Machine learning can guide suitability of consultation and patient referral through telemedicine for hepatobiliary diseases.

BACKGROUND AND AIM: Telemedicine is an evolving tool to provide health-care services. We evaluated the suitability of telemedicine to deliver effective consultation for hepatobiliary disorders. METHODS: In this prospective study spanning over a year, we interviewed hepatologists delivering the teleconsultations through a pre-validated questionnaire. A consult was deemed suitable based on the physician's judgment in the absence of unplanned hospitalization. We evaluated factors determining the suitability through inferential statistics and machine learning models, namely, extreme gradient boosting (XGB) and decision tree (DT). RESULTS: Of 1118 consultations, 917 (82.0%) were deemed suitable. On univariable analysis, patients with skilled occupation, higher education, out-of-pocket expenses, and diseases such as chronic hepatitis B, C, and non-alcoholic fatty liver disease (NAFLD) without cirrhosis were associated with suitability (P < 0.05). Patients with cirrhosis (compensated or decompensated), acute-on-chronic liver failure (ACLF), and biliary obstruction were likely unsuitable (P < 0.05). XGB and DT models predicted suitability with an area under the receiver operating curve of 0.808 and 0.780, respectively. DT demonstrated that compensated cirrhosis with higher education or skilled occupation with age < 55 years had 78% chance of suitability whereas hepatocellular carcinoma, decompensated cirrhosis, and ACLF patients were unsuitable with a 60-95% probability. In non-cirrhotic liver diseases, hepatitis B, C, and NAFLD were suitable, with a probability of 89.7%. Biliary obstruction and previous failure of teleconsultation were unsuitable, with a probability of 70%. Non-cirrhotic portal fibrosis, dyspepsia, and dysphagia not requiring intervention were suitable (probability: 88%). CONCLUSION: A simple decision tree can guide the referral of unsuitable and the management of suitable patients with hepatobiliary diseases through telemedicine.

Vitamin D as an adjunct to antibiotics for the treatment of acute childhood pneumonia.

BACKGROUND: Children with acute pneumonia may be vitamin D deficient. Clinical trials have found that prophylactic vitamin D supplementation decreases children's risk of developing pneumonia. Data on the therapeutic effects of vitamin D in acute childhood pneumonia are limited. This is an update of a Cochrane Review first published in 2018. OBJECTIVES: To evaluate the efficacy and safety of vitamin D supplementation as an adjunct to antibiotics for the treatment of acute childhood pneumonia. SEARCH METHODS: We searched CENTRAL, MEDLINE, Embase, and two trial registries on 28 December 2021. We applied no language restrictions. SELECTION CRITERIA: We included randomised controlled trials (RCTs) that compared vitamin D supplementation with placebo in children (aged one month to five years) hospitalised with acute community-acquired pneumonia, as defined by the World Health Organization (WHO) acute respiratory infection guidelines. For this update, we reappraised eligible trials according to research integrity criteria, excluding RCTs published from April 2018 that were not prospectively registered in a trials registry according to WHO or Clinical Trials Registry - India (CTRI) guidelines (it was not mandatory to register clinical trials in India before April 2018). DATA COLLECTION AND ANALYSIS: Two review authors independently assessed trials for inclusion and extracted data. For dichotomous data, we extracted the number of participants experiencing the outcome and the total number of participants in each treatment group. For continuous data, we used the arithmetic mean and standard deviation (SD) for each treatment group together with number of participants in each group. We used standard methodological procedures expected by Cochrane. MAIN RESULTS: In this update, we included three new trials involving 468 children, bringing the total number of trials to seven, with 1601 children (631 with pneumonia and 970 with severe or very severe pneumonia). We categorised three previously included studies and three new studies as 'awaiting classification' based on the research integrity screen. Five trials used a single bolus dose of vitamin D (300,000 IU in one trial and 100,000 IU in four trials) at the onset of illness or within 24 hours of hospital admission; one used a daily dose of oral vitamin D (1000 IU for children aged up to one year and 2000 IU for children aged over one year) for five days; and one used variable doses (on day 1, 20,000 IU in children younger than six months, 50,000 IU in children aged six to 12 months, and 100,000 IU in children aged 13 to 59 months; followed by 10,000 IU/day for four days or until discharge). Three trials performed microbiological diagnosis of pneumonia, radiological diagnosis of pneumonia, or both. Vitamin D probably has little or no effect on the time to resolution of acute illness (mean difference (MD) -1.28 hours, 95% confidence interval (CI) -5.47 to 2.91; 5 trials, 1188 children; moderate-certainty evidence). We do not know if vitamin D has an effect on the duration of hospitalisation (MD 4.96 hours, 95% CI -8.28 to 18.21; 5 trials, 1023 children; very low-certainty evidence). We do not know if vitamin D has an effect on mortality rate (risk ratio (RR) 0.69, 95% CI 0.44 to 1.07; 3 trials, 584 children; low-certainty evidence). The trials reported no major adverse events. According to GRADE criteria, the evidence was of very low-to-moderate certainty for all outcomes, owing to serious trial limitations, inconsistency, indirectness, and imprecision. Three trials received funding: one from the New Zealand Aid Corporation, one from an institutional grant, and one from multigovernment organisations (Bangladesh, Sweden, and UK). The remaining four trials were unfunded. AUTHORS' CONCLUSIONS: Based on the available evidence, we are uncertain whether vitamin D supplementation has important effects on outcomes of acute pneumonia when used as an adjunct to antibiotics. The trials reported no major adverse events. Uncertainty in the evidence is due to imprecision, risk of bias, inconsistency, and indirectness.

