Joint Involvement Can Predict Chikungunya in a Dengue Syndemic Setting in India.

Dengue and chikungunya have been endemic in India but have the tendency to cause periodic epidemics, often together, wherein they are termed 'syndemic'. Such a syndemic was observed in 2016 in India which resulted in a further scarcity of already resource-poor specific diagnostic infrastructure even in many urban conglomerates. A cross-sectional study was thus conducted, on 978 fever patients that consulted the ICMR-NIMR fever clinic, New Delhi, in September 2016, with an objective to identify symptom/s that could predict chikungunya with certainty. The overall aim was to rationally channelize the most clinically suitable patients for the required specific diagnosis of chikungunya. Based on their clinical profile, febrile patients attending NIMR's clinic, appropriate laboratory tests and their association analyses were performed. Bivariate analysis on 34 clinical parameters revealed that joint pain, joint swelling, rashes, red spots, weakness, itching, loss of taste, red eyes, and bleeding gums were found to be statistically significantly associated predictors of chikungunya as compared to dengue. While, in multivariate analysis, only four symptoms (joint pain in elbows, joint swelling, itching and bleeding gums) were found in statistically significant association with chikungunya. Hence, based on the results, a clinician may preferably channelize febrile patients with one or more of these four symptoms for chikungunya-specific diagnosis and divert the rest for dengue lab diagnosis in a dengue-chikungunya syndemic setting.

A competing risk study of menarcheal age distribution based on non-recall current status data.

In many cross-sectional studies, the chances that an individual will be able to exactly recall the event are very low. The possibility of recalling the exact time as well as the cause of occurrence of an event usually decreases as the gap between event and monitoring time increases. This gives rise to non-recall current status data. In this article, an efficient approach to deal with such non-recall current status data is established in a competing risk set up. In the classical method, a nested Expectation-Maximization technique is worked out for the estimation purpose and the information matrix is evaluated using the missing information principle. In the Bayesian paradigm, point and interval estimates are obtained using the Gibbs sampling algorithm. A recent anthropometric study data containing the menarcheal status of girls and age at menarche is analyzed using the considered methodology.

Latent Growth Curve Modeling for COVID-19 Cases in Presence of Time-Variant Covariate.

For the past two years, the entire world has been fighting against the COVID-19 pandemic. The rapid increase in COVID-19 cases can be attributed to several factors. Recent studies have revealed that changes in environmental temperature are associated with the growth of cases. In this study, we modeled the monthly growth rate of COVID-19 cases per million infected in 126 countries using various growth curves under structural equation modeling. Moreover, the environmental temperature has been introduced as a time-varying covariate to enhance the performance of the models. The parameters of growth curve models have been estimated, and accordingly, the results are discussed for the affected countries from August 2020 to July 2021.

A systematic review and meta-analysis on sub-microscopic Plasmodium infections in India: Different perspectives and global challenges.

Background: The long-term maintenance of parasite biomass below the detection threshold of microscopy may stymie malaria elimination. Variation in microscopists' competencies to detect and correctly identify parasite species reflect in microscopy sensitivity, resulting in incorrect species-specific burden. Methods: The study estimated Plasmodium SMI pooled burden from published reports using a random effect model & identifies their hotspots in India. The study applied a prediction model for the first time on Indian data, emphasizing the importance of such models that can predict PCR-prevalence from slide- prevalence. Findings: A total of 17,449 samples from 39 districts were examined for Plasmodium by microscopy and PCR. The overall heterogeneity in clinic-based and community-based studies was 91% and 96%, respectively, with the pooled prevalence of 3.63%. The SMI prevalence in individual studies ranged from 38.4% to 0.4%. Sensitivity of microscopy for mono-P. vivax (91%) was found to be better than mono-P. falciparum (82 %). But surprisingly, it was much lower for mixed PfPv (45%). Interpretation: Primary regional data in the form of SMIs hot spots should be generated from countries on the verge of malaria elimination, and genetic monitoring should be integrated into national programs, particularly in key areas for successful malaria elimination. Funding: Not applicable.

