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Background: Interleukin-2 is being investigated as a potential therapeutic option in systemic lupus erythematosus (SLE), but the current findings regarding its effectiveness remained inconclusive. Objectives: To assess the association between the administration of low-dose interleukin-2 and the SLE Disease Activity Index (SLEDAI) score among SLE patients. Methods: A meta-analysis was conducted by gathering articles from Scopus, Pubmed, and Embase databases (PROSPERO registration ID: 451971). Essential data from each study was extracted, and the impact of administering low-dose interleukin-2 on the SLEDAI score in SLE patients was assessed using the inverse variance method. Results: We conducted an analysis of 7 articles involving 194 patients. Our study revealed that the administration of low-dose interleukin-2 was associated with a decrease in the SLEDAI score, showing an average reduction of −4.3 points from baseline. Furthermore, when comparing SLE patients treated with standard of care plus low-dose interleukin-2 to those receiving standard of care alone, we observed a significantly greater improvement in the SLEDAI score, with an average difference of 2.91 points. Conclusion: Our results indicate the potential beneficial impact of low-dose interleukin-2 in reducing disease activity and enhancing outcomes in SLE management.

Background: Some Ebola vaccines have been developed and tested in phase III clinical trials. However, assessment of whether public have willingness to purchase or not, especially in unaffected areas, is lacking. The aim of this study was to determine willingness to pay (WTP) for a hypothetical Ebola vaccine in Indonesia. Methods: A cross-sectional study was conducted from 1 August to 30 December 2015 in five cities in Aceh province of Indonesia. Patients’ family members who visited outpatient departments were approached and interviewed about their sociodemographic characteristics, knowledge of Ebola, attitude towards vaccination practice and their WTP for a hypothetical Ebola vaccine. A multivariable linear regression model assessed the relationship between these explanatory variables and WTP. Results: During the study, 500 participants were approached and interviewed. There were 424 (84.8%) respondents who completed the interview and 74% (311/424) expressed their acceptance for an Ebola vaccine. There were 288 participants who were willing to pay for an Ebola vaccine (92.6% out of 311). The mean of WTP was US$2.08 (95% CI: 1.75-2.42). The final multivariable model indicated that young age, high educational attainment, working as a private employee, entrepreneur or civil servant (compared to farmers), being unmarried, and residing in a suburb (compared to a city) were associated with higher WTP. Conclusions: Although the proportion of the participants who would accept the Ebola vaccine was relatively high, the amount they were willing to pay for Ebola vaccine was very low. This finding would indicate the need of subsidies for Ebola vaccine in the country.

Background: The simple nutritional assessment tools by Mini Nutritional Assessment (MNA) and Patient Generated Subjective Global Assessment (PG – SGA) was proposed to affect the Quality of Life (QOL) in hemodialysis patients. However, currently, no evidence assessed the potency of MNA and PG - SGA for predicting the QOL in hemodialysis patients. Objective: To assess the potential implication of MNA and PG-SGA nutritional tools and the QOL among hemodialysis patients. Methods: A cross - sectional study was performed in Universitas Muhammadiyah Malang Hospital, Malang, Indonesia. A validated Kidney Disease Quality of Life – 36™ (KDQOL – 36™) instrument was used to assess the QOL. The nutritional status was assessed using MNA and PG - SGA checklist. The association between nutritional status and QOL was determined by using multiple logistic regression. Results: A total of 96 hemodialysis patients was enrolled in our study. Of them, good QOL was observed in 75 patients (78.12%). We found that hemodialysis patients with higher MNA score and lower PG - SGA score was associated with good QOL. We also found that normal MNA nutritional status was associated with good QOL. Moreover, we also found that the score of MNA ≥23.75 and PG - SGA score ≤3,5 were associated with good QOL. Conclusion: MNA and PG-SGA nutritional assessment tools are the important indicator in predicting the QOL in hemodialysis patients.

BackgroundSince 2020, Indonesian health professionals have been affected by burnout as the physiological impact due to the COVID-19 pandemic. Malang has contributed to a substantial number of new daily cases and death rates in East Java, an epicenter of COVID-19 in Indonesia. However, a study about how burnout affected Malang health professionals was never conducted.ObjectivesThis research aimed to assess the prevalence and factors associated with burnout among health professionals during the COVID-19 pandemic in Malang, Indonesia.Materials and MethodsA cross-sectional study was carried out with an online survey conducted in 5 major hospitals in Malang. We conducted a study about the prevalence rate of burnout in Malang and the association between sociodemographic factors, occupational hazards, and the Maslach Burnout Inventory-Human Services Survey (MBI-HSS). The associations were presented as odds ratio (OR) and 95% confidence interval (CI).ResultsWe analyzed 1,077 health professionals in Malang. Our result showed that the prevalence of burnout among health professionals in Malang is 22.0%. Respondents under the age of 30 tend to experience a higher level of burnout by 3.4-fold (OR = 3.43, p-value < 0.001), compared with those over the age of 40 years. Our data showed that respondents working longer than 100 h/week tend to experience burnout by 3.8-fold (OR = 3.83, p-value < 0.001).ConclusionApproximately one-fifth of the health professionals in Malang suffered from burnout during the COVID-19 pandemic, and MBI-HSS subscales are strongly associated with age and work hours.

Background: The gene FOXO3a has been elucidated to govern the development of chronic granulocytic leukemia (CGL). Moreover, it has been suggested that the levels of FOXO3a in circulation are affected by the FOXO3a rs4946936 gene polymorphism. However, no study has assessed the correlation between the FOXO3a rs4946936 gene polymorphism and the levels of FOXO3a. The objective of this study was to assess the association between the FOXO3a rs4946936 gene polymorphism and the levels of FOXO3a in CGL patients treated with imatinib mesylate. Methods: A cross-sectional study was conducted from February 2019 to February 2020. The genotyping of FOXO3a rs4946936 gene polymorphism was conducted using PCR-RFLP, and the levels of FOXO3a were assessed using ELISA. The association between the FOXO3a rs4946936 gene polymorphism and the levels of FOXO3a were assessed using multiple logistic regression. Results: A total of 60 CGL patients were assessed in our study. Among them, the CC, CT, and TT genotypes of the FOXO3a rs4946936 gene polymorphism were 35.0%, 48.3%, and 16.7% respectively. Our calculation revealed that elevated levels of FOXO3a were found in CGL patients with the CC genotype of the FOXO3a rs4946936 gene polymorphism. While we failed to clarify the association between either the CT or the TT genotype of FOXO3a rs4946936 gene polymorphism and the levels of FOXO3a. Conclusion: Our study identifies that the CC genotype of the FOXO3a rs4946936 gene polymorphism affects the elevated levels of FOXO3a in CGL patients treated with imatinib mesylate.

Abstract Backgrounds In the last two decades, studies have been widely carried out to assess the association between single-nucleotide polymorphisms (SNPs) of calcium-sensing receptor (CaSR) gene in exon 7 and the risk of urolithiasis. However, inconsistency across the studies was reported. Therefore, our current study aimed to perform a meta-analysis concerning the association between the risk of urolithiasis and the gene polymorphisms of CaSR R990G, CaSR A986S, and CaSR Q1011E. Methods Published papers from PubMed, Embase, Cohcrane, and Web of science were included for the study, and they were analyzed using fixed or random effect model. Results A total of 11 papers consisting of eight papers evaluating CaSR R990G, nine papers evaluating CaSR A986S, and five papers evaluating CaSR Q1011E were included in our analysis. Our pooled calculation found that protective effect against urolithiasis was observed in R allele and RR genotype of CaSR R990G and A allele and AA genotype of CaSR A986S. Conversely, increased susceptibility to urolithiasis was found in G allele and RG genotype of CaSR R990G and S allele of CaSR A986S. Interestingly, our findings in sub-group analysis confirmed that the correlation between CaSR R990G and urolithiasis was found in Caucasian population. Meanwhile, in Asian population, the association was observed in CaSR A986S. Conclusions CaSR R990G and CaSR A986S, but not CaSR Q1011E, are associated with the risk of urolithiasis.

Background: Cytokine storm has been widely known to contribute to the development of the critical condition in patients with coronavirus disease 2019 (COVID-19), and studies had been conducted to assess the potential aspect of cytokine storm elimination by performing therapeutic plasma exchange (TPE). However, contradictory findings were observed. The objective of this study was to assess the association between TPE and the reduction of mortality of critically ill COVID-19 patients. Methods: A meta-analysis was conducted by collecting data from PubMed, Scopus, and Web of Science. Data on the mortality rate of critically ill COVID-19 patients treated with TPE plus standard of care and that of patients treated with standard of care alone were analyzed using a Z test. Results: We included a total of four papers assessing the association between TPE and the risk of mortality among critically ill COVID-19 patients. Our findings suggested that critically ill COVID-19 patients treated with TPE had lower risk of mortality compared to those without TPE treatment. Conclusion: Our study has identified the potential benefits of TPE in reducing the risk of mortality among critically ill COVID-19 patients.

