Can Oral Zinc Supplementation Reduce Relapses in Childhood Steroid-Sensitive Nephrotic Syndrome? A Systematic Review.

Introduction: Frequent relapses and steroid dependence are common treatment challenges of steroid-sensitive nephrotic syndrome (SSNS) in children. Acute respiratory infection (ARI) is the most frequently reported trigger of relapse. Given the role of zinc supplementation in preventing ARI, some studies show that this targeted intervention may reduce relapses in childhood SSNS. Aim: This systematic review aimed to determine if oral zinc supplementation can significantly reduce relapses in this disease. Methods: We searched the PubMed and Google Scholar electronic databases for interventional and observational analytical studies without limiting their year or language of publication. We selected studies with primary data that met our inclusion criteria, screened their titles and abstracts, and removed duplicates. We used a preconceived structured form to extract data items from selected studies and conducted a quality assessment of randomized controlled trials (RCTs) and non-randomized studies with the Cochrane collaboration tool and the Newcastle Ottawa Scale, respectively. We qualitatively synthesized the extracted data to validate the review's objective. Results: Eight full-text articles were selected, comprising four RCTs and four observational analytical studies. Two of the RCTs had a high risk of bias in three parameters of the Cochrane collaboration tool, while three non-randomized studies had low methodological quality. A total of 621 pediatric patients with SSNS were investigated in the eight studies: six participants dropped out in one study. Three RCTs indicate that zinc supplementation may lead to sustained remission or reduction in relapse rate. Similarly, three observational analytical studies suggest a significant relationship between reduced serum zinc levels and disease severity. Conclusion: Despite the association of zinc deficiency with increased morbidity in SSNS and the reduction of relapse rates with zinc supplementation, there is no robust evidence to recommend its use as a therapeutic adjunct. We recommend more adequately-powered RCTs to strengthen the current evidence.

Vitamin D3 supplementation as an adjunct in the management of childhood infectious diarrhea: a systematic review.

BACKGROUND: Some studies have reported the possible role of vitamin D3 in ameliorating disease outcomes in childhood infectious diarrhea. However, findings about its effectiveness and the association of serum vitamin D levels with diarrhea risk appear inconsistent. We aimed to determine the efficacy of oral vitamin D3 as an adjunct in managing childhood infectious diarrhea and the relationship between vitamin D status and the disease. METHODS: We searched the PubMed and Google Scholar electronic databases for relevant articles without limiting their year of publication. We selected primary studies that met the review's inclusion criteria, screened their titles and abstracts, and removed duplicates. We extracted data items from selected studies using a structured data-extraction form. We conducted a quality assessment of randomized controlled trials (RCTs) and non-randomized studies with the Cochrane collaboration tool and the Newcastle Ottawa Scale, respectively. We assessed the strength of the relationship between serum vitamin D levels and diarrhea using the correlation model. We estimated the I2 and tau2 values to assess between-study heterogeneity. RESULTS: Nine full-text articles were selected, consisting of one RCT, three cross-sectional studies, two cohort studies, two longitudinal/prospective studies, and one case-control study. A total of 5,545 participants were evaluated in the nine studies. Six non-randomized studies provided weak evidence of the relationship between vitamin D levels and diarrhea risk as there was no correlation between the two variables. The only RCT failed to demonstrate any beneficial role of vitamin D3 in reducing the risk of recurrent diarrhea. The calculated I2 and tau2 values of 86.5% and 0.03, respectively suggested a high between-study heterogeneity which precluded a meta-analysis of study results. CONCLUSION: Oral vitamin D3 may not be an effective adjunct in managing childhood infectious diarrhea. Additionally, the relationship between vitamin D status and infectious diarrhea appears weak. We recommend more adequately-powered RCTs to determine the effectiveness of vitamin D3 as an adjunct therapy in infectious diarrhea.

Prevalence and determinants of psychosocial disorders in children and adolescents with asthma in Enugu, Nigeria: a comparative cross-sectional study.

