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OBJECTIVES: The cardiovascular homeostatic responses to hemorrhage are coordinated in the central nervous system. Coincidental brain injury, which is present in 64% of trauma patients, could impair these responses. Our objective was to test the hypothesis that mild to moderate traumatic brain injury alters cardiovascular reflex responses to acute hemorrhage. DESIGN: Experimental prospective, randomized study in terminally anesthetized rats. SETTING: Experimental laboratory of university. SUBJECTS: Twenty-four male Wistar rats weighing 240-260 g. INTERVENTIONS: Brain injury was induced using the lateral fluid percussion injury model in anesthetized rats. The fluid percussion device delivered an applied cortical pressure of 1.2 atm and 1.8 atm, producing mild and moderate injury, respectively. Control animals underwent identical surgical procedures but with no applied cortical pressure. Hemorrhage was carried out 10 mins after brain injury, at a rate of 2% of blood volume per minute until 40% blood volume was withdrawn. MEASUREMENTS AND MAIN RESULTS: The effects of acute traumatic brain injury on the biphasic heart rate and mean arterial blood pressure response to hemorrhage were studied. Traumatic brain injury attenuated the normal bradycardic response and delayed the hypotensive response to hemorrhage. This effect was graded according to the severity of brain injury. In mild injury, the depressor phase was delayed, but the biphasic pattern of heart rate response was maintained. No mortality was observed in this group. Following moderate brain injury, marked attenuation of the biphasic heart rate and mean arterial blood pressure response (p < .001 and p = .0007) was observed. Fifty percent of this group died within 90 mins of hemorrhage completion. Significant differences in the biphasic response were observed between survivors and nonsurvivors (p = .013, p = .001, respectively). In nonsurvivors, the biphasic response was abolished. CONCLUSIONS: Acute mild and moderate traumatic brain injury disrupts cardiovascular homeostatic responses to extracranial hemorrhage; this disruption is graded according to the severity of traumatic brain injury. Severe disruption is associated with an increase in early mortality. [ABSTRACT FROM AUTHOR]

Introduction: Fifteen years have passed since the International Society of Sexual Medicine first established the 3-pronged criteria for premature ejaculation (PE): a short ejaculation latency, lack of ejaculatory control, and bother/distress. Although the process of establishing valid criteria for any condition or disorder is an ongoing one, a dearth of targeted research on these criteria has hindered professional societies from updating and revising them., Objectives: To review and critique existing criteria used in the diagnosis of PE, to identify specific problems with them, and to recommend studies that will address shortcomings., Methods: Each of the PE criteria was evaluated and compared against standard procedures for establishing validated measures. Following each analysis, targeted research to address the gaps has been recommended., Results: Each PE criterion has shortcomings and each can be improved by using standard validation procedures, as noted by the targeted research outcomes. Professional societies can play an important role by encouraging broad participation in research that generates new and relevant data supporting, validating, or challenging the existing criteria., Conclusion: The concepts underlying the diagnostic criteria for PE have both broad consensus and functional utility. Nevertheless, much of the research investigating PE has uncritically adopted these criteria without concomitantly recognizing their limitations. These limitations prevent determining accurate prevalence rates, interpreting research findings with confidence, and establishing efficacious treatment outcomes. Rowland DL, Althof SE, McMahon CG. The Unfinished Business of Defining Premature Ejaculation: The Need for Targeted Research. Sex Med Rev 2022;10:323-340., (Copyright © 2021 International Society for Sexual Medicine. Published by Elsevier Inc. All rights reserved.)

Purpose: Men who ejaculate before or shortly after penetration, without a sense of control, and who experience distress related to this condition may be diagnosed with premature ejaculation (PE), while men who experience difficulty achieving sexual climax may be diagnosed with delayed ejaculation (DE). The experience of many clinicians suggest that these problems are not rare and can be a source of considerable embarrassment and dissatisfaction for patients. The role of the clinician in managing PE and DE is to conduct appropriate investigation, to provide education, and to offer available treatments that are rational and based on sound scientific data., Materials and Methods: The systematic review utilized to inform this guideline was conducted by a methodology team at the Pacific Northwest Evidence-based Practice Center. A research librarian conducted searches in Ovid MEDLINE (1946 to March 1, 2019), the Cochrane Central Register of Controlled Trials (through January 2019) and the Cochrane Database of Systematic Reviews (through March 1, 2019). An update search was conducted on September 5, 2019. Database searches resulted in 1,851 potentially relevant articles. After dual review of abstracts and titles, 223 systematic reviews and individual studies were selected for full-text dual review, and 8 systematic reviews and 59 individual studies were determined to meet inclusion criteria and were included in the review., Results: Several psychological health, behavioral, and pharmacotherapy options exist for both PE and DE; however, none of these pharmacotherapy options have achieved approval from the United States Food and Drug Administration and their use in the treatment of PE and DE is considered off-label., Conclusion: Disturbances of the timing of ejaculation can pose a substantial impediment to sexual enjoyment for men and their partners. The Panel recommends shared decision-making as fundamental in the management of disorders of ejaculation; involvement of sexual partner(s) in decision making, when possible, may allow for optimization of outcomes.

Background: There are several problems with diagnostic criteria for premature ejaculation (PE) that lack objectivity, clarity and precision. They hamper accurate determination of PE prevalence estimates, investigations into the etiology of the dysfunction, impact on partners, development of validated Patient Reported Outcomes, regulatory authority oversight, and which men might benefit from specific treatment interventions., Aim: We sought to review, analyze and comment on the evolution of the definitions of PE and offer suggestions for future directions for PE definitions. Our goal is to propose strategies whereby the criterion sets are useful to researchers, clinicians and governmental oversight agencies alike and bring harmony and scientific rigor among the conflicting and confusing definitions., Methods: There are several premature ejaculation definitions published in the peer reviewed medical literature. The PUBMED electronic database from 1970 to 2021 was searched for published definitions. Search terms included the medical subject headings of premature ejaculation, definition and diagnosis. In chronological order, Table 1 lists the various diagnosis and criteria sets for PE. We discuss the process by which constructs, which make up diagnostic criteria sets, are operationalized and validated., Results: We review definitions of PE beginning with Masters and Johnson's focus on partner orgasmic attainment and move through the nebulous and subjective criterion sets found in the early Diagnostic and Statistical Manuals and International Classification of Disease series, to the more evidenced-based definitions found in International Society of Sexual Medicine, Diagnostic and Statistical Manuals-5 and the American Urological Association (AUA) definitions. Additionally, we discuss how constructs and criteria sets have been adopted to minimize errors of inclusion and exclusion in defining disease/dysfunction., Strengths and Limitations: This manuscript offers a careful chronological analysis of the published definitions of PE. This historical lens allows the reader to perceive the shifting science underlying the development of PE definitions. The manuscript is limited regarding our comments on acquired PE as evidenced-based research is incomplete., Conclusion: Over the past 50 years there has been considerable forward momentum in defining PE based on well conducted scientific studies. We support the American Urological Association's modification in Intravaginal ejaculatory latency time to 2-minutes for lifelong PE, concur with the 11th revision of the International Classification of Diseases recommendation for changing the terminology from premature ejaculation to early ejaculation. We also recommend ongoing validation of definitions, moving away from the current heterosexist definition of PE based on penile-vaginal sex and urge further population based research into acquired PE to develop stronger evidenced-based criterion sets for this subtype. Althof SE, McMahon CG, Rowland DL. Advances and Missteps in Diagnosing Premature Ejaculation: Analysis and Future Directions. J Sex Med 2022;19:64-73., (Copyright © 2021 International Society for Sexual Medicine. Published by Elsevier Inc. All rights reserved.)

