Impact of mild acute kidney injury (AKI) on outcome after open repair of aortic aneurysms

Recently, mild AKI has been considered as a risk factor for mortality in different scenarios. We conducted a retrospective analysis of the risk factors for two distinct definitions of AKI after elective repair of aortic aneurysms. Logistic regression was carried out to identify independent risk factors for AKI ( defined as >= 25% or >= 50% increase in baseline SCr within 48 h after surgery, AKI 25% and AKI 50%, respectively) and for mortality. Of 77 patients studied ( mean age 68 +/- 10, 83% male), 57% developed AKI 25% and 33.7% AKI 50%. There were no differences between AKI and control groups regarding comorbidities and diameter of aneurysms. However, AKI patients needed a supra-renal aortic cross-clamping more frequently and were more severely ill. Overall in-hospital mortality was 27.3%, which was markedly higher in those requiring a supra-renal aortic cross-clamping. The risk factors for AKI 25% were suprarenal aortic cross-clamping ( odds ratio 5.51, 95% CI 1.05-36.12, p = 0.04) and duration of operation for AKI 25% ( OR 6.67, 95% CI 2.23-19.9, p < 0.001). For AKI 50%, in addition to those factors, post-operative use of vasoactive drugs remained as an independent factor ( OR 6.13, 95% CI 1.64-22.8, p = 0.005). The risk factors associated with mortality were need of supra-renal aortic cross-clamping ( OR 9.6, 95% CI 1.37-67.88, p = 0.02), development of AKI 50% ( OR 8.84, 95% CI 1.31-59.39, p = 0.02), baseline GFR lower than 49 mL/min ( OR 17.07, 95% CI 2.00 145.23, p = 0.009), and serum glucose > 118 mg/dL in the post-operative period ( OR 19.99, 95% CI 2.32-172.28, p = 0.006). An increase of at least 50% in baseline SCr is a common event after surgical repair of aortic aneurysms, particularly when a supra-renal aortic cross-clamping is needed. Along with baseline moderate chronic renal failure, AKI is an independent factor contributing to the high mortality found in this scenario.

Online monitoring of pulse pressure variation to guide fluid therapy after cardiac surgery

BACKGROUND: The arterial pulse pressure variation induced by mechanical ventilation (Delta PP) has been shown to be a predictor of fluid responsiveness. Until now, Delta PP has had to be calculated offline (from a computer recording or a paper printing of the arterial pressure curve), or to be derived from specific cardiac output monitors, limiting the widespread use of this parameter. Recently, a method has been developed for the automatic calculation and real-time monitoring of Delta PP using standard bedside monitors. Whether this method is to predict reliable predictor of fluid responsiveness remains to be determined. METHODS: We conducted a prospective clinical study in 59 mechanically ventilated patients in the postoperative period of cardiac surgery. Patients studied were considered at low risk for complications related to fluid administration (pulmonary artery occlusion pressure <20 mm Hg, left ventricular ejection fraction >= 40%). All patients were instrumented with an arterial line and a pulmonary artery catheter. Cardiac filling pressures and cardiac output were measured before and after intravascular fluid administration (20 mL/kg of lactated Ringer`s solution over 20 min), whereas Delta PP was automatically calculated and continuously monitored. RESULTS: Fluid administration increased cardiac output by at least 15% in 39 patients (66% = responders). Before fluid administration, responders and nonresponders were comparable with regard to right atrial and pulmonary artery occlusion pressures. In contrast, Delta PP was significantly greater in responders than in nonresponders, (17% +/- 3% vs 9% +/- 2%, P < 0.001). The Delta PP cut-off value of 12% allowed identification of responders with a sensitivity of 97% and a specificity of 95%. CONCLUSION: Automatic real-time monitoring of Delta PP is possible using a standard bedside rnonitor and was found to be a reliable method to predict fluid responsiveness after cardiac surgery. Additional studies are needed to determine if this technique can be used to avoid the complications of fluid administration in high-risk patients.