OBJECTIVE: Like most chronic illnesses, childhood asthma has a significant impact on the child's overall psychosocial well-being. Psychosocial disorders occur in children with uncontrolled asthma making their asthma control more difficult. We aimed to determine the prevalence and determinants of psychosocial disorders in children and adolescents with asthma. METHODS: A comparative cross-sectional study of children and adolescents (aged 6 to 17 years with and without asthma) was conducted in a Nigerian tertiary health facility. The Revised Children Manifest Anxiety Scale (RCMAS) and Center for Epidemiological Studies-Depression Scale for Children (CES-DC) were used to screen for anxiety and depression respectively. RESULTS: A total of 190 (95 asthma and 95 non-asthma) children were studied. Anxiety occurred in 15 (15.8%) of asthma and four (4.2%) of non-asthma children, OR 95% CI =4.3 (1.4-13.4). Forty-five (47.4%) of asthma and 32 (33.7%) of non-asthma children had depression (OR 95% CI =1.8 (0.9-3.2). Asthma was significantly associated with social problems such as difficulty in making friends (OR 95% CI = 58.5 (3.5-979.9); restriction from daily activities (OR 95% CI =34.0 (2.0-578.5); stigma from peers (OR 95% CI = 18.6 (1.1-326.2); and strengthened and overprotective relationship with parents, (OR 95% CI = 26.0 (1.5-447.8). Poor asthma control was significantly associated with restriction from play, OR (95%CI) = 0.12 (0.04-0.32); anxiety, OR 95%CI = 18.26 (3.80-87.76) and depression, OR 95%CI = 4.57 (1.85-11.33). CONCLUSIONS: Children with asthma are more prone to psychosocial disorders than their non-asthma counterparts. Poor asthma control influenced the psychosocial well-being of children with asthma negatively.

Physical growth and sexual maturation of perinatally HIV-infected adolescent males in a southeast Nigerian tertiary hospital: a comparative cross-sectional study.

BACKGROUND: The advent of highly-active anti-retroviral therapy (HAART) has resulted in the survival of children with Human Immunodeficiency Virus (HIV)/Acquired Immune Deficiency Syndrome (AIDS) into adolescence. Their prolonged survival has translated into co-morbidities like endocrine deficiencies which may manifest as growth and pubertal delay. This study aimed to determine the physical growth and sexual maturation of perinatally HIV-infected adolescent males and compare them with those of age-matched HIV-negative controls. METHODS: We conducted a comparative cross-sectional study of 104 perinatally HIV-infected males on HAART aged 10 to 19 years, and 104 age-matched HIV-negative males who served as controls. The subjects and controls were enrolled and assessed at a Nigerian tertiary hospital over six months. Anthropometric measurements such as weight, height, and BMI were obtained and Z scores for age were derived for weight, height, and BMI to determine physical growth using WHO AnthroPlus software. Sexual maturation was assessed using the method proposed by Marshall and Tanner. Data analysis and appropriate statistics were conducted with the Statistical Package for Social Sciences (SPSS) version 25 Chicago IL. A p-value < 0.05 was adopted as the level of statistical significance. RESULTS: The mean height, weight, and BMI Z scores of the subjects were all lower than those of the controls. The difference between the mean weight of the subjects (44.60 ± 13.32 kg) and the controls (49.97 ± 13.58 kg) was statistically significant (t = 2.88, p = 0.004). Similarly, the difference between the mean BMI Z-scores of the subjects (-0.96 ± 1.95) and the controls (-0.10 ± 0.86) was statistically significant (t = 4.10, p = < 0.001). The subjects showed a delay in pubic hair and testicular development for Stages 1, 2, and 3. Duration of HAART did not significantly affect the BMI of subjects who were in three groups: undernutrition, normal nutrition, and overnutrition (Kruskal-Wallis test, p = 0.30). CONCLUSION: Perinatal HIV infection negatively affects physical growth and the onset of pubic-hair development (PH 2) despite the duration of HAART. We recommend that screening for weight deficit or pubertal delay should form part of the management protocol for HIV-infected male children on HAART.

Postnatal probiotic supplementation can prevent and optimize treatment of childhood asthma and atopic disorders: A systematic review of randomized controlled trials.