Cirrhosis and fungal infections-a cocktail for catastrophe: A systematic review and meta-analysis with machine learning.

OBJECTIVES: We evaluated the magnitude and factors contributing to poor outcomes among cirrhosis patients with fungal infections (FIs). METHODS: We searched PubMed, Embase, Ovid and WOS and included articles reporting mortality in cirrhosis with FIs. We pooled the point and relative-risk (RR) estimates of mortality on random-effects meta-analysis and explored their heterogeneity (I 2 ) on subgroups, meta-regression and machine learning (ML). We assessed the study quality through New-Castle-Ottawa Scale and estimate-asymmetry through Eggers regression. (CRD42019142782). RESULTS: Of 4345, 34 studies (2134 patients) were included (good/fair/poor quality: 12/21/1). Pooled mortality of FIs was 64.1% (95% CI: 55.4-72.0, I 2 : 87%, p < .01), which was 2.1 times higher than controls (95% CI: 1.8-2.5, I 2 :89%, p < .01). Higher CTP (MD: +0.52, 95% CI: 0.27-0.77), MELD (MD: +2.75, 95% CI: 1.21-4.28), organ failures and increased hospital stay (30 vs. 19 days) were reported among cases with FIs. Patients with ACLF (76.6%, RR: 2.3) and ICU-admission (70.4%, RR: 1.6) had the highest mortality. The risk was maximum for pulmonary FIs (79.4%, RR: 1.8), followed by peritoneal FIs (68.3%, RR: 1.7) and fungemia (55%, RR: 1.7). The mortality was higher in FIs than in bacterial (RR: 1.7) or no infections (RR: 2.9). Estimate asymmetry was evident (p < 0.05). Up to 8 clusters and 5 outlier studies were identified on ML, and the estimate-heterogeneity was eliminated by excluding such studies. CONCLUSIONS: A substantially worse prognosis, poorer than bacterial infections in cirrhosis patients with FIs, indicates an unmet need for improving fungal diagnostics and therapeutics in this population. ACLF and ICU admission should be included in the host criteria for defining IFIs.

Global epidemiological burden of fungal infections in cirrhosis patients: A systematic review with meta-analysis.

BACKGROUND AND AIMS: Fungal infections (FIs) have serious implications, yet understated in cirrhosis. Therefore, we reviewed the epidemiology and trends of FIs among cirrhotics. METHODS: Four electronic databases were searched for full-text articles describing prevalence of FIs in cirrhosis. Studies from post-transplant, malignancy and classical-immuno-deficiency patients were excluded. A random-effects meta-analysis was done to pool estimates of FIs (overall, and by type and infection-site), and their variation(I2 ) was explored on moderator-analysis and meta-regression. Risk of bias and asymmetry in estimates was assessed by a checklist and Egger's regression, respectively.(CRD42019142782). RESULTS: Thirty-four low-risk and four moderate-risk studies (31 984 cirrhotics) were included. Pooled estimates of overall FIs (17 studies), invasive fungal infections (IFIs; 17 studies), invasive candidiasis (23 studies) and invasive aspergillosis (16 studies) in cirrhosis were 10.2%(6.0-16.9), 9.5%(5.4-16.2), 4.0%(2.0-8.0) and 2.8%(1.5-5.3), respectively (I2  > 90%;each). Site of FIs in decreasing order of pooled prevalence was pulmonary, urinary tract, bloodstream, peritoneal, oesophageal and cerebral. Geographic differences in these estimates were remarkable, with highest burden of overall FIs from Belgium, the United States and India. Non-albicans-Candida and Aspergillus infections have increased over the last decade in cirrhosis. Intensive-care-unit (ICU)-admitted and acute-on-chronic liver failure (ACLF) patients had the highest prevalence of IFIs. MELD score(cases), bias score and sample size across studies were the predictors of variance in overall FI estimates. Diabetes, steroid and broad-spectrum antibiotic-exposure, and multiple organ failures were the common predispositions reported in patients with FIs. CONCLUSIONS: FIs impose a substantial burden in cirrhosis. ACLF and ICU admission should be considered as a host factor for defining IFIs. Epidemiology of FIs can guide interpretation of biomarkers and antifungal treatment in cirrhosis.

The perceived need for evidence-based COVID-19 management and Tele-education in the North-East region of India: a cross-sectional survey.

