. We adjusted for severity of the underlying respiratory disease and disease and drug history. Results A hospitalisation for asthma/COPD in the year before index date increased risk of hip/femur fracture: crude OR 2.17 (95% CI, 1.41,3.34). Patients using higher doses of beta-2 agonists had increased risk of hip/femur fracture: crude OR 1.94 (95% CI, 1.41,2.66) for daily dosages of ,1600,µg albuterol equivalent. The excess fracture risk reduced after adjustment for disease severity (1.46; 95% CI, 1.02,2.08) and after exclusion of oral glucocorticoid users (1.31; 95% CI, 0.80,2.15). Risk of hip/femur fracture was similar between users of beta-2 agonists, inhaled glucocorticoids and anticholinergics. Conclusion We found increases in the risk of hip/femur fracture in patients using higher doses of beta-2 agonists. However, the excess risk of hip/femur fracture substantially reduced after exclusion of oral glucocorticoid users and after adjustment for the underlying disease. Risk of hip/femur fracture was similar between users of beta-2 agonists, inhaled glucocorticoids and anticholinergics. The severity of the underlying disease, rather than the use of beta-2 agonists, may play an important role in the aetiology of hip/femur fractures in patients using beta-2 agonists. Copyright © 2006 John Wiley & Sons, Ltd. [source]