Chronic periodontitis (CP) is an infection that affects the teeth supporting structure. Macrophage migration inhibitory factor (MIF) is an important effector cytokine of the innate immune system. Due to its functional characteristics, MIF may be involved in the immunopathology of CP. The aim of the present study was to evaluate MIF levels in gingival crevicular fluid (GCF), saliva, and serum of CP patients. A cross-sectional study was conducted on 60 subjects divided into two groups: subjects with CP (n= 30) and periodontally healthy subjects without CP (n=30). MIF was quantified in GCF, saliva, and serum of all participants by enzyme-linked immunosorbent assay. MIF concentrations were higher in GCF, saliva, and serum in the group with CP compared with the group without CP and a higher MIF concentration was observed in GCF (p=0.001) and saliva (p=0.009) in the group with CP. MIF intragroup comparisons between fluids demonstrated significant high levels of MIF in saliva compared with GCF and serum in both study groups (p<0.05). A positive correlation was found between clinical signs and MIF concentration in GCF (p<0.05). There is an association between the MIF and the clinical signs of the disease. Therefore, MIF could have an important role in the pathology and progression of CP. Porphyromonas gingivalis, Tannerella forsythia, and Treponema denticola [Chronic periodontitis (CP) is an inflammatory disease characterized by the loss of periodontal tissues that support the dental organs . The preenticola , 4, 5.The bacterial components of periodontopathogens, such as lipopolysaccharides (LPS), peptidoglycans, lipoteichoic acid, proteases, and toxins, induce inflammation . This inCytokines are an important component of the inflammatory process in CP. It has been shown that proinflammatory cytokines such as IL-1, IL-6, IL-17, and TNF-alpha are involved in the immunopathology of this disease .Macrophage migration inhibitory factor (MIF) is an important effector cytokine of the innate immune system . MIF is MIF regulates the innate immune response through modulation of the receptor recognition pattern, such as TLR4, and through increasing the expression of cytokines, such as TNF-alpha, IL-6, and prostaglandins E2 –14.Studies have shown that MIF is an enhancer of osteoclastogenesis by upregulating the signaling pathway of NF-kB in a periodontitis model  and a rhPrevious research has shown that MIF can participate in the pathophysiology of chronic degenerative and autoimmune diseases by significantly increasing body fluids, as in rheumatoid arthritis , diabeteAt the present time, the concentration of MIF in GCF, saliva, and serum from subjects with CP is unknown. Consequently, the aim of this work was to determine and compare the GCF, saliva, and serum concentrations of MIF in individuals with CP and healthy subjects and to correlate MIF concentrations with periodontal clinical parameters in individuals with CP.This is a cross-sectional study that was conducted in the Periodontal Clinic, Dentistry School of the University of Guadalajara.The study was carried out in 60 participants  and all participants provided informed written consent. Participants were periodontally examined and classified as follows: thirty patients with CP  and thirty individuals with clinically healthy periodontium served as controls (subjects without CP) .A complete clinical examination was performed, as well as complete medical and dental histories. All participants of the group with and without CP were in good health and had not received periodontal therapy. Pregnant women, alcohol users, smokers, and individuals with any systemic chronic degenerative, autoimmune, infectious, or contagious disease or who were under pharmacological treatment were exclusion criteria for participants of both groups.This study was approved by the Medical Ethics Review Committee of the University of Guadalajara. All participants were told the purpose of the study and accordingly signed the informed consent; they also answered a survey to determine if they met the inclusion criteria for the project.Periodontal examination was executed by a single calibrate examiner Periodontist (ALML), who established the periodontal diagnosis, considering radiographic and clinical parameters. Periodontal examination includes full-mouth clinical measurements of the plaque index (PI), bleeding on probing (BOP), clinical attachment level (CAL), and probing pocket depth (PD). BOP that was the average of the percentage of sites evaluated with the presence of bleeding was recorded as the mean percentage of sites. CAL and PD were assessed at six sites per tooth. Diagnosis was based on the criteria proposed by the International Workshop for a Classification of Periodontal Diseases and Conditions .Samples of GCF, saliva, and serum were taken in the morning (from 10:00 to 12:00 am) and the participants were instructed not to eat and drink anything except water or use dental hygiene products at least two hours before their appointment.Nonstimulated whole saliva samples were collected under resting conditions. Participants rinsed their mouths with water and, then, 3 mL of whole saliva was obtained by patients expectorating into disposable tubes . SamplesGCF samples were collected from a mesiobuccal and distobuccal site on each tooth . In individuals with CP, GCF samples were obtained from sites with a depth of ≥5 CAL. In the group without CP, GCF samples were collected from teeth showing PD ≤3 without CAL or BOP. Three GCF samples were collected from each participant. The sites were gently dried and isolated with cotton and GCF was collected by the intracrevicular absorption method , with paThe serum sample was obtained from whole blood by venipuncture and centrifuged at 1,972 g for 10 minutes at room temperature. The serum was separated and protease inhibitor was added. All the samples were stored at −80°C until analysis and a single freeze cycle was performed.MIF quantification was made by sandwich ELISA method  according to manufacturer's instructions. Absorbance was determined using a WHY101 microplate reader at a wavelength of 450 nm with a correction reading at 560 nm. MIF concentrations were calculated in ng/mL; these results were interpolated in a calibration curve of known concentrations included in the insert and the sensitivity of the kit was 8 pg/mL.Periodontal parameters are expressed as mean ± standard deviation (SD) and MIF concentrations as mean ± standard error (SE). All data were tested for normality using the Kolmogorov-Smirnov test. Differences in MIF concentrations were evaluated using Mann–Whitney's U test for intergroup comparisons and Wilcoxon test for intragroup comparisons. A Spearman correlation was performed to test the relationship between MIF concentration and periodontal clinical parameters. All tests were performed using the Statistical Program for Social Sciences (SPSS v11.0) for Windows . A p < 0.05 was considered statistically significant.Sociodemographic and clinical periodontal parameters are summarized in MIF concentrations in subjects without CP in GCF, saliva, and serum were 8.85±1.28 ng/mL, 31.5±5.76 ng/mL, and 7.08±0.58 ng/mL, respectively, while in the group with CP, these values were 17.85±1.04 ng/mL, 72.94±10.90 ng/mL, and 9.91±1.65 ng/mL, respectively . MIF conIntragroup comparisons of MIF concentrations were made between the three different fluids from each study group and we found that, in the group without CP, MIF levels were significantly higher in saliva (p=0.001) compared with GCF and serum (p=0.001) and no significant differences were observed between MIF levels in GCF and serum . HoweverIn order to associate MIF concentrations with clinical periodontal parameters, a positive significant correlation was found between MIF concentrations in GCF and clinical parameters  and between MIF concentrations in saliva and CAL (p= 0.03) . No signMIF has been proposed as a key proinflammatory cytokine in the development of various inflammatory and autoimmune pathologies , 28, 29.In CP, the severity of the disease is associated with the unregulated production of proinflammatory cytokines .MIF-173 G/C) increased the risk of CP [Some studies have identified MIF overexpression in GCF from subjects with gingivitis , in gingsk of CP . In our We found higher MIF levels in GCF and saliva in individuals with CP. The high levels of MIF in GCF and saliva could be attributed to the characterized microbial change  during the transition from health to periodontal disease , 33. TheIn the present work, no significant correlation was observed between serum levels of MIF and CAL, PD, BOP, and PI. However, a positive correlation was found between GCF levels of MIF and all clinical measurements as well as between salivary levels of MIF and CAL. The overall correlation between GCF levels of MIF and all clinical parameters in this work suggests that MIF may play an important role in inflamed periodontal tissue since the oral cavity and periodontal tissue are exposed to a wide variety of oral bacteria , 37, 38.GCF is obtained directly from the gingival sulcus where CP is developed. MIF concentration in GCF can be used as a biomarker of the progression of CP.However, salivary levels of MIF did not correlate with clinical parameters except with CAL. In the present work, the concentration of this cytokine in saliva did not show a strong lineal relationship with clinical parameters; this could be explained since MIF concentration in saliva is heterogeneous combined with the periodontal disease and the fact that the concentration of MIF could be affected by environmental factors of the oral cavity, such as microbes.γ, IL-1β, IL-2, IL-6, IL-8, MIF, PGE2, and MMP) [MIF acts in an autocrine manner and promotes the release of other proinflammatory molecules  , 38; theMIF has the ability to interact with chemokine receptors, such as CXCR2 , so thatWhat we can explain is that MIF is stimulus-dependent since dental plaque is the main etiological and persistent agent  because Serum levels of MIF were higher in the CP group, but no significant differences were found between the study groups. This could be explained since inflammatory mediators, bacteria, and endotoxins of CP can enter and travel through the circulation, because of the permeability of the gum due to the inflammation of periodontal tissue , 42.The serum concentrations of MIF obtained in the present work in individuals without CP coincide with values reported as normal in clinically healthy subjects ranging from 2 to 6 ng/ml .Furthermore, consider the intragroup comparisons to determine the behavior expressions of MIF in the biofluids: GCF , saliva , and serum (MIF systemic expressions) of the study groups. We observed that the concentrations of MIF in saliva were significantly higher than in GCF and serum in both groups and that MIF GCF level was greater than serum in the group with CP. In the CP group it is justifiable that saliva and GCF present higher MIF levels than serum. This increase may be due to the main stimulus for the release of MIF is found in the oral cavity, which is the presence of the disease and the bacterial component that causes the inflammatory response. On the other hand, in individuals without CP the same tendency was observed as in the group with CP.We hypothesized that this result may be due to the constitutive expression of MIF in cells that are in coating tissues, such as the mucosa, which is in direct contact with the external environment, so epithelial cells could be one of the main sources of MIF production . In the In this study, our results show that the presence of CP per se increases the levels of MIF in GCF and saliva. These results can position MIF in the panel of cytokines that promotes the inflammatory response in CP. However, it is important to continue carrying out more studies to further elucidate the participation of this cytokine in the pathology of CP.According to our results, it can be concluded that CP increases the concentrations of MIF in GCF and saliva. Furthermore, the association between MIF in GCF and clinical parameters suggests that MIF might be a biological marker of the severity of CP. This could reflect the participation of MIF in the microenvironment of the oral cavity.


