Long noncoding RNAs and circular RNAs as potential diagnostic biomarkers of inflammatory bowel diseases: a systematic review and meta-analysis

IntroductionInflammatory bowel disease (IBD) poses a growing global burden, necessitating the discovery of reliable biomarkers for early diagnosis. The clinical significance of dysregulated expression of long noncoding RNAs (lncRNAs) and circular RNAs (circRNAs) in diagnosing IBD has not been well established. Thus, our study aimed to investigate the diagnostic value of lncRNAs and circRNAs for IBD based on currently available studies.MethodsA comprehensive search was carried out in diverse electronic databases, such as PubMed, Embase, Scopus, Science Direct and Wiley Online Library to retrieve articles published until October 30, 2023. Stata 17.0 software was employed to determine pooled sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), diagnostic ratio (DOR), and area under the curve (AUC). Heterogeneity, subgroup analysis, and meta-regression were explored, and publication bias was assessed using Deeks’ funnel plot. Fagan’s nomogram and likelihood ratio scattergram were employed to evaluate the clinical validity.ResultA total of 11 articles encompassing 21 studies which involved 1239 IBD patients and 985 healthy controls were investigated. The findings revealed lncRNAs exhibit high level of pooled sensitivity 0.94 (95% CI: 0.87-0.97) and specificity 0.99 (95% CI: 0.89-1.00), along with PLR, NLR, DOR, and AUC values of 64.25 (95% CI: 7.39-558.66), 0.06 (95% CI: 0.03-0.13), 1055.25 (95% CI: 70.61-15770.77), and 0.99 (95% CI: 0.97-0.99), respectively. Conversely, CircRNAs showed moderate accuracy in IBD diagnosis, with sensitivity of 0.68 (95% CI: 0.61-0.73), specificity of 0.73 (95% CI: 0.65-0.79), PLR of 2.47 (95% CI: 1.94-3.16), NLR of 0.45 (95% CI: 0.38-0.53), DOR of 5.54 (95% CI: 3.88-7.93), and AUC value of 0.75 (95% CI: 0.71-0.79). Moreover, findings from subgroup analysis depicted heightened diagnostic efficacy when employing lncRNA H19 and a large sample size (≥100), with notable efficacy in diagnosing both ulcerative colitis (UC) and Crohn’s disease (CD).ConclusionLncRNAs exhibit high diagnostic accuracy in distinguishing patients with IBD from healthy controls signifying their possible use as potential biomarkers, while circRNAs showed moderate diagnostic accuracy. Nevertheless, to validate our findings and confirm the clinical utility of lncRNAs and circRNAs in IBD diagnosis, a large pool of prospective and multi-center studies should be undertaken.Systematic review registrationhttps://www.crd.york.ac.uk/PROSPERO, identifier CRD42023491840

The unfinished agenda of communicable diseases among children and adolescents before the COVID-19 pandemic, 1990-2019: a systematic analysis of the Global Burden of Disease Study 2019

BACKGROUND: Communicable disease control has long been a focus of global health policy. There have been substantial reductions in the burden and mortality of communicable diseases among children younger than 5 years, but we know less about this burden in older children and adolescents, and it is unclear whether current programmes and policies remain aligned with targets for intervention. This knowledge is especially important for policy and programmes in the context of the COVID-19 pandemic. We aimed to use the Global Burden of Disease (GBD) Study 2019 to systematically characterise the burden of communicable diseases across childhood and adolescence. METHODS: In this systematic analysis of the GBD study from 1990 to 2019, all communicable diseases and their manifestations as modelled within GBD 2019 were included, categorised as 16 subgroups of common diseases or presentations. Data were reported for absolute count, prevalence, and incidence across measures of cause-specific mortality (deaths and years of life lost), disability (years lived with disability [YLDs]), and disease burden (disability-adjusted life-years [DALYs]) for children and adolescents aged 0-24 years. Data were reported across the Socio-demographic Index (SDI) and across time (1990-2019), and for 204 countries and territories. For HIV, we reported the mortality-to-incidence ratio (MIR) as a measure of health system performance. FINDINGS: In 2019, there were 3·0 million deaths and 30·0 million years of healthy life lost to disability (as measured by YLDs), corresponding to 288·4 million DALYs from communicable diseases among children and adolescents globally (57·3% of total communicable disease burden across all ages). Over time, there has been a shift in communicable disease burden from young children to older children and adolescents (largely driven by the considerable reductions in children younger than 5 years and slower progress elsewhere), although children younger than 5 years still accounted for most of the communicable disease burden in 2019. Disease burden and mortality were predominantly in low-SDI settings, with high and high-middle SDI settings also having an appreciable burden of communicable disease morbidity (4·0 million YLDs in 2019 alone). Three cause groups (enteric infections, lower-respiratory-tract infections, and malaria) accounted for 59·8% of the global communicable disease burden in children and adolescents, with tuberculosis and HIV both emerging as important causes during adolescence. HIV was the only cause for which disease burden increased over time, particularly in children and adolescents older than 5 years, and especially in females. Excess MIRs for HIV were observed for males aged 15-19 years in low-SDI settings. INTERPRETATION: Our analysis supports continued policy focus on enteric infections and lower-respiratory-tract infections, with orientation to children younger than 5 years in settings of low socioeconomic development. However, efforts should also be targeted to other conditions, particularly HIV, given its increased burden in older children and adolescents. Older children and adolescents also experience a large burden of communicable disease, further highlighting the need for efforts to extend beyond the first 5 years of life. Our analysis also identified substantial morbidity caused by communicable diseases affecting child and adolescent health across the world. FUNDING: The Australian National Health and Medical Research Council Centre for Research Excellence for Driving Investment in Global Adolescent Health and the Bill & Melinda Gates Foundation

