Egyptian Pediatric Guidelines for the Management of Children with Isolated Thrombocytopenia Using the Adapted ADAPTE Methodology-A Limited-Resource Country Perspective.

BACKGROUND: Thrombocytopenia is a prevalent presentation in childhood with a broad spectrum of etiologies, associated findings, and clinical outcomes. Establishing the cause of thrombocytopenia and its proper management have obvious clinical repercussions but may be challenging. This article provides an adaptation of the high-quality Clinical Practice Guidelines (CPGs) of pediatric thrombocytopenia management to suit Egypt's health care context. METHODS: The Adapted ADAPTE methodology was used to identify the high-quality CPGs published between 2010 and 2020. An expert panel screened, assessed and reviewed the CPGs and formulated the adapted consensus recommendations based on the best available evidence. DISCUSSION: The final CPG document provides consensus recommendations and implementation tools on the management of isolated thrombocytopenia in children and adolescents in Egypt. There is a scarcity of evidence to support recommendations for various management protocols. In general, complete clinical assessment, full blood count, and expert analysis of the peripheral blood smear are indicated at initial diagnosis to confirm a bleeding disorder, exclude secondary causes of thrombocytopenia and choose the type of work up required. The International Society of Hemostasis and thrombosis-Bleeding assessment tool (ISTH-SCC BAT) could be used for initial screening of bleeding manifestations. The diagnosis of immune thrombocytopenic purpura (ITP) is based principally on the exclusion of other causes of isolated thrombocytopenia. Future research should report the outcome of this adapted guideline and include cost-analysis evaluations.

Transfusion of blood components in pediatric age groups: an evidence-based clinical practice guideline adapted for the use in Egypt using 'Adapted ADAPTE'.

Pediatric transfusion is a complex area of medicine covering a wide age range, from neonates to young adults. Compared to adult practice, there is a relative lack of high-quality research to inform evidence-based guidelines. We aimed to adapt the pre-existing high-quality practice guidelines for the transfusion of blood components in different pediatric age groups to be available for national use by general practitioners, pediatricians, and other health care professionals. The guideline panel included 17 key leaders from different Egyptian institutions. The panel used the Adapted ADAPTE methodology. The panel prioritized the health questions and recommendations according to their importance for clinicians and patients. The procedure included searching for existing guidelines, quality appraisal, and adaptation of the recommendations to the target context of use. The guideline covered all important aspects of the indications, dosing, and administration of packed red cells, platelets, and fresh frozen plasma. It also included transfusion in special situations, e.g., chronic hemolytic anemia and aplastic anemia, management of massive blood loss, malignancies, surgery, recommendations for safe transfusion practices, and recommendations for modifications of cellular blood components. The final version of the adapted clinical practice guideline (CPG) has been made after a thorough review by an external review panel and was guided by their official recommendations and modifications. A set of implementation tools included algorithms, tables, and flow charts to aid decision-making in practice. This adapted guideline serves as a tool for safe transfusion practices in different pediatric age groups.

Hemophilia Joint Health Score, Functional Independence Score in Hemophilia, and Pettersson Score in Pediatric Patients With Severe Hemophilia A.

Hemophilia is an X-linked recessive disorder. Children with hemophilia go through spontaneous and trauma-provoked bleeding. Recurring joint bleeds lead to ongoing incapacity. Achieving healthy joints is the primary target of hemophilia management. The current study objective was to assess hemophilic joints in individuals with hemophilic arthropathy clinically, radiographically, and functionally. This cross-sectional study included 50 children with severe hemophilia A who were selected from the pediatric hematology clinic. All children were assessed for Hemophilia Joint Health Score (HJHS). Joint assessed functionally by Functional Independence Score in Hemophilia (FISH) and radiologically by plain radiograph and scored by the Pettersson scoring system. Data were analyzed using Statistical Package for Social Sciences. The mean age of the studied cases of hemophilia was 8.5±3.1 years. The mean FISH score among the studied patients was 26.8±4.2, the mean HJHS was 16.8±12.8, and the Pettersson score was 4.9±2.7. The number of affected joints showed a significant negative correlation to the FISH score and a significant positive correlation to HJHS. The frequency of hemarthrosis/month showed a significant positive correlation to HJHS. The number of affected joints showed a significant negative correlation to the FISH score and a significant positive correlation to HJHS. Frequency of hemarthrosis/month showed a significant positive correlation to HJHS.

