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

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

Chuanxiongzine relaxes isolated corpus cavernosum strips and raises intracavernous pressure in rabbits

It has been shown that there are many Chinese traditional herbals that can enhance sexual activity. Chuanxiongzine is a vasoactive ingredient that has been isolated and purified from Ligusticum chuanxiong Hort. In previous studies, it has been found that chuanxiongzine was effective in relaxing rabbit corpus cavernosum smooth muscle. We determined the effects of chuanxiongzine on relaxation of isolated corpus cavernosum strips in vitro and on increase of intracavernous pressure (ICP) in vivo in rabbits. Chuanxiongzine caused a concentration-dependent relaxation of phenylephrine precontracted isolated corpus cavernosum strips (EC50 1.58 × 10−4 mol l−1), which were endothelium independent and NO independent. However, the guanylyl cyclase inhibitor 1-H-[1,2,4] oxadiazolo [4,3-a] quinoxalin-1-one significantly shifted the chuanxiongzine concentration–response relationship to the right. Although there was no significant difference in the level of cyclic guanosine monophosphate (cGMP) and cyclic adenosine monophosphate (cAMP) in isolated corpus cavernosum strips treated with chuanxiongzine or vehicle, chuanxiongzine caused a significant rise in the level of cGMP and cAMP in isolated corpus cavernosum strips pretreated with the activator of adenylyl cyclase forskolin and the source of NO sodium nitroprusside. In an in vivo study, chuanxiongzine dose-dependently raised ICP after the intracavernous injection of its cumulative doses (0.5, 1, 2 and 5 mg kg−1). The ICP increased from baseline to 19.1±3.7, 24.8±2.1, 30.2±4.8 and 39.7±6.1 mm Hg, respectively, and the duration of tumescence ranged from 8.5±2.8 to 22.9±7.3 min. Our results show that chuanxiongzine can relax isolated corpus cavernosum strips of rabbits in vitro and increase ICP of rabbits in vivo, which is neither endothelium dependent nor NO dependent, but may be partly mediated by the inhibition of cAMP phosphodiesterase or cGMP phosphodiesterase

Antimicrobial resistance among migrants in Europe: a systematic review and meta-analysis

BACKGROUND: Rates of antimicrobial resistance (AMR) are rising globally and there is concern that increased migration is contributing to the burden of antibiotic resistance in Europe. However, the effect of migration on the burden of AMR in Europe has not yet been comprehensively examined. Therefore, we did a systematic review and meta-analysis to identify and synthesise data for AMR carriage or infection in migrants to Europe to examine differences in patterns of AMR across migrant groups and in different settings. METHODS: For this systematic review and meta-analysis, we searched MEDLINE, Embase, PubMed, and Scopus with no language restrictions from Jan 1, 2000, to Jan 18, 2017, for primary data from observational studies reporting antibacterial resistance in common bacterial pathogens among migrants to 21 European Union-15 and European Economic Area countries. To be eligible for inclusion, studies had to report data on carriage or infection with laboratory-confirmed antibiotic-resistant organisms in migrant populations. We extracted data from eligible studies and assessed quality using piloted, standardised forms. We did not examine drug resistance in tuberculosis and excluded articles solely reporting on this parameter. We also excluded articles in which migrant status was determined by ethnicity, country of birth of participants' parents, or was not defined, and articles in which data were not disaggregated by migrant status. Outcomes were carriage of or infection with antibiotic-resistant organisms. We used random-effects models to calculate the pooled prevalence of each outcome. The study protocol is registered with PROSPERO, number CRD42016043681. FINDINGS: We identified 2274 articles, of which 23 observational studies reporting on antibiotic resistance in 2319 migrants were included. The pooled prevalence of any AMR carriage or AMR infection in migrants was 25·4% (95% CI 19·1-31·8; I2 =98%), including meticillin-resistant Staphylococcus aureus (7·8%, 4·8-10·7; I2 =92%) and antibiotic-resistant Gram-negative bacteria (27·2%, 17·6-36·8; I2 =94%). The pooled prevalence of any AMR carriage or infection was higher in refugees and asylum seekers (33·0%, 18·3-47·6; I2 =98%) than in other migrant groups (6·6%, 1·8-11·3; I2 =92%). The pooled prevalence of antibiotic-resistant organisms was slightly higher in high-migrant community settings (33·1%, 11·1-55·1; I2 =96%) than in migrants in hospitals (24·3%, 16·1-32·6; I2 =98%). We did not find evidence of high rates of transmission of AMR from migrant to host populations. INTERPRETATION: Migrants are exposed to conditions favouring the emergence of drug resistance during transit and in host countries in Europe. Increased antibiotic resistance among refugees and asylum seekers and in high-migrant community settings (such as refugee camps and detention facilities) highlights the need for improved living conditions, access to health care, and initiatives to facilitate detection of and appropriate high-quality treatment for antibiotic-resistant infections during transit and in host countries. Protocols for the prevention and control of infection and for antibiotic surveillance need to be integrated in all aspects of health care, which should be accessible for all migrant groups, and should target determinants of AMR before, during, and after migration. FUNDING: UK National Institute for Health Research Imperial Biomedical Research Centre, Imperial College Healthcare Charity, the Wellcome Trust, and UK National Institute for Health Research Health Protection Research Unit in Healthcare-associated Infections and Antimictobial Resistance at Imperial College London