The global burden of cancer attributable to risk factors, 2010-19 : a systematic analysis for the Global Burden of Disease Study 2019

Background Understanding the magnitude of cancer burden attributable to potentially modifiable risk factors is crucial for development of effective prevention and mitigation strategies. We analysed results from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2019 to inform cancer control planning efforts globally. Methods The GBD 2019 comparative risk assessment framework was used to estimate cancer burden attributable to behavioural, environmental and occupational, and metabolic risk factors. A total of 82 risk-outcome pairs were included on the basis of the World Cancer Research Fund criteria. Estimated cancer deaths and disability-adjusted life-years (DALYs) in 2019 and change in these measures between 2010 and 2019 are presented. Findings Globally, in 2019, the risk factors included in this analysis accounted for 4.45 million (95% uncertainty interval 4.01-4.94) deaths and 105 million (95.0-116) DALYs for both sexes combined, representing 44.4% (41.3-48.4) of all cancer deaths and 42.0% (39.1-45.6) of all DALYs. There were 2.88 million (2.60-3.18) risk-attributable cancer deaths in males (50.6% [47.8-54.1] of all male cancer deaths) and 1.58 million (1.36-1.84) risk-attributable cancer deaths in females (36.3% [32.5-41.3] of all female cancer deaths). The leading risk factors at the most detailed level globally for risk-attributable cancer deaths and DALYs in 2019 for both sexes combined were smoking, followed by alcohol use and high BMI. Risk-attributable cancer burden varied by world region and Socio-demographic Index (SDI), with smoking, unsafe sex, and alcohol use being the three leading risk factors for risk-attributable cancer DALYs in low SDI locations in 2019, whereas DALYs in high SDI locations mirrored the top three global risk factor rankings. From 2010 to 2019, global risk-attributable cancer deaths increased by 20.4% (12.6-28.4) and DALYs by 16.8% (8.8-25.0), with the greatest percentage increase in metabolic risks (34.7% [27.9-42.8] and 33.3% [25.8-42.0]). Interpretation The leading risk factors contributing to global cancer burden in 2019 were behavioural, whereas metabolic risk factors saw the largest increases between 2010 and 2019. Reducing exposure to these modifiable risk factors would decrease cancer mortality and DALY rates worldwide, and policies should be tailored appropriately to local cancer risk factor burden. Copyright (C) 2022 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license.Peer reviewe

Global, regional, and national burden of disorders affecting the nervous system, 1990–2021: a systematic analysis for the Global Burden of Disease Study 2021

