Supplementation of Vitamin D and Mental Health in Adults with Respiratory System Diseases: A Systematic Review of Randomized Controlled Trials.

Vitamin D is indicated to be beneficial for the prevention and treatment of both respiratory health and mental health problems, while mental health issues are a common consequence of diseases of the respiratory system. The aim of the presented systematic review was to gather available evidence regarding the influence of the supplementation of vitamin D on mental health in adults with respiratory system diseases obtained within randomized controlled trials (RCTs). The systematic review was conducted on the basis of the PubMed and Web of Science databases in agreement with the guidelines of Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA), while being registered within the database of the International Prospective Register of Systematic Reviews (PROSPERO) (CRD42020155779). A total of 8514 studies published before September 2021 were screened and 5 RCTs were included, which were assessed using the revised Cochrane risk-of-bias tool for randomized trials. Screening, inclusion, reporting, and assessment were conducted by two researchers independently. The studies focused on the assessment of patients with chronic obstructive pulmonary disease, but also increased susceptibility to respiratory tract infections, pulmonary tuberculosis, and bronchial asthma. The studies were conducted for various periods of time-from 2 months to a year-while the dose of vitamin D applied was also diverse-from 4000 IU applied daily, to 100,000 IU applied weekly, or monthly. The psychological measures applied within the studies allowed the assessment, mainly, of quality of life, but also well-being, and depression. For the majority of studies, some concerns regarding risk of bias were defined, resulting from the randomization process and selection of reported results; however, for one study, the risk was even defined as high. Within the included studies, three studies confirmed a beneficial effect of vitamin D (including those with a high risk of bias), but two studies did not confirm it. Taking into account the evidence gathered, in spite of a positive influence of vitamin D on mental health in individuals with increased susceptibility to respiratory tract infections and bronchial asthma, the conducted systematic review is not a strong confirmation of the beneficial effect of the supplementation of vitamin D on mental health in adults with respiratory system diseases.

Disaster preparedness in healthcare professionals amid COVID-19 and beyond: A systematic review of randomized controlled trials.

BACKGROUND: Disasters like COVID-19 are oftentimes inevitable, which makes disaster preparedness indispensable to global health and social stability. However, there is a dearth of understanding of how well healthcare professionals, who often have to work at the epicenter of disasters as they evolve, are trained to be sufficiently prepared for these crises. To this end, this study aims to examine the characteristics and effectiveness of existing interventions that aim to improve healthcare professionals' disaster preparedness. METHODS: We searched RCTs that aim to improve healthcare professionals' disaster preparedness in databases including PubMed, PsycINFO, CINAHL and Scopus. Results were screened against the eligibility criteria. The review was registered with PROSPERO (CRD42020192517) and conducted following the PRISMA guidelines. RESULTS: A total of 7382 articles were screened for eligibility, among which, 27 RCTs, incorporating 35,145, met the inclusion criteria. Review results show that most of the eligible RCTs were conducted in high-income countries. Only two RCTs were developed in disaster contexts that share similarities with COVID-19. Most of the interventions did not address critical disaster coping abilities, such as how can healthcare professionals protect or improve their personal or the general public's mental health amid pandemics. Furthermore, almost half of the disaster preparedness RCTs failed to generate statistically significant outcomes. CONCLUSIONS: Albeit inevitable, disasters are preventable. Our study results underscore the imperative of designing and developing effective and comprehensive interventions that could boost healthcare professionals' disaster preparedness, so that these frontline workers can better protect personal and public health amid global crises like COVID-19.

Megastudies: A New Approach to Reducing Vaccine Hesitation Worldwide.

Vaccine hesitancy is a considerable obstacle to achieving vaccine protection worldwide. There needs to be more evidence-based research for interventions for vaccine hesitancy. Existing effectiveness evaluations are limited to one particular hypothesis, and no studies have compared the effectiveness of different interventions. A megastudy takes a large-scale, multi-intervention, uniform participant and the same evaluation criteria approach to evaluate many interventions simultaneously and find the most effective ones. Therefore, megastudies can help us find the most effective interventions for vaccine hesitancy. Additionally, considering the complex causes of vaccine hesitancy, we design interventions that involve social factors in megastudies. Lastly, quality control and justice are critical issues for megastudies in the future.