Background: The pathogenesis of herniated nucleus pulposus (HNP) is complex and may involve the wide variety of gene polymorphism. However, the reports from the existing studies are inconclusive. The objective of this study was to determine the role of single nucleotide polymorphisms (SNPs) in interleukin 1 alpha (IL-1A), tumor necrosis factor-alpha (TNF-A), and vitamin D receptor (VDR) genes on the susceptibility to herniated nucleus pulposus (HNP). Methods: Four databases (PubMed, Embase, Cochrane, and Web of Science) were searched as of April 1 st, 2021. Authors, publication year, targeted genes, genotype and allele frequency in each case and control groups were collected. Newcastle-Ottawa scale was used to evaluate the publication quality. The pooled estimates of association of IL-1A -889C>T (rs1800587), TNF-A -238G>A (rs361525), and VDR TaqI (rs731236) and susceptibility to HNP were assessed using Z test. Results: We screened 3,067 unique studies for eligibility and three, two and nine case-control studies on IL-1A -889C>T, TNF-A -238G>A, and VDR TaqI were included, respectively, in our meta-analysis. The studies consisting 369 HNP cases and 433 controls for IL-1A -889C>T, 252 cases and 259 controls for TNF-A -238G>A and 1130 cases and 2096 controls for VDR TaqI. Our pooled estimates indicated that there was no significant association of those SNPs with the susceptibility to HNP in any genotype, dominant model, recessive model, or allele comparations. Conclusion: Although individual studies suggested the important role of gene expression dysregulation associated with SNPs in IL-1A, TNF-A, and VDR, our data indicated that IL-1A -889C>T, TNF-A -238G>A, and VDR TaqI had weak association with HNP susceptibility in both genotypes and allele distributions. However, since heterogeneity was identified among studies included in this meta-analysis, further meta-analysis with a larger population and subgroup analysis on specific population are warranted to support this finding.

Countries worldwide have deployed mass COVID-19 vaccination drives, but there are people who are hesitant to receive the vaccine. Studies assessing the factors associated with COVID-19 vaccination hesitancy are inconclusive. This study aimed to assess the global prevalence of COVID-19 vaccination hesitancy and determine the potential factors associated with such hesitancy. We performed an organized search for relevant articles in PubMed, Scopus, and Web of Science. Extraction of the required information was performed for each study. A single-arm meta-analysis was performed to determine the global prevalence of COVID-19 vaccination hesitancy; the potential factors related to vaccine hesitancy were analyzed using a Z-test. A total of 56 articles were included in our analysis. We found that the global prevalence of COVID-19 vaccination hesitancy was 25%. Being a woman, being a 50-year-old or younger, being single, being unemployed, living in a household with five or more individuals, having an educational attainment lower than an undergraduate degree, having a non-healthcare-related job and considering COVID-19 vaccines to be unsafe were associated with a higher risk of vaccination hesitancy. In contrast, living with children at home, maintaining physical distancing norms, having ever tested for COVID-19, and having a history of influenza vaccination in the past few years were associated with a lower risk of hesitancy to COVID-19 vaccination. Our study provides valuable information on COVID-19 vaccination hesitancy, and we recommend special interventions in the sub-populations with increased risk to reduce COVID-19 vaccine hesitancy.

Background: Recent evidence suggested that the higher titers of anti-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibody from convalescent plasma donors contributed to the clinical improvement in coronavirus disease 2019 (COVID-19) patients. However, the titers of anti-SARS-CoV-2 antibodies varied in each individual, and the precise factors that might govern such variation have not been elucidated. Objectives: To assess the factors associated with high titers of anti-SARS-CoV-2 antibody among COVID-19 convalescent plasma (CCP) donors. Methods: A cross-sectional study was conducted in Saiful Anwar General Hospital, Malang, Indonesia. Information of interest including demographic characteristics, clinical symptoms, comorbidities, laboratory findings, and the titers of anti-SARS-CoV-2 antibody among COVID-19 CCP donors were collected. The correlation was assessed using multiple logistic regression. Results: A total of 50 COVID-19 CCP donors with the titers of anti-SARS-CoV-2 antibody of more than 1:320 and 33 donors with the titers of less than 1:320 were analyzed. Our analysis revealed that CCP donors with history of cough, fever, dyspnea, and pneumonia significantly had higher titers of anti-SARS-CoV-2 antibody compared to asymptomatic donors. Moreover, CCP donors with elevated levels of eosinophils and immature granulocytes and low levels of albumins had higher levels of anti-SARS-CoV-2 antibody. The titer of antibody was not affected by comorbidities of donors. Conclusions: CPP donors who had experience of symptomatic COVID-19 with high eosinophils level, high immature granulocytes and low albumin level have higher titers of anti-SARS-COV-2 antibody than those who experienced asymptomatic COVID-19. Our current findings may be used as the additional baseline criteria for selecting the donors of CCP for the management of COVID-19.

Background: Convalescent plasma (CCP) has been used for treating some infectious diseases; however, the efficacy of CCP in coronavirus disease 2019 (COVID-19) remains controversial. The aim of this research was to assess the efficacy of CCP as an adjunctive treatment in COVID-19 patients. Methods: Embase, PubMed, Web of Science, Cochrane and MedRix were searched for potentially relevant articles. All included papers were assessed for the quality using modified Jadad scale and Newcastle-Ottawa scale for randomized controlled trial (RCT) and non – RCT, respectively. We used a Q test and Egger test to assess the heterogeneity and publication bias among studies, respectively. Mortality rates between patients treated with standard treatment and standard treatment with CCP were compared using a Z test. Results: A total of 12 papers consisting of three cross-sectional studies, one prospective study, five retrospective studies, and three RCT studies were included in our analysis. Of them, a total of 1,937 patients treated with CCP and 3,405 patients without CCP were included. The risk of mortality was 1.92-fold higher in patients without CCP compared to patients treated with CCP (OR: 1.92; 95%CI: 1.33, 2.77; p=0.0005). In severe COVID-19 sub-group analysis, we found that patients without CCP had a 1.32 times higher risk of mortality than those treated with CCP (OR: 1.32; 95%CI: 1.09, 1.60; p=0.0040). Conclusions: CCP, as adjunctive therapy, could reduce the mortality rate among COVID-19 patients.

Abstract Background Since first reported having the association with essential hypertension, angiotensin II type 1 receptor (AT1R) A1166C was globally investigated worldwide. However, controversy was found. Furthermore, previous meta-analyses did not adequate to clarify the precise correlation due to some limitations. Therefore, we aimed to perform a meta-analysis concerning the association between AT1R A1166C single-nucleotide polymorphism (SNP) and the risk of essential hypertension with eliminating the limitations of previous studies. Methods A meta-analysis was conducted from February to March 2019. Some information related to sample size of hypertension and control groups and genotype frequencies of hypertension and control groups were extracted from each study. Data were analyzed using fixed or random effect model to determine the overall correlation. Results A total of 45 papers consisting of 11911 cases and 1340 controls were enrolled for the study. Our overall analysis showed that C allele and AC genotype of AT1R A1166C was associated with 1.18-fold and 1.15-fold respectively increased risk of essential hypertension, while the decreased risk of essential hypertension was observed in A allele and AA genotype. In sub-group analysis, increased risk of essential hypertension was found in C allele, AC genotype, and CC genotype of both Asian population and PCR-RFLP sub-groups, while decreased risk was observed in A allele and AA genotype. Conclusions Our meta-analysis reveals that AT1R A1166C remains a valuable SNP having an association with the risk of essential hypertension.