Ulcerating vulvar lesions revealing a rare female case of monkeypox in Switzerland.

The human monkeypox virus is a zoonotic orthopoxvirus initially discovered in Africa that causes a disease similar to smallpox with less severe symptoms. Since May 2022, the virus is being transmitted from human to human at an increasing rate outside of Africa. Although monkeypox infection was endemic in Africa, it had sporadic surges in recent years. This has led the World Health Organization to declare its highest alert level on July 25, 2022. In Switzerland only, 456 individuals have been diagnosed with monkeypox infection from May 19, 2022, to August 29, 2022. To date, >99% of patients with monkeypox infection are men, in particular those who have sex with other men. Clinical cases of women with monkeypox infection are still very rare but will more likely be seen. With this case, we have highlighted the fact that this zoonosis is also starting to spread among women. We have presented the case of a female patient living in Switzerland who presented to our gynecologic emergency department for painful vulvar lesions after an episode of upper respiratory tract infection. The monkeypox infection was confirmed with a real-time polymerase chain reaction analysis at the University Hospital of Geneva, a center of reference for monkeypox in Switzerland. Shortly after, the patient developed generalized and typical lesions on the whole body.

Stromal Derived Factor-1 Gene Polymorphism in Pediatric Immune Thrombocytopenia.

Immune thrombocytopenia (ITP) is a multifactorial disease in which both environmental and genetic factors have been implicated. The study aimed to investigate a possible association of single nucleotide polymorphisms (SNPs rs266085 and rs2839693) in the stromal derived factor-1 (SDF-1) gene and its association to ITP and effect on ITP severity and response to treatment. Genomic DNA was extracted from peripheral blood and polymorphism in SDF-1 gene rs266085 and rs2839693 was analyzed using PCR-restriction fragment length polymorphism technique in DNA extracted from 60 children with ITP together with 90 healthy controls. On analysis of SDF-1 rs266085 polymorphism, there was a high frequency of CC genotype in cases than controls and that difference was significant at codominant, overdominant, and dominant models (P<0.05). Furthermore, carriers of the CC genotype were more susceptible to severe ITP at onset, steroid dependency, and chronicity than carriers of other genotypes (P<0.05). Otherwise, no significant differences between ITP patients and controls as regard SDF-1 rs2839693 genotypes and alleles, and we did not find a relation between this polymorphism and ITP severity, steroid dependency, or duration. SDF-1 gene rs266085 SNP C allele is associated with susceptibility to develop ITP as well as increases the risk for severe ITP at onset, chronic ITP and steroid dependency.

Diabetes Mellitus and Marital Status: Evidence from the National Longitudinal Mortality Study on the Effect of Marital Dissolution and the Death of a Spouse.

PURPOSE: This study evaluates the full impact of marital status on diabetes mellitus by stratifying the analysis by gender, including socioeconomic covariates and, unlike most studies, extending marital status by separating out previously conflated status categories. METHODS: Release 5 of the National Longitudinal Mortality Study (NLMS) was used for the data. Logistic regression was applied to the data from 1990 to 2011. The effective sample size consists of 1,384,507 individuals age 18 and above recruited into the study (via the Current Population Surveys), 3,955 of whom had died of diabetes mellitus by 2011. RESULTS: For minority men and non-Hispanic white men, divorced/separated status was significantly related to diabetes mortality, respectively (OR=1.318, CI=1.010, 1.719; and OR=1.283, CI=1.054, 1.562). For minority women and non-Hispanic white women, widowed status was related to diabetes mortality, respectively (OR=1.349, CI=1.107, 1.643; and OR=1.262, CI=1.113, 1.431). CONCLUSION: Contrary to recent epidemiological studies in which divorced/separated and widowed status were combined into one covariate, this United States study finds that divorced/separated men and widowed women are at increased risk for diabetes mellitus mortality, and that among these populations at risk, minorities are at higher risk than whites. The study highlights the importance of marital status and gender differences in the risk of death from diabetes.

Genetic association of interleukin 18 (-607C/A, rs1946518) single nucleotide polymorphism with asthmatic children, disease severity and total IgE serum level.

