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Terms modified by Evaluable Selected AbstractsRisperidone long-acting injection: a 6-year mirror-image study of healthcare resource useACTA PSYCHIATRICA SCANDINAVICA, Issue 2 2009D. Taylor Objective:, To evaluate naturalistic use of risperidone long-acting injection (RLAI) and its effect on healthcare resource use. Method:, Mirror-image comparison of healthcare resource use for 3 years before RLAI initiation and 3 years after. Results:, In total, 211 of 277 patients consecutively prescribed RLAI were evaluable over the full 6-year study period. Median days in hospital/patient increased significantly in the 3 years after RLAI initiation [87 days (inter-quartile range 25,236) before vs. 192 days (47,426) after; P < 0.001]. Those 34 patients who continued RLAI for 3 years showed no change in median bed days [64 days (6.5,182) before vs. 64 days (12,180) after] and median number of admissions was decreased [1.5 (1,2.25) before vs. 1.00 (0,1.25) after; P = 0.001]. Healthcare costs more than doubled for the whole cohort (P < 0.001) and discontinuers (P < 0.001) and increased significantly for continuers (P = 0.010). Conclusion:, RLAI did not decrease either time spent in hospital or overall healthcare costs in this patient cohort. [source] Concomitant low-dose cisplatin and three-dimensional conformal radiotherapy for locally advanced squamous cell carcinoma of the head and neck: Analysis of survival and toxicity,HEAD & NECK: JOURNAL FOR THE SCIENCES & SPECIALTIES OF THE HEAD AND NECK, Issue 3 2006Harold Lau MD Abstract Background. Our center sought to implement a simple chemoradiotherapy schedule for patients with locally advanced squamous cell carcinoma of the head and neck (SCCHN) with minimal toxicity to achieve rates of overall survival comparable to other schedules. Methods. The chemoradiotherapy schedule consisted of daily radiation to 70 Gy over 7 weeks with concurrent cisplatin 20 mg/m2 during days 1 to 4 of weeks 1 and 5. Acute and late toxicities were recorded according to the Radiation Therapy Oncology Group (RTOG) and common toxicity criteria (CTC) grading. The overall, disease-specific, and locoregional recurrence,free survival were calculated using the STATA statistics package. Possible factors influencing these endpoints were analyzed. Results. Fifty-seven patients were treated, and 56 patients were evaluable for follow-up. Median follow-up of alive patients was 16.1 months. There was an 82% complete response rate to chemoradiotherapy. The 2-year Kaplan,Meier overall, disease-specific, and locoregional recurrence,free survival rates were 62%, 67%, and 63%. Acute grade 3 and 4 radiation toxicity was noted in 61% and 2%, respectively. Grade 3 or 4 hematologic toxicity was noted in 7% of patients. Factors influencing overall survival included: Karnofsky performance status, receiving more than 50% of planned chemotherapy, age, and initial hemoglobin level. Conclusion. This regimen is tolerable and achieves overall survival and locoregional control rates comparable to other chemoradiotherapy schedules. © 2005 Wiley Periodicals, Inc. Head Neck27: XXX,XXX, 2005 [source] Phase II study of arsenic trioxide and ascorbic acid for relapsed or refractory lymphoid malignancies: a Wisconsin Oncology Network study,HEMATOLOGICAL ONCOLOGY, Issue 1 2009JE Chang Abstract Arsenic trioxide (As2O3) has established clinical activity in acute promyelocytic leukaemia and has pre-clinical data suggesting activity in lymphoid malignancies. Cell death from As2O3 may be the result of oxidative stress. Agents which deplete intracellular glutathione, such as ascorbic acid (AA), may potentiate arsenic-mediated apoptosis. This multi-institution phase II study investigated a novel dosing schedule of As2O3 and AA in patients with relapsed or refractory lymphoid malignancies. Patients received As2O3 0.25,mg/kg IV and AA 1000,mg IV for five consecutive days during the first week of each cycle followed by twice weekly infusions during weeks 2,6. Cycles were repeated every 8 weeks. The primary end point was objective response. In a subset of patients, sequential levels of intracellular glutathione and measures of Bcl-2 and Bax gene expression were evaluated in peripheral blood mononuclear cells during treatment. Seventeen patients were enrolled between March 2002 and February 2004. The median age was 71, and the majority of enrolled patients had non-Hodgkin's lymphoma (12/17). Sixteen patients were evaluable, and one patient with mantle cell lymphoma achieved an unconfirmed complete response after five cycles of therapy for an overall response rate of 6%. The trial, which had been designed as a two-stage study, was closed after the first stage analysis due to lack of activity. Haematologic toxicities were the most commonly reported events in this heavily pre-treated population, and comprised the majority of grade 3 and 4 toxicities. Intracellular depletion of glutathione was not consistently observed during treatment. As2O3 and AA in this novel dosing strategy was generally well tolerated but had limited activity in patients with relapsed and refractory lymphoid malignancies. Copyright © 2008 John Wiley & Sons, Ltd. [source] The potent bile acid sequestrant colesevelam is not effective in cholestatic pruritus: Results of a double-blind, randomized, placebo-controlled trial,,HEPATOLOGY, Issue 4 2010Edith M. M. Kuiper Colesevelam is an anion-exchange resin with a 7-fold higher bile acid,binding capacity and fewer side effects than cholestyramine, the current first-line treatment option for cholestatic pruritus. The aim of this trial was to compare the effects of colesevelam and a placebo in patients with cholestatic pruritus. In a randomized, double-blind, investigator-initiated, multicenter trial, patients with cholestatic pruritus, both treatment-naive and previously treated, received 1875 mg of colesevelam or an identical placebo twice daily for 3 weeks. The effect on pruritus was assessed with daily visual analogue scales, quality-of-life scores, and evaluations of cutaneous scratch lesions. The predefined primary endpoint was the proportion of patients with at least a 40% reduction in pruritus visual analogue scale scores. Thirty-eight patients were included, and 35 were evaluable: 17 took colesevelam, 18 took the placebo, 22 were female, 8 were treatment-naive, 14 had primary biliary cirrhosis, and 14 had primary sclerosing cholangitis. The mean serum bile acid levels were comparable between the groups before treatment (P = 0.74), but they were significantly different after treatment (P = 0.01) in favor of patients treated with colesevelam. Thirty-six percent of patients in the colesevelam group reached the primary endpoint versus 35% in the placebo group (P = 1.0). There were no significant differences between the groups with respect to pruritus scores, quality-of-life scores, and severity of cutaneous scratch lesions. Mild side effects occurred in one colesevelam-treated patient and four placebo-treated patients. Conclusion: Although colesevelam significantly decreased serum bile acid levels, this trial was unable to demonstrate that it was more effective than a placebo in alleviating the severity of pruritus of cholestasis. (HEPATOLOGY 2010) [source] Chromogenic in situ hybridization for Her-2/neu-oncogene in breast cancer: comparison of a