Mammaplasty with Inferior Pedicle Flap After Massive Weight Loss

After massive weight loss, one of the stigmas that afflict women is the remaining deformity of the breasts which become flaccid and ptotic, with an absent or flat upper pole. The authors propose the use of a well-established mammaplasty technique to fill the upper pole, reshape the breast cone, and correct ptosis with nipple-areola complex (NAC) repositioning. A total of 16 patients were analyzed; all underwent gastroplasty between 18 and 24 months prior to mammaplasty. The mean age was 41.6 years (range = 26-62) and the mean BMI previous to the mammaplasty was 29.2 kg/m(2) (range = 24.9-38.9). The technique included a dermo-lipo glandular flap pedicled on the inframammary fold (IMF) together with a superior flap containing the NAC. All patients who underwent surgery were satisfied with the outcomes since a more aesthetic breast shape was achieved, with projection of the upper pole and correction of ptosis. Adverse events included dehiscence at the junction point of the flaps in the inframammary fold, which resolved with secondary-intention wound healing in three patients; partial necrosis of the areola in one patient; epidermolysis in one of the NACs in one patient; and infection in one of the breasts in one patient, which resolved with proper antibiotic therapy. When compared to the current mammaplasty techniques performed in formerly obese patients, this is a good surgical option because it uses tissues adjacent to the breast itself and does not require silicone prosthesis for breast augmentation. The patients reported increased self-esteem and improvement in their quality of life.

Comparison of videolaparoscopic versus open surgery for benign renal diseases in children

Introduction: Laparoscopic nephrectomy in children has become a reasonable alternative to open nephrectomy and has replaced open surgery for many renal diseases. The purpose of our study is to evaluate transperitoneal videolaparoscopic procedures in renal benign diseases in comparison to an open surgery approach. Patients and methods: 34 children aged between 17 days and 15 years old (mean 6.14) were divided into two groups in order to be submitted to nephrectomy. The first one underwent transperitoneal videolaparoscopic nephrectomy and was composed by 21 patients aged from 2 months to 15 years (mean 7.42), from which 12 were females and 9 males. The second group was submitted to open nephrectomy and was composed by 13 patients aged from 17 days to 11 years (mean 3.91), 6 females and 7 males. The groups were compared regarding anesthesic time, operative time, length of hospital stay, postoperative pain and time of reintroduction of oral intake. Short and long term complications were also evaluated. Statistical analysis was performed by Student t-test with the level of significance set at P < 0.05. The study was previously approved by the Committee on Ethics in Research of our institution. Results: Significant statistical difference was observed only for the variable length of hospital stay. No laparoscopy group case was converted to open surgery. There was no immediate or late complication. Blood loss was negligible and no transfusion was required. Conclusions: In our experience, transperitoneal videolaparoscopic nephrectomy has similar results to open nephrectomy, except for time of hospitalization. (C) 2009 AEU. Published by Elsevier Espana, S.L. All rights reserved.

Massive Degeneration and Atrophy of the Native Heart After Heterotopic Transplantation: A Case Report

Extreme myocardial degeneration leading to advanced stages of cardiomyopathy with extensive atrophy is rarely observed before patients die. However, heterotopic transplantation is a special situation wherein this phenomenon can be observed. The greater part of the failed heart shows recuperation after receiving circulatory assistance by reduction of myocardial work. Herein we have reported an unusual behavior of degenerative cardiomyopathy associated with intense myocardial apoptosis resulting in extreme ventricular atrophy after heterotopic heart transplantation. An 11-year-old girl with end-stage heart failure due to dilated cardiomyopathy of undetermined etiology without pulmonary hypertension underwent heterotopic cardiac transplantation with an undersized (by weight mismatch) donor heart. After 9 years heart failure reappeared due to native heart enlargement leading to allograft compression. The patient underwent native heart replacement leaving her with 2 donor hearts. Despite normal hemodynamic recuperation, the patient experienced massive arterial microemboli which led to death. Pathological studies showed exuberant myocardial degeneration in the native heart with intense atrophy of the muscle and gigantic ventricular enlargement. The left ventricle wall was extremely thin with rarefaction of cardiomyocytes and replacement by fibrosis. The right ventricle showed old extensive thrombosis. In conclusion, this report is not usual as it is not frequent to observe cardiomyopathy with an intense degree of myocardial degeneration and atrophy, because the patient dies earlier. In special situations it is possible that a recipient may have 2 donor hearts with normal hemodynamics. Heterotopic heart transplantation is a surgical alternative in a priority situation offering excellent outcomes; however, the native heart must be removed when there is compromise of the function of the heterotopic allograft.