Due to the sudden rise in the cases of COVID-19 in the North-Eastern region of India, this study was conducted to survey the felt needs of the medical professionals with regards to education on the evidence-based management of COVID-19. A total of 25 North-East leaders were recruited and a baseline survey was conducted through the digital medium. Out of 25 North-East leaders, 52% were undergoing training in evidence-based medicine in the capacity-building program for evidence-based child health. Participants (48%) strongly agreed and 40% agreed on the possibility of enhanced care by capacity building in the areas of COVID-19 management through discussing cases. Out of 25 North East leaders, 48% agreed to join both as a speaker as well as a participant. Various priority topics on COVID-19 management e.g. childhood, adult, ocular manifestation, ICU management, telemedicine, vaccines, lab protocols, psychological distress, and treatment strategy have emerged. We have presented the findings of the survey which will help guide the mentoring program focusing on evidence-based management of COVID-19 in remote areas through Tele-education.

Effect of Probiotics on the Frequency of CD4+ T-Cells in HIV-Infected Children and Adolescents: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

BACKGROUND: Depletion of CD4+ T-cells in the gut-associated lymphoid tissue is the hallmark of HIV infection, with only partial restoration by potent antiretroviral therapy (ART). Gut dysbiosis, together with disruption of mucosal integrity contributes to chronic immune activation that further exacerbates the disease. Data from randomized controlled trials in pediatric HIV patients have indicated potential of probiotics in complementing routine ART in managing HIV-associated gastrointestinal complications. We have systematically extracted data from these trials and performed meta-analysis to quantify the effect of probiotics on CD4+ T-cell counts and any adverse events associated with their supplementation. METHODS: A systematic search through multiple databases yielded three studies that were pooled using fixed-effect model. Risk of bias assessment was done by the Cochrane risk of bias tool and publication bias was assessed by Egger's test. RESULTS: Included studies had moderate risk of bias and Egger's statistics revealed no publication bias (p > 0.05). Pooled analysis showed significant improvement in CD4+ T-cell counts, with mean difference, 123.92 (95% CI: 104.36-143.48), p < 0.0001, no heterogeneity (I2=0) among the included trials. Subgroup analysis also depicted improvement in CD4+ T-cell counts irrespective of treatment duration, in both ART naïve and treated patients. No adverse effects with probiotic consumption were reported. CONCLUSIONS: Probiotics supplementation led to an improvement in CD4+ T-cell counts among HIV-infected children with no observed adverse effects. Despite the inherent limitations of included studies, our systematic review would justify more well-designed, large-scale trials in children, which may guide pediatricians on whether to incorporate probiotics as an adjunct therapy to routine ART.

HIV infection is associated with a progressive decline of CD4+ T-cell numbers and increase in viral load. To keep the virus replication in check, patients need to take the antiretroviral therapy life-long, which is not without gastrointestinal discomfort. Probiotics have already shown multiple benefits ranging from reduction in diarrhea, nausea and bloating besides replenishment of CD4+ T-cells numbers. Based on this background information, we have compiled the data on probiotics among HIV-infected children. A pooled analysis from randomized clinical trials revealed significant improvement in CD4+ T-cell counts in HIV-infected children without any adverse effects. However, we recommend large and well-designed trials in future that would help in forming a concrete and high quality evidence in this context.

Potential toxicity of nickel nano and microparticles on the reproductive system of female rats: A comparative time-dependent study.

Increased application of engineered nanoparticles in different sectors viz. agriculture, commerce, industry, and medicine has raised serious public health issues. Nanoparticles of nickel have been increasingly used as catalysts, conductive pastes, adhesives, nanowires, and nanofilters. Human and animal exposure to these particles may cause toxicity in different organs/systems. Studies made in the past had demonstrated their toxicity in liver, kidney, and lungs. However, their reproductive effects remain poorly understood. Therefore, the present study on reproductive toxicity of nickel nanoparticles (<30 nm) was executed in female Wistar rats. A comparison of results obtained in nickel microparticle-treated rats was also made. Rats were administered nano and microparticles through gavage at a dosage of 5 mg/kg body weight each for two exposure periods; that is, 15 and 30 days. Ovaries removed from these rats were analyzed to study the effects of nickel bioaccumulation on synthesis of steroid hormones, lipid peroxidation, apoptosis, and oxidative stress. Structural changes were monitored through histopathological and ultrastructural observations. The present study showed exposure time-dependent differences in the toxicity of nickel nano and microparticles in the ovary of rats. Nano nickel was cumulative in the ovaries. It affected steroidogenesis. Further, increased generation of reactive oxygen species and enhanced oxidative stress may have contributed to cytotoxicity. It was concluded that exposure to nano nickel might induce irreversible damage in the ovaries of rat.

Effectiveness-of Calcium Phosphate derivative agents on the prevention and remineralization of caries among children- A systematic review & meta-analysis of randomized controlled trials.