Background: Although several randomized controlled trials (RCTs) published over the past 5 years show that prenatal or postnatal probiotics may prevent or optimize the treatment of childhood asthma and atopic disorders, findings from the systematic reviews and meta-analyses of these studies appear inconsistent. More recent RCTs have focused on postnatal probiotics, and linked specific probiotic strains to better disease outcomes. Objective: This systematic review aimed to determine if postnatal probiotics are as effective as prenatal probiotics in preventing or treating childhood asthma and atopic disorders. Methods: We searched the PubMed, Medline, Google Scholar, and EMBASE databases for RCTs published within the past 5 years (from 2017 to 2022). We included only full-text RCTs on human subjects published in or translated into the English language. We retrieved relevant data items with a preconceived data-extraction form and assessed the methodological quality of the selected RCTs using the Cochrane Collaboration's tool for assessing the risk of bias in randomized trials. We qualitatively synthesized the retrieved data to determine any significant differences in study endpoints of the probiotic and placebo groups. Results: A total of 1,320 participants (688 and 632 in the probiotic and placebo groups) from six RCTs were investigated. One RCT showed that early Lactobacillus rhamnosus GG (LGG) led to a reduction in the cumulative incidence rate of asthma. Another study demonstrated that mixed strains of Lactobacillus paracasei and Lactobacillus fermentum could support clinical improvement in children with asthma while one trial reported a significant reduction in the frequency of asthma exacerbations using a mixture of Ligilactobacillus salivarius and Bifidobacterium breve. Three trials showed that a combination of LGG and Bifidobacterium animalis subsp lactis, Lactobacillus rhamnosus alone, and a probiotic mixture of Lactobacillus LOCK strains improved clinical outcomes in children with atopic dermatitis and cow-milk protein allergy. Conclusions: Postnatal strain-specific probiotics (in single or mixed forms) are beneficial in preventing and treating atopic dermatitis and other allergies. Similarly, specific strains are more effective in preventing asthma or improving asthma outcomes. We recommend more interventional studies to establish the most useful probiotic strain in these allergic diseases.

The effectiveness of locally-prepared peritoneal dialysate in the management of children with acute kidney injury in a south-east Nigerian tertiary hospital.

Background: Peritoneal dialysis (PD) is the preferred mode of renal replacement therapy (RRT) in children with acute kidney injury (AKI). The gold standard remains the use of commercially-prepared PD fluid. In resource-poor nations, its availability and affordability remain a challenge. Aim: This study aims to report the effectiveness of locally-prepared PD fluid in the management of AKI in a south-east Nigerian tertiary hospital. Subjects and Methods: This was a retrospective study conducted at the paediatric ward of the University of Nigeria Teaching hospital, Enugu. The case records of 36 children seen over three years, diagnosed with AKI and requiring PD were reviewed. The retrieved information comprised biodata, aetiology of AKI, indications for PD, pre-and post-dialysis estimated glomerular filtration rate (eGFR) and patient outcomes. Results: The children (20 males and 16 females) were aged 3 to 36 months with a mean age of 9.92 ± 6.29 months. The common aetiologies of AKI were septicemia (30.6%), hemolytic uremic syndrome (19.4%), and toxic nephropathy (16.7%). The frequent indications for PD were uremic encephalopathy (58.3%) and severe metabolic acidosis (38.8%). The pre-and post-dialysis mean urine flow rate was 0.16 + 0.13 and 2.77 + 0.56 ml/kg/hour respectively. The eGFR before PD, at discontinuation, and a week later was 6.06 + 2.87, 24.44 + 15.71 and 59.07 + 22.22 mls/min/1.73m2 respectively. Conclusion: PD with locally-prepared dialysate is safe, effective and a life-saving alternative in the management of AKI in children.

Small-airway disease and its reversibility in human immunodeficiency virus-infected children on highly active antiretroviral therapy: A cross-sectional study in an African setting.

BACKGROUND: Lung function abnormalities may occur in children with human immunodeficiency virus (HIV) infection. Small-airway disease (SAD) precedes abnormalities in forced expiratory volume in 1 s (FEV 1). OBJECTIVE: This study aims to assess the presence and reversibility of SAD in HIV-infected children using the Global Lung Function Initiative standards. METHODS: A cross-sectional study was conducted over 6 months at the Paediatric HIV Clinic of the University of Nigeria Teaching Hospital in Enugu, Southeast Nigeria. Eligible consenting children with HIV infection were recruited. Lung function was measured, and the reversibility of FEV1 and forced vital capacity (FVC) was assessed at 12% while that of forced expiratory flow between 25% and 75% (FEF25-75) was assessed at 12%, 15%, and 20%. Predictors of abnormal Z-score values were determined by multivariate linear and logistic regressions. Statistically significant values were set at P < 0.05. RESULTS: The mean Z-score for FEV1, FVC, and FEF25-75 was - 2.19, -1.86, and - 1.60, respectively. Most patients (73%) had abnormal FEV1, while 52% had abnormal FEF25-75. Significant changes in FEV1 (P = 0.001) and FEF25-75 (P < 0.001) occurred after the bronchodilator response (BDR) test. Of the children whose FEV1 showed positive BDR, 70.9% had low zFEV1; 50% had low zFEF25-75, while all had low FEV1. Nutritional status (Z-score for body mass index) was significantly associated with low FEV1. CONCLUSIONS: Abnormal FEF25-75 as a marker of SAD and FEV1 with a positive BDR are common in HIV-infected children. These lung function abnormalities justify long-term follow-up for these patients.