new dual-colour chromogenic in situ hybridization with immunohistochemistry and fluorescence in situ hybridizationHISTOPATHOLOGY, Issue 6 2009Doris Mayr Aims:, Her-2/neu testing is used as a marker for Herceptin® therapy. The aim was to investigate new dual-colour chromogenic in situ hybridization (CISH), in a large number of breast carcinomas (n = 205) with DNA-specific dual-colour probes (ZytoVision, Bremerhaven, Germany) and to compare the results with immunohistochemistry (n = 205) and fluorescence in situ hybridization (FISH) (n = 129). Methods and results:, Paraffin-embedded tissue of 205 patients was used. After immunohistochemistry with a focus on immunohistochemically uncertain cases, Her-2/neu amplification using dual-colour CISH (ZytoVision®) was analysed. Validation by FISH was performed. The results were: immunohistochemistry, 27.8% with strong expression, 53.7% with uncertain overexpression and 18.5% with no expression; FISH, 25.6% amplified and 74.4% negative; CISH, 35.6% amplified, 62.9% negative and 1.5% not evaluable. Comparison of immunohistochemistry with CISH: CISH negative in 100% with immunohistochemistry 0/1+, amplified in 82.5% with immunohistochemistry 3+; 5.9% contradictory results: 4.4% immunohistochemistry 3+ and negative by CISH, 1.5% negative in immunohistochemistry but amplified by CISH; FISH (129 cases), 8.5% contradictory results to immunohistochemistry, 6.2% immunohistochemistry 3+ and negative by FISH, 2.3% negative by immunohistochemistry and amplified by FISH; comparison of CISH and FISH, 94.6% same results, 3.9% different ones, 1.6% CISH not analysable. Conclusions:, CISH, using dual-colour probes (ZytoVision®) is as good as FISH for Her-2/neu analysis. The few discrepant results are likely to be caused by polysomy or tumour heterogeneity. [source] Once-Daily Cefepime Versus Ceftriaxone for Nursing Home,Acquired PneumoniaJOURNAL OF AMERICAN GERIATRICS SOCIETY, Issue 5 2007Joseph A. Paladino PharmD OBJECTIVES: To compare once-daily intramuscular cefepime with ceftriaxone controls. DESIGN: Double-blind study. SETTING: Six skilled nursing facilities. PARTICIPANTS: Residents aged 60 and older with nursing home,acquired pneumonia. INTERVENTION: Cultures were obtained, and patients were randomized to cefepime or ceftriaxone 1 g intramuscularly every 24 hours. MEASUREMENTS: Clinical success: cure or improvement. Cure was defined as complete resolution of all symptoms and signs of pneumonia or a return to the patient's baseline state. Improvement was defined as clear improvement but incomplete resolution of all pretherapy symptoms or signs or incomplete return to the patient's usual baseline status. Safety and pharmacoeconomics were also assessed. RESULTS: Sixty-nine patients were randomized; 61 were evaluable: (32 to cefepime, 29 ceftriaxone). Patients were predominately female (76%). They had a mean age±standard deviation of 85±6, with a mean 5.8±1.9 comorbidities; they had age-appropriate renal dysfunction, with a mean estimated creatinine clearance of 35±7 mL/min. Clinical success occurred in 78% of cefepime- and 66% of ceftriaxone-treated patients (P=.39). Fifty-seven patients (93%) were switched to oral antibiotics after 3 days. Antibiotic-related adverse events occurred in 5% of patients. Seven patients (11.5%) were hospitalized. The overall mortality rate was 8%. Mean antibiotic costs were $117±40 for cefepime- and $215±68 for ceftriaxone-treated patients (P<.001). Cost-effectiveness analysis of total costs showed that cefepime would cost $597 and ceftriaxone $1,709 per expected successfully treated patient. One- and two-way sensitivity analyses using a generic price for ceftriaxone and improving its comparative efficacy revealed that the results were robust. CONCLUSIONS: Once-daily cefepime was a cost-effective alternative to ceftriaxone for the treatment of elderly nursing home residents who developed pneumonia and did not require hospitalization. [source] HIV-1 replication capacity and genotype changes in patients undergoing treatment interruption or lamivudine monotherapy,JOURNAL OF MEDICAL VIROLOGY, Issue 2 2008Nicola Gianotti Abstract The objective of this study was to investigate the mechanisms underlying the virological and immunological changes occurring in failing HIV-1 infected patients undergoing treatment interruption or lamivudine monotherapy (the E-184V Study). Associations were sought between the de-selection of individual reverse transcriptase and protease resistance mutations and replication capacity recovery, HIV-RNA changes, and immunological changes. The replication capacity recovery was defined as the ratio between the replication capacity at weeks 24 or 48, and that measured at baseline. The replication capacity recovery, which was evaluable in 21 patients at week 24 and in 18 at week 48, was significantly higher in the treatment interruption than in the lamivudine group at week 24 (P,=,0.002). Forty-eight week replication capacity recovery was greater when the 184V (P,=,0.023), the 41L (P,=,0.02), or the 215Y mutation (P,=,0.037) were deselected at week 12. A greater reduction in the CD4+/CD8+ ratio at week 48 (P,=,0.038) was observed as the 184V mutation was deselected and the de-selection of the 184V mutation at week 12 was the only independent predictor of the change of the CD4+/CD8+ ratio at week 48 from baseline at multivariable analysis (F -value,=,6.72, P,=,0.021). In conclusion, among patients undergoing treatment interruption or lamivudine monotherapy, the recovery of HIV-1 replication capacity was associated with the de-selection of reverse transcriptase mutations. The de-selection of the 184V mutation predicts independently a reduction in the CD4+/CD8+ ratio. J. Med. Virol. 80:201,208, 2008. © 2007 Wiley-Liss, Inc. [source] Ultrasound screening for asymptomatic deep vein thrombosis after major orthopaedic surgery: the VENUS studyJOURNAL OF THROMBOSIS AND HAEMOSTASIS, Issue 7 2007S. M. SCHELLONG Summary.,Background:,Venography is currently used to assess the incidence of deep vein thrombosis (DVT) in dose-finding and confirmatory trials of new antithrombotic agents. Centrally adjudicated, complete compression ultrasound (CCUS) could be a non-invasive alternative to venography. Objectives:,A substudy of two, similarly designed, phase IIb trials of a novel, oral anticoagulant for the prevention of venous thromboembolism after elective hip or knee arthroplasty was undertaken to validate CCUS against venography. Patients/Methods:,Patients received study drugs until mandatory, bilateral venography was performed 7 ± 2 days after surgery. CCUS was performed within 24 h after venography by sonographers blinded to the venography result. Sonographers were trained and certified for the standardized examination and documentation procedure. Venograms and sonograms were adjudicated centrally at different sites by two independent readers; discrepancies between readers were resolved by consensus. Results:,A total of 1104 matching pairs of evaluable venograms and sonograms were obtained from the participants of the two trials (n = 1435): 19% of venograms and 20% of sonograms were not evaluable. The observed frequency of any DVT was 18.9% with venography and 11.5% with CCUS. Sensitivity of CCUS compared with venography was 31.1% for any DVT (95% confidence interval 23.4, 38.9), 21.0% (2.7, 39.4) for proximal DVT, and 