Simvastatin improves the sexual health-related quality of life in men aged 40 years and over with erectile dysfunction : Additional data from the Erectile Dysfunction and Statin trial

© 2014 Trivedi et al. This is an Open Access article distributed under the terms of the Creative Commons Attribution License http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited.Background: Erectile dysfunction is prevalent in men over 40 years, affecting their quality of life and that of their partners. The aims of this study were:a)To evaluate the internal reliability of the male erectile dysfunction specific quality of life (MED-QoL) scale and explore its factor structure.b)To evaluate the effect of simvastatin on subscales of the MED-QoL in men over forty years with erectile dysfunction. Methods: This is a double blind randomised controlled trial of 40 mg simvastatin or placebo given once daily for six months to men over forty years with untreated erectile dysfunction, who were not at high cardiovascular risk and were not on anti-hypertensive or lipid-lowering medication. 173 eligible men were recruited from 10 general practices in East of England. Data were collected at two points over 30 weeks. We report on the factor structure of MED-QoL, the internal reliability of the scale and the derived subscales, and the effect of simvastatin on MED-QoL subscales. Results: An initial analysis of the MED-QoL items suggested that a number of items should be removed (MED-QoL-R). Exploratory factor analysis identified three subscales within the MED-QoL-R which accounted for 96% of the variance, related to feelings of Control, initiating Intimacy, and Emotional response to erectile dysfunction. The alpha value for the revised scale (MED-Qol-R) was >0.95 and exceeded .82 for each subscale. Regression analysis showed that patients in the placebo group experienced a significantly reduced feeling of Control over erectile dysfunction than those in the statin group. Those in the placebo group had significantly lower Emotional response than those in the statin group at the close of trial, but there was no significant treatment effect on Intimacy. Conclusions: Our revised MED-QoL-R identified three subscales. Secondary analysis showed a significant improvement in sexual health related quality of life, specifically in relation to perception of control and emotional health in men with untreated erectile dysfunction given 40 mg simvastatin for six months. Trial registration: Current Controlled Trials ISRCTN66772971.Peer reviewe

The fundamental pro-groupoid of an affine 2-scheme

A natural question in the theory of Tannakian categories is: What if you don't remember \Forget? Working over an arbitrary commutative ring $R$, we prove that an answer to this question is given by the functor represented by the \'etale fundamental groupoid \pi_1(\spec(R)), i.e.\ the separable absolute Galois group of $R$ when it is a field. This gives a new definition for \'etale \pi_1(\spec(R)) in terms of the category of $R$-modules rather than the category of \'etale covers. More generally, we introduce a new notion of "commutative 2-ring" that includes both Grothendieck topoi and symmetric monoidal categories of modules, and define a notion of $\pi_1$ for the corresponding "affine 2-schemes." These results help to simplify and clarify some of the peculiarities of the \'etale fundamental group. For example, \'etale fundamental groups are not "true" groups but only profinite groups, and one cannot hope to recover more: the "Tannakian" functor represented by the \'etale fundamental group of a scheme preserves finite products but not all products.Comment: 46 pages + bibliography. Diagrams drawn in Tik

Incydenty sercowo-naczyniowe u pacjentów stosujących sildenafil - wyniki badania International Men’s Health Study