Background: Up to half of patients presenting with falls, syncope or dizziness are admitted to hospital. Many are discharged without a clear diagnosis for their index episode, however, and therefore a relatively high risk of readmission., Aim: To examine the impact of ED-FASS (Emergency Department Falls and Syncope Service) a dedicated specialist service embedded within an ED, seeing patients of all ages with falls, syncope and dizziness., Design: Pre- and post-cohort study., Methods: Admission rates, length of stay (LOS) and readmission at 3 months were examined for all patients presenting with a fall, syncope or dizziness from April to July 2018 (pre-ED-FASS) inclusive and compared to April to July 2019 inclusive (post-ED-FASS)., Results: There was a significantly lower admission rate for patients presenting in 2019 compared to 2018 [27% (453/1676) vs. 34% (548/1620); X2 = 18.0; P < 0.001], with a 20% reduction in admissions. The mean LOS for patients admitted in 2018 was 20.7 [95% confidence interval (CI) 17.4-24.0] days compared to 18.2 (95% CI 14.6-21.9) days in 2019 (t = 0.98; P = 0.3294). This accounts for 11 344 bed days in the 2018 study period, and 8299 bed days used after ED-FASS. There was also a significant reduction in readmission rates within 3 months of index presentation, from 21% (109/1620) to 16% (68/1676) (X2 = 4.68; P = 0.030)., Conclusion: This study highlights the significant potential benefits of embedding dedicated multidisciplinary services at the hospital front door in terms of early specialist assessment and directing appropriate patients to effective ambulatory care pathways., (© The Author(s) 2020. Published by Oxford University Press on behalf of the Association of Physicians. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Objectives: Acute hospitals, in particular the emergency department, can be disorienting for people living with dementia. As part of a larger project to improve care for people living with dementia, dementia-inclusive modifications were made to two emergency department bays in a large acute care hospital in Ireland. Modifications to spatial configuration included noise reduction, altered lighting and the addition of an orientation aid and fixed seating for relatives., Method: A mixed methods approach was employed with both service user and service provider perspectives explored (survey of service providers ( n  = 16) and interviews with family carers ( n  = 10) at one time point and interviews with service providers ( n  = 8 and n  = 5) and key stakeholders ( n  = 3) as well as audit data (at two time points) to evaluate the impact of the modifications made to the emergency department., Results: Orientation and navigation within the modified bays were improved though technical issues with the orientation aid were highlighted. Further user information on the functionality of the adjustable lighting would be required to maximise its benefits. This lighting and use of calming colours, together with the addition of noise-reduction bay screens, served to reduce sensory stimulation. The provision of adequate space and seating for family carers was extremely beneficial. The removal of unnecessary equipment and use of new structures to store relevant clinical equipment were other positive changes implemented. A number of challenges in the design development of the modified bays were highlighted, as well as ongoing broader environmental challenges within the emergency department environment., Conclusion: The findings suggest that the modified bays contributed positively to the experience of people living with dementia and their families in the emergency department.

Erectile dysfunction (ED) is a common male sexual dysfunction associated with a reduced quality of life for patients and their partners. ED is associated with increasing age, depression, obesity, lack of exercise, diabetes mellitus, hypertension, dyslipidaemia, cardiovascular disease and lower urinary tract symptoms related to benign prostatic hyperplasia. The evaluation of men with ED requires a full medical and personally and culturally sensitive sexual history, a focused clinical examination, fasting glucose levels, a fasting lipid profile and, in select cases, a total testosterone level and a prostate-specific antigen test. Treatment of ED requires lifestyle modification, reduction of comorbid vascular risk factors, and treatment of organic or psychosexual dysfunction with either pharmacotherapy alone or in combination with psychosexual therapy. Between 60% and 65% of men with ED, including those with hypertension, diabetes mellitus, spinal cord injury and other comorbid medical conditions, can successfully complete intercourse in response to the phosphodiesterase type 5 inhibitors (PDE5i) sildenafil, tadalafil, vardenafil and avanafil. Patient-administered intracorporal injection therapy using vasodilator drugs such as alprostadil is an effective treatment and is useful in men who fail to respond to oral pharmacological agents. Surgical treatment of ED with multicomponent inflatable penile implants is associated with high satisfaction rates. Penile arterial revascularisation and venous ligation surgery are associated with relatively poor outcome results in men with penile atherosclerotic disease or corporal veno-occlusive dysfunction., (© 2019 AMPCo Pty Ltd.)

Aim: There is growing evidence of an overlap between unexplained falls and syncope in older adults. Our aim was to examine the prevalence and associated resource utilization of these conditions in an urban emergency department (ED)., Patients and Methods: A single-centre, prospective, observational study was carried out over a 6-month period. Consecutive patients older than 50 years who presented to the ED because of a fall, collapse or syncope were included. Univariate analysis of demographic data is presented as percentages, mean (SD), 95% confidence intervals (CIs) and medians (interquartile range). Logistic regression modelling was used to examine the association between falls and resource utilization., Results: A total of 561 patients fulfilled the inclusion criteria during the study period. Unexplained fallers accounted for 14.3% (n=80; 95% CI: 13.3-15.3) and syncope for 12.7% (n=71; 95% CI: 11.7-13.6) of all fall presentations. Overall, 50% (n=282; 95% CI: 48.20-52.34) of patients required admission to hospital. Patients with syncope [odds ratio (OR)=2.48, 95% CI: 1.45-4.23], and unexplained falls (OR=2.36, 95% CI: 1.37-4.08) were more likely to require admission than those with an explained falls. Unexplained fallers were nearly five times more likely to suffer recurrent falls (OR=4.97, 95% CI: 2.89-8.56)., Conclusion: One in four older fallers presenting to ED have symptoms suggestive of syncope or an unexplained fall. There are significant biological consequences of recurrent falls including greater rates of cognitive decline, gait and mobility disturbances, depression and frailty. Recognition that syncope can present as an unexplained fall in older adults is important to ensure that appropriate early modifiable interventions are initiated.

Introduction: Characteristics of older frequent users of Emergency Departments (EDs) are poorly understood. Our aim was to examine the characteristics of the ED frequent attenders (FAs) by age (under 65 and over 65 years)., Methods: We examined the prevalence of FA attending the ED of an Urban Teaching Hospital in a cross-sectional study between 2009 and 2011. FA was defined as an individual who presented to the ED four or more times over a 12-month period. Randomly selected groups of FA and non-FA from two age groups (under 65 and over 65 years) were then examined to compare the characteristics between older FAs and non-FAs and older FAs and younger FAs. Logistic regression was used to calculate the odds ratio and 95% confidence intervals for 12-month mortality in FA compared with non-FA aged at least 65 years., Results: Overall, 137 150 ED attendances were recorded between 2009 and 2011. A total of 21.6% were aged at least 65 years, 4.4% of whom were FAs, accounting for 18.4% of attendances by patients older than 65 years. There was a bimodal age distribution of FA (mean±SD; under 65 years 40±12.7; and over 65 years 76.9±7.4). Older FAs were five times more likely to present outside normal working hours and 5.5 times more likely to require admission. Cardiovascular emergencies were the most common complaint, in contrast with the younger FA group, where injury and psychosocial conditions dominated. The odds ratio for death at 12 months was 2.07 (95% confidence interval 0.93-4.63; P=0.07), adjusting for age and sex., Conclusion: One-in-five ED patients older than 65 years of age are FAs. Older FAs largely present with complex medical conditions. Enhanced access to expert gerontology assessment should be considered as part of effective intervention strategies for older ED users.

Background: Implantation of testosterone doses of at least 150 to 450 mg (ie, two to six pellets) is common clinical practice despite a lack of prospective data., Aim: To evaluate pharmacokinetics, clinical efficacy, safety, and patient-reported outcomes in men with androgen deficiency who received implantation of testosterone pellets (900 mg) in an open-label study., Methods: Men with androgen deficiency (serum testosterone < 300 ng/dL [10.4 nmol/L]) were screened and received 12 testosterone pellets (900 mg). Serum hormone measurements (total and free testosterone, dihydrotestosterone, and estradiol) were obtained on days 1, 5, 8, 15, 29, 57, 85, and 113. All hormones were assayed using validated liquid chromatography and tandem mass spectrometry., Outcomes: Pharmacokinetics of selected hormones was determined. The patient-reported International Index of Erectile Function (IIEF), Center for Epidemiologic Studies Depression (CES-D), and Androgen Deficiency in the Aging Male (qADAM) questionnaires also were performed. Patients rated their satisfaction on a scale from 1 (very satisfied) to 5 (very dissatisfied). Adverse events were monitored throughout., Results: Fifteen patients were included (mean age = 54.5 years, SD = 8.6 years). Mean baseline total testosterone concentration was 241.6 ng/dL (SD = 88.8 ng/dL; mean = 8.4 nmol/L, SD = 3.1 nmol/L). Mean testosterone serum concentrations fluctuated during the first 2 weeks (range = 300-1,000 ng/dL, 10.4-34.7 nmol/L) but remained higher than or equal to 300 ng/dL (10.4 nmol/L) through day 113. Concentrations of free testosterone, dihydrotestosterone, and estradiol mirrored that of total testosterone. Male functioning (IIEF score), depression (CES-D total score), and androgen-deficiency symptoms (qADAM total score) improved from baseline. Most patients were "very satisfied" (40.0%) or "quite satisfied" (26.7%) with treatment. Testosterone pellets were well tolerated. Pellet extrusion and polycythemia occurred in one patient each., Clinical Implications: Implantation of high doses (900 mg) of testosterone pellets are generally well tolerated and could provide clinical benefit for some patients., Strengths and Limitations: This study provides standardized data for the implantation of 12 testosterone pellets. However, the open-label uncontrolled design of this study and its small and ethnically non-diverse patient population limit the interpretation of these data, particularly the patient-reported outcomes., Conclusion: Implantation of 12 testosterone pellets (900 mg) was well tolerated and provided adequate and sustained serum testosterone concentrations. Additional randomized controlled trials are needed to confirm efficacy and safety findings. McMahon CG, Shusterman N, Cohen B. Pharmacokinetics, Clinical Efficacy, Safety Profile, and Patient-Reported Outcomes in Patients Receiving Subcutaneous Testosterone Pellets 900 mg for Treatment of Symptoms Associated With Androgen Deficiency. J Sex Med 2017;14:883-890., (Copyright © 2017. Published by Elsevier Inc.)

