Effects of Tadalafil on Lower Urinary Tract Symptoms Secondary to Benign Prostatic Hyperplasia and on Erectile Dysfunction in Sexually Active Men with Both Conditions: Analyses of Pooled Data from Four Randomized,Placebo‐Controlled Tadalafil Clinical Studies

IntroductionErectile dysfunction (ED) and lower urinary tract symptoms suggestive of benign prostatic hyperplasia (LUTS/BPH) are common in aging males and frequently occur together. Tadalafil has demonstrated efficacy in treating both conditions.AimThe study aims to evaluate the efficacy and safety of tadalafil 5 mg once daily vs. placebo over 12 weeks in treating both LUTS/BPH and ED in sexually active men. We also assessed relationships of baseline disease severity and prostate specific antigen (PSA) to outcomes.MethodsData were pooled from four multinational, randomized studies of men ≥45 years with LUTS/BPH, with analyses restricted to sexually active men with ED. Randomization (baseline) followed a 4‐week placebo run‐in; changes from baseline were assessed vs. placebo using analysis of covariance.Main Outcome MeasuresInternational Prostate Symptom Score (IPSS), IPSS subscores, Quality‐of‐Life Index (IPSS‐QoL), BPH Impact Index (BII), and International Index of Erectile Function‐Erectile Function (IIEF‐EF) Domain score were used in this study.ResultsTadalafil (N = 505) significantly improved total IPSS vs. placebo (N = 521); mean changes from baseline were ?6.0 and ?3.6, respectively (P < 0.001). Improvements in IIEF‐EF Domain score (tadalafil, 6.4; placebo, 1.4) were also significant vs. placebo, as were the IPSS storage and voiding subscores, IPSS‐QoL, and BII (all P < 0.001).No significant impact of baseline ED severity or PSA category on IPSS response was observed (interaction P values, 0.463 and 0.149, respectively). Similarly, improvement in IIEF‐EF Domain score was not significantly impacted by baseline LUTS/BPH severity or PSA category (interaction P values, 0.926 and 0.230, respectively). Improvements in IPSS and IIEF‐EF Domain score during treatment were weakly correlated (r = ?0.229). Treatment‐emergent adverse events were consistent with previous reports.ConclusionsTadalafil was efficacious and well tolerated in treating ED and LUTS/BPH in sexually active men with both conditions. Improvements in both conditions were significant regardless of baseline severity. Improvements in the total IPSS and the IIEF‐EF Domain score were weakly correlated. Porst H, Roehrborn CG, Secrest RJ, Esler A, and Viktrup L. Effects of tadalafil on lower urinary tract symptoms secondary to benign prostatic hyperplasia and on erectile dysfunction in sexually active men with both conditions: Analyses of pooled data from four randomized, placebo‐controlled tadalafil clinical studies. J Sex Med 2013;10:2044–2052.     

Evidence-based use of methotrexate in children with rheumatic diseases: a consensus statement of the Working Groups Pediatric Rheumatology Germany (AGKJR) and Pediatric Rheumatology Austria