Objectives: The aim of the study was to evaluate the correlation between left ventricular hypertrophy and the gene polymorphism of angiotensin-converting enzyme (ACE) intron deletion (I/D) and ACE G2350A. Methods: Information related to the sample size and genotype frequencies was extracted from each study. Results: Our results found that the D allele (p = 0.0180) and DD genotype (p = 0.0110) of ACE I/D had a significant association with increasing the risk of left ventricular hypertrophy, whereas the I allele (p = 0.0180), but not II (p = 0.1660) and ID genotypes (p = 0.1430), was associated with decreasing the risk of left ventricular hypertrophy. On other hand, we found that the A allele (p = 0.0020) and GA genotype of ACE G2350A (p = 0.0070) had the correlation with increasing the risk of left ventricular hypertrophy. Conclusions: Our meta-analysis reveals that the D allele of ACE I/D and the A allele of ACE G2350A are associated with increasing the risk of left ventricular hypertrophy. Keywords: Left ventricular hypertrophy, Angiotensin-converting enzyme, ACE I/D, ACE G2350A

Background: This study aimed to determine the cumulative prevalence of prolonged gastrointestinal (GI) symptoms, including nausea, vomiting, diarrhea, lack of appetite, abdominal pain, and dysgeusia, in survivors of both mild and severe COVID-19 worldwide and to discuss the potential pathogenesis. Methods: Three databases (PubMed, Scopus, and Web of Science) were searched for relevant articles up to January 30, 2021. Data on study characteristics, clinical characteristics during follow-up, the number of patients with prolonged GI symptoms, and total number of COVID-19 survivors were retrieved according to PRISMA guidelines. The quality of eligible studies was assessed using the Newcastle-Ottawa scale. The pooled prevalence of specific prolonged GI symptoms was calculated and the association between COVID-19 severity and the occurrence of prolonged GI symptoms was assessed if appropriate. Results: The global prevalence of prolonged nausea was 3.23% (95% CI: 0.54%–16.53%) among 527 COVID-19 survivors. Vomiting persisted in 93 of 2,238 COVID-19 survivors (3.19%, 95% CI: 1.62%–6.17%) and prolonged diarrhea was found in 34 of 1,073 survivors (4.12%, 95% CI: 1.07%–14.64%). A total of 156 patients among 2,238 COVID-19 survivors (4.41%, 95% CI: 1.91%–9.94%) complained of persistent decreased or loss of appetite. The cumulative prevalence of prolonged abdominal pain was 1.68% (95% CI: 0.84%–3.32%), whereas persistent dysgeusia was identified in 130 cases among 1,887 COVID-19 survivors (7.04%, 95% CI: 5.96%–8.30%). Data was insufficient to assess the relationship between COVID-19 severity and the occurrence of all prolonged GI symptoms. Conclusion: Persistent GI symptoms among COVID-19 survivors after discharge or recovery raises a concern regarding the long-term impact of the COVID-19 infection on the quality of life of the survivors. Despite several potential explanations proposed, studies that aim to follow patients after recovery from COVID-19 and determine the pathogenesis of the prolonged symptoms of COVID-19 survivors are warranted. PROSPERO registration: CRD42021239187.

Background: This study was conducted to determine the prevalence of headache in coronavirus disease 2019 (COVID-19) and to assess its association as a predictor for COVID-19. This study also aimed to discuss the possible pathogenesis of headache in COVID-19. Methods: Available articles from PubMed, Scopus, and Web of Science were searched as of September 2nd, 2020. Data on characteristics of the study, headache and COVID-19 were extracted following the PRISMA guidelines. Biases were assessed using the Newcastle-Ottawa scale. The cumulative prevalence of headache was calculated for the general population (i.e. adults and children). The pooled odd ratio (OR) with 95% confidence intervals (95%CI) was calculated using the Z test to assess the association between headache and the presence of COVID-19 cases. Results: We included 104,751 COVID-19 cases from 78 eligible studies to calculate the global prevalence of headache in COVID-19 and 17 studies were included to calculate the association of headache and COVID-19. The cumulative prevalence of headache in COVID-19 was 25.2% (26,464 out of 104,751 cases). Headache was found to be more prevalent, approximately by two-fold, in COVID-19 patients than in non-COVID-19 patients (other respiratory viral infections), OR: 1.73; 95% CI: 1.94, 2.5 with p=0.04. Conclusion: Headache is common among COVID-19 patients and seems to be more common in COVID-19 patients compared to those with the non-COVID-19 viral infection. No definitive mechanisms on how headache emerges in COVID-19 patients but several possible hypotheses have been proposed. However, extensive studies are warranted to elucidate the mechanisms. PROSPERO registration: CRD42020210332 (28/09/2020)

Background: While it has been known that the development of chronic kidney disease (CKD) and age-related cognitive impairment involves several mediators, the evidence in clinical practice only reveals nitride oxide synthase (NOS) and klotho. However, the evidence for this topic is conflicted. The aim of this study was to assess the role of NOS and klotho single nucleotide polymorphisms (SNPs) in the pathogenesis of CKD and age-related cognitive impairment. Methods: We performed a meta-analysis during October to December 2019. Paper collection was performed in major scientific websites, and we extracted information of interest from each paper. Data were analyzed using a Z-test with either random or fixed effect model. Results: Our initial assessment identified NOS3 G894T, NOS3 T786C, NOS3 4b/4a, klotho (KL) G395A, and KL C1818T as the gene candidate for our meta-analysis. Our pooled calculation revealed that NOS3 G894T was associated with the risk of both age-related cognitive impairment and CKD. Increased susceptibility to age-related cognitive impairment was observed in the GG genotype, and increased risk of CKD was found in patients with a single T allele and TT genotype for NOS3 nucleotide 894. For NOS3 4b/4a, increased risk of CKD was only found in 4a4a genotype. For NOS3 T786C, we failed to show the association with both CKD and age-related cognitive impairment. Subsequently, for KL G395A, A allele and GA genotype were found to correlate with increased susceptibility to CKD, while its correlation to age-related cognitive impairment was failed to clarify. For KL C1818T, our analysis failed to find the correlation with the risk of CKD. Conclusions: Our results reveal that the NOS3 G894T gene polymorphism has a crucial role in the pathogenesis of both CKD and age-related cognitive impairment.

Background: Several studies have revealed the potential use of tocilizumab in treating COVID-19 since no therapy has yet been approved for COVID-19 pneumonia. Tocilizumab may provide clinical benefits for cytokine release syndrome in COVID-19 patients. Methods: We searched for relevant studies in PubMed, Embase, Medline, and Cochrane published from March to October 2020 to evaluate optimal use and baseline criteria for administration of tocilizumab in severe and critically ill COVID-19 patients. Research involving patients with confirmed SARS-CoV-2 infection, treated with tocilizumab and compared with the standard of care (SOC) was included in this study. We conducted a systematic review to find data about the risks and benefits of tocilizumab and outcomes from different baseline criteria for administration of tocilizumab as a treatment for severe and critically ill COVID-19 patients. Results: A total of 26 studies, consisting of 23 retrospective studies, one prospective study, and two randomised controlled trials with 2112 patients enrolled in the tocilizumab group and 6160 patients in the SOC group, were included in this meta-analysis. Compared to the SOC, tocilizumab showed benefits for all-cause mortality events and a shorter time until death after first intervention but showed no difference in hospital length of stay. Upon subgroup analysis, tocilizumab showed fewer all-cause mortality events when CRP level ≥100 mg/L, P/F ratio 200-300 mmHg, and P/F ratio

Background: The unpredictability of the progression of coronavirus disease 2019 (COVID-19) may be attributed to the low precision of the tools used to predict the prognosis of this disease. Objective: To identify the predictors associated with poor clinical outcomes in patients with COVID-19. Methods: Relevant articles from PubMed, Embase, Cochrane, and Web of Science were searched as of April 5, 2020. The quality of the included papers was appraised using the Newcastle-Ottawa scale (NOS). Data of interest were collected and evaluated for their compatibility for the meta-analysis. Cumulative calculations to determine the correlation and effect estimates were performed using the Z test. Results: In total, 19 papers recording 1,934 mild and 1,644 severe cases of COVID-19 were included. Based on the initial evaluation, 62 potential risk factors were identified for the meta-analysis. Several comorbidities, including chronic respiratory disease, cardiovascular disease, diabetes mellitus, and hypertension were observed more frequent among patients with severe COVID-19 than with the mild ones. Compared to the mild form, severe COVID-19 was associated with symptoms such as dyspnea, anorexia, fatigue, increased respiratory rate, and high systolic blood pressure. Lower levels of lymphocytes and hemoglobin; elevated levels of leukocytes, aspartate aminotransferase, alanine aminotransferase, blood creatinine, blood urea nitrogen, high-sensitivity troponin, creatine kinase, high-sensitivity C-reactive protein, interleukin 6, D-dimer, ferritin, lactate dehydrogenase, and procalcitonin; and a high erythrocyte sedimentation rate were also associated with severe COVID-19. Conclusion: More than 30 risk factors are associated with a higher risk of severe COVID-19. These may serve as useful baseline parameters in the development of prediction tools for COVID-19 prognosis.

