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Eligible Patients (eligible + patient)
Selected AbstractsOutcomes Associated With Nesiritide Administration for Acute Decompensated Heart Failure in the Emergency Department Observation Unit: A Single Center ExperienceCONGESTIVE HEART FAILURE, Issue 3 2009Joseph F. Styron BA The authors' purpose was to determine 30- and 180-day readmission and mortality rates for acutely decompensated heart failure patients receiving nesiritide in the emergency department observation unit. The authors conducted a retrospective evaluation of all patients admitted to the emergency department observation unit, stratified by nesiritide administration, from January 2002 to January 2004. Eligible patients had a primary diagnosis of acutely decompensated heart failure. Observation unit treatment was by previously published protocols, except for nesiritide administration, which was per attending physician choice. Of 595 patients, 196 (33%) received nesiritide. The crude and adjusted odds ratios comparing readmission rates and mortality rates of the nesiritide group with the control group failed to demonstrate significant differences at either the 30- or the 180-day endpoints. The use of nesiritide for acute decompensated heart failure in the emergency department observation unit is not associated with mortality or readmission differences compared with standard therapy alone. [source] Referral of Emergency Department Patients for Pneumococcal VaccinationACADEMIC EMERGENCY MEDICINE, Issue 3 2004David E. Manthey MD Abstract Objectives: To determine what proportion of eligible patients, when referred to a primary care physician for pneumococcal vaccination with a prescription, actually obtain the vaccination. To ascertain the number of eligible patients who would receive the vaccination in the emergency department (ED), if available. Methods: The authors surveyed a convenience sample of patients presenting to an urban ED during a four-month period. Eligible patients were referred to specific sites with a prescription to be immunized. Data on those referred were collected by review of medical record and telephone follow-up. Results: A total of 2,299 surveys were distributed; 338 patients declined to participate, yielding an 85% response rate. The total number of patients identified as having an indication for the pneumovax was 711 (36%). Of these, 411 were not previously vaccinated; 167 of the 411 had a contraindication to vaccination. The remaining 244 qualified for referral to receive the pneumococcal vaccine. One hundred thirty-one of these accepted referral prescription. Of the patients given prescriptions, 12 followed up and received the vaccine, 81 did not follow up, and 38 were lost to follow-up. Seventy-four percent of patients would have received the pneumovax in the ED if it had been available. Conclusions: The percentage of ED patients who used prescription referral to the primary care network for pneumococcal vaccination was approximately 10%. The use of a referral by prescription method in this setting was not a reliable means of increasing the number of patients receiving the pneumococcal vaccination. [source] Stroke secondary prevention and blood pressure reduction: an observational study of the use of PROGRESS therapyFUNDAMENTAL & CLINICAL PHARMACOLOGY, Issue 2 2008Jean-Marc Bugnicourt Abstract The Perindopril pROtection aGainst REcurrent Stroke Study (PROGRESS) showed the efficacy of blood pressure reduction in secondary stroke prevention. This anti-hypertensive treatment (perindopril 4 mg daily plus indapamide 1.5 mg daily) is now routinely proposed to patients referred to our department for stroke or transient ischaemic attack (TIA). The aim of this study was to evaluate the prescription of PROGRESS therapy during hospitalization and to identify the predictors of therapy discontinuation after discharge. Eligible patients admitted to the Amiens University hospital for acute stroke or TIA from January to April 2003 were included (n = 101). At 1 year, the use of PROGRESS therapy was evaluated by structured phone interviews. In addition, each patient's general practitioner (GP) was also contacted to provide information. PROGRESS therapy was mentioned on the hospital discharge summary significantly less frequently after cardioembolic stroke (OR: 0.15; 95% CI: 0.05,0.5; P = 0.001) and TIA (OR: 0.12; 95% CI: 0.02,0.7; P = 0.02). At 1 year, only 25.7% of patients were treated with optimal PROGRESS therapy (perindopril 4 mg daily plus indapamide 1.5 mg daily). Mention of PROGRESS therapy in the discharge summary was the main predictor of optimal PROGRESS therapy at 1 year (OR: 10.8; 95% CI: 1.3,88.3; P = 0.03). This study shows that mention of PROGRESS therapy in the discharge summary must be improved as it is associated with a higher use of these anti-hypertensive agents 1 year after stroke/TIA. [source] The Efficacy of Factor VIIa in Emergency Department Patients With Warfarin Use and Traumatic Intracranial HemorrhageACADEMIC EMERGENCY MEDICINE, Issue 3 2010Daniel K. Nishijima MD Abstract Objectives:, The objective was to compare outcomes in emergency department (ED) patients with preinjury warfarin use and traumatic intracranial hemorrhage (tICH) who did and did not receive recombinant activated factor VIIa (rFVIIa) for international normalized ratio (INR) reversal. Methods:, This was a retrospective before-and-after study conducted at a Level 1 trauma center, with data from 1999 to 2009. Eligible patients had preinjury warfarin use and tICH on cranial computed tomography (CT) scan. Patients before (standard cohort) and after (rFVIIa cohort) implementation of a protocol for administering 1.2 mg of rFVIIa in the ED were reviewed. Glasgow Coma Scale (GCS) score, Revised Trauma Score (RTS), Injury Severity Score (ISS), INR, and Marshall score were collected. Outcome measures included mortality, thromboembolic complications, and INR normalization. Results:, Forty patients (median age = 80.5 years, interquartile range [IQR] = 63.5,85) were included (20 in each cohort). Age, GCS score, ISS, RTS, initial INR, and Marshall score were similar (p > 0.05) between the two cohorts. Survival was identical between cohorts (13 of 20, or 65.0%, 95% confidence interval [CI] = 40.8% to 84.6%). There were no differences in rate of thromboembolic complications in the standard cohort (1 of 20, 5.0%, 95% CI = 0.1% to 24.9%) than the rFVIIa cohort (4 of 20, 20.0%, 95% CI = 5.7% to 43.7%; p = 0.34). Time to normal INR was earlier in the rFVIIa cohort (mean = 4.8 hours, 95% CI = 3.0 to 6.7 hours) than in the standard cohort (mean = 17.5 hours, 95% CI = 12.5 to 22.6; p < 0.001). Conclusions:, In patients with preinjury warfarin and tICH, use of rFVIIa was associated with a decreased time to normal INR. However, no difference in mortality was identified. Use of rFVIIa in patients on warfarin and tICH requires further study to demonstrate important patient-oriented outcomes. ACADEMIC EMERGENCY MEDICINE 2010; 17:244,251 © 2010 by the Society for Academic Emergency Medicine [source] The Effects of Heparin Versus Normal Saline for Maintenance of Peripheral Intravenous Locks in Pregnant WomenJOURNAL OF OBSTETRIC, GYNECOLOGIC & NEONATAL NURSING, Issue 4 2003Kathryn M. Niesen MSN, RN director of clinical nursing Objective: To compare the efficacy of two available preparations (heparin, 10 U/mL, 1 mL, vs. normal saline, 1 mL) used for maintaining patency in peripheral intravenous (IV) locks during pregnancy. Design: Prospective, randomized, and double-blind. Eligible patients who were to receive a peripheral intermittent IV lock were randomly assigned to receive either heparin flushes or normal saline flushes for IV lock maintenance. IV locks were flushed after each medication administration, or at least every 24 hours, with the assigned blinded flush