Introduction: Collagenase Clostridium histolyticum (CCH) intralesional injection was efficacious for the management of Peyronie's disease (PD) in the double-blinded, randomized, placebo-controlled Investigation for Maximal Peyronie's Reduction Efficacy and Safety Studies I and II (IMPRESS I and II). Little is known about the consequences of PD or treatment on the sexual partners of affected men., Aim: To assess the safety and efficacy of CCH treatment in men who received placebo in the IMPRESS I or II study and to evaluate the men's PD symptoms and partner bother as reported by female sexual partners., Methods: In this phase 3, open-label study (NCT01685437), men (n = 189) received up to eight injections of CCH (0.58 mg/injection). Female sexual partners who provided informed consent at screening (n = 30) participated in the study., Main Outcome Measures: Co-primary end points were change or percentage of change in penile curvature deformity and change in PD symptom bother domain score of the Peyronie's Disease Questionnaire (PDQ) from baseline to week 36. Participating women completed the PDQ for female sexual partners (PDQ-FSP) and the Female Sexual Function Index (FSFI)., Results: Statistically significant mean improvements were observed in penile curvature deformity (36.3% decrease; 95% CI = -41.6 to -30.9) and PDQ symptom bother score (2.4-point decrease; 95% CI = -3.0 to -1.8) from baseline to week 36. Most treatment-emergent adverse events were mild or moderate. After CCH treatment of their male partners, female sexual partners reported improvement (using the PDQ-FSP) in their male partner's PD symptoms and female bother regarding their partner's PD. The percentage of female sexual partners with sexual dysfunction (FSFI total score ≤ 26.55) also decreased after male partner treatment, from 75.0% at baseline to 33.3%., Conclusions: These results support the safety and efficacy of CCH in the management of appropriate patients with PD and the potential benefits for patients' partners. Goldstein I, Knoll LD, Lipshultz LI, et al. Changes in the Effects of Peyronie's Disease After Treatment With Collagenase Clostridium histolyticum: Male Partners and Their Female Partners. Sex Med 2017;5:e124-e130., (Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.)

Introduction: Premature ejaculation (PE) is one of the most prevalent yet under-reported sexual disorders. Differing sociocultural norms across the Asia-Pacific region provide unique challenges in PE management., Methods: This web-based study collected data from 5,038 men and women across 11 countries in the Asia-Pacific region. Respondents were recruited from an existing database., Main Outcome Measures: The initiators and barriers for PE discussions and for seeking professional management following self-treatment, as well as their choices and expectations of healthcare professionals (HCPs)., Results: More than two-thirds of respondents have discussed PE with their partners, and men are more likely to initiate the discussion. Top drivers were for both partners to attain sexual satisfaction and greater fulfillment in the relationship. Emotional insecurity was the top barrier for men as they did not want to feel hurt or inadequate. Before consulting an HCP, more than two-thirds of men self-treated their PE for at least 20 months. The primary reason for stopping self-treatment and seeking medical management was a lack of improvement in sexual satisfaction. The ideal attributes that men seek in their HCP included trust and being knowledgeable about PE management., Conclusion: Attitudes and barriers to PE and its treatment in the Asia-Pacific region are poorly understood. Many men are reluctant to seek professional advice and therefore resort to self-treatment for extended periods. HCPs can play a key role to empower PE sufferers and partners to understand the prevalence, medical relevance, treatability, and negative impacts of PE on sexual and overall relationships. Greater awareness of the diverse cultural and social norms, education of both partners and HCPs, and the involvement of HCPs through a patient-centric approach are all pivotal in managing PE optimally across the Asia-Pacific region., (Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.)

Aims: The objective was to examine the impact of out-of-hours exercise treadmill tests (ETTs) on length of hospital stay (LOS) for patients admitted to a chest pain assessment unit with symptoms suggestive of acute coronary syndrome., Methods: Prospective observational study with 30-day follow-up of low-to-intermediate-risk chest pain patients undergoing out-of-hours ETT. Eligible patients had a nonischemic ECG, normal 6-12-h ST-segment monitoring, a negative 12-h troponin T assay, and no contraindications to exercise. Observed LOS was compared to expected LOS in the absence of out-of-hours ETT, using Wilcoxon rank-sum test. Estimated bed day savings and major adverse events at 30 days after discharge were examined., Results: Four hundred and twenty-two patients with a mean age of 52 years (SD 13 years, 25-83 years) were evaluated. Fifty-two per cent (n = 221) were men; 66% (n = 279) had one or less cardiovascular risk factors; and 79% (n = 334) of the patients presented on a Friday or Saturday. ETT was performed on a weekend day in 86% (n = 363) of the patients, facilitating same-day discharges in 71% (n =  300). The median LOS (interquartile range) was 1 day (1, 2 days) for patients assessed with out-of-hours ETT. The expected median LOS (IQR) was 3 days (2, 4 days) (P < 0.05) in the absence of out-of-hours ETT. Each out-of-hours ETT was estimated to save a mean (SD, range) of 1.6 (0.6, 1-4) bed days. Thirty-day mortality and readmission rates were 0 and 0.2% (1 of 422), respectively., Conclusion: The availability of out-of-hours ETT facilitates safe early discharge and reduced LOS for low-to-moderate-risk patients admitted with symptoms of acute coronary syndrome.

Large well-designed clinical efficacy and safety randomized clinical trials (RCTs) are required to achieve regulatory approval of new drug treatments. The objective of this article is to make recommendations for the criteria for defining and selecting the clinical trial study population, design and efficacy outcomes measures which comprise ideal premature ejaculation (PE) interventional trial methodology. Data on clinical trial design, epidemiology, definitions, dimensions and psychological impact of PE was reviewed, critiqued and incorporated into a series of recommendations for standardisation of PE clinical trial design, outcome measures and reporting using the principles of evidence based medicine. Data from PE interventional studies are only reliable, interpretable and capable of being generalised to patients with PE, when study populations are defined by the International Society for Sexual Medicine (ISSM) multivariate definition of PE. PE intervention trials should employ a double-blind RCT methodology and include placebo control, active standard drug control, and/or dose comparison trials. Ejaculatory latency time (ELT) and subject/partner outcome measures of control, personal/partner/relationship distress and other study-specific outcome measures should be used as outcome measures. There is currently no published literature which identifies a clinically significant threshold response to intervention. The ISSM definition of PE reflects the contemporary understanding of PE and represents the state-of-the-art multi-dimensional definition of PE and is recommended as the basis of diagnosis of PE for all PE clinical trials., Competing Interests: Dr. Mcmahon is or has been a consultant, investigator and speaker for Johnson & Johnson, Janssen Cilag, Menarini, Ixchelsis, Absorption Pharmaceuticals, NeuroHealing and Plethora.

