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    Selected Abstracts

    Patient-Reported Outcomes with Botulinum Toxin Type A Treatment of Glabellar Rhytids: A Double-Blind, Randomized, Placebo-Controlled Study

    DERMATOLOGIC SURGERY, Issue 2007
    FACS, STEVEN FAGIEN MD
    BACKGROUND Global patient-reported outcomes do not evaluate specific aspects of treatment that are important to patients. OBJECTIVE The objective was to evaluate self-perception of age and specific outcomes that are important to patients receiving botulinum toxin type A or placebo for moderate to severe glabellar lines (using the Facial Line Outcomes Questionnaire to assess how much facial lines bother them, make them look older, detract from their facial appearance, prevent a smooth facial appearance, and make them look tired, stressed, or angry). METHODS AND MATERIALS In the double-blind phase of this 12-week study, 70 patients were randomly assigned to treatment with 20 U botulinum toxin type A (BOTOX Cosmetic) or placebo. At Week 4, those still with moderate or severe glabellar lines were offered open-label 20 U botulinum toxin type A. RESULTS Median glabellar line severity was significantly lower after botulinum toxin treatment than after placebo. Compared with placebo, botulinum toxin also resulted in significantly superior patient assessments and a greater proportion of patients considering they looked younger than their current age. CONCLUSIONS Botulinum toxin type A can achieve specific goals of treatment that are important to patients and help them feel that they look younger than their current age. [source]

    Novel Approach to the Treatment of Hyperpigmented Photodamaged Skin: 4% Hydroquinone/0.3% Retinol versus Tretinoin 0.05% Emollient Cream

    DERMATOLOGIC SURGERY, Issue 2005
    Zoe Diana Draelos MD
    Background. Mild to moderately photodamaged skin is characterized by dyspigmentation, fine wrinkles, and tactile roughness. An optimal approach to the topical treatment of photoaging would simultaneously address all appearance issues. Objective. This study was undertaken to evaluate the effect of 4% hydroquinone and 0.3% retinol in photoaging. Materials and Methods. A 16-week study was designed to evaluate the efficacy and tolerance of a single cream containing prescription topical 4% hydroquinone for dyspigmentation and the cosmeceutical 0.3% retinol for fine wrinkles in an emollient vehicle for tactile roughness. This novel formulation was compared with 0.05% tretinoin emollient cream, the standard against which all other topical photoaging treatments are compared. Investigator assessments, subject assessments, and photography represented the evaluation end points. Results. The cosmeceutical emollient 4% hydroquinone/0.3% retinol cream more effectively diminished the collective signs of photodamage than 0.05% tretinoin emollient cream in terms of dyspigmentation, fine wrinkles, and tactile roughness in 16 weeks. Conclusion. Combination therapy of hydroquinone and retinol may improve photoaging-associated hyperpigmentation. THIS STUDY WAS CONDUCTED AS PART OF A RESEARCH GRANT FROM MEDICIS THE DERMATOLOGY COMPANY, PHOENIX, ARIZONA. DR. DRAELOS HAS NO FINANCIAL INTEREST IN ANY OF THE MEDICATIONS DISCUSSED IN THIS RESEARCH. [source]

    Addition of insulin lispro protamine suspension or insulin glargine to oral type 2 diabetes regimens: a randomized trial