solution. Intermittent IV lock sites were also evaluated every 12 hours for the development of phlebitis. Setting: A large academic medical center in the Midwest that has both community-based and regional-referral obstetric practices with more than 2,000 deliveries per year. Participants: A convenience sample included 73 hospitalized pregnant women who were between 24 and 42 weeks gestation. Exclusions from the study were women with significant abnormalities in the fetal heart tracing on admission, cervical dilation > 4 cm, presence of hypersensitivity to heparin, presence of clotting abnormalities, and anticoagulation therapy (including low-dose aspirin). Results: Data indicate there were no statistically significant differences in IV lock patency nor in phlebitis between heparin or normal saline flushes. Conclusions: This study provides support that both normal saline and heparin in the doses studied may be equally effective in the maintenance of peripheral IV locks. Due to small sample size, additional studies are needed to determine optimal therapy over time. [source] Integrated Management of Physician-delivered Alcohol Care for Tuberculosis Patients: Design and ImplementationALCOHOLISM, Issue 2 2010Shelly F. Greenfield Background:, While the integration of alcohol screening, treatment, and referral in primary care and other medical settings in the U.S. and worldwide has been recognized as a key health care priority, it is not routinely done. In spite of the high co-occurrence and excess mortality associated with alcohol use disorders (AUDs) among individuals with tuberculosis (TB), there are no studies evaluating effectiveness of integrating alcohol care into routine treatment for this disorder. Methods:, We designed and implemented a randomized controlled trial (RCT) to determine the effectiveness of integrating pharmacotherapy and behavioral treatments for AUDs into routine medical care for TB in the Tomsk Oblast Tuberculosis Service (TOTBS) in Tomsk, Russia. Eligible patients are diagnosed with alcohol abuse or dependence, are newly diagnosed with TB, and initiating treatment in the TOTBS with Directly Observed Therapy-Short Course (DOTS) for TB. Utilizing a factorial design, the Integrated Management of Physician-delivered Alcohol Care for Tuberculosis Patients (IMPACT) study randomizes eligible patients who sign informed consent into 1 of 4 study arms: (1) Oral Naltrexone + Brief Behavioral Compliance Enhancement Therapy (BBCET) + treatment as usual (TAU), (2) Brief Counseling Intervention (BCI) + TAU, (3) Naltrexone + BBCET + BCI + TAU, or (4) TAU alone. Results:, Utilizing an iterative, collaborative approach, a multi-disciplinary U.S. and Russian team has implemented a model of alcohol management that is culturally appropriate to the patient and TB physician community in Russia. Implementation to date has achieved the integration of routine alcohol screening into TB care in Tomsk; an ethnographic assessment of knowledge, attitudes, and practices of AUD management among TB physicians in Tomsk; translation and cultural adaptation of the BCI to Russia and the TB setting; and training and certification of TB physicians to deliver oral naltrexone and brief counseling interventions for alcohol abuse and dependence as part of routine TB care. The study is successfully enrolling eligible subjects in the RCT to evaluate the relationship of integrating effective pharmacotherapy and brief behavioral intervention on TB and alcohol outcomes, as well as reduction in HIV risk behaviors. Conclusions:, The IMPACT study utilizes an innovative approach to adapt 2 effective therapies for treatment of alcohol use disorders to the TB clinical services setting in the Tomsk Oblast, Siberia, Russia, and to train TB physicians to deliver state of the art alcohol pharmacotherapy and behavioral treatments as an integrated part of routine TB care. The proposed treatment strategy could be applied elsewhere in Russia and in other settings where TB control is jeopardized by AUDs. If demonstrated to be effective, this model of integrating alcohol interventions into routine TB care has the potential for expanded applicability to other chronic co-occurring infectious and other medical conditions seen in medical care settings. [source] Clinical trial: the glucagon-like peptide-1 analogue ROSE-010 for management of acute pain in patients with irritable bowel syndrome: a randomized, placebo-controlled, double-blind studyALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 2 2009P. M. HELLSTRÖM Summary Background, There is currently no treatment available to manage acute pain attacks in IBS patients regardless of subtype. Aims, To evaluate efficacy and safety of the GLP-1 analogue ROSE-010 in patients with irritable bowel syndrome (IBS) through a randomized, double-blind, placebo-controlled study. Methods, Eligible patients (n = 166) meeting Rome II criteria were randomly assigned to receive single subcutaneous injections of ROSE-010 100 ,g, 300 ,g and placebo in a cross-over design. Safety was assessed from spontaneously reported adverse events and measurement of vital signs. Patient-rated pain relief and intensity were measured on a 100-mm visual analogue scale. The primary efficacy variable was proportion of patients with >50% maximum total pain relief response from 10 to 60 min after treatment. Secondary endpoints included the maximum summed pain intensity difference, time to meaningful pain relief and patient ratings of satisfaction with treatment. Results, Twice as many patients were responders in the primary efficacy endpoint after both ROSE-010 injections compared to placebo (24%P = 0.011, 23%P = 0.005, and 12% after 300 ,g, 100 ,g and placebo injections, respectively). Similar results were obtained for the proportion of patients with total pain intensity response. Times to meaningful and total pain relief were shorter for both doses of ROSE-010 compared with placebo. Compared with placebo, more patients (P < 0.05) were satisfied with ROSE-010 and considered ROSE-010 better than previous IBS medications used. Conclusion, ROSE-010 was well tolerated and provided fast and effective relief of acute pain attacks on demand in IBS patients. [source] Physiotherapy rehabilitation in patients with massive, irreparable rotator cuff tearsMUSCULOSKELETAL CARE, Issue 3 2006Roberta Ainsworth FSCP SRP MSc BA (Hons) Abstract Background:,Massive rotator cuff tears provide a challenge for effective rehabilitation. Work has been ongoing at Torbay Hospital, Devon since 2000 to develop an exercise programme for the management of this patient group. This programme has been evaluated in a pilot study and a further randomised controlled trial is currently taking place which will enable us to estimate the treatment effect. This paper discusses the background to the development of the rehabilitation programme, the programme itself and the results of the pilot study. The pilot study was an evaluation of the rehabilitation programme. Objectives:,This study examined the effectiveness of a physiotherapy regime for the treatment of patients with massive rotator cuff tears. Methods: Patients identified through primary and secondary care referrals to physiotherapy with a clinical diagnosis of a massive rotator cuff tear underwent an ultrasound scan to confirm the diagnosis. A massive cuff tear was one where the leading edge of the tear had retracted past the glenoid margin. The clinical diagnosis was based on the presence of some or all of the following signs: positive humeral thrust on elevation, gross weakness and wasting of supraspinatus and infraspinatus, infraspinatus lag and rupture of the long head of biceps. Eligible patients were invited to take part in the study and informed consent was obtained. The baseline assessment was carried out and then the patient undertook the treatment programme. Outcome