Efficacy and safety of Finasteride (5 alpha-reductase inhibitor) monotherapy in patients with benign prostatic hyperplasia: A critical review of the literature

BACKGROUND: Combination therapy with 5 alpha-reductase inhibitor (5-ARI) and alpha-blocker can be considered as a gold standard intervention for medical management of lower urinary tract symptoms related to benign prostatic hyperplasia (LUTS/BPH). On the other hand, 5-ARI monotherapy and in particular Finasteride alone is currently getting focus of attention especially due to lack of systematic reviews investigating efficacy outcomes and/or adverse events associated. OBJECTIVES: Aim of the present critical review was to analyze current knowledge of clinical efficacy and incidence of adverse events associated with 5-ARI treatment for LUTS/BPH. MATERIALS AND METHODS: A systematic review of clinical trials of the literature of the past 20 years was performed using database from PubMed, Cochrane Collaboration and Embase. A total of 8821 patients were included in this study and inclusion criteria for studies selection were: data from randomized clinical trials (RCTs) focusing their attention on the clinical role of Finasteride monotherapy for symptomatic BPH. Parameters of research included prostate specific antigen (PSA), prostate volume (PV), International Prostate Symptom Score (IPPS), postvoid residual urine (PVR), voiding symptoms of IPSS (voiding IPSS), maximum urinary flow rate (Qmax), and adverse events (AEs). RESULTS: Overall 12 original articles were included and critically evaluated. Sample sizes of patient actively treated with finasteride varied from 13 to 1524 cases analyzed in a single study. Follow-up after treatments ranged from 3 to 54 months. The effect of finasteride in reducing prostate volume (PV) was moderate (standardized mean difference (SMD) effect between 0.5 to 0.8 for all trials evaluable) while the effect on IPSS score and Qmax was considered significant (SMD in the 0.2 to 0.5 variation range). No severe AEs and/or psychiatric disorders were retrieved among the studies. Sexual health dysfunctions were significantly influenced by finasteride therapy when compared with placebo treated patients. CONCLUSIONS: Although significant clinical benefits of finasteride monotherapy were demonstrated, the effective size of the available reports included in the analysis is limited. Additional head-to-head studies would be needed to re-evaluate clinical efficacy and safety of 5-ARI in combination or not with alpha blockers

Accounting for erroneous model structures in biokinetic process models

In engineering practice, model-based design requires not only a good process-based model, but also a good description of stochastic disturbances and measurement errors to learn credible parameter values from observations. However, typical methods use Gaussian error models, which often cannot describe the complex temporal patterns of residuals. Consequently, this results in overconfidence in the identified parameters and, in turn, optimistic reactor designs. In this work, we assess the strengths and weaknesses of a method to statistically describe these patterns with autocorrelated error models. This method produces increased widths of the credible prediction intervals following the inclusion of the bias term, in turn leading to more conservative design choices. However, we also show that the augmented error model is not a universal tool, as its application cannot guarantee the desired reliability of the resulting wastewater reactor design. © 2020 Elsevier LtdMarc B. Neumann acknowledges financial support provided by the Spanish Government through the BC3 María de Maeztu excellence accreditation 2018–2022 (MDM-2017-0714) and the Ramón y Cajal grant (RYC-2013-13628); and by the Basque Government through the BERC 2018-2021 program

Long-term follow-up of Philadelphia chromosome-positive (Ph+) chronic myeloid leukaemia (CML) in children and adolescents managed at a single institution over a 20-year period

Chronic myeloid leukaemia (CML) is rare in childhood. In our Institution we managed 30 consecutive Ph+CML patients aged <18 years, according to our adults’ guidelines. Patients with HLA-identical related donor (RD) underwent stem cell transplant (SCT). Since 1989, patients without RD were systematically treated with -interferon (IFN) (median dosage: 6 MU/day). Of 18/19 evaluable patients, 17 (94.5%) achieved haematologic response (HR), 11/17 (65%) cytogenetic response (CyR), complete (CCyR) in 4 (23.5%). Three patients remain in CCyR, 2 achieved BCR-ABL transcript disappearance. Of 13 patients without CCyR, 5 underwent SCT, 4 switched to STI571, 4 progressed. All patients receiving STI571 in chronic phase (CP) obtained sustained CCyR and 3 a persistent molecular response. 8-year survival among IFN-treated patients, censored or not for subsequent therapies, is 62% and 63%. Overall, 13/30 patients underwent SCT: 5 HLA-identical-RD, 5 matched unrelated donor, 2 mismatched-RD, 1 unrelated mismatched umbilical cord blood. Eight allotransplanted patients (6/6 in 1st CP) are in cytogenetic and molecular remission with 8-year survival of 61% from SCT and 69% from diagnosis. In our 20-year experience, the use of IFN in children without matched RD led to prolonged cytogenetic and molecular responses and long-term survival, without impairing the outcome of subsequent SCT