    DIABETES OBESITY & METABOLISM, Issue 10 2010
    K. Strojek
    Aims: The addition of basal insulin to existing oral therapy can help patients with type 2 diabetes (T2D) achieve glycaemic targets. This study compares the efficacy and safety of insulin lispro protamine suspension (ILPS) and insulin glargine in insulin-naive patients with T2D and inadequate control on oral antihyperglycaemic medication (OAM). Materials and Methods: An open-label, randomized, multicentre, multinational 24-week study of 471 patients receiving ,2 OAMs for ,3 months with a body mass index between 25 and 45 kg/m2 and HbA1c 7.5,10.0% was conducted. ILPS was injected once or twice daily vs. glargine injected once daily plus prestudy OAMs. Primary objective compared the HbA1c change from baseline. Results: HbA1c change from baseline to endpoint was similar in both groups [,1.46% (ILPS) and ,1.41% (glargine)]. Least-squares mean difference (95% CI) for HbA1c (,0.05 [,0.21, 0.11]%), glycaemic variability (0.06 [,0.06, 0.19] mmol/l) and weight change (,0.01 [,0.61, 0.59] kg) showed non-inferiority (margins of 0.4%, 0.8 mmol/l and 1.5 kg, respectively). Percentages of patients achieving HbA1c <7.0% were 43.8% ILPS and 41.2% glargine. Mean daily insulin dose was 0.39 vs. 0.35 U/kg (p = 0.02) and weight gain was 1.04 vs. 1.07 kg for ILPS vs. glargine (p = 0.98). Overall hypoglycaemia (episodes/patient/year) was similar for ILPS and glargine (24.2 ± 28.8 vs. 23.0 ± 30.9); nocturnal (6.1 ± 10.6 vs. 4.1 ± 9.4, p < 0.001) rates were higher for ILPS. Severe hypoglycaemia was higher for ILPS vs. glargine (n = 9 vs. n = 2; p = 0.04). Conclusions: At endpoint, ILPS was non-inferior to glargine in HbA1c change from baseline, but associated with increased risk of hypoglycaemia. [source]

    Efficacy and safety of sitagliptin when added to insulin therapy in patients with type 2 diabetes

    DIABETES OBESITY & METABOLISM, Issue 2 2010
    T. Vilsbøll
    Objective: To evaluate the efficacy and tolerability of sitagliptin when added to insulin therapy alone or in combination with metformin in patients with type 2 diabetes. Methods: After a 2 week placebo run-in period, eligible patients inadequately controlled on long-acting, intermediate-acting or premixed insulin (HbA1c , 7.5% and , 11%), were randomised 1:1 to the addition of once-daily sitagliptin 100 mg or matching placebo over a 24-week study period. The study capped the proportion of randomised patients on insulin plus metformin at 75%. Further, the study capped the proportion of randomised patients on premixed insulin at 25%. The metformin dose and the insulin dose were to remain stable throughout the study. The primary endpoint was HbA1c change from baseline at week 24. Results: Mean baseline characteristics were similar between the sitagliptin (n = 322) and placebo (n = 319) groups, including HbA1c (8.7 vs. 8.6%), diabetes duration (13 vs. 12 years), body mass index (31.4 vs. 31.4 kg/m2), and total daily insulin dose (51 vs. 52 IU), respectively. At 24 weeks, the addition of sitagliptin significantly (p < 0.001) reduced HbA1c by 0.6% compared with placebo (0.0%). A greater proportion of patients achieved an HbA1c level < 7% while randomised to sitagliptin as compared with placebo (13 vs. 5% respectively; p < 0.001). Similar HbA1c reductions were observed in the patient strata defined by insulin type (long-acting and intermediate-acting insulins or premixed insulins) and by baseline metformin treatment. The addition of sitagliptin significantly (p < 0.001) reduced fasting plasma glucose by 15.0 mg/dl (0.8 mmol/l) and 2-h postmeal glucose by 36.1 mg/dl (2.0 mmol/l) relative to placebo. A higher incidence of adverse experiences was reported with sitagliptin (52%) compared with placebo (43%), due mainly to the increased incidence of hypoglycaemia (sitagliptin, 16% vs. placebo, 8%). The number of hypoglycaemic events meeting the protocol-specified criteria for severity was low with sitagliptin (n = 2) and placebo (n = 1). No significant change from baseline in body weight was observed in either group. Conclusion: In this 24-week study, the addition of sitagliptin to ongoing, stable-dose insulin therapy with or without concomitant metformin improved glycaemic control and was generally well tolerated in patients with type 2 diabetes. [source]