Juvenile idiopathic arthritis (JIA) is the most common diagnosis in children and adolescents with rheumatic disorders. In many children and adolescents, JIA is successfully treated with non-steroidal anti-inflammatory drugs (NSAID) and physiotherapy. However, in a significant number of cases the disease is resistant to this therapy, and treatment with second line disease-modifying antirheumatic drugs (DMARDs) is required. Methotrexate (MTX) is frequently referred to as first-choice second-line agent for the treatment of JIA. To increase drug safety, the Working Groups for Children and Adolescents with Rheumatic Diseases in Germany (AGKJR) and Pediatric Rheumatology Austria have initiated the formulation of evidence-based recommendations. Evidence is based on consensus expert meetings, a MEDLINE search with the key words Methotrexate and juvenile arthritis limited to age 0–18 years, standard textbooks and review articles, data from the central registry of the German Research Center for Rheumatic Diseases (Deutsches Rheumaforschungszentrum Berlin DRFZ), experience with MTX in adults with rheumatoid arthritis (RA), and recommendations of the German Society of Rheumatology (DGRh). Based on these data, evidence and recommendations are graded, and evidence-based recommendations for the use of MTX in children and adolescents with rheumatic disease are presented.Section Pharmacotherapy of the Working Group Pediatric Rheumatology Germany and Austria: I. Foeldvari; J.P. Haas, A. Haeffner, D. Hobusch,G. Horneff, A. Hospach, R. Keitzer, G. Klaus, M. Metzler, H. Michels, T. Niehues, I. Pilz, M. Sailer Höck, M. Schöntube, L. Schuchmann, K. Schumacher, H.W. Seyberth, E. Siemers, A. Urban, E. Weißbarth-Riedl. Working Group Pediatric Rheumatology North-Rhine-Westfalia: S. Benseler, G. Bürk, S. Fahl, I. Foeldvari, D. Föll, M. Frosch, G. Ganser, S. Kastner, I. Kleine, E. Lainka, K. Mönkemöller, J. Neubert, U. Neudorf, T. Niehues, J. Roth, S. Seeliger, N. Wagner, R. Wieland, H. Winowski.     

Experimental calibration of a two-stage prism-grating system for measuring cell velocity

A new optical system for the measurement of the erythrocyte velocity in microvessels is extensively applied for the first time. It is based on the projection of the erythrocyte image onto two photodiodes through a prism grating. The differential signal of the photodiodes is proportional to the velocity. The system is comparable to those of M. Anliker, M. Casty, P. Friedli, R. Kubli, and H. Keller ((1977). Noninvasive measurement of blood flow. In “Cardiovascular Flow Dynamics and Measurement” (N. H. Hwang and N. Normann, eds.), pp. 43–88. Univ. Park Press, Baltimore) and D. W. Slaaf, J. P. S. M. Rood, G. J. Tangelder, and T. Arts ((1979). Microvasc. Res.17, S173). It measures an instantaneous velocity. The system is calibrated by a velocity which is constant over the total measuring field and by a known flow rate and profile. Concerning applicability and results the device is compared to the two-slit methods, the laser-Doppler-anemometry and high-speed cinematography.     

Comparative Efficacies and Tolerabilities of Intravenous Azithromycin Plus Ceftriaxone and Intravenous Levofloxacin with Step-Down Oral Therapy for Hospitalized Patients with Moderate to Severe Community-Acquired Pneumonia

Objective: To compare the efficacy and tolerability of ceftriaxone plus azithromycin with those of levofloxacin in the treatment of hospitalized patients with moderate to severe community-acquired pneumonia (CAP). Design: Randomized, open-label multicenter trial with 1 : 1 treatment allocation in an inpatient setting. Patients: 212 male or female inpatients with a clinical diagnosis of CAP were included in the study. In each treatment group >50% of patients had a pneumonia severity index of IV or V. Interventions: Open-label treatment with either intravenous (IV) ceftriaxone 1g and IV azithromycin 500mg daily or IV levofloxacin 500mg daily. Patients who improved clinically were switched to oral follow-on therapy with either azithromycin 500 mg/day or levofloxacin 500 mg/day. At the clinician’s discretion, oral cefuroxime axetil was added to the treatment regimen of patients who received oral azithromycin if a macrolide resistant pneumococcal isolate was documented. Results: Overall, both study treatments were well tolerated. Favorable clinical outcomes in clinically evaluable patients were demonstrated in 91.5% of patients treated with ceftriaxone plus azithromycin and 89.3% (95% CI ?7.1%, 11.4%) of patients treated with levofloxacin at the end of therapy visit and in 89.2% and 85.1% (95% CI ?6.7%, 14.8%) patients, respectively, at the end of study visit. Bacteriological eradication rates for both treatments were equivalent with the exception of Streptococcus pneumoniae; 44% of isolates were eradicated with levofloxacin compared with 100% of isolates with ceftriaxone plus azithromycin. Conclusions: As acknowledged by international CAP treatment guidelines, the combination of a third-generation cephalosporin and a macrolide is at least as efficacious as monotherapy with a fluoroquinolone with enhanced anti-pneumococcal activity, for hospitalized patients with moderate to severe CAP. Combined medication with a macrolide and third-generation cephalosporin may be preferred over fluoroquinolones as first-line therapy of hospitalized patients with CAP to minimize the development of multiresistant nosocomial Gram-negative bacilli.     