As long as man has breathed, his fascination, pursuit and quest for the perfect sexual experience have remained one of his principal raisons d'être. After thousands of years, millions of words and pictures, and billions of attempts, he still often finds the goal largely unobtainable. Until recently, our understanding of premature ejaculation (PE) was an eclectic mix and homogenization of ancient historical and culturally diverse influences. However, recent basic and clinical research has resulted in a new understanding and a paradigm shift in the way we classify, define, evaluate, diagnose and treat PE., Competing Interests: Dr. Mcmahon is a consultant, investigator and speaker for Johnson & Johnson, Janssen Cilag, Menarini, Ixchelsis, Absorption Pharmaceuticals, Neurohealing and Plethora.

Over the past 20-30 years, the premature ejaculation (PE) treatment paradigm, previously limited to behavioural psychotherapy, has expanded to include drug treatment. Pharmacotherapy for PE predominantly targets the multiple neurotransmitters and receptors involved in the control of ejaculation which include serotonin, dopamine, oxytocin, norepinephrine, gamma amino-butyric acid (GABA) and nitric oxide (NO). The objective of this article is to review emerging PE interventions contemporary data on the treatment of PE was reviewed and critiqued using the principles of evidence-based medicine. Multiple well-controlled evidence-based studies have demonstrated the efficacy and safety of selective serotonin reuptake inhibitors (SSRIs) in delaying ejaculation, confirming their role as first-line agents for the medical treatment of lifelong and acquired PE. Daily dosing of SSRIs is likely to be associated with superior fold increases in IELT compared to on-demand SSRIs. On-demand SSRIs are less effective but may fulfill the treatment goals of many patients. Integrated pharmacotherapy and CBT may achieve superior treatment outcomes in some patients. PDE-5 inhibitors alone or in combination with SSRIs should be limited to men with acquired PE secondary to co-morbid ED. New on-demand rapid acting SSRIs, oxytocin receptor antagonists, or single agents that target multiple receptors may form the foundation of more effective future on-demand medication. Current evidence confirms the efficacy and safety of dapoxetine, off-label SSRI drugs, tramadol and topical anaesthetics drugs. Treatment with α1-adrenoceptor antagonists cannot be recommended until the results of large well-designed RCTs are published in major international peer-reviewed medical journals. As our understanding of the neurochemical control of ejaculation improves, new therapeutic targets and candidate molecules will be identified which may increase our pharmacotherapeutic armamentarium., Competing Interests: Dr. Mcmahon is or has been a consultant, investigator and speaker for Johnson & Johnson, Janssen Cilag, Menarini, Ixchelsis, Absorption Pharmaceuticals, NeuroHealing and Plethora.

Competing Interests: Dr. Mcmahon is a consultant, investigator and speaker for Johnson & Johnson, Janssen Cilag, Menarini, Ixchelsis, Absorption Pharmaceuticals, Neurohealing and Plethora.

The second Ad Hoc International Society for Sexual Medicine (ISSM) Committee for the Definition of Premature Ejaculation defined acquired premature ejaculation (PE) as a male sexual dysfunction characterized by a the development of a clinically significant and bothersome reduction in ejaculation latency time in men with previous normal ejaculatory experiences, often to about 3 minutes or less, the inability to delay ejaculation on all or nearly all vaginal penetrations, and the presence of negative personal consequences, such as distress, bother, frustration and/or the avoidance of sexual intimacy. The literature contains a diverse range of biological and psychological etiological theories. Acquired PE is commonly due to sexual performance anxiety, psychological or relationship problems, erectile dysfunction (ED), and occasionally prostatitis and hyperthyroidism, consistent with the predominant organic etiology of acquired PE, men with this complaint are usually older, have a higher mean BMI and a greater incidence of comorbid disease including hypertension, sexual desire disorder, diabetes mellitus, chronic prostatitis, and ED compared to lifelong, variable and subjective PE., Competing Interests: Dr. Mcmahon is a consultant, investigator and speaker for Johnson & Johnson, Janssen Cilag, Menarini, Ixchelsis, Absorption Pharmaceuticals, Neurohealing and Plethora.

Ejaculatory disorders lie along a conceptual continuum with premature ejaculation anchoring one end, normal ejaculation in the center, and difficulties with delayed or anejaculation at the opposite end. Retrograde ejaculation, painful ejaculation, and postorgasmic illness syndrome can occur at any point on the continuum. This manuscript defines the ejaculatory dysfunctions, reviews the anatomy and physiology of orgasm and ejaculation, and summarizes the pharmacological, psychological, and combined treatment approaches to ejaculatory dysfunctions., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Aims: Unexplained falls account for 20% of falls in older cohorts. The role of the implantable loop recorder (ILR) in the detection of arrhythmias in patients with unexplained falls is unknown. We aimed to examine the diagnostic utility of the ILR in detection of arrhythmogenic causes of unexplained falls in older patients., Methods: A single centre, prospective, observational cohort study of recurrent fallers over the age of 50 years with two or more unexplained falls presenting to an emergency department. Insertion of an ILR (Reveal, Medtronic, Minnesota, USA) was used to detect arrhythmia. The primary outcome was detection of cardiac arrhythmia associated with a fall or syncope. The secondary outcome was detection of cardiac arrhythmia independent of falls or syncope, and falls or syncope without associated arrhythmia., Results: Seventy patients, mean age 70 years (51-85 years) received an ILR. In 70% of patients cardiac arrhythmias were detected at a mean time of 47.3 days (SD 48.25). In 20%, falls were attributable to a modifiable cardiac arrhythmia; 10 (14%) received a cardiac pacemaker, 4 (6%) had treatment for supraventricular tachycardia. Patients who had a cardiac arrhythmia detected were more likely to experience a further fall., Conclusions: 14 (20%) patients demonstrated an arrhythmia which was attributable as the cause of their fall. Patients who have cardiac arrhythmia are significantly more likely to experience future falls. Further research is important to investigate if early detection of arrhythmogenic causes of falls using the ILR prevents future falls in older patients., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/)

Introduction: In 2014, the International Society for Sexual Medicine (ISSM) convened a panel of experts to develop an evidence-based process of care for the diagnosis and management of testosterone deficiency (TD) in adult men. The panel considered the definition, epidemiology, etiology, physiologic effects, diagnosis, assessment and treatment of TD. It also considered the treatment of TD in special populations and commented on contemporary controversies about testosterone replacement therapy, cardiovascular risk and prostate cancer., Aim: The aim was to develop clearly worded, practical, evidenced-based recommendations for the diagnosis and treatment of diagnosis and management of TD for clinicians without expertise in endocrinology, such as physicians in family medicine and general urology practice., Method: A comprehensive literature review was performed, followed by a structured, 3-day panel meeting and 6-month panel consultation process using electronic communication. The final guideline was compiled from reports by individual panel members on areas reflecting their special expertise, and then agreed by all through an iterative process., Results: This article contains the report of the ISSM TD Process of Care Committee. It offers a definition of TD and recommendations for assessment and treatment in different populations. Finally, best practice treatment recommendations are presented to guide clinicians, both familiar and unfamiliar with TD., Conclusion: Development of a process of care is an evolutionary process that continually reviews data and incorporates the best new research. We expect that ongoing research will lead to new insights into the pathophysiology of TD, as well as new, efficacious and safe treatments. We recommend that this process of care be reevaluated and updated by the ISSM in 4 years., (© 2015 International Society for Sexual Medicine.)

Introduction: Over the past 20-30 years, the premature ejaculation (PE) treatment paradigm, previously limited to behavioral psychotherapy, has expanded to include drug treatment. Pharmacotherapy for PE predominantly targets the multiple neurotransmitters and receptors involved in the control of ejaculation, which include serotonin, dopamine, oxytocin, norepinephrine, gamma amino-butyric acid (GABA) and nitric oxide (NO)., Aim: The objective of this article is to review current and emerging PE interventions., Methods: Contemporary data on the treatment of PE were reviewed and critiqued using the principles of evidence-based medicine., Main Outcome Measure: Integrated pharmacotherapy and cognitive behavioral therapy (CBT) may achieve superior treatment outcomes in some patients. Phosphodiesterase type 5 inhibitors alone or in combination with selective serotonin reuptake inhibitors (SSRIs) should be limited to men with acquired PE secondary to comorbid erectile dysfunction (ED). New on-demand rapid-acting SSRIs, oxytocin receptor antagonists, or single agents that target multiple receptors may form the foundation of more effective future on-demand medication., Results: Multiple well-controlled evidence-based studies have demonstrated the efficacy and safety of SSRIs in delaying ejaculation, confirming their role as first-line agents for the medical treatment of lifelong and acquired PE. Daily dosing of SSRIs is likely to be associated with superior fold increases in intravaginal ejaculation latency time compared with on-demand SSRIs. On-demand SSRIs are less effective but may fulfill the treatment goals of many patients., Conclusions: Current evidence suggests that psychosexual CBT has a limited role in the contemporary management of PE and confirms the efficacy and safety of dapoxetine, off-label SSRI drugs, and topical anesthetics drugs. Treatment with tramadol, α1-adrenoceptor antagonists cannot be recommended until the results of large, well-designed randomized controlled trials are published in major international peer-reviewed medical journals. As our understanding of the neurochemical control of ejaculation improves, new therapeutic targets and candidate molecules will be identified, which may increase our pharmacotherepeutic armamentarium. McMahon CG. Current and emerging treatments for premature ejaculation. Sex Med Rev 2015;3:183-202., (Copyright © 2015 International Society for Sexual Medicine. Published by Elsevier Inc. All rights reserved.)

