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.
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.
<b><i>Objectives: </i></b>Psychological morbidity as well as cognitive impairment are increasingly reported in prostate cancer (PCa) patients. However, despite growing numbers of PCa survivors and the well estimated negative impact of cognitive decline and emotional distress on survivors' quality of life, no study has assessed the whole range of cognitive and psychological sequelae as a response to treatment options for PCa. The objective of the present review was to systematically characterize the types and estimate the prevalence of the cognitive impairment and emotional burdens that were found in PCa survivors secondary to different treatment options. <b><i>Methods: </i></b>Systematic, general reviews, meta-analysis, and overviews of review studies in English, that were published in PubMed during the last 10 years until l August 2019 and that reported psychological distress, anxiety, depression, cognitive decline, or dementia among individuals with PCa exposed to a particular treatment option were analyzed. <b><i>Results: </i></b>A total of 21 articles were reviewed. Some of the studies described one or more cognitive or psychological consequences of only one therapeutic strategy while others compared the psychological impacts among different strategies. Most of these studies suggested that either radical prostatectomy or active surveillance and radiotherapy were well-tolerated treatments in terms of psychological modifications. However, many of these patients may require additional emotional support. There is also increasing evidence that androgen deprivation therapy may be associated with depression, while controversy surrounding the association between cognitive dysfunction, dementia, and androgen deprivation therapy remains ambivalent. <b><i>Conclusion: </i></b>Emotional distress and cognitive decline may accompany every PCa treatment option to different degrees. Accurate information on the short- and long-term effect of treatments on cognitive and psychological aspects should be provided to patients during treatment decision-making. There is also a need to develop well-targeted psychological and neurological interventions that could help those experiencing ongoing post-treatment difficulties.
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. Current 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 CSF biomarker of axonal degeneration) and neurogranin (CSF biomarker of synaptic functioning)—to clinical trials allows more precise staging of AD. Additionally, use of the Bayesian statistics, modifiable clinical trial designs, and clinical trial simulators enrich the trial methodology. Besides, combination therapy regimens are currently assessed in clinical trials. The abovementioned diagnostic and statistical advances, which have been recently integrated in clinical trials, are consequential to the recent failures of studies of disease-modifying treatments. Their experiential rather than theoretical origins may better equip potentially successful drug-development strategies.
Donepezil is one of the cholinesterase inhibitors that are indicated for the treatment of mild to moderate Alzheimer’s disease (AD). Pharmacokinetic analysis has shown that donepezil is primarily eliminated by renal excretion rather than biliary excretion in humans. Therefore, patients with impaired renal function are at high risk of toxicity caused by accumulation of this drug. It is also well known that dialysis patients have very often cholinergic disorders. On the other hand, with the increasing number of long-term chronic dialysis patients, the prevalence of cognitive disorders is increasing in elderly dialysis patients. Because of the above-mentioned special risks of these patients, acetylcholinesterase inhibitors, such as donepezil, are avoided to be prescribed for them. We studied 5 cases of chronic hemodialysis outpatients (3 men [70, 72, and 86 years old] and 2 women [65 and 71 years old]) who were diagnosed as having moderate AD. We administered donepezil at 2.5 mg/day orally to the patients. After 1 month’s treatment, their behavioral symptoms were improved, without them having any adverse events. We enhanced the dose to 5 mg/day without the patients experiencing any episodes of drug toxicity. After 3 months of treatment with the higher dose, their cognitive and executive functions were slightly improved and their behavioral disorders were remarkably milder, without them experiencing any episodes of drug toxicity. The patients’ condition remained stable for 6 months after the initial administration of the drug. All of them were followed for the 10 following years, showing a mild cognitive decline per year for the first 5 years and more severe decline for the remaining years of the follow-up. Our cases indicate that donepezil treatment under prudent use may be well tolerated and have a beneficial impact on chronic hemodialysis patients with AD.
Low back pain affects an estimated half a billion people at any time worldwide. Although several noninvasive treatment strategies have been developed, in many cases, they cannot relief patients' symptoms, thus low back discectomy is the appropriate treatment of choice. It is widely accepted that surgery alters the biomechanics of the functional motion segment and results in additional disc herniation at the adjacent level or the opposite side, more commonly than expected. After the discectomy, changes in vertebral load properties and kinetics could occur. As a result, biomechanical stress on the affected level as well as cyclic loads can cause lumbar disc reherniation (rLDH).Since the rate of recurrent disc herniation is about 5%-15%, further research should be done so as to quantify the postoperative lumbar spine kinematic pattern, with the use of wearable sensors technology, that could be a potential biomechanical factor causing rLDH.
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