measures were reassessed 12 weeks from the baseline assessment. Design:,A cohort study of 10 patients evaluating the change from baseline to twelve weeks in the shoulder function of patients undergoing a programme of anterior deltoid strengthening and functional rehabilitation. The outcome measures used were the Oxford Shoulder Disability Questionnaire (OSDQ) and SF36. The OSDQ is validated for use with the UK population and has 12 questions with 5 point responses. The lowest (best) score is 12 and the highest (worse) score is 60. Results: Scores on the OSDQ improved with all patients. The mean improvement was 9 (range 3 to 16, standard deviation 10.3). The SF36 showed an improvement in the pain scores for all patients (mean 22 points) and an overall improvement of 10 points for the sections on role limitation due to physical health. There was an overall decline in perceived general health (9 points) and in role limitation due to emotional health (23 points). Conclusions:,As all 10 patients showed improved scores on the OSDQ, in spite of the long-standing nature of many of their shoulder problems, this rehabilitation programme was shown to improve shoulder function in this group of patients. The variation shown in the quality of life scores reflects the age group of this cohort who had a mean age of 75.5 years. All patients deemed their pain and function to have improved over the three-month period. [source] Exploring the risk of diabetes mellitus and dyslipidemia among ambulatory users of atypical antipsychotics: a population-based comparison of risperidone and olanzapine,PHARMACOEPIDEMIOLOGY AND DRUG SAFETY, Issue 6 2005Jocelyne Moisan PhD Abstract Purpose To compare the incidence rates of diabetes mellitus and dyslipidemia in ambulatory first-time users of risperidone and olanzapine. Methods The database for the Prescription Drug Insurance Plan in the province of Quebec was used as the data source for a population-based cohort study. Denominalized data were extracted for all ambulatory patients who first received an atypical antipsychotic between 1 January 1997 and 31 August 1999. Eligible patients were categorized as taking: no antidiabetic medication; no lipid reducing medication; neither type of medication. Those who started to use an outcome drug (an antidiabetic or lipid-lowering medication) before the end of the follow-up period (31 August 2000) were considered to have developed the corresponding outcome disease. Incidence rate ratios (IRR) (and 95% confidence intervals) for initiating antihyperglycemic or lipid-lowering drug treatment, or both were calculated. Outcomes on risperidone were compared to those on olanzapine. Results A total of 19,582 eligible patients were included in the analysis. Relative to risperidone, olanzapine was associated with a higher risk of initiating a pharmacologic treatment for diabetes [IRR: 1.33 (1.03,1.74)], dyslipidemia [IRR: 1.49 (1.22,1.83)], or either condition [1.47 (1.23,1.76)]. Conclusions Olanzapine seems to be associated with a higher risk of developing diabetes and/or dyslipidemia than risperidone. Further prospective studies are needed to rigorously assess the safety of olanzapine. Copyright © 2005 John Wiley & Sons, Ltd. [source] Pharmacokinetics for Once- Versus Twice-Daily Tacrolimus Formulations in De Novo Kidney Transplantation: A Randomized, Open-Label TrialAMERICAN JOURNAL OF TRANSPLANTATION, Issue 11 2009Z. Wlodarczyk Tacrolimus, a cornerstone immunosuppressant, is widely available as a twice-daily formulation (Tacrolimus BID). A once-daily prolonged-release formulation (Tacrolimus QD) has been developed that may improve adherence and impart long-lasting graft protection. This study compared the pharmacokinetics (PK) of tacrolimus in de novo kidney transplant patients treated with Tacrolimus QD or Tacrolimus BID. A 6-week, open-label, randomized comparative study was conducted in centers in Europe and Australia. Eligible patients received Tacrolimus QD or Tacrolimus BID. PK profiles were obtained following the first tacrolimus dose (day 1), and twice under steady-state conditions. As secondary objectives, efficacy and safety parameters were also evaluated. Sixty-six patients completed all PK profiles (34 Tacrolimus QD, 32 Tacrolimus BID). Mean AUC0,24 of tacrolimus on day 1 was approximately 30% lower for Tacrolimus QD than Tacrolimus BID (232 and 361 ng.h/mL, respectively), but was comparable by day 4. There was a good correlation and a similar relationship between AUC0,24 and Cmin for both formulations. Efficacy and safety data were also comparable over the 6-week period. Tacrolimus QD can be administered once daily in the morning on the basis of the same systemic exposure and therapeutic drug monitoring concept as Tacrolimus BID. [source] Combination antibiotics as a treatment for chronic Chlamydia -induced reactive arthritis: A double-blind, placebo-controlled, prospective trial,ARTHRITIS & RHEUMATISM, Issue 5 2010J. D. Carter Objective Chlamydia trachomatis and Chlamydophila (Chlamydia) pneumoniae are known triggers of reactive arthritis (ReA) and exist in a persistent metabolically active infection state in the synovium, suggesting that they may be susceptible to antimicrobial agents. The goal of this study was to investigate whether a 6-month course of combination antibiotics is an effective treatment for patients with chronic Chlamydia- induced ReA. Methods This study was a 9-month, prospective, double-blind, triple-placebo trial assessing a 6-month course of combination antibiotics as a treatment for Chlamydia -induced ReA. Eligible patients had to be positive for C trachomatis or C pneumoniae by polymerase chain reaction (PCR). Groups received 1) doxycycline and rifampin plus placebo instead of azithromycin; 2) azithromycin and rifampin plus placebo instead of doxycycline; or 3) placebos instead of azithromycin, doxycycline, and rifampin. The primary end point was the number of patients who improved by 20% or more in at least 4 of 6 variables without worsening in any 1 variable in both combination antibiotic groups combined and in the placebo group at month 6 compared with baseline. Results The primary end point was achieved in 17 of 27 patients (63%) receiving combination antibiotics and in 3 of 15 patients (20%) receiving placebo. Secondary efficacy end points showed similar results. Six of 27 patients (22%) randomized to combination antibiotics believed that their disease went into complete remission during the trial, whereas no patient in the placebo arm achieved remission. Significantly more patients in the active treatment group became negative for C trachomatis or C pneumoniae by PCR at month 6. Adverse events were mild, with no significant differences between the groups. Conclusion These data suggest that a 6-month course of combination antibiotics is an effective treatment for chronic Chlamydia -induced ReA. [source] Classification, presentation, and initial treatment of Wegener's granulomatosis in childhoodARTHRITIS & RHEUMATISM, Issue 11 2009David A. Cabral Objective To compare the criteria for Wegener's granulomatosis (WG) of the American College of Rheumatology (ACR) with those of the European League Against Rheumatism/Pediatric Rheumatology European Society (EULAR/PRES) in a cohort of children with WG and other antineutrophil cytoplasmic antibody (ANCA),associated vasculitides (AAVs), and to describe the interval to diagnosis, presenting features, and initial treatment for WG. Methods Eligible patients had been diagnosed by site rheumatologists (termed the "MD diagnosis") since 2004. This diagnosis was used as a reference standard for sensitivity and specificity testing of the 2 WG classification criteria. Descriptive analyses were confined to ACR-classified WG patients. Results MD diagnoses of 117 patients (82 of whom were female) were WG (n = 76), microscopic