The mean body mass index in women tended to be higher than in men. After adjusting for age and education, the gender effect on obesity persisted in women and was more significant than in men. There was also a positive and significant effect on obesity of sedentary behaviors and unhealthy foods intake. Moreover, fatty and fried foods displayed a positive multiplicative interaction, increasing obesity risk in women more than in men and indicating a possible dietary risk in in women in relation to obesity. The study suggests that the implementation of educational programs on nutrition and physical activity is particularly important for promoting a healthy body weight among Indonesian women.Sedentary behaviors and dietary intake are independently associated with obesity risk. In the literature, only a few studies have investigated gender differences for such associations. The present study aims to assess the association of sedentary behaviors and unhealthy foods intake with obesity in men and women in a comparative manner. The analysis presented in this study was based on the data from a population-based, cross-sectional, nationally representative survey . In total, 222,650 men and 248,590 women aged 19–55 years were enrolled. A validated questionnaire, physical activity card, and food card were used for the assessments. The results showed that the prevalence of obesity (body mass index of ≥27.5 kg/m Obesity has become a major problem in developing countries and third-world countries in Southeast Asia, including Indonesia. Not only it has increased the risk of non-communicable diseases, such as hypertension, diabetes, dyslipidemia, and renal dysfunction , but alsChanges in the dietary patterns and decreased physical activity are considered the most important determining factors of overweight and obesity in Indonesia ,4. IndivEvidence showed a strong increase in overweight and obesity prevalence in the female population . Gender Therefore, using nationally representative data from 2013 Indonesia Basic Health Research (Riskesdas/Riset Kesehatan Dasar), we first compared the prevalence of obesity, the sedentary behaviors, and unhealthy foods intake in Indonesian adult men and women of different ages and then explored the associations of sedentary behaviors and unhealthy foods intake with obesity in the two genders.We used a population-based, cross-sectional, nationally representative survey  conducted by the National Institute of Health Research Development (NIHRD), Ministry of Health, Indonesia. A two-stage stratified cluster sampling method was used to draw the study sample from 33 provinces of the 497 Indonesian districts. The sampling and survey methods have been described in detail (website) . CompletThe 1,027,763 participants were aged from 0 months to 75 years in the national survey, but our study only focused on 518,111 participants aged 19–55 years. Out of those, 46,871 (9.05%) adults who were underweight (BMI < 18.5) or morbidly obese (BMI > 40) were excluded and, finally, 471,240 (90.95%) adults were included in the study.The protocol, study design, data, and survey were reviewed and approved (LB.02.01/5.2/KE.006/2013) by the Health Research Ethics Committee—University of Indonesia, Hasanuddin University, the University of Airlangga, and The National Institute of Health Research and Development (NIHRD), Ministry of Health Republic of Indonesia.2) and was determined on the basis of the World Health Organization (WHO) criteria for the Asian population: normal weight (18.5 to <23 kg/m2), overweight (23.0 to <27.5 kg/m2), and obese (≥27.5 kg/m2) [Basic characteristics and anthropometric measurements (height and weight) were collected on the basis of a standardized protocol by well-trained interviewers. The standing height was measured by a multi-function brand Stadiometer with a capacity of 2 m and a precision of 0.1 cm. The body weight was measured by a Camry digital weight scale with a capacity of 150 kg. The weight scale was calibrated daily before using it. The body mass index (BMI) was calculated as weight (kg)/height squared  was further investigated for certainty. The data were excluded if a respondent was sick or could not move. The activities were: (1) a job in a paid and unpaid work environment, domestic work, harvesting agricultural products, fishing or animal hunting, searching for work, etc.; (2) relaxing time, including sports and recreation; (3) travel  to the workplace, marketplace, or for recreation. Once recorded, all activities were grouped according to the type of physical activity. Sedentary behavior was defined as (i) sitting at work or home (ii); sitting for transport (including waiting for transport); (iii) sitting or lying down to watch television or play electronic games; (iv) sitting or lying down to do other activities , not including sleeping (or napping). The duration of the sedentary activities was recorded in hours or minutes. Similar to another study in our domain , sedentaThe respondents were asked about the frequency of refined carbohydrates, fatty fried foods, sweet foods, and beverages intake in the last week using a questionnaire and food card. Food frequency was recorded as >one time (1x)/day, 1x/day, 3–6x/week, 1–2x/week, ≤3x/month, and never. It was categorized in a binary form: frequently (≥1x/day) and infrequently (<1x/day) . In foodp ≤ 0.05.Pearson’s Chi-squared test was used to test the obesity status, using age groups, gender, education, sedentary activities, and dietary intake as categorical variables see . Mean anThe characteristics of all participants stratified by age and gender are reported in In terms of sedentary behaviors, increased sedentary habits were found both in young and in middle-aged women compared to men. Similar observations were made for the proportions of refined carbohydrates and fatty and fried foods habitually consumed, but not for sweet foods and beverages. In general, the proportions of sweet foods and beverages and fatty and fried foods were higher in middle-aged groups than in young groups. In contrast, refined carbohydrates intake was higher in young-aged groups than in middle-aged groups.p < 0.0001). Moreover, the prevalence of obesity increased by age. In the group aged 46–55 years, the prevalence of obesity slightly decreased in both men and women. In all age groups, the prevalence of obesity was significantly higher in women than in men.  in the proportions of high sedentary behaviors (inactivity) between young overweight and obese men and women and among middle-aged overweight and obese men and women   .p < 0.0001) in the refined carbohydrates, sweet foods and beverages, and fatty and fried foods intakes between men and women in the young, overweight and obese groups and between men and women in the middle-aged, overweight and obese groups  in women and of 2.2% (14.8% in 2007 to 17% in 2010) in men in three years . In 2013In our study, before adjusting for unhealthy foods intake, the obesity risk for women seemed to increase more than for men as a consequence of sedentary behaviors . The meaMoreover, fatty and fried foods indicated a positive multiplicative effect in obesity risk in women in Our study showed that women had a higher obesity risk than men even if they consumed refined carbohydrates or fatty fried foods with the same frequency. However, gender differences regarding the relationship between dietary habits and obesity are inconsistent. The biological actions of endogenous estrogen may also be influenced by macronutrient intake . EstrogeThe strength of this study is that we used a large and representative sample of the Indonesian population. The questionnaires about physical activity and dietary behaviors were specific, and additional physical activity and dietary intake cards were utilized. Therefore, the reporting bias from the participants was minimized. Second, this study is the first in Indonesia exploring the prevalence of obesity and the associations between obesity and sedentary behaviors and unhealthy foods intake in the adult population.However, one of the limitations of this study is the cross-sectional design. Further research should consider a prospective cohort study to explore the different effects of sedentary behaviors and unhealthy foods on obesity, especially in women. Also, we were unable to explain the different mechanisms leading to obesity because of the unavailability of additional data. For example, we were unable to find the exact weight of foods consumed (gram), the energy intake , and the metabolic equivalents of the different activities. Moreover, we could not include some confounders, such as co-morbidities or estrogen levels.Based on the Indonesian Basic Health Research Survey data, this study reports an increase in obesity prevalence, high sedentary behaviors, and unhealthy foods intake especially in women. Our findings also suggest that unhealthy intake of fatty fried foods positively interacts with gender to increase the prevalence ratio of obesity in women more than in men. Future investigations should consider longitudinal studies to explore the different effects on obesity of sedentary behaviors and dietary patterns in the two genders. Nutritional and physical activity educational programs should be conducted, as they can play an important role in improving the physical activity levels, developing healthy eating behaviors, and maintaining a healthy lifestyle.


