ABSTRACT
A dynamical model linking stress, social support, and health has been recently proposed and numerically analyzed from a classical point of view of integer-order calculus. Although interesting observations have been obtained in this way, the present work conducts a fractional-order analysis of that model. Under a periodic forcing of an environmental stress variable, the perceived stress has been analyzed through bifurcation diagrams and two well-known metrics of entropy and complexity, such as spectral entropy and C0 complexity. The results obtained by numerical simulations have shown novel insights into how stress evolves with frequency and amplitude of the perturbation, as well as with initial conditions for the system variables. More precisely, it has been observed that stress can alternate between chaos, periodic oscillations, and stable behaviors as the fractional order varies. Moreover, the perturbation frequency has revealed a narrow interval for the chaotic oscillations, while its amplitude may present different values indicating a low sensitivity regarding chaos generation. Also, the perceived stress has been noted to be highly sensitive to initial conditions for the symptoms of stress-related ill-health and for the social support received from family and friends. This work opens new directions of research whereby fractional calculus might offer more insight into psychology, life sciences, mental disorders, and stress-free well-being.
Subject(s)
Calculi , Nonlinear Dynamics , Entropy , Humans , Social Support , Stress, PsychologicalABSTRACT
Background In the beginning of the COVID-19 pandemic, many hospitalized patients received empiric hydroxychloroquine/chloroquine (HC/CQ). Although some retrospective-observational trials suggested potential benefit, all subsequent randomized clinical trials (RCTs) failed to show benefit and use generally ceased. Herein, we summarize key studies that clinicians advising patients on HC/CQ efficacy:safety calculus in hospitalized COVID-19 patients would want to know about in a practical one-stop-shopping source. Methods Pubmed and Google were searched on November 4, 2021. Search words included: COVID-19, hydroxychloroquine, chloroquine, in vitro, animal studies, clinical trials, and meta-analyses. Studies were assessed for import and included if considered impactful for benefit:risk assessment. Results These searches led to inclusion of 12 in vitro and animal reports; 12 retrospective-observational trials, 19 interventional clinical trials (17 RCTs, 1 single-arm, 1 controlled but unblinded), and 51 meta-analyses in hospitalized patients. Inconsistent efficacy was seen in vitro and in animal studies for coronaviruses and nil in SARS-CoV-2 animal models specifically. Most retrospective-observational studies in hospitalized COVID-19 patients found no efficacy; QT prolongation and increased adverse events and mortality were reported in some. All RCTs and almost all meta-analyses provided robust data showing no benefit in overall populations and subgroups, yet concerning safety issues in many. Conclusions HC/CQ have inconsistent anti-coronavirus efficacy in vitro and in animal models, and no convincing efficacy yet substantial safety issues in the overwhelming majority of retrospective-observational trials, RCTs, and meta-analyses in hospitalized COVID-19 patients. HC/CQ should not be prescribed for hospitalized COVID-19 patients outside of clinical trials.