Epidemiological profiles and associated risk factors of SARS-CoV-2 positive patients based on a high-throughput testing facility in India.

We describe the epidemiological characteristics and associated risk factors of those presenting at a large testing centre for SARS-CoV-2 infection. This is a retrospective record review of individuals who underwent SARS-CoV-2 testing by reverse transcription-polymerase chain reaction (RT-PCR) at a high-throughput national-level government facility located in the north of India. Samples collected from 6 April to 31 December 2020 are included in this work and represent four highly populous regions. Additionally, there was a prospective follow-up of 1729 cases through telephone interviews from 25 May 2020 to 20 June 2020. Descriptive analysis has been performed for profiling clinic-epidemiological aspects of suspect cases. Multivariable logistic regression analysis was undertaken to determine risk factors that are associated with SARS-CoV-2 test positivity and symptom status. A total of 125 600 participants' details have been included in this report. The mean (s.d.) age of the participants was 33.1 (±15.3) years and 66% were male. Among these tested, 9515 (7.6%) were positive for COVID-19. A large proportion of positive cases were asymptomatic. In symptomatic positive cases, the commonest symptoms were cough and fever. Increasing age (groups 20-59 and ≥60 years compared to age group less than 5 years), male sex, history of international travel, symptoms for SARS-CoV-2, and participants from Delhi and Madhya Pradesh were positively associated with SARS-CoV-2 test positivity. Having co-morbidity, risk behaviours and intra-familial positivity were associated with a positive odds ratio for exhibiting SARS-CoV-2 symptoms. Intensified testing and isolation of cases, identification of both asymptomatic and symptomatic individuals and additional care of those with co-morbidities and risk behaviours will all be collectively important for disease containment in India. Reasons for differentials in testing between men and women remain an important area for in-depth study. The increased deployment of vaccines is likely to impact the trajectory of COVID-19 in the coming time, and therefore our data will serve as a comparative resource as India experiences the second wave of infection in light of newer variants that are likely to accelerate disease spread.

Comparison of statistical methods for recurrent event analysis using pediatrics asthma data.

When the same type of event is experienced by a subject more than once it is called recurrent event, which possess two important characteristics, namely "within-subject correlation" and "time-varying covariate." As a result, the traditional statistical methods do not work well on recurrent event data. Over the past few decades, many alternatives methods have been proposed for the analysis of recurrent event data. In this article, the six most prominent methods for recurrent event analysis have been compared on pediatric asthma data. Three variance corrected models (viz "Anderson and Gill [AG] model," "Prentice, William, and Peterson-Counting Process [PWP-CP] model," and "Prentice, William, and Peterson-Gap Time [PWP-GT] model") and three corresponding frailty variants (AG-frailty, PWP-CP-frailty, and PWP-GT-frailty) were compared using three mathematical criterion (AIC, BIC, and log-likelihood) and one graphical criteria (Cox-Snell goodness of fit, visual test). All model comparison indices showed the PWP-GT model as the most appropriate model on asthma data over other models. By using PWP-GT model, seven predictors of asthma exacerbation (viz "abdominal pain at previous visit," "Z5 (%) at previous visit," "diagnosis of asthma at previous visit," "calendar month of exacerbation," "history of maternal asthma," "monthly per capita income," and "emotional stress") were identified. The PWP-GT model was identified as the most appropriate model over other models on pediatrics asthma data.

Delayed haemolysis after treatment with intravenous artesunate in patients with severe malaria in India.