Anemia is one of the global public health problems affecting more than one-third of the world population. It has been strongly associated with limited psychomotor development; and poor growth and performance in cognitive, social, and emotional function in children. Despite published data revealed that anemia is a public health problem among children in Ethiopia, there is no a pooled national estimate on the prevalence and associated risk factors of anemia.2 statistics. Subgroup analysis was employed in the evidence of heterogeneity. Publication bias was assessed by visual inspection of the funnel plot and Egger’s regression test statistic.Published articles until December 31, 2017, were searched using comprehensive search strings through PubMed/Medline, EMBASE, SCOPUS, HINARI, Web of Science, Google Scholar and Google. Reference probing of published articles and hand searching were employed for grey literature. Two groups of review authors independently appraised the studies for eligibility and extracted the data. The quality of articles was assessed using Joana Brigg’s institute critical appraisal checklist for prevalence and analytical studies. The pooled estimates were determined using random effect model. Heterogeneity between the included studies was assessed using the IOf the total 871 articles retrieved, 34 articles which involved 61,748 children were eligible for meta-analysis. The overall pooled prevalence of anemia using random effect model was 31.14% . In subgroup analysis, the pooled prevalence of anemia was higher among preschool-aged children  than school-aged children . Furthermore, the odds of anemia was higher among children who were male , stunted , and wasted .The pooled prevalence of anemia among children was high, indicating that it had been continuing to be a public health problem. Therefore, there is a need to design a comprehensive prevention and control strategies to reduce its burden.The online version of this article (10.1186/s13052-018-0513-x) contains supplementary material, which is available to authorized users. Anemia is a pathological condition in which the number and size of red blood cells or the hemoglobin concentration of red blood cells drops below an established cutoff value. Anemia can be caused by Iron, Folate, vitamin B12 and vitamin A deficiency, chronic inflammation, parasitic infections, and inherited disorders . In deveAccording to the World Health Organization (WHO) report, anemia is considered to be an indicator of both poor nutrition and health . It is rThe prevalence of anemia remains high and is of priority area in low-income countries. According to WHO 2015 report, about 43% of under-five children were anemic, with regional variations of 62.3% in African, 53.8% in South-East Asia and 21.9% in Western Pacific Region [According to the global estimates 2011, the prevalence of anemia among infants and children aged 6–59 months was 40–59.9% in Ethiopia , 10–12 aEven though the prevalence of severe to moderate anemia in the last fifteen years has significantly declined in Ethiopia, children and pregnant women are still suffering from the consequences of anemia due to high iron requirements, low intake of iron from foods, and frequent episodes of infection , 13. As The government of Ethiopia has been working to end childhood anemia. Accordingly, it endorsed national nutrition and bimanual school deworming programs; developed micronutrient deficiency prevention and control guideline. But studies from different corners of the country show that childhood anemia is still a major public health problem in Ethiopia. In addition, there is no a single national figure about childhood anemia and also inconclusive evidence about factors associated with it. Systematic review and meta-analysis generates concrete evidence in which it may urge policymakers and program managers to design an appropriate intervention to control and minimize the negative consequence of anemia. There is no meta-analysis conducted showing the pooled prevalence of childhood anemia in Ethiopia so far. Therefore, the aim of this review is to estimate the pooled prevalence and identify factors associated with anemia among children in Ethiopia.2, making it the 27th largest country in the world. The country is working in reduction of maternal and child under-nutrition through implementing different programs and working jointly with international partners.This systematic review and meta-analysis was conducted in Ethiopian setting. Ethiopia is one of the developing countries located in the horn of Africa having nearly 100 million people with an area of 1,100,000 kmThis systematic review was designed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analysis Protocols (PRISMA-P 2015 Guidelines) [Relevant articles published until December 31, 2017 were searched in PubMed/Medline, HINARI, SCOPUS, EMBASE and Web of Sciences electronic databases. Grey literature were searched in Google Scholar and Google. The search terms were developed in accordance with the Medical Subject Headings thesaurus using the following terms in combination with free text key terms, “anemia”, “iron deficiency anemia”, “nutritional anemia”, “hemoglobin”, “nutritional status”, “hematological parameters” “children”, “preschool” “adolescent”, “determinant factors of anemia”, “associated factors of anemia”, and “Ethiopia”. The above terms were searched by a combination of Boolean operators . Hand searching of articles published in Ethiopian journal of health sciences, Ethiopian Medical Journal, Ethiopian Journal of Health and Development, and Ethiopian Journal of Health and Biomedical Sciences was conducted. Reference lists of retrieved articles were probed to identify any studies that are not retrieved from electronic databases.All articles retrieved through search strategy were imported to EndNote X7 . After excluding duplicated articles, titles/abstracts were independently screened by two groups of review authors: group one  and group two . Differences were resolved through thorough discussion. In case of disagreement between the two groups of review authors, the decision was determined by the third group of review authors . For articles deemed to appear relevant during title/abstract screening, the full-text was appraised for inclusion in systematic review and meta-analysis. The quality of articles was assessed using Joana Brigg’s institute (JBI) critical appraisal tools for simple prevalence  and analThe primary outcome of this review was to estimate the pooled prevalence of anemia among children in Ethiopia. The prevalence was calculated by dividing the number of anemic cases for the total number of children. Also, three determinant factors including sex, stunting, and wasting were assessed. Accordingly, the odds of developing anemia among male, stunted, and wasted children were calculated.Studies published until December 31, 2017Studies reported the outcome of interest among children in EthiopiaObservational studies like cross-sectional, prospective cohort studies and repeated cross-sectional studiesStudies conducted in healthcare facilitiesStudies that used visual comparative method  and Copper Sulphate densitometer to ascertain the outcome (anemia)Studies conducted among children living with HIV/AIDSThe JBI tool was adopted for data extraction. Information such as the name of first author, year of publication, age group of children, year of study, study area/region, study design, the total number of children, number of anemic case, and number of anemic and non-anemic cases for the reported associated factors were extracted. The data were recorded in Microsoft Excel spreadsheet. When authors found multiple publications from the same dataset, the article that reported the prevalence and associated factors in an extractable form were included. Moreover, for prospective cohort and repeated cross-sectional studies, the baseline data were used for our systematic review and meta-analysis to facilitate comparability of results across studies and to reduce a loss to follow-up bias.2 statistics) [2 value of 25, 50 and 75% are assumed to represent low, medium and high heterogeneity, respectively. The significance of heterogeneity was determined by a p-value of I2 statistics, and a p-value < 0.05 was considered as an evidence of heterogeneity. When the I2 value was greater than 50%, we used Dersimonian and Liard random effect model to determine the pooled estimate [The data were entered into Microsoft Excel, and then exported to STATA version 14  for analysis. The magnitude of heterogeneity between included studies was quantitatively measured by the index of heterogeneity (Itistics) . The I2 estimate . SubgrouA total of 781 records were retrieved, of which 38 articles were removed due to duplication. Seven hundred articles were also removed as their titles and abstract was irrelevant to the current analysis. The remaining 42 full-text articles were assessed for eligibility based on the pre-set criteria  and 1(2.9%) of the included studies were cross-sectional, and repeated cross-sectional studies, respectively. Concerning study settings where the studies were conducted, it has been as follows: 26.5% in Amhara Regional State  , showing a high level of heterogeneity between the included studies. Subgroup analyses were done by considering age and region as grouping variables. Accordingly, the pooled prevalence of anemia among preschool-aged children was 44.17% , whereas it 22.19%  among school-aged children   times higher compared to females  Fig. . On the Anemia has been a public health problem affecting the low, middle and high-income countries. It has also been significantly associated with negative consequences on health, social and economic development , 53. GloThe overall pooled prevalence of anemia was 31.14% . This implies that anemia is a moderate public health problem among children in Ethiopia , which nIn subgroup analysis, the pooled prevalence of anemia among school-aged children was 22.19% , which is lower than pooled estimate among preschool-aged children, 44.17% . It is reasonable that the magnitude of anemia declines as the age of children advanced. Compared to school-aged children, preschool-aged children have high dietary requirement owing to rapid rate of growth  and expaIn random effect model, the pooled effect size of anemia among male children is higher than female children . Consistent with previous studies , 64, theIn this meta-analysis, a higher odds of anemia was noted among stunted  and wasted  children. Previous literature also supported that stunting , 72–74 aThe review has some limitations. The extent of heterogeneity between included studies was high, which can be attributed to differences in methodology, study period, and geographic location. Moreover, some of the studies did not consider an altitudinal adjustment to define anemia, which may underestimate the burden of anemia among children. Given these limitations, the review was conducted according to the preferred reporting items for systematic review and meta-analysis (PRISMA-P statement) protocol. Besides, a comprehensive searching with no language restriction and the involvement of experts from biomedical, public health and clinical fields improved quality of evidence generated.In conclusion, the pooled national prevalence of anemia among children was high. As to the WHO classification of anemia on the basis of public health importance, it is a moderate public health problem among children in Ethiopia. The pooled prevalence was higher among preschool-aged children than school-aged children. Moreover, the likelihood of anemia was higher among male and undernourished children. Therefore, optimizing the nutritional supplementation, improving access to child health care, and sustaining the socio-economic development need to be emphasized to reduce the burden of childhood anemia in Ethiopia.Additional file 1:Figure S1. Funnel Plot. The Funnel plot showing the pooled estimate of anemia among children in Ethiopia. This is a visual method to see small-study effect or publication bias. (DOC 26 kb)Additional file 2:Figure S2. Egger’s Plot. A Plot of Egger’s test of publication bias for pooled estimate of anemia among children in Ethiopia. Egger’s test is a statistical method to test the presence of small-study effect or publication bias on the pooled estimate. (DOC 26 kb)