Counseling patients about sexual health when considering post-prostatectomy radiation treatment

Prostate cancer is the second most frequently diagnosed cancer in men in the United States. Many men with clinically localized prostate cancer survive for 15 years or more. Although early detection and successful definitive treatments are increasingly common, a debate regarding how aggressively to treat prostate cancer is ongoing because of the effect of aggressive treatment on the quality of life, including sexual functioning. We examined current research on the effect of post-prostatectomy radiation treatment on sexual functioning, and suggest a way in which patient desired outcomes might be taken into consideration while making decisions with regard to the timing of radiation therapy after prostatectomy

Surgical site infection after gastrointestinal surgery in high-income, middle-income, and low-income countries: a prospective, international, multicentre cohort study

Background: Surgical site infection (SSI) is one of the most common infections associated with health care, but its importance as a global health priority is not fully understood. We quantified the burden of SSI after gastrointestinal surgery in countries in all parts of the world. Methods: This international, prospective, multicentre cohort study included consecutive patients undergoing elective or emergency gastrointestinal resection within 2-week time periods at any health-care facility in any country. Countries with participating centres were stratified into high-income, middle-income, and low-income groups according to the UN's Human Development Index (HDI). Data variables from the GlobalSurg 1 study and other studies that have been found to affect the likelihood of SSI were entered into risk adjustment models. The primary outcome measure was the 30-day SSI incidence (defined by US Centers for Disease Control and Prevention criteria for superficial and deep incisional SSI). Relationships with explanatory variables were examined using Bayesian multilevel logistic regression models. This trial is registered with ClinicalTrials.gov, number NCT02662231. Findings: Between Jan 4, 2016, and July 31, 2016, 13 265 records were submitted for analysis. 12 539 patients from 343 hospitals in 66 countries were included. 7339 (58·5%) patient were from high-HDI countries (193 hospitals in 30 countries), 3918 (31·2%) patients were from middle-HDI countries (82 hospitals in 18 countries), and 1282 (10·2%) patients were from low-HDI countries (68 hospitals in 18 countries). In total, 1538 (12·3%) patients had SSI within 30 days of surgery. The incidence of SSI varied between countries with high (691 [9·4%] of 7339 patients), middle (549 [14·0%] of 3918 patients), and low (298 [23·2%] of 1282) HDI (p < 0·001). The highest SSI incidence in each HDI group was after dirty surgery (102 [17·8%] of 574 patients in high-HDI countries; 74 [31·4%] of 236 patients in middle-HDI countries; 72 [39·8%] of 181 patients in low-HDI countries). Following risk factor adjustment, patients in low-HDI countries were at greatest risk of SSI (adjusted odds ratio 1·60, 95% credible interval 1·05–2·37; p=0·030). 132 (21·6%) of 610 patients with an SSI and a microbiology culture result had an infection that was resistant to the prophylactic antibiotic used. Resistant infections were detected in 49 (16·6%) of 295 patients in high-HDI countries, in 37 (19·8%) of 187 patients in middle-HDI countries, and in 46 (35·9%) of 128 patients in low-HDI countries (p < 0·001). Interpretation: Countries with a low HDI carry a disproportionately greater burden of SSI than countries with a middle or high HDI and might have higher rates of antibiotic resistance. In view of WHO recommendations on SSI prevention that highlight the absence of high-quality interventional research, urgent, pragmatic, randomised trials based in LMICs are needed to assess measures aiming to reduce this preventable complication