Do text messages increase voter registration? Evidence from RCTs with a local authority and an advocacy organisation in the UK

In the wake of the Covid-19 pandemic, text messages have become an increasingly attractive tool of voter registration. At the same time, in countries without automated registration, advocacy organisations play a more prominent role in supplementing the efforts of official bodies in registering voters. However, most available, robust evidence on whether voter registration campaigns work is based on campaigns conducted by official bodies charged with electoral registration. We present the results of two RCTs that aimed to increase voter registration in the UK using SMS-text messages, relying mainly on behavioural messaging. One was conducted by a local authority, while the other was implemented by an issue advocacy organisation that had no prior involvement in voter registration. In line with previous findings, the local authority's text messages resulted in an increased registration rate of eight percentage-points, which translates into a three percentage-point increase in voter turnout. However, the advocacy organisation's text messages neither increased voter registration, nor turnout, no matter whether the text message offered a personal follow-up conversation, or not. Given that many voter registration campaigns are run by advocacy organisations and text messages are an increasingly important mobilisation tool, this raises questions about the scope conditions of existing findings.

Vitamin D status can affect COVID-19 outcomes also in pediatric population.

Background: vitamin D influences the immune system and the inflammatory response. It is known that vitamin D supplementation reduces the risk of acute respiratory tract infection. In the last two years, many researchers have investigated vitamin D's role in the pathophysiology of COVID-19 disease. Results: the findings obtained from clinical trials and systematic reviews highlight that most patients with COVID-19 have decreased vitamin D levels and low levels of vitamin D increase the risk of severe disease. This evidence seems to be also confirmed in the pediatric population. Conclusions: further studies (systematic review and meta-analysis) conducted on children are needed to confirm that vitamin D affects COVID-19 outcomes and to determine the effectiveness of supplementation and the appropriate dose, duration and mode of administration.

Efficacy, immunogenicity and safety of COVID-19 vaccines in older adults: a systematic review and meta-analysis.

Background: Older adults are more susceptible to severe health outcomes for coronavirus disease 2019 (COVID-19). Universal vaccination has become a trend, but there are still doubts and research gaps regarding the COVID-19 vaccination in the elderly. This study aimed to investigate the efficacy, immunogenicity, and safety of COVID-19 vaccines in older people aged ≥ 55 years and their influencing factors. Methods: Randomized controlled trials from inception to April 9, 2022, were systematically searched in PubMed, EMBASE, the Cochrane Library, and Web of Science. We estimated summary relative risk (RR), rates, or standardized mean difference (SMD) with 95% confidence interval (CI) using random-effects meta-analysis. This study was registered with PROSPERO (CRD42022314456). Results: Of the 32 eligible studies, 9, 21, and 25 were analyzed for efficacy, immunogenicity, and safety, respectively. In older adults, vaccination was efficacious against COVID-19 (79.49%, 95% CI: 60.55-89.34), with excellent seroconversion rate (92.64%, 95% CI: 86.77-96.91) and geometric mean titer (GMT) (SMD 3.56, 95% CI: 2.80-4.31) of neutralizing antibodies, and provided a significant protection rate against severe disease (87.01%, 50.80-96.57). Subgroup and meta-regression analyses consistently found vaccine types and the number of doses to be primary influencing factors for efficacy and immunogenicity. Specifically, mRNA vaccines showed the best efficacy (90.72%, 95% CI: 86.82-93.46), consistent with its highest seroconversion rate (98.52%, 95% CI: 93.45-99.98) and GMT (SMD 6.20, 95% CI: 2.02-10.39). Compared to the control groups, vaccination significantly increased the incidence of total adverse events (AEs) (RR 1.59, 95% CI: 1.38-1.83), including most local and systemic AEs, such as pain, fever, chill, etc. For inactivated and DNA vaccines, the incidence of any AEs was similar between vaccination and control groups (p > 0.1), while mRNA vaccines had the highest risk of most AEs (RR range from 1.74 to 7.22). Conclusion: COVID-19 vaccines showed acceptable efficacy, immunogenicity and safety in older people, especially providing a high protection rate against severe disease. The mRNA vaccine was the most efficacious, but it is worth surveillance for some AEs it caused. Increased booster coverage in older adults is warranted, and additional studies are urgently required for longer follow-up periods and variant strains.

The effect of Vitamin C and Zn supplementation on the immune system and clinical outcomes in COVID-19 patients.

SARS-CoV-2 (Severe Acute Respiratory Syndrome-Coronavirus-2) is the most dangerous form of the coronavirus, which causes COVID-19. In patients with severe COVID-19, the immune system becomes markedly overactive. There is evidence that supplementation with select micronutrients may play a role in maintaining immune system function in this patient population. Throughout the COVID-19 pandemic, significant emphasis has been placed on the importance of supplementing critical micronutrients such as Vitamin C and Zinc (Zn) due to their immunomodulatory effects. Viral infections, like COVID-19, increase physiological demand for these micronutrients. Therefore, the purpose of this review was to provide comprehensive information regarding the potential effectiveness of Vitamin C and Zn supplementation during viral infection and specifically COVID-19. This review demonstrated a relation between Vitamin C and Zn deficiency and a reduction in the innate immune response, which can ultimately make patients with COVID-19 more vulnerable to viral infection. As such, adequate intake of Vitamin C and Zn, as an adjunctive therapeutic approach with any necessary pharmacological treatment(s), may be necessary to mitigate the adverse physiological effects of COVID-19. To truly clarify the role of Vitamin C and Zn supplementation in the management of COVID-19, we must wait for the results of ongoing randomized controlled trials. The toxicity of Vitamin C and Zn should also be considered to prevent over-supplementation. Over-supplementation of Vitamin C can lead to oxalate toxicity, while increased Zn intake can reduce immune system function. In summary, Vitamin C and Zn supplementation may be useful in mitigating COVID-19 symptomology.