30.8% (23.1, 38.6) for distal DVT. The figures for specificity were 93.0% (91.0, 95.1), 98.7% (98.0, 99.5), and 93.3% (91.5, 95.3), respectively. Conclusions:,Based on these results, centrally adjudicated CCUS will be unable to replace venography for DVT screening early after major orthopaedic surgery in studies evaluating anticoagulant drugs. [source] Clinical trial: comparison of ibuprofen-phosphatidylcholine and ibuprofen on the gastrointestinal safety and analgesic efficacy in osteoarthritic patientsALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 4 2008F. L. LANZA Summary Background, Chronic use of NSAIDs is associated with gastrointestinal (GI) toxicity that increases with age. Aim, To evaluate the GI safety and therapeutic efficacy of ibuprofen chemically associated with phosphatidylcholine (PC) in osteoarthritic (OA) patients. Methods, A randomized, double-blind trial of 125 patients was performed. A dose of 2400 mg/day of ibuprofen or an equivalent dose of ibuprofen-PC was administered for 6 weeks. GI safety was assessed by endoscopy. Efficacy was assessed by scores of analgesia and anti-inflammatory activity. Bioavailability of ibuprofen was pharmacokinetically assessed. Results, Ibuprofen-PC and ibuprofen provided similar bioavailability/therapeutic efficacy. In the evaluable subjects, a trend for improved GI safety in the ibuprofen-PC group compared with ibuprofen that did not reach statistical significance was observed. However, in patients aged >55 years, a statistically significant advantage for ibuprofen-PC treatment vs. ibuprofen in the prevention of NSAID-induced gut injury was observed with increases in both mean Lanza scores and the risk of developing >2 erosions or an ulcer. Ibuprofen-PC was well tolerated with no major adverse events observed. Conclusion, Ibuprofen-PC is an effective osteoarthritic agent with an improved GI safety profile compared with ibuprofen in older OA patients, who are most susceptible to NSAID-induced gastroduodenal injury. [source] Efficacy and safety of single- and multiple-dose ketotifen fumarate 0.025% ophthalmic solution in a pediatric populationPEDIATRIC ALLERGY AND IMMUNOLOGY, Issue 6 2004Mark B. Abelson Allergic conjunctivitis can seriously disrupt children's daily activities. This study assessed the efficacy (onset and duration of action) and safety of ketotifen fumarate 0.025% ophthalmic solution compared with vehicle placebo in pediatric subjects after single and multiple dosing. This was a double-masked, multicenter, fellow-eye, placebo-controlled, conjunctival allergen challenge trial. Eligible subjects (8,16-yr-olds) who produced a qualifying reaction to allergen were randomized to a single dose (one drop) of ketotifen fumarate in one eye and vehicle placebo in the fellow eye, followed by an allergen challenge at 15 min and 8 h post-dose. Subjects who had a qualifying reaction to allergen in the placebo-treated eye and a qualifying response to ketotifen in the active-treated eye following the single dose were re-randomized to a multiple-dose treatment period. They were instructed to instill one drop of ketotifen fumarate in one eye and placebo in the other eye twice daily for 4 wk. An allergen challenge was conducted 8 h after the last dose. The primary efficacy assessment was ocular itching, judged by the subject at 3, 7, and 10 min post-allergen challenge after single- and multiple-dose treatments. Other ocular signs and symptoms were assessed at 7, 10, and 15 min post-dose. A total of 133 subjects were randomized to single-dose treatment; 105 were evaluable for efficacy. Of these, 60 were re-randomized to multiple-dose treatment, and 55 were evaluable for efficacy. After single and multiple doses, ketotifen fumarate significantly inhibited ocular itching compared with placebo at all post-challenge timepoints (p < 0.001) and also significantly reduced hyperemia, chemosis, and lid swelling (p = 0.031). No drug-related systemic adverse events were reported, and ocular adverse events were comparable to placebo. No subject discontinued prematurely due to an adverse event. These results indicate that ketotifen fumarate 0.025% ophthalmic solution is an effective and safe treatment option for children with allergic conjunctivitis. [source] Cytoreductive therapy in 108 adults with systemic mastocytosis: Outcome analysis and response prediction during treatment with interferon-alpha, hydroxyurea, imatinib mesylate or 2-chlorodeoxyadenosine,AMERICAN JOURNAL OF HEMATOLOGY, Issue 12 2009Ken H. Lim Cytoreductive therapy in systemic mastocytosis (SM) includes several drugs whose individual merit has not been well characterized. We retrospectively studied 108 Mayo Clinic patients who met the 2008 WHO diagnostic criteria for SM and received at least one cytoreductive drug. The numbers of patients who were evaluable for response to treatment with interferon-alpha with or without prednisone (IFN-,), hydroxyurea (HU), imatinib mesylate (IM) or 2-chlorodeoxyadenosine (2-CdA) were 40, 26, 22, and 22, respectively. The corresponding overall (major) response rates, according to recently published consensus criteria, were 53% (18%), 19% (0%), 18% (9%), and 55% (37%). The respective overall response rates in indolent SM, aggressive SM and SM associated with another clonal hematological nonmast cell lineage disease (SM-AHNMD) were 60%, 60%, 45% for IFN-,, 0, 0, 21% for HU, 14%, 50%, 9% for IM and 56%, 50%, 55% for 2-CdA. The absence of mast cell mediator release symptoms in IFN-,-treated patients and presence of circulating immature myeloid cells in 2-CdA-treated patients predicted inferior response. TET2 mutational status did not influence treatment response. Although the major response rates with these four cytoreductive agents were still suboptimal and HU was mainly used in patients with SM-AHNMD, the current study favors 2-CdA or IFN-, as first-line current therapy in SM and identifies patients who are likely to respond to such therapy. Am. J. Hematol., 2009. © 2009 Wiley-Liss, Inc. [source] Phase I study of bortezomib combined with chemotherapy in children with relapsed childhood acute lymphoblastic leukemia (ALL): A report from the therapeutic advances in childhood leukemia (TACL) consortium,PEDIATRIC BLOOD & CANCER, Issue 2 2010Yoav Messinger MD Abstract Background Outcomes remain poor for children after relapse of acute lymphoblastic leukemia (ALL), especially after early marrow relapse. Bortezomib is a proteasome inhibitor with in vitro synergy with corticosteroids and clinical activity in human lymphoid malignancies. Procedure This is a Phase I study of escalating doses bortezomib administered days 1, 4, 8, and 11, added to 4-drug induction chemotherapy with vincristine, dexamethasone, pegylated L -asparaginase, and doxorubicin (VXLD) in children with relapsed ALL. Results Ten patients were enrolled, five in first marrow relapse, and five in second relapse. Four patients were enrolled at dose level 1 (bortezomib 1,mg/m2). One patient was not evaluable for toxicity because of omitted dexamethasone doses. No dose-limiting toxicity (DLT) was observed. Six patients were enrolled at dose level 2 (bortezomib 1.3,mg/m2). One patient had dose-limiting hypophosphatemia and rhabdomyolysis after 1 dose of bortezomib, and died from a diffuse zygomyces infection on day 17. Five additional patients were enrolled with no subsequent