INTRODUCTION: Bronchial asthma is a chronic inflammatory disease. Interleukin 18 (IL-18) single nucleotide polymorphisms (SNPs) can influence IL-18 production and activity. IL-18-607C/A and -137 C/G are two of the commonly studied SNPs of IL-18 due to their role in the etiopathogenesis of allergic diseases. AIM OF THE STUDY: The case control study was conducted to investigate the genetic association between IL-18-607C/A polymorphism and pediatric asthma. Also attempts were made to evaluate the prognostic effect of -607C/A SNP with disease severity and total serum IgE. MATERIAL AND METHODS: The case control study was conducted on 60 asthmatic children and 40 healthy subjects; aged 2 to 12 years. PCR-RFLP was used to detect IL-18-607C/A SNP and total serum IgE level was detected using ELISA technique. RESULTS: Regarding IL-18-607C/A SNP, the frequency of the A allele and CA genotype was significantly higher in asthmatic children compared to healthy control subjects (p < 0.001). Further on, asthmatic children carrying the AA/AC genotype of -607C/A SNP were associated with an increased risk of occurrence of asthma (OR = 6.417; CI = 2.432-17.289). IgE was higher in asthmatic patients carrying the heterozygous CA genotype compared to patients carrying the AA and CC genotypes (p = 0.054). CONCLUSION: The frequency of the heterozygous CA genotype and A allele in IL-18-607C/A SNP was higher in asthmatic children. There is no association between the severity of asthma and -607C/A SNP. Total IgE was higher in patients carrying the CA genotypes compared to patients carrying the AA and CC genotypes, respectively.

New Findings On Gender: The Effects Of Employment Status On Suicide.

BACKGROUND AND OBJECTIVES: The purpose of the study was to evaluate the impact of gender and employment on suicide with the use of expanded unemployment statuses as covariates. METHODS: Data were obtained from release 5 of the National Longitudinal Mortality Study, a prospective study of deaths in the United States. Proportional hazards regression models were fitted to the data based on follow-up from 1990 to 2011. RESULTS: Unemployment was significantly associated with suicide (ARR=1.628, 95% CI=1.356, 1.954), and men had suicide deaths that were five times greater than women (ARR=5.104, 95% CI=4.565, 5.707), however when the sample was stratified by sex, the impact of unemployment on suicide was much higher among women (ARR=2.988, 95% CI=2.045, 4.366) than among men (ARR=1.393, 95% CI=1.131, 1.717). CONCLUSION: Contrary to many findings and gender assumptions, unemployed women in the U.S. have higher deaths from suicide than unemployed men. Discussion focused on explanations for gender disparities in unemployment.

A randomized controlled trial evaluating the effects of amlodipine on myocardial iron deposition in pediatric patients with thalassemia major.

BACKGROUND: Mortality rates increase due to iron deposition in the cardiac muscles of thalassemia major (TM) patients. Iron overload cardiomyopathy could be treated with a combination therapy of an iron chelator and an L-type calcium channel blocker. We designed a randomized controlled study to assess the potential of amlodipine, alongside chelation, in reducing myocardial iron concentration in TM patients compared with a placebo. OBJECTIVES: This study aims to estimate the change in myocardial iron concentration (MIC) determined by magnetic resonance imaging after 6 months of treatment with amlodipine, as well as measuring the changes in the secondary outcomes (liver iron concentration (LIC), serum ferritin level (SF), and left ventricle ejection fraction (LVEF)) of study participants. METHODS: A single, randomized, placebo-controlled trial was performed in 40 ß-Thalassemia major patients aged between 6 and 20 years old, who received either oral amlodipine 2.5-5 mg/day or a placebo, in addition to a Deferasirox chelation regimen in a 1:1 allocation ratio. RESULTS: After 6 months, a significant reduction was noted in the MIC of patients receiving amlodipine (n=20), compared with the patients receiving the placebo (n=20). At baseline, the mean was 0.76±0.11 mg/g dry weight, while at 6 months, the mean was 0.51±0.07 mg/g dry weight (p<0.001). Also, there was a significant change in the myocardial T2* after 6 months; the amlodipine increased the myocardial T2* from 40.63±5.45 ms at baseline to 43.25±5.35 ms (p<0.001). However, amlodipine did not significantly affect the secondary outcomes by the end of the study. CONCLUSION: The addition of amlodipine to the standard chelation therapy in transfusion-dependent thalassemia major patients improves myocardial iron overload without increasing the adverse effects.