Recent developments in antibiotic treatment

Antibiotic resistance of gram-positive and gram-negative bacteria remains a major challenge for clinicians treating HAP. Since the recent release of linezolid and QD, treatment options for resistant gram-positive bacteria have improved. The development of new substances continues and it is hoped that some of them will be available soon. Investigation has centered on gram-positive bacteria, although multiresistant gram-negative pathogens, such as A haumanii, S maltophilia, and resistant P aeruginosa, are of major clinical relevance. New treatment options are unfortunately not in sight. No antibiotic, however, is a miraculous magic wand against resistant bacteria. The bugs are smart; they have been on this world far longer than humans. Regardless of how innovative the mechanism of action of new substances is, resistance will emerge. The solution is certainly not a nihilistic approach leading to a fearful restriction in the use of new substances. No antibiotic, regardless of its potency, can free the clinician from keeping the difficult balance between individual undertreatment and general overtreatment.     

Peripheral blood progenitor cells mobilized by chemotherapy plus granulocyte-colony stimulating factor accelerate both neutrophil and platelet recovery after high-dose VP16, ifosfamide and cisplatin

Summary. We report on the chemotherapy plus granulocyte colony-stimulating factor (G-CSF) induced mobilization of peripheral blood progenitor cells (PBPCs) and their impact on haematopoietic recovery following high-dose chemotherapy. Twenty-four patients with advanced solid tumours or lymphomas received standard-dose chemotherapy with VP16, ifosfamide and cisplatin (VIP) followed by filgrastim (G-CSF; 5 μg/kg s.c. daily for 14 d) for the prevention of chemotherapy induced neutropenia and for the simultaneous mobilization of PBPCs. Maximal numbers of progenitors of different lineages were reached at day 11 (range 9–14) after VIP chemotherapy. A median of 0·415 × 10⁹/1 CD34⁺ cells (range 0·11–1·98), 9000 CFU-GM/ml (range 2800–17700). 3500 BFU-E/ml (range 400–10800) and 200 CFU-GEMM/ml (range 0–4400) were recruited. One single apheresis yielded a median of 1·6 × 10⁸ mononuclear cells/kg (range 0·2–5·4) or 5·4 × 10⁶ CD34⁺ cells/kg body weight (range 0·2–24·2). Fourteen patients who showed at least a partial remission after two cycles of the standard-dose chemotherapy regimen were subjected to high-dose VIP chemotherapy (cumulative doses of 1500 mg/m² VP16, 12 g/m² ifosfamide and 150 mg/m² cisplatin) with or without PBPC support. The first six patients were treated with growth factors only (IL-3/GM-CSF) and did not receive PBPCs, whereas the following eight patients were supported with PBPCs in addition to IL-3 and GM-CSF. Neutrophil recovery as well as platelet recovery were significantly faster in patients receiving PBPCs with a median of 6·5 d below 0·1 × 10⁹ neutrophils/1 and 3 d below 20 × 10⁹ platelets/1 as compared to 10·5 d and 8 d in control patients receiving growth factors only. The accelerated platelet recovery in patients supported with PBPCs might be explained—in the absence of detectable colony-forming units megakaryocyte—by the presence of glycoprotein IIb/IIIa⁺, non-proliferating endomitotic megakaryocytic precursor cells within G-CSF mobilized PBPCs. Our data demonstrate that chemotherapy plus G-CSF mobilized PBPCs accelerate both neutrophil and platelet recovery after high-dose VIP chemotherapy in patients with solid tumours or lymphomas.