BACKGROUND: Parenteral artesunate is the treatment of choice for severe malaria. It is safe, efficacious and well tolerated anti-malarial. However, delayed haemolysis has been reported in travellers, non-immune individuals and in African children. METHODS: A prospective, observational study was carried out in admitted severe malaria patients receiving parenteral artesunate. The patients were followed up until day 28 for monitoring clinical as well as laboratory parameters for haemolytic anaemia. RESULTS: Twenty-four patients with severe malaria receiving injection artesunate were enrolled in the study. Post-artesunate delayed haemolysis following parenteral artesunate therapy was observed in three of 24 patients (12.5%, 95% confidence interval 4.5-31.2%). Haemolysis was observed in two more patients possibly due to other reasons. The haemoglobin fall ranged from 13.6 to 38.3% from day 7 to day 28 in these patients. CONCLUSION: The possibility of delayed haemolysis should be considered while treating the severe malaria patients with parenteral artesunate. The study highlights the need for further studies in different epidemiological settings.

A new clinical respiratory distress score for surfactant therapy in preterm infants with respiratory distress.

The guidelines for surfactant therapy are largely based on studies done in developed coun1tries wherein the facility infrastructure, patient profile, and clinical practices are different from low- and middle-income countries (LMICs). Though SRT is widely practiced in developing countries, there exists variability in clinical practice. Our objective was to identify the factors which would predict the need of surfactant administration and develop a "clinical respiratory distress (RD) score" for surfactant administration in preterm neonates with respiratory distress. A prospective observational study was conducted in 153 preterm infants (260/7 to 346/7 weeks gestation) with respiratory distress who were managed with CPAP and/or surfactant where indicated. Gestation < 32 weeks, no antenatal corticosteroid (ANS), hypothermia at admission, Apgar score < 3 at 1 minute, and Silverman score > 2 at 2 hours were found to be the significant factors in predicting surfactant requirement in multivariate regression analysis. A seven point scale was developed and categorized into two categories as < 4 and ≥ 4. The sensitivity, specificity, PPV, and NPV were 67%, 87%, 86%, and 68%, respectively, with a cutoff score ≥ 4. The positive likelihood ratio was 5.07 (95% CI 2.71-9.48), and negative likelihood ratio was 0.38 (95% CI 0.28-0.52). The observed rate of surfactant administration was found to be around 32% when the composite score was below four, and the rate increased to almost 86% when the composite score was ≥ 4. The predictive accuracy of the model was subsequently evaluated in a cohort of 56 preterm infants with respiratory distress.. Sensitivity, specificity and positive and negative predictive value during the validation phase were 97%, 73%, 85%, and 94%, respectively. With a composite score less than 4, the observed rate of surfactant administration was 6% (95% CI 1%-28%) as against the model predicted rate of 24%, while with composite score ≥ 4, the observed rate was 85% (95% CI 69%-94%) as against the model predicted rate of 90%.Conclusion: "Clinical RD score" is a simple score, which can be utilized for decision-making for early surfactant administration for preterm infants (260/7 to 346/7 weeks gestation) with respiratory distress.Trial Registration: NCT03273764What is Known:• Both CPAP and surfactant therapy are effective in management of preterm infants with RDS.• The efficacy of surfactant replacement therapy is better when it is administered early in the course of disease.What is New:• Many of the known risk factors for RDS do not predict surfactant requirement.• "Composite RD score" comprising of five independent predictors of surfactant requirement with a numeric cutoff may help decide which preterm neonates with respiratory distress need early surfactant administration in low- and middle-income countries.

Effect of change in sequence of administration of DTwP and Hepatitis B vaccines on perception of pain in infants: A randomized control trial.

OBJECTIVE: This study was designed with objective to study pain response of infants to change in sequence of administration of Hepatitis B and DTwP vaccines. METHODS: This was a randomized parallel control trial. The study was carried out in the immunization clinic of the Department of Pediatrics, LLRM Medical College, Meerut. One hundred and thirty healthy term infants up to 4 months of age were injected either DTwP vaccine first or Hepatitis B vaccine first, followed one minute later by the other vaccine. RESULT: Baseline characteristics did not differ between the groups. The mean (SD) of AUC of MFCS and NIPS was significantly more in DF group as compared to HF group (for MFCS 25.5 ± 5.4 versus 22.5 ± 5.5, p<0.01; for NIPS 31.77 ± 5.5 versus 27.64 ± 6.9, p < 0.01). Similarly mean (SD) of AUC of Heart rate and saturation of oxygen showed significant variation in DF group as compared to HF group (for heart rate 591.6 ± 55 versus 559.6 ± 49, p< 0.01; for SpO2 326.4 ± 12 versus 335 ± 8, p < 0.01). CONCLUSION: These results showed that infant experienced lesser pain when Hepatitis B was administered first than when DTwP vaccine was given first.