Effective method of evaluating myocardial iron concentration in pediatric patients with thalassemia major.

BACKGROUND: The use of T2* magnetic resonance imaging (MRI) has been promoted by recent studies as a noninvasive method for the detection of iron overload in thalassemia major patients. This study aims to estimate the iron load in the heart and liver of thalassemia major patients using T2* MRI and to determine its correlation with the left ventricle ejection fraction and serum ferritin level. METHODS: Forty ß-Thalassemia major patients were included in the study. We evaluated the serum ferritin level, echocardiography, cardiac T2*, myocardial iron concentration (MIC), liver iron concentration (LIC) and hepatic T2* in all patients. CMR T2* findings were categorized as normal cardiac T2* (T2* >20 ms) or abnormal cardiac T2* (T2* <20 ms). RESULTS: The study found that 85% of patients had a normal cardiac T2* value. The median serum ferritin level was 2189. A significant inverse correlation was found between the serum ferritin level and the cardiac T2* (r=-0.381, =0.015); however, the correlations between serum ferritin and the hepatic T2* and liver iron concentration were statistically non-significant (P=0.539 and P=0.637, respectively). Additionally, the LVEF correlation was statistically non-significant with SF, hepatic T2* and cardiac T2*. CONCLUSION: Regardless of the serum ferritin level or left ventricle function, a cardiac T2* MRI should be done for all patients with ß-Thalassemia major in order to estimate the myocardial iron concentration.

Religiosity,Conservatism, and Acceptability of Anti-Female Spousal Violence in Egypt.

Physical violence directed at women is a significant social and public health problem globally. Initial studies tended to concentrate on developed countries, often relying on clinical or shelter samples to assess incidence and prevalence. Although prevalence is critical, reducing or eliminating some problems also requires comprehension of cultural norms and expectations. In the present study, we use a population-based survey to understand factors contributing to attitudes in support of physical violence against married women. More specifically, the aim of the study was to investigate the impact of religiosity and social conservatism on acceptability of physical spousal violence in the Arab Republic of Egypt. Data utilized were derived from Wave 6 of the World Values Survey conducted in 2013. Bivariate and multivariate regression models were fitted to the data. It was found that religiosity was significantly associated with physical spousal violence ( b = -123, t = -4.480). Individuals who attended more often were less apt to accept physical spousal violence. Social conservatism was strongly tied to approval of physical violence ( b = .368, t = -4.115). It was concluded that culturally biased and patriarchal attitudes that devalue women in Egypt, instead of religion, may be the underlying reason for spousal abuse. It was also concluded that improving higher education for both men and women would reduce physical spousal violence.

Urinary CD80 as a Replacement for Renal Biopsy for Diagnosis of Pediatric Minimal Change Disease.

INTRODUCTION: Early diagnosis of minimal change disease (MCD) is challenging in nephrotic children. CD80 is a protein expressed on the surface of podocytes associated with nephrotic syndrome and it is implicated in the induction of proteinuria. This study aimed to investigate the use of urinary CD80 for the diagnosis of MCD. MATERIALS AND METHODS: Urinary CD80 levels were evaluated in 36 children with nephrotic syndrome and normal glomerular filtration rate. They were divided into three groups of MCD (n = 21), focal segmental glomerulosclerosis (n = 9), and other glomerulopathies (n = 6). The MCD group was subdivided into 2 of those with remission (n = 11) and those in the active stage (n = 10). Forty healthy children were included as controls. RESULTS: The urinary CD80 level was significantly higher in the MCD group (3.5 ± 2.1 ng/mg creatinine) than in the focal segmental glomerulosclerosis group (1.2 ± 0.5 ng/mg creatinine, P < .001), the other glomerulopathies group (1.4 ± 0.7 ng/mg creatinine, P < .001), and the control group (0.7 ± 0.2 ng/mg creatinine, P < .001), while it showed no significant difference among the non-MCD groups. There was no significant difference between MCD in remission and MCD in relapse, either. A urinary CD80 cutoff value of 1.5 ng/gm creatinine showed a sensitivity of 100% and a specificity of 86% for diagnosis of MCD. CONCLUSIONS: Urinary CD80 levels were significantly higher in the children with MCD than in the controls and patients with other causes of nephrotic syndrome.