Reliability of generic quality-of-life instruments in assessing health-related quality of life among children and adolescents with idiopathic nephrotic syndrome: a systematic review.

INTRODUCTION: Most of the studies reporting the negative impact of idiopathic nephrotic syndrome on health-related quality of life in children and adolescents were conducted with generic quality-of-life instruments rather than disease-specific instruments. The consistency of these studies' findings using these generic instruments is not well established. AIM: This systematic review aims to determine the reliability of current generic quality-of-life instruments in assessing health-related quality of life among children and adolescents with idiopathic nephrotic syndrome. METHODS: We searched the PubMed, MEDLINE, EMBASE, and Google Scholar databases for articles published between 2000 and 2020, using appropriate descriptors. We included primary studies that met the eligibility criteria, independently screened their titles and abstracts, and removed all duplicates during the study-selection process. We resolved disagreements until a consensus was reached on study selection. We independently retrieved relevant data, including the generic quality-of-life instruments and the subjects' and controls' aggregate health-related quality of life scores, using a preconceived data-extraction form. RESULTS: Ten original articles were selected for qualitative and quantitative analyses. Some of the studies reported the following significant findings. The mean health-related quality of life scores for children with prevalent and incident nephrotic syndrome were 68.6 (range, 52.6-84.6) and 73.7 (range, 55.9-91.5), respectively. Children with idiopathic nephrotic syndrome and their controls with other chronic diseases had median scores of 65 (interquartile range, 59-68.75) and 62.2 (interquartile range, 58.05-65.78). Patients on oral immunosuppressive drug and intravenous rituximab reportedly had median scores of 76.2 and 72.6 and mean scores of 71.4 (range, 55.4-87.4) and 61.6 (range, 42.1-81.1) respectively for quality-of-life assessment on the 'school functioning domain.' CONCLUSIONS: The health-related quality of life scores in patients with idiopathic nephrotic syndrome are consistently low. Lower scores occur in prolonged disease duration and severe clinical phenotypes, whereas the scores are higher than the scores obtained in other chronic diseases. These consistent findings underscore the reliability of the current generic instruments in assessing health-related quality of life in patients with idiopathic nephrotic syndrome.

Vitamin D Analogs Can Retard the Onset or Progression of Diabetic Kidney Disease: A Systematic Review.

Introduction: Previous studies have shown that vitamin D analogs (such as paricalcitol) can reduce albuminuria in patients with diabetes mellitus and retard the progression of diabetic kidney disease (DKD). A recent systematic review reported significant improvement of renal function in patients with DKD who received vitamin D or its analogs. Study-driven data about their use in improving DKD outcomes have continued to accumulate over the years. Aim: This paper aims to systematically review the contemporary evidence about the effectiveness of vitamin D analogs in retarding the onset or progression of DKD. Methods: With appropriate descriptors, two electronic databases (PubMed and Google Scholar) were searched for articles published between 2015 and 2021 in the English language. Primary studies that fulfilled the inclusion criteria were selected; their titles and abstracts were screened, and duplicates were removed. Relevant data were retrieved from the final selected studies using a preconceived data-extraction form. Results: A total of eight studies (three randomized-controlled trials, one prospective study, and four cross-sectional studies) were reviewed. A total of 6,243 participants were investigated in the eight studies and comprised young adults, middle-aged adults, and the elderly with a male-gender predominance. One randomized controlled trial reported that paricalcitol significantly improved renal function in type 1 diabetes patients with renal impairment when combined with renin-angiotensin-aldosterone system (RAAS) blockers. A strong correlation between vitamin D deficiency and DKD risk was noted in the majority of the cross-sectional studies. High doses of cholecalciferol (4,000 or 10,000 IU/day), given early in DKD, significantly reduced disease prevalence. Conclusion: Paricalcitol may retard the onset or progression of DKD, especially if administered in combination with RAAS blockers. The association of vitamin D deficiency with DKD risk also supports this therapeutic effect. Future systematic reviews are still needed to strengthen the current evidence on therapeutic benefit of vitamin D or its analogs in DKD.

A short course of oral ranitidine as a novel treatment for toddler's diarrhea: a parallel-group randomized controlled trial.

