Personalized Computerized Training for Cognitive Dysfunction after COVID-19: A Before-and-After Feasibility Pilot Study.

The current pilot study was set to evaluate the feasibility and potential benefit of a personalized computerized cognitive training (CCT) intervention to improve cognitive function among people living with post-acute sequelae of COVID-19 (PASC). Seventy three adults who self-reported cognitive dysfunction more than 3 months after a diagnosis of COVID-19 took part in an 8-week training study. Participants' general cognitive function was assessed before they completed as many cognitive daily training sessions as they wished during an 8-week period, using a personalized CCT application at home. At the end of this period, participants repeated the general cognitive function assessment. The differences between the scores at 8 weeks and baseline in five cognitive domains (attention, memory, coordination, perception, reasoning), complemented with analyses of the changes based on the participants' age, training time, self-reported health level at baseline and time since the initial COVID-19 infection. Participants had significant cognitive dysfunction and self-reported negative health levels at baseline. Most of the participants obtained higher scores after CCT in each of the domains as compared with baseline. The magnitude of this score increase was high across domains. It is concluded that a self-administered CCT based on gamified cognitive tasks could be an effective way to ameliorate cognitive dysfunction in persons with PASC. The ClinicalTrials.gov identifier is NCT05571852.

No Time to Waste: Real-World Repurposing of Generic Drugs as a Multifaceted Strategy Against COVID-19.

Real-world drug repurposing-the immediate "off-label" prescribing of drugs to address urgent clinical needs-is an indispensable strategy gaining rapid traction in the current COVID-19 crisis. Although off-label prescribing (ie, for a nonapproved indication) is legal in most countries, it tends to shift the burden of liability and cost to physicians and patients, respectively. Nevertheless, in urgent public health crises, it is often the only realistic source of a meaningful potential solution. To be considered for real-world repurposing, drug candidates should ideally have a track record of safety, affordability, and wide accessibility. Although thousands of such drugs are already available, the absence of a central repository of off-label uses presents a barrier to the immediate identification and selection of the safest, potentially useful interventions. Using the current COVID-19 pandemic as an example, we provide a glimpse at the extensive literature that supports the rationale behind six generic drugs, in four classes, all of which are affordable, supported by decades of safety data, and pleiotropically target the underlying pathophysiology that makes COVID-19 so dangerous. Having previously fast-tracked this paper to publication in summary form, we now expand on why cimetidine/famotidine (histamine type-2 receptor antagonists), dipyridamole (antiplatelet agent), fenofibrate/bezafibrate (cholesterol/triglyceride-lowering agents), and sildenafil (phosphodiesterase-5 inhibitor) are worth considering for patients with COVID-19 based on their antiviral, anti-inflammatory, renoprotective, cardioprotective, and anticoagulation properties. These examples also reveal the unlimited opportunity to future-proof public health by proactively mining, synthesizing, and cataloging the off-label treatment opportunities of thousands of safe, well-established, and affordable generic drugs.

Delivering Benefits at Speed Through Real-World Repurposing of Off-Patent Drugs: The COVID-19 Pandemic as a Case in Point.

Real-world drug repurposing-the immediate "off-label" prescribing of drugs to address urgent clinical needs-is a widely overlooked opportunity. Off-label prescribing (ie, for a nonapproved indication) is legal in most countries and tends to shift the burden of liability and cost to physicians and patients, respectively. Nevertheless, health crises may mean that real-world repurposing is the only realistic source for solutions. Optimal real-world repurposing requires a track record of safety, affordability, and access for drug candidates. Although thousands of such drugs are already available, there is no central repository of off-label uses to facilitate immediate identification and selection of potentially useful interventions during public health crises. Using the current coronavirus disease (COVID-19) pandemic as an example, we provide a glimpse of the extensive literature that supports the rationale behind six generic drugs, in four classes, all of which are affordable, supported by decades of safety data, and targeted toward the underlying pathophysiology that makes COVID-19 so deadly. This paper briefly summarizes why cimetidine or famotidine, dipyridamole, fenofibrate or bezafibrate, and sildenafil citrate are worth considering for patients with COVID-19. Clinical trials to assess efficacy are already underway for famotidine, dipyridamole, and sildenafil, and further trials of all these agents will be important in due course. These examples also reveal the unlimited opportunity to future-proof our health care systems by proactively mining, synthesizing, cataloging, and evaluating the off-label treatment opportunities of thousands of safe, well-established, and affordable generic drugs.