    Original Article: Treatment: Dose-dependent effects of the once-daily GLP-1 receptor agonist lixisenatide in patients with Type 2 diabetes inadequately controlled with metformin: a randomized, double-blind, placebo-controlled trial

    DIABETIC MEDICINE, Issue 9 2010
    R. E. Ratner
    Diabet. Med. 27, 1024,1032 (2010) Abstract Aims, To evaluate the dose,response relationship of lixisenatide (AVE0010), a glucagon-like peptide-1 (GLP-1) receptor agonist, in metformin-treated patients with Type 2 diabetes. Methods, Randomized, double-blind, placebo-controlled, parallel-group, 13 week study of 542 patients with Type 2 diabetes inadequately controlled [glycated haemoglobin (HbA1c) , 7.0 and < 9.0% (, 53 and < 75 mmol/mol)] on metformin (, 1000 mg/day) treated with subcutaneous lixisenatide doses of 5, 10, 20 or 30 ,g once daily or twice daily or placebo. The primary end-point was change in HbA1c from baseline to 13 weeks in the intent-to-treat population. Results, Lixisenatide significantly improved mean HbA1c from a baseline of 7.55% (59.0 mmol/mol); respective mean reductions for 5, 10, 20 and 30 ,g doses were 0.47, 0.50, 0.69 and 0.76% (5.1, 5.5, 7.5 and 8.3 mmol/mol), on once-daily and 0.65, 0.78, 0.75 and 0.87% (7.1, 8.5, 8.2 and 9.5 mmol/mol) on twice-daily administrations vs. 0.18% (2.0 mmol/mol) with placebo (all P < 0.01 vs. placebo). Target HbA1c < 7.0% (53 mmol/mol) at study end was achieved in 68% of patients receiving 20 and 30 ,g once-daily lixisenatide vs. 32% receiving placebo (P < 0.0001). Dose-dependent improvements were observed for fasting, postprandial and average self-monitored seven-point blood glucose levels. Weight changes ranged from ,2.0 to ,3.9 kg with lixisenatide vs. ,1.9 kg with placebo. The most frequent adverse event was mild-to-moderate nausea. Conclusions, Lixisenatide significantly improved glycaemic control in mildly hyperglycaemic patients with Type 2 diabetes on metformin. Dose,response relationships were seen for once- and twice-daily regimens, with similar efficacy levels, with a 20 ,g once-daily dose of lixisenatide demonstrating the best efficacy-to-tolerability ratio. This new, once-daily GLP-1 receptor agonist shows promise in the management of Type 2 diabetes to be defined further by ongoing long-term studies. [source]

    Time Course of Adverse Events in Patients with Localization-related Epilepsy Receiving Topiramate Added to Carbamazepine

    EPILEPSIA, Issue 5 2005
    Jerzy Majkowski
    Summary:,Purpose: To explore the time course of treatment-emergent adverse events (AEs) during topiramate (TPM) adjunctive therapy. Methods: Post hoc analyses were performed by using data from a large (264 subjects) multicenter, double-blind, placebo-controlled trial in which 200 mg/day TPM was added to carbamazepine (CBZ) with or without another antiepileptic drug (AED) in adults with treatment-resistant partial-onset seizures. The daily incidence and mean duration of the most common (,5% incidence) AEs were calculated for patients completing the 12-week study. Results: The daily incidence of somnolence, headache, loss of appetite, nervousness, fatigue, dizziness, upper respiratory tract infection, and vertigo peaked during titration and declined to rates similar to that of placebo after the target TPM dose had been reached. In contrast, the daily incidence of paresthesia increased during titration and was maintained for the study duration. Relatively few patients had cognitive symptoms (9% with TPM, 5% with placebo), but these were the most common AEs associated with treatment discontinuation. Patient/investigator reports of weight loss increased gradually over the course of the trial, corresponding with the pattern of change in weight measured at study visits. Conclusions: This study demonstrates that most of the more common AEs with TPM adjunctive therapy are transient. Patients can be counseled that most AEs emerging when TPM is initially added to CBZ can be expected to diminish with continued therapy. [source]