Chagas disease is a neglected tropical disease. About 6 to 8 million people are chronically infected and 10% to 15% develop irreversible gastrointestinal disorders, including megaesophagus. Treatment focuses on improving symptoms, and isosorbide and nifedipine may be used for this purpose.We conducted a systematic review to evaluate the effectiveness of pharmacological treatment for Chagas’ megaesophagus. We searched MEDLINE, Embase and LILACS databases up to January 2018. We included both observational studies and RCTs evaluating the effects of isosorbide or nifedipine in adult patients with Chagas’ megaesophagus. Two reviewers screened titles and abstracts, selected eligible studies and extracted data. We assessed the risk of bias using NIH ‘Quality Assessment Tool for Before-After (Pre-Post) Studies with No Control Group’ and RoB 2.0 tool. Overall quality of evidence was assessed using GRADE.We included eight studies . Three studies evaluated the effect of isosorbide on lower esophageal sphincter pressure (LESP), showing a significant reduction . Three studies reported the effect of isosorbide on esophageal emptying, showing a decrease in esophageal retention rates . In one study, patients on isosorbide reported improvement in the frequency and severity of dysphagia . Studies evaluating nifedipine observed a decrease in LESP but no effect on esophageal emptying . Isosorbide had a higher incidence of headache as a side effect than nifedipine.Although limited, available evidence shows that both isosorbide and nifedipine are effective in reducing esophageal symptoms. Isosorbide appears to be more effective, and its use is supported by a larger number of studies; nifedipine, however, appears to have a better tolerability profile.CRD42017055143.PROSPERO CRD42017055143.ClinicalTrials.gov  Chagas disease is a chronic neglected tropical disease that has increased in prevalence in the last decade. About 10% of chronically infected patients develop the digestive form of the disease. Megaesophagus is a common manifestation, and symptoms include difficulty or discomfort in swallowing and regurgitation. Treatment approaches include dietary interventions, medications, and endoscopic and surgical interventions. Regarding pharmacological treatment, only a few small studies have evaluated the effects of isosorbide and nifedipine, mainly on surrogate outcomes. According to our systematic review, the use of isosorbide reduced lower esophageal sphincter pressure, esophageal retention after meal ingestion, and the frequency and severity of dysphagia, while nifedipine reduced esophageal retention after meal ingestion. In light of this, both medications are effective in the treatment of symptoms associated with Chagas disease. Isosorbide appears to be more effective, and its use is supported by a larger number of studies; nifedipine, however, appears to have a better tolerability profile. Both drugs are valid alternatives, and the decisions about pharmacological treatment should be tailored to each patient. Trypanosoma cruzi. Once confined to Latin America, it has now spread to other continents. It is estimated that about 6 to 8 million people are infected worldwide. Infection is lifelong and can be life threatening, killing more than 10 000 people every year. Despite its relevance, it is considered by the World Health Organization a neglected tropical disease [Chagas disease, also known as American trypanosomiasis, is an infectious zoonosis caused by the protozoan parasite  disease .Chagas disease is transmitted by triatomine vectors (popularly known as kissing bugs), vertically (from mother to fetus), orally (by ingestion), by blood transfusion, by organ transplants, and by laboratory accidents. During the first weeks or few months, the disease presents in its acute form, which has no or only mild symptoms, such as fever, fatigue, and headache; thus, infection often goes unnoticed. The host’s immune system then controls parasite replication, and patients enter the chronic phase. Most patients remain asymptomatic, but approximately 30% of infected people develop medical complications from Chagas disease over the course of their lives, usually several years or even decades after the initial infection. The disease mainly affects the heart, digestive system, and nervous system .T. cruzi strains. They are more frequent in central and southern South America  and very rare in other regions [T. cruzi. Any organ of the digestive system can be affected, but the esophagus and colon are most often injured, causing megaesophagus and megacolon [Digestive disorders are the second most common manifestation of Chagas disease, affecting about 10% to 15% of patients [ regions –8. Gastregacolon . The esoegacolon , 9. The egacolon , 6, 10. T. cruzi are similar, but not equal, to those caused by idiopathic (primary) achalasia. Although differences have been described, both conditions are treated similarly [The changes in esophageal function caused by imilarly , 16. Treimilarly , 18 , Embase and LILACS databases to retrieve potentially relevant articles from inception to January 2018. We also screened the reference lists of identified publications for additional studies and contacted authors for further information as needed. We conducted two independent searches, one for each intervention (isosorbide and nifedipine). Search terms included “Chagas disease”, “We included studies that met the following criteria: (A) observational studies or clinical trials; (B) studies that assessed the effects of isosorbide or nifedipine on esophageal symptoms or esophageal function in patients with Chagas disease; and (C) individuals aged >18 years with digestive or cardiodigestive form of Chagas disease, according to original studies definitions. We excluded reviews, letters, and editorials.The outcomes of interest were (A) esophageal symptoms (e.g. dysphagia and regurgitation), (B) esophageal function , and (C) adverse events. We did not include other gastrointestinal symptoms caused by Chagas disease, because isosorbide and nifedipine are used only for esophageal symptoms.In order to screen and select eligible studies, we combined the results from both searches. All identified citations were entered into a software for reference management, and duplicates were excluded. Two independent reviewers (CBM and CS) screened the titles and abstracts of all potentially relevant articles identified by the searches, and studies not meeting the eligibility criteria were excluded. The same reviewers assessed the full-text articles of selected abstracts for inclusion according to the pre-specified eligibility criteria. If the study was reported in duplicate, the study published earlier or the one that provided more information was included. Independently, the same reviewers extracted data from the full text of included studies using a pre-designed data extraction form. Data extracted included study characteristics and outcomes of interest. When needed, data were extracted from figures or graphs using WebPlotDigitizer . DisagreTwo reviewers (CBM and CS) independently assessed the methodological quality of included studies. We used the NIH ‘Quality Assessment Tool for Before-After (Pre-Post) Studies with No Control Group’  for all The overall quality of evidence was assessed using GRADE .P value ≤ 0.05 was considered statistically significant. Statistical heterogeneity among studies was assessed using Cochran’s Q test and the I2 statistic. All meta-analyses were performed using the R statistical software version 3.3.3, with meta package version 4.8–1 [Where possible, data were pooled using a meta-analytic approach. A random-effects model, with DerSimonian and Laird’s variance estimator, was used, and the results were presented as mean difference or pooled prevalence, with 95% confidence intervals (95%CI). A on 4.8–1 , 27.P value; or input of the highest SD found in other studies for the same outcome.When a study did not report the standard deviation (SD), one of the following three strategies was used: estimation of individual patient data from the study’s graphs and calculation of mean and SD; calculation of SD from Studies not included in the meta-analysis were presented descriptively.A total of 66 studies were retrieved for ‘isosorbide’ and 40 for ‘nifedipine’. Of these 106 studies, eight met the eligibility criteria and were included in our review. P values for the analysis. Among crossover trials, only one study was rated as having a low risk of bias, with no major concerns [The quality of all before-after studies was rated as fair –31. All concerns . The othconcerns ,34,35. RThree before-after studies evaluated the effect of isosorbide on LESP and were included in the meta-analysis , 29, 30.2 = 0%), and the quality of evidence was rated as very low due to the high risk of bias and imprecision. The full GRADE assessment is available in After 10 minutes of administration, isosorbide decreased LESP by 10.52mmHg , leading to improvement in dysphagia . These rThree crossover trials assessing the effect of isosorbide on esophageal emptying were included in the meta-analysis ,34,35. IS5 Appendix2 = 0%). The quality of evidence was rated as low due to the high risk of bias and imprecision , which is indicative of an increase in esophageal emptying . These rrecision .versus placebo on the frequency and severity of dysphagia and global well-being in 23 patients with Chagas disease. Patients took both isosorbide and placebo, for 1 week each, in a randomly allocated order. During the weekly interviews, patients were asked to rate the frequency and severity of dysphagia and global well-being compared with prior treatment. Scores for the frequency and severity of dysphagia were significantly lower after isosorbide treatment compared with prior treatment and placebo. Regarding global well-being, 12 out of 20 patients reported improvements compared with the pretreatment condition. However, there was no difference in scores between isosorbide and placebo, probably because of side effects. Three patients did not complete the study, one because of headache and fainting during isosorbide treatment. The quality of evidence was rated as moderate due to imprecision   assessedrecision .Four studies evaluated side effects caused by isosorbide and were included in a meta-analysis of prevalence data, shown in The prevalence of headache after sublingual intake of isosorbide was 31.60% . Furthermore, 9.50% of patients  reported palpitation