Introduction: The International Society for Sexual Medicine (ISSM) Ad Hoc Committee for the Definition of Premature Ejaculation developed the first evidence-based definition for lifelong premature ejaculation (PE) in 2007 and concluded that there were insufficient published objective data at that time to develop a definition for acquired PE., Aim: The aim of this article is to review and critique the current literature and develop a contemporary, evidence-based definition for acquired PE and/or a unified definition for both lifelong and acquired PE., Methods: In April 2013, the ISSM convened a second Ad Hoc Committee for the Definition of Premature Ejaculation in Bangalore, India. The same evidence-based systematic approach to literature search, retrieval, and evaluation used by the original committee was adopted., Results: The committee unanimously agreed that men with lifelong and acquired PE appear to share the dimensions of short ejaculatory latency, reduced or absent perceived ejaculatory control, and the presence of negative personal consequences. Men with acquired PE are older, have higher incidences of erectile dysfunction, comorbid disease, and cardiovascular risk factors, and have a longer intravaginal ejaculation latency time (IELT) as compared with men with lifelong PE. A self-estimated or stopwatch IELT of 3 minutes was identified as a valid IELT cut-off for diagnosing acquired PE. On this basis, the committee agreed on a unified definition of both acquired and lifelong PE as a male sexual dysfunction characterized by (i) ejaculation that always or nearly always occurs prior to or within about 1 minute of vaginal penetration from the first sexual experience (lifelong PE) or a clinically significant and bothersome reduction in latency time, often to about 3 minutes or less (acquired PE); (ii) the inability to delay ejaculation on all or nearly all vaginal penetrations; and (iii) negative personal consequences, such as distress, bother, frustration, and/or the avoidance of sexual intimacy., Conclusion: The ISSM unified definition of lifelong and acquired PE represents the first evidence-based definition for these conditions. This definition will enable researchers to design methodologically rigorous studies to improve our understanding of acquired PE., (© 2014 International Society for Sexual Medicine.)

Introduction: In 2009, the International Society for Sexual Medicine (ISSM) convened a select panel of experts to develop an evidence-based set of guidelines for patients suffering from lifelong premature ejaculation (PE). That document reviewed definitions, etiology, impact on the patient and partner, assessment, and pharmacological, psychological, and combined treatments. It concluded by recognizing the continually evolving nature of clinical research and recommended a subsequent guideline review and revision every fourth year. Consistent with that recommendation, the ISSM organized a second multidisciplinary panel of experts in April 2013, which met for 2 days in Bangalore, India. This manuscript updates the previous guidelines and reports on the recommendations of the panel of experts., Aim: The aim of this study was to develop clearly worded, practical, evidenced-based recommendations for the diagnosis and treatment of PE for family practice clinicians as well as sexual medicine experts., Method: A comprehensive literature review was performed., Results: This article contains the report of the second ISSM PE Guidelines Committee. It offers a new unified definition of PE and updates the previous treatment recommendations. Brief assessment procedures are delineated, and validated diagnostic and treatment questionnaires are reviewed. Finally, the best practices treatment recommendations are presented to guide clinicians, both familiar and unfamiliar with PE, in facilitating treatment of their patients., Conclusion: Development of guidelines is an evolutionary process that continually reviews data and incorporates the best new research. We expect that ongoing research will lead to a more complete understanding of the pathophysiology as well as new efficacious and safe treatments for this sexual dysfunction. We again recommend that these guidelines be reevaluated and updated by the ISSM in 4 years., (© 2014 International Society for Sexual Medicine.)

Ejaculatory dysfunction is a common complaint and is often associated with a reduced quality of life for sufferer and partner. The spectrum of ejaculatory dysfunction extends from premature ejaculation (PE) to delayed ejaculation (DE) and anejaculation. Over the past 20-30 years, the PE treatment paradigm, previously limited to behavioural psychotherapy, has expanded to include drug treatment. Multiple well-controlled, evidence-based studies have demonstrated the efficacy and safety of selective serotonin re-uptake inhibitors in delaying ejaculation, confirming their role as first-line agents for the treatment of lifelong and acquired PE. More recently, there has been increased attention to the psychosocial consequences of PE, its epidemiology, its aetiology and its pathophysiology by both clinicians and the pharmaceutical industry. DE and anejaculation are probably the least common, least studied and least understood of the male sexual dysfunctions. However, their impact is significant as they may result in a lack of sexual fulfilment for both the man and his partner, an effect further compounded when procreation is among the couple's goals of sexual intercourse. The causes of DE, anejaculation and anorgasmia are manifold. Numerous psychotherapeutic treatments are described for the management of delayed or anejaculation. Although some appear to be effective, none has been properly evaluated in large-scale samples. Treatment of DE or anejaculation with pharmacotherapy has met with limited success. No drugs have been approved by regulatory agencies for this purpose, and most drugs that have been identified for potential use have limited efficacy, impart significant side-effects or are yet considered experimental in nature., (© 2014 The Author; Internal Medicine Journal © 2014 Royal Australasian College of Physicians.)

In the past 30 years, advances in basic science have been instrumental in the evolution of the male sexual health treatment paradigm from a psychosexual model to a new model, which includes oral and intracavernosal injection pharmacotherapy, vacuum constriction devices and penile prostheses for the treatment of erectile dysfunction. This progress has coincided with an increased understanding of the nature of male sexual health problems, and epidemiological data that confirm that these problems are widely prevalent and the source of considerable morbidity, both for individuals and within relationships., (© 2014 The Author; Internal Medicine Journal © 2014 Royal Australasian College of Physicians.)

Background: certain medications increase falls risk in older people., Objective: to assess if prescribing modification occurs in older falls presenting to an emergency department (ED)., Design: before-and-after design: presentation to ED with a fall as the index event., Subjects: over 70's who presented to ED with a fall over a 4-year period., Methods: dispensed medication in the 12 months pre- and post-fall was identified using a primary care reimbursement services pharmacy claims database. Screening Tool of Older Person's PIP (STOPP) and Beers prescribing criteria were applied to identify potentially inappropriate prescribing (PIP). Polypharmacy was defined as four or more regular medicines. Psychotropic medication was identified using the WHO Anatomical Therapeutic Chemical classification system. Changes in prescribing were compared using McNemar's test (significance P < 0.05)., Results: One thousand sixteen patients were eligible for analysis; 53.1% had at least one STOPP criteria pre-fall with no change post-fall (53.7%, P = 0.64). Beers criteria were identified in 44.0% pre-fall, with no change post-fall (41.5%, P = 0.125). The most significant individual indicators to change were neuroleptics, which decreased from 17.5 to 14.7% (P = 0.02) and long-acting benzodiazepines decreased from 10.7 to 8.6% (P = 0.005). Polypharmacy was observed in 63% and was strongly predictive of PIP, OR 4.0 (95% CI 3.0, 5.32). A high prevalence of psychotropic medication was identified pre-fall: anxiolytics (15.7%), antidepressants (26%), hypnosedatives (30%). New initiation of anxiolytics and hypnosedatives occurred in 9-15%, respectively, post-fall., Conclusion: a significant prevalence of PIP was observed in older fallers presenting to the ED. No substantial improvements in PIP occurred in the 12 months post-fall, suggesting the need for focused intervention studies to be undertaken in this area.

