Tocilizumab and COVID-19: A meta-analysis of 2120 patients with severe disease and implications for clinical trial methodologies

Background/aim: Since the outbreak of the COVID-19, numerous therapies to counteract this severe disease have emerged. The benefits of Tocilizumab for severely infected COVID-19 patients and the methodologies of ongoing clinical trials are explored.Materials and methods: A systematic search adhering to PRISMA guidelines was conducted in PubMed, Cochrane Central, medRxiv, and bioRxiv using the following keywords: “Tocilizumab,” “Actemra,” “COVID-19.” An additional subsearch was conducted on Clinicaltrials.gov to locate ongoing tocilizumab trials.Results: A total of 13 studies were included in the meta-analysis comprising 2120 patients. The treatment group had lower mortality compared to the control group (OR = 0.42, 95% CI = 0.26 to 0.69, P = 0.0005, I2 = 55%). A descriptive analysis of 50 registered trials was conducted.Conclusion: This review meta-analyzed the therapeutic benefits of tocilizumab in COVID-19 patients with severe disease for mortality, mechanical ventilation, and the characteristics of COVID-19 registered trials

Contact dermatitis due to personal protective equipment use and hygiene practices during the COVID-19 pandemic: A systematic review of case reports

Background: Prolonged use of personal protective equipment (PPE) may lead to contact dermatitis during the coronavirus disease 19 (COVID-19) pandemic. This paper aims to identify the causative factors of contact dermatitis from PPE and hygiene practices.Methods: The search was conducted adhering to PRISMA 2020 guidelines. A Delphi process was employed to ensure that the aims of this study were met. PubMed and Web of Science databases were systematically searched through September 12, 2021, using search terms: Contact dermatitis, case report, covid-19. The findings were tabulated as author/year, gender, age, presentation, cause, dermatological diagnosis, testing modality, provided treatment, symptom resolution (time in days), prognosis, and follow-up.Results: The mean age of all individuals was 29.75 years, with 75% females. All cases presented with erythema, with 62.5% reporting pruritus and 37.5% reporting burning facial symptoms. Surgical masks and hand-hygiene products (37.5%) were the most commonly reported causative agent with 25% due to KN95/FFP type 2 use. Allergic contact dermatitis (50%) and irritant contact dermatitis (25%) were common diagnoses. Treatments included creams, emollients, and desloratadine, with restriction of irritant-causing factors. The prognosis was generally good among the cases, with 62.5% presenting complete resolution within a week and 12.5% showing moderate improvement at the fourth month after discontinuing use.Conclusion: This study finds pertinent links between PPE use and contact dermatitis during the COVID-19 pandemic. While many cases are bound to go underreported in literature, well-designed, large-scale studies in the future may help promote these associations in a more comprehensive manner

Social contributors for the rise of COVID-19 infections in South Asia: A large cross-sectional survey

Background: The ongoing global coronavirus disease 2019 (COVID-19) pandemic, caused by the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) was first reported in South Asia on 30th January 2020 in India. Ever since, certain countries have witnessed multiple waves of COVID-19, requiring attention by public health experts and strategists in the region. The objectives of this study are to assess social contributors to the recurrent waves of COVID-19 in South Asia including first demographic traits, second household characteristics and social measures, third workplace trends and personal protective equipment use, and fourth satisfaction and attitudes concerning public health measures and vaccination status. The study also aims to plan for control strategies focusing on India, Pakistan, Bangladesh, Sri Lanka, and Nepal, countries with the highest burden of COVID-19 in South Asia.Methods: A population-based large cross-sectional study was conducted from 1st July to August 10th, 2021 using online mediums. The survey consisted of 31 questions divided into sociodemographic and COVID-19 status information, household characteristics and social measures, workplace trends and personal protective measures, satisfaction and attitudes towards public health measures, and vaccination status. Bivariate, receiver operating characteristic (ROC) analysis, and the Kruskal Wallis test was conducted for factors associated to COVID-19 infection and positive vaccination status.Findings: We enrolled 1046 participants with 57.1% females and 41.8% males, comprising 48.9% healthcare workers. Statistically significant associations were found using ANOVA based on the Kruskal-Wallis test for differences between thoughts towards public health authorities implementing standard operating procedures (SOPs) and HCW status were statistically significant (P = 0.002). The most important social predictors for positive vaccination status based on the ROC analysis were gender (P \u3c 0.001), job role (P \u3c 0.001), income group (P \u3c 0.001), healthcare worker status (P \u3c 0.001), household member tested positive (P = 0.007), personal vehicle ownership (P \u3c 0.001), job requiring close contacts (P \u3c 0.001) and co-worker masking habits (P = 0.02).Conclusions: Public health experts and strategists are required to focus control strategies on political and religious gatherings, reopening offices, noncompliance of SOPs by the masses, and crowded commuting to limit the reemergence of COVID-19 infections in countries with the highest burden in the region

Acute-on-chronic Liver Failure: MELD Score 30-day Mortality Predictability and Etiology in a Pakistani Population