and 7.74%  reported faintness after isosorbide ingestion .Only one before-after study evaluated the effect of nifedipine on LESP in patients with Chagas disease . Dantas Figueiredo et al. (1992)  assessedTwo studies reported side effects caused by nifedipine administration , 34. TheNifedipine caused headache in 10.48% of patients  . No studThis review evaluated the effect of isosorbide and nifedipine on esophageal symptoms in patients with Chagas disease. Studies investigating the effect of isosorbide showed that this medication decreased LESP and esophageal retention; moreover, it improved the severity and frequency of dysphagia as reported by patients. Among the studies, mean baseline LESP was 17.4mmHg. The reduction of 10.52mmHg correspond to 1.33 standard deviation, which is considered a large magnitude of effect, indicating the intervention is highly effective in reducing LESP . HoweverEven though digestive symptoms are a well-known manifestation of Chagas disease, recommendations for their treatment are often neglected. In a review of published guidelines for the management of Chagas disease, 10 documents were found, but only two of them provided recommendations for the pharmacological treatment of megaesophagus .Both isosorbide and nifedipine led to improvement in esophageal symptoms. However, only one study, involving 11 patients, directly compared the two drugs of interest . By indiAlthough current evidence potentially indicates greater certainty that isosorbide is more effective, it is important to consider potential side effects when choosing treatment. In our systematic review, from 30 to 50% of patients on isosorbide reported side effects such as headache, faintness, and palpitation, which may impact long-term adherence to the medication. The rate of side effects of nifedipine was lower, a result similar to that reported in studies of patients without Chagas disease , 39. AltTo our knowledge, this is the first systematic review to evaluate the effects of isosorbide and nifedipine in patients with Chagas disease. We performed a comprehensive literature search without language or date restrictions and systematically evaluated the risk of bias and quality of evidence for the proposed interventions. Included studies applied diagnostic and staging methods currently in use, enhancing the external validity of our findings. Additionally, we performed a meta-analysis of several outcomes of interest, thereby increasing statistical power and precision and making it possible to assess the consistency of the findings.Our systematic review has some limitations, mostly due to the characteristics of included studies. First, the number of included studies is small, a consequence of the sparse number of publications in the field. Besides, all studies were conducted in Brazil, most of them in the same city. This may limit generalizability of the findings, which may be an issue of concern especially nowadays when Chagas disease has spread globally. Moreover, the studies were conducted at least 23 years ago, and since then the healthcare provided to patients has probably changed. Furthermore, all included studies were very small and had methodological limitations. Regarding outcome evaluation, most studies evaluated only surrogate outcomes for symptom improvement, and these measurements may not directly reflect clinical improvement. Besides, no study assessed the long-term effects of these medications; thus, our conclusions provide direct evidence only to short-term outcomes, and the long-term effects for these interventions are still unknown. It is important to note that our systematic review evaluated only studies of patients with Chagas disease; for the assessment of side effects, we did not include information from further studies conducted in other relevant fields, such as cardiology. Although including the results of patients without Chagas disease would increase the heterogeneity and indirectness of our findings, it could give more precision to the prevalence estimates of some side effects that may be similar in patients with and without Chagas disease.Based on the findings of our systematic review, while also acknowledging the lack of rigorous studies such as long-term clinical trials, isosorbide and nifedipine are effective in the treatment of esophageal manifestations of Chagas disease. Isosorbide appears to be more effective, and its use is supported by a larger number of studies. However, nifedipine appears to have a better tolerability profile. Both drugs seem to be valid alternatives, and the decisions about pharmacological treatment should be tailored to each patient.S1 Appendix(PDF)Click here for additional data file.S2 Appendix(PDF)Click here for additional data file.S3 Appendix(PDF)Click here for additional data file.S4 Appendix(PDF)Click here for additional data file.S5 Appendix(PDF)Click here for additional data file.S6 Appendix(PDF)Click here for additional data file.S7 Appendix(PDF)Click here for additional data file.


The incidence of tuberculosis (TB) remains high worldwide. Current strategies will not eradicate TB by 2035; instead, by 2182 is more likely. Therefore, it is urgent that new risk factors be identified.An ecological study was conducted in 340 prefectures in China from 2005 to 2015. The spatial distribution of TB incidence was shown by clustering and hotspot analysis. The relationship between the distribution patterns and six meteorological factors was evaluated by the geographically weighted regression (GWR) model.p < 0.05).During the 11 years of the study period, TB incidence was persistently low in the east and high in the west. Local coefficients from the GWR model showed a positive correlation between TB incidence and yearly average rainfall (AR) but a negative correlation with other meteorological factors. Average relative humidity (ARH) was negatively correlated with the incidence of TB in all prefectures  contains supplementary material, which is available to authorized users. M. tuberculosis) [M. tuberculosis, but the pathogen is very sensitive to ultraviolet (UV) light, which is found in sunlight [M. tuberculosis to a certain extent. Therefore, the aim of this study was to explore whether meteorological factors from the prefecture level are potential determinants of TB incidence in China in order to provide a theoretical basis for the prevention and control measures of TB.Tuberculosis (TB) is still one of the most infectious diseases worldwide with an estimated 10.0 million new cases and 1.3 million deaths according to the Global Tuberculosis Report from 2018 [culosis) –6. The pculosis) . Howeverculosis) –11. To fsunlight . TherefoAll TB patients were from the Infectious Disease Reporting System (IDRS) and the Tuberculosis Information Management System (TBIMS) from the Chinese Center for Disease Control and Prevention (CCDC) , 14, whiWe also obtained daily meteorological data for each prefecture during the study period from the China Meteorological Data Sharing Service System , includiAdditionally, the size of the population in each prefecture in every year was obtained from the Chinese Statistical Bureau , which wFrequently used descriptive epidemiologic methods were applied to analyse the distribution patterns of TB incidence. The Anselin Local Moran’s I statistic and the Getis-Ord Gi* statistic were used to analyse the clustering of TB incidence and to identify TB incidence hotspots, respectively. The geographically weighted regression (GWR) model was used to explore the spatial variation of the relationship between TB incidence and meteorological factors. Spatial positions of the data were taken into consideration in the GWR model, so the local parameters changed with the spatial position . Variancj, νj) is the spatial coordinate of sample point j; β0 and βi are the regression constant and the regression coefficient of sample point j, respectively; and εj is the random error of the independent distribution. Considering that the samples were not regularly spaced in 340 prefectures, the adaptive bandwidth and Gaussian kernel were implemented to build the model, which provides the same number of samples for each local estimate and is based on the whitepaper for GWR [A conventional GWR model can be described by the following equation: for GWR , 20.P-values less than 0.05 were considered statistically significant.The GWR model was built with the GWR4.0 software. All statistical tests were two-sided, and A total of 10,271,169 TB cases were reported from 1 January 2005 to 31 December 2015. After excluding cases with missing or abnormal values, our final sample included a total of 10,268,212 TB cases.In general, the spatial analysis indicated an unbalanced geographical distribution of TB incidence in China, with high rate in the west and a low rate in the east between 2005 and 2015. The Xinjiang Uygur Autonomous Region had the highest incidence among 31 provinces. Specifically, Hotan Prefecture, Kashi Prefecture and Aksu Prefecture, located in the south of the Xinjiang Uygur Autonomous Region, had the highest TB incidence of over 180/100000. Additionally, some other prefectures adjacent to the border between the Tibet Autonomous Region and Gansu Province, Heilongjiang Province, Guizhou Province and Hainan Province also had a high TB incidence  compared with the ordinary least squares regression (OLS) model . There were large differences in the distribution characteristics of meteorological factors in 340 prefectures , while AR was significant for all prefectures except some in the southeastern China, and ASD was significant for all prefectures except some in the western China. In addition, the relationships between the other three meteorological factors and TB incidence were not consistent across the study area. Specifically, AT was statistically significant only in north-eastern and central China . In aerosol form only, M. tuberculosis can be inhaled into the lung to cause TB. Humanity has reduced dust emissions and the formulation of aerosols, and has thus reduced the spread of TB. In addition, TB incidence was associated with AWS and AAP in many prefectures. The higher AWS could accelerate ventilation, dilute the concentration of bacteria and help reduce the risk of becoming infected. For the AAP, increased atmosphere flow usually forms from high air pressure regions to low air pressure regions, so the mechanism of negative correlation between air pressure and TB incidence may be similar to wind speed, but further explorations are needed.There are some limitations of the study. First, the potential for under-reporting of cases is inevitable in surveillance data, which is dependent on healthcare-seeking behaviours. In addition, if there is less healthcare available in certain areas, one might expect less reporting, so TB incidence would be underestimated. Second, this is a cross-sectional study with all data collapsed from 2005 to 2015, so the time effects, such as a lag effect, were ignored. Third, we took only meteorological factors into consideration, and some other risk factors associated with TB incidence, such as healthcare access, socioeconomic status and individual-level factors that correlate with geography were not considered due to the unavailability of data. Therefore, further studies should control for other factors affecting TB at a more detailed time scale. Moreover, an ecological study cannot provide conclusive results but can only generate and develop hypotheses.In this study, we found that meteorological factors may play an important role in TB incidence in many prefectures in mainland China. Therefore, the prevention and control strategies of TB should take meteorological factors into account. Next, we will proceed to further study about meteorological factors according to the results of this study.Additional file 1:Table S1. The number of reported TB cases in 31 provinces of mainland China, 2005–2015. Figure S1. Spatial distribution of six meteorological factors in 340 prefectures from 2005 to 2015. (DOC 1020 kb)


