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Background: Acute kidney injury (AKI) is the most frequent complication in critically ill neonatal and pediatric patients receiving extracorporeal membrane oxygenation (ECMO) support. This study analyzed risk factors for in-hospital mortality and the incidence of AKI in neonatal and pediatric patients received ECMO support. Methods: We reviewed the medical records of 105 neonatal and 171 pediatric patients who received ECMO support at the intensive care unit (ICU) of a tertiary care university hospital between January 2008 and December 2015. Demographic, clinical, and laboratory data were retrospectively collected as survival and AKI predictors, utilizing the Kidney Disease Improving Global Outcome (KDIGO) consensus definition for AKI. Results: In the 105 neonatal and 171 pediatric patients, the overall in-hospital mortality rate were 58% and 55% respectively. The incidence of AKI at post-ECMO 24 h were 64.8% and 61.4%. A greater KDIGO24-h severity was associated with a higher in-hospital mortality rate (chi-square test; p

Background The routine application of whole-body CT after extracorporeal cardiopulmonary resuscitation (ECPR) in out-of-hospital cardiac arrest (OHCA) has not been extensively investigated. We aimed to evaluate the benefit of CT in this context. Methods We retrospectively analyzed all OHCA patients who had received ECPR between January 2006 to May 2019. Electronic records were reviewed to filter out patients who had a whole-body CT as their first clinical evaluation after ECPR. CT findings and major hospital outcomes were evaluated. Results From January 2006 to May 2019, 700 patients had received ECPR in our institution. We identified 93 OHCA patients who received whole-body CT as the first clinical evaluation after ECPR. 22.6% of those had no acute findings detected on CT requiring immediate treatment. In the remaining 77.4%, CT had findings that might lead to alterations in clinical course. Most important findings were myocardial infarction (57.0%), hypoxic brain injury (29.0%), sternal/rib fractures (16.1%), aortic dissection (7.5%), pulmonary embolism (5.4%), and cardiac tamponade (5.4%). There were no significant differences in ICU/hospitalization days, time on ECMO support, survival and neurological outcomes between those with and without immediate CT. In our OHCA cohort, there were 27 patients with CT evidence of hypoxic brain injury, of whom 22.2% (n = 2) managed to wean from ECMO support, 14.8% (n = 4) survived to discharge, but only 3.7% (n = 1) survived with good neurological outcome. Hypoxic brain injury on CT has a 95% specificity in predicting poor neurological outcome, with a false positive rate of only 3.7%. Logistic regression suggested a potential correlation between CT findings of hypoxic brain injury and poor neurological outcome [Odds ratio (OR) = 12.53 (1.55 to 10.1), p = 0.02)]. Conclusions Routine whole-body CT after ECPR in OHCA patients appears to have a limited role, as the majority is caused by ACS. However, it may be a useful tool when CPR-related injury or non-ACS causes of OHCA are suspected, as well as in cases where the cause of OHCA is unknown. On the contrary, routine brain CT may be a valuable tool in guiding anticoagulant therapy during ECMO and in aiding outcome prediction.

Objective To focus on the potential beneficial effects of the pleiotropic effects of dipeptidyl peptidase-4 inhibitors (DPP4is) on attenuating progression of diabetic kidney disease in reducing the long-term effect of the acute kidney injury (AKI) to chronic kidney disease (CKD) transition. Patients and Methods Data from the National Health Insurance Research Database from January 1, 1999, to July 31, 2011, were analyzed, and patients with diabetes weaning from dialysis-requiring AKI were identified. Cox proportional hazards models and inverse-weighted estimates of the probability of treatment were used to adjust for treatment selection bias. The outcomes were incident end-stage renal disease (ESRD) and mortality, major adverse cardiovascular events, and hospitalized heart failure. Results Of a total of 6165 patients with diabetes weaning from dialysis-requiring AKI identified, 5635 (91.4%) patients were DPP4i nonusers and 530 (8.6%) patients were DPP4i users. Compared with DPP4i nonusers, DPP4i users had a lower risk of ESRD (hazard ratio, 0.81; 95% CI, 0.70-0.94; P=.04) and all-cause mortality (hazard ratio, 0.28; 95% CI, 0.23-0.34; P

Background Clinical study and practice data have shown sildenafil improves sexual function in men with erectile dysfunction (ED). However, some men treated with placebo in double-blind, placebo-controlled sildenafil studies also report improved erectile function as measured by International Index of Erectile Function (IIEF)–Erectile Function Domain (EFD) scores. Aim This analysis estimated the relationship between post-baseline IIEF-EFD scores and demographic variables, including co-morbidities, in men with ED receiving placebo in flexible-dose sildenafil studies. Methods Placebo-treated participants in the intent-to-treat population of 42 double-blind, placebo-controlled, flexible-dose, sildenafil studies were included. A participant was classified as a placebo responder if the IIEF-EFD score was ≥26 at the last visit. Outcomes Variables assessed were age ( Results A total of 4,360 men were included; 13.5% were responders. Odds estimates indicated the largest likelihood of placebo response occurred in men who were black (odds = 20.2, P < .0001), were younger than 45 years (odds = 7.3, P < .0001), had mild ED (baseline IIEF-EFD ≥17; odds >100, P < .0001), and did not have diabetes (odds = 4.5, P < .0001). The likelihood of a placebo response decreased as ED duration increased (odds = 0.74, P < .0001). The frequency of common adverse events was similar between placebo responders and non-responders. Clinical Translation These findings contribute to the improved understanding of predictors of placebo response in sildenafil clinical studies. Elucidation of these factors may contribute to the development of further interventions and treatment strategies and best practices for clinical trials. Strengths and conclusions Strengths of this analysis include the large and diverse population and the duration of follow-up. Limitations include those associated with retrospective analyses and the inability to ascertain to what extent other demographic factors might have contributed to the placebo responses or how these placebo responses might be related to the natural course of ED. Conclusions Certain demographics, co-morbidities, and condition characteristics predicted the odds of a placebo response in sildenafil clinical studies of ED. Underlying reasons behind a placebo response warrant further evaluation.

Background Patient-reported outcomes, such as the Erectile Dysfunction Inventory of Treatment Satisfaction (EDITS) index, are essential for successful evaluation and treatment of patients with erectile dysfunction. Aim To enrich interpretation of the EDITS index score and to complement the existing 0 to 100 scoring. Methods This supplemental analysis evaluated EDITS questionnaire data (11 items; index score range = 0–100; higher scores indicate more treatment satisfaction) after completion of an 8-week double-blinded trial of 279 men 18 to 65 years old with erectile dysfunction randomized to sildenafil 100 mg, sildenafil 50 mg, or placebo. Response options for each EDITS item were grouped into “success” (the 2 most satisfied or favorable responses) and “no success” (the remaining 3 responses). The binary response (success or no success) for each item was expressed as a function of overall EDITS score in a simple logistic regression model with all treatments combined. Outcomes Odds ratios and success probabilities (using Wald χ2 tests) were calculated for specified point differences and total EDITS index scores, respectively. Results EDITS index score increases corresponded with significant increases in odds of success in different EDITS aspects (P < .0001 for all comparisons). For instance, a 10-point EDITS index score difference was associated with odds ratios of 11.3, 42.0, 17.7, and 6.8 for overall treatment satisfaction, treatment meeting expectations, satisfaction with treatment quickness, and satisfaction with how long treatment lasts, respectively. For a given EDITS index score, likelihood of success was determined for different aspects of treatment satisfaction. For example, a mean EDITS index score of 78 (sildenafil 100 mg; SD = 18) corresponded to 96%, 88%, 94%, and 88% chances of success for the 4 EDITS items referenced earlier, respectively. Corresponding probabilities for a mean EDITS index score of 50 (placebo; SD = 18) were 3%, less than 0.1%, 1%, and 4%, respectively. Clinical Implications Interpretation of the EDITS index score can be augmented using key aspects of treatment satisfaction as reported by the patient. Strengths and Limitations This analysis used a well-established anchor-based approach to interpret EDITS index scores. The methodology used and corresponding results are appropriate for clinical practice and clinical trial settings. Limitations include data evaluation only for the Patient EDITS and not the complementary Partner EDITS and use of data from a clinical trial enrolling a well-defined patient population only in stable relationships. Conclusion These results enable a meaningful interpretation of EDITS index scores, facilitating decision making by stakeholders for better-informed health care choices.