Wstęp: Celem pracy było oszacowanie częstości występowania poważnych incydentów sercowo-naczyniowych (np. zawał serca, udar) oraz całkowitej śmiertelności wśród mężczyzn z zaburzeniami erekcji otrzymujących sildenafil. Metody: Prospektywnym, obserwacyjnym badaniem kohortowym International Men’s Health Study (IMHS) objęto pacjentów ze zdiagnozowanymi zaburzeniami erekcji oraz wcześniej stosujących sildenafil lub dopiero zaczynających przyjmować ten preparat. Dane wyjściowe oraz z obserwacji odległej dotyczące chorób sercowo-naczyniowych (CVD), czynników ryzyka oraz zaburzeń erekcji uzyskano za pomocą odpowiednich kwestionariuszy. Do osób, które przebyły epizod sercowo-naczyniowy, wysłano kwestionariusze w celu zebrania informacji związanych z ekspozycją na sildenafil/leczeniem zaburzeń erekcji przed incydentem. Wyniki: W analizowanej grupie (n = 3813) odnotowano 35 incydentów sercowo-naczyniowych u 30 chorych. Częstość zgonu z jakiejkolwiek przyczyny, zawału serca oraz udaru wynosiła odpowiednio 0,4; 0,6 i 0,1 na każdych 100 pacjentolat obserwacji. W grupie 6 mężczyzn, którzy zgłosili stosowanie sildenafilu na miesiąc przed incydentem sercowo-naczyniowym, 2 podało jego użycie w czasie 24 godzin poprzedzających zdarzenie. Wnioski: Wyniki badania IMHS potwierdzają wcześniejsze doniesienia o współwystępowaniu zaburzeń erekcji oraz CVD i o podobnych czynnikach ryzyka tych chorób

Mosaicism for combined tetrasomy of chromosomes 8 and 18 in a dysmorphic child: A result of failed tetraploidy correction?

<p>Abstract</p> <p>Background</p> <p>Mosaic whole-chromosome tetrasomy has not previously been described as a cause of fetal malformations.</p> <p>Case presentation</p> <p>In a markedly dysmorphic child with heart malformations and developmental delay, CGH analysis of newborn blood DNA suggested a 50% dose increase of chromosomes 8 and 18, despite a normal standard karyotype investigation. Subsequent FISH analysis revealed leukocytes with four chromosomes 8 and four chromosomes 18. The child's phenotype had resemblance to both mosaic trisomy 8 and mosaic trisomy 18. The double tetrasomy was caused by mitotic malsegregation of all four chromatids of both chromosome pairs. A possible origin of such an error is incomplete correction of a tetraploid state resulting from failed cytokinesis or mitotic slippage during early embryonic development.</p> <p>Conclusion</p> <p>This unique case suggests that embryonic cells may have a mechanism for tetraploidy correction that involves mitotic pairing of homologous chromosomes.</p

Indirect comparison of interventions using published randomised trials: systematic review of PDE-5 inhibitors for erectile dysfunction

BACKGROUND: There are no randomised and properly blinded trials directly comparing one PDE-5 inhibitor with another in a normal home setting. Valid indirect comparisons with a common comparator must examine equivalent doses, similar duration, similar populations, with the same outcomes reported in the same way. METHODS: Published randomised, double-blind trials of oral PDE-5 inhibitors for erectile dysfunction were sought from reference lists in previous reviews and electronic searching. Analyses of efficacy and harm were carried out for each treatment, and results compared where there was a common comparator and consistency of outcome reporting, using equivalent doses. RESULTS: Analysis was limited by differential reporting of outcomes. Sildenafil trials were clinically and geographically more diverse. Tadalafil and vardenafil trials tended to use enriched enrolment. Using all trials, the three interventions were similar for consistently reported efficacy outcomes. Rates of successful intercourse for sildenafil, tadalafil and vardenafil were 65%, 62%, and 59%, with placebo rates of 23–28%. The rates of improved erections were 76%, 75% and 71%, respectively, with placebo rates of 22–24%, and NNTs of 1.9 or 2.0. Reporting of withdrawals was less consistent, but all-cause withdrawals for sildenafil, tadalafil and vardenafil were 8% 13% and 20%. All three drugs were well tolerated, with headache being the most commonly reported event at 13–17%. There were few serious adverse events. CONCLUSION: There were differences between trials in outcomes reported, limiting comparisons, and the most useful outcomes were not reported. For common outcomes there was similar efficacy between PDE-5 inhibitors

Hardness, function, emotional well-being, satisfaction and the overall sexual experience in men using 100-mg fixed-dose or flexible-dose sildenafil citrate