Impact of COVID-19 on cardiovascular testing in the United States versus the rest of the world

Objectives: This study sought to quantify and compare the decline in volumes of cardiovascular procedures between the United States and non-US institutions during the early phase of the coronavirus disease-2019 (COVID-19) pandemic. Background: The COVID-19 pandemic has disrupted the care of many non-COVID-19 illnesses. Reductions in diagnostic cardiovascular testing around the world have led to concerns over the implications of reduced testing for cardiovascular disease (CVD) morbidity and mortality. Methods: Data were submitted to the INCAPS-COVID (International Atomic Energy Agency Non-Invasive Cardiology Protocols Study of COVID-19), a multinational registry comprising 909 institutions in 108 countries (including 155 facilities in 40 U.S. states), assessing the impact of the COVID-19 pandemic on volumes of diagnostic cardiovascular procedures. Data were obtained for April 2020 and compared with volumes of baseline procedures from March 2019. We compared laboratory characteristics, practices, and procedure volumes between U.S. and non-U.S. facilities and between U.S. geographic regions and identified factors associated with volume reduction in the United States. Results: Reductions in the volumes of procedures in the United States were similar to those in non-U.S. facilities (68% vs. 63%, respectively; p = 0.237), although U.S. facilities reported greater reductions in invasive coronary angiography (69% vs. 53%, respectively; p < 0.001). Significantly more U.S. facilities reported increased use of telehealth and patient screening measures than non-U.S. facilities, such as temperature checks, symptom screenings, and COVID-19 testing. Reductions in volumes of procedures differed between U.S. regions, with larger declines observed in the Northeast (76%) and Midwest (74%) than in the South (62%) and West (44%). Prevalence of COVID-19, staff redeployments, outpatient centers, and urban centers were associated with greater reductions in volume in U.S. facilities in a multivariable analysis. Conclusions: We observed marked reductions in U.S. cardiovascular testing in the early phase of the pandemic and significant variability between U.S. regions. The association between reductions of volumes and COVID-19 prevalence in the United States highlighted the need for proactive efforts to maintain access to cardiovascular testing in areas most affected by outbreaks of COVID-19 infection

Efficacy and safety of pomegranate juice on improvement of erectile dysfunction in male patients with mild to moderate erectile dysfunction: a randomized, placebo-controlled, double-blind, crossover study,”

This randomized-controlled trial examined the efficacy of wonderful variety pomegranate juice versus placebo in improving erections in 53 completed subjects with mild to moderate erectile dysfunction. The crossover design consisted of two 4-week treatment periods separated by a 2-week washout. Efficacy was assessed using International Index of Erectile Function (IIEF) and Global Assessment Questionnaires (GAQ). Of the 42 subjects who demonstrated improvement in GAQ scores after beverage consumption, 25 reported improvement after drinking pomegranate juice. Further, 17 subjects showed preference of one beverage to the other. Subjects were more likely to have improved scores when pomegranate juice was consumed (P ¼ 0.058). Although overall statistical significance was not achieved, this pilot study suggests the possibility that larger cohorts and longer treatment periods may achieve statistical significance