Introduction This report describes a post hoc analysis of data from a randomized, double-blinded, placebo-controlled, flexible-dose, sildenafil trial in men with erectile dysfunction. Aims To simplify interpretation of erectile function (EF) domain scores of the International Index of Erectile Function (IIEF). Methods Men at least 18 years old with erectile dysfunction were randomized to receive sildenafil or placebo for 12 weeks. Men taking nitrates or nitric oxide donors were excluded. Responses for each IIEF EF domain question (questions 1–5 and 15) were combined into two broad categories (“success” for responses of the two most favorable categories of a question and “no success” for other responses). Each question was expressed in a logistic regression model (sildenafil and placebo groups combined) as a function of overall EF domain score. Main Outcome Measures IIEF EF domain score and items. Results A four-point increase in the IIEF EF domain score was associated with an odds ratio of success of 6.1 for getting an erection, 29.2 for having a firm erection, 10.0 for able to penetrate,12.8 for maintaining erection, 4.0 for maintaining erection to completion, and 3.7 for erection confidence. An EF domain score of 22 was associated with a probability of success of 81% for getting an erection, 86% for having a firm erection, 89% for able to penetrate, 67% for maintaining an erection, 70% for maintaining an erection to completion, and 32% for erection confidence. For an EF domain score of 16, the corresponding probabilities of success were 22%, 4%, 20%, 4%, 22%, and 6%, respectively. Conclusion These results provide stakeholders with a simplified and meaningful interpretation of IIEF EF domain scores based on six key aspects of EF.

Introduction: Hemophilia A is a rare bleeding disorder caused by pathogenic variants in the F8 gene, resulting in insufficient factor VIII (FVIII) activity. Adeno-associated virus (AAV)-mediated gene transfer enables the delivery of a modified functional F8 gene to hepatocytes that subsequently synthesize FVIII at levels that may prevent bleeding events in the absence of exogenous FVIII. Updated results and follow-up from the Alta study, an ongoing gene therapy study in patients with severe hemophilia A, are presented. Methods: The Alta study is a phase 1/2 dose-ranging, single-dose study of giroctocogene fitelparvovec (also known as SB-525 and PF-07055480), a recombinant AAV serotype 6 (rAAV6) vector encoding a modified F8 gene. Adults aged ≥18 years with severe hemophilia A were eligible for inclusion. Giroctocogene fitelparvovec was infused into patients in 4 cohorts of 2 patients each across 4 ascending doses (9e11, 2e12, 1e13, and 3e13 vg/kg). The 3e13 vg/kg dose cohort was expanded with 3 additional patients. Key end points included safety, circulating FVIII activity, use of FVIII replacement therapy, and frequency of bleeding events. Presented data are from the ongoing Alta study (NCT#03061201; data cutoff date, 26 May 2020; database not locked; data reflect those at time of data cutoff, have not undergone standard quality checks, and may be subject to change). Results: Eleven male patients participated in the study (mean [SD] age, 30.3 [7.8] years; white, 81.8%). As of the cutoff date, patients have been followed for 35 to 144 weeks; one patient in the 1e13 vg/kg cohort discontinued from the study. Overall, the most commonly reported adverse events (AEs; n) included increased alanine aminotransferase (ALT; 8 [72.7%]), increased aspartate aminotransferase (AST; 5 [45.5%]), upper respiratory tract infection (4 [36.4%]), and pyrexia (4 [36.4%]). Treatment-related serious AEs were reported in 1 patient (in the 3e13 vg/kg cohort) who experienced hypotension and fever ≈6 hours after giroctocogene fitelparvovec infusion; the events fully resolved with treatment and did not delay post-infusion discharge. In the 3 lower-dose cohorts, no ALT elevation requiring more than 7 days of corticosteroid treatment was observed. Of the 5 patients in the 3e13 vg/kg cohort, 4 had elevations in ALT that were managed with a tapering course of corticosteroids (ranging from 10-134 days) without loss of clinically relevant FVIII activity through 40 weeks, as evidenced by a lack of bleeding events before and after treatment with corticosteroids. Increases in FVIII activity from baseline were generally dose-dependent. Patients in the 3e13 vg/kg cohort achieved a mean normal-range of FVIII activity within 5 weeks post-infusion, with mean FVIII activity maintained through week 40, which is the last time point with data for all 5 patients in this cohort (Table). Following the initial prophylactic period of up to ≈3 weeks after giroctocogene fitelparvovec administration, no bleeding events occurred in any patient treated in the 3e13 vg/kg cohort. Use of FVIII replacement therapy ≥3 weeks after giroctocogene fitelparvovec administration was reported in 5/6 patients in the lower-dose cohorts (range: 9-115 infusions); none of the patients in the 3e13 vg/kg cohort required FVIII replacement beyond initial use of prophylactic factor for up to ≈3 weeks (prophylactic coverage stopped 3 weeks and 2 days after giroctocogene fitelparvovec administration in 1 patient in the 3e13 vg/kg cohort). Conclusions: To date, a single infusion of giroctocogene fitelparvovec gene therapy in patients with severe hemophilia A resulted in dose-dependent and sustained increases in FVIII levels without administration of exogenous FVIII, bleeding episodes or sustained adverse events in the highest-dose cohort (3e13 vg/kg). Additionally, patients treated in the highest-dose cohort achieved a mean FVIII activity in the normal range within 5 weeks, which was maintained through week 40. Data on all patients with more than 1 year of follow-up will also be presented. The study is ongoing, and these interim results support further development of giroctocogene fitelparvovec for the treatment of patients with severe hemophilia A. Disclosures Leavitt: BioMarin: Membership on an entity's Board of Directors or advisory committees. Konkle:Sanofi: Consultancy, Research Funding; Takeda: Research Funding; Uniquire: Research Funding; CSL Behring: Consultancy; BioMarin: Consultancy; Baxalta: Research Funding; Spark: Consultancy, Research Funding; Pfizer: Consultancy, Research Funding; Sigilon: Consultancy, Research Funding; Roche: Consultancy. Stine:Biomarin: Consultancy; Applied Stem Cell Therapeutics: Consultancy. Visweshwar:Biogen Idec: Membership on an entity's Board of Directors or advisory committees. Giermasz:uniQure: Consultancy, Research Funding; Sangamo Therapeutics: Research Funding; Bioverativ/Sanofi: Consultancy, Research Funding, Speakers Bureau; BioMarin: Consultancy, Research Funding, Speakers Bureau; Genentech/Roche: Consultancy, Research Funding, Speakers Bureau. Arkin:Pfizer: Current Employment, Current equity holder in publicly-traded company, Other: own stock/options in the company. Fang:Pfizer Inc.: Current Employment, Other: own stock/options in the company. Plonski:Pfizer Inc.: Current Employment, Other: own stock/options in the company. Smith:Pfizer Inc.: Current Employment, Other: own stock/options in the company. Tseng:Pfizer Inc.: Current Employment, Other: own stock/options in the company. Di Russo:Pfizer Inc.: Current Employment, Other: own stock/options in the company. Cockroft:Sangamo Therapeutics: Current Employment, Other: Shareholder of Sangamo Therapeutics. Rupon:Pfizer Inc.: Current Employment, Other: own stock/options in the company. Rouy:Sangamo Therapeutics: Current Employment, Other: Shareholder of Sangamo Therapeutics.

Extracorporeal cardiopulmonary resuscitation (ECPR) has gradually come to be regarded as an effective therapy, but the hospital mortality rate after ECPR is still high and unpredictable. The present study tested whether age-adjusted Charlson comorbidity index (ACCI) can be used as an objective selection criterion to ensure the most efficient utilization of medical resources. Adult patients (age &ge, 18 years) receiving ECPR at our institution between 2006 and 2015 were included. Data regarding ECPR events and ACCI characteristics were collected immediately after the extracorporeal membrane oxygenation (ECMO) setup. Adverse events during hospitalization were also prospectively collected. The primary endpoint was survival to hospital discharge. The second endpoint was the short-term (2-year) follow-up outcome. A total of 461 patients included in the study were grouped into low ACCI (ACCI 0&ndash, 3) (240, 52.1%) and high ACCI (ACCI 4&ndash, 13) (221, 47.9%) groups. The median ACCI was 2 (interquartile range (IQR): 1&ndash, 3) and 5 (IQR: 4&ndash, 7) for the low and high ACCI groups, respectively. Cardiopulmonary resuscitation (CPR)-to-ECMO duration was comparable between the groups (42.1 &plusmn, 25.6 and 41.3 &plusmn, 20.7 min in the low and high ACCI groups, respectively, p = 0.754). Regarding the hospital survival rate, 256 patients (55.5%) died on ECMO support. A total of 205 patients (44.5%) were successfully weaned off ECMO, but only 138 patients (29.9%) survived to hospital discharge (32.1% and 27.6% in low and high ACCI group, p = 0.291). Multivariate logistic regression analysis revealed CPR duration before ECMO run (CPR-to-ECMO duration) and a CPR cause of septic shock to be significant risk factors for hospital survival after ECPR (p = 0.043 and 0.014, respectively), whereas age and ACCI were not (p = 0.334 and 0.164, respectively). The 2-year survival rate after hospital discharge for the 138 hospital survivors was 96% and 74% in the low and high ACCI groups, respectively (p = 0.002). High ACCI before ECPR does not predict a poor outcome of hospital survival. Therefore, ECPR should not be rejected solely due to high ACCI. However, high ACCI in hospital survivors is associated with a higher 2-year mortality rate than low ACCI, and patients with high ACCI should be closely followed up.