Background: In this study, we aimed to determine the global prevalence, chronological order of symptom appearance, and mortality rates with regard to hemorrhagic and ischemic stroke in patients with coronavirus disease 2019 (COVID-19) and to discuss possible pathogeneses of hemorrhagic and ischemic stroke in individuals with the disease. Methods: We searched the PubMed, Scopus, and Web of Science databases for relevant articles published up to November 8, 2020. Data regarding study characteristics, hemorrhagic stroke, ischemic stroke, and COVID-19 were retrieved in accordance with the PRISMA guidelines. The Newcastle-Ottawa scale was used to assess the quality of the eligible studies. The pooled prevalence and mortality rate of hemorrhagic and ischemic stroke were calculated. Results: The pooled estimate of prevalence of hemorrhagic stroke was 0.46% (95% CI 0.40%–0.53%; I2=89.81%) among 67,155 COVID-19 patients and that of ischemic stroke was 1.11% (95% CI 1.03%–1.22%; I2=94.07%) among 58,104 COVID-19 patients. Ischemic stroke was more predominant (incidence: 71.58%) than hemorrhagic stroke (incidence: 28.42%) in COVID-19 patients who experienced a stroke. In COVID-19 patients who experienced a stroke, hospital admission with respiratory symptoms was more commonly reported than that with neurological symptoms (20.83% for hemorrhagic stroke and 5.51% for ischemic stroke versus 6.94% for hemorrhagic stroke and 5.33% for ischemic stroke, respectively). The pooled mortality rate of COVID-19 patients who experienced a hemorrhagic and ischemic stroke was 44.72% (95% CI 36.73%–52.98%) and 36.23% (95% CI 30.63%–42.24%), respectively. Conclusions: Although the occurrence of hemorrhagic and ischemic stroke is low, the mortality rates of both stroke types in patients with COVID-19 are concerning, and therefore, despite several potential pathogeneses that have been proposed, studies aimed at definitively elucidating the mechanisms of hemorrhagic and ischemic stroke in individuals with COVID-19 are warranted. PROSPERO registration: CRD42020224470 (04/12/20)

Background: The present study aimed to determine the global prevalence of anosmia and dysgeusia in coronavirus disease 2019 (COVID-19) patients and to assess their association with severity and mortality of COVID-19. Moreover, this study aimed to discuss the possible pathobiological mechanisms of anosmia and dysgeusia in COVID-19. Methods: Available articles from PubMed, Scopus, Web of Science, and preprint databases (MedRxiv, BioRxiv, and Researchsquare) were searched on November 10th, 2020. Data on the characteristics of the study (anosmia, dysgeusia, and COVID-19) were extracted following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guideline. Newcastle–Ottawa scale was used to assess research quality. Moreover, the pooled prevalence of anosmia and dysgeusia were calculated, and the association between anosmia and dysgeusia in presence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was assessed using the Z test. Results: Out of 32,142 COVID-19 patients from 107 studies, anosmia was reported in 12,038 patients with a prevalence of 38.2% (95% CI: 36.5%, 47.2%); whereas, dysgeusia was reported in 11,337 patients out of 30,901 COVID-19 patients from 101 studies, with prevalence of 36.6% (95% CI: 35.2%, 45.2%), worldwide. Furthermore, the prevalence of anosmia was 10.2-fold higher (OR: 10.21; 95% CI: 6.53, 15.96, p < 0.001) and that of dysgeusia was 8.6-fold higher (OR: 8.61; 95% CI: 5.26, 14.11, p < 0.001) in COVID-19 patients compared to those with other respiratory infections or COVID-19 like illness. To date, no study has assessed the association of anosmia and dysgeusia with severity and mortality of COVID-19. Conclusion: Anosmia and dysgeusia are prevalent in COVID-19 patients compared to those with the other non-COVID-19 respiratory infections. Several possible mechanisms have been hypothesized; however, future studies are warranted to elucidate the definitive mechanisms of anosmia and dysgeusia in COVID-19. Protocol registration: PROSPERO CRD42020223204.

Background: There is controversy among physicians regarding the use of dual antiplatelet therapy (DAPT) in acute coronary syndrome (ACS) patients treated with coronary artery bypass grafting (CABG). Moreover, the evidence of previous studies about this topic remained inconclusive. This study aimed to perform a meta-analysis concerning the relation between the risk of major bleeding and the use of different DAPT (clopidogrel or ticagrelor) in ACS patients treated with CABG. Methods: A meta-analysis was conducted during March to October 2019. Searches were carried out in Pubmed, Embase, Cochrane, and Web of Science. The predictor covariate in our present study was DAPT (clopidogrel or ticagrelor), and the outcome measure was the risk of major bleeding. Sub-group analysis was also performed, where data were classified into pre- and post-CABG. Furthermore, to determine the correlation and effect estimation, data were analyzed using fixed or random effect model. Results: A total of 13 studies consisting 34,015 patients treated with clopidogrel and 32,661 patients treated with ticagrelor was included in our study. Our pooled calculation revealed that the incidence of major bleeding was not different significantly between clopidogrel and ticagrelor. In pre- and post-CABG sub-groups, our results also found no significant difference in major bleeding incidence between clopidogrel and ticagrelor groups. Conclusions: Our meta-analysis clarifies that clopidogrel, compared to ticagrelor, or vice versa, is not associated with the risk of major bleeding in ACS patients treated with CABG.

Background: The unpredictability of the progression of coronavirus disease 2019 (COVID-19) may be attributed to the low precision of the tools used to predict the prognosis of this disease. Objective: To identify the predictors associated with poor clinical outcomes in patients with COVID-19. Methods: Relevant articles from PubMed, Embase, Cochrane, and Web of Science were searched and extracted as of April 5, 2020. Data of interest were collected and evaluated for their compatibility for the meta-analysis. Cumulative calculations to determine the correlation and effect estimates were performed using the Z test. Results: In total, 19 papers recording 1,934 mild and 1,644 severe cases of COVID-19 were included. Based on the initial evaluation, 62 potential risk factors were identified for the meta-analysis. Several comorbidities, including chronic respiratory disease, cardiovascular disease, diabetes mellitus, and hypertension were observed more frequent among patients with severe COVID-19 than with the mild ones. Compared to the mild form, severe COVID-19 was associated with symptoms such as dyspnea, anorexia, fatigue, increased respiratory rate, and high systolic blood pressure. Lower levels of lymphocytes and hemoglobin; elevated levels of leukocytes, aspartate aminotransferase, alanine aminotransferase, blood creatinine, blood urea nitrogen, high-sensitivity troponin, creatine kinase, high-sensitivity C-reactive protein, interleukin 6, D-dimer, ferritin, lactate dehydrogenase, and procalcitonin; and a high erythrocyte sedimentation rate were also associated with severe COVID-19. Conclusion: More than 30 risk factors are associated with a higher risk of severe COVID-19. These may serve as useful baseline parameters in the development of prediction tools for COVID-19 prognosis.

Background: Angiotensin-converting enzyme (ACE) inhibitors-related cough had been reported to contribute for discontinuation of ACE inhibitors therapy. The role of ACE I/D and bradykinin B2 receptor T/C genes in ACE inhibitors-related cough is still unclear. Objectives: To determine ACE I/D and bradykinin B2 receptor T/C genes polymorphisms in patients with ACE-inhibitors-related cough. Subjects and methods: An analytical study with cross-sectional design was conducted at Saiful Anwar General Hospital from June 2013 to September 2014. We used the polymerase chain reaction to genotype ACE I/D and bradykinin B2 receptor T/C genes. Data on both ACE I/D and bradykinin B2 receptor T/C genes polymorphisms in cough and non cough group of hypertensive patients treated with ACE inhibitors in our Hospital during the period were analyzed using multiple logistic regression. Moreover, a meta-analysis was performed to summarize findings from other regions. Results: A total of 18 patients with cough (21%) and 67 patients without cough (79%) of hypertensive patients treated with ACE inhibitors from our Hospital during the period were analyzed for this study. In our population, no correlation was observed between ACE inhibitors-related cough and both ACE I/D (p = 0.560) and bradykinin B2 receptor T/C (p = 0.475) genes polymorphism. However, our meta-analysis of five studies consisting of 267 patients with cough and 346 patients without cough revealed that higher risk of ACE inhibitors-related cough was 1.82-fold associated with T allele of bradykinin B2 receptor T/C gene polymorphism (p = 0.0310). Conclusions: While the evidence in our meta-analysis suggests strong role for bradykinin gene polymorphism in ACE inhibitors-related cough, however, in our population, we did not find any association. Keywords: ACE inhibitors-related cough, ACE I/D gene polymorphism, Bradykinin B2 receptor T/C gene polymorphism, Hypertension

Background: Several studies have reported hip geometry to predict the femoral neck fractures. However, they showed inconsistency. Objectives: To determine the association between hip geometry and femoral neck fractures. Methods: Published literature from PubMed and Embase databases (until May 25th, 2017) was searched for eligible publications. The information related to (1) name of first author; (2) year of publication; (3) country of origin; (4) sample size of cases and controls and (5) mean and standard deviation of cases and controls were extracted. The pooled odds ratios (ORs) and 95% confidence intervals (95% CIs) for the association between hip geometry and femoral neck fractures were assessed using random or fixed effect model. A Comprehensive Meta-analysis software, version 2.0, was used to analyse the data. Results: A total of 11 studies were included in this study. Our results showed that increase in hip axis length (OR 95% CI = 1.53 [1.06–2.21], p = 0.025), femoral neck angle (OR 95% CI = 1.47 [1.01–2.15], p = 0.044) and neck width (OR 95% CI = 2.68 [1.84–3.91], p

