Azithromycin regulates bacterial virulence and immune response in a murine model of ceftazidime-treated Pseudomonas aeruginosa acute pneumonia.

Pseudomonas aeruginosa (PA) remains one of the leading causes of nosocomial acute pneumonia. The array of virulence factors expressed by PA and the intense immune response associated with PA pneumonia play a major role in the severity of these infections. New therapeutic approaches are needed to overcome the high resistance of PA to antibiotics and to reduce the direct damage to host tissues. Through its immunomodulatory and anti-virulence effects, azithromycin (AZM) has demonstrated clinical benefits in patients with chronic PA respiratory infections. However, there is relatively little evidence in PA acute pneumonia. We investigated the effects of AZM, as an adjunctive therapy combined with ceftazidime (CAZ), in a murine model of PA acute pneumonia. We observed that the combined therapy (i) reduces the weight loss of mice 24 h post-infection (hpi), (ii) decreases neutrophil influx into the lungs at 6 and 24 hpi, while this effect is absent in a LPS-induced pneumonia or when PA is pretreated with antibiotics and mice do not receive any antibiotics, and that (iii) AZM, alone or with CAZ, modulates the expression of PA quorum sensing regulators and virulence factors (LasI, LasA, PqsE, PhzM, ExoS). Our findings support beneficial effects of AZM with CAZ on PA acute pneumonia by both bacterial virulence and immune response modulations. Further investigations are needed to clarify the exact underlying mechanisms responsible for the reduction of the neutrophils influx and to better discriminate between direct immunomodulatory properties of AZM, and indirect effects on neutrophilia resulting from bacterial virulence modulation.

Metatarsal lengthening by distraction osteogenesis for brachymetatarsia in paediatric patients: is it safe and effective?

PURPOSE: The primary aim is to assess the efficacy of the surgical callus distraction technique of the metatarsus in paediatric patients. Secondary objectives are to assess complications and treatment duration. We have also described the details of our surgical technique. MATERIALS AND METHODS: A case series review of paediatric patients who had metatarsal lengthening at our unit between 2014 and 2022. Patient demographics, duration of time in frame, complications and metatarsal length achieved were recorded. The AOFAS Midfoot and the MOXFQ were taken pre-operatively and at final follow-up. RESULTS: Sixteen metatarsals in 8 patients (14 feet) underwent lengthening between 2014 and 2022 using the MiniRail OrthoFix 100 (Orthofix Medical Inc, Lewisville, TX, USA). The mean age was 13.3 (12-17) years. The average duration between surgery and implant removal was 5.2 months. According to Paley's classification, there was one obstacle encountered in a patient who required a revision of their osteotomy and one problem in another patient who had an infected metatarsophalangeal joint stabilising k-wire treated with oral antibiotics. The Mean AOFAS Midfoot score improved from 53.10 to 86.40 (p < 0.0001) and the Mean MOXFQ improved from 32.5000 to 12.1250 (p < 0.05); these were statistically significant. CONCLUSION: Gradual metatarsal lengthening using the MiniRail external fixator is a safe and effective method to treat brachymetatarsia in paediatric patients. This preliminary report describes and supports metatarsal lengthening in appropriate patients. Holistic care in terms of a pre-operative assessment, psychological support and preparation for the extended rehabilitation period are vital.

Investigating the Stability of Six Phenolic TMZ Ester Analogues, Incubated in the Presence of Porcine Liver Esterase and Monitored by HPLC.

Previous published data from our group showed the encouraging in vitro activities of six phenolic temozolomide (TMZ) ester analogues (ES8-ES12 and ES14) with up to a five-fold increase in potency compared to TMZ against glioblastoma multiform cell lines and TMZ-resistant O6-methylguanine-DNA methyl transferase (MGMT)-positive primary cells. This study investigated the stabilities of the six phenolic TMZ ester analogues in the presence of porcine liver esterase (PLE) as a hydrolytic enzyme, using high-performance liquid chromatography (HPLC), monitored by a diode-array detector (DAD). Determining the rates of hydrolysis of the esters provided a useful insight into the feasibility of progressing them to the next phase of drug development. Fifty percent of TMZ esters consisting of para nitro, chloro, phenyl and tolyl groups (ES9, ES10, ES12 and ES14) were hydrolysed within the first 4.2 min of PLE exposure, while the TMZ esters consisting of para methoxy and nitrile groups (ES8 and ES11) demonstrated increased stability, with 50% hydrolysis achieved in 7.3 and 13.7 min, respectively. In conclusion, the survival of these phenolic TMZ esters on route to the target site of a brain tumor would be a challenge, mainly due to the undesirable rapid rate of hydrolysis. These findings therefore pose a question regarding the effectiveness of these esters in an in vivo setting.