The influence of acute kidney injury (AKI) on subsequent incident atrial fibrillation (AF) has not yet been fully addressed. This retrospective nationwide cohort study was conducted using Taiwan&rsquo, s National Health Insurance Research Database from 1 January 2000 to 31 December 2010. A total of 41,463 patients without a previous AF, mitral valve disease, and hyperthyroidism who developed de novo dialysis-requiring AKI (AKI-D) during their index hospitalization were enrolled. After propensity score matching, &ldquo, non-recovery group&rdquo, (n = 2895), &ldquo, AKI-recovery group&rdquo, (n = 2895) and &ldquo, non-AKI group&rdquo, (control group, n = 5790) were categorized. Within a follow-up period of 6.52 &plusmn, 3.88 years (median, 6.87 years), we found that the adjusted risks for subsequent incident AF were increased in both AKI-recovery group (adjusted hazard ratio (aHR) = 1.30, 95% confidence intervals (CI), 1.07&ndash, 1.58, p &le, 0.01) and non-recovery group (aHR = 1.62, 95% CI, 1.36&ndash, 1.94) compared to the non-AKI group. Furthermore, the development of AF carried elevated risks for major adverse cardiac events (aHR = 2.11, 95% CI, 1.83&ndash, 2.43), ischemic stroke (aHR = 1.33, 95% CI, 1.19&ndash, 1.49), and all stroke (aHR = 1.28, 95% CI, 1.15&ndash, 1.43). (all p &le, 0.001, except otherwise expressed) The authors concluded that AKI-D, even in those who withdrew from temporary dialysis, independently increases the subsequent risk of de novo AF.

Acute kidney injury (AKI) is detrimental after cardiac surgery. In this multicenter study, the novel biomarker hemojuvelin (HJV) was evaluated for AKI prediction following cardiac surgery. Urinary HJV, neutrophil gelatinase-associated lipocalin (NGAL), and urinary creatinine were measured in 151 patients after surgery. The outcomes of advanced AKI (KDIGO stages 2 and 3) and all causes of in-hospital mortality as the composite outcome were recorded. Areas under the receiver operator characteristic curves (AUC) and a multivariate generalized additive model (GAM) were applied to predict these outcomes of interest. Urinary HJV differentiated patients with/without AKI, advanced AKI or composite outcome after surgery (p p p ponding AUC values of 0.768 and 0.828, respectively. The performance of creatinine-adjusted HJV was also superior to NGAL in predicting advanced AKI (AUC = 0.784 and 0.694; p = 0.037) and composite outcome (AUC = 0.842 and 0.676; p = 0.002). The integration of HJV into the Cleveland Clinic score for advanced AKI led to a significant increase in risk stratification (net reclassification improvement [NRI] = 0.598; p

BACKGROUND Postoperative acute kidney injury (AKI) is common following cardiac surgery (CS). Body weight (BW) may be an amenable variable by representing the summation of the nutritional and the fluid status. However, the predictive role of perioperative BW changes in CS patients with severe postoperative AKI is never explored. This study aimed to evaluate this association. METHODS This study was conducted using a prospectively collected multicenter cohort, NSARF (National Taiwan University Hospital Study Group on Acute Renal Failure) database. The adult CS patients with postoperative AKI requiring renal replacement therapy (RRT), who had clear initial consciousness, received CS within 14 days of hospitalization, and underwent RRT within seven days after CS in intensive care units from January 2001 to January 2014 were enrolled. With the endpoint of 30-day postoperative mortality, we evaluated the association between the clinical factors denoting fluid status and patients outcomes. RESULTS A total of 188 patients (70 female, mean age 63.7 ± 15.2 years) were enrolled. Comparing with the survivors (n = 124), the non-survivors (n = 64) had a significantly higher perioperative BW change [3.6 ± 6.1% versus 0.1 ± 8.3%, p = 0.003] but not the postoperative and pre-RRT BW changes. By using multivariate Cox proportional hazards model, the independent indicators of 30-day postoperative mortality included perioperative BW change (p = 0.026) and packed red blood cells transfusion (p = 0.007), postoperative intra-aortic balloon pump (p = 0.001) and central venous pressure level (p = 0.005), as well as heart rate (p = 0.022), sequential organ failure assessment score (p < 0.001), logistic organ dysfunction score (p = 0.001), and blood total bilirubin level (p = 0.044) at RRT initiation. The generalized additive models further demonstrated, in a multivariate manner, that the mortality risk rose significantly during a perioperative BW change of 2% to 15%. CONCLUSIONS Perioperative BW change was independently associated with an increased risk for 30-day postoperative mortality in CS patients with RRT-requiring AKI.

Background: Elevated plasma C-terminal fibroblast growth factor-23 (cFGF-23) levels are associated with higher mortality in patients with chronic kidney disease (CKD) and acute kidney injury (AKI). Our study explored the outcome forecasting accuracy of cFGF-23 in critically ill patients with CKD superimposed with AKI (ACKD). Methods: Urine and plasma biomarkers from 149 CKD patients superimposed with AKI before dialysis were checked in this multicenter prospective observational cohort study. Endpoints were 90-day mortality and 90 days free from dialysis after hospital discharge. Associations with study endpoints were assessed using hierarchical clustering analysis, the generalized additive model, the Cox proportional hazard model, competing risk analysis, and discrimination evaluation. Results: Over a median follow up of 40 days, 67 (45.0%) patients died before the 90th day after hospital discharge and 39 (26.2%) progressed to kidney failure with replacement therapy (KFRT). Hierarchical clustering analysis demonstrated that cFGF-23 levels had better predictive ability for 90-day mortality than did other biomarkers. Higher serum cFGF-23 levels were independently associated with greater risk for 90-day mortality [hazard ratio (HR): 2.5; 95% confidence interval (CI) 1.5–4.1; p Conclusions: In patients with ACKD, plasma cFGF-23 levels are an independent risk factor to forecast 90-day mortality and 90-day progression to KFRT. In combination with the clinical risk score, plasma cFGF-23 levels could substantially improve mortality risk prediction.

Urinary biomarkers augment the diagnosis of acute kidney injury (AKI), with AKI after cardiovascular surgeries being a prototype of prognosis scenario. Glutathione S-transferases (GST) were evaluated as biomarkers of AKI. Urine samples were collected in 141 cardiovascular surgical patients and analyzed for urinary alpha-(α-) and pi-(π-) GSTs. The outcomes of advanced AKI (KDIGO stage 2, 3) and all-cause in-patient mortality, as composite outcome, were recorded. Areas under the receiver operator characteristic (ROC) curves and multivariate generalized additive model (GAM) were applied to predict outcomes. Thirty-eight (26.9%) patients had AKI, while 12 (8.5%) were with advanced AKI. Urinary π-GST differentiated patients with/without advanced AKI or composite outcome after surgery (p

Background Varenicline is an α4β2 partial nicotinic agonist approved for smoking cessation. There have been spontaneous postmarketing reports of neuropsychiatric adverse events (NPAEs) in smokers without a history of psychiatric illness quitting with varenicline. Methods One hundred ten smokers without history of psychiatric illness (screened by Structured Clinical Interview for DSM-IV) were randomized to 12 weeks of varenicline 1 mg twice daily ( n = 55) or placebo. Adverse events were solicited systematically. Depressive symptoms, anxiety, aggression, and irritability were measured at baseline and weekly using the Montgomery-Asberg Depression Rating Scale (MADRS), the Hamilton Anxiety Scale (HAM-A), and the Overt Aggression Scale—Modified (OAS-M). The Profile of Mood States (POMS) was administered daily. Mixed-model analysis of repeated measures was conducted to compare mean changes in scores between groups across study periods. Results Participants' mean baseline characteristics were 33 years of age, 22 cigarettes/day and Fagerstrom Test for Nicotine Dependence score > 7. Reported NPAEs were similar between groups. No suicidal events were reported. There were no significant differences between groups for the MADRS (treatment difference vs. placebo=.03, 95% confidence interval [CI] −.68–.73; NS), HAM-A (treatment difference [TD] = .14, 95% CI −.62–.90; NS), OAS-M Aggression subscale (TD = .5, 95% CI −1.18–2.18; NS), OAS-M Irritability subscale (TD = .08, 95% CI −.17–.34; NS), and the POMS total scores (TD = .5, 95% CI −.52–1.53; NS). Conclusions There were no significant differences between groups on measures of depressive symptoms, anxiety, or aggression/hostility. Systematically solicited NPAEs were similar between the varenicline and placebo groups.