Background: There are many studies about the association of β fibrinogen gene G-455A polymorphism and the risk of coronary heart disease (CHD). However, the results of these studies are inconsistent. Objective: This study aimed to investigate the association of β fibrinogen gene G-455A polymorphism with the risk of CHD using meta analysis. This study was limited to the Asian population. Methods: Published studies from PubMed, Embase, and CNKI databases (up to December 20th, 2015) were searched for eligible publications. The following information was extracted from each study: (1) name of first author; (2) year of publication; (3) country of origin; (4) sample size of cases and controls, and (5) size of each allele. The combined odds ratios (ORs) and 95% confidence intervals (95% CIs) for the association between β fibrinogen gene G-455A polymorphism and the risk of CHD were assessed using random or fixed effect model. A comprehensive meta analysis (CMA) 2.0 was used to analyze the data. Results: Nineteen studies (4011 cases/3673 controls) regarding the association of β fibrinogen gene G-455A polymorphism and the risk of CHD were included in this meta analysis. The results indicated that β fibrinogen gene G-455A polymorphism was associated with increased (A vs. G: OR 95% CI = 1.42 [1.19–1.70], p

Objective: The mode of delivery in breech presentation (BP) is controversial. Several studies have reported the advantages and disadvantages of delivery mode in BP. The aim of this study was to compare the Apgar scores in BPs between vaginal and cesarean delivery. Materials and Methods: A retrospective study was conducted at Dr. Zainoel Abidin General Hospital from January 2010 to December 2012. Data on the mode of delivery and Apgar scores at 1 and 5 min for infants with a BP were extracted from the medical records. Logistic regression was employed to assess the correlation between mode of delivery and Apgar scores. In addition, a meta-analysis was conducted to summarize findings from other regions. Results: A total of 205 (3.9%) BPs among 5252 deliveries between January 2010 and December 2012 were analyzed for this study. There were 26% (52 cases) vaginal and 74% (153 cases) cesarean deliveries. The mode of delivery for BP had a significant association with Apgar score at 1 min (odds ratio [OR] 95% confidence interval [CI] = 6.462 [2.476–16.870], P = 0.0001) and 5 min (OR 95% CI =7.727 [1.416–42.175], P = 0.018). Our meta-analysis showed that the delivery mode had a significant association with Apgar score in BP (OR: 3.69; 95% CI: 2.18–6.26, P = 0.0001). Conclusions: There was a significant association between Apgar scores in BPs and mode of delivery. Our results suggest better outcomes for cesarean than vaginal delivery in BPs.

Objective: To investigate the no reflow risk factors after percutaneous coronary intervention in ST elevation myocardial infarction patients. Method: Sample size, mean ± standard deviation (SD) or frequencies (percent) of normal and no reflow groups were extracted from each study. Results: Of 27 retrospective and prospective studies, we found that increasing risks of no reflow were associated with advanced age, male, family history of coronary artery disease, smoking, diabetes mellitus, hypertension, delayed reperfusion, killip class ≥2, elevated blood glucose, increased creatinine, elevated creatine kinase (CK), higher heart rate, decreased left ventricular ejection fraction (LVEF), collateral flow ≤1, longer lesion length, multivessel disease, reference luminal diameter, initial thrombolysis in myocardial infarction (TIMI) flow, and high thrombus burden. Moreover, initial TIMI flow ≤1 and high thrombus burden had the greater impact on no reflow (OR95%CI = 3.83 [2.77–5.29], p

Background: Recently, atherosclerosis-associated disease has been reported simultaneously increased. Whereas, to date, no atherosclerosis vaccine is available. Since the epitope mimicry between malondialdehyde low-density lipoprotein (MDA-LDL) and arginine specific epitope gingipain (Rgp) on the Porphyromonas gingivalis vesicles has been reported, it raises an opportunity to employ the potency of P. gingivalis as an atherosclerosis vaccine. Objective: To evaluate the potency of P. gingivalis vesicles to prevent atherosclerosis, by assessing MDA-LDL level, visceral fat, body weight, and aortic wall thickness, in rats model. Methods: Five groups of rats (n = 10 per group), three treatment groups, one positive and negative control group were assigned and adapted with high fat diet for 8 weeks. The treatment groups were injected with P. gingivalis vesicles with and without adjuvant with four booster doses. The level of MDA-LDL serum, visceral fat, body weight, and aortic wall thickness were measured in the end of the course. Results: Our present study found that decreased in MDA-LDL levels (p = 0.037) and aortic wall thickness (p = 0.016) were observed in rats treated with vesicles and adjuvants, but not with vesicles or adjuvants only, compared to negative control. Moreover, MDA-LDL levels in rats immunized with vesicles and adjuvants were significantly lower than healthy rats. However, body weight (p = 0.329 and visceral fat (p = 0.789) were not significantly different in all treatment groups compared to control. Conclusions: Immunization with P. gingivalis vesicles and adjuvants significantly reduces MDA-LDL level and aortic wall thickness in rats model.

Introduction: Several studies have reported the incidence of herniated nucleus pulposus (HNP) in some hospitals. Surgery is one of the options in HNP management. HNP surgery results in Aceh have not been reported yet. Therefore, this study reported the HNP surgery in Zainoel Abidin General Hospital, Banda Aceh period 2010-2012. Methods: This was a descriptive retrospective survey conducted in Zainoel Abidin General Hospital Banda Aceh at August-September 2012. Results: The incidence of HNP who underwent surgery was 28 patients. There was no HNP case in the age group I (0-18 years), seven patients (25%) were age group II (19-40 years), and 21 patients (75%) were age group III (over 40 years). Based on HNP location, no HNP located in the L1-L2 and L3-L4, one patient (3.57%) was L2-L3, 20 patients (71.42%) were L4-L5, three patients (10.71%) were L5-S1, and there were four HNP patients in multiple lumbar (14.28%). Laminectomy was the most common type of surgery performed (27 patients or 96.42%), followed by laminotomy (one patients or 3.57%). Conclusion: There was significant association between the incidence of HNP with age, but not with gender. In summary, the most common lumbar disc herniation was in L4-L5. Laminectomy was the most common procedure performed in HNP patient in Aceh.

Introduction: Several studies regarding the association of the ectonucleotide pyrophosphatase/phosphodiesterase 1 (ENPP1) K121Q gene polymorphism with the risk of type 2 diabetes mellitus (T2DM) showed inconsistent results. This study aimed to investigate the association of ENPP1 K121Q gene polymorphism with T2DM risk using meta-analysis. The study was limited to the American, European, and African populations. Methods: PubMed and Embase databases were searched for eligible publications. The following information was extracted from each study: name of first author, publication year, country of origin, sample size of cases and controls, and size of each allele. The combined odds ratios (ORs) and 95% confidence intervals (95% CIs) for the association between ENPP1 K121Q gene polymorphism and T2DM risk were assessed using random or fixed effect model. A comprehensive meta-analysis (CMA) 2.0 was used to analyze the data. Results: Nineteen studies (17717 cases/28022 controls) on the association between ENPP1 K121Q gene polymorphism and T2DM risk were included in this meta-analysis. The results indicated that the ENPP1 K121Q gene polymorphism was associated with increased T2DM risk (Q vs. K genetic model, OR 95% CI = 1.11 [1.02–1.22], p = 0.014; QQ vs. KK + KQ, OR 95% CI = 1.14 [1.01–1.23], p = 0.039) and decreased T2DM risk (K vs. Q, OR 95% CI = 0.90 [0.82–1.00], p = 0.014; KK vs. KQ + QQ, OR 95% CI = 0.89 [0.80–0.98], p = 0.024). Conclusions: The results indicate that the ENPP1 K121Q gene polymorphism is associated with the risk of T2DM in the American, European, and African populations.

The complex interaction between inflammatory mediators in allergic rhinitis (AR) is determined by the role of genetic polymorphisms, including interleukin (IL) and toll-like receptor (TLR) genes. This study aimed to discuss the effects of H1-antihistamines on IL and TLR systems. Several ILs involved in AR pathogenesis are: IL-4 (rs2243250, rs1800925, rs1801275, rs2227284, rs2070874), IL-6 (rs1800795, rs1800797), IL-10 (rs1800871, rs1800872), IL-12R (rs438421), IL-13 (rs1800925, rs20541), IL-17 (rs3819024), IL-18 (rs360721, rs360718, rs360717, rs187238), IL-23R (rs7517847), and IL-27 (rs153109, rs17855750). In the IL system, histamines stimulate the IL production in Type 2 helper T (Th2) cells through protein kinase A (PKA), janus kinase-signal transducer and activator of transcription (JAK-STAT) pathway, and the activation of H1-histamine receptor and histidine decarboxylase (HDC) genes. On contrary, antihistamines down-regulate the H1-histamine receptor gene expression through the transcription suppression of HDC and IL genes and suppress histamine basal signaling through the inverse agonistic activity. TLRs involved in AR pathogenesis are TLR2 (rs4696480, rs3804099, rs5743708), TLR4 (rs4986790), TLR6 (rs2381289), TLR7 (rs179008, rs5935438), TRL8 (rs2407992, rs5741883, rs17256081, rs4830805, rs3788935, rs178998), and TLR10 (rs11466651). In the TLR system, histamines trigger the TLR expression by stimulating interferon-γ (IFN-γ) to up-regulate mast cells and by stimulating receptor-interacting protein (RIP) to activate IκB kinase-β. Contrastingly, antihistamines suppress TIR-domain-containing adaptor protein inducing IFN-β (TRIF) and RIP protein and thus inhibit the expression of TLR. In addition, several studies indicated that H1-antihistamines inhibit the IL and TLR systems indirectly.

