A systematic review of clinical trials of pharmacological interventions for acute ischaemic stroke (1955-2008) that were completed, but not published in full

<p>Abstract</p> <p>Background</p> <p>We assessed the prevalence, and potential impact of, trials of pharmacological agents for acute stroke that were completed but not published in full. Failure to publish trial data is to be deprecated as it sets aside the altruism of participants' consent to be exposed to the risks of experimental interventions, potentially biases the assessment of the effects of therapies, and may lead to premature discontinuation of research into promising treatments.</p> <p>Methods</p> <p>We searched the Cochrane Stroke Group's Specialised Register of Trials in June 2008 for completed trials of pharmacological interventions for acute ischaemic stroke, and searched MEDLINE and EMBASE (January 2007 - March 2009) for references to recent full publications. We assessed trial completion status from trial reports, online trials registers and correspondence with experts.</p> <p>Results</p> <p>We identified 940 trials. Of these, 125 (19.6%, 95% confidence interval 16.5-22.6) were completed but not published in full by the point prevalence date. They included 16,058 participants (16 trials had over 300 participants each) and tested 89 different interventions. Twenty-two trials with a total of 4,251 participants reported the number of deaths. In these trials, 636/4251 (15.0%) died.</p> <p>Conclusions</p> <p>Our data suggest that, at the point prevalence date, a substantial body of evidence that was of relevance both to clinical practice in acute stroke and future research in the field was not published in full. Over 16,000 patients had given informed consent and were exposed to the risks of therapy. Responsibility for non-publication lies with investigators, but pharmaceutical companies, research ethics committees, journals and governments can all encourage the timely publication of trial data.</p

European Association of Urology Guidelines on Vasectomy

Context: The European Association of Urology presents its guidelines for vasectomy. Vasectomy is highly effective, but problems can arise that are related to insufficient preoperative patient information, the surgical procedure, and postoperative follow-up. Objective: These guidelines aim to provide information and recommendations for physicians who perform vasectomies and to promote the provision of adequate information to the patient before the operation to prevent unrealistic expectations and legal procedures. Evidence acquisition: An extensive review of the literature was carried out using Medline, Embase, and the Cochrane Database of Systematic Reviews from 1980 to 2010. The focus was on randomised controlled trials (RCTs) and meta-analyses of RCTs (level 1 evidence) and on well-designed studies without randomisation (level 2 and 3 evidence). A total of 113 unique records were identified for consideration. Non-English language publications were excluded as well as studies published as abstracts only Evidence synthesis: The guidelines discuss indications and contraindications for vasectomy, preoperative patient information and counselling, surgical techniques, postoperative care and subsequent semen analysis, and complications and late consequences. Conclusions: Vasectomy is intended to be a permanent form of contraception. There are no absolute contraindications for vasectomy. Relative contraindications may be the absence of children, age <30 yr, severe illness, no current relationship, and scrotal pain. Preoperative counselling should include alternative methods of contraception, complication and failure rates, and the need for postoperative semen analysis. Informed consent should be obtained before the operation. Although the use of muc

The first-generation phosphodiesterase 5 inhibitors and their pharmacokinetic issue

Background: Erectile dysfunction (ED) is a relatively frequent disease that negatively impacts the overall quality of life, well-being, and relationships. Although the use of phosphodiesterase 5 inhibitors (PDE5is) has revolutionized the treatment of ED, a high percentage of ED patients discontinue PDE5i treatment. Objectives: (i) To analyze the reasons for patient dissatisfaction leading to PDE5i discontinuation; (ii) analyze the pharmacokinetics of new formulations focusing on the time needed to reach an effective plasma concentration of PDE5is (Tonset) following drug intake; and (iii) summarize the physicochemical properties of sildenafil to understand which excipients may increase the absorption rate. Material and methods: An online PubMed literature search was conducted to identify English language publications from inception to January 2019. Results: The main reasons for patient dissatisfaction when using PDE5is on demand are the relatively long Tonset after taking vardenafil and sildenafil, including formulations such as film-coated tablets, fine granules, orally disintegrating tablets (ODTs), and oral thin films (ODFs). The relatively long Tonset, further worsened when accompanied by eating, highlights the following: (i) the need for planning intercourse, determining partner-related issues; (ii) issues when having sex before the maximum effect of the drug; and (iii) lower drug-related placebo effects. Some data suggest that sildenafil is a ‘difficult’ molecule, but Tonset can be improved following absorption by buccal mucosa using appropriate excipients. Conclusions: We conclude that several ODT and ODF formulations can improve the ‘discretion’ issue because they are taken without water, but they have similar pharmacokinetics to corresponding film-coated tablet formulations. One ODF formulation of sildenafil was characterized by a shorter Tonset and could potentially increase patient satisfaction following treatment. However, more clinical studies are needed to confirm the findings. Surfactants and ascorbic acid appear to be crucial excipients for achieving a high absorption rate, but more studies are needed