Background: Cirrhosis is a pathological condition that ultimately leads to liver failure. Acute on chronic liver failure (ACLF) has a high short term mortality rate. Viral hepatitis is the most common cause of liver failure in our local population. We carried out this study to identity the 30-day mortality and etiology of patients presenting with ACLF using Model for End-Stage Liver Disease (MELD) score predictability. Methodology: This was a descriptive case series, conducted at Sheikh Zayed Hospital, Lahore, Pakistan from January 31, 2018 to July 30, 2018. One hundred and eighty five patients who met the inclusion criteria were enrolled using 95% confidence level and 4% margin of error. Data was entered and analyzed with SPSS version 23.0. Numerical variables including age was presented by Mean ± S.D. Categorical variables i.e. gender, etiology of acute-on-chronic liver failure and 30-day mortality were presented by frequency and percentage. Data was stratified for age, gender, duration of chronic liver disease and MELD grade to address the effect modifiers. Post-stratification chi-square test was calculated using 95% significance (p≤0.05). Results: Majority of the enrolled patients were male (74.6%) while only 25.4% of the patients were female. One hundred and thirty patients (70.3%) had underlying viral hepatitis while twelve patients (6.5%) and forty three patients (23.2%) presented with alcoholic liver disease and drug-induced ACLF, respectively. Eighty patients (43.2%) died within 30 days of admission.The 30-day mortality with respect to MELD grade was statistically significant (p<0.001) with the highest mortality noted in grade-IV and thirty five patients (43.8%) dying within 30 days of admission (p<0.001). Grade-II and III MELD scores also contributed to the 30-day mortality with twenty three patients (28.8%) and nineteen patients (23.8%) dying within 30 days of admission (p<0.001). Conclusion: MELD scores are able to accurately predict the short-term mortality in patients with ACLF and viral hepatitis was the most common etiology in our population. Early detection and use of appropriate prognostic models may alleviate mortality and morbidity in paitents with ACLF

COVID-19 vaccine-associated thrombosis with thrombocytopenia syndrome (TTS): A systematic review and post hoc analysis

Background: A new clinical syndrome has been recognized following the COVID-19 vaccine, termed thrombosis with thrombocytopenia syndrome (TTS). The following systematic review focuses on extrapolating thrombotic risk factors, clinical manifestations, and outcomes of patients diagnosed with TTS following the COVID-19 vaccine.Methods: We utilized the World Health Organization\u27s criteria for a confirmed and probable case of TTS following COVID-19 vaccination and conducted a systematic review and posthoc analysis using the PRISMA 2020 statement. Data analysis was conducted using SPSS V25 for factors associated with mortality, including age, gender, anti-PF4/heparin antibodies, platelet nadir, D-dimer peak, time to event diagnosis, arterial or venous thrombi.Results: Of the 175 studies identified, a total of 25 studies with 69 patients were included in this systematic review and post hoc analysis. Platelet nadir (P \u3c .001), arterial or venous thrombi (χ2 = 41.911, P = .05), and chronic medical conditions (χ2 = 25.507, P = .041) were statistically associated with death. The ROC curve analysis yielded D-dimer (AUC = .646) and platelet nadir (AUC = .604) as excellent models for death prediction.Conclusion: Adenoviral COVID-19 vaccines have been shown to trigger TTS, however, reports of patients having received mRNA COVID-19 vaccines are also present. Healthcare providers are recommended to maintain a high degree of suspicion among individuals who have received the COVID-19 vaccine within the last 4 weeks

Understanding and promoting racial diversity in healthcare settings to address disparities in pandemic crisis management

Background: Health disparities have become apparent since the beginning of the COVID-19 pandemic. When observing racial discrimination in healthcare, self-reported incidences, and perceptions among minority groups in the United States suggest that, the most socioeconomically underrepresented groups will suffer disproportionately in COVID-19 due to synergistic mechanisms. This study reports racially-stratified data regarding the experiences and impacts of different groups availing the healthcare system to identify disparities in outcomes of minority and majority groups in the United States.Methods: Studies were identified utilizing PubMed, Embase, CINAHL Plus, and PsycINFO search engines without date and language restrictions. The following keywords were used: Healthcare, raci*, ethnic*, discriminant, hosti*, harass*, insur*, education, income, psychiat*, COVID-19, incidence, mortality, mechanical ventilation. Statistical analysis was conducted in Review Manager (RevMan V.5.4). Unadjusted Odds Ratios, P-values, and 95% confidence intervals were presented.Results: Discrimination in the United States is evident among racial groups regarding medical care portraying mental risk behaviors as having serious outcomes in the health of minority groups. The perceived health inequity had a low association to the majority group as compared to the minority group (OR = 0.41; 95% CI = 0.22 to 0.78; P = .007), and the association of mental health problems to the Caucasian-American majority group was low (OR = 0.51; 95% CI = 0.45 to 0.58; P \u3c .001).Conclusion: As the pandemic continues into its next stage, efforts should be taken to address the gaps in clinical training and education, and medical practice to avoid the recurring patterns of racial health disparities that become especially prominent in community health emergencies. A standardized tool to assess racial discrimination and inequity will potentially improve pandemic healthcare delivery