Chronic bacterial prostatitis: efficacy of short-lasting antibiotic therapy with prulifloxacin (Unidrox®) in association with saw palmetto extract, lactobacillus sporogens and arbutin (Lactorepens®)

Bacterial prostatitis (BP) is a common condition accounting responsible for about 5-10% of all prostatitis cases; chronic bacterial prostatitis (CBP) classified as type II, are less common but is a condition that significantly hampers the quality of life, (QoL) because not only is it a physical condition but also a psychological distress. Commonly patients are treated with antibiotics alone, and in particular fluoroquinolones are suggested by the European Urology guidelines. This approach, although recommended, may not be enough. Thus, a multimodal approach to the prolonged antibiotic therapy may be helpful.210 patients affected by chronic bacterial prostatitis were enrolled in the study. All patients were positive to Meares-Stamey test and symptoms duration was &gt; 3&nbsp;months. The purpose of the study was to evaluate the efficacy of a long lasting therapy with a fluoroquinolone in association with a nutraceutical supplement (prulifloxacin 600&nbsp;mg for 21&nbsp;days and an association of Serenoa repens 320&nbsp;mg, Lactobacillus Sporogens 200&nbsp;mg, Arbutin 100&nbsp;mg for 30&nbsp;days). Patients were randomized in two groups (A and B) receiving respectively antibiotic alone and an association of antibiotic plus supplement.Biological recurrence at 2&nbsp;months in Group A was observed in 21 patients (27.6%) and in Group B in 6 patients (7.8%). Uropathogens found at the first follow-up were for the majority Gram - (E. coli and Enterobacter spp.). A statistically significant difference was found at the time of the follow-up between Group A and B in the NIH-CPSI questionnaire score, symptoms evidence and serum PSA.Broad band, short-lasting antibiotic therapy in association with a nutritional supplement (serenoa repens, lactobacillus sporogens and arbutin) show better control and recurrence rate on patients affected by chronic bacterial prostatitits in comparison with antibiotic treatment alone.NCT02130713Date of trial Registration: 30/04/2014

Dissipative Dynamic Libraries (DDLs) and Dissipative Dynamic Combinatorial Chemistry (DDCC)

This Concept is focused on the key features of dissipative dynamic combinatorial chemistry (DDCC). DDCC deals with transient libraries of compounds, maintained out-of-equilibrium by the consumption of a fuel, whose composition changes upon the selection pressure of kinetic and/or thermodynamic processes. Concepts and definitions of kinetic and thermodynamic dissipative dynamic libraries ("KDDL" and "TDDL"), are introduced and illustrated by a number of actual cases, thus showing the consistency of the present approach. Such concepts and definitions can help establish a common language for this emerging field, which, in our view, has the potential to become highly relevant to supramolecular chemistry

Torque range, a new parameter to evaluate new and used instrument safety

The aim of the present study is to evaluate operative torque, torque at failure and the difference between these two values-the "torque range"-of two different NiTi files. We also sought to evaluate and compare these parameters for new and used files. Forty S-One 20.06 and forty M-Two 20.06 were tested, divided in four equal groups (n = 10) for each brand. Ten instruments from each brand performed three root canal treatments each on standardized extracted single-rooted teeth. Afterwards, each group was subjected to the following two tests: operative torque and torsional resistance. Mean values for all the tested groups were calculated. The results for new instruments showed that S-One developed significantly higher operative torque, but higher torsional resistance. The results for used instruments showed that the S-One 20.06 developed less operative torque and higher mean torsional resistance value compared to the M-Two. Moreover, the percentage reduction of both values was significantly higher for M-Two. The results of the present study showed a safer torsional behavior of the S-One. These results could be related to the heat treatment and the manufacturing process

Valuation of ecological retrofitting technology in existing buildings: A real-world case study