Propionibacterium/Cutibacterium species-related positive samples, identification, clinical and resistance features: a 10-year survey in a French hospital.

A 10-year retrospective study of Propionibacterium/Cutibacterium-positive samples gathered from hospitalized patients was conducted at Nantes University hospital. A total of 2728 Propionibacterium/Cutibacterium-positive samples analyzed between 2007 and 2016 were included. Due to the implementation of MALDI-TOF identification in 2013, most non-Cutibacterium acnes isolates were identified a second time using this technology. Over that period, Cutibacterium acnes remained the most predominant species accounting for 91.5% (2497/2728) of the isolates, followed by Cutibacterium avidum (4.2%, 115/2728) and Cutibacterium granulosum (2.4%, 64/2728). Regarding the origin of samples, the orthopaedic department was the main Cutibacterium sample provider representing 51.9% (1415/2728) of all samples followed by the dermatology department (11.5%, 315/2728). Samples were recovered from various tissue locations: 31.5% (858/2728) from surgery-related samples such as shoulder, spine or hip replacement devices and 19.1% (520/2728) from skin samples. MALDI-TOF method revealed misidentification before 2013. Cutibacterium avidum was falsely identified as C. granulosum (n = 33). Consequently, MALDI-TOF technology using up-to-date databases should be preferred to biochemical identification in order to avoid biased species identification. Regarding antibiotic resistance, 14.7% (20/136) of C. acnes was resistant to erythromycin. 4.1% (41/1005) of C. acnes strains, 17.9% (12/67) of C. avidum strains and 3.6% (1/28) of C. granulosum strains were found resistant to clindamycin.

Low prevalence of Cutibacterium acnes in prostatic tissue biopsies in a French hospital.

We evaluated the Cutibacterium acnes prevalence in prostatic biopsies and characterized the strains at a molecular level. 18 out of 36 biopsies (50%) were sterile after seven days in culture. C. acnes was observed in only two biopsies. Its prevalence was low (5.6%). Finally, the molecular characterization revealed diverse clusters including phylotypes IA1, IB and II.

[Impacts of a brief contact intervention in suicide prevention on medical care consumptions]. / Impacts d'un système de veille en prévention du suicide sur les consommations de soins.

INTRODUCTION: Suicide prevention is a major objective in public health. The development of alternative approaches to the prevention of suicide, such as monitoring systems, is growing quickly. The results are encouraging, but the analysis of the effectiveness remains complex. The objective of this study is to evaluate the medico-economic impact of the ALGOS brief contact intervention (BCI) on the consumption of medical care. METHOD: ALGOS is a prospective, comparative, multicentre, single-blind, randomized, controlled trial, which compared two groups after a suicide attempt (SA). The ALGOS algorithm assigned each BCI to the subgroup of participants. The medico-economic impact of each intervention was evaluated at 6 and 13 months after inclusion. RESULTS: In all, 987 patients were included. There was no significant difference between the two groups at 6 months and at 13 months after SA in the total number of patients who had been hospitalized in psychiatry or other care services. However, the average number of rheumatology visits was significantly higher in the control group (P=0.01) at 13 months. The total number of rheumatologist and physiotherapist visits was significantly higher in the control group at 6 and 13 months. CONCLUSION: Our results suggest that the use of a BCI after SA does not lead to increased consumption of medical care.

Impact of Radiation and Transcorporeal Artificial Sphincter Placement in Patients with Prior Urethral Cuff Erosion: Results from a Retrospective Multicenter Analysis.