BACKGROUND: The current paradigm for treating toddler's diarrhea comprises dietary modification and fluid restriction. Previous studies show that probiotics and proton-pump inhibitors (PPIs) or H2 blockers could control diarrhea associated with functional gastrointestinal disorders (FGIDs). This study aims to determine and compare the efficacy of a short course of oral ranitidine and a probiotic in the treatment of toddler's diarrhea. METHODS: This study was a parallel-group randomized controlled trial (RCT). We sequentially enrolled 40 patients who met the eligibility criteria. We randomly assigned 20 patients to the oral ranitidine group, ten patients to the probiotic group, and ten patients to the placebo group. In the oral ranitidine group, patients received oral ranitidine (3 mg/kg/day) once daily for 10 days; in the probiotic and placebo groups, they were administered 5 to 10 billion colony-forming units (CFUs) per day of lyophilized Lactobacillus rhamnosus and 50 mg of once-daily oral vitamin C tablet respectively for 10 days. Stool frequency and consistency on the 10th day of the interventions were recorded as the primary outcomes. We used the Student's t-test to determine if there were significant differences in the mean daily stool frequencies in the three intervention groups. A p-value < 0.05 was adopted as the level of statistical significance. RESULTS: In the ranitidine group, stool frequency decreased significantly from an average of five per day on the first day to an average of approximately one per day on the 10th day of intervention (t = 10.462, p <  0.001). Additionally, stool consistency normalized on the 10th day of intervention. In the probiotic group, there was a significant reduction in stool frequency from an average of five per day on the first day to four per day on the 10th day (t = 2.586, p = 0.041), although stool consistency remained loose. However, stool consistency and frequency were not significantly affected in the placebo group (t = 1.964, p = 0.072). CONCLUSION: Oral ranitidine is more effective than probiotics in reducing stool frequency and normalizing stool consistency in toddler's diarrhea. We recommend multi-center trials with appropriate study designs to confirm and validate this finding. TRIAL REGISTRATION: ISRCTN, ISRCTN10783996 . Registered 8 April 2016-Registered retrospectively.

The Supportive Treatment of IgA Nephropathy and Idiopathic Nephrotic Syndrome: How Useful are Omega-3 Polyunsaturated Fatty Acids?

IgA nephropathy (IgAN) is the most prevalent glomerular disease in young adults worldwide, while idiopathic nephrotic syndrome (INS) represents the most frequent manifestation of glomerular disease in childhood. Over the years, studies have speculated about the potential benefits of omega-3 polyunsaturated fatty acids (PUFAs) in improving morbidity in both forms of chronic kidney disease (CKD). The proposed mechanisms of action include reduction of proteinuria and modulation of dyslipidemia. Although in vitro and in vivo experimental studies report the suppressive effect of omega-3 PUFAs on inflammatory pathways linked with the progression of nephropathy, the evidence supporting their beneficial effect in IgAN and INS is still weak. Also, their ability to regulate levels of total cholesterol, low-density lipoprotein-cholesterol (LDL-C), and triglycerides (TG) suggests that they could delay both dyslipidemia-associated nephrotoxicity and atherosclerosis. Most of the clinical trials that were conducted on their therapeutic benefits in IgAN patients reported positive outcomes with low and high doses of omega-3 PUFAs. However, few of the trials noted inconclusive findings, with low-quality evidence suggesting potential improvements in surrogate renal function outcomes. If the beneficial effect of omega-3 PUFAs is predicated on their hypolipidemic action, much higher doses could be used in well-designed randomized-controlled trials (RCTs) to determine if they could produce better renal function outcomes and provide much stronger evidence of their therapeutic benefits in IgAN and INS. However, the current hypothetical mechanisms of action in these forms of CKD also include the effect of omega-3 PUFAs on renal inflammatory pathways and glomerular proteinuria. Perhaps, the unresolved therapeutic efficacy of these fatty acids in IgAN and INS suggests that their exact mechanisms of action are yet to be fully established. In this narrative review, we aim to appraise the current evidence of their potential therapeutic benefits in these diseases.

Prevalence rates of histopathologic subtypes associated with steroid resistance in childhood nephrotic syndrome in Sub-Saharan Africa: a systematic review.

