Pharmacological interventions to improve sleep in people with Alzheimer's disease: a meta-analysis of randomized controlled trials.

INTRODUCTION: This systematic review and meta-analysis evaluates the evidence from randomized controlled trials (RCTs) involving pharmacological interventions for improving sleep in people with Alzheimer's disease (AD). METHODS: A systematic literature search in eight databases from January 2000 to July 2023 focusing on RCTs that compared a pharmacological intervention with a placebo for enhancing sleep in people with AD. The authors registered the study protocol at Prospero, followed the PRISMA guidelines, and produced the pooled estimates using random-effect or IVhet models. RESULTS: Eight different interventions and 29 different sleep outcomes were examined in 14 RCTs included in this review. Eszopiclone positively affected sleep efficiency, as did orexin antagonists. However, there was no difference when melatonin was used. The interventions demonstrated low discontinuation rates and a few adverse drug reactions. CONCLUSION: Although melatonin was the most investigated intervention, the evidence for its efficacy is inconclusive. On the other hand, trazodone and orexin receptor antagonists showed promising results; however, more RCTs are needed for definite answers.

Pharmacological and non-pharmacological treatment options for sleep disturbances in Alzheimer's disease.

INTRODUCTION: Alzheimer's disease (AD) is one of the most common neurodegenerative disorders among the older population. Sleep disruption and circadian rhythm disorders often develop in AD patients, and many experience sleeping difficulties requiring pharmacological and non-pharmacological interventions. AREAS COVERED: This review appraised the evidence from clinical studies on various pharmacological and non-pharmacological therapies for sleep disturbances in AD patients and proposed an algorithm to manage sleep disturbances in this population of patients. EXPERT OPINION: Non-pharmacological interventions are generally preferred as the first-line approach to improve sleep-related symptoms in AD due to their favorable safety profile. However, when non-pharmacological interventions alone are insufficient, a range of pharmacological agents can be considered. Trazodone and melatonin are commonly used as adjunctive therapies, while Z-drugs including zopiclone and zolpidem are specifically employed to treat insomnia in patients with late-onset AD. Furthermore, a newer class of agents known as dual orexin receptor antagonists has emerged and gained approval for improving sleep onset and maintenance in AD patients.

Association between Mesenchymal Stem Cells and COVID-19 Therapy: Systematic Review and Current Trends.

Background: The novel coronavirus first emerged in Wuhan, China, and quickly spread across the globe, spanning various countries and resulting in a worldwide pandemic by the end of December 2019. Given the current advances in treatments available for COVID-19, mesenchymal stem cell (MSC) therapy seems to be a prospective option for management of ARDS observed in COVID-19 patients. This present study is aimed at exploring the therapeutic potential and safety of using MSC obtained by isolation from health cord tissues in the treatment of patients with COVID-19. Methods: A systematic search was done based on the guidelines of the PRISMA 2020 statement. A literature search was executed using controlled vocabulary and indexing of trials to evaluate all the relevant studies involving the use of medical subject headings (MeSH) in electronic databases like PubMed, Embase, Scopus, Cochrane Central Register of Controlled Trials (CENTRAL), and clinicaltrials.gov up to 31 December 2021. The protocol was registered in the PROSPERO register with ID CRD42022301666. Findings. After screening finally, 22 remaining articles were included in this systematic review. The studies revealed that MSC exosomes are found to be superior to MSC alone in terms of safety owing to being smaller with a lesser immunological response which leads to free movement in blood capillaries without clumping and also cannot further divide, thus reducing the oncogenic potential of MSC-derived exosomes as compared to MSC only. The studies demonstrated that the lungs healed with the use of exosomes compared to how they presented initially at the hospital. MSCs are found to increase the angiogenesis process and alveolar reepithelization, reducing markers like TNF alpha, TGF beta, and COL I and III, reducing the growth of myofibroblasts and increasing survivability of endothelium leading to attenuated pulmonary fibrosis and even reversing them. Interpretation. We can conclude that the use of mesenchymal stem cells or their derived exosomes is safe and well-tolerated in patients with COVID-19. It improves different parameters of oxygenation and helps in the healing of the lungs. The viral load along with different inflammatory cells and biomarkers of inflammation tend to decrease. Chest X-ray, CT scan, and different radiological tools are used to show improvement and reduced ongoing destructive processes.

Russia-Ukraine conflict and COVID-19: a double burden for Ukraine's healthcare system and a concern for global citizens.

The conflict between Ukraine and Russia significantly influences the healthcare sector. The ongoing COVID-19 pandemic and the armed conflict have badly devastated the established healthcare system. Only 36.08% of the Ukrainian population has received the COVID-19 vaccination, with the majority receiving two doses, and currently, Ukraine records the highest mortality rate in the world. In addition to the conflict injuries, increased susceptible deaths to COVID-19 can be found due to inadequate vaccination rates for the disease. To save their lives and for their well-being, many individuals have been relocating to the underground metro stations, other cities, nearby towns and countries. In these settings, social distancing, hand sanitation and wearing masks are not prioritised. In the current circumstances, the broken healthcare system needs to be rebuilt, and the Non-Governmental Organizations (NGOs), doctors and all the front-line workers should extend their humanitarian support to the Ukrainian population. Conclusion: It is an arduous task for healthcare organisations to supply vaccines and medicines in this 'armed conflict' between Russia and Ukraine. This can only happen when both parties extend their support to rebuild the shattered healthcare infrastructure.