PURPOSE: Many providers elect to use a transcorporeal approach for artificial urinary sphincter placement in an attempt to minimize risks, given the increased risk of complications in revision cases. We present outcomes in a multicenter retrospective analysis of artificial urinary sphincter cuff reimplantation in patients with prior cuff erosion with special consideration given to the transcorporeal approach. MATERIALS AND METHODS: We compiled a multi-institutional database of patients who underwent artificial urinary sphincter reimplantation after prior urethral erosion. Of the 34 identified patients 24 underwent transcorporeal cuff replacement. Patients with transcorporeal cuff replacement were further analyzed with specific stratification for radiation therapy. RESULTS: The rate of subsequent complications after eroded cuff reimplantation was 32.4% (11 of 34 patients). The most frequent complication was recurrent erosion, which developed in 9 of the 34 patients (26.4%). Repeat artificial urinary sphincter complications developed more frequently in patients with history of radiation compared to nonirradiated patients (8 of 16 or 50% vs 3 of 18 or 16.7%). However, this difference was not statistically significant (p = 0.066). The transcorporeal technique was applied in 24 of 33 patients (70.5%) and relative to the nontranscorporeal group there was no difference in the complication rate (p = 0.438). On subgroup analysis of the transcorporeal group there was a higher rate of repeat complications in irradiated patients (p = 0.006). CONCLUSIONS: These data suggest that transcorporeal cuff reimplantation may not decrease the incidence of repeat complications after prior cuff erosion. However, radiation therapy is associated with a worse outcome even when transcorporeal cuff placement is performed.

Prior Radiation Therapy Decreases Time to Idiopathic Erosion of Artificial Urinary Sphincter: A Multi-Institutional Analysis.

PURPOSE: Substantial controversy and conflicting data exist regarding the survival of the artificial urinary sphincter in patients with prior radiation therapy. We present data from a multi-institutional analysis examining the effect of prior radiation for prostate cancer on device survival. MATERIALS AND METHODS: A database was compiled of patients with artificial urinary sphincter cuff erosion, which included demographic and comorbid patient characteristics, functional analyses and interventions. We identified 80 patients with iatrogenic or idiopathic artificial urinary sphincter erosion. Idiopathic erosion cases were further analyzed to determine factors influencing device survival with specific stratification for radiation therapy. RESULTS: A total of 56 patients were identified with idiopathic artificial urinary sphincter erosion. Of those men 33 (58.9%) had not undergone radiation treatment while 23 (41.1%) had a history of brachytherapy or external beam radiotherapy. In patients without radiation erosion-free median device survival was 3.15 years (95% CI 1.95-5.80), in contrast to the median device survival of only 1.00 year (95% CI 0.36-3.00) in irradiated patients. The erosion-free survival experience of patients with vs without radiation differed significantly (Wilcoxon-Breslow test for equality of survivor functions p = 0.03). CONCLUSIONS: Radiation therapy in patients with known idiopathic cuff erosion in this contemporary analysis correlated with significantly increased time to erosion. Mean time to idiopathic cuff erosion was accelerated by approximately 2 years in irradiated cases. To our knowledge these data represent the first demonstration of substantial outcome differences associated with radiation in patients with an artificial urinary sphincter who present specifically with cuff erosion.

[Quality of life and symptoms before and after surgical treatment of rectovaginal fistula]. / Évaluation de la qualité de vie et des symptômes avant et après prise en charge chirurgicale des fistules rectovaginales.

INTRODUCTION: Rectovaginal fistula requires a complex management because it has an important psychological impact associated with impaired quality of life of patients. Thus, the aim of our study was to evaluate the improvement of the quality of life of patients after surgical management. METHODS: This is a retrospective study. We included patients operated between 2009 and 2014 for the treatment of a rectovaginal fistula, whose data were available and who agreed to answer a questionnaire. We evaluated the satisfaction of short-term and long-term patients on the answer to the basic PFDI-20 and PFIQ-7 questionnaires. We then evaluated whether there was an improvement in symptoms and quality of life after surgery. RESULTS: Nine patients were included but only 4 patients completed the PFDI-20 and PFIQ-7 questionnaires. Fistula was secondary to either surgical intervention (44%, n=4) or complicated perineal tear (44%, n=4) or unknown cause (11%, n=1). After surgery, we found the short term a significant decrease in stool incontinence, as there was no stool incontinence (0/5) in the postoperative period, while preoperatively 55% (5/9) (P=0.03). Postoperatively, 33% (3/9) of the patients had genital discomfort and 44% (4/9) had gas incontinence compared to 0% preoperatively (P=0.2 and P=0.6). There appears to be an improvement in pelvic static disorders after surgical management. However, we found a slight improvement in nauseous leucorrhoea in the immediate postoperative period, as the prevalence decreased from 33% (3/9) preoperatively to 22% (2/9) postoperatively (P>0.9). In the long term, we observed an improvement in the sensation of perineal heaviness and gas incontinence because only 25% (1/4) of the 75% (3/4) preoperative patients still showed slight discomfort (P=0.5). The quality of life and the emotional state of the patients were no altered postoperatively. Indeed, preoperatively, 50% (2/4) of the patients reported anxiety compared to 0% (0/4) postoperatively (P=0.4). Similarly, 75% (3/4) complained of a decrease in their quality of life (social, sports, etc.) preoperatively compared with 0% (0/4) postoperatively (P>0.9). CONCLUSION: A simple surgical management of rectovaginal fistulas would allow a significant decrease in stool incontinence and improved quality of life and their emotional state, which confirms the beneficial effect of this therapeutic strategy. LEVEL OF EVIDENCE: 4.