    Olanzapine does not enhance cognition in non-agitated and non-psychotic patients with mild to moderate Alzheimer's dementia

    INTERNATIONAL JOURNAL OF GERIATRIC PSYCHIATRY, Issue 11 2005
    John Kennedy
    Abstract Objective This was an exploratory study of olanzapine as potential treatment for improvement in cognition in patients with Alzheimer's disease without prominent psychobehavioral symptoms. Methods Non-psychotic/non-agitated patients (n,=,268) with Alzheimer's disease, who had baseline Mini-Mental State Examination (MMSE) scores of 14,26 were randomized to treatment with olanzapine (2.5 to 7.5,mg/d) or placebo for 26 weeks. The primary objectives were to determine if treatment with olanzapine improved cognition as indexed by the Alzheimer's disease Assessment Scale for Cognition (ADAS-Cog) and the Clinician's Interview-Based Impression of Change (CIBIC) after 26 weeks of therapy. Results Patients treated with olanzapine vs placebo experienced significant worsening ADAS-Cog scores at weeks 12 (p,=,0.03) and 26 (p,=,0.004). Changes in CIBIC scores were not significantly different between treatment groups at either assessment. A post hoc analysis revealed that olanzapine-treated patients with more cognitive impairment at baseline (MMSE scores of 14,18) (n,=,35) experienced significantly greater deterioration in ADAS-Cog performance than patients in the placebo group (n,=,24; p,<,0.001); whereas in patients with less cognitive impairment (n,=,78, baseline MMSE scores of 23,26) between-group ADAS-Cog changes were not significant. Conclusions In this 26-week study non-psychotic/non-agitated patients with Alzheimer's disease treated with olanzapine experienced significant worsening of cognition as compared to placebo. Copyright © 2005 John Wiley & Sons, Ltd. [source]

    A dictation system for reporting prescribing errors in community pharmacies

    INTERNATIONAL JOURNAL OF PHARMACY PRACTICE, Issue 1 2004
    Amanda G. Kennedy assistant professor of medicine
    ABSTRACT Objective To pilot and evaluate dictation as a novel method of reporting prescribing errors in community pharmacies. Setting Seven community pharmacies in northwestern Vermont. Method An intervention reporting form was developed and implemented in seven community pharmacies. Using a crossover design, pharmacists reported by both dictation and paper methods for six weeks each. The primary objective was to determine if dictation stimulated more prescribing error reports than a paper-based reporting method. Secondary objectives included a qualitative assessment of dictation feasibility, pharmacist satisfaction with reporting in general, pharmacist preference for a dictation or paper reporting method, and a content description of the prescribing errors reported. Key findings Pharmacists completed a total of 72 reports, describing 80 interventions, during the 12-week study. Thirty-three reports were dictated and 39 were completed on paper (P= 0.56). There were no differences in completeness of reports between paper and dictation (P = 0.62). Seven out of the nine pharmacists (78%) stated they preferred the paper method to dictation. Conclusion Dictation does not appear to increase prescribing error reporting as compared with a paper method. Implementing dictation in community pharmacies proved feasible although most of the pharmacists in this study preferred the paper method. Further investigation to explore dictation as a useful technology in community pharmacies is warranted. [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]