INTRODUCTION: The prevalence rates of the common histopathologic subtypes of childhood nephrotic syndrome associated with steroid resistance appear to be changing globally. In Sub Saharan Africa (SSA), the trend is similar over the past few decades. AIM: This systematic review aims to determine the current prevalence rates of the histopathologic subtypes associated with childhood steroid-resistant nephrotic syndrome (SRNS) in SSA. METHODS: A search of the PubMed, Google and African Journals Online databases was conducted from January to December 2018 using PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) flow-chart to identify relevant articles which met the aim of the systematic review. A qualitative synthesis and descriptive analysis of the extracted data were then conducted. The mean values for the prevalence rates of the reported histopathologic subtypes were calculated. A meta-analysis was not done due to few numbers of studies reviewed. The review is registered with PROSPERO, number CRD42018111916. RESULTS: In the West African sub-region, the currently reported histopathologic subtypes associated with childhood nephrotic syndrome are focal segmental glomerulosclerosis (FSGS), minimal-change nephropathy (MCN), membrano-proliferative glomerulonephritis (MPGN), membranous nephropathy (MN) and mesangial proliferative glomerulonephritis (MesPGN). The picture is the same in South Africa. More importantly, the predominant histopathologic lesions associated with steroid resistance are FSGS (West Africa) and MCN/FSGS (South Africa), with mean prevalence rates of 57.2% and 36.1% respectively. CONCLUSION: The prevalence of FSGS is currently high in childhood nephrotic syndrome in SSA. This histopathologic subtype remains the commonest lesion associated with SRNS in this part of the globe.

The prevalence and risk of urinary tract infection in malnourished children: a systematic review and meta-analysis.

BACKGROUND: There are vast differences in prevalence rates of urinary tract infection (UTI) reported among malnourished children globally. We conducted a systematic review and meta-analysis to provide estimates of pooled prevalence of UTI among these children and combined UTI risk in comparison with their well-nourished counterparts. METHODS: We systematically searched electronic databases (MEDLINE, EMBASE, ISI Web of Science and African Journals Online; date of the last search: 22 December 2018) for studies reporting either the prevalence of UTI in malnourished children or parallel healthy controls. Eligible primary studies were observational studies of children in English Language reporting UTI prevalence with background malnutrition or with enough data to compute these estimates, as well as studies which reported at the same time UTI prevalence in healthy controls. We synthesized published prevalence rates or associations (odds ratios [OR]) between malnutrition and UTI and their 95% confidence intervals (CI) using random effects meta-regression and explored potential heterogeneity determinants using meta-regression analysis. This review is registered with PROSPERO, number- CRD42018084765. RESULTS: We included 26 cross-sectional and 8 case-control studies reporting on UTI prevalence in malnourished children, and in malnourished children vs. healthy controls, respectively. The pooled prevalence of UTI in 3294 malnourished children was 17% (95% CI, 13, 21%). Heterogeneity was high (I2 = 87.6%; Tau2 = 0.06) as studies varied in their sample size, degree of malnutrition, and study period. Multivariate meta-regression model, including these factors, explained 34.6% of the between-study variance. Pooled OR of UTI in association with malnutrition in 2051 children (1052 malnourished children vs. 999 controls) was 2.34 (95% CI, 1.15, 3.34), with lower between-study heterogeneity (I2 = 53.6%; Tau2 = 0.47). CONCLUSIONS: UTI is more prevalent in malnourished children than in their well-nourished counterparts. Screening and treatment for UTI should be incorporated in the management protocol of malnourished children to improve disease outcomes.

Vaso-occlusive crisis in sickle cell disease: current paradigm on pain management.

This narrative review aims to highlight the current paradigm on pain management in sickle cell vaso-occlusive crisis. It specifically examines the pathophysiologic mechanisms of sickle cell pain as well as the pharmacologic and nonpharmacologic methods of pain management. Recurrent painful episodes constitute the major morbidity in sickle cell disease (SCD). While adolescents and young adults experience mostly acute episodic nociceptive pain, it is now recognized that a significant number of adult patients develop chronic neuropathic and centralized pain. In fact, current evidence points to an age-dependent increase in the frequency of SCD patients with chronic pain. Management of disease-related pain should be based on its pathophysiologic mechanisms instead of using recommendations from other non-SCD pain syndromes. Pain management in vaso-occlusive crisis is complex and requires multiple interventions such as pharmacologic, nonpharmacologic, and preventive therapeutic interventions. Pharmacologic treatment involves the use of non-opioid and opioid analgesics, and adjuvants - either singly or in combination - depending on the severity of pain. The basic approach is to treat SCD pain symptomatically with escalating doses of non-opioid and opioid analgesics. Given the moderate-to-severe nature of the pain usually experienced in this form of SCD crisis, opioids form the bedrock of pharmacologic treatment. Multimodal analgesia and structured, individualized analgesic regimen appear more effective in achieving better treatment outcomes. Although the current evidence is still limited on the supportive role of cognitive behavioral therapy in pain management, this nonpharmacologic approach is reportedly effective, but needs further exploration as a possible adjunct in analgesia.