Biochemical testing for the diagnosis of Wilson\u27s disease: A systematic review

Background: Wilson\u27s disease (WD) is a rare inherited disorder that leads to copper accumulation in the liver, brain, and other organs. WD is prevalent worldwide, with an occurrence of 1 per 30,000 live births. Currently, there is no gold standard diagnostic test for WD. The objective of this systematic review is to determine the diagnostic accuracy for WD of three biochemical tests, namely hepatic copper, 24-hour urinary copper, and ceruloplasmin using the Leipzig criteria.Methods: Adhering to PRISMA guidelines, databases including PubMed/MEDLINE, CINAHL Plus, Web of Science, and Cochrane were searched. Studies that comprised of confirmed or suspected WD along with normal populations were included with adult and pediatric group. The sensitivity, specificity, negative predictive value and positive predictive value were computed using RevMan 5.4.Results: Nine studies were included. The best practice evidence for 24-hour urinary copper test ranged from a cutoff value of 0.64-1.6 μmol/24 h (N = 268; sensitivity = 75.6%, specificity = 98.3%). Hepatic copper test was optimally cutoff based on the ROC curve analysis at 1.2 μmol/g yielding a power of 96.4% sensitivity and 95.4% specificity (N = 1,150); however, the tried and tested 4 μmol/g cutoff, with 99.4% sensitivity and 96.1% specificity, is more widely accepted. The ceruloplasmin test cutoff value was found to be ranging from 0.14 to 0.2 g/L (N = 4,281; sensitivity = 77.1%-99%, specificity = 55.9%-82.8%).Conclusion: This paper provides a large-scale analysis of current evidence pertaining to the biochemical diagnosis of WD employing the Leipzig criteria. The laboratory values are typically based on specific subgroups based on age, ethnicity, and clinical subgroups. The findings of this systematic review must be used with caution, given the over- or under-estimation of the index tests

Industry 4.0 technologies for the manufacturing and distribution of COVID-19 vaccines

Background: The evolutionary stages of manufacturing have led us to conceptualize the use of Industry 4.0 for COVID-19 (coronavirus disease 2019), powered by Industry 4.0 technologies. Using applications of integrated process optimizations reliant on digitized data, we propose novel intelligent networks along the vaccine value chain. Vaccine 4.0 may enable maintenance processes, streamline logistics, and enable optimal production of COVID-19 vaccines.Vaccine 4.0 framework: The challenge in applying Vaccine 4.0 includes the requirement of large-scale technologies for digitally transforming manufacturing, producing, rolling-out, and distributing vaccines. With our framework, Vaccine 4.0 analytics will target process performance, process development, process stability, compliance, quality assessment, and optimized maintenance. The benefits of digitization during and post the COVID-19 pandemic include first, the continual assurance of process control, and second, the efficacy of big-data analytics in streamlining set parameter limits. Digitization including big data-analytics may potentially improve the quality of large-scale vaccine production, profitability, and manufacturing processes. The path to Vaccine 4.0 will enhance vaccine quality, improve efficacy, and compliance with data-regulated requirements.Discussion: Fiscal and logistical barriers are prevalent across resource-limited countries worldwide. The Vaccine 4.0 framework accounts for expected barriers of manufacturing and equitably distributing COVID-19 vaccines. With amalgamating big data analytics and biometrics, we enable the identification of vulnerable populations who are at higher risk of disease transmission. Artificial intelligence powered sensors and robotics support thermostable vaccine distribution in limited capacity regions, globally. Biosensors isolate COVID-19 vaccinations with low or limited efficacy. Finally, Vaccine 4.0 blockchain systems address low- and middle-income countries with limited distribution capacities.Conclusion: Vaccine 4.0 is a viable framework to optimize manufacturing of vaccines during and post the COVID-19 pandemic

THE INCIDENCE OF ALCOHOL USE DISORDERS DURING THE COVID-19 PANDEMIC

Background: The COVID-19 pandemic has introduced a myriad of challenges to healthcare systems and public health policies across the globe. Individuals with alcohol use disorders are at peaked risk due to mental, socio-demographic, and economic factors leading to hindered mental health service access, misinformation and adherence. Methods: Keywords including “alcohol use”, “death”, “hand sanitizer", "overdose" and "COVID-19" were used to obtain 8 media reports for case analysis. A review of 34 manually extracted records were also conducted using PubMed, MEDLINE, Scopus, and the Embase database with no time and language restrictions. Results: A total of 2,517 individuals with alcohol overdose across the United States, India, Canada, and Iran were presented. The majority of cases were male, ages 21-65. Common contributors were linked to socio-economic changes, disruption to mental health services, and physical isolation. Conclusion: While original studies are essential to evaluate the etiologies of alcohol use and misuse during pandemics, the dissemination of misinformation must be curbed by directing vulnerable individuals towards accurate information and access to mental health services