BackgroundDisorders affecting the nervous system are diverse and include neurodevelopmental disorders, late-life neurodegeneration, and newly emergent conditions, such as cognitive impairment following COVID-19. Previous publications from the Global Burden of Disease, Injuries, and Risk Factor Study estimated the burden of 15 neurological conditions in 2015 and 2016, but these analyses did not include neurodevelopmental disorders, as defined by the International Classification of Diseases (ICD)-11, or a subset of cases of congenital, neonatal, and infectious conditions that cause neurological damage. Here, we estimate nervous system health loss caused by 37 unique conditions and their associated risk factors globally, regionally, and nationally from 1990 to 2021.MethodsWe estimated mortality, prevalence, years lived with disability (YLDs), years of life lost (YLLs), and disability-adjusted life-years (DALYs), with corresponding 95% uncertainty intervals (UIs), by age and sex in 204 countries and territories, from 1990 to 2021. We included morbidity and deaths due to neurological conditions, for which health loss is directly due to damage to the CNS or peripheral nervous system. We also isolated neurological health loss from conditions for which nervous system morbidity is a consequence, but not the primary feature, including a subset of congenital conditions (ie, chromosomal anomalies and congenital birth defects), neonatal conditions (ie, jaundice, preterm birth, and sepsis), infectious diseases (ie, COVID-19, cystic echinococcosis, malaria, syphilis, and Zika virus disease), and diabetic neuropathy. By conducting a sequela-level analysis of the health outcomes for these conditions, only cases where nervous system damage occurred were included, and YLDs were recalculated to isolate the non-fatal burden directly attributable to nervous system health loss. A comorbidity correction was used to calculate total prevalence of all conditions that affect the nervous system combined.FindingsGlobally, the 37 conditions affecting the nervous system were collectively ranked as the leading group cause of DALYs in 2021 (443 million, 95% UI 378–521), affecting 3·40 billion (3·20–3·62) individuals (43·1%, 40·5–45·9 of the global population); global DALY counts attributed to these conditions increased by 18·2% (8·7–26·7) between 1990 and 2021. Age-standardised rates of deaths per 100 000 people attributed to these conditions decreased from 1990 to 2021 by 33·6% (27·6–38·8), and age-standardised rates of DALYs attributed to these conditions decreased by 27·0% (21·5–32·4). Age-standardised prevalence was almost stable, with a change of 1·5% (0·7–2·4). The ten conditions with the highest age-standardised DALYs in 2021 were stroke, neonatal encephalopathy, migraine, Alzheimer's disease and other dementias, diabetic neuropathy, meningitis, epilepsy, neurological complications due to preterm birth, autism spectrum disorder, and nervous system cancer.InterpretationAs the leading cause of overall disease burden in the world, with increasing global DALY counts, effective prevention, treatment, and rehabilitation strategies for disorders affecting the nervous system are needed

Hepatitis C Virus Infection among HIV-Infected Patients Attending Dessie Referral Hospital, Northeastern Ethiopia

Objective. Hepatitis C Virus (HCV) and Human Immunodeficiency Virus (HIV) coinfection increases the incidence of end-stage liver disease which is more severe in immune-compromised HIV-infected patients than HCV infection alone. The aim of this study was to assess HCV infection and the associated risk factors among HIV/AIDS patients attending Dessie Referral Hospital, Northeastern Ethiopia. Methods. A hospital-based cross-sectional study was conducted among 249 HIV-infected adults selected by a systematic random sampling technique from January to March 2018. A structured questionnaire was used to collect sociodemographic and risk factor data. Moreover, the blood specimen was collected and tested for CD4 count and anti-HCV antibody detection according to standard operating procedures. The data obtained were entered into SPSS version 20, and descriptive statistics, bivariate and multivariate logistic regression analyses were performed. A P value ≤0.05 with a corresponding 95% confidence interval was considered as statistically significant. Result. Of a total of 249 HIV-infected study subjects, 120 (48.2%) were male and 129 (51.8%) were females, while the mean (±SD) age and CD4+ cells/mm3 were 39.10 (±11.507) years and 316.08 + 290.607 cells/mm3, respectively. Anti-HCV antibody was detected in 13 (5.2%) patients with higher prevalence rate found in males P=0.078 and elders >50 years of age P=0.013 than their counterparts. Age group of >50 years of age (AOR = 9.070, 95% CI: 1.578, 52.117, P=0.013), longer duration of HIV treatment (AOR = 5.490, 95% CI: 1.341, 34.458, P=0.041), WHO clinical stage III/IV (AOR = 12.768, 95% CI: 2.293, 71.106, P=0.004), previous history of hospitalization (AOR = 10.234, 95% CI: 2.049, 51.118, P=0.005), tooth extraction (AOR = 6.016, 95% CI: 1.137, 36.837, P=0.048), and liver disease (AOR = 11.398, 95% CI: 1.275, 101.930, P=0.029) were statistically significant predictors of HCV infection. Conclusion. The prevalence of HCV infection is still higher and causes concern. Therefore, screening of these high-risk groups should be critical to reduce mortality and to improve clinical outcomes

Knowledge, attitude, practice towards COVID-19 pandemic and its prevalence among hospital visitors at Ataye district hospital, Northeast Ethiopia.