Formation of asteroid pairs by rotational fission.

Pairs of asteroids sharing similar heliocentric orbits, but not bound together, were found recently. Backward integrations of their orbits indicated that they separated gently with low relative velocities, but did not provide additional insight into their formation mechanism. A previously hypothesized rotational fission process may explain their formation-critical predictions are that the mass ratios are less than about 0.2 and, as the mass ratio approaches this upper limit, the spin period of the larger body becomes long. Here we report photometric observations of a sample of asteroid pairs, revealing that the primaries of pairs with mass ratios much less than 0.2 rotate rapidly, near their critical fission frequency. As the mass ratio approaches 0.2, the primary period grows long. This occurs as the total energy of the system approaches zero, requiring the asteroid pair to extract an increasing fraction of energy from the primary's spin in order to escape. We do not find asteroid pairs with mass ratios larger than 0.2. Rotationally fissioned systems beyond this limit have insufficient energy to disrupt. We conclude that asteroid pairs are formed by the rotational fission of a parent asteroid into a proto-binary system, which subsequently disrupts under its own internal system dynamics soon after formation.

Guided Growth of the Distal Posterior Tibial Physis and Short Term Results: A Potential Treatment Option for Children With Calcaneus Deformity.

BACKGROUND: We present our experience of using tension band plates to achieve guided growth in children for correction of calcaneus deformity around the ankle. METHODS: Our study included 9 consecutive patients (11 ankles) with calcaneus deformity, over a period of 4 years. Surgical treatment with extra periosteal application of flexible 2 hole plate and screws on posterior aspect of distal tibial physis was carried out.The indications for treatment were residual clubfoot deformity in 9, posttraumatic in 1, and neurologic in 1. The average age of the patients was 10 years (range, 4 to 13 y). There were 7 males and 2 females.Serial preoperative and postoperative radiographs were used to measure deformity correction and anterior distal tibia angle (ADTA), lateral distal tibial angle (LDTA), and Screw Divergence Angle (angle subtended by lines passing through the screws) were measured. A 2-tailed student t test was used to determine statistical significance. RESULTS: The ADTA showed mean correction of 8.41 degrees (range, 3.1 to 16.6 degrees) this was statistically significant with P-value of 0.0003.The change in LDTA was not statistically significant (P-value=0.05) reinforcing the aptness of the procedure and that the procedure did not result in coronal plane deformities. Six ankles required revision of fixation: 4 due to metalwork reaching its maximum limit of divergence at an average of 1 year, 1 ankle had screw pull-out, and another ankle was revised due to technical error in screw selection. In our study there were no cases of infection. CONCLUSIONS: We report satisfactory short-term results of correction of calcaneus deformity using flexible tension band plates and screws. In our opinion this is an effective alternative providing gradual correction with easy and minimally invasive surgical technique. It does not violate the physis and is easy to remove and revise. It is safe and well tolerated and can be grouped with other procedures with ease. LEVEL OF EVIDENCE: Level IV­case series.

Reservoir alternate surgical implantation technique: preliminary outcomes of initial PROPPER study of low profile or spherical reservoir implantation in submuscular location or traditional prevesical space.