In Senegal in 2015, an estimated 4800 children were living with HIV, with 1200 receiving ARV treatment, of whom half had follow-up care in decentralized sites outside Dakar.However, until now no studies have determined the efficacy of pediatric treatment in decentralized settings, even though the emergence of viral resistance, particularly among children in Africa, is a well-known phenomenon. This study aimed to assess the virological status of HIV-infected children in all decentralized facilities to help improve access to quality care.A cross-sectional epidemiological and virological study was conducted in all of Senegal’s regions, except Dakar, between March and June 2015 and sought to include all HIV-infected children and adolescents (0–19 years), treated or not with ARVs.10).Socio-demographic and clinical data and a blood sample on blotting paper were collected for children from treatment sites. Samples were routed on public transportation, assisted by a network of community health workers. A viral load (VL) assay was performed for each child, followed by genotyping when it exceeded 1000 copies/mL  were enrolled in the study. Half of the children were girls, and the average age was 8 years (6 months–19 years). Most of the children (96.7%) were infected with HIV-1, and 90% were treated with ART, primarily with AZT + 3TC + NVP/EFV therapeutic regimen. The median duration of time on ART was 21 months (1–129). VL was measured for 2% of children before this study. Almost two-thirds (64%) of the children are experiencing virological failure. Among them, there was resistance to at least one drug for 86.5% of cases. Also, 25% children presented resistance to one drug and 40% to two out of three. For nearly one-third of the children presenting resistance, none of the three drugs of the treatment was active. Factors associated with virological failure were male sex, follow-up by a generalist rather than a specialist, and treatment interruptions.We observed a high level of virological failure and a high percentage of viral resistance among children receiving health care in decentralized facilities in Senegal. The use of antiretroviral therapy (ART) has considerably reduced morbidity and mortality among HIV-infected children. In 2013, WHO recommended universal treatment for all children up to age 10 years in 2015 . Ten percent of children had a VL greater than 5 log10  had resistance to at least one drug , follow-up care by a generalist rather than a pediatrician (0.036), and prolonged treatment interruptions (0.001). No significant difference was found in terms of mother’s vital status, parents’ marital status, existence of an HIV-positive sibling, declared compliance, or regularity of follow-up  presented resistance to at least one antiretroviral drug. This study is the first national assessment in Senegal of the virological status of HIV-infected children who are receiving care outside of reference centers located in Dakar. Its interest lies in the large number of children included and its reach across the entire country. All health facilities that treat HIV-infected children throughout Senegal, with a wide range of technical platforms and economic and geographic environments, were included. Resistance tests were performed for 95% of the children with high VL, which provides a good estimation of their virological situation. Therefore, this study accurately reflects decentralized treatment for children in Senegal. The collected data were transmitted to each site’s physicians so that they could adapt each child’s antiretroviral treatment based on the biological results.Nevertheless, there are limitations: 21% of the children were not included for various reasons, including travel at time of the survey and difficulties reaching the family. Moreover, this is a cross-sectional study, with a single sample. The reliability of this type of survey is weak and factors associated with treatment failure should be interpreted cautiously. Also, since there were many sites and a very small number of children in some of them, we were not able to analyze the factors due to site effect.Compliance data were based solely on physicians’ estimates, with some subjectivity. Socio-economic factors related to therapeutic failure have not been explored. Missing data on some variables must also be considered.In this study, percentage of observed PMTCT failure (2%) is close to the 3.1% transmission rate for the entire country in 2015 [Coverage in Senegal is relatively low, with only 36% of women having received ART during PMTCT in 2015. This rate is close to that of some neighboring countries, such as Mali (33%) or Niger (28%), but lower than others, such as Burkina Faso (79%) or Côte d’Ivoire (89%) .Along with expanding PMTCT coverage, testing strategies for children outside of these programs must be strengthened. The study shows that testing for children remains low in affected families, as evidenced by the high percentage of siblings of HIV-infected children who were not tested. In addition, the number of children receiving care is low compared to the number of adult PLHIV who do, since it amounts to less than 7% of infected people treated by ART nationwide; this exemplifies one of the consequences of limited testing . While bThis study reveals that nearly two-thirds of children treated by ART and receiving care in decentralized sites are experiencing treatment failure, according to the 2013 WHO standards. Various studies have shown high rates for virological failure in children treated with ART in resource-limited countries. Meta-analyses of countries in Africa, Asia, the Caribbean, and Latin America have reported average treatment failure rates from 26 to 36% with wide variations 13 to 71%) depending on the countries, the type of study, treatment duration, and VL thresholds used to define virological failure 1% depend. In AfriSome factors associated with virological failure—poor adherence, prolonged treatment interruption, and irregular follow-up—are known , 13, 20.Most children with virological failure show resistance to one or two classes of antiretrovirals. Resistance, particularly to NNRTIs, is high and remains stable over time. For nearly one-third of the children presenting resistance, no drug is active, and 40% are only sensitive to one drug. The rate of cross-resistance is concerning. Accumulated resistance mutations not only make children resistant to their treatment, but also create resistance to alternative drugs.Similar results are found in urban settings in Senegal , as wellThe properties of drugs (low genetic barrier), difficult adherence for children, young children’s poorer response to ART, frequently high VLs at treatment initiation, and administration of sub-therapeutic doses are known factors of failure . Non-exiFortunately, the situation is reversible. Through measures implemented with support from research and public health programs, the Albert Royer Children’s Hospital in Dakar managed to invert the proportions of viral suppression, from 34 to 80% between 2010 and 2016 . Thus, iRoutine virological monitoring is rarely done in the decentralized sites. While 90% of children are treated with ART, only 2% have had VL tested at least once, and measuring VL has only been recently included in both international and national recommendations.For most of the children, this study was an opportunity to have their first virological test. It helped diagnose treatment failures, which are more difficult to detect using clinical and immunological criteria , 27. ThoThis study has shown the feasibility of virological monitoring of HIV-infected children, living throughout Senegal, by implementing a DBS-collection and -routing circuit. This circuit, supported by a network of community health workers and public transportation, has proven to be flexible, effective, and inexpensive. It is easily reproducible by the national AIDS control program, but its sustainability depends on funding for the circuit, the availability of reagents, its continuous coordination, and rapid reporting of results.The problem of therapeutic failures and viral resistance has become a major international issue for children and adults alike. In 2017, a WHO report noted the rapid development of viral resistance to ARVs. Its 2017–2021 action plan recommends widespread virological follow-up, switching treatment regimens, better support systems for adherence, and resistance surveillance at country level , 29. TheThis study is the first of its type conducted in the regions of Senegal. The high number of children in treatment failure in decentralized facilities shows the limited efficacy of care services, a situation also found in other resource-limited countries. However, improvement is possible through targeted measures. This involves overall strengthening of facilities, managing notifications, improvements in children’s social and economic environment such as community people involvement, social support for families , support for adherence, and a system for regular virological monitoring. It also requires adjusting treatments quickly for children with virological failure, by introducing protease inhibitors, considering first-line therapies with high genetic barriers, and lastly, ensuring the availability of third-line ART. Implementing these measures is crucial if we hope to achieve the UNAIDS 90–90-90 goals and eradicate the epidemic by 2030 [