BackgroundCoronavirus disease 19 (COVID-19) is currently a global health threat and public health emergency of international concern. Africa is the last continent to be hit by this pandemic and the population is still prone to misconceptions and may not take it seriously. In developing countries including Ethiopia, where trained human resources and equipment for the treatment of COVID-19 are scarce, working on prevention of the viral spread should be a priority as a feasible intervention strategy. The aim of this study was to determine the level of knowledge, attitude, practice (KAP) towards COVID-19 and its prevalence among hospital visitors.MethodsHealth institution based cross sectional study was conducted among 513 hospital visitors who are recruited by using simple random sampling technique at Ataye district hospital, Northeast Ethiopia from June 3, 2020 to August 10, 2020. A pre-tested structured questionnaire was used to obtain information related to socio-demographic characteristics, knowledge (11 questions), attitude (9 questions) and practice (9 questions). Oro-pharyngeal specimen was collected by trained healthcare provider and processed in a molecular laboratory. After extraction of viral nucleic acid, the Real-time fluorescent polymerase chain reaction (RT-PCR) kit was used for detecting novel coronavirus (2019-nCoV). Data was analyzed using bi-variable and multivariable logistic regression model with 95% CI (confidence interval). From the bi-variable analysis, variables having a P-value ResultsMajority (72.9%) of the study participants were male; and most were urban dwellers. From the total study participants, 17 (3.3%) were found to be infected with the virus. The magnitude of low-level of knowledge was 4.9%; and of the analyzed risk factors, female gender, age (category less than 16 years and category between 16 and 65 years), and usual alcohol drinking habit had statistically significant association with low level knowledge. The proportion of study participants who had low level of practice was 75/513 (14.62%). Family size, age category between 16 and 65 years, and low-level knowledge were associated with low-level practice.ConclusionLimited number of study participants had high-level knowledge and practice towards COVID-19; while majority of the study candidates demonstrated moderate level of knowledge and practice. Good knowledge, positive attitude and good practice can be a guarantee for the prevention and control of COVID-19. Hence, various measurements to combat the pandemic should be taken by different stakeholders including the community members, religious leader, health professionals and others

Asymptomatic nasopharyngeal bacterial carriage, multi-drug resistance pattern and associated factors among primary school children at Debre Berhan town, North Shewa, Ethiopia

Abstract Background Nasopharyngeal carriage of bacteria is the main source for transmission of pathogens across individuals and horizontal spread of organisms in the community. It is an important risk factor for the acquisition of community-acquired respiratory tract infection. It is the major public health problem among children. The asymptomatic carriage of nasopharyngeal bacteria is different globally, particularly in Africa, carriage is higher in children and decreases with increasing age, 63.2% in children less than 5 years, 42.6% in children 5–15 years, and 28.0% in adults older than 15 years. Objective The aims of this study was to determine asymptomatic nasopharyngeal bacterial carriage, multi-drug resistance pattern and associated factors among primary school children at Debre Berhan town, North Shewa, Ethiopia. Methods Institutional based cross-sectional study was conducted at Debre Berhan town primary schools from February 1 to April 30, 2021. Primarily, the schools were stratified into two strata, public and private primary schools. From a total of sixteen government and fourteen private primary schools, five government and five private schools were selected by using a simple random sampling technique. Socio-demographic variables and potential risk factors were assessed using a structured questionnaire. A total of 384 nasopharyngeal swab samples were collected using sterile swabs aseptically; and inoculated on Blood agar, Chocolate agar, MacConkey agar, and Mannitol salt agar. The colony was characterized to isolate bacteria, and bacterial identification was performed by Gram reaction, hemolysis patterns, colonial characteristics and pigmentation, catalase test, coagulase test, mannitol fermentation test, oxidase test, fermentation of carbohydrates, H2S production, motility, formation of indole, triple sugar iron agar (TSI), citrate utilization, lysine decarboxylase or methyl red vogues proskur utilization, urea hydrolysis and satellitism tests. Antimicrobial sensitivity tests were performed by using modified Kirby-Bauer disk diffusion method. Data were entered into statistical package Epi data 4.0.0.6 and transferred to and analyzed using SPSS software version-23. P value of  5 members [AOR = 2.17, 95%CI 1.24–3.81], and number of students in the classroom [AOR = 2.35,95%CI 1.37–4.02] were statistically significant associated risk factors for nasopharyngeal bacteria carriage. Conclusion Asymptomatic nasopharyngeal bacteria carriage in children is alarming for community-acquired infection. The overall multidrug resistance was very high. The risk of the carriage was increased with having a history of passive smoking, being in large family size and number of students per class. Longitudinal follow-up studies would be helpful for better understanding the infection risk in bacterial pathogen carriers