BACKGROUND:Dengue virus infection is the most rapidly spreading vector-borne disease in the world. Essential research on dengue virus transmission and its prevention requires community participation. Therefore, it is crucial to understand the factors that are associated with the willingness of communities in high prevalence areas to participate in dengue research. The aim of this study was to explore factors associated with the willingness of healthy community members in Aceh province, Indonesia, to participate in dengue research that would require phlebotomy. METHODOLOGY/PRINCIPAL FINDINGS:A community-based cross-sectional study was carried out in nine regencies and municipalities of Aceh from November 2014 to March 2015. Interviews using a set of validated questionnaires were conducted to collect data on demography, history of dengue infection, socioeconomic status, and knowledge, attitude and practice regarding dengue fever. Two-step logistic regression and Spearman's rank correlation (rs) analysis were used to assess the influence of independent variables on dependent variables. Among 535 participants, less than 20% had a good willingness to participate in the dengue study. The factors associated with good willingness to participate were being female, working as a civil servant, private employee or entrepreneur, having a high socioeconomic status and good knowledge, attitude and practice regarding dengue. Good knowledge and attitude regarding dengue were positive independent predictors of willingness to participate (OR: 2.30 [95% CI: 1.36-3.90] and 3.73 [95% CI: 2.24-6.21], respectively). CONCLUSION/SIGNIFICANCE:The willingness to participate in dengue research is very low among community members in Aceh, and the two most important associated factors are knowledge and attitude regarding dengue. To increase participation rate, efforts to improve the knowledge and attitude of community members regarding dengue fever and dengue-related research is required before such studies are launched.

Background: Interleukin-2 (IL-2) stimulation had been reported as having a beneficial impact to the expression of CD56 bright, CD56 dim, and interferon-γ (IFN-γ) in the case of immunological dysfunction diseases. However, in the case of systemic lupus erythematosus (SLE), the role of IL-2 had never been investigated. The objective of this study was to assess the impact of IL-2 on the expression of CD56 bright, CD56 dim, and IFN-γ in SLE patients. Methods: An experimental study was conducted by involving peripheral blood mononuclear cells isolated from six SLE patients. The study consisted of four groups based on IL-2 stimulation: D0 (0U/ml), D1 (50U/ml), D2 (150U/ml), and D3 (250U/ml); and they were then cultured for 72 hours. The levels of CD56 bright and CD56 dim were measured by FACSMelody TM, while the levels of IFN-γ were measured using ELISA. Results: In group D0, D1, D2, and D3; the levels of CD56 bright were 57.27±37.27, 241.16±64.41, 256.94±50.95, and 259.37±36.44 x1000 cells/mm3 respectively. Moreover, the levels of CD56 dim were 812.85±167.37, 631.98±129.90, 616.42±157.97, and 615.90±155.57 x1000 cells/mm3 respectively. On the other hand, the levels of IFN-γ were 24.01±2.56, 26.09±4.79, 30.11±5.34, and 32.43±7.14 pg/ml respectively. Our analysis elucidated that the administration of IL-2 provided potential impact to the levels of CD56 bright, but not to the levels of CD56 dim and IFN-γ. Our findings indicated that the increased dosage of IL-2 resulted in a more significant impact on CD56 bright. Conclusions: Our study clarifies that IL-2 provides a beneficial impact on CD56 bright expression in SLE patients.

Background: Some Ebola vaccines have been developed and tested in phase III clinical trials. However, assessment of whether public have willingness to purchase or not, especially in unaffected areas, is lacking. The aim of this study was to determine willingness to pay (WTP) for a hypothetical Ebola vaccine in Indonesia. Methods: A cross-sectional study was conducted from 1 August to 30 December 2015 in five cities in Aceh province of Indonesia. Patients’ family members who visited outpatient departments were approached and interviewed about their sociodemographic characteristics, knowledge of Ebola, attitude towards vaccination practice and their WTP for a hypothetical Ebola vaccine. A multivariable linear regression model assessed the relationship between these explanatory variables and WTP. Results: During the study, 500 participants were approached and interviewed. There were 424 (84.8%) respondents who completed the interview and 74% (311/424) expressed their acceptance for an Ebola vaccine. There were 288 participants who were willing to pay for an Ebola vaccine (92.6% out of 311). The mean of WTP was US$2.08 (95% CI: 1.75-2.42). The final multivariable model indicated that young age, high educational attainment, working as a private employee, entrepreneur or civil servant (compared to farmers), being unmarried, and residing in a suburb (compared to a city) were associated with higher WTP. Conclusions: Although the proportion of the participants who would accept the Ebola vaccine was relatively high, the amount they were willing to pay for Ebola vaccine was very low. This finding would indicate the need of subsidies for Ebola vaccine in the country.

Background: Cases of myocarditis development have been reported after administration of messenger ribonucleic acid (mRNA)-based coronavirus disease (COVID-19) vaccines. However, the reports vary among the studies, and the types of mRNA vaccines with potential to cause myocarditis remain unidentified. The objective was to assess the cumulative prevalence of myocarditis and determine the association between myocarditis and mRNA-based COVID-19 vaccination. Methods: We performed a network meta-analysis by searching articles in PubMed, Scopus, and Web of Science. Information on the prevalence of myocarditis after the mRNA-based COVID-19 vaccination was collected from each study. Analysis was performed by calculating the pooled prevalence rate, and the association was determined using the Z-test. Data networking was performed using the Bayesian method. Results: A total of 18 papers was included in our analysis. We found that the cumulative prevalence of myocarditis was 1.7, 1.9, 1.2, and 1.1 per 100,000 population after vaccination with different types of mRNA-based COVID-19 vaccines, namely all mRNA COVID-19 vaccines, BNT162b1, mRNA-1273, and the combination of BNT162b1 and mRNA-1273, respectively. Moreover, the results revealed that BNT162b1 vaccination increased the risk of myocarditis by 1.64- and 1.71-folds compared to mRNA-1273 and the combination of BNT162b2 and mRNA-1273, respectively. Similar risks of developing myocarditis were observed after mRNA-1273 and the combination of BNT162b1 and mRNA-1273 vaccination. Conclusions: Our findings suggest the cumulative prevalence of myocarditis after mRNA-based COVID-19 vaccination with maximum prevalence was observed after BNT162b2 administration. BNT162b2 was associated with a higher risk of developing myocarditis than the other mRNA-based COVID-19 vaccines.

Background: The gene FOXO3a has been elucidated to govern the development of chronic granulocytic leukemia (CGL). Moreover, it has been suggested that the levels of FOXO3a in circulation are affected by the FOXO3a rs4946936 gene polymorphism. However, no study has assessed the correlation between the FOXO3a rs4946936 gene polymorphism and the levels of FOXO3a. The objective of this study was to assess the association between the FOXO3a rs4946936 gene polymorphism and the levels of FOXO3a in CGL patients treated with imatinib mesylate. Methods: A cross-sectional study was conducted from February 2019 to February 2020. The genotyping of FOXO3a rs4946936 gene polymorphism was conducted using PCR-RFLP, and the levels of FOXO3a were assessed using ELISA. The association between the FOXO3a rs4946936 gene polymorphism and the levels of FOXO3a were assessed using multiple logistic regression. Results: A total of 60 CGL patients were assessed in our study. Among them, the CC, CT, and TT genotypes of the FOXO3a rs4946936 gene polymorphism were 35.0%, 48.3%, and 16.7% respectively. Our calculation revealed that elevated levels of FOXO3a were found in CGL patients with the CC genotype of the FOXO3a rs4946936 gene polymorphism. While we failed to clarify the association between either the CT or the TT genotype of FOXO3a rs4946936 gene polymorphism and the levels of FOXO3a. Conclusion: Our study identifies that the CC genotype of the FOXO3a rs4946936 gene polymorphism affects the elevated levels of FOXO3a in CGL patients treated with imatinib mesylate.