polyangiitis (n = 17), ANCA-positive pauci-immune glomerulonephritis (n = 5), Churg-Strauss syndrome (n = 2), and unclassified vasculitis (n = 17). The sensitivities of the ACR and EULAR/PRES classification criteria for WG among the spectrum of AAVs were 68.4% and 73.6%, respectively, and the specificities were 68.3% and 73.2%, respectively. Two more children were identified as having WG by the EULAR/PRES criteria than by the ACR criteria. For the 65 ACR-classified WG patients, the median age at diagnosis was 14.2 years (range 4,17 years), and the median interval from symptom onset to diagnosis was 2.7 months (range 0,49 months). The most frequent presenting features by organ system were constitutional (89.2%), pulmonary (80.0%), ear, nose, and throat (80.0%), and renal (75.4%). Fifty-four patients (83.1%) commenced treatment with the combination of corticosteroids and cyclophosphamide, with widely varying regimens; the remainder received methotrexate alone (n = 1), corticosteroids alone (n = 4), or a combination (n = 6). Conclusion The EULAR/PRES criteria minimally improved diagnostic sensitivity and specificity for WG among a narrow spectrum of children with AAVs. Diagnostic delays may result from poor characterization of childhood WG. Initial therapy varied considerably among participating centers. [source] Potential Impact of Adjusting the Threshold of the Quantitative D-dimer Based on Pretest Probability of Acute Pulmonary EmbolismACADEMIC EMERGENCY MEDICINE, Issue 4 2009Christopher Kabrhel MD Abstract Objectives:, The utility of D-dimer testing for suspected pulmonary embolism (PE) can be limited by test specificity. The authors tested if the threshold of the quantitative D-dimer can be varied according to pretest probability (PTP) of PE to increase specificity while maintaining a negative predictive value (NPV) of >99%. Methods:, This was a prospective, observational multicenter study of emergency department (ED) patients in the United States. Eligible patients had a diagnostic study ordered to evaluate possible PE. PTP was determined by the clinician's unstructured estimate and the Wells score. Five different D-dimer assays were used. D-dimer test performance was measured using 1) standard thresholds and 2) variable threshold values: twice (for low PTP patients), equal (intermediate PTP patients), or half (high PTP patients) of standard threshold. Venous thromboembolism (VTE) within 45 days required positive imaging plus decision to treat. Results:, The authors enrolled 7,940 patients tested for PE, and clinicians ordered a quantitative D-dimer for 4,357 (55%) patients who had PTPs distributed as follows: low (74%), moderate (21%), or high (4%). At standard cutoffs, across all PTP strata, quantitative D-dimer testing had a test sensitivity of 94% (95% confidence interval [CI] = 91% to 97%), specificity of 58% (95% CI = 56% to 60%), and NPV of 99.5% (95% CI = 99.1% to 99.7%). If variable cutoffs had been used the overall sensitivity would have been 88% (95% CI = 83% to 92%), specificity 75% (95% CI = 74% to 76%), and NPV 99.1% (95% CI = 98.7% to 99.4%). Conclusions:, This large multicenter observational sample demonstrates that emergency medicine clinicians currently order a D-dimer in the majority of patients tested for PE, including a large proportion with intermediate PTP and high PTP. Varying the D-dimer's cutoff according to PTP can increase specificity with no measurable decrease in NPV. [source] Evaluating therapeutic effect in symptoms of moderate-to-severe premenstrual syndrome with Vitex agnus castus (BNO 1095) in Chinese womenAUSTRALIAN AND NEW ZEALAND JOURNAL OF OBSTETRICS AND GYNAECOLOGY, Issue 2 2010Linlin MA Objectives:, To assess therapeutic effect of an extract of Vitex agnus castus (VAC, BNO 1095) in premenstrual syndrome (PMS) in Chinese women. Design:, It was a prospective, randomised, double-blind, placebo-controlled study carried out in China. Eligible patients were treated with VAC extract or placebo for three cycles. Symptoms were documented with PMS diary (PMSD), a daily rating scale with 17 items. Main efficacy variable was the reduction percentage of 17 symptom score documented in PMSD during the luteal phase of the third treatment cycle. Results:, A total of 67 patients were enrolled and randomly assigned to VAC group or placebo group. Of these, 64 patients completed the study (31 vs. 33). All the 17 symptoms showed a significantly greater improvement with VAC than placebo (P < 0.05) except lower abdominal cramping (P > 0.05). Conclusion:, Vitex agnus castus is more effective than placebo in the treatment of moderate-to-severe PMS in Chinese women, especially in symptoms of negative effect and insomnia. [source] Short-term Functional Decline and Service Use in Older Emergency Department Patients With Blunt InjuriesACADEMIC EMERGENCY MEDICINE, Issue 7 2010Scott T. Wilber MD ACADEMIC EMERGENCY MEDICINE 2010; 17:679,686 © 2010 by the Society for Academic Emergency Medicine Abstract Background:, Injuries are a common reason for emergency department (ED) visits by older patients. Although injuries in older patients can be serious, 75% of these patients are discharged home after their ED visit. These patients may be at risk for short-term functional decline related to their injuries or treatment. Objectives:, The objectives were to determine the incidence of functional decline in older ED patients with blunt injuries not requiring hospital admission for treatment, to describe their care needs, and to determine the predictors of short-term functional decline in these patients. Methods:, This institutional review board,approved, prospective, longitudinal study was conducted in two community teaching hospital EDs with a combined census of 97,000 adult visits. Eligible patients were , 65 years old, with blunt injuries <48 hours old, who could answer questions or had a proxy. We excluded those too ill to participate; skilled nursing home patients; those admitted for surgery, major trauma, or acute medical conditions; patients with poor baseline function; and previously enrolled patients. Interviewers collected baseline data and the used the Older Americans Resources and Services (OARS) questionnaire to assess function and service use. Potential predictors of functional decline were derived from prior studies of functional decline after an ED visit and clinical experience. Follow-up occurred at 1 and 4 weeks, when the OARS questions were repeated. A three-point drop in activities of the daily living (ADL) score defined functional decline. Data are presented as means and proportions with 95% confidence intervals (CIs). Logistic regression was used to model potential predictors with functional decline at 1 week as the dependent variable. Results:, A total of 1,186 patients were evaluated for eligibility, 814 were excluded, 129 refused, and 13 were missed, leaving 230 enrolled patients. The mean (±SD) age was 77 (±7.5) years, and 70% were female. In the first week, 92 of 230 patients (40%, 95% CI = 34% to 47%) had functional decline, 114 of 230 (49%, 95% CI = 43% to 56%) had new services initiated, and 76 of 230 had an unscheduled medical contact (33%, 95% CI = 27% to 39%). At 4 weeks, 77 of 219 had functional decline (35%, 95% CI = 29% to 42%), 141 of 219 had new services (65%, 95% CI = 58% to 71%), and 123 of 219 had an unscheduled medical contact (56%, 95% CI = 49% to 63%), including 15% with a repeated ED visit and 11% with a hospital admission. Family members provided the majority of new services at both time periods. Significant predictors of functional decline at 1 week were female sex (odds ratio [OR] = 2.2, 95% CI = 1.1 to 4.5), instrumental ADL dependence (IADL; OR = 2.5, 95% CI = 1.3 to 4.8), upper extremity fracture or dislocation (OR = 5.5, 95% CI = 2.5 to 11.8), lower extremity fracture or dislocation (OR = 4.6, 95% CI = 1.4 to 15.4), trunk injury (OR = 2.4, 95% CI = 1.1 to 5.3), and head injury (OR = 0.48, 95% CI = 0.23 to 1.0). Conclusions:, Older patients have a significant risk of short-term functional decline and other adverse outcomes after ED visits for injuries not requiring hospitalization for treatment. The most significant predictors of functional decline are upper and lower extremity fractures. [source] Impact of fesoterodine on quality of life: pooled data from two randomized trialsBJU INTERNATIONAL, Issue 1 2008Con J. Kelleher OBJECTIVE To evaluate the effect of fesoterodine on health-related quality of life (HRQoL) in patients with overactive bladder (OAB) syndrome. PATIENTS AND METHODS Pooled data from two randomized placebo-controlled phase III studies were analysed. Eligible patients with frequency and urgency or urgency urinary incontinence were randomized to placebo or fesoterodine 4 or 8 mg for 12 weeks; one trial also included tolterodine extended release (tolterodine-ER) 4 mg. HRQoL was assessed using the King's Health Questionnaire (KHQ), International Consultation on Incontinence Questionnaire,Short Form (ICIQ-SF), a six-point Likert scale measuring the severity of bladder-related problems, and treatment response. RESULTS By the end of treatment, all active-treatment groups had significantly improved HRQoL compared with those on placebo, as shown by an improvement in the KHQ and ICIQ-SF scores, treatment response rate, and a major improvement in self-reported bladder-related problems. The fesoterodine 8-mg group had statistically significant improvements over placebo in eight of nine KHQ domains. Fesoterodine 4 mg and tolterodine-ER produced statistically significant improvements in seven of nine KHQ domains. Fesoterodine 8 mg gave better results than 4 mg in two domains; Emotions and Symptom Severity (P < 0.05). A major improvement (,2 points) in bladder-related problems was reported by 33% of patients on fesoterodine 4 mg, 38% on fesoterodine 8 mg, and 34% on tolterodine-ER, vs 21% on placebo (P < 0.001). CONCLUSIONS Fesoterodine significantly improved HRQoL in patients with OAB. Both fesoterodine 4 and 8 mg produced significant improvements on most KHQ domains, the ICIQ-SF, treatment response rate, and a Likert scale measuring bladder-related problems. [source] A pilot dose-escalation study of the effects of nordihydroguareacetic acid on hormone and prostate specific antigen levels in patients with relapsed prostate cancerBJU INTERNATIONAL, Issue 4 2008Charles J. Ryan OBJECTIVE To assess the tolerability of the effects of nordihydroguareacetic acid (NDGA) and its effect on prostate-specific antigen (PSA) kinetics in patients with relapsed prostate cancer, as among the many biological effects of NDGA is the inhibition of the insulin-like growth factor 1 receptor (IGF-1R) tyrosine kinase. PATIENTS AND METHODS Eligible patients were those with an increasing PSA level after definitive local therapy, in either the non-castrate (androgen-dependent prostate cancer, ADPC) or the castrate state (castration-resistant prostate cancer, CRPC) with no evidence of metastatic disease by bone scan or computed tomography of the abdomen or pelvis. Treatment consisted of continuous oral daily dosing according to a planned dose escalation of 750, 1250, 1750, 2250 and 2500 mg of NDGA. PSA levels were measured every 28 days. Serial levels of testosterone, dihydrotestosterone, oestradiol and sex hormone-binding globulin were measured at baseline and monthly while on study therapy. RESULTS Fifteen patients were enrolled, including 11 with ADPC and four with CRPC. There were asymptomatic increases in transaminase in six patients, two of which were grade 3, all occurring at ,3 months. The increases in transaminase resolved after stopping NDGA but recurred with repeated dosing. Doses of NDGA up to 2500 mg/day caused no other toxicities. A median (range) of 5.5 (1,13) cycles were delivered. Of the 11 patients with ADPC, one had a decline in PSA level of >50% of the baseline value and one a decline of <50%. Three patients with ADPC had a greater than three-fold increase in PSA doubling time while on therapy, one from 11 to 46 months (750 mg), one from 9.5 to 49.5 months (1750 mg), and one from 5.9 to 46.2 months (2500 mg). There were no reductions in PSA level in patients with CRPC. There were no significant effects on levels of testosterone, dihydrotestosterone, oestradiol or sex hormone-binding globulin. CONCLUSIONS Continuous daily dosing with NDGA is reasonably well tolerated but is associated with transaminitis in some patients, that occurs after several months on therapy. There were apparent effects on the rate of increase in PSA. Further study is required to determine the optimum pharmacokinetics and antitumour effects of this therapy. [source] Effect of homeopathy on analgesic intake following knee ligament reconstruction: a phase III monocentre randomized placebo controlled studyBRITISH JOURNAL OF CLINICAL PHARMACOLOGY, Issue 2 2008A. Paris What is already known about this subject ,,The efficacy of homeopathy is still under debate and a recent meta-analysis recommended further randomized double-blind clinical trials to identify any clinical situation in which homeopathy might be effective. What this study adds ,,The complex of homeopathy tested in this study (Arnica montana 5 CH, Bryonia alba 5 CH, Hypericum perforatum 5 CH and Ruta graveolens 3 DH) is not superior to placebo in reducing 24 h morphine consumption after knee ligament reconstruction. Aims The efficacy of homeopathy is still under debate. The objective of this study was to assess the efficacy of homeopathic treatment (Arnica montana 5 CH, Bryonia alba 5 CH, Hypericum perforatum 5 CH and Ruta graveolens 3 DH) on cumulated morphine intake delivered by PCA over 24 h after knee ligament reconstruction. Methods This was an add-on randomized controlled study with three parallel groups: a double-blind homeopathic or placebo arm and an open-label noninterventional control arm. Eligible patients were 18,60 years old candidates for surgery of the anterior cruciate ligament. Treatment was administered the evening before surgery and continued for 3 days. The primary end-point was cumulated morphine intake delivered by PCA during the first 24 h inferior or superior/equal to 10 mg day,1. Results One hundred and fifty-eight patients were randomized (66 in the placebo arm, 67 in the homeopathic arm and 25 in the noninterventional group). There was no difference between the treated and the placebo group for primary end-point (mean (95% CI) 48% (35.8, 56.3), and 56% (43.7, 68.3), required less than 10 mg day,1 of morphine in each group, respectively). The homeopathy treatment had no effect on morphine intake between 24 and 72 h or on the visual analogue pain scale, or on quality of life assessed by the SF-36 questionnaire. In addition, these parameters were not different in patients enrolled in the open-label noninterventional control arm. Conclusions The complex of homeopathy tested in this study was not superior to placebo in reducing 24 h morphine consumption after knee ligament reconstruction. [source] Impact of childhood vitiligo on adult lifeBRITISH JOURNAL OF DERMATOLOGY, Issue 4 2008M.W. Linthorst Homan Summary Background, The onset of vitiligo occurs before the age of 20 years in 50% of patients. Having a chronic disease in childhood can impede a child's health-related quality of life (HRQL). Objectives, Firstly, to compare the social and psychosexual development and current HRQL of young adult patients with childhood vitiligo with those of a group of healthy controls. Secondly, to compare these outcomes in patients reporting negative childhood experiences with those of patients not reporting negative childhood experiences. Methods, Eligible patients were mailed questionnaires on (i) sociodemographic and