Study Type – Therapy (cohort) Level of Evidence 2b What’s known on the subject? and What does the study add? Fesoterodine is an effective treatment for overactive bladder. However, the length of time until the effects begin to be seen was not known. The study demonstrates that the effect of Fesoterodine 4 mg on overactive bladder symptoms can be seen at one week. OBJECTIVE To assess the onset of efficacy of fesoterodine 4 mg once daily on overactive bladder (OAB) symptoms after 1 week of treatment. PATIENTS AND METHODS This was a prespecified analysis of data collected during the first week of a 12-week, open-label, single-arm, flexible-dose study of fesoterodine. Eligible subjects were adult men and women (aged ≥ 18 years) who reported urinary frequency (eight or more micturitions per 24 h) and urgency (three or more episodes per 24 h) in 5-day bladder diaries at baseline, and dissatisfaction with previous tolterodine or tolterodine extended-release treatment received within 2 years of screening. All subjects received fesoterodine 4 mg once daily during the first 4 weeks of treatment (with an optional dose increase to fesoterodine 8 mg after week 4). Early onset of efficacy of fesoterodine 4 mg was assessed based on changes from baseline to week 1 in variables recorded in 5-day bladder diaries, including total micturitions, urgency episodes, urgency urinary incontinence (UUI) episodes and nocturnal micturitions. Urgency and severe urgency episodes were defined as those rated ≥ 3 and ≥4, respectively, on the five-point Urinary Sensation Scale (USS) (1 = no urgency, 5 = UUI); frequency-urgency sum (a combined measure of micturition frequency and urgency) was defined as the sum of all USS ratings. RESULTS All bladder diary variables, including total and nocturnal micturitions, UUI episodes, urgency episodes, severe urgency episodes and frequency-urgency sum per 24 h, were significantly improved (all P < 0.0001) after 1 week of treatment with fesoterodine 4 mg compared to baseline. The diary-dry rate at week 1 (i.e. subjects with at least one UUI episode at baseline who subsequently reported no UUI episodes on week 1 diary) was 38%. CONCLUSION In this open-label study of subjects with OAB who had been previously treated and dissatisfied with tolterodine, fesoterodine 4 mg showed a rapid onset of efficacy at 1 week.

Study Type – Therapy (cohort) Level of Evidence 2b What’s known on the subject? and What does the study add? We know that bladder-relaxing agents antimuscrinics act on symptoms of overactive bladder and are the first treatment in such patients. We know that fesoterodine is a newer antimuscarinic with a good activity safety profile. This study adds to the experience that changing the dose of antimuscrinics as fesoterodine is often needed by patients, that the decision can be made by the patients, and the change in dose adds to the clinical result. OBJECTIve To assess changes in overactive bladder (OAB) symptoms and patient-reported outcomes in a post hoc analysis in which subjects from a 12-week, open-label, flexible-dose fesoterodine study were stratified according to whether they opted for dose escalation. PATIENTS AND METHODS Subjects with OAB (eight or more micturitions and three or more urgency episodes per 24 h) who reported dissatisfaction with tolterodine within 2 years of screening received fesoterodine 4 mg once daily for 4 weeks, with an optional dose increase to 8 mg after week 4 based on discussion of efficacy and tolerability between the subject and investigator. Subjects completed 5-day diaries, the Patient Perception of Bladder Condition (PPBC) and Urgency Perception Scale (UPS) at baseline and weeks 4 and 12, and the Overactive Bladder Questionnaire (OAB-q) at baseline and week 12. Subjects rated treatment satisfaction at week 12. RESULTS Dose escalation to 8 mg at week 4 was chosen by 255 (50%) of 513 subjects. At baseline, subjects who opted for dose escalation at week 4 (escalators) had significantly higher means for all diary variables except urgency urinary incontinence (UUI) episodes, significantly greater OAB-q Symptom Bother scores and significantly lower OAB-q health-related quality of life (HRQL) scores (all P < 0.05) compared to subjects who did not opt for dose escalation (non-escalators). There was no significant difference in the percentage of escalators (51%) and non-escalators (48%) who reported at least one UUI episode on baseline diary. At week 4 (before the decision to escalate was made), all outcomes were significantly improved vs baseline among both groups (all P < 0.0001), although non-escalators had significantly greater improvements in all diary variables and in PPBC and UPS scores than escalators (all P < 0.05), and the 5-day diary-dry rate (i.e. the percentage of subjects with at least one UUI episode on baseline diary and no UUI episodes on week 4 diary) was significantly higher (P= 0.0016) among non-escalators (62%) than among escalators (42%). At week 12, all outcomes were again significantly improved vs baseline among both groups (all P < 0.0001). There were no significant differences between non-escalators and escalators in week 12 improvements for most diary variables, UPS scores, OAB-q Symptom Bother scores, the diary-dry rate (68% vs 60%) or the percentage of subjects who reported treatment satisfaction (82% vs 78%). However, escalators still had significantly greater improvements from baseline in urgency episodes, PPBC scores and OAB-q total HRQL and Coping domains (P < 0.05). Adverse event rates were similar between non-escalators and escalators. Dry mouth was the most frequently reported adverse event; most cases were mild. CONCLUSION Flexible-dose fesoterodine significantly improved OAB symptoms and patient-reported outcomes in subjects who chose to remain on the initial 4-mg dose, as well as in the 50% of subjects who escalated to the 8-mg dose after 4 weeks. Non-escalators had significantly fewer OAB symptoms at baseline and significantly greater improvements than escalators before dose escalation. Escalators showed increased symptom relief after dose escalation; improvements in most outcomes were similar among non-escalators and escalators by week 12. Flexible-dose fesoterodine was well tolerated, with similar adverse-event profiles observed in the escalator and non-escalator groups. These results may help clinicians to identify patients more likely to require fesoterodine 8 mg to achieve maximum relief of OAB symptoms and thus facilitate dose escalation in these patients.

Aim To determine what constitutes a clinically important difference (CID) on the Erectile Dysfunction Inventory of Treatment Satisfaction (EDITS), an 11-item validated questionnaire assessing treatment satisfaction used in clinical trials for patients with erectile dysfunction (ED). Methods Erectile Dysfunction Inventory of Treatment Satisfaction data were evaluated from a double-blind, fixed-dose trial of 279 men aged 18-65 years with ED who were treated with sildenafil 50 or 100 mg or placebo. The primary anchor measure was the erectile function (EF) domain of the International Index of Erectile Function (IIEF), which has a 4-point minimal CID. The CID on the EDITS index score was determined using a regression analysis comparing EDITS and IIEF EF scores at the end of the 8-week treatment. A similar analysis was performed for EDITS and the Erection Hardness Score (EHS) instrument, a single-item questionnaire measuring hardness, which was used as a secondary anchor measure. Results Erectile Dysfunction Inventory of Treatment Satisfaction and IIEF EF domain scores were highly correlated (Pearson correlation coefficient = 0.75). EDITS total scores across treatments at week 8 averaged (mean ± standard deviation [SD]) 67.5 ± 21.6 (range, 0-100; higher scores indicate greater treatment satisfaction); IIEF EF domain scores averaged 22.2 ± 6.9 (range, 1-30; higher scores indicate higher erectile functioning). The calculated CID for EDITS scores was 9.5 (95% CI, 8.5-10.4; 0.44 SD units), corresponding to a medium effect size. EDITS and EHS instrument scores also correlated highly (Pearson correlation coefficient = 0.64). Placebo-adjusted EDITS mean scores were more than twice the CID, at 23 (95% CI, 17-28) and 28 (95% CI, 23-33) for the 50- and 100-mg doses, respectively. Conclusion Approximately 10 points on the EDITS index score is considered a CID. Serving as a benchmark, this finding aids interpretation of the clinical relevance of a difference in mean EDITS index scores between treatments for patients with ED.

We report a rare case of diffuse esophageal intramural pseudodiverticulosis in a 35-year-old man complaining of severe dysphagia and vomiting for several months. The advanced morphological change in the esophagus caused irregular track formation, mimicking an ulcerative lesion on esophagogram. Endoscopic examination revealed an esophageal stricture with intact mucosa. Endoscopic ultrasonography and chest computed tomography showed multiple hyperechoic lesions of unknown nature and multiple air collection sites in the esophageal wall, respectively, making diagnosis difficult. The patient finally received a subtotal esophagectomy because of severe symptoms. The lesion was pathologically proven to be intramural pseudodiverticulosis with marked submucosal fibrosis. Our experience suggests that awareness of this rare pathology and the related image changes will be helpful for early diagnosis and treatment in the future.

Introduction Sildenafil citrate 50 mg is the recommended starting dose for men with erectile dysfunction (ED); however, most men are later titrated to sildenafil 100 mg for improved efficacy. Aim Assess the tolerability and efficacy of sildenafil initiated at the 100-mg dose in men with ED. Methods Men with ED (score Main outcome measures Efficacy, tolerability, treatment satisfaction, and other end points were measured at baseline and/or the end of the double-blind and open-label phases and compared between placebo and sildenafil initiated at doses of 50 and 100 mg. Results Improvements in DBPC patient-reported outcomes from baseline were statistically significant for both sildenafil 50 and 100 mg compared with placebo. At the end of DBPC treatment, 56% of men on the 100-mg dose felt no anxiety about the next intercourse attempt compared with 39% in the 50-mg group (odds ratio 2.03; P = 0.0197). Changes in functional scores from baseline were not statistically significant with the 100-mg dose compared with the 50-mg dose in the DBPC. Measures of treatment satisfaction and sexual experience significantly favored the 100-mg dose compared with the 50-mg dose in the DBPC. There was no increase in adverse events with the higher dose. Conclusions Sildenafil at 50 mg or 100 mg significantly improved erection quality, treatment satisfaction, anxiety levels, and the sexual experience compared with placebo during DBPC. Sildenafil 100 mg improved the sexual experience and treatment satisfaction, and reduced feelings of anxiety compared with the 50-mg dose.