OBJECTIVES: Dental caries among children is a highly prevalent yet easily preventable oral health issue among children. Various calcium phosphate (CaP) derivatives are implicated to exhibit caries preventive potential; however, no study has summarized the anti-caries effectiveness of these agents. This systematic review and meta-analysis sought to assess the caries-preventive and tooth-remineralizing effect of various (CaP) derivative agents compared to no-intervention/placebo or Fluoride (F) use alone among children. MATERIALS AND METHODS: EMBASE, Ovid, PubMed, Scopus, Web of Science, Cochrane central register of controlled trials (CENTRAL), and grey literature were searched for relevant articles up to April 2021. Only English-language articles were included. Total 2636 articles were searched through different databases; out of the 2161 articles were screened after duplicate removal. 26 studies fulfilling the eligibility criteria were included in this systematic review. Methodological quality assessment and quantitative analysis were done using RevMan. GRADE was used to evaluate the certainty of evidence. RESULTS: A total of 26 trials fulfilling the eligibility criteria were included. The meta-analysis of 10 studies revealed that complete white spot lesions (WSLs) regression (RR=1.56; 95% CI, 1.27 to 1.91; P < .0001, I2=0%), post intervention active WSLs (RR=0.80; 95% CI, 0.70 to 0.90; P = .0004, I2=0%) and post intervention Salivary S. mutans count (RR= 0.69; 95% CI, 0.48 to 0.99; P = .47, I2=0%) significantly favored the CaP+F combined therapy as compared to F alone. No significant differences in the lesion area, Delta F, and DIAGNOdent values were observed between the 2 groups. Low certainty of the evidence was found in the present systematic review due to the high/unclear risk of bias, imprecision, and indirectness of included trials. CONCLUSIONS: Topical treatment using CaP+F group showed superior remineralization potential as well as the antibacterial effect on dental caries among children as compared to no intervention and/or placebo or F alone. Apart from CPP-ACP, other CaP derivatives like TCP and fTCP seem to have promising effects in remineralizing early lesions, however, very few trials exist on these potential agents. To provide definitive recommendations in this area, more clinical trials on caries preventive effectiveness of various CaP agents are warranted.

Cytokine signaling pathway in cystic fibrosis: expression of SOCS and STATs genes in different clinical phenotypes of the disease.

This was an observational cross-sectional study which was done to assess the expression profile of STATs and SOCS genes in cystic fibrosis. The mRNA was isolated from peripheral blood mononuclear cells of CF patients in exacerbation, colonization and post exacerbation phases of the disease. The relative gene expression level for SOCS 1, -3, -5 and STAT 1, -3,-4,-6 genes was quantified by Real-time PCR. The levels of IL-6 were also measured in the serum by ELISA. The expression of the Th1 pathway associated genes (SOCS1, SOCS5, STAT4 and STAT1) was downregulated while the expression of Th2/Th17 pathway genes (SOCS3, STAT3, STAT6) was upregulated in both exacerbation and colonization phases as compared to healthy controls. The serum levels of IL-6 were also elevated in both the disease groups. After antibiotic treatment, the expression of SOCS5 and STAT4 was increased while the expression of rest of the genes showed downregulation which shows a shift in immune response from Th2/Th17 to Th1. Our results suggest that infection alters the cytokine signaling pathway through modulation of STATs and SOCS genes which is not able to regulate the overstimulation of cytokine signaling further leading to chronic inflammation in CF.

Factors determining the mortality in cirrhosis patients with invasive candidiasis: A systematic review and meta-analysis.

The impact of invasive candidiasis (IC) on the outcomes in the non-conventional high-risk cirrhosis population is poorly characterized. Therefore, we reviewed the outcomes and their influencing factors in cirrhosis patients with IC. PubMed, Embase, Ovid, CINHAL, and Web of Science were searched for full-text observational studies describing mortality due to IC in cirrhosis. We did a systematic review and random-effects meta-analysis to pool the point-estimate and comparative-odds of mortality. The estimate's heterogeneity was explored on sub-groups, outliers-test, and meta-regression. We evaluated the asymmetry in estimates on funnel plot and Eggers regression. Quality of studies was assessed on the New-Castle Ottawa scale. Of 3143 articles, 13 studies (611 patients) were included (good/fair quality: 6/7). IC patients were sick with a high model for end-stage liver disease (MELD: 27.0) and long hospital stay (33.2 days). The pooled-mortality was 54.7% (95% CI: 41.3--67.5), I2: 80%, P < 0.01. Intensive care unit (ICU) admission (P < 0.001), site of infection; viz. peritonitis and candidemia (P = 0.014) and high MELD of cases (P = 0.029) were predictors of high mortality. The odds of mortality due to IC was 4.4 times higher than controls and was 8.5 and 3.3 times higher than non-infected, and bacterially-infected controls. Studies in ICU-admitted (OR: 5.0) or acute-on-chronic liver failure (ACLF, OR: 6.3) patients had numerically higher odds of mortality than all-hospitalized cirrhosis patients (OR: 4.0). In conclusion, substantially high mortality is reported in cirrhosis patients with IC. ICU admission, ACLF, high MELD, peritonitis, and candidemia are key factors determining high mortality in cirrhosis patients with IC. LAY SUMMARY: We report a high mortality rate of 55% in patients with liver cirrhosis and invasive candidiasis. Higher odds (4.4 times) of death, especially in patients with ACLF (6.3 times) or ICU admission (5.0 times) were seen. Candida peritonitis and candidemia are associated with high mortality in cirrhosis.