Antiviral potential of garlic (Allium sativum) and its organosulfur compounds: A systematic update of pre-clinical and clinical data.

BACKGROUND: Garlic (Allium sativum L.) is a common herb consumed worldwide as functional food and traditional remedy for the prevention of infectious diseases since ancient time. Garlic and its active organosulfur compounds (OSCs) have been reported to alleviate a number of viral infections in pre-clinical and clinical investigations. However, so far no systematic review on its antiviral effects and the underlying molecular mechanisms exists. SCOPE AND APPROACH: The aim of this review is to systematically summarize pre-clinical and clinical investigations on antiviral effects of garlic and its OSCs as well as to further analyse recent findings on the mechanisms that underpin these antiviral actions. PubMed, Cochrane library, Google Scholar and Science Direct databases were searched and articles up to June 2020 were included in this review. KEY FINDINGS AND CONCLUSIONS: Pre-clinical data demonstrated that garlic and its OSCs have potential antiviral activity against different human, animal and plant pathogenic viruses through blocking viral entry into host cells, inhibiting viral RNA polymerase, reverse transcriptase, DNA synthesis and immediate-early gene 1(IEG1) transcription, as well as through downregulating the extracellular-signal-regulated kinase (ERK)/mitogen activated protein kinase (MAPK) signaling pathway. The alleviation of viral infection was also shown to link with immunomodulatory effects of garlic and its OSCs. Clinical studies further demonstrated a prophylactic effect of garlic in the prevention of widespread viral infections in humans through enhancing the immune response. This review highlights that garlic possesses significant antiviral activity and can be used prophylactically in the prevention of viral infections.

Antiviral Activity of Vitamin D and COVID 19: Current Understanding

Innate and adaptive immune responses, which are intimately related to the evolution of many infectious diseases, are influenced by the biologically active form of vitamin D. From a mechanical perspective, there are several rationales to assume that vitamin D positively modifies host responses to SARS-CoV-2, either in the early infection or subsequent hyper-inflammatory stages of COVID-19. It has been long known that vitamin D metabolites induce antiviral effects through indirect and direct mechanisms via antimicrobial peptides, immune modulation, the interaction between major viral and cellular particles, initiation of apoptosis and autophagy, and diversity of hereditary and epigenetic aspects. The remarkable overlap between the deficiency of vitamin D and risk factors for severe COVID-19, including obesity, aging, and Black or Asian ethnicity, has motivated researchers to assume that supplementation of vitamin D can be promising as a preventive or treatment agent for COVID-19. Since the outset of the pandemic, researchers have integrated literature searches and cross-sectional statistical studies to appraise the vitamin D level impact of COVID-19, whereby nearly 30 observational studies have confirmed that the incidence, severity, and mortality of COVID-19 are inversely related to the serum 25OHD concentrations. Also, some recently announced clinical trials indicated that vitamin D supplementation has a positive effect on the severity of COVID-19;however, other studies, including clinical trials, have not supported that, especially if we take into account what was revealed in a recent clinical trial, i.e., airway diseases are related to the irregular metabolism of vitamin D increasing the potential of developing vitamin D deficiency due to pulmonary inflammation. Therefore, more dedicated studies are required without critical limitations to ascertain the actual effect of vitamin D in preventing and treating COVID-19, and if its effectiveness is proven, the effective dose must be determined. © 2021 Bentham Science Publishers. All rights reserved.

Cardiovascular drugs and COVID-19 clinical outcomes: a systematic review and meta-analysis of randomized controlled trials.