clinical characteristics, (ii) social and psychosexual development, (iii) generic and dermatology-specific HRQL, (iv) presence of negative childhood experiences related to vitiligo, (v) specification of these negative experiences and (vi) patients' recommendations for further care. Results, A total of 232 patients with vitiligo completed the questionnaires. Social and psychosexual development and generic HRQL in young adult patients with childhood vitiligo were not different from those of healthy controls. However, patients reporting negative childhood experiences reported significantly more problems in social development than those not reporting negative experiences. Furthermore, negative childhood experiences were significantly associated with more HRQL impairment in early adulthood. Conclusions, Reporting negative experiences from childhood vitiligo appears to be associated with HRQL impairment in young adults with vitiligo. [source] Long-term outcomes for patients with limited stage follicular lymphoma,CANCER, Issue 16 2010Involved regional radiotherapy versus involved node radiotherapy Abstract BACKGROUND: Given the indolent behavior of follicular lymphoma (FL), it is controversial whether limited stage FL can be cured using radiotherapy (RT). Furthermore, the optimal RT field size is unclear. The authors of this report investigated the long-term outcomes of patients with limited stage FL who received RT alone and studied the impact of reducing the RT field size from involved regional RT (IRRT) to involved node RT with margins up to 5 cm (INRT,5 cm). METHODS: Eligible patients had limited stage, grade 1 through 3A FL diagnosed between 1986 and 2006 and treated were with curative-intent RT alone. IRRT encompassed the involved lymph node group plus ,1 adjacent, uninvolved lymph node group(s). INRT,5 cm covered the involved lymph node(s) with margins ,5 cm. RESULTS: In total, 237 patients were identified (median follow-up, 7.3 years) and included 48% men, 54% aged >60 years, stage IA disease in 76% of patients, elevated lactate dehydrogenase (LDH) in 7% of patients, grade 3A tumors in 12% of patients, and lymph node size ,5 cm in 19% of patients. The 2 RT groups were IRRT (142 patients; 60%) and INRT,5 cm (95 patients; 40%). At 10 years, the progression-free survival (PFS) rate was 49%, and the overall survival (OS) rate was 66%. Only 2 patients developed recurrent disease beyond 10 years. The most common pattern of first failure was a distant recurrence only, which developed in 38% of patients who received IRRT and in 32% of patients who received INRT,5 cm. After INRT,5 cm, 1% of patients had a regional-only recurrence. Significant risk factors for PFS were lymph nodes ,5 cm (P = .008) and male gender (P = .042). Risk factors for OS were age >60 years (P < .001), elevated LDH (P = .007), lymph nodes ,5 cm (P = .016), and grade 3A tumors (P = .036). RT field size did not have an impact on PFS or OS. CONCLUSIONS: Disease recurrence after 10 years was uncommon in patients who had limited stage FL, suggesting that a cure is possible. Reducing RT fields to INRT,5 cm did not compromise long-term outcomes. Cancer 2010. © 2010 American Cancer Society. [source] Vincristine sulfate liposomes injection (Marqibo) in heavily pretreated patients with refractory aggressive non-Hodgkin lymphoma,CANCER, Issue 15 2009Report of the Pivotal Phase 2 Study Abstract BACKGROUND: Marqibo, a sphingosomal/cholesterol encapsulation of vincristine sulfate has targeted, increased, and sustained delivery of vincristine to tumor tissues. A phase 2, open-label, single-arm, and multinational study evaluated the efficacy and tolerability of Marqibo as a single agent in patients with multiply relapsed or refractory aggressive non-Hodgkin lymphoma (NHL). METHODS: Eligible patients had relapsed or refractory de novo or transformed aggressive NHL and prior treatment with at least 2 multiagent chemotherapy regimens. Marqibo was administered at 2 mg/m2, every 2 weeks, for a maximum of 12 cycles or until toxicity or disease progression. RESULTS: One hundred and nineteen patients were enrolled and treated on trial. Ninety-six had histological confirmed de novo (N = 89) or transformed (N = 7) aggressive NHL. Median number of cycles was 4 (median dose/cycle 4 mg). Overall response (CR and complete response unconfirmed and PR) was 25% (95% confidence interval [CI], 17, 35), CR and complete response unconfirmed confirmed by external reviewers was 5%. Median overall survival was 6.6 months (Kaplan-Meier estimate, 95% CI, 4.7, 9.8). Grade 3 of 4 neurotoxicity occurred in 32% of patients. All patients had prior neurotoxic agents, and 85% had baseline residual neuropathy symptoms (grades 1-2) from prior treatment. CONCLUSIONS: Marqibo is an active agent in patients with heavily pretreated aggressive NHL, and tolerated at approximately twice the dose intensity of standard vincristine. Its activity supports further investigation as a substitution for vincristine in combination treatment of lymphoid disorders. Cancer 2009. © 2009 American Cancer Society. [source] Erlotinib plus bevacizumab in previously treated patients with malignant pleural mesotheliomaCANCER, Issue 4 2008David M. Jackman MD Abstract BACKGROUND. We conducted a phase 2, multicenter, open-label study of erlotinib plus bevacizumab in patients with malignant pleural mesothelioma who had previously received 1 prior chemotherapy regimen. These agents have activity in non,small cell lung cancer, but their role in mesothelioma is unclear. The primary endpoint is response rate. Secondary endpoints include time to progression, survival, and toxicity. METHODS. Eligible patients with mesothelioma who had previously received 1 chemotherapy regimen were treated with erlotinib 150 mg per os daily and bevacizumab 15 mg/kg administered intravenously on Day 1 of a 21-day cycle. Treatment continued until disease progression or development of significant toxicity. Tumor response was assessed after every 2 cycles using previously established mesothelioma response criteria from Byrne and Nowak. RESULTS. Twenty-four eligible patients initiated therapy with erlotinib and bevacizumab between February 2004 and October 2006. There were no complete or partial responses, although 12 patients achieved stable disease for at least 2 cycles of treatment. The median time to progression was 2.2 months (95% confidence interval [CI], 1.4 months-5.9 months). The median survival was 5.8 months (95% CI, 2.8 months-10.1 months). The most common toxicities were rash and diarrhea. There were no treatment-related deaths, intracranial bleeding, or hemoptysis. CONCLUSIONS. The combination of erlotinib and bevacizumab was tolerated reasonably well, but there was no evidence of radiographic response. This study demonstrates the feasibility of conducting trials in mesothelioma patients who have failed first-line therapy. More therapeutic studies with effective agents are needed for these patients. Cancer 2008. © 2008 American Cancer Society. [source] Treatment options for muscle-invasive urothelial cancer for patients who were not eligible for cystectomy or neoadjuvant chemotherapy with methotrexate, vinblastine, doxorubicin, and cisplatinCANCER, Issue 10 2008Report of Southwest Oncology Group Trial 873 Abstract BACKGROUND. Many patients with invasive urothelial cell cancer are poor candidates for cisplatin-based chemotherapy, and many are high risk for cystectomy. Southwest Oncology Group Trial 8733 was designed to address treatment for such patients. METHODS. Eligible patients had primary or recurrent muscle-invasive disease with transitional cell or squamous cell histology, a performance status from 0 to 2, no extrapelvic disease, a life expectancy >3 months, and adequate hematologic function. The treating clinician assigned patients to operable or inoperable groups. All patients