Invasive aspergillosis is a critical determinant of mortality in cirrhosis: a systematic review with meta-analysis.

Invasive fungal infections pose a severe threat in unconventional immunocompromised hosts such as cirrhosis. Herein we review the impact of invasive aspergillosis (IA) on the prognosis of cirrhosis patients. An electronic search for full-text articles describing IA in cirrhosis was conducted and the disease outcomes and mortality (point-estimate and comparative risk) were pooled on random-effects meta-analysis. Of 4127 articles, 11 studies (9 with good/fair and 2 with poor quality) were included. IA was associated with high disease severity and multi-organ failures in cirrhosis. The pooled-mortality of IA was 81.8% (95% CI: 64.3-91.8, I2 = 59%, P < 0.01). Estimate's-heterogeneity (I2) was explored through sub-groups, meta-regression, and influential diagnostics. Mortality estimates were higher among subgroups of acute-on-chronic liver failure (ACLF, 86.4%) and intensive care unit (ICU)-admitted patients (84.0%). The odds of mortality related to IA were 8.9 times higher than controls and much higher in ACLF (OR: 22.5) and ICU-admitted patients (OR: 36.4). The odds of mortality in IA were 4.1, 12.9, and 48.6 times higher than bacterial, no-fungal infections, and no-infection controls. There was no asymmetry in mortality estimates or odds ratios and mortality in IA was high irrespective of country of origin, site of infection, proven or probable category, and quality of study. Thus, IA is associated with very high mortality in cirrhosis patients, especially in ACLF and ICU-admitted patients. Intensive research is needed for the rapid diagnosis and treatment of IA in cirrhosis. LAY SUMMARY: We report a high mortality rate of 81.8% in patients with liver cirrhosis and invasive aspergillosis. Higher odds (8.9 times) of death, especially in patients with ACLF or ICU admission were seen. Mortality was not affected by the country of study, site of infection, proven or probable nature of infection category, and quality of study.

Comparative accuracy of 1,3 beta-D glucan and galactomannan for diagnosis of invasive fungal infections in pediatric patients: a systematic review with meta-analysis.

Invasive fungal infections (IFI) cause considerable morbidity and mortality in pediatric patients. Serum biomarkers such as 1,3-beta-D glucan (BDG) and galactomannan (GM) have been evaluated for the IFI diagnosis. However, most evidence regarding their utility is derived from studies in adult oncology patients. This systematic review aimed to compare the diagnostic accuracy of BDG and GM individually or in combination for diagnosing IFI in pediatric patients. PubMed, CINAHL, Embase, and Cochrane Library were searched until March 2019 for diagnostic studies evaluating both serum GM and BDG for diagnosing pediatric IFI. The pooled diagnostic odds ratio (DOR), specificity and sensitivity were computed. Receiver operating characteristics (ROC) curve and area under the curve (AUC) were used for summarizing overall assay performance. Six studies were included in the meta-analysis. The summary estimates of sensitivity, specificity, pooled DOR, AUC of the GM assay for proven or probable IFI were 0.74, 0.76, 13.25, and 0.845. The summary estimates of sensitivity, specificity, pooled DOR, AUC of the BDG assay were 0.70, 0.69, 4.3, and 0.722. The combined predictive ability of both tests was reported in two studies (sensitivity: 0.67, specificity: 0.877). Four studies were performed in hematology-oncology patients, while two were retrospective studies from pediatric intensive care units (ICUs). In the subgroup of hematology-oncology patients, DOR of BDG remained similar at 4.25 but increased to 40.28 for GM. We conclude that GM and BDG have a modest performance for identifying IFI in pediatric patients. GM has a better accuracy over BDG. Combining both improves the specificity at the cost of sensitivity.

Comparison of performances of loop-mediated isothermal amplification, XPERT MTB/RIF and BACTEC MGIT in the diagnosis of childhood tuberculosis.