Introduction: Peyronie's disease (PD) is a localized penile collagen disorder of the tunica albuginea associated with significant physical deformity and psychological impairment. Current understanding of pretreatment characteristics in patients with chronic PD is limited by small samples, varied quality of assessments, and the lack of a PD-specific, validated measure of the psychosexual impact of PD., Aims: Reporting baseline demographic and disease characteristics of the large multinational cohort of subjects with chronic PD who participated in the collagenase clostridium histolyticum (CCH, an investigational intralesional injection and minimally invasive intervention) phase 3 clinical study program. Findings from well-defined assessments, including the Peyronie's Disease Questionnaire (PDQ), the first validated PD-specific patient-reported measure of psychosexual impact, are reported., Methods: Subjects included men≥18 years old with PD symptoms≥12 months and penile deformity between 30° and 90°. Analysis data included demographics, disease history, and psychosexual impact., Main Outcome Measures: Penile deformity, disease symptoms, the International Index of Erectile Function, and the PDQ were assessed., Results: Eight hundred thirty-two subjects were enrolled from 64 sites across the United States and Australia. The mean age was 57.7 years; mean PD duration was 4.1 years. The majority of subjects had penile deformity≤60° (77.3%); mean penile deformity was 50.5°. Subjects reported having intercourse a mean of 10.2 times in the previous 3 months, 70.8% reported difficulty in performing vaginal intercourse, and 80.4% reported less frequent vaginal intercourse. Approximately 71.5% of subjects with severe (>60°) and 58.1% of subjects with mild/moderate (≤60°) penile deformity were "very bothered" or "extremely bothered" upon last look at their erect penis (P=0.0041), as measured by the PDQ., Conclusions: These data add to the body of knowledge regarding the clinical impact of chronic phase PD, including the PD-specific patient-reported psychosexual symptoms, using a large multinational chronic PD cohort in the CCH phase 3 clinical program., (© 2013 International Society for Sexual Medicine.)

Introduction: Men with comorbid erectile dysfunction (ED) and premature ejaculation (PE) may be concomitantly prescribed a phosphodiesterase type 5 (PDE5) inhibitor and dapoxetine., Aim: Evaluate efficacy and safety of dapoxetine 30 mg and 60 mg on demand (prn) in men with PE and ED who were being treated with PDE5 inhibitors., Methods: This randomized, double-blind, placebo-controlled, flexible-dose, multicenter study enrolled men ≥18 years who met diagnostic criteria for PE including intravaginal ejaculatory latency time (IELT) of ≤2 minutes in ≥75% of sexual intercourse episodes; were on stable regimen of a PDE5 inhibitor; and had International Index of Erectile Function-erectile function domain score ≥21. Subjects received placebo, dapoxetine 30 mg, or dapoxetine 60 mg prn (1-3 hours before intercourse) for 12 weeks., Main Outcome Measure: Stopwatch-measured average IELT, Clinical Global Impression of Change (CGIC) in PE, Premature Ejaculation Profile (PEP), and treatment-emergent adverse events (TEAEs)., Results: Of 495 subjects randomized, 429 completed the study. Arithmetic mean average IELT significantly increased with dapoxetine vs. placebo at end point (5.2 vs. 3.4 minutes) and weeks 4, 8, and 12 (P ≤ 0.002 for all). Men who described their PE at least "better" using the CGIC were significantly greater with dapoxetine vs. placebo at end point (56.5% vs. 35.4%) and weeks 4, 8, and 12 (P ≤ 0.001 for all). Significantly better outcomes were also reported with dapoxetine vs. placebo on PEP measures. Incidence of TEAEs was 20.0% and 29.6% in placebo- and dapoxetine-treated subjects, respectively (P = 0.0135). TEAEs led to discontinuation in 1.6% of subjects in both groups. Most frequent TEAEs were known adverse drug reactions of dapoxetine treatment including nausea (9.2%), headache (4.4%), diarrhea (3.6%), dizziness (2.4%), and dizziness postural (2.4%)., Conclusions: In men with PE and comorbid ED on a stable regimen of PDE5 inhibitor, dapoxetine provided meaningful treatment benefit and was generally well tolerated., (© 2013 Janssen Pharmaceutical Research & Development, LLC. Journal of Sexual Medicine © 2013 International Society for Sexual Medicine.)

Purpose: IMPRESS (Investigation for Maximal Peyronie's Reduction Efficacy and Safety Studies) I and II examined the clinical efficacy and safety of collagenase Clostridium histolyticum intralesional injections in subjects with Peyronie disease. Co-primary outcomes in these identical phase 3 randomized, double-blind, placebo controlled studies included the percent change in the penile curvature abnormality and the change in the Peyronie disease questionnaire symptom bother score from baseline to 52 weeks., Materials and Methods: IMPRESS I and II examined collagenase C. histolyticum intralesional injections in 417 and 415 subjects, respectively, through a maximum of 4 treatment cycles, each separated by 6 weeks. Men received up to 8 injections of 0.58 mg collagenase C. histolyticum, that is 2 injections per cycle separated by approximately 24 to 72 hours with the second injection of each followed 24 to 72 hours later by penile plaque modeling. Men were stratified by baseline penile curvature (30 to 60 vs 61 to 90 degrees) and randomized to collagenase C. histolyticum or placebo 2:1 in favor of the former., Results: Post hoc meta-analysis of IMPRESS I and II data revealed that men treated with collagenase C. histolyticum showed a mean 34% improvement in penile curvature, representing a mean ± SD -17.0 ± 14.8 degree change per subject, compared with a mean 18.2% improvement in placebo treated men, representing a mean -9.3 ± 13.6 degree change per subject (p <0.0001). The mean change in Peyronie disease symptom bother score was significantly improved in treated men vs men on placebo (-2.8 ± 3.8 vs -1.8 ± 3.5, p = 0.0037). Three serious adverse events (corporeal rupture) were surgically repaired., Conclusions: IMPRESS I and II support the clinical efficacy and safety of collagenase C. histolyticum for the physical and psychological aspects of Peyronie disease., (Copyright © 2013 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.)

Introduction: Ejaculatory/orgasmic disorders are common male sexual dysfunctions and include premature ejaculation (PE), inhibited ejaculation, anejaculation, retrograde ejaculation, and anorgasmia., Aim: To provide recommendations and guidelines of the current state-of-the-art knowledge for management of ejaculation/orgasmic disorders in men as standard operating procedures (SOPs) for the treating health care professional., Methods: The International Society of Sexual Medicine Standards Committee assembled over 30 multidisciplinary experts to establish SOPs for various male and female sexual medicine topics. The SOP for the management of disorders of orgasm and ejaculation represents the opinion of four experts from four countries developed in a process over a 2-year period., Main Outcome Measure: Expert opinion was based on grading of evidence-based medical literature, limited expert opinion, widespread internal committee discussion, public presentation, and debate., Results: PE management is largely dependent upon etiology. Lifelong PE is best managed with PE pharmacotherapy (selective serotonin reuptake inhibitors and/or topical anesthetics). The management of acquired PE is etiology specific and may include erectile dysfunction (ED) pharmacotherapy in men with comorbid ED. All men seeking treatment for PE should receive basic psychosexual education. Graded behavioral therapy is indicated when psychogenic or relationship factors are present and is often best combined with PE pharmacotherapy in an integrated treatment program. Delayed ejaculation, anejaculation, and/or anorgasmia may have a biogenic and/or psychogenic etiology. Men with age-related penile hypoanesthesia should be educated, reassured, and instructed in revised sexual techniques which maximize arousal. Retrograde ejaculation is managed by education, patient reassurance, and pharmacotherapy., Conclusions: Additional research is required to further the understanding of the disorders of ejaculation and orgasm., (© 2012 International Society for Sexual Medicine.)