The area under ROC curves of the random forest model was significantly greater than that of Acute Physiology and Chronic Health Evaluation (APACHE) II , Therapeutic Intervention Scoring System (TISS) , and Glasgow Coma scales . The results revealed that the random forest model was the best model to predict the mortality of UE patients in ICUs.Unplanned extubation (UE) can be associated with fatal outcome; however, an accurate model for predicting the mortality of UE patients in intensive care units (ICU) is lacking. Therefore, we aim to compare the performances of various machine learning models and conventional parameters to predict the mortality of UE patients in the ICU. A total of 341 patients with UE in ICUs of Chi-Mei Medical Center between December 2008 and July 2017 were enrolled and their demographic features, clinical manifestations, and outcomes were collected for analysis. Four machine learning models including artificial neural networks, logistic regression models, random forest models, and support vector machines were constructed and their predictive performances were compared with each other and conventional parameters. Of the 341 UE patients included in the study, the ICU mortality rate is 17.6%. The random forest model is determined to be the most suitable model for this dataset with F Although some UE patients may have successful extubation without re-intubation, other patients experiencing UE may have severe complications, such as aspiration pneumonia, unstable hemodynamic status, airway obstruction, bronchospasm, respiratory failure, prolonged MV uses, and a prolonged length of stay in ICUs and hospitals13. Most unfortunately, some UE patients may present a fatal outcome; the mortality rate can even be as high as 25%14.Acute respiratory failure is a common clinical condition in the intensive care unit (ICU), and most patients with acute respiratory failure require endotracheal intubation with mechanical ventilation (MV) support. For these patients, both endotracheal tube and mechanical ventilator are essential for life support devices. However, unplanned extubation (UE) – an accidental removal of an endotracheal tube (ETT), may develop in about 2–16% of acute respiratory failure patients requiring MV15. Since clinical assessment of illness severity is especially important for the prediction of the mortality and morbidity of critically ill patients, several researchers have attempted to design various scoring systems to determine illness severity for the prediction of patient prognosis. The Acute Physiology, Age, Chronic Health Evaluation (APACHE-II) score predicts the mortality risk for critically ill patients in the ICU16, whereas the Therapeutic Intervention Scoring System (TISS) assesses illness severity. Both systems are often used in conjunction to assess patient prognosis17. The usage of these scales, however, comes with limitations. The TISS-28 includes 28 items, divided into seven groups: basic activities, ventilatory support, cardiovascular support, renal support, neurological support, metabolic support, and specific interventions18. However, its accuracy in predicting actual mortality, alongside the APACHE II system, is limited19.Several studies reported that tachypnea before UE, underlying uremia or liver cirrhosis, severe conditions with higher APACHE II scores, not undergoing the weaning process, reintubation, chronic neurological disease, and emergency surgery were found to be significantly associated with high mortality among UE patients25. In this study, we aim to construct several machine learning models to predict the mortality of UE patients and compare their predicting performance with other conventional parameters.In recent years, multivariate outcome prediction models such as artificial neural networks (ANN), logistic regression models (LR), random forest models (RF), and support vector machines (SVM) have been developed in many areas of health care researchThis study was conducted in eight adult ICUs of Chi-Mei Medical Center from December 1, 2008 through July 31, 2017. This is a 1288-bed tertiary medical center with 96 ICU beds: 48 medical ICU beds, 9 cardiac beds, and 39 surgical beds for adults. Every year, an average of more than 5,000 patients are admitted to the ICU. The ICU is covered by intensivists, senior residents, nurses, respiratory therapists, dietitians, physical therapists, and clinical pharmacists. Each shift had the same workload and the patient-to-nursing staff ratio is of 2:1. There were no differences in nursing experience by shift. Each respiratory therapist was responsible for fewer than 10 patients at the same time on every shift. The ICU team made rounds at least once daily, and respiratory therapists were responsible for all the weaning processes and spontaneous breathing trials of all MV patients. An UE was defined as the dislodgement or removal of the ETT from the trachea in a patient undergoing invasive MV at a time that was not specifically planned for or ordered by the physicians in charge of the patient. During the study period, a total of 341 patients experiencing UE were enrolled in this study, and their demographic and clinical information, laboratory results, comorbidities, severity scores, mortality, and length of stays for both ICU and hospital were collected for analysis. Our elderly patients (≥65 years) were about 58.7% (201/341) of all UE patients. The data were retrospectively collected and then analyzed. Therefore, informed consent was specifically waived and the study was approved by the Institutional Review Board of Chi Mei Medical Center (IRB: 10705–011). All methods were performed in accordance with the relevant guidelines and regulations.All features are extracted from the original dataset. The categorical data is cleaned and one-hot encoded in RStudio. The age data, which is continuous, is unity-based normalized and standardized. After data processing, there are 16 input features. The features include subject sex, age, APACHE II scores, Glasgow Coma Scale (GCS), TISS scale, comorbidities, ICU length of stay in days, and hospital length of stay in days. These features are chosen due to their wide availability in ICUs.The entire data set is comprised of 341 data points. The data is split into training and test sets at an approximate 9:1 ratio. 307 subjects are placed into the train set while 34 subjects are placed in the test set. In the overall dataset, the data distribution is unbalanced: ratio between patient death and survival is 1:4.683. To ensure that the output of the prediction model does not overfit the data, the data is weighted according to their outcome ratios when training the models.k-fold cross-validation accuracy (k = 10). We decided to use k-fold cross-validation instead of holdout cross-validation due to the limited number of subjects. The hyperparameter selection process was independently performed for each model type.The configuration of each model was reached through a hyperparameter selection process using the tanh)) and the output layer (Softmax and sigmoid). If the model was under-fitting, we increased the number of hidden layers and neurons. If the model was over-fitting, we added regularization or decreased the number of hidden layers and neurons. Once the model achieved high precision and recall, we applied various optimizers (Root Mean Square Propagation (RMSProp), Adam, Adadelta, Adam with Nesterov Momentum, and PowerSign) to the same architecture and determined if the model would perform better. We would decrease the learning rate if the model did not converge, but this was not found necessary.We began the model construction process by testing a three-layer perceptron network with a hidden layer that has half the number of neurons compared to the input layer. Using this configuration, we tested various activation functions in the hidden layer (Rectified Linear Unit (ReLU), Scaled Exponential Linear Unit (SeLU), and inverse tangent 29.The final ANN model consists of one input layer of 16 dimensions, a hidden layer of 24 dimensions, and an output layer of 2 dimensions. The network is trained using stochastic gradient descent and optimized using Adam with default parameters outlined by Kingma First, we used the default configuration to determine the best optimizer. We tested different solvers, which include the Newton-conjugate gradient method (Newton-CG), Limited-memory Broyden–Fletcher–Goldfarb–Shanno (L-BFGS) algorithm, stochastic average gradient descent, and the liblinear solver, and compared their performances. Then, we trained models with different regularization strengths on a linear scale.2 regularization with primal formulation. Primal formulation was used because there are more samples than features. Stochastic average gradient descent was used as the optimizer. The one-vs-rest scheme was used as the loss function. The regularization strength was set to 1.0, and the model was trained for 100 iterations before convergence. The LR software was implemented using the scikit-learn library (version 0.19.1)30 and the LIBLINEAR library (version 3.21)31.The final LR model used LFirst, we trained the data on a single decision tree model to determine the optimal depth. We started with a depth of one and increased the depth until the model began to overfit, or when the precision and recall of the train and test sets began to diverge. Then, we trained random forest models with various number of trees. We started with one tree and increased the number of trees until the out-of-bag error did not decrease further.30.The final RF model used ten separate decision tree estimators. Each decision tree used Gini impurity to measure the quality of split. The minimum number of samples required to split a node was set to two, and the minimum samples per leaf is set to one. All trees had a maximum depth of four; this was done to prevent the model from overfitting the training set. Probability estimates were used to plot the ROC curve. The RF model was implemented with the scikit-learn framework (version 0.19.2)The SVM model is a C-support vector classification (C-SVC) model. We began by testing out various kernel types  using the default kernel coefficient (gamma) and C value. We tested the polynomial kernel with degree three. Then, we trained different models with varying gamma and C values on a logarithmic scale.32.The final SVM model used a radial basis function (RBF) as its kernel with the shrinking heuristic enabled. The model used a C value of one and a gamma value of the reciprocal of the number of features. Additionally, probability estimates were calculated in order to plot a ROC curve for the model. The SVM model was implemented using the LIBSVM library (version 3.21)t test and a Chi-square test. A p value < 0.05 was considered statistically significant. Statistical analysis of the data was done with SPSS 13.0 for Windows .Mean values, standard deviations, and group sizes were used to summarize the results for continuous variables. The differences between the survival and non-survival group at hospital discharge were examined by univariate analysis with a Student 33. Instead, we used the weighted averaged F1, precision and recall values to measure model performance. These three metrics are calculated for the train set, the test set, and all data.Since the data distribution is unbalanced, accuracy is not a reliable measurement of prediction model performance34. The area under ROC curve of the prediction models were also compared to the those of the control predictors of the original data set, which include the APACHE II score, GCS, and TISS scale.The Receiving Operating Characteristic (ROC) curve is also used as a metric to measure prediction model performance. The area under ROC curve (AUROC) of each prediction model was pairwise-compared using the DeLong testp < 0.001). The non-survivor group had higher risks of underlying cancer, liver cirrhosis and uremia than the survivor group. The mean length of stay in ICU and hospital were 13.7 days and 36.12 days respectively for the survivor group, and 21.66 and 44.55 days respectively for the non-survivor group.Table 1, precision, and recall values of all models are shown in Table 1 value among all models, followed by the SVM, ANN, and LR models. The RF model also has the greatest recall and precision values among all models in the test set.The Fp values between the RF model and all other models (p ≈ 0.08) were lower than the other comparisons.The area under ROC curves of the control predictors are outlined in Table p < 0.0001)  Table . The ANN1) Table .Table 5P1 value across all data, the RF model achieves the best performance among all models. The RF model is also the only model that performed significantly better than APACHE II, GCS, and TISS according to the area under ROC curve. The RF model has F1 0.860, precision 