Introduction The validated Quality of Erection Questionnaire (QEQ) evaluates satisfaction with erection quality. Aim To collate QEQ data, including correlations between QEQ outcomes and outcomes assessing emotional well-being, treatment satisfaction, and erection hardness after sildenafil citrate treatment. Methods In four trials, men older than 18 years and with erectile dysfunction, a stable sexual partner, and no recent phosphodiesterase type 5 inhibitor use were randomized to double-blind flexible-dose sildenafil or placebo (1:1 ratio) for 6 or 10 weeks (two trials), fixed-dose 50 mg, 100 mg, and placebo (1:1:1 ratio) for 8 weeks (one trial), and 50 mg and 100 mg (1:1 ratio) for 4 weeks after 4 weeks of single-blind sildenafil 50 mg. Exclusion criteria included recent significant cardiovascular disease, use of nitrates, nitric oxide donors, cytochrome P450 3A4 inhibitors, or other erectile dysfunction treatment, and sildenafil hypersensitivity or previous severe or serious treatment-related adverse event. Main Outcomes Measures Scores on the QEQ, QEQ Question 5 (satisfaction with erection hardness), the Self-Esteem and Relationship Questionnaire, and the Erectile Dysfunction Inventory of Treatment Satisfaction; the percentage of occasions with Erection Hardness Score 3 (EHS 3, hard enough for penetration but not completely hard) and/or EHS 4 (completely hard and fully rigid); and Pearson correlation coefficients. Results 1,296 men (18–80 years) were randomized. Except for the percentage of occasions with EHS 3, all outcomes improved in men treated with sildenafil and correlated positively with the change in QEQ scores in all trials. Conclusions Satisfaction with the quality of erections, which is easily monitored with the QEQ, correlated positively with measures of emotional well-being and treatment satisfaction and with the change in percentage of erections that were completely hard and fully rigid, but not with the change in percentage of erections that were hard enough for penetration but not completely hard. Kaminetsky JC, Depko AJ, Stroberg P, Buvat J, Tseng L-J, and Stecher VJ. In men with erectile dysfunction, satisfaction with quality of erections correlates with erection hardness, treatment satisfaction, and emotional well-being. J Sex Med 2009;6:800–808.

Aims: To evaluate the efficacy and tolerability of flexible-dose fesoterodine in subjects with overactive bladder (OAB) who were dissatisfied with previous tolterodine treatment. Methods: This was a 12-week, open-label, flexible-dose study of adults with OAB (¡Ý 8 micturitions and ¡Ý 3 urgency episodes per 24 h) who had been treated with tolterodine (immediate- or extended-release) for OAB within 2 years of screening and reported dissatisfaction with tolterodine treatment. Subjects received fesoterodine 4 mg once daily for 4 weeks; thereafter, daily dosage was maintained at 4 mg or increased to 8 mg based on the subject's and physician's subjective assessment of efficacy and tolerability. Subjects completed 5-day diaries, the Patient Perception of Bladder Condition (PPBC) and the Overactive Bladder Questionnaire (OAB-q) at baseline and week 12 and rated treatment satisfaction at week 12 using the Treatment Satisfaction Question (TSQ). Safety and tolerability were assessed. Results: Among 516 subjects treated, approximately 50% opted for dose escalation to 8 mg at week 4. Significant improvements from baseline to week 12 were observed in micturitions, urgency urinary incontinence episodes, micturition-related urgency episodes and severe micturition-related urgency episodes per 24 h (all p < 0.0001). Approximately 80% of subjects who responded to the TSQ at week 12 reported satisfaction with treatment; 38% reported being very satisfied. Using the PPBC, 83% of subjects reported improvement at week 12 with 59% reporting improvement ¡Ý 2 points. Significant improvements from baseline (p < 0.0001) exceeding the minimally important difference (10 points) were observed in OAB-q Symptom Bother and Health-Related Quality of Life (HRQL) scales and all four HRQL domains. Dry mouth (23%) and constipation (5%) were the most common adverse events; no safety issues were identified. Conclusion: Flexible-dose fesoterodine significantly improved OAB symptoms, HRQL, and rates of treatment satisfaction and was well tolerated in subjects with OAB who were dissatisfied with prior tolterodine therapy.

Introduction Psychosocial manifestations of erectile dysfunction (ED) differ across cultures. Understanding the treatment response to ED medications within cultural groups can aid in resource allocation and in developing treatment strategies. Aim Evaluate the effect of sildenafil treatment on self-esteem, confidence, and sexual relationship satisfaction in Brazilian men with ED. Main Outcome Measure The Self-Esteem and Relationship (SEAR) questionnaire, a validated, 14-question instrument developed to specifically address self-esteem and relationship issues within the context of ED. Methods Men aged 18 years or older with a clinical diagnosis of ED (≤21 on the Sexual Health Inventory for Men) and in a stable relationship with a partner during the study were eligible. The primary end point was a change from baseline in the self-esteem subscale of the SEAR questionnaire. Thirteen Brazilian sites participated in a randomized, double-blind, placebo-controlled trial of sildenafil treatment for ED. Patients were randomized to receive either 50 mg of sildenafil (adjustable to 25 mg or 100 mg based on patient response) or matching placebo approximately 1 hour before anticipated sexual activity but not more than once a day. Results At the end of double-blind treatment, 63 and 66 patients in the placebo and sildenafil groups, respectively, from 13 Brazilian sites were assessed for efficacy. Brazilian patients receiving sildenafil had significantly greater improvements in their scores on the SEAR self-esteem subscale (42.9 [95% confidence interval 35.7–50.0]) compared with placebo (21.1 [95% confidence interval 13.7–28.6]; P Conclusions The psychosocial parameters in Brazilian men with ED assessed by the SEAR questionnaire showed significant improvements in self-esteem, confidence, and relationships after treatment with sildenafil. Glina S, Damiao R, Abdo C, Afif-Abdo J, Tseng L-J, and Stecher V. Self-esteem, confidence, and relationships in Brazilian men with erectile dysfunction receiving sildenafil citrate: A randomized, parallel-group, double-blind, placebo-controlled study in Brazil.

The Sexual Experience Questionnaire (SEX-Q) enables quick and easy assessment of functional, emotional, and satisfaction-related aspects of the sexual experience in men with erectile dysfunction (ED).To assess correlations between improvement on the SEX-Q and outcomes on other validated questionnaires. METHODS. Men with ED (scoreor =25 on the Erectile Function domain of the International Index of Erectile Function [IIEF]) who had used less than or equal to six doses of any phosphodiesterase 5 inhibitor (none within 6 months) were randomized to 10 weeks of double-blind, placebo-controlled (DBPC) flexible-dose sildenafil citrate (50 or 100 mg, as needed), followed by 6 weeks of open-label (OL) sildenafil.SEX-Q, IIEF, Quality of Erection Questionnaire (QEQ), Self-Esteem and Relationship (SEAR) Questionnaire, Erection Hardness Score (EHS), successful intercourse attempts (SIAs), Erectile Dysfunction Inventory of Treatment Satisfaction (EDITS), and global efficacy questions (GEQs).Compared with the placebo group (N = 105), the sildenafil group (N = 104) at DBPC end of treatment (EOT) had significantly more improvement (P0.05) on all SEX-Q, IIEF (except the Sexual Desire domain), QEQ, and SEAR outcomes, more frequent SIAs and EHS 3 (hard enough for penetration but not completely hard) or EHS 4 (completely hard) erections (odds ratio [OR], 2.52 and 3.46, respectively), EHS 4 erections four times as often (OR, 6.41), more men satisfied with treatment (EDITS; OR, 2.6), approximately twice as many men with improved erections (GEQ1; OR, 5.8) and ability to have sexual intercourse (GEQ2; OR, 5.4), and GEQ3 scores that indicated better sex (P0.0001). SEX-Q score improvements correlated positively with all other outcomes. At OL EOT, most outcomes were60% (and approximately half wereor =80%) of the maximum positive result.SEX-Q change scores correlate with several other functional, emotional, and satisfaction-related outcomes in men treated with sildenafil for ED, allowing a simple and focused evaluation of the sexual experience.

Erectile dysfunction (ED) negatively impacts self-esteem and relationship satisfaction. The Self-Esteem and Relationship (SEAR) questionnaire is a validated, ED-specific, patient-reported instrument that specifically addresses self-esteem and relationship issues within the context of ED. Effective ED treatment with sildenafil in a double-blind, placebo-controlled clinical trial conducted in Brazil, Mexico, Australia and Japan showed pooled cross-cultural improvements in self-esteem, confidence and relationship satisfaction. This report focuses on the results from the subgroup of men from nine Mexican centers who participated in the multinational study. A total of 95 men agedor=18 years with clinically diagnosed ED and currently in a stable relationship were randomized to placebo (n=47) or sildenafil (n=48). The SEAR results for Mexican men showed that sildenafil treatment led to significant improvements in self-esteem, confidence and relationship satisfaction. These data support an earlier study showing that Latin American men taking sildenafil have similar safety and efficacy profiles compared to non-Latin counterparts.