AIM: Key to the successful management of paediatric pulmonary tuberculosis (PTB) lies in the early detection and proper treatment. We evaluated the performances of modern diagnostic tests: loop-mediated isothermal amplification (LAMP-IS6110), Xpert MTB/RIF (Cepheid) and mycobacteria growth indicator tube (BACTEC MGIT 960 culture) against a modified version of international consensus diagnostic definition (i.e. composite reference standard (CRS)). METHODS: A cross-sectional analytical study was conducted in a tertiary care hospital in North India from July 2016 to December 2017 involving 100 children <14 years with suspected PTB. Respiratory specimens (sputum, gastric lavage and/or bronchoalveolar lavage) were collected and subjected to LAMP-IS6110, Xpert MTB/RIF and BACTEC MGIT 960 culture assay. RESULTS: Fifty-five children had confirmed and probable TB according to the CRS (prevalence = 58.5%). The sensitivity of BACTEC MGIT 960 culture, Xpert MTB/RIF and LAMP-IS6110 assay was 14%, 9.1% and 10.91%, respectively, when compared against the predefined CRS. The specificity for all these tests was 100%. When compared with BACTEC MGIT 960 culture as the gold standard, the LAMP-IS6110 assay and Xpert MTB/RIF assay had the sensitivity of 85.71% (95% CI: 42.13-99.64%) and 71.43% (95% CI: 29.04-96.33%), respectively. The specificity of both assays was 100%. CONCLUSIONS: We noted that LAMP-IS6110 performed better than Xpert MTB/RIF (Cepheid) in terms of sensitivity when compared against BACTEC MGIT 960 culture as reference standard, though specificity of both the tests was comparable. The diagnostic performance of BACTEC MGIT 960 culture was better than LAMP-IS6110 and Xpert MTB/RIF in paediatric PTB, when compared against CRS.

Flexible Fibreoptic Bronchoscopy and Bronchoalveolar Lavage for Confirmation of Pulmonary Hydatid Disease in Children: A Case Series.

Hydatid disease of the lungs is common in endemic regions. It can be suspected clinically by non-specific respiratory symptoms in children living in endemic regions, especially when they are close to sheep or dogs. Chest imaging X-ray or computed tomography may show characteristic cysts in some cases, but typical findings are absent in many children. Hydatid serology may contribute to the diagnosis, but does not have sufficient sensitivity for pulmonary cysts. Thus, there is no confirmatory diagnostic test, other than surgical excision and histopathologic examination. Hence, there is a need for more reliable diagnostic tests. We present a series of children, both with and without suspected pulmonary hydatid, wherein flexible fibreoptic bronchoscopy (FFOB) performed under conscious sedation, revealed hydatid membranes in the airways. Bronchoalveolar lavage (BAL) analysis revealed hydatid in most of them. Thus the diagnosis could be confirmed even before surgical excision of cysts was performed. We propose that FFOB with BAL could be useful to confirm the diagnosis of pulmonary hydatid in children. This will be particularly helpful in children without characteristic radiological or serological findings. To the best of our knowledge, this is a completely novel approach to the condition with potential to alter the diagnostic paradigm Lay summary Hydatid disease of the lungs is commonly encountered in endemic regions. However, there is no confirmatory diagnostic test for pulmonary hydatid cyst, other than surgical excision and histopathologic examination. Imaging including chest X-ray and computed tomography may not be typical, especially in complicated cysts and hydatid serology does not have a satisfactory sensitivity for diagnosing lung cysts. Thus, there is a need for more reliable diagnostic tests. We present a series of children, both with and without suspected pulmonary hydatid, wherein flexible fibreoptic bronchoscopy (FFOB) under conscious sedation, revealed hydatid membranes in the airways. Bronchoalveolar lavage (BAL) analysis confirmed hydatid in most of them. We propose FFOB with BAL as a useful diagnostic modality to confirm pulmonary hydatid in children, prior to surgical excision. To the best of our knowledge, this is a completely novel approach to the condition with potential to alter the diagnostic paradigm.

Comparative Efficacy of Treatment Options for Minimal Hepatic Encephalopathy: A Systematic Review and Network Meta-Analysis.

BACKGROUND & AIMS: We aimed to synthesize evidence for most effective treatments for minimal hepatic encephalopathy (HE) and prevention of overt HE in patients with cirrhosis. METHODS: We performed a systematic search of the PubMed, EMBASE, OvidSP, and Cochrane Central Register of Controlled Trials databases through July 26, 2018, for randomized controlled trials evaluating treatments for minimal HE in patients with cirrhosis, with primary outcomes of reversal of minimal HE or prevention of overt HE. We conducted a meta-analysis and then used network meta-analysis and surface under cumulated ranking (SUCRA) to pool the direct and indirect estimates and rank the different treatments. We appraised study quality using the Grading of Recommendations Assessment, Development and Evaluation system. RESULTS: Our meta-analysis and network meta-analysis included 25 trials, comprising 1563 participants. Agents found to be effective in reversing minimal HE compared with placebo or no treatment included rifaximin (odds ratio [OR], 7.53; 95% predictive interval [PrI], 4.45-12.73; SUCRA, 89.2%; moderate quality), lactulose (OR, 5.39; 95% PrI, 3.60-8.0; SUCRA, 67.2%; moderate quality), the combination of probiotics and lactulose (OR, 4.66; 95% PrI, 1.90-11.39; SUCRA, 52.4%; low quality), L-ornithine L-aspartate (OR, 4.45; 95% PrI, 2.67-7.42; SUCRA, 47.2%; low moderate quality), and probiotics (OR, 3.89; 95% PrI, 2.52-6.02; SUCRA, 34.1%; low quality). Agents found to be effective in preventing episodes of overt HE compared with placebo or no treatment included L-ornithine L-aspartate (OR, 0.19; 95% PrI, 0.04-0.91; SUCRA, 75.1%; high moderate quality), lactulose (OR, 0.22; 95% PrI, 0.09-0.52; SUCRA, 73.9%; moderate quality), and probiotics (OR, 0.27; 95% PrI, 0.11-0.62; SUCRA, 59.6%; low quality). CONCLUSIONS: In a meta-analysis of data from 25 trials, we found rifaximin and lactulose to be most effective for reversal of minimal HE in patients with cirrhosis. L-ornithine L-aspartate and lactulose are most effective in the prevention of overt HE. Lactulose was the only agent that was effective in reversing minimal HE, preventing overt HE, reducing ammonia, and improving quality of life, with tolerable adverse effects. International prospective register of systematic reviews ID: 107003.