DLTs. As planned, no further dose escalation was pursued. The regimen had predictable toxicity related to the chemotherapy drugs. Two patients had mild peripheral neuropathy (grades 1 and 2). Six of nine evaluable patients (67%) achieved a complete response (CR), and one had a bone marrow CR with persistent central nervous system leukemia. Conclusions The combination of bortezomib (1.3,mg/m2) with VXLD is active with acceptable toxicity in pretreated pediatric patients with relapsed ALL. We are expanding the 1.3,mg/m2 cohort for a phase II estimate of response. Study registered at ClinicalTrials.gov (http://clinicaltrials.gov/ct2/show/NCT00440726). Pediatr Blood Cancer 2010;55:254,259. © 2010 Wiley-Liss, Inc. [source] Extended phase I evaluation of vincristine, irinotecan, temozolomide, and antibiotic in children with refractory solid tumors,PEDIATRIC BLOOD & CANCER, Issue 7 2010René Y. McNall-Knapp MD Abstract Background The combination of irinotecan, temozolomide, and vincristine is appealing because of potentially synergistic mechanisms of action and non-overlapping toxicities. This phase I study was designed to determine the toxicity and maximum tolerated dose (MTD) of escalating daily protracted doses of irinotecan given in this combination. With extended accrual, we more fully explored the toxicity of multiple courses at the MTD. Procedure Patients under 22 years with recurrent or refractory solid tumors were eligible. A course of chemotherapy was given every 28 days. Cefpodoxime was given for diarrhea prophylaxis. Vincristine (1.5,mg/m2, max 2,mg) was given intravenously (IV) on days 1 and 8. Temozolomide (100,mg/m2/day) was given orally on days 1,5. Irinotecan was given IV over 1,hr on days 1,5 and 8,12. Dose escalation was done in the standard 3,+,3 cohort design, starting at 15,mg/m2/day. Results Twenty-five of 26 eligible patients were evaluable for toxicity and response. They received 111 courses (1,13, median 4). Dose limiting toxicity (DLT,pancreatitis, transaminitis) was seen in two of three patients at dose level 2 (20,mg/m2). No patients at level 1 had DLT during the first two cycles. Thus, the MTD of irinotecan in this combination is 15,mg/m2/day,×,10 doses. Hematologic toxicity was mild and not prolonged. Grade 3 diarrhea was seen in five courses. Responses included two complete and two partial with 12 stable disease (SD) (median 6 months). Conclusions This combination is safe and shows activity in pediatric patients with recurrent malignancy. Pediatr Blood Cancer 2010;54:909,915 © 2010 Wiley-Liss, Inc. [source] Phase I study of paclitaxel with standard dose ifosfamide in children with refractory solid tumors: A Pediatric Oncology Group study (POG 9376)PEDIATRIC BLOOD & CANCER, Issue 3 2009James I. Geller MD Abstract Purpose A dose-escalation Phase I study of taxol (paclitaxel) administered in combination with standard dose ifosfamide was conducted in children with relapsed or refractory solid tumors. Primary objectives were to estimate the maximum tolerated dose (MTD) and to describe the dose-limiting toxicities (DLTs). Patients and Methods Paclitaxel was administered as a 6-hr continuous infusion (hr 0,6), followed by intravenous ifosfamide (2 g/m2/day,×,3 days) over 1 hr at hours 6,7, 24,25, and 48,49. Patients at dose level 1 received 250 mg/m2 paclitaxel. Subsequent dose escalation proceeded using a standard 3,×,3 Phase I design. Results Fifteen patients received a combined 46 courses of therapy. The median age was 14.5 years (range, 2,19 years), and diagnoses included sarcoma (7), neuroblastoma (3), and other (5). Three patients received paclitaxel at 250 mg/m2 (10 courses), six at 325 mg/m2 (19 courses), three at 425 mg/m2 (8 courses), and three at 550 mg/m2 (9 courses). DLTs occurred in 2/3 patients at 550 mg/m2 paclitaxel during cycle 1, including grade 3 hypotension and grade 4 anaphylaxis in 1 patient each. Common non-dose-limiting toxicities included bone marrow suppression and peripheral neuropathy. Response was evaluable in 14 patients and included mixed response (3), stable disease (5), and progressive disease (6). Conclusion Paclitaxel hypersensitivity reactions were dose limiting when the drug was administered as a 6-hr infusion. The MTD and recommended Phase II dose of paclitaxel administered as a 6-hr continuous intravenous infusion followed by standard dose intravenous ifosfamide is 425 mg/m2 paclitaxel. Pediatr Blood Cancer 2009;52:346,350. © 2008 Wiley-Liss, Inc. [source] A phase II study of 5-day intravenous azacitidine in patients with myelodysplastic syndromes,AMERICAN JOURNAL OF HEMATOLOGY, Issue 9 2009Mike G. Martin The approved 7-day schedule of subcutaneous azacitidine for myelodysplastic syndrome is associated with injection site reactions and bruising and may be inconvenient because of the need for weekend doses. Although pharmacokinetic data with IV azacitidine suggests equivalence, there are no efficacy data published. Patients with all myelodysplastic syndromes (MDS) FAB subtypes were enrolled and received 75 mg/m2/d of azacitidine by 20-min intravenous infusion for 5 days in every 28 days. Global methylation studies were performed at baseline and prior to Cycle 3. Twenty-five patients were enrolled and 22 were evaluable. Median age was 69.5 years; 9 (41%) patients had lower-risk disease (IPSS Low or Int-1) and 13 (59%) had higher-risk disease (IPSS Int-2 or High). Twenty-seven percent of patients responded (5 CRs and 1 PR). The median time to response was 108 days. The median PFS was 339 days (11.3 months), the median OS was 444 days (14.8 months) and the median duration of response (DOR) was 450 days (15.0 months). Global methylation studies suggest a greater degree of demethylation in responders. This regimen appeared to offer a PR + CR rate and median DOR somewhat similar to what has been reported with the 7-day subcutaneous regimen; however, OS was shorter. Am. J. Hematol. 2009. © 2009 Wiley-Liss, Inc. [source] A phase 2 trial of all- trans -retinoic acid in combination with interferon-,2a in children with recurrent neuroblastoma or Wilms tumor: A Pediatric Oncology Branch, NCI and Children's Oncology Group StudyPEDIATRIC BLOOD & CANCER, Issue 5 2007Peter C. Adamson MD Abstract Background The combination of the antiproliferative and differentiation-inducing effects of retinoids together with the antiproliferative, immunostimulatory, and differentiation-potentiating effects of interferon-, (IFN-,) were the basis for the development of this combination in pediatric patients with refractory neuroblastoma or Wilms tumor. Procedure A phase 2 trial of all- trans -retinoic acid (ATRA), administered orally at a dose of 90 mg/m2/day in three divided doses for 3 consecutive days per week, and IFN-,2a, administered subcutaneously daily at a dose of 3,×,106 U/m2/day for 5 consecutive days per week, in 4 week cycles was performed. A two-stage design was used for each disease stratum. Results Seventeen patients (16 evaluable) with neuroblastoma, median age 9 years, and 15 patients (14 evaluable) with Wilms tumor, median age 6 years, were enrolled. Overall, the combination was well tolerated, with headache being the most common toxicity observed. There were no complete or partial responses. The median number of cycles administered was 1 (range 1,9). Four patients with neuroblastoma had stable disease for 12 or more weeks. Conclusions