To clarify the period of responsiveness to sildenafil.Under a double-blind protocol, men with mild to moderate erectile dysfunction (International Index of Erectile Function [IIEF] Erectile Function domain score, 11 to 25) were randomized to sildenafil (100 mg) or placebo and attempted intercourse 8 hours (range, 7 to 9 hours) postdose (first 4-week phase) and 12 hours (11 to 13 hours) postdose (second 4-week phase after treatment crossover). The primary outcome was the per-patient proportion (PPP; least squares means [95% confidence interval]) of affirmative responses to the Sexual Encounter Profile question 3 (SEP3: "Did your erection last long enough for you to have successful intercourse?").For sildenafil (n = 174) versus placebo (n = 177), baseline values were similar but the PPP of successful intercourse attempts increased to 76% (69% to 82%) versus 50% (43% to 57%) in phase 1 (odds ratio [OR] = 3.2) and 79% (72% to 85%) versus 52% (44% to 60%) in phase 2 (OR = 3.5), and the PPP of Erection Hardness Score 4 erections (completely hard and fully rigid) was 41% (34% to 48%) versus 10% (7% to 15%) in phase 1 (OR = 6.2) and 44% (37% to 51%) versus 17% (12% to 23%) in phase 2 (OR = 4.0). Thus, at 12 hours, the odds of successful intercourse tripled and of a completely hard erection quadrupled. The sildenafil group achieved greater (P0.001) PPP of successful penetration (SEP2), satisfaction with erection hardness (SEP4), and satisfaction with the sexual experience (SEP5); improvement in IIEF domain scores; and treatment satisfaction on the Erectile Dysfunction Inventory of Treatment Satisfaction.In men with mild to moderate ED, responsiveness to sildenafil may persist much longer than 4 hours.

Summary Aims: To evaluate once-daily 100-mg sildenafil for the treatment of erectile dysfunction (ED) in men with ED and lower urinary tract symptoms (LUTS) associated with benign prostatic hyperplasia (BPH). Methods: This was a 12-week, randomised, double-blind, placebo-controlled (DBPC) trial, with an 8-week open-label (OL) extension, in men ≥ 45 years of age who scored ≤ 25 on the erectile function (EF) domain of the International Index of Erectile Function (IIEF) and ≥ 12 on the International Prostate Symptom Score. Results: At DBPC end of treatment (EOT), the sildenafil group (n = 189, vs. placebo, n = 180) had improved EF (IIEF), improved emotional well-being [Self-Esteem And Relationship questionnaire (SEAR)], and greater treatment satisfaction (Erectile Dysfunction Inventory of Treatment Satisfaction) (p

We evaluated sildenafil for erectile dysfunction and lower urinary tract symptoms in men with the 2 conditions.This was a 12-week, double-blind, placebo controlled study of sildenafil in men 45 years or older who scored 25 or less on the erectile function domain of the International Index of Erectile Function and 12 or greater on the International Prostate Symptom Score. Men with confirmed or suspected prostate malignancy, or prostate specific antigen 10 ng/ml or more were excluded. End points were changes in International Index of Erectile Function domain scores, International Prostate Symptom Score (irritative, obstructive and quality of life), the Benign Prostatic Hyperplasia Impact Index, the Self-Esteem And Relationship questionnaire and Erectile Dysfunction Inventory of Treatment Satisfaction Index Score.The 189 men receiving sildenafil had significant improvements in erectile function domain score vs the 180 on placebo (9.17 vs 1.86, p0.0001) and on all other International Index of Erectile Function domains. In men on sildenafil vs placebo significant improvements were observed in International Prostate Symptom Score (-6.32 vs -1.93, p0.0001), Benign Prostatic Hyperplasia Impact Index (-2.0 vs -0.9, p0.0001), mean International Prostate Symptom Score quality of life score (-0.97 vs -0.29, p0.0001) and total Self-Esteem And Relationship questionnaire scores (24.6 vs 4.3, p0.0001). There was no difference in urinary flow between the groups (p=0.08). Significantly more sildenafil vs placebo treated patients were satisfied with treatment (71.2 vs 41.7, p0.0001). Sildenafil was well tolerated.Improved erectile dysfunction and lower urinary tract symptoms with sildenafil in men with the 2 conditions were associated with improved quality of life and treatment satisfaction. Daily dosing with sildenafil may improve lower urinary tract symptoms. However, the lack of effect on urinary flow rates may mean that a new basic pathophysiology paradigm is needed to explain the etiology of lower urinary tract symptoms.

Introduction Sildenafil, an oral phosphodiesterase type 5 inhibitor, has been extensively investigated for the treatment of erectile dysfunction in randomized controlled trials. Aim To assess the efficacy and safety of sildenafil vs placebo according to age subgroups ( Methods Most trials had a 12-week treatment duration. The starting sildenafil dose was 50 mg, taken 1 hour before sexual activity, with subsequent adjustment to 100 or 25 mg based on efficacy and safety. Men taking nitrate therapy or nitric oxide donors and men with severe cardiac failure, unstable angina, or recent stroke or myocardial infarction were excluded. Efficacy analyses included all subjects with baseline and at least one postrandomization evaluation. Safety analyses included subjects who received study medication. Main Outcome Measures The International Index of Erectile Function and a global assessment question (“Did the treatment improve your erections?”). Results Mean International Index of Erectile Function scores for question 3 (frequency of penetration), question 4 (maintenance of erections after penetration), and the erectile function domain were statistically significantly improved with sildenafil vs placebo for each age subgroup; orgasmic function, intercourse satisfaction, sexual desire, and overall satisfaction domain scores also were statistically significantly improved with sildenafil vs placebo. The percentage of men reporting improved erections on the global assessment question was statistically significantly higher with sildenafil vs placebo for all age subgroups; the percentage with sildenafil tended to decrease with increasing age ( Conclusion Sildenafil is an effective and well-tolerated treatment for erectile dysfunction regardless of patient age, including men at least 75 years old.

Extracorporeal membrane oxygenation (ECMO) has been repeatedly used to rescue patients with cardiopulmonary arrest. However, its clinical utility in endocrine emergencies remains unclear. Herein, we describe a case series of 12 patients presenting with refractory shock secondary to endocrine emergencies who were rescued by ECMO support. Patients were identified between 2005 and 2012 from our ECMO registry. The diagnostic distribution was as follows: pheochromocytoma crisis (n = 4), thyroid storm (n = 5) and diabetic ketoacidosis (n = 3). The initial presentation of pheochromocytoma crisis was indistinguishable from acute myocardial infarction (AMI) and frequently accompanied by paroxysmal hypertension and limb ischemia. Thyroid storm was characterized by hyperbilirubinemia and severe gastrointestinal bleeding, whereas neurological symptoms were common in diabetic ketoacidosis. The clinical outcomes of patients with endocrine emergencies were compared with those of 80 cases with AMI who received ECMO because of cardiogenic shock. The cardiac function and the general conditions showed a significantly faster recovery in patients with endocrine emergencies than in those with AMI. We conclude that ECMO support can be clinically useful in endocrine emergencies. The screening of endocrine diseases should be considered during the resuscitation of patients with refractory circulatory shock.

The quality of life consequences of erectile dysfunction (ED) include depression, anxiety, and loss of self-esteem. The Self-Esteem And Relationship (SEAR) questionnaire is a validated, patient-administered, psychometric instrument specific to ED.To determine correlations between erectile function (EF), intercourse success, and emotional well-being measured with the SEAR questionnaire in men treated with sildenafil citrate for ED and stratified by age (50 years, 50-65 years, and65 years).This was an open-label, flexible-dose trial of sildenafil (25, 50 and 100 mg) administered for 10 weeks to 382 men with ED (mean +/- SD age, 55 +/- 13 years; mean ED duration, 4 years), which was conducted at 62 centers in the United States.Analysis (by intent-to-treat, n = 368) of the change from baseline to the week-10 endpoint in the SEAR questionnaire Self-Esteem subscale, the intercourse success rate (percent of occasions at which an erection that lasted long enough for successful intercourse was achieved), and their correlation.For the overall population, there was mean +/- SD improvement (p0.0001, paired t-tests) in the Self-Esteem subscale (56 +/- 25 to 79 +/- 22) and intercourse success rate (21 +/- 30% to 70 +/- 36%), which showed positive correlation (p0.0001). Secondary outcomes (i.e., EF domain of the International Index of Erectile Function; event log frequency of erection hard enough for sexual intercourse and of ejaculation/orgasm) also improved (p0.0001) and correlated positively with the SEAR Self-Esteem subscale and Sexual Relationship domain (p0.05 for all correlations). All 10 correlations were positive (p0.05) in men aged 50 to 65 years, eight were positive in men aged65 years, and six were positive in men aged50 years. The most common treatment-related adverse events were mild-to-moderate headache (12% of patients), vasodilatation (7%), and rhinitis (4%).Men treated with sildenafil for ED demonstrated improved erectile function and an increased intercourse success rate, which correlated positively with improvement in SEAR measures of self-esteem and sexual relationship.