Short-term specialized enteral diet fails to attenuate malnutrition impairment of experimental open wound acute healing

Objective: We assessed the effect of enteral refeeding on the morphology, gene expression, and contraction of acute open wounds in previously malnourished rats using two different enteral diets. Methods: Adult male isogenic Lewis rats divided into two groups (eutrophic, n = 30; and previously malnourished, 12-15% body weight loss, n = 27) were subjected to cutaneous dorsal wounds and gastrostomy. Control rats received a standard oral diet (AIN-93M chow) plus enteral saline solution. Subject rats received chow plus a standard enteral diet or an enteral diet enriched with arginine and antioxidants. On post-trauma days 7 and 14, wound granulation tissue samples were collected for morphologic analysis using hematoxylin and eosin and picrosirius stain or immunohistochemistry slides and real-time polymerase chain reaction for collagen I and III gene expression. Wound contraction was also evaluated by comparing wound images from days 0,7, and 14. Results: Malnourished control rats had increased intensity and duration of wound inflammation, impaired increase of fibroblast cells contingent on post-trauma days 7 to 14, decreased expression of collagen III, and less wound contraction compared with eutrophic control rats. A specialized enteral diet did not improve wound healing of malnourished rats but did promote wound contraction at post-trauma day 7 in eutrophic rats. Conclusion: Short-term enteral refeeding, even with a specialized diet, failed to protect previously wounded malnourished rats from a prolonged inflammatory phase and impaired healing. (C) 2010 Elsevier Inc. All rights reserved.

Treatment of advanced hepatocellular carcinoma with very low levels of amplitude-modulated electromagnetic fields

BACKGROUND: Therapeutic options for patients with advanced hepatocellular carcinoma (HCC) are limited. There is emerging evidence that the growth of cancer cells may be altered by very low levels of electromagnetic fields modulated at specific frequencies. METHODS: A single-group, open-label, phase I/II study was performed to assess the safety and effectiveness of the intrabuccal administration of very low levels of electromagnetic fields amplitude modulated at HCC-specific frequencies in 41 patients with advanced HCC and limited therapeutic options. Three-daily 60-min outpatient treatments were administered until disease progression or death. Imaging studies were performed every 8 weeks. The primary efficacy end point was progression-free survival >= 6 months. Secondary efficacy end points were progression-free survival and overall survival. RESULTS: Treatment was well tolerated and there were no NCI grade 2, 3 or 4 toxicities. In all, 14 patients (34.1%) had stable disease for more than 6 months. Median progression-free survival was 4.4 months (95% CI 2.1-5.3) and median overall survival was 6.7 months (95% CI 3.0-10.2). There were three partial and one near complete responses. CONCLUSION: Treatment with intrabuccally administered amplitude-modulated electromagnetic fields is safe, well tolerated, and shows evidence of antitumour effects in patients with advanced HCC. British Journal of Cancer (2011) 105, 640-648. doi:10.1038/bjc.2011.292 www.bjcancer.com Published online 9 August 2011 (C) 2011 Cancer Research UK

Urticaria unresponsive to antihistaminic treatment: An open study of therapeutic options based on histopathologic features

Background: The non- or low-sedating H1 receptor antagonists represent the basic therapy for urticaria. Objective: To test an alternative approach to patients unresponsive to conventional treatment. Materials and methods: A total of 22 patients with chronic urticaria unresponsive to conventional antihistamine treatment were enrolled for this study. They had uncontrolled urticaria even using multiple combinations of antihistamines on maximum doses and corticosteroids in short cycles (prednisone 20-40 mg, per os once a day, 3-7 days per month). Cutaneous biopsies of the urticaria lesions were taken. These findings were classified as: (I) a mixture of perivascular dermal inflammatory infiltrate composed of lymphocytes, monocytes and neutrophils and/or eosinophils; (II) inflammatory infiltrate composed chiefly of neutrophils; and (III) inflammatory infiltrate composed mainly of eosinophils. According to histology, the patients were submitted to one of the following therapeutic schemes: class A - antihistamine treatment plus dapsone; class B - colchicine or dapsone; class C montelukast. Results: Four patients in class A, 08 in class B and seven in class C displayed complete control of urticaria after 12 weeks of treatment; one patient in class B and two in class C did not respond to treatment. Two years after discontinuation, 16 patients are still free of urticaria. Conclusions: This study suggests an alternative approach for treating unresponsive chronic urticaria.