BACKGROUND: The COVID-19 vaccination program, which uses various types of vaccines, has been applied since the beginning of 2021. However, the efficacy in the context of seroconversion rate remains unclear. OBJECTIVE: To assess the seroconversion rates among different COVID-19 vaccines using a network meta-analysis approach. METHODS: A network meta-analysis of randomized controlled trials (RCTs) was conducted during the study period. Data of interest, such as seroconversion rate and the type of COVID-19 vaccine, were extracted from each study. The analysis was performed using single-arm analysis by calculating the cumulative seroconversion rate. A network meta-analysis was conducted using the Bayesian method. RESULTS: A total of 31 RCTs were included in our analysis. Our pooled calculation revealed that the seroconversion rates of inactivated messenger ribonucleic acid (mRNA), protein subunit, and vector COVID-19 vaccines during the follow-up periods were 93.2%, 93.9%, 65.3%, and 54.7%, respectively, at ≤ 15 days; 96.0%, 94.8%, 91.2%, and 89.7%, respectively, between days 16–30; and 98.5%, 98.6%, 98.5%, and 96.2%, respectively, between days 31–60.The indirect comparison revealed that in the follow-up periods of ≤ 15 and 16–30 days, the inactivated and mRNA COVID-19 vaccines had superior seroconversion rates compared with those of the protein subunit and vector vaccines. In the follow-up period of 31–60 days, the highest seroconversion rates were found in the inactivated, mRNA, and protein subunit COVID-19 vaccines. CONCLUSION: This study provides valuable information regarding the comparison of seroconversion rates of COVID-19 vaccines.

Background: The gene FOXO3a has been elucidated to govern the development of chronic granulocytic leukemia (CGL). Moreover, it has been suggested that the levels of FOXO3a in circulation are affected by the FOXO3a rs4946936 gene polymorphism. However, no study has assessed the correlation between the FOXO3a rs4946936 gene polymorphism and the levels of FOXO3a. The objective of this study was to assess the association between the FOXO3a rs4946936 gene polymorphism and the levels of FOXO3a in CGL patients treated with imatinib mesylate. Methods: A cross-sectional study was conducted from February 2019 to February 2020. The genotyping of FOXO3a rs4946936 gene polymorphism was conducted using PCR-RFLP, and the levels of FOXO3a were assessed using ELISA. The association between the FOXO3a rs4946936 gene polymorphism and the levels of FOXO3a were assessed using multiple logistic regression. Results: A total of 60 CGL patients were assessed in our study. Among them, the CC, CT, and TT genotypes of the FOXO3a rs4946936 gene polymorphism were 35.0%, 48.3%, and 16.7% respectively. Our calculation revealed that elevated levels of FOXO3a were found in CGL patients with the CC genotype of the FOXO3a rs4946936 gene polymorphism. While we failed to clarify the association between either the CT or the TT genotype of FOXO3a rs4946936 gene polymorphism and the levels of FOXO3a. Conclusion: Our study identifies that the CC genotype of the FOXO3a rs4946936 gene polymorphism affects the elevated levels of FOXO3a in CGL patients treated with imatinib mesylate.

Background: Cytokine storm has been widely known to contribute to the development of the critical condition in patients with coronavirus disease 2019 (COVID-19), and studies had been conducted to assess the potential aspect of cytokine storm elimination by performing therapeutic plasma exchange (TPE). However, contradictory findings were observed. The objective of this study was to assess the association between TPE and the reduction of mortality of critically ill COVID-19 patients. Methods: A meta-analysis was conducted by collecting data from PubMed, Scopus, and Web of Science. Data on the mortality rate of critically ill COVID-19 patients treated with TPE plus standard of care and that of patients treated with standard of care alone were analyzed using a Z test. Results: We included a total of four papers assessing the association between TPE and the risk of mortality among critically ill COVID-19 patients. Our findings suggested that critically ill COVID-19 patients treated with TPE had lower risk of mortality compared to those without TPE treatment. Conclusion: Our study has identified the potential benefits of TPE in reducing the risk of mortality among critically ill COVID-19 patients.

Background: The gene FOXO3a has been elucidated to govern the development of chronic granulocytic leukemia (CGL). Moreover, it has been suggested that the levels of FOXO3a in circulation are affected by the FOXO3a rs4946936 gene polymorphism. However, no study has assessed the correlation between the FOXO3a rs4946936 gene polymorphism and the levels of FOXO3a. The objective of this study was to assess the association between the FOXO3a rs4946936 gene polymorphism and the levels of FOXO3a in CGL patients treated with imatinib mesylate. Methods: A cross-sectional study was conducted from February 2019 to February 2020. The genotyping of FOXO3a rs4946936 gene polymorphism was conducted using PCR-RFLP, and the levels of FOXO3a were assessed using ELISA. The association between the FOXO3a rs4946936 gene polymorphism and the levels of FOXO3a were assessed using multiple logistic regression. Results: A total of 60 CGL patients were assessed in our study. Among them, the CC, CT, and TT genotypes of the FOXO3a rs4946936 gene polymorphism were 35.0%, 48.3%, and 16.7% respectively. Our calculation revealed that elevated levels of FOXO3a were found in CGL patients with the CC genotype of the FOXO3a rs4946936 gene polymorphism. While we failed to clarify the association between either the CT or the TT genotype of FOXO3a rs4946936 gene polymorphism and the levels of FOXO3a. Conclusion: Our study identifies that the CC genotype of the FOXO3a rs4946936 gene polymorphism affects the elevated levels of FOXO3a in CGL patients treated with imatinib mesylate.

Background: The pathogenesis of herniated nucleus pulposus (HNP) is complex and may involve the wide variety of gene polymorphism. However, the reports from the existing studies are inconclusive. The objective of this study was to determine the role of single nucleotide polymorphisms (SNPs) in interleukin 1 alpha ( IL-1A), tumor necrosis factor-alpha ( TNF-A), and vitamin D receptor ( VDR) genes on the susceptibility to herniated nucleus pulposus (HNP). Methods: Four databases (PubMed, Embase, Cochrane, and Web of Science) were searched as of April 1 st, 2021. Authors, publication year, targeted genes, genotype and allele frequency in each case and control groups were collected. Newcastle-Ottawa scale was used to evaluate the publication quality. The pooled estimates of association of IL-1A -889C>T (rs1800587), TNF-A -238G>A (rs361525), and VDR TaqI (rs731236) and susceptibility to HNP were assessed using Z test. Results: We screened 3,067 unique studies for eligibility and three, two and nine case-control studies on IL-1A -889C>T, TNF-A -238G>A, and VDR TaqI were included, respectively, in our meta-analysis. The studies consisting 369 HNP cases and 433 controls for IL-1A -889C>T, 252 cases and 259 controls for TNF-A -238G>A and 1130 cases and 2096 controls for VDR TaqI. Our pooled estimates indicated that there was no significant association of those SNPs with the susceptibility to HNP in any genotype, dominant model, recessive model, or allele comparations. Conclusion: Although individual studies suggested the important role of gene expression dysregulation associated with SNPs in IL-1A, TNF-A, and VDR, our data indicated that IL-1A -889C>T, TNF-A -238G>A, and VDR TaqI had weak association with HNP susceptibility in both genotypes and allele distributions. However, since heterogeneity was identified among studies included in this meta-analysis, further meta-analysis with a larger population and subgroup analysis on specific population are warranted to support this finding.

Background: The objective of this study was to determine the role of single nucleotide polymorphisms (SNPs) in interleukin 1 alpha ( IL-1A), tumor necrosis factor-alpha ( TNF-A), and vitamin D receptor ( VDR) genes on the susceptibility to herniated nucleus pulposus (HNP). Methods: Four databases (PubMed, Embase, Cochrane, and Web of Science) were searched as of April 1 st, 2021. Authors, publication year, targeted genes, genotype and allele frequency in each case and control groups were collected. Newcastle-Ottawa scale was used to evaluate the publication quality. The pooled estimates of association of IL-1A -889C>T (rs1800587), TNF-A -238G>A (rs361525), and VDR TaqI (rs731236) and susceptibility to HNP were assessed using Z test and presented as odd ratio (OR) and 95% confidence intervals (95%CI). Results: We screened 3,067 unique studies for eligibility and three, two and nine studies on IL-1A -889C>T, TNF-A -238G>A, and VDR TaqI were included, respectively, in our meta-analysis. The studies consisting 369 HNP cases and 433 controls for IL-1A -889C>T, 252 cases and 259 controls for TNF-A -238G>A and 1130 cases and 2096 controls for VDR TaqI. Our pooled estimates indicated that there was no significant association of those SNPs with the susceptibility to HNP in any genotype, dominant model, recessive model, or allele comparations. Conclusion: Although individual studies suggested the important role of gene expression dysregulation associated with SNPs in IL-1A, TNF-A, and VDR, our data indicated that IL-1A -889C>T, TNF-A -238G>A, and VDR TaqI had weak association with HNP susceptibility in both genotypes and allele distributions. However, since heterogeneity was identified among studies included in this meta-analysis, further meta-analysis with a larger population and subgroup analysis on specific population are warranted to support this finding.