PURPOSE: Alternative reservoir site placement has become an accepted technique for patients who require an inflatable penile prosthesis. To our knowledge there has been no prospective evaluation of this technique, which is currently off label. We performed a prospective, multicenter, multinational, internal review board approved study to evaluate the effectiveness and safety of alternative reservoir site placement. MATERIALS AND METHODS: PROPPER initiated in June 2011, is a database containing patient outcomes of inflatable penile prosthesis implantation. Patients with AMS® penile prostheses continue to be enrolled at 13 North American sites. We examined PROPPER study data to determine surgical implantation use patterns for the AMS 700™ series. We evaluated reservoir implantation site and complications by implantation site. RESULTS: A total of 759 patients had been implanted with an AMS 700 series implant by the time of evaluation. Mean patient followup was 17.8 months (range 0 to 36). There was no reported case of revision surgery for a palpable reservoir and no report of vascular or hollow viscous injury associated with alternative reservoir site placement. Two cases of reservoir herniation in the alternative reservoir site placement group and 2 in the space of Retzius group were treated with reservoir reimplantation. Patients with 1-year assessment available were satisfied or very satisfied with the device and reported a frequency of use of more than once per month. CONCLUSIONS: Alternative reservoir placement in the submuscular location is an option in patients who undergo inflatable penile prosthesis surgery. Implant surgeons should consider alternative reservoir site placement a safe, effective alternative to reservoir placement in the space of Retzius.

Health-related quality of life in patients with melanoma expressed as utilities and disability weights.

BACKGROUND: Few studies about health-related quality of life (HRQoL) in patients with melanoma have expressed their results in terms of utilities or disability weights (DWs). Utilities are required for calculating quality-adjusted life years and therefore for cost-effectiveness analyses. DWs are useful to assess the burden of diseases through disability-adjusted life years. OBJECTIVES: To provide utilities and DWs regarding patients with melanoma. METHODS: The patients were classified into eight groups using four stages based on the 2009 American Joint Committee on Cancer stages, with each stage subdivided into treatment and remission phases. The EuroQoL Five Dimensions Five Levels (EQ-5D-5L) questionnaire was completed by the patients with melanoma to provide a mean utility for each group. In addition to this, the EuroQoL visual analogue scale (VAS) and a validated quality-of-life questionnaire dedicated to patients with melanoma [Functional Assessment of Cancer Therapy Melanoma (FACT-M)] were completed by the same patients in order to compare their results with the obtained utilities. DWs were obtained by calculating, for each patient, the difference between his/her utility and the corresponding sex- and age-specific population norm. RESULTS: A total of 395 questionnaire sets were completed. Utilities and DWs showed significant differences between follow-up groups. Treatment groups had similar utilities and DWs but these results were obtained during different treatment durations and therefore have different weights. The VAS and the FACT-M were found to be less sensitive. Nevertheless, the FACT-M identified some problems not found by the EQ-5D-5L questionnaire. CONCLUSIONS: The EQ-5D-5L questionnaire seems adequate to provide utilities and DWs in patients with melanoma. Lower HRQoL in female patients with melanoma is probably linked to lower HRQoL in the general population.

Comparative analysis of quality scores images between second- and third-trimester ultrasound scan.

OBJECTIVES: To evaluate whether the quality scores validated for second-trimester ultrasound scan can be used for third-trimester ultrasound scan. METHODS: Prospective multicenter ancillary study using data from the RECRET study. Nulliparous women, with no reported history, with second- and third-trimester ultrasound examinations performed by the same ultrasonographer and using the same ultrasound machine were recruited. The global score and the individual score of each ultrasound image were compared between second- and third-trimester ultrasound scan. The sample size was calculated for a non-inferiority (one-sided) paired Student t test. RESULTS: 103 women with 1606 anonymized ultrasound images were included. The median term at second- and third-trimester ultrasound scan was 22.2 weeks gestation (22.0-22.7) and 31.6 weeks gestation (30.7-34.7), respectively. The mean global score of ultrasound images was comparable between the second- and the third-trimester ultrasound examination (32.37 ± 2.62 versus 31.80 ± 3.27, p = 0.13). Means scores for each biometric parameters i.e. head circumference, abdominal circumference, and femur diaphysis length were comparable. The scores for the four-chamber view (5.11 ± 0.91 versus 5.36 ± 0.75, p = 0.02) and the spine (4.18 ± 1.17 versus 5.22 ± 1.02, p < 0.001) were significantly lower in the third trimester compared to the second trimester. The score for the kidney image was significantly higher for third trimester images compared to second trimester images (4.73 ± 0.51 versus 4.32 ± 0.67, p < 0.001. CONCLUSIONS: Biometrics parameters quality scores images previously validated for the second trimester ultrasound scan can be also used for the third trimester scan. However, anatomical quality scores images performances may vary between the second and the third trimester scan.