Association of -308G/A Polymorphism and Serum Level of TNF- α with Bronchial asthma in Children.

Genetic polymorphism of Tumor necrosis factor alpha (TNF-α)-308 G/A is one of the potential markers involved in bronchial asthma pathogenesis. This highly polymorphic gene can influence TNF-α serum levels which has major biological effects on airway inflammation, remodeling, and hyper responsiveness. This study was designed to evaluate the association between TNF-α-308 G/A polymorphism, serum levels of TNF-α and the susceptibility to bronchial asthma in children. The study included 102 pediatric patients with bronchial asthma recruited from Pediatric Allergy and Pulmonology Clinic, Specialized Pediatric Beni Suef University Hospital. Bronchial asthma was classified according to Global Initiative for Asthma (GINA) Guidelines. Moreover, 104 healthy age and sex matched children were enrolled as normal control. Serum TNF-α was measured by ELISA. Analysis of TNF-alpha G308A Polymorphisms was done by allele- specific Polymerase Chain Reaction (PCR). TNF-α level was significantly higher in bronchial asthma patients when compared with the control group, p value 0.001. Individuals with mutant genotype (GA and AA) expressed higher levels of serum TNF-α in comparison to the wild type GG carriers, P value 0.01. The GA genotype frequency of TNF-α-308 G > A polymorphism was significantly higher in patients (34.3%) than (vs.) controls (21.2%) P value 0.028, OR = 2.04; 95% CI = 1.11-3.84. The frequency of combined (AA + GA) genotypes showed a significant difference among cases in comparison with the controls (41.2% vs. 26%), p value 0.027. The pooled OR was 1.99(95% CI=1.1-3.6). In the same context, the A allele was significantly more frequent in asthmatic patients (24%) vs. control (15.4%), P value 0.035 (OR = 1.74, 95% CI = 1.05-2.8) which demonstrated an evidence of possible association between TNF-α-308 G/A polymorphism and bronchial asthma. We concluded that TNF-alpha genetic polymorphisms could have a role in the development of bronchial asthma among Egyptian children.

Role of Cannabinoid CB2 Receptor Gene (CNR2) Polymorphism in Children with Immune Thrombocytopenic Purpura in Beni-Suef Governorate in Egypt.

The cannabinoid system is involved in the immune regulation by modulation of Th cells type 1 and 2. It is composed of the CB2 receptor which is expressed at 10 to 100 folds greater levels on immune cells than the CB1 receptors. The CB2 is encoded by the cannabinoid CB receptor gene (CNR2) gene. This study aims to investigate the polymorphism in CNR2 gene variation rs 35761398 (Q63R) in Egyptian children with immune thrombocytopenic purpura and to investigate the relation between this gene polymorphism and either the susceptibility to or the chronicity of the disease. Forty children diagnosed as ITP were included in this study and 20 healthy children as normal control. CNR2 gene was investigated in those children by PCR RFLP technique (restriction fragment length polymorphism). CNR2 genotyping revealed that 45% of ITP patients had the QR heterotype, 50% had the RR homotype and 5% had QQ, the wild type with significantly higher frequency of homomutant genotype in comparison to controls. The relative odds ratio suggested a double risk for developing ITP in RR homotype (OR 2.152). A significant overpresentation of the RR genotype and of R allele was observed in the chronic patients (P=0.002 and 0.003, respectively). The associated risk to develop chronic ITP increased more than two folds for the RR homotype (OR=2.854). In conclusion, this study confirms the role of CNR2 Q63R polymorphism in the susceptibility to ITP in children and chronicity of the disease.

Differential Expression of T-bet and GATA3 in Egyptian Children with Idiopathic Thrombocytopenic Purpura.