Background: Convalescent plasma (CCP) has been used for treating some infectious diseases; however, the efficacy of CCP in coronavirus disease 2019 (COVID-19) remains controversial. The aim of this research was to assess the efficacy of CCP as an adjunctive treatment in COVID-19 patients. Methods: Embase, PubMed, Web of Science, Cochrane and MedRix were searched for potentially relevant articles. All included papers were assessed for the quality using modified jadad scale and Newcaste-ottawa scale for randomized controlled trial (RCT) and non – RCT, respectively. We used a Q test and Egger test to assess the heterogeneity and publication bias among studies, respectively. Mortality rates between patients treated with standard treatment and standard treatment with CCP were compared using a Z test. Results: A total of 12 papers consisting of three cross-sectional studies, one prospective study, five retrospective studies, and two RCT studies were included in our analysis. Of them, a total of 1,937 patients treated with CCP and 3,405 patients without CCP were involved.. The risk of mortality was 1.92-fold higher in patients without CCP compared to patients treated with CCP (OR: 1.92; 95%CI: 1.33, 2.77; p=0.0005). In severe COVID-19 sub-group analysis, we found that patients without the CCP had a 1.32 times higher risk of mortality than those treated with the CCP (OR: 1.32; 95%CI: 1.09, 1.60; p=0.0040). Conclusions: CCP, as adjunctive therapy, reduces the mortality rate among COVID-19 patients.

Background: Convalescent plasma (CCP) has been used for treating some infectious diseases; however, the efficacy of CCP in coronavirus disease 2019 (COVID-19) remains controversial. The aim of this research was to assess the efficacy of CCP as an adjunctive treatment in COVID-19 patients. Methods: Four bibliographic databases and a preprint database were searched for potentially relevant articles. Mortality rates between patients treated with standard treatment and standard treatment with CCP were compared using a Z test. Results: A total of 1,937 patients treated with CCP and 3,405 patients without CCP retrieved from 12 studies were included. The risk of mortality was 1.92-fold higher in patients without CCP compared to patients treated with CCP (OR: 1.92; 95%CI: 1.33, 2.77; p=0.0005). In severe COVID-19 sub-group analysis, we found that patients without the CCP had a 1.32 times higher risk of mortality than those treated with the CCP (OR: 1.32; 95%CI: 1.09, 1.60; p=0.0040). Conclusions: CCP, as adjunctive therapy, reduces the mortality rate among COVID-19 patients.

Background: In this study, we aimed to determine the global prevalence, chronological order of symptom appearance, and mortality rates with regard to hemorrhagic and ischemic stroke in patients with coronavirus disease 2019 (COVID-19) and to discuss possible pathogeneses of hemorrhagic and ischemic stroke in individuals with the disease. Methods: We searched the PubMed, Scopus, and Web of Science databases for relevant articles published up to November 8, 2020. Data regarding study characteristics, hemorrhagic stroke, ischemic stroke, and COVID-19 were retrieved in accordance with the PRISMA guidelines. The Newcastle-Ottawa scale was used to assess the quality of the eligible studies. The pooled prevalence and mortality rate of hemorrhagic and ischemic stroke were calculated. Results: The pooled estimate of prevalence of hemorrhagic stroke was 0.46% (95% CI 0.40%–0.53%; I 2 =89.81%) among 67,155 COVID-19 patients and that of ischemic stroke was 1.11% (95% CI 1.03%–1.22%; I 2 =94.07%) among 58,104 COVID-19 patients. Ischemic stroke was more predominant (incidence: 71.58%) than hemorrhagic stroke (incidence: 28.42%) in COVID-19 patients who experienced a stroke. In COVID-19 patients who experienced a stroke, hospital admission with respiratory symptoms was more commonly reported than that with neurological symptoms (20.83% for hemorrhagic stroke and 5.51% for ischemic stroke versus 6.94% for hemorrhagic stroke and 5.33% for ischemic stroke, respectively). The pooled mortality rate of COVID-19 patients who experienced a hemorrhagic and ischemic stroke was 44.72% (95% CI 36.73%–52.98%) and 36.23% (95% CI 30.63%–42.24%), respectively. Conclusions: Although the occurrence of hemorrhagic and ischemic stroke is low, the mortality rates of both stroke types in patients with COVID-19 are concerning, and therefore, despite several potential pathogeneses that have been proposed, studies aimed at definitively elucidating the mechanisms of hemorrhagic and ischemic stroke in individuals with COVID-19 are warranted. PROSPERO registration: CRD42020224470 (04/12/20)

Background: This study was conducted to determine the prevalence of headache in coronavirus disease 2019 (COVID-19) and to assess its association as a predictor for COVID-19. This study also aimed to discuss the possible pathogenesis of headache in COVID-19. Methods: Available articles from PubMed, Scopus, and Web of Science were searched as of September 2 nd, 2020. Data on characteristics of the study, headache and COVID-19 were extracted following the PRISMA guidelines. Biases were assessed using the Newcastle-Ottawa scale. The cumulative prevalence of headache was calculated for the general population (i.e. adults and children). The pooled odd ratio (OR) with 95% confidence intervals (95%CI) was calculated using the Z test to assess the association between headache and the presence of COVID-19 cases. Results: We included 104,751 COVID-19 cases from 78 eligible studies to calculate the global prevalence of headache in COVID-19 and 17 studies were included to calculate the association of headache and COVID-19. The cumulative prevalence of headache in COVID-19 was 25.2% (26,464 out of 104,751 cases). Headache was found to be more prevalent, approximately by two-fold, in COVID-19 patients than in non-COVID-19 patients with symptoms of other respiratory viral infections, OR: 1.73; 95% CI: 1.94, 2.5 with p=0.04. Conclusion: Headache is common among COVID-19 patients and seems to be more common in COVID-19 patients compared to those with the non-COVID-19 viral infection. No definitive mechanisms on how headache emerges in COVID-19 patients but several possible hypotheses have been proposed. However, extensive studies are warranted to elucidate the mechanisms. PROSPERO registration: CRD42020210332 (28/09/2020)

Background: While it has been known that the development of chronic kidney disease (CKD) and age-related cognitive impairment involves several mediators, the evidence in clinical practice only reveals nitride oxide synthase (NOS) and klotho. However, the evidence for this topic is conflicted. The aim of this study was to assess the role of NOS and klotho single nucleotide polymorphisms (SNPs) in the pathogenesis of CKD and age-related cognitive impairment. Methods: We performed a meta-analysis during October to December 2019. Paper collection was performed in major scientific websites, and we extracted information of interest from each paper. Data were analyzed using a Z-test with either random or fixed effect model. Results: Our initial assessment identified NOS3 G894T, NOS3 T786C, NOS3 4b/4a, klotho ( KL) G395A, and KL C1818T as the gene candidate for our meta-analysis. Our pooled calculation revealed that NOS3 G894T was associated with the risk of both age-related cognitive impairment and CKD. Increased susceptibility to age-related cognitive impairment was observed in the GG genotype, and increased risk of CKD was found in patients with a single T allele and TT genotype for NOS3 nucleotide 894. For NOS3 4b/4a, increased risk of CKD was only found in 4a4a genotype. For NOS3 T786C, we failed to show the association with both CKD and age-related cognitive impairment. Subsequently, for KL G395A, A allele and GA genotype were found to correlate with increased susceptibility to CKD, while its correlation to age-related cognitive impairment was failed to clarify. For KL C1818T, our analysis failed to find the correlation with the risk of CKD. Conclusions: Our results reveal that the NOS3 G894T gene polymorphism has a crucial role in the pathogenesis of both CKD and age-related cognitive impairment.

Background: There is controversy among physicians regarding the use of dual antiplatelet therapy (DAPT) in acute coronary syndrome (ACS) patients treated with coronary artery bypass grafting (CABG). Moreover, the evidence of previous studies about this topic remained inconclusive. This study aimed to perform a meta-analysis concerning the relation between the risk of major bleeding and the use of different DAPT (clopidogrel or ticagrelor) in ACS patients treated with CABG. Methods: A meta-analysis was conducted during March to October 2019. Searches were carried out in Pubmed, Embase, Cochrane, and Web of Science. The predictor covariate in our present study was DAPT (clopidogrel or ticagrelor), and the outcome measure was the risk of major bleeding. Sub-group analysis was also performed, where data were classified into pre- and post-CABG. Furthermore, to determine the correlation and effect estimation, data were analyzed using fixed or random effect model. Results: A total of 13 studies consisting 34,015 patients treated with clopidogrel and 32,661 patients treated with ticagrelor was included in our study. Our pooled calculation revealed that the incidence of major bleeding was not different significantly between clopidogrel and ticagrelor. In pre- and post-CABG sub-groups, our results also found no significant difference in major bleeding incidence between clopidogrel and ticagrelor groups. Conclusions: Our meta-analysis clarifies that clopidogrel, compared to ticagrelor, or vice versa, is not associated with the risk of major bleeding in ACS patients treated with CABG.