0.882, and recall 0.850 in the test set, and an area under ROC curve of 0.910 . Therefore, in this study, we demonstrated that a random forest model is a good predictor of UE patient mortality.In terms of the FWe showed that when a model with a combination of multiple existing physiological scores, including APACHE II, GCS, TISS scores and eight comorbidities, are analyzed using a random forest model, the outcome of death or survival can be predicted reasonably. The usage of random forests in this study opens the feasibility for an aggregate index for a reliable patient prognosis modelling using existing scoring systems. Furthermore, the model used in this study includes features that are not included in standard APACHE II scoring such as chronic liver disease, which in Table 37. In a medical-neurological Indian ICU, Nimgaonkar et al.35 showed that an ANN using 15 variables was superior to APACHE II in predicting hospital mortality (p < 0.001). Another study using the University of Kentucky Hospital’s data showed that the performance of ANN was as good as APACHE II in predicting ICU mortality36. Though this study had similar findings in that this ANN model had a slight edge over APACHE II, TISS, and GCS, for predicting ICU mortality, this study further compared among different machine learning models including ANN, LR, RF, and SVM models and found that the RF model results in the highest AUROC, hence the best predictive power. It indicates that RF model may be a better machine learning method for prediction of the outcome of UE patients. In summary, while all of the tentative models can help in predicting the outcome of ICU patients, even for a specific group – UE patients; the RF model may even outperform conventional predicting tools, such as APACHE scores.Several studies had tried to compare the predictive power in ICU mortality between different machine learning models4, and remind intensivists that they should be aware of the high mortality of UE patients, especially for the patients with multiple co-morbidities. In contrast to mortality cases, more than 80% of patients had successful extubation and survival-to-discharge. This finding might hint that the extubation was delayed in these cases with successful UE. The possible cause of delayed extubation may be due to that the final decision regarding extubation should be made by intensivists even though hospitals have standard weaning and extubation protocols.In this study, the overall mortality rate of UE patients was 17.6%, and the mortality cases had more underlying cancer, liver cirrhosis, and uremia. All these findings are consistent with the previous studyThe results revealed that the random forest model was the best model for predicting the mortality of UE patients in the ICUs. Such a model will be helpful for predicting ICU patients’ mortality.et al. recommends that a supervised deep learning algorithm will generally achieve acceptable performance with more than 5000 data points38. However, this study shows that we can still develop a good prediction model using a limited data set. Future studies can be performed to determine whether similar datasets with a larger number of samples will produce comparable results. In addition, clinical lab data, such as liver and renal function, are omitted because these features fluctuate frequently during the patient’s stay. We chose features that were consistent for each patient and were known to predict patient mortality, which could yield good results according to this study.Limitations of our study include the lack of more patient data and features. Goodfellow


Using the National Health Insurance Research Database of Taiwan, we investigated whether undergoing a hysterectomy increases the risk of depression. A total of 7872 patients aged 30–49 years who underwent a hysterectomy from 2000 to 2013 were enrolled as the hysterectomy group. The comparison group was randomly selected from women who had never undergone a hysterectomy and was four times the size of the hysterectomy group. We calculated adjusted hazard ratios and 95% confidence intervals (CIs) for depression  in these cohorts after adjusting for age, comorbidities, oophorectomy, and hormone therapy. The overall incidence of depression was 1.02 and 0.66 per 100 person-years in the hysterectomy and comparison cohorts, respectively, yielding an adjusted hazard ratio of 1.35 (95% CI = 1.22–1.50) for depression risk. When we stratified patients by age, comorbidities, oophorectomy, and hormone use, hysterectomy increased the risk of depression. Hysterectomy, oophorectomy, and post-surgery hormone use were associated with an increased risk of depression when they occurred alone, but conferred a greater risk if they were considered jointly. Hysterectomy would be a predisposing factor for increased risk of subsequent depression. Our findings provide vital information for patients, clinicians, and the government for improving the treatment strategy in the future. Hysterectomy is a common gynecological surgery performed to remove the uterus in women with uterine myoma, endometriosis, uterine prolapse, genital cancers, and other benign conditions ,2. The pIt has been commonly assumed that undergoing a hysterectomy could cause adverse effects on psychological well-being that might be associated with an increased risk of depression. Some studies have suggested that hysterectomy may lead to decreased psychological well-being, whereas others have not found evidence of an association between this type of surgery and depression ,7. ReporWomen with depression were reported to fare worse 24 months after undergoing a hysterectomy than women who either had depression alone, or neither underwent a hysterectomy nor had depression . A prospTaiwan is located in Eastern Asia and the government launched the National Health Insurance (NHI) program covering more than 99% of Taiwan’s population in 1995 ,17. TherThe National Health Research Institute released the National Health Insurance Research Database (NHIRD) for research purposes. The Longitudinal Health Insurance Database 2000 (LHID2000) is a database based on data in the NHIRD. The LHID2000 randomly selected 1 million patients from the NHIRD, and included the patients’ personal information and insurance claims. To protect patient privacy, identification numbers were recoded. This study was approved by the Institutional Review Board (IRB) of China Medical University and Hospital (CMUH) Research Ethics Committee (REC) (IRB permit number: CMUH-104-REC2-115).We enrolled women aged 30–49 years who underwent a hysterectomy with or without an oophorectomy from 2000 to 2013 as the hysterectomy group for this study. The date of surgery was the index date. We excluded patients who had been diagnosed with depression  or withdrew from the insurance program before the index date. The comparison group for this study was randomly selected from women who had not undergone a hysterectomy and was four-fold in size matched with the hysterectomy group by sex, age, and index year. The selection process is illustrated in The outcome of this study was depression, and the endpoint was the date when a patient received a diagnosis of depression, withdrew from insurance, or the end of 2013. Person-years were the sum of the follow-up time for each individual, and the follow-up time was the period from the index date to the endpoint. The comorbidities controlled for in this study were anxiety (ICD-9-CM code 300), cancer (ICD-9-CM codes 140–208), stroke (ICD-9-CM codes 430–438), and coronary artery disease . We considered whether the patients who underwent hysterectomies also underwent an oophorectomy and used hormone replacement after the hysterectomy. t-test for continuous variables. The incidence rate of depression was calculated by person-years. The hazard ratio (HR) and 95% confidence interval (CI) of the two groups were estimated using univariate and multivariate Cox proportional hazards regression models. The variables analyzed in the multivariate model were age, oophorectomy, hormone use, and comorbidities of anxiety, cancer, stroke, and CAD. We used the Kaplan–Meier’s method to describe the depression-free probability of the two groups and tested the difference between the two groups using the log-rank test. The data analysis for this study was performed using SAS statistical software . The level of statistical significance was set as p < 0.05. To analyze the demographics of the hysterectomy group and the comparison group, we used the Chi-squared test for category variables and the The study cohort consisted of 7872 patients who had undergone a hysterectomy, and the comparison cohort consisted of 31,488 patients who had not. As evident in Then, we divided our patients into four subgroups based on whether they underwent hysterectomy or oophorectomy . CompareWe also analyzed the joint effects of hysterectomy and hormone replacement on the risk of depression in patients. Compared to non-hysterectomy and non-hormone used women, the risk of depression for hysterectomy women with hormone use was 1.63 (95% CI = 1.40–1.91), for hysterectomy ones without hormone use was 1.42 (95% CI = 1.26–1.60), and for non-hysterectomy women with hormone use was 1.34 (95% CI = 1.19–1.52) .In For comorbidities, we further analyzed whether hysterectomy women have an increased risk of depression if they had comorbidities of anxiety, stroke, and CAD . CompareTaiwanese women who underwent a hysterectomy in the 30–49-year-old age group had a higher post-hysterectomy depression risk compared with the general population. This was true for the patients regardless of whether they had also undergone an oophorectomy or had one of the comorbidities of anxiety, cancer, stroke, or CAD. The results of this observational study revealed that hysterectomy, oophorectomy, and post-surgery hormone use are associated with an increased risk of depression when they occur alone, but confer a greater risk if they are experienced jointly. The same findings were observed for the comorbidities. Our findings and the results of another study  suggest Luteinizing hormone (LH) closely regulates ovarian function, and any abnormal control of LH pulsatile release has major implications for all levels of the hypothalamic-pituitary-ovarian (HPO) axis. In LH regulation, estrogen is not only a steroidal hormone released from the ovary for controlling the estrous or menstrual cycle in women, but also has a role in numerous other systems such as the neuroendocrine, skeletal, and immune systems in both sexes . DisruptEstradiol therapy slows the clearance of serotonin by activating estrogen receptors that decrease serotonin clearance. Ovariectomized rats receiving estradiol therapy exhibited antidepressant effects similar to those from serotonin supplementation . Among aThis study included a nationwide population-based sample with little risk of recall and selection bias; thus, as with similar studies using NHIRD data ,25,26, oHysterectomy with oophorectomy and hormone use jointly affect the increase in depression risk. However, hysterectomy alone increases the risk of subsequent depression in patients, regardless of whether or not they also underwent oophorectomy, with or without hormone replacement, and with or without various comorbidities. Our findings provide vital information for patients, clinicians, and the government for improving depression treatment strategies in the future.