ABO histo-blood group and risk of respiratory atopy in children: a review of published evidence.

Besides their fundamental role in transfusion medicine, ABO and other histo-blood group antigens are associated with the pathogenesis of some human diseases such as malignancy and thrombosis. Reports also show a possible relationship with the risk of asthma and other forms of respiratory atopy. This paper aims to critically review the current evidence linking ABO histo-blood group with the risk of respiratory atopy in children and adults. A literature search was conducted with PubMed to gather baseline data about this relationship. The search extended to studies published within the past 45 years. First, the molecular mechanism underpinning the role of ABO antigenic system in human diseases comprises a fascinating relationship with von Willebrand factor and several pro-inflammatory and adhesion molecules. Second, specific blood group types vary with asthma phenotypes; severe asthma is associated with B phenotype, while mild and moderate asthma is associated with O and A phenotypes. Third, O phenotype has been linked to allergic rhinitis but only in males. Furthermore, asthma risk is related to O/Lewis negative/secretor phenotypes, while a significant relationship has also been established with B phenotype but not with A and O phenotypes. However, one study failed to establish a significant relationship with any of the ABO blood group antigens. In conclusion, there is no unanimity on the specific histo-blood groups linked to respiratory atopy risk, although asthma phenotypes are associated with specific blood groups. Despite the prospect that this relationship holds for the use of blood-group typing in evaluating respiratory atopy risk in children, more evidence-based studies are still required for its validation.

Chronic kidney disease in children: Using novel biomarkers as predictors of disease.

Chronic kidney disease (CKD) in children contributes to the global health burden. The focus on using novel biomarkers to predict the onset and progression of the disease has increased tremendously over the past decade. Discovery of these biomarkers offers prospects for the early anticipation of the late stages of CKD, slowing down disease progression, and achieving better disease outcomes. The aim of this article is to classify and highlight the utility of these novel biomarkers in predicting disease-onset and progression. Biomarkers of CKD are broadly classified into biomarkers of kidney function and biomarkers of kidney damage. Glomerular filtration rate (GFR) remains the most important marker of kidney function, but it cannot be easily measured in most clinical and research settings. Its estimating equations, therefore, depend on filtration biomarkers such as serum creatinine and serum cystatin C. For instance, the CKD-epidemiology collaboration equation has been suggested as the preferred prediction equation for the staging and classification of estimated GFR (eGFR) in CKD. Although albuminuria is the traditional biomarker of kidney damage, it precedes any decline in eGFR and may be absent in tubulointerstitial disease. Thus, more sensitive and specific novel biomarkers of kidney damage are emerging which hold prospects for earlier prediction of CKD in children. They have been classified as tubular and miscellaneous biomarkers. Tubular biomarkers are represented by markers such as kidney injury molecule-1, neutrophil gelatinase-associated lipocalin, N-acetyl-ß-D glucosaminidase, liver-type fatty-acid binding protein, cystatin C and a-1-microglobulin. Miscellaneous biomarkers include monocyte chemoattractant protein-1, interleukin-18, and retinol binding protein 4. Despite their advantages over albuminuria, they still require validation before they can be applied in clinical practice.

Severe bronchial asthma in children: a review of novel biomarkers used as predictors of the disease.

Severe asthma or therapy-resistant asthma in children is a heterogeneous disease that affects all age-groups. Given its heterogeneity, precision in diagnosis and treatment has become imperative, in order to achieve better outcomes. If one is thus able to identify specific patient phenotypes and endotypes using the appropriate biomarkers, it will assist in providing the patient with more personalized and appropriate treatment. However, there appears to be a huge diagnostic gap in severe asthma, as there is no single test yet that accurately determines disease phenotype. In this paper, we review the published literature on some of these biomarkers and their possible role in bridging this diagnostic gap. We also highlight the cellular and molecular mechanisms involved in severe asthma, in order to show the basis for the novel biomarkers. Some markers useful for monitoring therapy and assessing airway remodeling in the disease are also discussed. A review of the literature was conducted with PubMed to gather baseline data on the subject. The literature search extended to articles published within the last 40 years. Although biomarkers specific to different severe asthma phenotypes have been identified, progress in their utility remains slow, because of several disease mechanisms, the variation of biomarkers at different levels of inflammation, changes in relying on one test over time (eg, from sputum eosinophilia to blood eosinophilia), and the degree of invasive tests required to collect biomarkers, which limits their applicability in clinical settings. In conclusion, several biomarkers remain useful in recognizing various asthma phenotypes. However, due to disease heterogeneity, identification and utilization of ideal and defined biomarkers in severe asthma are still inconclusive. The development of novel serum/sputum-based biomarker panels with enhanced sensitivity and specificity may lead to prompt diagnosis of the disease in the future.