The combination of ATRA and IFN-,2a was inactive in children with relapsed or refractory neuroblastoma and Wilms tumor. The lack of activity with this combination in children with refractory neuroblastoma is similar to the disappointing phase 2 results of single agent 13- cis -retinoic-acid (13cRA) and does not support further development of ATRA for children with relapsed neuroblastoma. Pediatr Blood Cancer 2007;49:661,665. © 2006 Wiley-Liss, Inc. [source] Phase II study of bryostatin 1 and vincristine for aggressive non-Hodgkin lymphoma relapsing after an autologous stem cell transplant,AMERICAN JOURNAL OF HEMATOLOGY, Issue 8 2009Paul M. Barr Bryostatin 1, isolated from a marine bryozoan, enhances the efficacy of cytotoxic agents through modulation of the protein kinase C pathway and is active in combination with vincristine for diffuse large B-cell lymphoma. Further, the apoptotic frequency of peripheral blood T lymphocytes as determined by flow cytometry may predict which patients will respond to this combination. We tested the efficacy and safety of bryostatin 1 50 ,g/m2 given over 24 hr and vincristine 1.4 mg/m2 on days 1 and 15 every 28 days in aggressive B-cell non-Hodgkin lymphoma (NHL) relapsing after autologous stem cell transplantation. End points included tumor response, toxicity, and survival. Responses were correlated with an increase in apoptotic frequency of CD5+ cells by flow cytometry using annexin V staining. Fourteen patients were enrolled with 13 being evaluable for a response. The overall response rate was 31% with two patients achieving a complete response. The most common toxicities were Grade 3 lymphopenia (seven patients), Grade 3 to 4 neutropenia (two patients), and Grade 3 hypophosphatemia (two patients). Median progression-free and overall survivals for all patients were 5.7 and 21.4 months, respectively. One patient demonstrated an increase in T-cell apoptotic frequency, also achieving a complete response. Bryostatin 1 and vincristine have efficacy in select patients with aggressive NHL. Future investigations of agents targeting the protein kinase C pathway may benefit from early response assessment using flow cytometry to evaluate T-cell apoptosis. Am. J. Hematol., 2009. © 2009 Wiley-Liss, Inc. [source] Postmarketing drug dosage changes of 499 FDA-approved new molecular entities, 1980,1999,PHARMACOEPIDEMIOLOGY AND DRUG SAFETY, Issue 6 2002James Cross MS Abstract Purpose Risks and benefits of marketed drugs can be improved by changing their labels to optimize dosage regimens for indicated populations. Such postmarketing label changes may reflect the quality of pre-marketing development, regulatory review, and postmarketing surveillance. We documented dosage changes of FDA-approved new molecular entities (NMEs), and investigated trends over time and across therapeutic groups, on the premise that improved drug development methods have yielded fewer postmarketing label changes over time. Methods We compiled a list of NMEs approved by FDA from 1 January 1980 to 31 December 1999 using FDA's website, Freedom of Information Act request, and PhRMA (Pharmaceutical Research and Manufacturers of America) database. Original labeled dosages and indicated patient populations were tracked in labels in the Physician's Desk Reference®. Time and covariate-adjusted risks for dosage changes by 5-year epoch and therapeutic groups were estimated by survival analysis. Results Of 499 NMEs, 354 (71%) were evaluable. Dosage changes in indicated populations occurred in 73 NMEs (21%). A total of 58 (79%) were safety-motivated, net dosage decreases. Percentage of NMEs with changes by therapeutic group ranged from 27.3% for neuropharmacologic drugs to 13.6% for miscellaneous drugs. Median time to change following approval fell from 6.5 years (1980,1984) to 2.0 years (1995,1999). Contrary to our premise, 1995,1999 NMEs were 3.15 times more likely to change in comparison to 1980,1984 NMEs (p,=,0.008, Cox analysis). Conclusions Dosages of one in five NMEs changed, four in five changes were safety reductions. Increasing frequency of changes, independent of therapeutic group, may reflect intensified postmarketing surveillance and underscores the need to improve pre-marketing optimization of dosage and indicated population. Copyright © 2002 John Wiley & Sons, Ltd. [source] Breast Cancer Incidence in a Cohort of Women with Benign Breast Disease from a Multiethnic, Primary Health Care PopulationTHE BREAST JOURNAL, Issue 2 2007Maria J. Worsham PhD Abstract:, Women with benign breast diseases (BBD), particularly those with lesions classified as proliferative, have previously been reported to be at increased risk for subsequent development of breast cancer (BC). A cohort of 4970 women with biopsy-proven BBD, identified after histopathology review of BBD biopsies, was studied for determination of subsequent development of BC. We report on 4537 eligible women, 28% of whom are African-American, whose BBD mass was evaluable for pathologic assessment of breast tissue. Ascertainment of subsequent progression to BC from BBD was accomplished through examination of the tumor registries of the Henry Ford Health system, the Detroit SEER registry, and the State of Michigan cancer registry. Incidence rates (IR) are reported per 100,000 person years at risk (100 k pyr). Poisson regression models were used to evaluate the association of demographic and lesion characteristics with BC incidence, using person years at the time of BBD diagnosis as the offset variable. The estimated overall BC IR for this cohort is 452 (95% confidence interval [CI] = 394,519) per 100 k pyr. Incidence for women age 50 and older is 80% greater than for younger women (p = 0.007, IRR = 1.8, 95% CI = 1.36,2.36). Neither marital status (p = 0.91, IRR = 0.97, 95% CI = 0.73,1.29) nor race (p = 0.67, IRR = 0.9, 95% CI = 0.54,1.48) is associated with differences in BC IR. Compared with women having nonproliferative lesions, the risk for BC is greater for women with atypical ductal hyperplasia of (IRR = 5.0; 95%CI = 2.26,11.0; p < 0.001) and other proliferative lesions (IR = 1.7, 95% CI = 1.02,2.95; p = 0.04). BC risk for woman with atypical lesions is significantly higher than for women with proliferative lesions without atypia (IRR = 2.58, 95% CI = 1.35,4.90; p = 0.0039). Neither race nor marital status was a factor for BC incidence from BBD in this cohort. Age retained its importance as a predictor of risk. BBD lesion histopathology in the outcome categories of either proliferative without atypia or proliferative with atypia are significant risk factors for BC, even when adjusted for the influence of demographic characteristics. The risks associated with BBD histological classifications were not different across races. [source] Fluorouracil, Doxorubicin, and Cyclophosphamide Followed by Tamoxifen as Adjuvant Treatment for Patients with Stage IV Breast Cancer with No Evidence of DiseaseTHE BREAST JOURNAL, Issue 1 2002Edgardo Rivera MD We conducted a single-institution study to determine whether local therapy plus six cycles of chemotherapy with 5-fluorouracil, doxorubicin, and cyclophosphamide (FAC) followed by 5 years of tamoxifen is superior to local treatment alone in terms of disease-free survival (DFS) and overall survival (OS) in patients with stage IV breast cancer with no evidence of disease (stage IV-NED breast