Despite all scientific efforts and many protracted and expensive clinical trials, no new drug has been approved by FDA for treatment of Alzheimer disease (AD) since 2003. Indeed, more than 200 investigational programs have failed or have been abandoned in the last decade. The most probable explanations for failures of disease-modifying treatments (DMTs) for AD may include late initiation of treatments during the course of AD development, inappropriate drug dosages, erroneous selection of treatment targets, and mainly an inadequate understanding of the complex pathophysiology of AD, which may necessitate combination treatments rather than monotherapy. Clinical trials’ methodological issues have also been criticized. Drug-development research for AD is aimed to overcome these drawbacks. Preclinical and prodromal AD populations, as well as traditionally investigated populations representing all the clinical stages of AD, are included in recent trials. Systematic use of biomarkers in staging preclinical and prodromal AD and of a single primary outcome in trials of prodromal AD are regularly integrated. The application of amyloid, tau, and neurodegeneration biomarkers, including new biomarkers—such as Tau positron emission tomography, neurofilament light chain (blood and Cerebrospinal fluid (CSF) biomarker of axonal degeneration) and neurogranin (CSF biomarker of synaptic functioning)—to clinical trials allows more precise staging of AD. Additionally, use of Bayesian statistics, modifiable clinical trial designs, and clinical trial simulators enrich the trial methodology. Besides, combination therapy regimens are assessed in clinical trials. The above-mentioned diagnostic and statistical advances, which have been recently integrated in clinical trials, are relevant to the recent failures of studies of disease-modifying treatments. Their experiential rather than theoretical origins may better equip potentially successful drug-development strategies.

Electrical injury can affect any system and organ. Central nervous system (CNS) complications are especially well recognised, causing an increased risk of morbidity, while peripheral nervous system (PNS) complications, neurourological and cognitive and psychological abnormalities are less predictable after electrical injuries.

No abstract

Penile fractures are generally rare and underreported. The mechanism of injury is due to a rupture of the corpora cavernosa following blunt or sexual trauma to the penis when fully erect. Penile fractures usually present with a ‘popping’ sound with concomitant sudden swelling and ecchymosis of the penis followed by rapid detumescence. Urethral involvement occurs only in a small part of the cases. Isolated spongiosal injury after sexual intercourse is also extremely rare. The cardinal sign of urethral injury is blood at the meatus. A small laceration can be repaired by simple closure with absorbable sutures, while a complete rupture requires a more complex anastomotic repair. We report a case of a typically presenting penile fracture that was eventually proven to be an isolated corpus spongiosum injury, with no corpora cavernosa involvement.