The world’s existing buildings are aged, in a state of deterioration and in need of inter-ventions. When selecting the type of possible intervention to be applied, the choice falls between two alternatives: simple unsustainable ordinary maintenance versus ecological retrofitting i.e., an increase in the quality of the indoor environment and building energy saving using local bio-natural materials and products. The present research seeks to respond to the requests of recent comprehen-sive reviews which ask for the retrofitting of the world’s huge existing building stocks and portfolios by proposing an approach and testing it in a specific case study (at the unit, building and urban block level) which can then be carried out and repeated in the future on a larger urban scale. The real-world experimentation in the provided case study achieved the important outcome and goal of a Green Building strategy and post-carbon city framework i.e. the significant enhancement of the thermal performance of the buildings as a result of a few targeted key external works and the con-sequent saving of energy in those already existing (but not preserved and not included in the state national register or record of monuments) Liberty-style constructions. All the above show that these important existing buildings can be ecologically retrofitted at an affordable cost, although initially slightly more expensive than the cost of ordinary unsustainable maintenance. However, this difference is offset by the favorable pay-back period, which is fast, acceptable and of short duration. The tried and tested approach, the positive proposed case study and the experimental database-GIS joint platform (the details of which can be found in an additional supplementary research which is currently being carried out) are the bases on which a future decision support system will be proposed. This support system can be carried out as a tailor-made solution for the ecological retrofitting of the enormous existing building stocks and portfolios which must be considered on a larger scale i.e., at ward, quartier, city, regional and country level

Time Programmable Locking/Unlocking of the Calix[4]arene Scaffold by Means of Chemical Fuels

In this work, we report that 2-cyano-2-phenylpropanoic acid and its p-Cl, p-CH3 and p-OCH3 derivatives can be used as chemical fuels to control the geometry of the calix[4]arene scaffold in its cone conformation. It is shown that, under the action of the fuel, the cone calix[4]arene platform assumes a “locked” shape with two opposite aromatic rings strongly convergent and the other two strongly divergent (“pinched cone” conformation). Only when the fuel is exhausted, the cone calix[4]arene scaffold returns to its resting, “unlocked” shape. Remarkably, the duration of the “locked” state can be controlled at will by varying the fuel structure or amount. A kinetic study of the process shows that the consume of the fuel is catalyzed by the “unlocked” calixarene that behaves as an autocatalyst for its own production. A mechanism is proposed for the reaction of fuel consumption

Torsional resistance of two new heat treated nickel titanium rotary instruments: an in vitro evaluation

Objective: To evaluate the difference in torsional resistance, angular deflection and fragment length between two new rotary instruments: AF Blue S4 and S-One. These files share all features except cross-sectional design. Material and Methods: A total of 40 new Nickel-Titanium instruments of 25 mm in length were tested in this study and divided in two groups: 20 AF Blue S4, tip 25 and constant 6% taper and 20 AF-Blue S4 tip 25 and constant 6% taper. The torsional test was performed by the use of a torque recording endodontic motor (KaVo, Biberac, Germany). Torque to Fracture (TtF), Angular Deflection (AD) and Fragment Length (FL) was recorded for each instrument. To ensure an immovable block at 3mm of the instrument tip, an auto-polymerizing resin (DuraLay; Reliance Dental Mfg Co, Worth, IL) was used. Each file was rotated clockwise at a speed of 300 rpm until fracture occurred. Results: Group A (AF Blue S4) showed higher TtF and AD than Group B (S-One), and statistical analysis found significant differences between the two instruments (p&lt;0.05). The mean values for FL showed no significant differences (p&gt;0.05) between the two instruments. Conclusion: The AF Blue S4 seems to have a higher resistance to torsional stress in vitro. Clinically, the use of AF Blue S4 could be safer in narrow canals

Temporal Control of the Host-Guest Properties of a Calix[6]arene Receptor by the Use of a Chemical Fuel

The host-guest interaction of a 1,3,5-trisaminocalix[6]arene receptor with N-methylisoquinolinium trifluoromethanesulfonate (Kassof 500 ± 30 M-1in CD2Cl2) can be dissipatively driven by means of 2-cyano-2-(4′-chloro)phenylpropanoic acid used as a convenient chemical fuel. When the fuel is added to a dichloromethane solution containing the above complex, the host is induced to immediately release the guest in the bulk solution. Consumption of the fuel allows the guest to be re-uptaken by the host. The operation can be satisfactorily reiterated with four subsequent additions of fuel, producing four successive release-reuptake cycles. The percentage of the guest temporarily released in the bulk solution by the host and the time required for the reuptake process can be finely regulated by varying the quantities of added fuel