cancer). Patients with breast cancer were eligible if they had histologic proof of a locoregional or distant recurrence that had been curatively resected, irradiated, or both and had no other evidence of disease. Patients who had received prior anthracycline therapy were not eligible. All patients received six cycles of intravenous FAC, with cycles repeated every 3 weeks. After completion of chemotherapy, patients whose tumors had not previously demonstrated resistance to tamoxifen and had positive or unknown estrogen receptor status received tamoxifen 20 mg by mouth daily for 5 years. Patients in this study were compared with a historical control population (patients with stage IV-NED breast cancer who never received systemic therapy) as well as with the patients in two previously reported trials of chemotherapy for stage IV-NED disease. Forty-seven patients were registered, but only 45 were evaluable. There was a highly statistically significant difference ( p < 0.001) in OS and DFS among the four groups, with patients in our most recent study having the best OS and DFS at 3 years compared with the control group (84% vs. 55% and 66% vs. 11%, respectively). When patients in all four groups were analyzed together in search of prognostic factors, we found that patients whose primary tumors had negative axillary lymph nodes had a statistically significant improvement in OS and DFS ( p < 0.01) compared with patients with positive axillary lymph nodes. No survival differences were found between patients with positive and those with negative hormone receptor status. This study demonstrates a benefit in terms of OS and DFS for patients with stage IV-NED breast cancer who receive doxorubicin-based adjuvant chemotherapy. The benefit was greater on patients with node-negative primary tumors. In patients with stage IV-NED disease, doxorubicin-based chemotherapy should be considered standard treatment after adequate local control is achieved. [source] Efficacy and Safety of Tadalafil 20 mg on Demand vs.THE JOURNAL OF SEXUAL MEDICINE, Issue 8 2010Tadalafil 5 mg Once-a-Day in the Treatment of Post-Radiotherapy Erectile Dysfunction in Prostate Cancer Men: A Randomized Phase II Trial ABSTRACT Introduction., The role of phosphodiesterase type 5 inhibitors in the treatment of post-radiotherapy erectile dysfunction (ED) has not been extensively investigated. Aim., To compare the efficacy and safety of on-demand 20-mg tadalafil (arm A) with the newly released tadalafil 5-mg once-a-day dosing (arm B) in patients with ED following radiotherapy for prostate cancer (PC). Methods., Randomized study to receive on-demand 20-mg or once-a-day 5-mg tadalafil for 12 weeks. Main Outcome Measures., Changes in the International Index of Erectile Function (IIEF) domain scores and Sexual Encounter Profile (SEP) question 2 and 3 positive response rates. Results., Fifty-two out of 86 screened patients were randomized. Forty-four patients were evaluable for efficacy. A significant improvement in all domains of the IIEF was observed in both arms (P = 0.0001) with mean erectile function domain scores values of 25 and 27.1 for the 20-mg and 5-mg tadalafil, respectively (P = 0.19). SEP 2 and 3 positive response rates increased from 0% in both arms at baseline to 81% and 70% in the 20-mg arm and 90% and 73% in the 5-mg arm, respectively, at the end of treatment (P = 0.27). End of treatment global efficacy question positive answers were 86% in the 20-mg arm and 95% in the 5-mg arm (P = 0.27). Higher treatment compliance was shown in arm B (100%) as compared with arm A (86%). There was a nonstatistically significant trend toward fewer side effects in favor of the 5-mg daily dose arm. Conclusions., In the study population, both tadalafil formulations generated significantly high response rates according to the outcome measures and were well tolerated. The once-a-day 5-mg dosing showed higher compliance and marginally reduced side effects, thus making it an attractive alternative to on-demand therapy for ED in post-radiotherapy PC patients. Ricardi U, Gontero P, Ciammella P, Badellino S, Valentino F, Munoz F, Guarneri A, Rondi N, Moretto F, Filippi AR, Ragona R, and Tizzani A. Efficacy and safety of tadalafil 20 mg on demand vs. tadalafil 5 mg once-a-day in the treatment of post-radiotherapy erectile dysfunction in prostate cancer men: A randomized phase II trial. J Sex Med 2010;7:2851,2859. [source] Response of patients with advanced prostatic cancer to administration of somatostatin analog RC-160 (vapreotide) at the time of relapseTHE PROSTATE, Issue 3 2003David González Barcena Abstract BACKGROUND The aim of this study was to evaluate the effects of administration of the somatostatin analog RC-160 (vapreotide) at the time of relapse in patients with androgen independent prostate cancer. METHODS Our study included 13 patients with biopsy-proven prostate cancer, stage D3. Eight patients had been treated with a depot formulation of the agonist D-Trp-6-LH-RH, with a median remission time of 68 (range 48,102 months). Five patients were initially treated by surgical orchiectomy, but relapsed after a median time of 33 months (range 17,91 months). A new remission period with a median duration of 10 months (range 2,29 months) was induced with Ketoconazole in the orchiectomy group. At the relapse time, all the patients received 1 mg of vapreotide t.i.d., by subcutaneous route, in addition to D-Trp-6-LH-RH, or Ketoconazole in the orchiectomy group. RESULTS Eight of 13 patients demonstrated clinical improvement after 3 months of therapy with vapreotide, six showing a decrease in serum prostate specific antigen (PSA) from 234.5,±,308.5 to 68.2,±,60.5 ng/ml (mean decline 71,±,8%; P,<,0.05). Two additional patients presented a fall in serum prostatic acid phosphatase (PAP). Responding patients showed a decrease in the bone pain score from 2.62,±,0.48 to 0.37,±,0.69 and an increase in the Karnofsky performance status from 72.3,±,4.21 to 83.6,±,23.2 (P,<,0.05). In accord with the ECOG criteria, two patients had a complete response; four had partial response, and two had a stable response. Four patients did not respond and one was not evaluable. Two patients died in remission, one at 16 months due to myocardial infarction and the other at 24 months due to pneumonia. Three patients relapsed at 5, 17, and 19 months respectively. Three patients who have been followed-up for more than 3 years continued in remission (79, 45, and 45 months) respectively. Vapreotide was well tolerated, only three patients having transitory mild diarrhea. CONCLUSIONS Our results indicate that therapy with the somatostatin analog vapreotide at the time of relapse can induce objective clinical responses in some patients with prostate cancer who are refractory to androgen ablation induced by LH-RH analogs or orchiectomy. Prostate 56: 183,191, 2003. © 2003 Wiley-Liss, Inc. [source] Prospective evaluation of angiogenic, hypoxic and EGFR-related biomarkers in recurrent glioblastoma multiforme treated with cetuximab, bevacizumab and irinotecanAPMIS, Issue 8 2010Benedikte Hasselbalch Hasselbalch B, Eriksen JG, Broholm H, Christensen IJ, Grunnet K, Horsman MR, Poulsen HS, Stockhausen M-T, Lassen U. Prospective evaluation of angiogenic, hypoxic and EGFR-related biomarkers in recurrent glioblastoma multiforme treated with cetuximab, bevacizumab and irinotecan. APMIS 