The Escalating Magnitude of COVID-19 Infections among the Northeastern Ethiopia Region: A Community-Based Cross-Sectional Study

Background. The novel coronavirus disease (COVID-19) is lethal and extremely contagious, with a rapidly rising global prevalence. The World Health Organization has declared the outbreak a global pandemic; it is reported to have spread to nearly every country in the world. However, the prevalence varies across developed and developing countries, as well as within different regions of the same country. It is not hidden that estimating the magnitude of COVID-19 infection from the community surveys is critical for public health policymakers to make decisions to deal with the outbreak, optimize measures, and design mitigation plans. Methods. A community-based cross-sectional study was conducted from 01 July to 31 August 2020 in the northeastern Ethiopia region. A simple random sampling technique was used to select study participants from the community survey, contact traces from confirmed cases, and infection suspects. After extraction of viral nucleic acid from oropharyngeal specimen, the real-time fluorescent polymerase chain reaction (RT-PCR) kit was used for detecting novel coronavirus. Results. A total of 8752 study participants were included in this study. About 63.6% were males and 36.4% were females. Out of the total 8752 study participants, 291 (3.3%) were found to be infected with the virus. The first laboratory-confirmed cases of COVID-19 were detected in the fourth week of the study period, that is, from July 24 to July 31, 2020, and the peak prevalence was observed in the last two weeks. The COVID-19 infection was more prevalent among males and in the age group of 36–52 years. Participants tested via contact trace had 1.65 times (AOR = 1.65, 95% CI = 1.09–2.51, P=0.018) the likelihood of COVID-19 infection in comparison to the other forms of community surveys. Conclusion. The trend in the prevalence of COVID-19 infection in the northeastern region has shown increment, and increasing testing capacity has a greater benefit in identifying early infection for the prevention, treatment, and control of the international pandemic

Multidrug-Resistant and Carbapenemase-Producing Enterobacteriaceae in Addis Ababa, Ethiopia

Background. The emergence and spread of multi-drug resistant (MDR) bacteria have become a public health problem in recent years. For the last many years, carbapenem antibiotics have been used successfully to treat infections caused by MDR Enterobacteriaceae. However, recently, Enterobacteriaceae producing carbapenemases have emerged, which confer broad resistance to most β-lactam antibiotics including carbapenems. Therefore, this study is aimed at determining the magnitude of MDR and carbapenemase-producing Enterobacteriaceae (CPE) isolated from various clinical specimens in Addis Ababa, Ethiopia. Methods. A cross-sectional study was conducted from January to April 2018. A total of 312 Enterobacteriaceae isolates were identified from various clinical specimens. The Phoenix automated system (BD Phoenix100) was used for bacterial identification and antimicrobial susceptibility testing. Potential carbapenemase producers were confirmed by the modified carbapenem inactivation test, and KPC, MBL, and OXA-48 were phenotypically characterized by the disk diffusion method. The data obtained were entered and analyzed using SPSS version 20 software. Descriptive statistics, chi square, bivariate and multivariable logistic regression analyses were performed. P value ≤ 0.05 with corresponding 95% confidence interval was considered for statistical significance. Results. A total of 312 Enterobacteriaceae were recovered. Of these isolates, 68.6% were MDR and 2.6% were CPE with different classes including OXA-48 1.6% (5/312), MBL 0.6% (2/312), and KPC and OXA-48 0.3% (1/312). The predominant bacterial isolates were E. coli 72.4% (226/312) followed by K. pneumoniae 13.8% (43/312). The antibiotic resistance rates of CPE isolates were significantly higher than other MDRE including ampicillin (100% versus 77.6%), cefoxitin (75% versus 20.6%), and piperacillin/tazobactam (50% versus 13.1%). Conclusion. In this study, a relatively higher prevalence of MDR was observed, and the highest resistance was recorded against ampicillin, amoxicillin with clavulanic acid, and sulfamethoxazole-trimethoprim. Detection of CPE is important for implementing appropriate antimicrobial therapy and in controlling the spread of the infection. Furthermore, continuous screening and investigations, including genotypic characterization of CPE, are required for the prevention and control of the spread of antimicrobial-resistant pathogens