Objective: To evaluate the efficacy of short-term treatment with sildenafil citrate in men with serotonin reuptake inhibitor (SRI)-associated erectile dysfunction (ED). Method: Men (aged ≥ 18 years) with major depressive disorder (MDD; DSM-IV criteria) in remission and taking SRIs who experienced SRI-associated ED were enrolled in this multicenter, 6-week, randomized, flexible-dose, double-blind, placebo-controlled trial. The primary study measures were questions 3 (Q3: frequency of penetration) and 4 (Q4: frequency of maintained erections after penetration) of the International Index of Erectile Function (IIEF) questionnaire. Secondary study measures were all other questions and domains of the IIEF, the Erectile Dysfunction Index of Treatment Satisfaction (EDITS), a global efficacy questionnaire (GEQ), and a patient-maintained event log of sexual activity. Results: Patients receiving sildenafil (N =71) versus placebo (N = 71) reported significantly higher mean ± SE scores on Q3 (3.9 ± 0.2 vs. 3.1 ± 0.2, p =.003) and Q4 (3.7 ± 0.2 vs. 2.8 ± 0.2, p

Objectives Research is lacking on the correlation between treatment satisfaction and confidence, self-esteem, and relationships for men receiving treatment for erectile dysfunction (ED). We sought to correlate scores between the validated Erectile Dysfunction Inventory of Treatment Satisfaction (EDITS) index and the validated Self-Esteem And Relationship (SEAR) questionnaire following treatment with sildenafil citrate (VIAGRA). Methods This study was based on an open-label, flexible-dose trial of 93 sildenafil-naive patients with ED. Pearson correlation coefficients between EDITS index and SEAR questionnaire scores, each of which can range from 0 to 100 (most favorable), were calculated at end of treatment (EOT). An analysis of covariance model was applied to associate changes from baseline to EOT in SEAR scores with EDITS score at EOT, controlling for baseline SEAR score. Results Significant and sizable Pearson's correlations between SEAR and EDITS scores ( P ≤ 0.0001; range: 0.49–0.84) were observed. A 10-point higher EDITS scores at EOT corresponded to a significant and tangible average improvement in SEAR scores from baseline to EOT ( P ≤ 0.0001; range: 6.6–8.7). Average SEAR scores at EOT were markedly different between patients with greater treatment satisfaction at EOT (EDITS score ≥ median EDITS score of 88.6; n = 50) and those with lesser treatment satisfaction at EOT (EDITS score Conclusions The data add to the validity of the SEAR questionnaire, suggest a tangible relationship between treatment satisfaction and psychosocial benefit among men with ED treated with sildenafil, and highlight the importance of assessing the psychosocial impact of ED in men undergoing treatment.

Erectile dysfunction (ED) is commonly associated with depressed mood and diminished quality of life (QoL), but few studies have investigated the causal associations involved. Therefore, we evaluated the correlation between several measures of mood, QoL, and sexual function in a retrospective analysis of a sample of depressed men (n=152), with ED enrolled in a clinical trial of sildenafil citrate (VIAGRA). Strong correlations were observed at baseline among measures of erectile function (EF), mood, and overall QoL. Significant treatment effects were observed on all three domains, with significant interactions between changes in mood and QoL. Based on multiple regression and path analysis, a model was developed in which EF changes were associated with improved mood and quality of sexual life, which resulted in improved partner satisfaction, family life, and overall life satisfaction. These data suggest that QoL changes associated with ED therapy may be mediated by changes in sexual function, mood, and family relationships.

SummaryAims The aim of this study was to assess erection quality with sildenafil vs placebo and adverse events (AEs) according to age (≤45, 46-55 and ≥56 years) in 997 men with erectile dysfunction (ED) using pooled data from four randomized, double-blind, placebo-controlled, flexible-dose trials. Methods The trials included 6- to 10-week treatment periods. The starting sildenafil dose was 50 mg, taken ~1 hour before sexual activity but not more than once daily, with subsequent adjustment to 100 or 25 mg based on efficacy and safety. Exclusion criteria included blood pressure 170/110 mmHg, taking nitrate therapy or nitric oxide donors, severe cardiac failure/unstable angina or recent stroke or myocardial infarction. Changes from baseline in Quality of Erection Questionnaire (QEQ), International Index of Erectile Function (IIEF) and Erectile Dysfunction Inventory of Treatment Satisfaction (EDITS) scores were analysed. Results Improvements in QEQ scores with sildenafil vs placebo were significant (P

Introduction Sildenafil has been evaluated in >16 000 men with erectile dysfunction (ED) in double-blind, placebo-controlled trials. Aim To assess efficacy and safety of sildenafil in ED by ethnicity (white, black Asian) and age (≤45, 46-60, ≥61 years). Methods Data were pooled from 38 double-blind, placebo-controlled, flexible-dose trials. Most had starting sildenafil doses of 50 mg once daily, ~1 hour before sexual activity, with adjustment to 100 or 25 mg as needed. Main Outcome Measures Change from baseline in International Index of Erectile Function erectile function (IIEF-EF) domain score assessed with analysis of covariance and a Global Assessment Question (GAQ; “Did the treatment improve your erections?”) at endpoint assessed with logistic regression analysis. Results 4120 and 3714 men received sildenafil and placebo, respectively (2740 and 2671 White; 407 and 385 Black; 973 and 658 Asian). For sildenafil vs. placebo groups, overall treatment differences for IIEF-EF domain and GAQ were significant for each ethnic and age group (P

The aim was to investigate the effects of extracorporeal cardiopulmonary resuscitation (ECPR) for out-of-hospital cardiac arrest (OHCA) and compare the results with those of in-hospital cardiac arrest (IHCA).We analyzed our extracorporeal membrane oxygenation (ECMO) results for patients who received ECPR for OHCA or IHCA in the last 5 years. Pre-arrest, resuscitation, and post-resuscitative data were evaluated.In the last 5 years, ECPR was used 230 times for OHCA (n=31) and IHCA (n=199). The basic demographic data showed significant differences in age, cardiomyopathy, and location of the initial CPR. Duration of ischemia was shorter in the IHCA group (44.4±24.7 min vs. 67.5±30.6 min, p0.05). About 50% of each group underwent a further intervention to treat the underlying etiology. ECMO was maintained for a shorter duration in the OHCA patients (61±48 h vs. 94±122 h, p0.05). Survival to discharge was similar in the two groups (38.7% for OHCA vs. 31.2% for IHCA, p0.05), as was the favorable outcome rate (25.5% for OHCA vs. 25.1% for IHCA, p0.05). Survival was acceptable (about 33%) in both groups when the duration of ischemia was no longer than 75 min.In addition to having a beneficial effect in IHCA, ECPR can lead to survival and a positive neurological outcome in selected OHCA patients after prolonged resuscitation. Our results suggest that further investigation of the use of ECMO in OHCA is warranted.

Background: Intraductal ultrasound (IDUS) as an adjunct to ERCP for detection of extrahepatic bile duct stones is technically easy, accurate, and safe. This prospective study evaluated IDUS with an "over-the-wire" catheter US probe as an adjunct to ERCP. Methods: Sixty-five patients, highly suspected to have choledocholithiasis, underwent IDUS during ERCP. The IDUS probe was inserted by means of the duodenoscope into the bile duct without performing a sphincterotomy. All stones identified by IDUS or retrograde cholangiography were removed with either a basket or retrieval balloon after endoscopic sphincterotomy. Results: The final diagnosis was choledocholithiasis in 59 patients. Bile duct diameter ranged from 0.6 to 2.3 cm and stone size from 2 mm to 2 cm. IDUS successfully identified all stones in these patients. IDUS resulted in 2 false-positive diagnoses in the remaining 6 patients without stones (overall accuracy 97%, sensitivity 100%, specificity 67%). Cholangiography detected stones in 55 of the patients with stones (accuracy 94%, sensitivity 93%, specificity 100%). Conclusion: IDUS, a safe, technically easy procedure, is highly accurate in the detection of extrahepatic bile duct stones regardless of the diameter of the bile ducts. The "over-the-wire" technique preserves access to the cannulated duct. IDUS is an excellent adjunct to ERCP for the diagnosis of choledocholithiasis. IDUS differentiates stones from air bubbles and prevents unnecessary sphincterotomy. (Gastrointest Endosc 2001;54:720-3.)