2010; 118: 585,94. Several recent studies have demonstrated a beneficial effect of anti-angiogenic treatment with the vascular endothelial growth factor-neutralizing antibody bevacizumab in recurrent high-grade glioma. In the current study, immunohistochemical evaluation of biomarkers involved in angiogenesis, hypoxia and mediators of the epidermal growth factor receptor (EGFR) pathway were investigated. Tumor tissue was obtained from a previous phase II study, treating recurrent primary glioblastoma multiforme (GBM) patients with the EGFR inhibitor cetuximab in combination with bevacizumab and irinotecan. Of the 37 patients with available tumor tissue, 29 were evaluable for response. We concurrently performed immunohistochemical stainings on tumor tissue from 21 GBM patients treated with bevacizumab and irinotecan. We found a tendency of correlation between the hypoxia-related markers, indicating that they share the same regulatory mechanisms. None of the EGFR-related biomarkers showed any significant correlations with each other. None of the biomarkers tested alone or in combination could identify a patient population likely to benefit from bevacizumab and irinotecan, with or without the addition of cetuximab. There is still an urgent need for one or more reliable and reproducible biomarkers able to predict the efficacy of anti-angiogenic therapy. [source] Phase II study of irinotecan in combination with capecitabine as a first-line chemotherapy in Asian patients with inoperable hepatocellular carcinomaASIA-PACIFIC JOURNAL OF CLINICAL ONCOLOGY, Issue 2 2009Tony MOK Abstract Aim: Hepatocellular carcinoma (HCC) is one of the most commonly fatal malignancies in Asia but treatment options are limited. Methods: This multinational, nonrandomized phase II trial using the combination of irinotecan (Campto or CPT-11) and capecitabine (Xeloda) was conducted to determine efficacy and safety of this combination in Asian patients with advanced inoperable HCC. The starting dose was irinotecan 200 mg/m2 every 3 weeks followed by capecitabine 1000 mg/m2 orally twice daily for 14 days followed by a 7-day rest. The primary endpoint was tumor response rate, based on response evaluation criteria in solid tumors criteria. Secondary objectives included the safety and tolerability of the treatment combination, time to progression, duration of overall response, tumor growth control rate (complete response, partial response plus stable disease) and overall survival. Results: Of the 63 recruited patients, 47 were evaluable. Of these, three (6.4%) achieved a partial response (lasting 2.2, 3.4 and 8.0 months, respectively). The median overall survival was 4.5 months. Grade 4 diarrhea was reported in four patients. Hematologic grade 4 laboratory abnormalities observed in patients while on study treatment included neutropenia (5.2%) and anemia (1.7%). Seven patients (12.1%) had grade 4 elevations in their total bilirubin. Both irinotecan and capecitabine were generally well tolerated, with manageable and reversible toxicities. Conclusion: Combination therapy with irinotecan and capecitabine has limited efficacy in the treatment of advanced-stage HCC. Further investigation of this combination is not warranted. [source] Phase II study of gemcitabine and docetaxel in combination for the treatment of metastatic breast cancerASIA-PACIFIC JOURNAL OF CLINICAL ONCOLOGY, Issue 1 2009Shom GOEL Abstract Aim: Gemcitabine (G) and docetaxel (D) have both shown activity in the treatment of anthracycline-pretreated patients with metastatic breast cancer. This phase II study was designed to evaluate the safety and efficacy of the GD combination. Methods: Patients with measurable locally advanced or metastatic breast cancer who had previously received anthracycline-based therapy were eligible. The patients received D 40 mg/m2 followed by G 800 mg/m2 IV on days 1 and 8 every 3 weeks for a maximum of eight cycles. Results: Thirty patients were enrolled and received a median of five cycles (range 0,8). Of these, 24 were evaluable for efficacy, with an overall response rate of 29.2% (95% CI, 12.6,51.1%). An additional 36.7% had a stable disease for an overall clinical benefit of 65.9%. The median duration of response was 2.1 months (95% CI, 2.0,3.6 months) and the median time to disease progression was 5.5 months (95% CI, 2.0,8.9 months). The median survival time was 16.7 months (95% CI, 7.3,32.0 months). Myelosuppression was the major toxicity, with grade 3/4 neutropenia in 73.3% of patients and febrile neutropenia in 6.7%. Conclusion: Weekly G and D is an active and safe regimen in treating metastatic breast cancer. The response rate was lower than that previously reported for this combination, which may relate to the lower doses used and the weekly D schedule. It may be worthwhile to further explore this combination to determine the optimal dosing schedule. [source] Phase II study of S-1 and irinotecan combination chemotherapy as a first-line therapy for patients with advanced gastric cancer.ASIA-PACIFIC JOURNAL OF CLINICAL ONCOLOGY, Issue 1 2009Korean Cancer Study Group Protocol ST05-0 Abstract Background: Irinotecan plus intravenous 5-fluorouracil (5-FU) with leucovorin is effective against gastrointestinal cancer. S-1 is an oral fluoropyrimidine derivative and has a high response rate of about 40% for patients with advanced gastric cancer (AGC). We evaluated the antitumor activity and toxicities of an S-1 and irinotecan combination as a first-line therapy for patients with AGC. Methods: Patients with histologically confirmed unresectable or metastatic AGC were treated with S-1 40 mg/m2 PO twice daily on days 1,14 and irinotecan 150 mg/m2 i.v. on day 1 every 3 weeks until disease progression or unacceptable toxicities resulted. Results: A total of 45 patients were enrolled between September 2005 and March 2007. After a median of seven cycles of chemotherapy (range: 1,20, total: 350), 42 and 44 patients were evaluable for response and toxicity, respectively. On the intention-to-treat analysis, the overall response rate was 48.9% (95% C.I. 34.3,63.5%). The median time to progression was 5.7 months (95% C.I. 4.3,7.1) and the median overall survival was 10.4 months (95% C.I. 6.1,14.7). The commonly observed grade 3/4 adverse events were neutropenia (29.5% of patients) and vomiting (13.6%). Conclusion: An S-1 and irinotecan combination chemotherapy is active and tolerable as a first-line therapy for AGC. [source] Twin pregnancy outcomes for women with gestational diabetes mellitus compared with glucose tolerant womenAUSTRALIAN AND NEW ZEALAND JOURNAL OF OBSTETRICS AND GYNAECOLOGY, Issue 1 2003Robert G. Moses Abstract Objective: To examine pregnancy outcomes for women with gestational diabetes mellitus (GDM) and a twin pregnancy compared with glucose tolerant women with a twin pregnancy. Design: Comparison of selected pregnancy outcomes. Setting: Wollongong, New South Wales, Australia. Population: Women with GDM seen over a 10-year period by an endocrinologist, and women from a selected year of an obstetric database including Wollongong and Shellharbour Hospitals. Methods: Examination of pregnancy outcome data from the two sources. Main outcome measures: Fetal birthweights and method of delivery. Results: There were 28 GDM women with a twin pregnancy from 1229 consecutive referrals (2.3%) of women with GDM for medical