Palliative drug treatments for breathlessness in cystic fibrosis.

BACKGROUND: Cystic fibrosis is a life-limiting autosomal recessive genetic illness. A feeling of shortness of breath is common in cystic fibrosis, especially as the disease progresses. Reversing the underlying cause is the priority when treating breathlessness (dyspnoea), but when it is not feasible, palliation (easing) becomes the primary goal to improve an individual's quality of life. A range of drugs administered by various routes have been used, but no definite guidelines are available. A systematic review is needed to evaluate such treatments. OBJECTIVES: To assess the efficacy and safety of drugs used to ease breathlessness in people with cystic fibrosis. SEARCH METHODS: We searched the Cochrane Cystic Fibrosis Trials Register, compiled from electronic database searches and handsearching of journals and conference abstract books. Date of last search: 18 November 2019. We searched databases (clinicaltrials.gov, the ISRCTN registry, the Clinical Trials Registry India and WHO ICTRP) for ongoing trials. These searches were last run on 06 March 2020. SELECTION CRITERIA: We planned to include randomised and quasi-randomised controlled trials in people with cystic fibrosis (diagnosed by a positive sweat chloride test or genetic testing) who have breathlessness. We considered studies comparing any drugs used for easing breathlessness to another drug administered by any route (inhaled (nebulised), intravenous, oral, subcutaneous, transmucosal (including buccal, sublingual and intra-nasal) and transdermal). DATA COLLECTION AND ANALYSIS: The authors assessed the search results according to the pre-defined inclusion criteria. MAIN RESULTS: The new searches in 2020 yielded two ongoing studies that were not relevant to the review question. Previous searches had found only one study (cross-over in design), which did not fulfil the inclusion criteria as no data were available from the first treatment period alone. AUTHORS' CONCLUSIONS: Due to the lack of available evidence, this review cannot provide any information for clinical practice. The authors call for specific research in this area after taking into account relevant ethical considerations. The research should focus on the efficacy and safety of the drugs with efficacy being measured in terms of improvement in quality of life, dyspnoea scores and hospital stay.

Loop-mediated isothermal amplification (LAMP) in the respiratory specimens for the diagnosis of pediatric pulmonary tuberculosis: A pilot study.

BACKGROUND: Loop-mediated isothermal amplification (LAMP) assay is a novel molecular diagnostic technique that can be used for the diagnosis of tuberculosis (TB). It is most suited for developing countries as it is rapid, inexpensive, highly sensitive, requiring minimal infrastructure, training and manpower. Studies in pediatric TB are lacking. We evaluated LAMP in the diagnosis of pediatric pulmonary TB. METHODOLOGY: This was a cross-sectional analytical study conducted at a tertiary care teaching hospital in North India from July 2014 to June 2015 involving 60 children with suspected pulmonary TB. Respiratory specimens (sputum, gastric lavage, bronchoalveolar lavage and/or endotracheal aspirates) were collected and subjected to BACTEC MGIT 960 culture, IS6110 PCR, and LAMP assay targeting IS6110 gene of Mycobacterium tuberculosis. RESULTS: Thirty seven children had confirmed and probable TB according to the composite reference standard (CRS). Among all the 3 tests used for diagnosis of Pulmonary TB, LAMP had highest sensitivity (37.8%) followed by PCR (27%), and culture (21.6%) when compared against the predefined CRS. Culture had maximum specificity of 100%; and PCR, and LAMP had specificity of 95-96%. The sensitivity, specificity, PPV, and NPV of LAMP against culture as reference standard were 75%, 72.4%, 42.9%, and 91.3% respectively. Similarly sensitivity, specificity, PPV, and NPV of PCR against culture as reference standard were 75%, 86.2%, 60%, and 86.2% respectively. On combining LAMP with culture, sensitivity increased to 45.7% (7.8% increase, p = 0.04). CONCLUSION: We noted that LAMP had highest sensitivity when compared to culture and PCR and comparable specificity.

Association of Serum TGF-ß1 Levels with Different Clinical Phenotypes of Cystic Fibrosis Exacerbation.