GATA3 and T-box (T-bet) expressed in T-cells are transcriptional factors that play a critical role in development of Th2 and Th1 immunity respectively. GATA3 is expressed during Th2 differentiation and T-bet is expressed exclusively in Th1 cells. Thus, a balance between GATA3 and T-bet is believed to control Th2/Th1 polarization. Therefore, the high expression of T-bet and low expression of GATA3 indicate the existence of Th1 polarization in children with acute immune thrombocytopenic purpura (ITP). This might be related to the regulation of T-bet and GATA3. The objective of this work was to study the expression of transcriptional factors T-bet and GATA3 m RNA in children with idiopathic thrombocytopenic purpura and correlate it with clinical findings, laboratory findings, and outcome of patients. In this study the expression of T-bet and GATA3 genes was analysed in 20 normal healthy individuals and 40 children with ITP (20 acute and 20 persistent) using reverse transcriptase polymerase chain reaction to investigate a possible relation, association or correlation with the type of ITP and prognosis. T-bet was expressed significantly in 60 % of acute ITP children (12/20) (P value 0.001) and not expressed in persistent ITP children (0/20), while GATA3 was expressed in 25 % of persistent ITP patients (5/20) (P value 0.017) and not expressed in acute ITP patients (0/20). Both genes were not detected in healthy controls. We concluded that the high expression of T-bet and the low expression of GATA3 indicate the existence of Th1 polarization in children with acute ITP. This might be related to the regulation of T-bet and GATA3. Intensive studies of abnormal cytokine profiles in ITP have led to cytokine therapies that exploit the effects of IFN-γ on Th2 cells, but such therapies are often ineffective to develop safe and effective therapeutic tools. Targeting specific molecules such as T-bet and GATA3 may be a novel therapeutic tool in ITP.

Correlation of Notch1/Hes1 Genes Expression Levels in Egyptian Paediatric Patients with Newly Diagnosed and Persistent Primary Immune(Idiopathic) Thrombocytopenic Purpura.

Notch signalling is involved in the development of several autoimmune diseases, one of such diseases is ITP. The aim of this study was to investigate and compare the expression levels of Notch1 receptor and its target Hes1 gene in Egyptian paediatric ITP patients. Real-time quantitative reverse transcriptase polymerase chain reaction was used to analyse the expression levels of Notch1 and Hes1 in 42 children with primary ITP (22 newly diagnosed and 20 persistent) cases. Twenty age and sex matched non-ITP controls were included. The expression levels of Notch1 were higher in newly diagnosed and persistent cases than controls with high statistical significant difference (P value < 0.001, P < 0.001) respectively, similarly as regards the expression levels of HES1 (P value < 0.001, P < 0.007) respectively. A significant positive correlation was found between Notch1 and Hes1 expression levels in newly diagnosed cases (r = 0.587, P value = 0.004). There was an association between levels of both genes in most of ITP patients but Hes1 was markedly elevated than Notch1 in few cases. High expression levels of Notch1/Hes1 indicated the important role of Notch signalling in both newly diagnosed and persistent ITP. High expression levels of Hes1 than Notch1 may shed light on its value as a therapeutic target for future research in ITP.

Prevalence and determining factors of anemia and malnutrition among Egyptian children.

BACKGROUND: The first Millennium Development Goal to "eradicate extreme poverty and hunger" implied reducing by 50% the prevalence of underweight status among children younger than five years between 1990 and 2015. AIM OF WORK: This study investigates the prevalence and determining factors of anemia and malnutrition among children of Albasra village, one of the Egyptian villages, to produce directives for a management program. MATERIALS AND METHODS: All inhabitants aged between six months and 15 years (397 children) were subjected to a structured interview, clinical assessment, anthropometric assessment, and laboratory examination. A complete blood picture analysis and a hemoglobin percentage assessment were done. RESULTS: The main prevailing symptom in the two weeks preceding the survey was diarrhea (55%). Complete weaning before the age of 18 months occurred in 20.5% of the below-six children. The children more likely to be anemic were those under the age of two years, children having the first or more than the fourth order among their siblings, and those who suffered a diarrheal attack, vomiting, grunting, or chest in drawing within two weeks preceding the survey, among children completely weaned after the age of 24 months and those from a low socioeconomic level. Stunting was highest among younger children from extended families. Children who suffered a chronic disease were more likely to be wasted (13.2%). CONCLUSION: An understanding of the risk factors for anemia and malnutrition among a population is fundamental to provide efficient preventive and control measures.