Premature ejaculation (PE) is a common male sexual disorder which is associated with substantial personal and interpersonal negative psychological consequences. Pharmacotherapy of PE with off-label antidepressant selective serotonin reuptake inhibitors (SSRIs) is common, effective and safe. Development and regulatory approval of drugs specifically for the treatment of PE will reduce reliance on off-label treatments and serve to fill an unmet treatment need. The objective of this article is to review evidence supporting the efficacy and safety of dapoxetine in the treatment of PE. MEDLINE, Web of Science, PICA, EMBASE and the proceedings of major international and regional scientific meetings were searched for publications or abstracts published during the period 1993-2012 that used the word 'dapoxetine' in the title, abstract or keywords. This search was then manually cross referenced for all papers. This review encompasses studies of dapoxetine pharmacokinetics, animal studies, human phase I, II and III studies, independent postmarketing and pharmacovigilance efficacy and safety studies and drug-interaction studies. Dapoxetine is a potent SSRI which is administered on demand 1-3 h prior to planned sexual contact. It is rapidly absorbed and eliminated, resulting in minimal accumulation, and has dose-proportional pharmacokinetics which are unaffected by multiple dosing. Dapoxetine 30 mg and 60 mg has been evaluated in five industry-sponsored randomized, double-blind, placebo-controlled studies in 6081 men aged at least 18 years. Outcome measures included stopwatch-measured intravaginal ejaculatory latency time (IELT), Premature Ejaculation Profile (PEP) inventory items, Clinical Global Impression of Change (CGIC) in PE, and adverse events. Mean IELT, all PEP items and CGIC improved significantly with both doses of dapoxetine versus placebo (all p <0.001). The most common treatment-related adverse effects included nausea (11.0% for 30 mg, 22.2% for 60 mg), dizziness (5.9% for 30 mg, 10.9% for 60 mg), and headache (5.6% for 30 mg, 8.8% for 60 mg), and evaluation of validated rated scales demonstrated no SSRI class-related effects with dapoxetine use. Dapoxetine, as the first drug developed for PE, is an effective and safe treatment for PE and represents a major advance in sexual medicine.

Objective: The aim of this study was to evaluate the diagnostic efficacy of multiple tests-heart-type fatty acid-binding protein (H-FABP), cardiac troponin I (cTnI), creatine kinase-MB, and myoglobin-for the early detection of acute myocardial infarction among patients who present to the emergency department with chest pain., Methods: A total of 1128 patients provided a total of 2924 venous blood samples. Patients with chest pain were nonselected and treated according to hospital guidelines. Additional cardiac biomarkers were assayed simultaneously at serial time points using the Cardiac Array (Randox Laboratories Ltd, Crumlin, United Kingdom)., Results: Heart-type fatty acid-binding protein had the greatest sensitivity at 0 to 3 hours (64.3%) and 3 to 6 hours (85.3%) after chest pain onset. The combination of cTnI measurement with H-FABP increased sensitivity to 71.4% at 3 to 6 hours and 88.2% at 3 to 6 hours. Receiver operating characteristic curves demonstrated that H-FABP had the greatest diagnostic ability with area under the curve at 0 to 3 hours of 0.841 and 3 to 6 hours of 0.894. The specificity was also high for the combination of H-FABP with cTnI at these time points. Heart-type fatty acid-binding protein had the highest negative predictive values of all the individual markers: 0 to 3 hours (93%) and 3 to 6 hours (97%). Again, the combined measurement of cTnI with H-FABP increased the negative predictive values to 94% at 0 to 3 hours, 98% at 3 to 6 hours, and 99% at 6 to 12 hours., Conclusion: Testing both H-FABP and cTnI using the Cardiac Array proved to be both a reliable diagnostic tool for the early diagnosis of myocardial infarction/acute coronary syndrome and also a valuable rule-out test for patients presenting at 3 to 6 hours after chest pain onset., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Introduction: Premature ejaculation (PE) is a common male sexual dysfunction. The prevalence of PE in the Asia-Pacific region has not been comprehensively studied., Aim: The aim of this study is to evaluate PE prevalence in nine Asia-Pacific countries and the impact of PE on sufferers., Methods: A random sample of heterosexual males aged 18-65 years in a stable sexual relationship currently or in the past 2 years completed a 48-question survey by computer-assisted interviewing, online, or in-person; the survey and recruitment methodologies varied by location. The survey included demographic questions, the five-question Premature Ejaculation Diagnostic Tool (PEDT), the five-question Sexual Health Inventory for Men (SHIM), and the 10-question Index of Premature Ejaculation (IPE). Separately, men self-reported having PE (lifelong or acquired) or erectile dysfunction (ED)., Main Outcome Measures: The PEDT was used to diagnose PE or probable PE; the SHIM was used to diagnose ED; and the IPE was used to assess respondent's attitudes toward PE., Results: Of the 4,997 men who completed the survey, the prevalences of PEDT-diagnosed PE, PEDT-diagnosed probable PE, and self-reported PE were 16%, 15%, and 13%, respectively. Less than half of men with PEDT-diagnosed PE (N = 816) or probable PE (N = 738) self-reported the condition (40% and 19%, respectively), and 6% of men with a PEDT diagnosis of no PE self-reported PE. In contrast, more respondents self-reported ED (8%) than had SHIM-diagnosed moderate or severe ED (5%). IPE responses indicated that 45%, 46%, and 23% of men with PEDT-diagnosed PE were somewhat or very dissatisfied with the length of intercourse before ejaculation, their control over ejaculation, and with sexual intercourse, respectively., Conclusions: In this study, PE was more prevalent than ED in the Asia-Pacific countries surveyed, but only 40% of men with PEDT-diagnosed PE self-reported PE., (© 2011 International Society for Sexual Medicine.)

Background: The prevalence of older trauma patients is rising in Westernised populations. Age has an independent adverse affect on survival from injury. Factors contributing to this increased mortality are incompletely understood., Objective: To examine the independent effects of age, time and mechanism of injury on survival from trauma at 30 days., Methods: We analysed prospectively collected data from the Trauma Audit and Research Network database. Isolated femoral neck and pubic rami fractures are not included in this data set. Univariate and multivariate regression analyses were undertaken. Independent effects of age, time of injury and mechanism of injury on survival following trauma were evaluated., Results: A total of 137,521 trauma patients were included in the study. Trauma victims aged over 65 years had increased odds of death of 9.58 (95% CI: 8.78-10.45), adjusting for known confounders of outcome. Analysis of two-way interactions of age and time of arrival to hospital, revealed patients ≥65 years had a higher odds of death if they presented between midnight and 8 a.m., compared with 08:00-16:00 h; OR = 1.5, (95% CI: 1.29-1.73). Further analysis of this older group, examining the interaction of time and mechanism of injury, revealed a doubling of the odds of death in patients injured following a fall <2 m, when they presented between midnight and 8 a.m.; OR = 2.1, (95% CI: 1.32-3.30). This diurnal variation in mortality was exclusive to older fallers., Conclusions: Age over 65 years has an independent detrimental affect on survival from trauma. A distinct diurnal variation in mortality from injury occurs in older patients injured as a result of a low velocity fall.

Introduction: New diagnostic criteria for lifelong premature ejaculation (PE) have been proposed by the International Society of Sexual Medicine (ISSM), including an intravaginal ejaculatory latency time (IELT) of less than about 1 minute, lack of control over ejaculation, and PE-related distress or bother., Aim: The aim of this study was to review evidence supporting the efficacy and safety of oral agents for the treatment of PE in the context of the new ISSM criteria., Methods: The PubMed database was searched for randomized, double-blind, placebo-controlled studies of oral agents in PE that included stopwatch measurements of IELT., Main Outcome Measures: The main outcome measure used for this study was a review of the efficacy and safety data of oral agents for PE aligned with ISSM criteria., Results: Since the latest meta-analyses using similar criteria (conducted in 2004 and 2005 for selective serotonin reuptake inhibitors [SSRIs] and phosphodiesterase type 5 [PDE-5] inhibitors, respectively), eight studies evaluated SSRIs vs. placebo, one compared SSRIs, two evaluated PDE-5 inhibitors, and one evaluated an SSRI/PDE-5 inhibitor combination. New agents included dapoxetine (five studies) and tramadol (one study). Six studies enrolled men who met an approximation of the ISSM criteria. Although evidence suggests that most SSRIs, tramadol, and dapoxetine increase IELT to varying degrees, few studies included control over ejaculation and PE-related distress or bother as enrollment criteria or used validated patient-reported outcome instruments to evaluate these parameters. Among studies that provided comprehensive adverse event data, safety and tolerability observations in men with PE were generally similar to those observed in other populations; however, with the exception of dapoxetine, known SSRI-class effects (e.g., withdrawal syndrome) were not evaluated in men with PE., Conclusions: This systematic review of well-controlled clinical trials in PE has demonstrated that while many oral agents, particularly SSRIs, tramadol, and dapoxetine, have proven effective and safe for the treatment of men with PE, few have been evaluated for their effects on the specific elements of the ISSM criteria., (© 2011 International Society for Sexual Medicine.)