    Novel pharmacology: asimadoline, a ,-opioid agonist, and visceral sensation

    NEUROGASTROENTEROLOGY & MOTILITY, Issue 9 2008
    M. Camilleri
    Abstract, Asimadoline is a potent ,-opioid receptor agonist with a diaryl acetamide structure. It has high affinity for the , receptor, with IC50 of 5.6 nmol L,1 (guinea pig) and 1.2 nmol L,1 (human recombinant), and high selectively with , : , : , binding ratios of 1 : 501 : 498 in human recombinant receptors. It acts as a complete agonist in in vitro assay. Asimadoline reduced sensation in response to colonic distension at subnoxious pressures in healthy volunteers and in irritable bowel syndrome (IBS) patients without alteration of colonic compliance. Asimadoline reduced satiation and enhanced the postprandial gastric volume (in female volunteers). However, there were no significant effects on gastrointestinal transit, colonic compliance, fasting or postprandial colonic tone. In a clinical trial in 40 patients with functional dyspepsia (Rome II), asimadoline did not significantly alter satiation or symptoms over 8 weeks. However, asimadoline, 0.5 mg, significantly decreased satiation in patients with higher postprandial fullness scores, and daily postprandial fullness severity (over 8 weeks); the asimadoline 1.0 mg group was borderline significant. In a clinical trial in patients with IBS, average pain 2 h post- on-demand treatment with asimadoline was not significantly reduced. Post hoc analyses suggest that asimadoline was effective in mixed IBS. In a 12-week study in 596 patients, chronic treatment with 0.5 mg and 1.0 mg asimadoline was associated with adequate relief of pain and discomfort, improvement in pain score and number of pain-free days in patients with IBS-D. The 1.0 mg dose was also efficacious in IBS-alternating. There were also weeks with significant reduction in bowel frequency and urgency. Asimadoline has been well tolerated in human trials to date. [source]

    Modified Directly Observed Therapy (MDOT) for Injection Drug Users with HIV Disease

    THE AMERICAN JOURNAL ON ADDICTIONS, Issue 4 2002
    Elinore F. McCance-Katz M.D., Ph.D.
    Injection drug use is an important factor in the spread of HIV infection, and strategies to enhance adherence to HIV therapeutics are critically important to controlling viral transmission and improving clinical outcomes. To this end, the authors sought (1) to enhance adherence to highly active antiretroviral therapy (HAART) among methadone-maintained injection drug users (IDUs) using modified directly observed therapy (MDOT), and (2) to define interactions between methadone and HAART and the potential contribution of drug interactions to adherence and HIV outcomes in this population. Adherence was explored here through a pilot, unblinded, 24-week study in a methadone maintenance program in which simplified HAART (efavirenz and didanosine [once daily] and a second nucleoside [twice daily]) was administered 6 days/week by clinic staff to HIV-infected IDUs (n = 5) with their methadone. Evening doses of riboflavin-tagged nucleoside and one full day of medication weekly were given as take home doses. As a result of HAART administration, four of five participants with mean viral load at baseline of 105 copies/ml had undetectable viral load by 8 weeks of treatment (p = 043). Methadone area under the curve (AUC) decreased by 55% (p = 007) within 2 weeks of initiating this HAART regimen, and a mean methadone dose increase of 52%o was required. The authors conclude that MDOT is a promising intervention for the treatment of IDUs with HIV disease, though significant drug interactions must be monitored for carefully and rapidly addressed. [source]

    Efficacy of Phosphodiesterase Type 5 Inhibitor Treatment in Men with Erectile Dysfunction and Dyslipidemia: A Post Hoc Analysis of the Vardenafil Statin Study