Surgical Outcomes after Preceptored Laparoscopic Colorectal Surgery: Results of a Brazilian Preceptorship Program

Background/Aims: Safety of laparoscopic colectomy education methods remains unknown. This study aimed at comparing the outcomes of patients undergoing preceptored laparoscopic colectomy with patients operated on by the same preceptor. Methodology: A prospective analysis of 30 preceptored operations performed by nine surgeons (PD group) between 2006 and 2008 was conducted. Data of 30 operations matched for diagnosis and surgery type conducted by the same preceptor (P group) were evaluated. Results: Median age was 56.2 (26-80) and 55.2 (22-81) respectively in P and PD group (p=0.804). Eleven (36.7%) were male in P group, 16 (53.3%) in PD group (p=0.194). Preceptored operations were not significantly longer than operations performed by the preceptor (198 vs. 156 min) - p=0.072. Length of hospital stay did not differ [4 days (3-12) in P group, and 5 (3-15) in PD group, p=0.296]. Conversion occurred in 4 cases in PD and in 2 in P group (p=0.389). Morbidity was similar (23.3% in P and 26.7% in PD group). One patient from P and two from PD group needed re-operation. No deaths occurred. Conclusions: Laparoscopic colorectal surgery preceptorship programs in surgeon learner`s place are safe. Surgeons` introduction through basic and hands-on courses is required for skills acquisition needed to minimize adverse outcomes.

Additive Intraocular Pressure Reduction Effect of Fixed Combination of Maleate Timolol 0.5%/Dorzolamide 2% (Cosopt) on Monotherapy With Latanoprost (Xalatan) in Patients With Elevated Intraocular Pressure A Prospective, 4-week, Open-label, Randomized, Controlled Clinical Trial

Purpose: To evaluate the additive effect of dorzolamide/timolol fixed combination in patients under monotherapy with latanoprost. Patients and Methods: In this prospective, 4-week, randomized, open-label controlled clinical trial, patients with open-angle glaucoma or ocular hypertension, which presented at least 15% intraocular pressure (IOP) reduction after a minimum period of 15 days of monotherapy with latanoprost and whose IOP level was considered above the established target-IOP level were randomized to receive fixed combination of timolol/dorzolamide twice daily in one of eyes. The fellow eye was kept under monotherapy and was included in the control group. A modified diurnal tension curve (mDTC) followed by the water drinking test were performed in the baseline and week 4 visits to evaluate IOP profile between groups. Results: Forty-nine per-protocol patients were analyzed. After latanoprost monotherapy run-in period, IOP levels were significantly reduced (P<0.001) in both control and study groups to 15.34 +/- 2.96 mm Hg and 15.24 +/- 2.84 mm Hg (30.8% and 32.2% IOP reduction, respectively; P=0.552). At week 4, mean baseline diurnal IOP levels were 15.60 +/- 3.09 and 14.44 +/- 3.03 (7.4% difference; P=0.01). Mean baseline IOP modified diurnal tension curve peak after latanoprost run-in period were 17.47 +/- 3.68 mm Hg and 17.02 +/- 3.35 mm Hg (control and study eyes, respectively; P=0.530). At week 4 visit, mean water-drinking test peaks were significantly reduced in the study eye group in comparison with the control group: 19.02 +/- 3.81 mm Hg and 20.39 +/- 4.19 mm Hg, respectively (6.7% reduction; P=0.039). Conclusions: In our sample, dorzolamide 2%/timolol 0.5% fixed combination as add-on therapy in patients with open-angle glaucoma or ocular hypertension under monotherapy with latanoprost with IOP already in mid-teens levels may further enhance pressure reduction.

Alpha-Tricalcium Phosphate Bone Cement in the Surgical Treatment of Open Mastoid Cavity

Hypothesis: This study aimed to evaluate the biocompatibility of alpha-tricalcium phosphate bone cement in the obliteration of the mastoid cavity in guinea pigs. Background: Treatment with open cavity mastoidectomy can present poor functional results in chronic otitis media with cholesteatoma, especially if the cavity is large. Partial or total obliteration of the cavity can overcome these problems. Alpha-tricalcium phosphate bone cement has physicochemical characteristics that suggest its potential in mastoid cavity obliteration. Materials and Methods: Twenty guinea pigs were studied. All animals underwent surgery involving the dorsal tympanic bulla. In the study group animals (n = 10), mastoid cavity obliteration was performed with alpha-tricalcium phosphate bone cement. In the control group animals (n = 10), the cavity was left unfilled. On postoperative day 60, the animals were sacrificed and studied for signs of rejection of the material and other complications. Temporal bones were removed for histopathological study, in which the type and degree of inflammatory response, as well as the degree of ossification, were analyzed. Results: The mortality rate was the same in both groups. Deaths were attributed to anesthetic complications in the initial postoperative period. In the animals that survived, there were no complications, and there was good healing of the incision in both groups. There were no clinical signs of rejection of the material, and the histopathological analysis of the cement group revealed no signs of foreign body reaction (inflammatory response). Conclusion: Alpha-tricalcium phosphate bone cement is biocompatible in the mastoid cavity of guinea pigs.