Unraveling enhanced brain delivery of paliperidone-loaded lipid nanoconstructs: pharmacokinetic, behavioral, biochemical, and histological aspects.

Antipsychotics are accompanied by extrapyramidal side effects that deter treatment adherence and patient compliance. Paliperidone (PPD), an atypical (second-generation) antipsychotic recommended for managing schizophrenia presents biopharmaceutical challenges and pharmacological constraints which dissuade it from crossing the brain barrier. The present research aimed to assess paliperidone-loaded lipid nanoconstruct (PPD-LNC) for an improved antipsychotic activity for managing schizophrenia. High % cell viability in Neuro-2a cells (70-98%) exhibited the safety of PPD-LNC. The pharmacokinetic data showed a 3.46-fold improvement in the relative bioavailability in the brain for PPD-LNC compared to a drug suspension. The pharmacodynamic evaluation demonstrated a significant (p < .05) reduction in cataleptic behavior, attenuated escape latency, and prolonged stay in the open arm with PPD-LNC, thus showing its effectiveness in reducing extrapyramidal symptoms. The histopathological images further validated the safety of the formulation. Reduction in NF-κB levels as identified by immunohistochemical analysis exhibited the anti-inflammatory effect of PPD-LNC. The formulation demonstrated significant (p < .01) improvement in the activity of oxidative stress parameters and attenuation of neuroinflammatory markers. Based on the study findings, it was observed that formulating LNC of PPD would surmount the pharmacological constraints, improve the in vivo performance, and diminish the associated side effects.

Clinical outcomes of sofosbuvir-based antivirals in patients with COVID-19: a systematic review and meta-analysis of randomized trials.

BACKGROUND: Several randomized trials have evaluated the effects of sofosbuvir-based direct-acting antivirals on the clinical outcomes in patients with COVID-19. METHODS: A systematic literature search with no language restrictions was performed on electronic databases and preprint repositories to identify eligible randomized trials published up to 8 July 2021. A random-effects model was used to estimate the pooled odds ratio (OR) for outcomes of interest with the use of sofosbuvir combined with direct-acting antiviral agents relative to the nonuse of sofosbuvir-based direct-acting antiviral agents at 95% confidence intervals (CI). RESULTS: The meta-analysis of 11 trials (n = 2,161) revealed statistically significant reduction in the odds of mortality (pooled odds ratio = 0.59; 95% confidence interval 0.36 to 0.99) but no statistically significant difference in the odds of development of composite endpoint of severe illness (pooled odds ratio = 0.79; 95% confidence interval 0.43 to 1.44) with the administration of sofosbuvir-based direct-acting antiviral agents among patients with COVID-19, relative to non-administration of sofosbuvir-based direct-acting antiviral agents.Subgroup analysis with seven trials involving sofosbuvir-daclatasvir revealed no significant mortality benefit (pooled odds ratio = 0.77; 95% confidence interval 0.48 to 1.22). CONCLUSION: Sofosbuvir-based direct-acting antiviral agents have no protective effects against the development of severe illness in patients with COVID-19 with the current dosing regimen. Whether sofosbuvir-based direct-acting antiviral agents could offer mortality benefits would require further investigations.

Neurological Associations of SARS-CoV-2 Infection: A Systematic Review.

BACKGROUND: The current ongoing COVID-19 pandemic has compelled us to scrutinize major outbreaks in the past two decades, Severe Acute Respiratory Syndrome (SARS), in 2002, and Middle East Respiratory Syndrome (MERS), in 2012. We aimed to assess the associated neurological manifestations with SARS CoV-2 infection. METHODS: In this systematic review, a search was carried out by key-electronic databases, controlled vocabulary, and indexing of trials to evaluate the available pertinent studies which included both medical subject headings (MeSH) and advanced electronic databases comprising PubMed, Embase, Scopus, Cochrane Central Register of Controlled Trials (CENTRAL). Peer-reviewed studies published in English and Spanish were considered, which reported data on the neurological associations of individuals with suspected or laboratory-confirmed SARS-CoV-2 infection. Outcomes were nervous signs or symptoms, symptom severity, and diagnoses. RESULTS: Our search identified 45 relevant studies, with 21 case reports, 3 case series, 9 observational studies, 1 retrospective study, 9 retrospective reviews, and 2 prospective reviews. This systematic review revealed that most commonly reported neuronal presentations involved headache, nausea, vomiting and muscular symptoms like fibromyalgia. Anosmia and ageusia, defects in clarity or sharpness of vision (error in visual acuity), and pain may occur in parallel. Notable afflictions in the form of anxiety, anger, confusion, post-traumatic stress symptoms, and post-intensive care syndrome were observed in individuals who were kept in quarantine and those with long-stay admissions in healthcare settings. SARS CoV-2 infection may result in cognitive impairment. Patients with more severe infection exhibited uncommon manifestations, such as acute cerebrovascular diseases (intracerebral haemorrhage, stroke), rhabdomyolysis, encephalopathy, and Guillain-Barré syndrome. CONCLUSION: SARS-CoV-2 patients experience neuronal presentations varying with the progression of the infection. Healthcare professionals should be acquainted with the divergent neurological symptoms to curb misdiagnosis and limit long-term sequelae. Health-care planners and policymakers must prepare for this eventuality, while the ongoing studies increase our knowledge base on acute and chronic neurological associations of this pathogen.