    THE JOURNAL OF SEXUAL MEDICINE, Issue 5 2010
    Martin M. Miner MD
    ABSTRACT Introduction., Dyslipidemia occurs often in subjects with erectile dysfunction (ED), but there is little information about how this condition affects ED treatment responses. Aim., To determine whether low-density lipoprotein cholesterol (LDL-C) levels, total cholesterol (TC)/high-density lipoprotein cholesterol (HDL-C) ratio; or the presence of metabolic syndrome influenced efficacy of vardenafil in men with ED and dyslipidemia. Methods., Post hoc subgroup analysis of a 12-week study of the influence of lipid levels and presence of metabolic syndrome on the efficacy of vardenafil as measured by International Index of Erectile Function-Erectile Function (IIEF-EF) domain score, responses to Sexual Encounter Profile (SEP) SEP2 and SEP3 questions, duration of erection leading to successful intercourse, and erection duration regardless of the answer to SEP3. Lipid values were obtained at study start, after patients had received at least 3 months of therapy with a statin. Main Outcome Measures., Outcomes in subjects with LDL-C <100, ,100 to <130, or ,130 mg/dL [<2.59, ,2.59 to <3.36, or ,3.36 mmol/L]; TC/HDL-C ratio <3.5 vs. ,3.5, and presence or absence of metabolic syndrome. Results., Vardenafil improved all endpoints evaluated compared with placebo in all subgroups, however, nominally significant treatment by subgroup interaction terms did not follow a distinct pattern. Increasing LDL-C (P = 0.033), but not TC/HDL-C ratio or metabolic syndrome, was associated with an increase in treatment response measured by the IIEF-EF domain score. Responses to SEP3 were nominally influenced by LDL-C levels (P = 0.019), but were not significantly influenced by TC/HDL-C ratio, or the metabolic syndrome. Only higher TC/HDL-C ratios (,3.5) were associated with larger treatment differences in duration of erection leading to successful intercourse (P = 0.028). Conclusions., Vardenafil was effective in men with dyslipidemia regardless of LDL-C levels, TC/HDL-C ratio, and/or presence of metabolic syndrome. Despite the known presence of ED and dyslipidemia, other cardiovascular risk factors were apparently not aggressively managed. Miner MM, Barnes A, and Janning S. Efficacy of phosphodiesterase type 5 inhibitor treatment in men with erectile dysfunction and dyslipidemia: A post hoc analysis of the vardenafil statin study. J Sex Med 2010;7:1937,1947. [source]

    Rapamycin versus methotrexate in early diffuse systemic sclerosis: Results from a randomized, single-blind pilot study

    ARTHRITIS & RHEUMATISM, Issue 12 2009
    Tien-I Karleen Su
    Objective To assess the safety and efficacy of rapamycin in the treatment of diffuse systemic sclerosis (SSc; scleroderma). Methods Eighteen patients with diffuse SSc of ,5 years duration were randomized to receive rapamycin or methotrexate (MTX) in a single-blind, 48-week study. Abnormalities in clinical and laboratory parameters were compared between the 2 treatment groups. The potential efficacy of the study drugs was evaluated by comparing results of the baseline and 48-week assessments, including the modified Rodnan skin thickness score (MRSS) and the Health Assessment Questionnaire disability index. Results The baseline characteristics of the patients were similar in both groups (n = 9 in each). One patient in the rapamycin group who never received the study drug was excluded from the analysis. Three patients in each group withdrew from the study; 2 of the withdrawals were treatment-related (severe hypertriglyceridemia associated with rapamycin, and pancytopenia associated with MTX), and 4 were SSc-related. Hypertriglyceridemia was the most notable side effect associated with rapamycin, but it was generally well tolerated and treatable. The incidence and severity of other adverse drug reactions were comparable between the 2 groups. Within each group, the MRSS improved significantly from baseline. In the rapamycin group, the patient's global assessment showed a significant improvement from baseline, while forced vital capacity values declined from baseline. The disease activity scores at 48 weeks and the changes in these scores from baseline were not significantly different between the 2 groups. Conclusion Rapamycin has a reasonable safety profile in a select group of patients with scleroderma. Larger trials are needed to assess the efficacy of rapamycin in patients with early diffuse SSc. [source]

    An investigation of dose titration with darifenacin, an M3 -selective receptor antagonist