Introduction: Premature ejaculation (PE) is a common male sexual disorder which is associated with substantial personal and interpersonal negative psychological factors. Pharmacotherapy of PE with off-label antidepressant SSRI drugs is common. Development and regulatory approval of drugs specifically for the treatment of PE will reduce reliance on off-label treatments and serve to fill a unmet treatment need., Aim: To review evidence supporting the efficacy and safety of dapoxetine in the treatment of PE., Methods: MEDLINE and the proceedings of major international and regional scientific meetings during the period 1994-2010 were searched for publications or abstracts using the word dapoxetine in the title, abstract or keywords. This search was then manually cross-referenced for all papers. This review encompasses studies of dapoxetine pharmacokinetics, animal studies, human phase 1, 2 and 3 efficacy and safety studies and drug-interaction studies., Results: Dapoxetine is a potent selective serotonin re-uptake inhibitor, which is administered on-demand 1-3 hours prior to planned sexual contact. Dapoxetine is rapidly absorbed and eliminated, resulting in minimal accumulation and has dose-proportional pharmacokinetics, which are unaffected by multiple dosing. Dapoxetine 30 mg and 60 mg has been evaluated in 5 randomized, double-blind, placebo-controlled studies in 6081 men aged ≥18 years. Outcome measures included stopwatch-measured intravaginal ejaculatory latency time (IELT), Premature Ejaculation Profile (PEP) inventory items, clinical global impression of change (CGIC) in PE, and adverse events. Mean IELT, all PEP items and CGIC improved significantly with both doses of dapoxetine vs. placebo (P < 0.001 for all). The most common treatment related adverse effects included nausea (11.0% for 30 mg, 22.2% for 60 mg), dizziness (586% for 30 mg, 10.9% for 60 mg), and headache (5.6% for 30 mg, 8.8% for 60 mg), and evaluation of validated rated scales demonstrated no SSRI class-related effects with dapoxetine use., Conclusion: Dapoxetine, as the first drug developed for PE, is an effective and safe treatment for PE and represents a major advance in sexual medicine.

Introduction: Dapoxetine has been evaluated for the on-demand treatment of premature ejaculation (PE) in five phase 3 studies in various populations worldwide and has recently been approved in several countries., Aim: To present integrated efficacy and safety data from phase 3 trials of dapoxetine., Methods: Data were from five randomized, multicenter, double-blind, placebo-controlled studies conducted in over 25 countries. Men (N=6,081)≥18 years who met the Diagnostic and Statistical Manual of Mental Disorders, fourth edition, text revision criteria for PE; four studies required a baseline intravaginal ejaculatory latency time (IELT) of ≤2 minutes. Dapoxetine 30 and 60 mg on demand (prn; 1-3 hours before intercourse) were evaluated for either 12 or 24 weeks in four studies; one study evaluated dapoxetine 60 mg daily (qd; included in safety assessments only) or prn for 9 weeks., Main Outcome Measures: End points included stopwatch-measured IELT, Premature Ejaculation Profile (PEP) items, clinical global impression of change (CGIC) in PE, and adverse events (AEs)., Results: Average IELT (mean [standard deviation], geometric mean [standard error]) increased from baseline (across groups, 0.9 [0.49] minutes, 0.8 [1.01] minutes) to a significantly greater extent with dapoxetine 30 (3.1 [3.91] minutes, 2.0 [1.03] minutes) and 60 mg (3.6 [3.85] minutes, 2.3 [1.03] minutes) vs. placebo (1.9 [2.43] minutes, 1.3 [1.02] minutes; P<0.001 for all) at week 12 (geometric mean fold increase, 2.5, 3.0, and 1.6, respectively). All PEP items and CGIC improved significantly with both doses of dapoxetine vs. placebo (P<0.001 for all). The most common AEs included nausea, dizziness, and headache, and evaluation of validated instruments demonstrated no anxiety, akathisia, suicidality, or changes in mood with dapoxetine use and no discontinuation syndrome following abrupt withdrawal., Conclusions: In this diverse population, dapoxetine significantly improved all aspects of PE and was generally well tolerated., (© 2010 International Society for Sexual Medicine.)

The integrity of the arterial baroreflex is central to cardiovascular homeostasis. There is evidence of altered cardiovascular regulation after acute traumatic brain injury (TBI). We hypothesized that arterial baroreflex is modified by acute TBI. An experimental study using 18 terminally anesthetized male Wistar rats weighing 240 to 260 g was undertaken at a university laboratory setting. Brain injury was induced using the lateral fluid percussion brain injury model. The fluid percussion device delivered an applied cortical pressure of 1.2 atm and 1.8 atm, producing mild and moderate TBI, respectively. Control animals underwent identical surgical procedures but no applied cortical pressure. Arterial baroreflex was assessed by determining the relationship between heart period (R - R interval) and systolic blood pressure using the modified phenylephrine pressor test adapted for the rat. The arterial baroreflex was tested before (Tcon), post-TBI, at 10 min (T10), and 30 min (T30). Analysis of baroreflex function after moderate TBI using repeated-measures analysis of variance revealed significant differences in baroreflex sensitivity (BRS) at T10 and T30 (F2,15 = 10.18; P = 0.005) compared with pre-TBI (weighted mean ± SD; Tcon, 0.39 ± 0.00 ms mmHg; T10, 0.85 ± 0.01 ms mmHg; T30, 0.81 ± 0.01 ms mmHg). The changes in BRS were not significant after mild TBI (P = 0.152). Repeated-measures analysis of variance comparing trends between the three groups indicated significant differences between the control and moderate TBI groups only (F2,15 = 6.26; P = 0.01). Acute TBI of moderate severity is associated with an early significant modification in arterial BRS. This is a key component of cardiovascular homeostasis. The clinical implications of this observation require further investigation.

Background: Syncope is a common clinical problem accounting for up to 6% of hospital admissions. Little is known about resource utilisation for patients admitted for syncope management in Ireland., Aim: To determine the utilisation of resources for patients admitted for syncope management., Methods: Single centre observational case series of consecutive adult patients presenting to an acute hospital Emergency Department with syncope over a 5-month period., Results: Two-hundred and fourteen of 18,898 patients (1.1%) had a syncopal episode, 110 (51.4%) of whom were admitted. Mean length of stay was 6.9 days. Sixty-four of these admissions were deemed unnecessary by retrospective review when compared to ESC guidelines. Eighty-five (77.3%) admitted patients had cardiac investigations and 56 (51%) had brain imaging performed., Conclusions: Syncope places a large demand on overstretched hospital resources. Most cases can be managed safely as an outpatient and to facilitate this, hospitals should develop outpatient Syncope Management Units.

Background: Shock index (SI) is recognized to be a more reliable early indicator of hemorrhage than traditional vital signs. Acute traumatic brain injury (TBI) can be associated with autonomic uncoupling and may therefore alter the reliability of SI in patients with combined TBI and peripheral hemorrhage. The aim of this study was to evaluate the performance of SI when acute TBI of mild and moderate severity were associated with progressive simple hemorrhage., Methods: This study was undertaken in a laboratory setting. Brian injury was induced using the lateral fluid percussion model in anesthetized rats. The fluid percussion device delivered an applied cortical pressure of 1.2 atm and 1.8 atm, producing mild and moderate TBI, respectively. Control animals underwent identical procedures but with no applied cortical pressure. Hemorrhage was induced 10 minutes after brain injury, at a rate of 2% of blood volume per minute until 40% blood volume was withdrawn., Results: The SI response to increasing volume of hemorrhage was unaltered when control and mild TBI groups were compared (test of interaction p = 0.39). There was a 50% mortality rate observed 20 to 60 minutes after hemorrhage in the moderate TBI group. The SI response to hemorrhage in the moderate TBI group compared with the control group became significantly different at 40% blood volume loss (test of interaction p = 0.048). Comparison of the SI response with hemorrhage between survivors and nonsurvivors of moderate TBI revealed a significant difference (p = 0.007). SI was markedly attenuated in the presence of increasing hemorrhage in the nonsurvivor subgroup of moderate TBI., Conclusions: SI significantly underestimated underlying hemorrhage in the presence of acute TBI of moderate severity where attenuation of the biphasic heart rate and blood pressure response was also most pronounced.