An Eight-week, Multicentric, Randomized, Interventional, Open-label, Phase 4, Parallel Comparison of the Efficacy and Tolerability of the Fixed Combination of Timolol Maleate 0.5%/Brimonidine Tartrate 0.2% Versus Fixed Combination of Timolol Maleate 0.5%/Dorzolamide 2% in Patients With Elevated Intraocular Pressure

Purpose: To compare the efficacy and tolerability of the fixed combination of timolol maleate 0.5%/brimonidine tartrate 0.2% versus fixed combination of timolol maleate 0.5%/dorzolamide 2% in patients with elevated intraocular pressure (IOP) over 8 weeks. Patients and Methods: This 8-week, multicentric. interventional, randomized, open-label, parallel group study was conducted Lit 4 centers in Brazil and 1 center in Argentina. Patients with open-angle glaucoma or ocular hypertension were randomized to receive bilaterally fixed combination of brimonidine/timolol maleate 0.5% or fixed combination of dorzolamide 2%/timolol 0.5% twice daily at 8:00 AM and 8:00 PM. A modified diurnal tension curve (8:00 AM 10:30 AM, 02:00 PM, and 4:00 PM) followed by the water drinking test (WDT), which estimates IOP peak of diurnal tension curve, were performed in the baseline and week-8 visits. Adverse events data were recorded at each visit. Results: A total of 210 patients were randomized (brimonidine/timolol, n = 111; dorzolamide/timolol, n = 99). Mean baseline IOP was 23.43 +/- 3.22 mm Hg and 23.43 +/- 4.06 mm Hg in the patients treated with brimonidine/timolol and dorzolamide/timolol, respectively (P = 0.993). Mean diurnal IOP reduction after 8 weeks were 7.02 +/- 3.06 mm Hg and 6.91 +/- 3.67 mm Hg. respectively (P = 0.811). The adjusted difference between groups (analysis of covariance) Lit week 8 was not statistically significant (P = 0.847). Mean baseline WDT peak was 27.79 +/- 4.29 mm Hg in the brimonidine/timolol group and 27.68 +/- 5.46 mm Hg in the dorzolamide/timolol group. After 8 weeks of treatment, mean WDT peaks were 20.94 +/- 3.76 mm Hg (P < 0.001) and 20.98 +/- 4.19 (P < 0.001), respectively. The adjusted difference between groups (analysis of covariance) was not statistically significant (P = 0.469). No statistical difference in terms of adverse events was Found between groups. Conclusions: Both fixed combinations were capable of significantly reducing the mean diurnal IOP, mean diurnal peak, and mean WDT peak after 8 weeks of treatment. Also, both fixed combinations are well tolerated with few side effects.

Relative Bioavailability of Two Oral Formulations of Risperidone 2 mg: A Single-Dose, Randomized-Sequence, Open-Label, Two-Period Crossover Comparison in Healthy Brazilian Volunteers