management. For comparison there were 29 glucose tolerant women with twin pregnancies evaluable who had delivered over a 1-year period. For the women with GDM and a twin pregnancy there were no significant differences in demographics or outcomes except for a higher rate of elective Caesarean section. Conclusion: The higher rate of Caesarean section appeared to be related to the combination of a twin pregnancy and GDM rather than the twin pregnancy or the GDM independently. [source] Predictive value for preterm birth of abnormal vaginal flora, bacterial vaginosis and aerobic vaginitis during the first trimester of pregnancyBJOG : AN INTERNATIONAL JOURNAL OF OBSTETRICS & GYNAECOLOGY, Issue 10 2009GG Donders Introduction, Abnormal vaginal flora (AVF) before 14 gestational weeks is a risk factor for preterm birth (PTB). The presence of aerobic microorganisms and an inflammatory response in the vagina may also be important risk factors. Aim, The primary aim of the study was to investigate the differential influences of AVF, full and partial bacterial vaginosis, and aerobic vaginitis in the first trimester on PTB rate. The secondary aim was to elucidate why treatment with metronidazole has not been found to be beneficial in previous studies. Setting, Unselected women with low-risk pregnancies attending the prenatal unit of the Heilig Hart General Hospital in Tienen, Belgium, were included in the study. Materials and methods, At the first prenatal visit, 1026 women were invited to undergo sampling of the vaginal fluid for wet mount microscopy and culture, of whom 759 were fully evaluable. Abnormal vaginal flora (AVF; disappearance of lactobacilli), bacterial vaginosis (BV), aerobic vaginitis (AV), increased inflammation (more than ten leucocytes per epithelial cell) and vaginal colonisation with Candida (CV) were scored according to standardised definitions. Partial BV was defined as patchy streaks of BV flora or sporadic clue cells mixed with other flora, and full BV as a granular anaerobic-type flora or more than 20% clue cells. Vaginal fluid was cultured for aerobic bacteria, Mycoplasma hominis and Ureaplasma urealyticum. Outcome was recorded as miscarriage ,13 weeks + 6 days [early miscarriage (EM), n = 8 (1.1%)], between 14 + 0 and 24 weeks + 6 days [late miscarriage (LM), n = 7 (0.9%)], delivery or miscarriage ,34 weeks + 6 days n = 29 (3.8%)], ,36 weeks + 6 days n = 70 (9.2%)]. PTB between 25 + 0 and 36 weeks + 6 days was further divided in severe PTB (SPTB, 25 + 0 to 34 weeks + 6 days) and mild PTB (MPTB, 35 + 0 to 36 weeks + 6 days). Results, Women without abnormalities of the vaginal flora in the first trimester had a 75% lower risk of delivery before 35 weeks compared with women with AVF [odds ratio (OR) 0.26; 95% confidence interval (CI) 0.12,0.56]. The absence of lactobacilli (AVF) was associated with increased risks of PTB (OR 2.4; 95% CI 1.2,4.8), EPTB (OR 6.2; 95% CI 2.7,14) and miscarriage (OR 4.9; 95% CI 1.4,17). BV was associated with increased risks of PTB (OR 2.4; 95% CI 1.1,4.7), EPTB (OR 5.3; 95% CI 2.1,12.9) and miscarriage (OR 6.6; 95% CI 2.1,20.9) and coccoid AV was associated with increased risks of EPTB (OR 3.2; 95% CI 1.2,9.1) and miscarriage (OR 5.2; 95% CI 1.5,17). In women with BV, partial BV had a detrimental effect on the risk of PTB for all gestational ages, but full BV did not. Preterm deliveries later than 24 weeks+ 6 days were more frequent when M. hominis was present (EPTB OR 13.3; 95% CI 3.2,55). Discussion, Bacterial vaginosis, AV and AVF are associated with PTB, especially LM and severe PTB between 25 and 35 weeks. The absence of lactobacilli (AVF), partial BV and M. hominis, but not full BV, were associated with an increased risk of preterm delivery after 24 weeks+ 6 days. As metronidazole effectively treats full BV, but is ineffective against other forms of AVF, the present data may help to explain why its use to prevent PTB has not been successful in most studies. [source] 92 Photoselective vaporisation of the prostate randomised against turp-preliminary resultsBJU INTERNATIONAL, Issue 2006D.M. BOUCHIER-HAYES Introduction:, Many technologies have attempted to supplant TURP as the surgical treatment of choice in the treatment of lower urinary tract symptoms, but have not undergone randomised trials. Photoselective vaporization of the prostate (PVP) using the Greenlight® laser system (Laserscope, San Jose, Ca.) gives an 80-watt laser ablation system and here is compared to TURP in the world's first randomised trial. Study Design:, One hundred and twenty patients are to be randomised to undergo TURP or PVP after evaluation which is repeated at 1, 3, 6 and 12 months. Irrigation use, length of catherisation time (LOC), length of hospital stay (LOS), blood loss and operative time are also assessed. All procedures were performed by fellows/registrars. Results:, To date 90 patients are randomised and 68 are evaluable and were similar at baseline. Both techniques produced equivalent significant improvement in flow rates and IPSSs, and significantly shorter length of time of catherisation (LOC) and length of stay (LOS) in the PVP group. Adverse events were less frequent in the PVP group, and the procedure was 22% cheaper than TURP. Conclusions:, This trial demonstrates with preliminary data that PVP may be an effective technique when compared to TURP, producing equivalent improvements in flow rates and IPSS scores with markedly reduced LOS, LOC and adverse events. [source] The effect of intestinal urinary reservoirs on renal function: a 10-year follow-upBJU INTERNATIONAL, Issue 3 2000E. Fontaine Objective To study the effect of the storage of urine in intestinal reservoirs on long-term renal function and the possible causes of deterioration. Patients and methods Eighty-seven patients (aged 4,35 years) with bladder exstrophy who underwent reconstruction of the lower urinary tract using a bowel segment were enrolled in a prospective protocol. The glomerular filtration rate (GFR) was measured before and after surgery at 1, 2, 5 and 10 years using 51Cr-ethylenediamine tetra-acetic acid. Patients with a decline in GFR of > 5% were investigated to identify the cause. Results Of 58 patients with a follow-up of , 10 years, 53 were evaluable, four having been lost to follow-up and one refusing to accept the protocol. In these 53 patients, the mean ( sd) GFR decreased from 97.9 (20.4) to 92.9 (23.6) mL/min/1.73 m2 (P = 0.24). However, this decrease was accounted for by 10 patients (19%) whose GFR fell by ,,20% over the 10 years. The causes of renal deterioration in these 10 patients were; chronic retention and/or infection caused by inadequate catheterization in poorly compliant patients (five), uretero-ileal stenosis (one), a high-pressure reservoir (one) and uncertain causes (three). Conclusions For 80% of the patients, the storage of urine in intestinal reservoirs did not change renal function for at least 10 years. However, ,,20% of patients had some deterioration in renal function during the 10-year follow-up, usually from identifiable and remediable causes. The storage of urine in bowel does not appear to be inherently damaging to kidney function. Patients with an enterocystoplasty need regular monitoring of renal function; when deterioration is detected the urinary tract must be functionally assessed. [source] | ||||||||||||||||||||||||||||||||||