    BJU INTERNATIONAL, Issue 4 2005
    William Steers
    OBJECTIVES To evaluate the efficacy, tolerability and safety of a flexible-dosing strategy with darifenacin, an M3 -selective receptor antagonist, in patients with symptoms of overactive bladder (OAB). PATIENTS AND METHODS In this multicentre double-blind 12-week study, 395 patients (aged 22,89 years; 84% female) with OAB symptoms for >6 months were randomized (2 : 1) and received once-daily treatment with darifenacin controlled-release tablets 7.5 mg (268 patients) or matching placebo (127). After 2 weeks of treatment, the efficacy, safety and tolerability were assessed and the dose increased to 15 mg once daily (pseudo-increase for placebo recipients) if additional efficacy was required by both the patient and physician. In the week before clinic visits (at 2 and 12 weeks), patients recorded incontinence episodes (primary efficacy endpoint) and several secondary efficacy variables in an electronic daily diary. Safety and tolerability were evaluated from withdrawal rates and adverse-event reports. RESULTS The treatment groups had comparable baseline characteristics. Similar proportions of darifenacin (59%) and placebo (68%) recipients increased the dose at 2 weeks; at 12 weeks patients on darifenacin (overall group) had a significantly greater reduction in the median number of incontinence episodes per week than had those on placebo, at ,,8.2 (,62.9%) and ,,6.0 (,48.1%), respectively (P = 0.035). There were also significant improvements in voiding frequency (P = 0.001), bladder capacity (volume voided; P=,0.036), frequency of urgency (P < 0.001), severity of urgency (P = 0.013) and number of significant leaks/week (i.e. incontinence episodes needing a change of clothing or pads, per week; P = 0.010) for darifenacin over placebo. Subset analysis suggested that some patients (those remaining on darifenacin 7.5 mg) were more sensitive to darifenacin than those who increased the dose, based on both efficacy and adverse events. Continued treatment with 7.5 mg for ,sensitive' patients, and an increased dose (to 15 mg) for remaining patients, resulted in comparable outcomes by 12 weeks. The most common treatment-related adverse events were mild-to-moderate dry mouth and constipation, which led to discontinuation in <,3.0% of darifenacin-treated patients and <1.0% of the placebo group. Central nervous system and cardiovascular adverse events were comparable to those with placebo. CONCLUSIONS Darifenacin appears to be an effective, well-tolerated and flexible treatment for patients with OAB, allowing individualized dosing according to patient needs. [source]

    Long-Term Efficacy and Safety of Cerivastatin 0.8 mg in Patients with Primary Hypercholesterolemia

    CLINICAL CARDIOLOGY, Issue S4 2001
    Jonathan Isaacsohn M.D.
    Abstract Background: Statins are the agents of choice in reducing elevated plasma low-density lipoprotein cholesterol (LDL-C). Hypothesis: Cerivastatin 0.8 mg has greater long-term efficacy in reducing LDL-C than pravastatin 40 mg in primary hypercholesterolemia. Methods: In this double-blind, parallel-group, 52-week study, patients (n = 1,170) were randomized (4:1:1) to cerivastatin 0.8 mg, cerivastatin 0.4 mg, or placebo daily. After 8 weeks, placebo was switched to pravastatin 40 mg. Patients with insufficient LDL-C lowering after 24 weeks were allowed open-labeled resin therapy. Results: Cerivastatin 0.8 mg reduced LDL-C versus cerivastatin 0.4 mg (40.8 vs. 33.6%, p<0.0001) or pravastatin 40 mg (31.5%, p<0.0001), and brought 81.8% of all patients, and 54.1% of patients with atherosclerotic disease, to National Cholesterol Education Program (NCEP) goals. Cerivastatin 0.8 mg improved mean total C (-29.0%), triglycerides (-18.3%), and high-density lipoprotein cholesterol (HDL-C) (+9.7%) (all , 0.013 vs. pravastatin 40 mg). Higher baseline triglycerides were associated with greater reductions in triglycerides and elevations in HDL-C with cerivastatin. Cerivastatin was well tolerated; the most commonly reported adverse events were arthralgia, headache, pharyngitis, and rhinitis. Symptomatic creatine kinase > 10 × the upper limit of normal (ULN) occurred in 1,1.5, and 0% of patients receiving cerivastatin 0.8 mg, cerivastatin 0.4 mg, and pravastatin 40 mg, respectively. Repeat hepatic transaminases >3 × ULN occurred in 0.3,0.5,0.5, and 0% of patients, respectively. Conclusion: In long-term use, cerivastatin 0.8 mg effectively and safely brings the majority of patients to NCEP goal. [source]