Background: Risperidone (RSP) is a benzisoxazole antipsychotic agent used to treat schizophrenia and other psychiatric illnesses in adults and children (including those with autism). After oral administration, RSP is completely absorbed from the gastrointestinal tract and undergoes hydroxylation to yield 9-hydroxyrisperidone (9-OH-RSP), an active metabolite that has a pharmacologic profile and potency similar to RSP. Objectives: The aims of this study were to compare the relative bioavailability of a pharmaceutical-equivalent (test) formulation with a reference formulation of oral RSP 2 mg, both available commercially on the Brazilian pharmaceutical market, and to generate data regarding the oral bioavailability of the tested drug in healthy Brazilian volunteers. Methods: This single-dose, randomized-sequence, open-label, 2-period crossover study was conducted in healthy Brazilian volunteers from August to December 2008. Subjects were randomly assigned to receive the test formulation followed by the reference formulation or vice versa, with a 30-day washout period between doses. Study drugs were administered after a 12-hour overnight fast. For pharmacokinetic analysis, blood samples were drawn at 0 (baseline), 0.25, 0.5, 1, 1.5, 3, 5, 8, 12, 24, 48, 72, 96, and 120 hours after administration. Plasma concentrations of RSP and 9-OH-RSP were determined using LC-MS/MS. The test and reference formulations were to be considered bioequivalent if the 90% CIs for the geometric mean test/reference ratios were within a predetermined range of 80% to 125%, in accordance with the policies of the Brazilian Sanitary Surveillance Agency and the US Food and Drug Administration. Tolerability was determined using clinical assessments, monitoring of vital signs, analysis of laboratory test results, and subject interviews regarding adverse events. Results: A total of 22 subjects were enrolled (11 men, 11 women; mean [SD] age, 32 [12] years [range, 18-58 years]; weight, 70.4 [11.9] kg [range, 50-103 kg]; height, 1.67 [0.08] m [range, 1.56-1.80 m]; and body mass index, 25 [4] kg/m(2) [range, 18-29 kg/m(2)]). For RSP, mean (SD) C(max) values were 12.6 (2.7) and 16.0 (2.3) ng/mL for the test and reference formulations, respectively. For 9-OH-RSP, mean C(max) values were 17.8 (1.3) and 21.0 (1.7) ng/mL for the test and reference formulations. The 90% CIs for the mean test/reference ratios for RSP C(max), AUC(0-120), and AUC(0-infinity) were 74% to 82%, 75% to 85%, and 76% to 85%, respectively, and 83% to 87%, 75% to 79%, and 75% to 78% for 9-OH-RSP. The related adverse events (headache, low back pain, drowsiness, standing hypotension, local postvenipuncture ecchymoses, insomnia, nausea, and vomiting) were transient and mild. Conclusions: This single-dose study found that the test and reference formulations of oral RSP 2 mg did not meet the Brazilian and US regulatory criteria for bioequivalence in these fasting, healthy volunteers. The study formulations appeared to be well tolerated. (Clin Ther 2010;32:2106-2115) (C) 2010 Elsevier HS Journals, Inc.

Timing of Dose Relative to Sexual Intercourse Attempt in Previous Sildenafil Citrate Users Treated with Tadalafil: A Geographical Comparison from a Single Arm, Open-Label Study

Introduction. Previous research has demonstrated that sildenafil citrate users alter dosing-sexual attempt behavior when switched to tadalafil. The impact of geography and culture on sexual behavior with phosphodiesterase type 5 (PDE5) inhibitor treatment has not been fully investigated. Aim. To describe and compare the changes in dosing-sexual attempt behavior with sildenafil citrate vs. tadalafil treatment across four distinct geographies: Asia, Australia/New Zealand (ANZ), Central Eastern Europe/Middle East (CEE/ME), and Latin America (LA). Methods. Data from a single-arm, open-label clinical trial conducted in 21 countries from November 2002 to May 2004 were used in this analysis. Men with erectile dysfunction and a history of >= 6-week prior sildenafil citrate use continued sildenafil citrate treatment for 4 weeks then switched to tadalafil for 8 weeks. Dosing instructions were provided. Main Outcomes Measures. Timing of dose and sexual intercourse was assessed through patient diaries for the final 4 weeks of each treatment period. Results. A total of 2,760 men were enrolled: Asia 15.8%; ANZ 29.4%; CEE/ME 19.7%; LA 35.1%. The median time from dosing to intercourse was significantly increased during tadalafil treatment across all geographical regions; however, the magnitude of increase differed significantly by geography (P < 0.0001). The Asian cohort demonstrated the shortest duration between dosing and sexual intercourse attempts (irrespective of drug), and altered sexual behavior the least upon switching to tadalafil. The ANZ cohort demonstrated the longest duration between dosing and sexual intercourse attempts (irrespective of drug), and altered sexual behavior the most upon switching to tadalafil. Conclusion. Men with a history of established sildenafil citrate use alter their dose-attempt behavior when treated with tadalafil irrespective of geography. However, the extent to which sexual behavior alters is not uniform across geographical regions, suggesting that dosing instructions and duration of drug effectiveness, in combination with personal and cultural preferences, may determine sexual behavior with PDE5 inhibitor use. Rubio-Aurioles E, Glina S, Abdo CHN, Hernandez-Serrano R, Rampazzo C, Sotomayor M, West TM, Gallagher GL, and Lenero E. Timing of dose relative to sexual intercourse attempt in previous sildenafil citrate users treated with tadalafil: A geographical comparison from a single arm, open-label study. J Sex Med 2009;6:2836-2850.