The prescribing information for sildenafil citrate (VIAGRA, Pfizer, New York, NY, USA) recommends flexible dosing (50 mg initially, adjusted to 100 or 25 mg based on effectiveness and tolerability) in most men with erectile dysfunction (ED). In many men, however, 100 mg may be the most appropriate initial dose because it would reduce the need for titration and could prevent discouragement and treatment abandonment should 50 mg be insufficient. Results of two previously published double-blind, placebo-controlled sildenafil trials of similar design except for a fixed-dose vs flexible-dose regimen were analyzed. Relative to the flexible-dose, approximately one-third more men were satisfied with an initial and fixed dose of 100 mg. In addition, tolerability was similar, and improvements from baseline in outcomes on validated, ED-specific, patient-reported questionnaires were either similar (erectile function and the percentage of completely hard and fully rigid erections) or greater (emotional well-being and the overall sexual experience). The similarity in outcomes is not surprising given that almost 90% of the men in the flexible-dose trial titrated to 100 mg after 2 weeks. These data suggest prescription of an initial dose of 100 mg for men with ED, except in those for whom it is inappropriate

Fizikokemijska karakterizacija čvrstih disperzijskih sustava tadalafila s poloksamerom 407

Dissolution behaviour of a poorly water-soluble drug, tadalafil, from its solid dispersion systems with poloxamer 407 has been investigated. Solid dispersion systems of tadalafil were prepared with poloxamer 407 in 1:0.5, 1:1.5 and 1:2.5 ratios using the melting method. Characterization of binary systems with FTIR and powder XRPD studies demonstrated the presence of strong hydrogen bonding interactions, a significant decrease in crystallinity and the possibility of existence of amorphous entities of the drug. In the binary systems tested, 1:0.5 proportion of tadalafil/poloxamer 407 showed rapid dissolution of tadalafil (DE30 70.9 ± 3.6 %). In contrast, higher proportions of poloxamer 407 (1:1.5 and 1:2.5) offered no advantage towards dissolution enhancement of the drug from corresponding binary systems indicating altered rheological characteristics of the polymer, at its higher concentration, which might have retarded the release rate of tadalafil.U radu je ispitivano oslobađanje u vodi teško topljivog lijeka tadalafila iz čvrstih disperzijskih sustava. Ti sustavi pripravljeni su s poloksamerom 407 u omjeru lijeka i polimera 1:0,5, 1:1,5 i 1:2,5, koristeći metodu taljenja. Karakterizacija binarnih sustava s FTIR i rendgenskom difrakcijom praha XRD ukazuje na prisutnost snažnih vodikovih veza, značajno smanjenje kristaliničnosti i moguću prisutnost amorfnog lijeka. Iz binarnog sustava tadalafil/poloksamer 1:0,5 oslobađanje ljekovite tvari je brzo (DE30 70,9 ± 3,6 %). Nasuprot tome, iz pripravaka s višim omjerima lijeka i polimera (1:1,5 i 1:2,5) oslobađanje ljekovite tvari nije povećano. Usporavanje oslobađanja tadalafila moglo bi biti posljedicom promjene reoloških svojstava polimera pri višim koncentracijama

Identifying Highly Conserved and Highly Differentiated Gene Ontology Categories in Human Populations

Detecting and interpreting certain system-level characteristics associated with human population genetic differences is a challenge for human geneticists. In this study, we conducted a population genetic study using the HapMap genotype data to identify certain special Gene Ontology (GO) categories associated with high/low genetic difference among 11 Hapmap populations. Initially, the genetic differences in each gene region among these populations were measured using allele frequency, linkage disequilibrium (LD) pattern, and transferability of tagSNPs. The associations between each GO term and these genetic differences were then identified. The results showed that cellular process, catalytic activity, binding, and some of their sub-terms were associated with high levels of genetic difference, and genes involved in these functional categories displayed, on average, high genetic diversity among different populations. By contrast, multicellular organismal processes, molecular transducer activity, and some of their sub-terms were associated with low levels of genetic difference. In particular, the neurological system process under the multicellular organismal process category had low levels of genetic difference; the neurological function also showed high evolutionary conservation between species in some previous studies. These results may provide a new insight into the understanding of human evolutionary history at the system-level