PURPOSE: Cystic Fibrosis (CF) is a multi-organ genetic disorder and Transforming Growth Factor (TGF-ß1) is a modifier gene which modulates lung pathology in CF. There is great phenotypic variability among CF patients who even have similar genotype. The aim of the present study was to associate the serum levels of TGF-ß1 with several clinical phenotypes of CF. METHODS: The diagnosed cases of CF were recruited and the blood sample was withdrawn at different time points: during exacerbation (n = 26), non-exacerbation (n = 9) and after antibiotic therapy (n = 11). The concentration of the total TGF-ß1 in serum was measured with commercial ELISA kit. The ΔF508 mutation was assessed by the Amplification Refractory Mutation System (ARMS-PCR). RESULTS: The levels of TGF-ß1 were increased in exacerbation phase (119.89 ± 29.64 ng/mL), infection with P. aeruginosa (121.8 ± 28.83 ng/mL) and in subjects with ΔF508 mutation (139.2 ± 19.59 ng/mL). The levels of TGF-ß1 in CF patients with Allergic Bronchopulmonary Aspergillosis (ABPA) (109.97 ± 27.71 ng/mL) were decreased as compared to CF patients without ABPA (123.55 ± 30.20 ng/mL). It was observed that the serum levels of TGF-ß1 were decreased significantly after antibiotic therapy (p < 0.05). CONCLUSIONS: The present study has determined that the serum levels of TGF-ß1 vary with the type of infections, ΔF508 CFTR mutation, presence of ABPA and response to therapy.

Compliance to spectacle use in children with refractive errors- a systematic review and meta-analysis.

BACKGROUND: Primary objective of this review was to measure compliance with spectacle use in children with refractive errors. Secondary objective was to understand the reasons for non-compliance. METHODS: The databases searched were Ovid, EMBASE, CINAHL and Pubmed. All studies up to March, 2018 were included. The search terms were- ((((((Compliance [Title/Abstract]) OR Adherence [Title/Abstract]) OR Compliant [Title/Abstract]) OR Adherent [Title/Abstract])) AND (((Spectacle [Title/Abstract]) OR Spectacles [Title/Abstract]) OR Eye Glasses [Title/Abstract])) AND ((((Child [Title/Abstract]) OR Children [Title/Abstract]) OR Adolescent [Title/Abstract]) OR Adolescents [Title/Abstract]). Two researchers independently searched the databases and initial screening obtained 33 articles. The PRISMA guidelines were followed for conducting and writing the systematic review. Two reviewers assessed data quality independently using the Quality Assessment tool for systematic reviews of observational studies (QATSO). Poor quality studies were those, which had a score of less than 33% on the QATSO tool. Sensitivity analysis was done to determine if poor quality studies effected compliance. Galbraith plot was used to investigate statistical heterogeneity amongst studies. A random effects model was used to pool compliance. RESULTS: Twenty-three studies were included in the review, of which 20 were included in the quantitative analysis. All the studies were cross sectional. The overall compliance with spectacle use was 40.14% (95% CI- 32.78-47.50). The compliance varied from 9.84% (95% CI = 2.36-17.31) to 78.57% (95% CI = 68.96-88.18). The compliance derived in sensitivity analysis was 40.09%. Reasons for non-compliance were broken/lost spectacles, forgetfulness, and parental disapproval. CONCLUSION: Appropriate remedial measures such as health education and strengthening vision care services will be required to address poor compliance with spectacle use among children.

Age-related differences in height gain with dairy protein and micronutrient supplements in Indian primary school children.

BACKGROUND AND OBJECTIVES: The efficacy of nutrient interventions to prevent/reverse stunting is considered to be restricted to early life. Whether such interventions are equally effective in later childhood is not clear. The present study evaluated the effect of a food-based high-quality protein and micronutrient intervention on the linear growth of Indian primary school children. METHODS AND STUDY DESIGN: A secondary analysis of a one-year milkprotein and micronutrient fortified food product intervention (protein-energy ratio: 12.8%) on the height of 550 children aged 6-10 years, of poor-socioeconomic background, was carried out. Height and weight increments were compared between groups of each year of age using multiple linear regression. Comparisons in prevalence of stunting and underweight between these groups was also made. RESULTS: The overall mean height increment at the end of 1-year was 6.10±1.07 cm, the highest being for 6-year olds (6.38±0.84 cm). The mean height increments in 6, 7 and 8-year-olds were significantly higher (all p<0.05) than the expected median growth. Height-forage score increased across all age-groups (by 0.14±0.18) and was significantly higher in 6-year olds compared to the rest. Stunting reduced by 12% in 6- year olds in comparison to the older age-groups. No significant association was observed between height gain and gender. The increased BMI-for-age scores were significantly lower for the 6-year olds compared to older children. CONCLUSIONS: Food supplements containing high-quality protein (like milk) along with micronutrients, can continue to influence height of children even in primary school, although the most effect is seen in younger children.