AIMS: To update our previously reported systematic review and meta-analysis of observational studies on cardiovascular drug exposure and COVID-19 clinical outcomes by focusing on newly published randomized controlled trials (RCTs). METHODS: More than 500 databases were searched between 1 November 2020 and 2 October 2021 to identify RCTs that were published after our baseline review. One reviewer extracted data with other reviewers verifying the extracted data for accuracy and completeness. RESULTS: After screening 22 414 records, we included 24 and 21 RCTs in the qualitative and quantitative syntheses, respectively. The most investigated drug classes were angiotensin-converting enzyme inhibitors (ACEIs)/angiotensin receptor blocker (ARBs) and anticoagulants, investigated by 10 and 11 studies respectively. In meta-analyses, ACEI/ARBs did not affect hospitalization length (mean difference -0.42, 95% confidence interval [CI] -1.83; 0.98 d, n = 1183), COVID-19 severity (risk ratio/RR 0.90, 95% CI 0.71; 1.15, n = 1661) or mortality (risk ratio [RR] 0.92, 95% CI 0.58; 1.47, n = 1646). Therapeutic anticoagulation also had no effect (hospitalization length mean difference -0.29, 95% CI -1.13 to 0.56 d, n = 1449; severity RR 0.86, 95% CI 0.70; 1.04, n = 2696; and, mortality RR 0.93, 95% CI 0.77; 1.13, n = 5689). Other investigated drug classes were antiplatelets (aspirin, 2 trials), antithrombotics (sulodexide, 1 trial), calcium channel blockers (amlodipine, 1 trial) and lipid-modifying drugs (atorvastatin, 1 trial). CONCLUSION: Moderate- to high-certainty RCT evidence suggests that cardiovascular drugs such as ACEIs/ARBs are not associated with poor COVID-19 outcomes, and should therefore not be discontinued. These cardiovascular drugs should also not be initiated to treat or prevent COVID-19 unless they are needed for an underlying currently approved therapeutic indication.

Suspend or amend? Randomized controlled trial on neuropsychological rehabilitation for epilepsy: A COVID-19 impact.

COVID-19 caused devastating effects of human loss and suffering along with disruption in clinical research, forcing reconceptualization and modification of studies. This paper attempts to outline the steps followed and detail the modifications undertaken to deal with the impacts of the pandemic on the first ongoing randomized controlled trial on effectiveness of neuropsychological rehabilitation in adult patients with drug-resistant epilepsy in India. All modifications were based on evolving guidelines and circumstantial context and were planned, reviewed and approved by important stakeholders. Results obtained from the trial need to be interpreted and analysed within this context. These modifications have implications for wider outreach of neuropsychology services in India.

Fragility Index and Fragility Quotient in Randomized Controlled Trials on Corticosteroids in ARDS Due to COVID-19 and Non-COVID-19 Etiology.

BACKGROUND: The effectiveness of corticosteroids in acute respiratory distress syndrome (ARDS) and COVID-19 still remains uncertain. Since ARDS is due to a hyperinflammatory response to a direct injury, we decided to perform a meta-analysis and an evaluation of robustness of randomised clinical trials (RCTs) investigating the impact of corticosteroids on mortality in ARDS in both COVID-19 and non-COVID-19 patients. We conducted a systematic search of the literature from inception up to 30 October 2020, using the MEDLINE database and the PubMed interface. We evaluated the fragility index (FI) of the included RCTs using a two-by-two contingency table and the p-value produced by the Fisher exact test; the fragility quotient (FQ) was calculated by dividing the FI score by the total sample size of the trial. RESULTS: Thirteen RCTs were included in the analysis; five of them were conducted in COVID-19 ARDS, including 7692 patients, while 8 RCTS were performed in non-COVID ARDS with 1091 patients evaluated. Three out of eight RCTs in ARDS had a FI > 0 while 2 RCTs out of five in COVID-19 had FI > 0. The median of FI for ARDS was 0.625 (0.47) while the median of FQ was 0.03 (0.014). The median of FI for COVID-19 was 6 (2) while the median of FQ was 0.059 (0.055). In this systematic review, we found that FI and FQ of RCTs evaluating the use of corticosteroids in ARDS and COVID-19 were low.

Prospective individual patient data meta-analysis: Evaluating convalescent plasma for COVID-19.

As the world faced the devastation of the COVID-19 pandemic in late 2019 and early 2020, numerous clinical trials were initiated in many locations in an effort to establish the efficacy (or lack thereof) of potential treatments. As the pandemic has been shifting locations rapidly, individual studies have been at risk of failing to meet recruitment targets because of declining numbers of eligible patients with COVID-19 encountered at participating sites. It has become clear that it might take several more COVID-19 surges at the same location to achieve full enrollment and to find answers about what treatments are effective for this disease. This paper proposes an innovative approach for pooling patient-level data from multiple ongoing randomized clinical trials (RCTs) that have not been configured as a network of sites. We present the statistical analysis plan of a prospective individual patient data (IPD) meta-analysis (MA) from ongoing RCTs of convalescent plasma (CP). We employ an adaptive Bayesian approach for continuously monitoring the accumulating pooled data via posterior probabilities for safety, efficacy, and harm. Although we focus on RCTs for CP and address specific challenges related to CP treatment for COVID-19, the proposed framework is generally applicable to pooling data from RCTs for other therapies and disease settings in order to find answers in weeks or months, rather than years.