received 2 cycles of 5-fluorouracil (5-FU) at a dose of 1000mg/m2 per day × 4 starting concurrently with radiation at a dose of 200 centigrays per day × 10 each cycle. After 2 cycles, operable patients with positive biopsies underwent cystectomy, and patients with negative biopsies received a third cycle of chemoradiotherapy. Patients in the inoperable group received 3 cycles without interim biopsy. RESULTS. Eighteen of 24 eligible patients in the operable group were evaluable for response. Five patients had a complete response (CR), 9 patients had stable disease, 1 patient had progressive disease, and 3 patients were not assessable. The median progression-free survival was 10 months (95% confidence interval [95% CI], 4,14 months), and the median overall survival was 18 months (95% CI, 7,28 months). In the inoperable group, 35 of 37 eligible patients were evaluable for response with 17 CRs (49%; 95% CI, 31%,66%). The median progression-free survival was 13 months (95% CI, 10,17 months), and the median overall survival was 20 months (95% CI, 11,53 months). There were no episodes of grade 4 toxicity. CONCLUSIONS. In the current study, the combination of 5-FU and radiation was found to be tolerated well by patients with numerous comorbidities who could not tolerate cisplatin-based therapy or cystectomy. Cancer 2008. © 2008 American Cancer Society. [source] Phase 2 trial of docetaxel and gefitinib in the first-line treatment of patients with advanced nonsmall-cell lung cancer (NSCLC) who are 70 years of age or older,CANCER, Issue 9 2008George R. Simon MD Abstract BACKGROUND This is a phase 2 study of chemotherapy-naive patients, 70 years of age or older, with nonsmall-cell lung cancer (NSCLC) who were treated with docetaxel and gefitinib. The primary endpoint was response rate (RR). Secondary endpoints were overall survival (OS) and progression-free survival (PFS). METHODS Eligible patients were treated with docetaxel 75 mg/m2 every 3 weeks and gefitinib 250 mg orally, daily. Docetaxel and gefitinib were given for 2 cycles beyond maximal response. Gefitinib was continued until disease progression. Comorbidities and activities of daily living were assessed (IADL). RESULTS Forty-four patients initiated therapy between March 2003 and May 2005. Seventeen patients (40%; 95% confidence interval [CI], 26%,57%) had a partial response and 48% had stable disease. The median PFS was 6.9 months (95% CI, 3.95,7.8 months). Median survival time was 9.6 months (95% CI, 4.6,16.3 months). On univariate analyses, sex, Eastern Cooperative Oncology Group Performance Status (ECOG PS), and Charlson comorbidities index (CCI) score were predictors of improved survival. On multivariate analyses female sex was a statistically significant predictor of survival. The median survivals were 22.8 months in women and 4.8 months in men. This regimen was well tolerated, with the most common adverse events being hyperglycemia, fatigue, and lymphopenia. CONCLUSIONS Docetaxel combined with gefitinib is active and well tolerated in patients with advanced NSCLC who are 70 years of age and older. This paradigm of treatment merits further investigation as a first-line treatment strategy. Female sex-specific confirmatory clinical trials with this regimen may be warranted. Cancer 2008. © 2008 American Cancer Society. [source] An open-label, multinational, multicenter study of G17DT vaccination combined with cisplatin and 5-fluorouracil in patients with untreated, advanced gastric or gastroesophageal cancer : The GC4 studyCANCER, Issue 9 2006Jaffer A. Ajani M.D. Abstract BACKGROUND Gastrin hormone is trophic to in vitro gastric cancer, and the antigastrin antibodies (AGAs) are antiproliferative and antimetastatic. Human gastric cancers overexpress gastrin genes and receptors that react to gastrin's trophic effects. Immunogen G17DT elicits a specific and high-affinity AGA. The authors evaluated G17DT vaccination given with cisplatin plus 5-fluorouracil for the treatment gastric adenocarcinoma. METHODS In this multicenter, Phase II study, patients received G17DT vaccination intramuscularly on Weeks 1, 5, 9 and 25 and cisplatin plus 5-fluorouracil every 28 days. Eligible patients had untreated, metastatic, or unresectable gastric or gastroesophageal adenocarcinoma with near-normal organ function. The primary endpoint of the study was the over response rate (ORR), and secondary endpoints included overall survival (OS), safety, and the impact of successful vaccination on patient outcome. RESULTS In total, 103 patients were enrolled in 5 countries. Seven patients who were overdosed inadvertently with 5-fluorouracil (a major protocol violation) were removed from the analysis. The confirmed ORR was 30% in 79 patients who were evaluated for response. The median time-to-progression (TTP) was 5.4 months, and the median survival (MS) was 9.0 months (n = 96 patients). Sixty-five of 94 patients who were vaccinated (69%) had 2 consecutive AGA titers of ,1 units (successfully vaccinated patients or immune-responders). The TTP was longer in immune-responders than in immune-nonresponders (P = .0005). Similarly, the MS was longer in immune-responders than in immune-nonresponders (10.3 months vs. 3.8 months; P ,.0001). In a multivariate analysis, successful vaccination was an independent OS prognosticator (P = .0001). G17DT did not have an adverse effect on safety. CONCLUSIONS The results demonstrated that successful G17DT vaccination was correlated with longer TTP and MS. AGA response was an independent OS prognosticator. A Phase III evaluation of G17DT in gastric cancer is warranted. Cancer 2006. © 2006 American Cancer Society. [source] Capecitabine combined with gemcitabine (CapGem) as first-line treatment in patients with advanced/metastatic biliary tract carcinomaCANCER, Issue 12 2005Jae Yong Cho M.D., Ph.D. Abstract BACKGROUND Biliary tract carcinoma is an aggressive cancer, with median survival rarely exceeding 6 months. There is currently no established palliative standard of care. A Phase II trial was conducted to study a combination of oral capecitabine and gemcitabine (CapGem) as first-line therapy in patients with advanced and/or metastatic biliary carcinoma. METHODS Patients with unresectable or metastatic intrahepatic or extrahepatic biliary duct carcinoma and gallbladder carcinoma were enrolled. Eligible patients had histologically or cytologically confirmed, measurable adenocarcinoma and had not received prior therapy with capecitabine or gemcitabine. Treatment consisted of intravenous (i.v.) gemcitabine (1000 mg/m2 on Days 1 and 8) plus oral capecitabine (650 mg/m2 twice daily on Days 1,14) every 3 weeks for up to 6 cycles. Tumor response, survival, and safety were determined. RESULTS A total of 44 patients were evaluable. Primary tumor sites were: intrahepatic (n = 14) and extrahepatic biliary duct (n = 16); gallbladder (n = 7); and ampulla (n = 7). Fourteen (32%) patients had a partial response and 15 (34%) patients had stable disease. Median time to disease progression and overall survival were 6.0 (range, 3.8,8.1) and 14 (range, 11.4,16.6) months, respectively. The 1-year survival rate was 58%. No Grade 4 adverse events were seen. Transient Grade 3 neutropenia/thrombocytopenia and manageable (almost invariably Grade 2) nausea, diarrhea, and hand,foot syndrome were the most common adverse events. CONCLUSIONS CapGem is an active and well tolerated first-line combination chemotherapy regimen for patients with advanced/metastatic biliary tract carcinoma that offers a convenient home-based therapy. Cancer 2005. © 2005 American Cancer Society. [source] Phase I study of TZT-1027, a novel synthetic dolastatin 10 derivative and inhibitor of tubulin polymerization, given weekly to advanced solid tumor patients for 3 weeksCANCER SCIENCE, Issue 2 2009Nobuyuki Yamamoto TZT-1027 is a novel synthetic dolastatin 10 