The role of novel biomarkers in predicting diabetic nephropathy: a review.

Diabetic nephropathy (DN) is one of the microvascular complications of the kidney arising commonly from type 1 diabetes mellitus (T1DM), and occasionally from type 2 diabetes mellitus (T2DM). Microalbuminuria serves as an early indicator of DN risk and a predictor of its progression as well as cardiovascular disease risk in both T1DM and T2DM. Although microalbuminuria remains the gold standard for early detection of DN, it is not a sufficiently accurate predictor of DN risk due to some limitations. Thus, there is a paradigm shift to novel biomarkers which would help to predict DN risk early enough and possibly prevent the occurrence of end-stage kidney disease. These new biomarkers have been broadly classified into glomerular biomarkers, tubular biomarkers, biomarkers of inflammation, biomarkers of oxidative stress, and miscellaneous biomarkers which also include podocyte biomarkers, some of which are also considered as tubular and glomerular biomarkers. Although they are potentially useful for the evaluation of DN, current data still preclude the routine clinical use of majority of them. However, their validation using high-quality and large longitudinal studies is of paramount importance, as well as the subsequent development of a biomarker panel which can reliably predict and evaluate this renal microvascular disease. This paper aims to review the predictive role of these biomarkers in the evaluation of DN.

Spirometry in Asthma Care: A Review of the Trends and Challenges in Pediatric Practice.

BACKGROUND: Given the rising incidence of noncommunicable diseases (NCDs) globally, especially bronchial asthma, there is the need to reduce the associated morbidity and mortality by adopting an objective means of diagnosis and monitoring. AIM: This article aims to review the trends and challenges in the use of spirometry for managing childhood bronchial asthma especially in developing countries. METHODS: We conducted a literature search of published data on the use of spirometry for the diagnosis of childhood bronchial asthma with special emphasis resource-poor countries. RESULTS: Guidelines for the diagnosis and treatment of childhood asthma recommend the use of spirometry, but this is currently underused in both tertiary and primary care settings especially in developing countries. Lack of spirometers and proper training in their use and interpretation of findings as well as a dearth of asthma guidelines remains core to the underuse of spirometry in managing children with asthma. Targeting education of health care staff was, however, observed to improve its utility, and practical implementable strategies are highlighted. CONCLUSIONS: Spirometry is not frequently used for asthma diagnosis in pediatric practice especially in resource-poor countries where the NCD burden is higher. Strategies to overcome the obstacles are implementable and can make a difference in reducing the burden of NCD.

The role of novel biomarkers in childhood idiopathic nephrotic syndrome: a narrative review of published evidence.

Two histological subtypes of idiopathic nephrotic syndrome are commonly recognized in children, namely minimal change nephropathy and focal segmental glomerulosclerosis. Children with minimal change nephropathy (the majority of whom are steroid-sensitive) and focal segmental glomerulosclerosis (the majority of whom are steroid-resistant) require early identification in order to ensure appropriate therapeutic intervention and better outcome. Although renal biopsy and histology remain the ideal diagnostic steps to identify these histological subtypes, reports indicate that serum and urinary biomarkers are now being utilized in the investigation of childhood idiopathic nephrotic syndrome. This paper aims to review the diagnostic and prognostic utility of novel biomarkers in childhood idiopathic nephrotic syndrome and to highlight their role in differentiating steroid-sensitive nephrotic syndrome (SRNS) from steroid-resistant nephrotic syndrome (SSNS). Using the terms "idiopathic nephrotic syndrome," "children," and "biomarkers" the PubMed database was searched for relevant studies related to the topic. Biomarkers such as adiponectin, neopterin, ß2-microglobulin, and N-acetyl-ß-D glucosaminidase were reported as diagnostic markers. In addition to neopterin and N-acetyl-ß-D glucosaminidase, urine vitamin D-binding protein and α1ß-glycoprotein were shown to differentiate SRNS from SSNS while N-acetyl-ß-D glucosaminidase and ß2-microglobulin could predict steroid responsiveness and renal outcome in SRNS. Although progress has been made in demonstrating the diagnostic and prognostic utility of these biomarkers, their limited availability in most laboratories has precluded a complete paradigm shift from the conventional renal biopsy. Nevertheless, further longitudinal studies are required to establish their usefulness as noninvasive predictors of disease response to immunosuppressive therapy.