Purpose The purpose of this retrospective study was to compare the sensitivity of endoscopic sonography (EUS), transabdominal sonography (US), and CT in the detection of, local staging of, and prediction of vascular involvement by or distant metastasis from periampullary tumors. Methods Seventy-four consecutive patients with presumed periampullary tumors were evaluated by EUS, US, and CT during a 3.25-year period. The local staging accuracy of the modalities was assessed in the 36 patients with solid tumors who underwent surgery. The sensitivity of the modalities in predicting vascular involvement and distant metastasis was assessed in the 56 patients with carcinomas. Results EUS was the most sensitive modality in the detection (EUS, 97%; US, 24%; and CT, 39%; p < 0.001 for EUS versus US or CT) and T classification (EUS, 72%; US, 11%; CT, 22%; p < 0.001 for EUS versus US or CT) of periampullary tumors. EUS also had better sensitivity than US in detecting lymph node metastasis from periampullary cancers (EUS, 47%; US, 7%; and CT, 33%; p = 0.02 for EUS versus US; p = 0.7 for EUS versus CT). The accuracy of EUS in determining the T classification (without stent, 81%; with stent, 65%) and N classification (without stent, 80%; with stent, 70%) tended to decrease in the presence of an endobiliary stent, but the differences were not significant. EUS was the most sensitive modality in demonstrating vascular involvement (EUS, 100%; US, 0%; and CT, 33%; p = 0.002 for EUS versus US; p = 0.03 for EUS versus CT) but was not significantly different in detecting distant metastasis (EUS, 11%; US, 44%; and CT, 44%). Conclusions EUS is superior to US and CT in the local assessment of periampullary tumors. The staging accuracy of EUS is minimally but not significantly affected by the presence of an endobiliary stent. © 2001 John Wiley & Sons, Inc. J Clin Ultrasound 29:313–321, 2001.

Rationale The effectiveness of varenicline for smoking cessation has been established, but little is known about the psychological processes that mediate this clinical outcome. Objectives This study evaluated the effect of a single dose of varenicline on tonic and cue-provoked changes in craving, withdrawal, and affect using a randomized, double-blind, placebo-controlled, cross-over design. Methods Following overnight abstinence, 38 non-treatment-motivated smokers received either varenicline 2 mg or matched placebo, then tonic measures of craving, withdrawal, and positive and negative affect were obtained at 30-min intervals. At 4-h post-administration, a cue exposure session obtained the same subjective measures at three time-points following the physical handling of a lit cigarette versus the sharpening and handling of a pencil. Results At 4-h post-administration, varenicline reduced tonic craving as well as craving across the smoking and neutral cue conditions, relative to placebo. By contrast, the capacity of the smoking cue to enhance craving relative to the neutral cue was unaffected by varenicline. Measures of withdrawal and positive and negative affect produced mixed results. Conclusions Acute varenicline selectively attenuates tonic but not cue-provoked craving. This dissociation provides insight into the specific psychological processes that might mediate the effectiveness of varenicline, and highlights cue-provoked craving as a discrete target for advancing smoking cessation pharmacotherapy.

OBJECTIVE To evaluate the effect of sildenafil citrate on each item of the 14-item Self-Esteem And Relationship (SEAR) questionnaire, which is used to measure self-esteem, confidence, satisfaction with sexual relationship, and overall relationship satisfaction in men with erectile dysfunction (ED). PATIENTS AND METHODS Data were combined from two 12-week, double-blind, placebo-controlled, flexible-dose sildenafil trials having identical protocols, one conducted in the USA and the other in Mexico, Brazil, Australia and Japan. All men had ED and were aged >or=18 years. Response categories of each SEAR item used a 4-week reference period and were based on a five-point scale (1, almost never/never; 2, a few times; 3, sometimes; 4, most times; 5, almost always/always). The difference (sildenafil vs placebo) in the change from baseline to week 12 was evaluated with a Wilcoxon rank sum test using ridit analysis, and an analysis of covariance model that included treatment group, centre, study and baseline item score. RESULTS Compared with the 274 patients receiving placebo, the 279 receiving sildenafil reported significantly greater mean and median improvements (P < 0.001) in each of the 14 SEAR items. The probability of increased psychosocial benefit from baseline to week 12 was higher with sildenafil for each SEAR item, and ranged from 0.60 ('My partner was unhappy with the quality of our sexual relations'[item reverse-scored]) to 0.72 ('I was satisfied with my sexual performance'). Across all items, the mean (sd) probability was 0.67 (0.04) that a randomly selected patient in the sildenafil group would have a more favourable change relative to a randomly selected patient in the placebo group. CONCLUSIONS Sildenafil produced substantial and meaningful improvements at the item-specific level. This analysis complements previously published work on self-esteem, confidence and relationship satisfaction.

We investigated the effect of early sildenafil dose optimization and personalized instructions on sexual intercourse success in 1109 men beginning sildenafil therapy for erectile dysfunction. In phase 1 (4 weeks), patients followed the instructions contained in the sildenafil (50 mg) sample pack and had 1.4 sexual intercourse attempts per week with 82% success. Patients (17%) had a second intercourse attempt (80% successful): 58% occurred within 4 h, 20% within 5-8 h, and 22% within 9-24 h of the first attempt. In phase 2 (4 weeks), sildenafil was adjusted as needed (53% to 100 mg, and 2% to 25 mg), and investigators provided personalized instructions to facilitate patient success. Sexual intercourse attempts increased to 1.7 per week, with 91% success, and 18% were followed by a second attempt, of which 91% were successful. Most patients requested the 100-mg dose, which helped improve sexual intercourse frequency, flexibility and success.

Men with erectile dysfunction (ED) often have low self-esteem, confidence, and sexual relationship satisfaction.We evaluated the impact of sildenafil citrate and its generalizability across cultures on self-esteem, confidence, and sexual relationship satisfaction in men with ED using the Self-Esteem And Relationship (SEAR) questionnaire.Pooled analysis of 2 double-blind, placebo-controlled, flexible-dose trials of sildenafil with identical protocols: 1 was conducted in the United States and the other in Mexico, Brazil, Australia, and Japan.Menor = 18 years old with ED.The impact of treatment on psychosocial factors associated with ED was determined by patient responses to the SEAR questionnaire. Erectile function was determined using the International Index of Erectile Function (IIEF) and a global efficacy question. Successful sexual intercourse attempts were derived from event logs of sexual activity. Treatment effect sizes were calculated for all study outcomes.Compared with patients who received placebo (n = 274), patients who received sildenafil (n = 279) reported significantly greater improvements (P.0001) in self-esteem, confidence, sexual relationship satisfaction, and in all sexual function domains of the IIEF. Treatment effect sizes were large (range, 0.7 to 1.2) for all SEAR components, and improvement in psychosocial measures showed moderate to high correlations (range, 0.50 to 0.83, P.0001) with improvement in erectile function, percentage of successful intercourse attempts, and global efficacy.In men with ED from 5 different nations, sildenafil produced substantial improvements in self-esteem, confidence, and sexual relationship satisfaction. Improvements in these psychosocial factors were observed crossculturally and correlated significantly and tangibly with improvements in erectile function.

The first double-blind, placebo controlled trial in the United States of the Self-Esteem And Relationship questionnaire revealed that treatment with sildenafil citrate improves erectile function and measures of quality of life in men with erectile dysfunction. We investigated long-term improvement, and correlations between improved erectile function and confidence, self-esteem and sexual relationship satisfaction in men with erectile dysfunction.This was a 36-week open label extension of the double-blind, placebo controlled trial. The blind was not broken. Patients were 18 years or older with clinically diagnosed erectile dysfunction. Erectile function was assessed using the International Index of Erectile Function. Self-esteem, confidence and relationship satisfaction were assessed using the Self-Esteem And Relationship questionnaire. Correlations were determined using Pearson's product moment coefficients.A total of 204 participants were enrolled in the open label extension, including 108 on placebo and 96 on sildenafil. In men who received placebo in the double-blind, placebo controlled phase mean erectile function scores and self-esteem, confidence and relationship satisfaction scores were increased significantly at week 36 of the open label extension (p0.0001). Men who received sildenafil in the double-blind, placebo controlled phase maintained high scores in the open label extension. Correlations between improved erectile function, and self-esteem, confidence and relationship satisfaction were strong and positive (p0.0001).Open label extension sildenafil after double-blind, placebo controlled placebo significantly improved erectile function, self-esteem, confidence and relationship satisfaction. Following an initial 12 weeks of double-blind, placebo controlled sildenafil therapy for erectile dysfunction improvements were sustained an additional 9 months. Positive correlations between erectile function, and self-esteem, confidence and relationship satisfaction suggest that improved erectile quality can improve long-term psychosocial quality of life.

To determine the minimal time to successful intercourse after taking sildenafil citrate for erectile dysfunction (ED).Male patients with ED (mean age 60 years; mean ED duration 7.0 years) who were successfully treated with sildenafil (100 mg) for 2 months or longer were randomized to sildenafil (n = 115) or placebo (n = 113) for 4 weeks of double-blind treatment. Using a stopwatch, patients recorded the time needed to obtain an erection hard enough for sexual intercourse after taking the study drug at least 2 hours after eating.Within 14 and 20 minutes of sildenafil dosing, 35% and 51% of sildenafil-treated patients, respectively, versus 22% and 30% of placebo-treated patients, respectively, had an erection that led to successful intercourse (P0.05 for both). The median time to erection leading to successful intercourse after sildenafil dosing was 36 minutes compared with 141 minutes for placebo.In this study, slightly more than one half of a population of prior sildenafil responders achieved an erection that led to successful sexual intercourse within 20 minutes of sildenafil administration, suggesting that the onset of action of sildenafil can be less than 30 minutes in men with ED.