derivative that inhibits tubulin polymerization. A phase I study was conducted to determine the maximum tolerated dose (MTD) of TZT-1027, and to assess its pharmacokinetic profile in Japanese patients with advanced solid tumors following administration of the drug weekly for 3 weeks. Eligible patients had advanced solid tumors that failed to respond to standard therapy or for which no standard therapy was available, and met the following criteria: performance status ,2 and acceptable organ function. The MTD was defined as the highest dose at which more than two-thirds of the patients experienced grade 4 hematological toxicity or grade 3/4 non-hematological toxicity during weekly TZT-1027 administration for 3 weeks. Forty patients were enrolled in the present study. Twelve doses between 0.3 and 2.1 mg/m2 were evaluated. Grade 4 neutropenia was the principal dose-limiting toxicity (DLT). At a dose of 2.1 mg/m2, two patients developed DLT: one patient developed grade 4 neutropenia, grade 3 myalgia, and grade 4 constipation, and the other one developed grade 4 neutropenia and grade 3 constipation. At a dose level of 1.8 mg/m2, toxicity was acceptable and no DLT was observed. The area under the curve and maximum concentration of TZT-1027 tended to increase linearly with the dose. The DLT observed were neutropenia, myalgia, and constipation, and the MTD was 2.1 mg/m2. The recommended dose for a phase II study was determined to be 1.8 mg/m2 for the drug administered weekly for 3 weeks. (Cancer Sci 2009; 100: 316,321) [source] Phase I study of dexamethasone, methotrexate, ifosfamide, l -asparaginase, and etoposide (SMILE) chemotherapy for advanced-stage, relapsed or refractory extranodal natural killer (NK)/T-cell lymphoma and leukemiaCANCER SCIENCE, Issue 5 2008Motoko Yamaguchi Extranodal natural killer (NK)/T-cell lymphoma, nasal type, and aggressive NK-cell leukemia are rare, and their standard therapy has not been established. They are Epstein,Barr virus-associated lymphoid malignancies, and tumor cells express P-glycoprotein leading to multidrug resistance of the disease. Patients with stage IV, relapsed or refractory diseases have a dismal prognosis, with survival measured in months only. To develop an efficacious chemotherapeutic regimen, we conducted a dose-escalation feasibility study of a new chemotherapeutic regimen, SMILE, comprising the steroid dexamethasone, methotrexate, ifosfamide, l -asparaginase, and etoposide. The components of SMILE are multidrug resistance-unrelated agents and etoposide. Etoposide shows both in vitro and in vivo efficacy for Epstein,Barr virus-associated lymphoproliferative disorders. Eligible patients had newly diagnosed stage IV, relapsed or refractory diseases after first-line chemotherapy, were 15,69 years of age, and had satisfactory performance scores (0,2). Four dose levels of methotrexate and etoposide were originally planned to be evaluated. At level 1, six patients with extranodal NK/T-cell lymphoma, nasal type, were enrolled. Their disease status was newly diagnosed stage IV (n = 3), first relapse (n = 2), and primary refractory (n = 1). All of the first three patients developed dose-limiting toxicities, and one of them died of sepsis with grade 4 neutropenia. A protocol revision stipulating early granulocyte colony-stimulating factor administration was made. Two out of three additional patients developed dose-limiting toxicities that were all manageable and transient. For the six enrolled patients, the overall response rate was 67% and the complete response rate was 50%. Although its safety and efficacy require further evaluation, we recommend a SMILE chemotherapy dose level of 1 for further clinical studies. (Cancer Sci 2008; 99: 1016,1020) [source] Switching from a preserved to a preservative-free prostaglandin preparation in topical glaucoma medicationACTA OPHTHALMOLOGICA, Issue 3 2010Hannu Uusitalo Abstract. Purpose:, The purpose of this study was to investigate the tolerability and intraocular pressure (IOP) reducing effect of the first preservative-free prostaglandin tafluprost (Taflotan®) in patients exhibiting ocular surface side-effects during latanoprost (Xalatan®) treatment. Methods:, A total of 158 patients were enrolled in this open-label multicentre study. Eligible patients had to have at least two ocular symptoms, or one sign and one symptom, during treatment with latanoprost. At baseline, the patients were directly switched from latanoprost to preservative-free tafluprost for 12 weeks. The patients were queried for ocular symptoms, and ocular signs were assessed by using tear break-up time, Schirmer's test, fluorescein staining and evaluation of conjunctival hyperaemia and blepharitis. In addition, HLA-DR and MUC5AC in conjunctival impression cytology specimens were analyzed, and a drop discomfort/quality of life (QoL) questionnaire was employed. IOP was measured at all visits. Results:, Preservative-free tafluprost maintained IOP at the same level after 12- weeks treatment (16.4 ± 2.7 mmHg) as latanoprost at baseline (16.8 ± 2.5 mmHg). During treatment with preservative-free tafluprost, the number of patients having irritation/burning/stinging (56.3%), itching (46.8%), foreign body sensation (49.4%), tearing (55.1%) and dry eye sensation (64.6%) decreased to 28.4%, 26.5%, 27.1%, 27.1% and 39.4% correspondingly. The number of the patients with abnormal fluorescein staining of cornea (81.6%) and conjunctiva (84.2%), blepharitis (60.1%), conjunctival hyperaemia (84.2%) and abnormal Schirmer's test (71.5%) was also reduced significantly to 40.6%, 43.2%, 40.6%, 60.0% and 59.4% correspondingly. The tear break-up time improved significantly from 4.5 ± 2.5 seconds to 7.8 ± 4.9 seconds. A reduction in the number of patients with abnormal conjunctival cells based on HLA-DR and MUC5AC was also detected. Conclusions:, Preservative-free tafluprost maintained IOP at the same level as latanoprost, but was better tolerated in patients having signs or symptoms while on preserved latanoprost. Preservative-free tafluprost treatment resulted in improved QoL, increased patient satisfaction and drop comfort. [source] Efficacy and safety of tafluprost 0.0015% versus latanoprost 0.005% eye drops in open-angle glaucoma and ocular hypertension: 24-month results of a randomized, double-masked phase III studyACTA OPHTHALMOLOGICA, Issue 1 2010Hannu Uusitalo Abstract. Purpose:, The objective of the study was to compare the long-term efficacy and safety of tafluprost 0.0015% with latanoprost 0.005% eye drops in patients with open-angle glaucoma or ocular hypertension. Methods:, This double-masked, active-controlled, parallel-group, multinational, multicentre, phase III study was conducted at 49 centres in 8 countries. Eligible patients were assigned to treatment administered once daily at 20:00 hrs for up to 24 months. Change from baseline intraocular pressure (IOP) was the primary efficacy variable. Adverse events were recorded and ocular safety was evaluated. Both tafluprost and latanoprost were preserved with benzalkonium chloride. Results:, From 533 patients randomized, 402 patients completed 24 months of therapy. Both treatments had a substantial IOP-lowering effect which persisted throughout the study (,7.1 mmHg for tafluprost and ,7.7 mmHg for latanoprost at 24 months). Although the IOP-lowering effect during the study was slightly larger with latanoprost, this difference was clinically small and the noninferiority of tafluprost to latanoprost over all diurnal IOP measurements was shown with anova and almost reached with ancova (upper limits of the 95% confidence intervals 1.38 and 1.52 for the overall period, respectively). The noninferiority limit was 1.5 mmHg. Conclusions:, Tafluprost is a new effective and well-tolerated treatment for glaucoma and ocular hypertension. [source] | |||||||||||||||||||||||||||||||||||||