Clostridial prosthetic joint infections: A series of 16 cases and literature review.

OBJECTIVES: Prosthetic joint infections (PJIs) due to the Clostridium species have not been widely investigated. We aimed to characterize these uncommon infections. METHODS: We conducted a retrospective study between 2003 and 2020 in six French hospitals combined with a review of the literature. RESULTS: The main conclusions obtained from the 16 patients included were reinforced by the literature analysis: (i) Clostridium perfringens was the most frequently involved species, (ii) patients presented an advanced age at the time of prosthesis placement and infection, (iii) most of the infections were early- or delayed-onset, (iv) the prognosis for these PJIs remains poor, (v) when performed (n = 5), DAIR with 12-week antimicrobial therapy led to a favorable outcome in 80% of cases. CONCLUSIONS: Given the low incidence of this infection, our work represents the largest series of clostridial PJIs reported to date and highlights some specificities of these infections. Further prospective studies are needed to confirm these results.

Magnetically localized and wash-free fluorescence immunoassay (MLFIA): proof of concept and clinical applications.

Immunoassays are used for many applications in various markets, from clinical diagnostics to the food industry, generally relying on gold-standard ELISAs that are sensitive, robust, and cheap but also time-consuming and labour intensive. As an alternative, we propose here the magnetically localized and wash-free fluorescence immunoassay (MLFIA): a no-wash assay to directly measure a biomolecule concentration, without mixing nor washing steps. To do so, a fluorescence no-wash measurement is performed to generate a detectable signal. It consists of a differential measurement between the fluorescence of fluorophores bound to magnetic nanoparticles specifically captured by micro-magnets against the residual background fluorescence of unbound fluorophores. Targeted biomolecules (antibodies or antigens) are locally concentrated on micro-magnet lines, with the number of captured biomolecules quantitatively measured without any washing step. The performance of the MLFIA platform is assessed and its use is demonstrated with several biological models as well as clinical blood samples for HIV, HCV and HBV detection, with benchmarking to standard analyzers of healthcare laboratories. Thus, we demonstrated for the first time the versatility of the innovative MLFIA platform. We highlighted promising performances with the successful quantitative detection of various targets (antigens and antibodies), in different biological samples (serum and plasma), for different clinical tests (HCV, HBV, HIV).

A randomized, double-blind, placebo-controlled evaluation of the safety and efficacy of avanafil in subjects with erectile dysfunction.

INTRODUCTION: Phosphodiesterase type 5 (PDE5) inhibitors have become standard treatment for erectile dysfunction (ED). AIM: To prospectively evaluate the safety and efficacy of avanafil, a novel PDE5 inhibitor, in men with mild to severe ED. METHODS: In this multicenter, double-blind, Phase 3 trial, 646 subjects were randomized to receive avanafil (50 mg, 100 mg, 200 mg) or placebo throughout a 12-week treatment period. Subjects were instructed to take study drug 30 minutes prior to initiation of sexual activity. At least a 12-hour separation time between doses was required; no restrictions were placed on food or alcohol intake. MAIN OUTCOME MEASURES: Improvement in erectile function (EF) was measured by Sexual Encounter Profile questions 2 and 3 (SEP2 and SEP3) and by the EF domain of the International Index of Erectile Function (IIEF) questionnaire. RESULTS: Mean change in percentage of successful sexual attempts (SEP2 and SEP3) and IIEF-EF domain score significantly favored all doses of avanafil over placebo (P ≤ 0.001). Secondary analyses demonstrated achievement of successful intercourse by subjects within 15 minutes of dosing. Of the 300 sexual attempts made during this interval, 64% to 71% were successful in avanafil-treated subjects compared with 27% in placebo-treated subjects. Successful intercourse was also demonstrated >6 hours post dosing, with 59% to 83% of the 80 sexual attempts successful in avanafil-treated subjects compared with 25% of placebo-treated subjects. The most commonly reported adverse events in subjects taking avanafil included headache, flushing, and nasal congestion; there were no drug-related serious adverse events. CONCLUSION: Following 12 weeks of avanafil treatment without food or alcohol restrictions, significant improvements in sexual function were observed with all 3 doses of avanafil compared with placebo. Successful intercourse was observed as early as 15 minutes and >6 hours after dosing in some subjects. Avanafil was generally well tolerated for the treatment of ED.