Validity of non-invasive point-of-care hemoglobin estimation in healthy and sick children-a method comparison study.

This study was conducted at a tertiary care center in northern India to evaluate the validity of non-invasive transcutaneous hemoglobin estimation in healthy and sick children in comparison to hemoglobin estimation by traditional lab method. A method comparison study was conducted including 150 subjects. Enrolled patients included 80 neonates with average age of 3.9 ± 2.1 days, and 70 children with average age of 5.8 ± 2 years. Each population (newborn and children) comprised of almost equal numbers of healthy and critically ill patients with shock. Hemoglobin (Hb) was estimated on enrolment by transcutaneous spectrophotometry (SpHb) and traditional automated lab analyzer (Hb-Lab). Difference between Hb levels by the two methods (called bias) was measured and analyzed using Bland-Altman method. Out of 148 data pairs analyzed, bias between SpHb and Hb-Lab was -1.52 ± 1.91 g/dl (mean ± SD). SpHb showed excellent positive correlation with Hb-Lab (r = 0.94 (p < 0.001)) and good visual agreement on Bland-Altman plots. Bias was higher in sick subjects with shock as compared to healthy ones in both neonatal and pediatric population (-2.31 ± 2.21 g/dl versus -0.77 ± 1.2 g/dl, respectively). CONCLUSIONS: SpHb showed good accuracy and correlated well with lab estimated Hb levels in healthy children. However, in children with impaired peripheral perfusion, its diagnostic accuracy was inadequate to justify routine use for quantification of severity of anemia and making transfusion decisions solely on non-invasive estimation of hemoglobin. WHAT IS KNOWN: Non-invasive hemoglobin estimation is a relatively new and novel method which has given mixed results regarding its potential efficacy in adults. There is limited data regarding usefulness and accuracy of non-invasive Hb estimation by SpHb in sick neonates and children. WHAT IS NEW: Non-invasive Hb estimation by SpHb monitor is reasonably accurate in healthy neonates and children. It can be used in critically ill children and neonates, but in conjunction with lab confirmation of Hb values.

Comparison of three types of intervention to enhance placental redistribution in term newborns: randomized control trial.

OBJECTIVE: To compare the effect of combined delayed cord clamping and umbilical cord milking to either of them had done alone, on hematological parameters at 6 weeks of age in term neonates. STUDY DESIGN: It was a randomized controlled trial, conducted during January to December 2014. Three hundred eligible neonates were randomly allocated to three parallel groups. Primary outcome was hemoglobin and serum ferritin at 6 weeks of age. Data were analyzed using analysis of variance and Kruskal-Wallis test. RESULTS: Baseline characteristics and hemodynamic parameters were comparable in all the three groups. The median serum ferritin level at 6 weeks was significantly higher in the group receiving both delayed cord clamping and milking the cut cord group (295.49 (233.5 to 346.54) ng ml(-1)) as compared with the group that received only milking of the cut cord (184.55 (131.22 to 256.5) ng ml(-1)) or only delayed cord clamping (268.8 (189.4 to 315.44) ng ml(-1)). CONCLUSION: Delayed cord clamping with milking the cut cord improved iron stores at 6 weeks of age in term infants, then either of the two interventions alone.

Quantification of Oleanolic acid in the flower of Gentiana olivieri Griseb. by HPLC.

High Performance Liquid Chromatography (HPLC) method is a potent analytical technique for determining phytoconstituents even in minute quantities particularly that are generally present in traces concentrations in medicinal plants. The concentration of oleanolic acid (OA) in the Gentiana olivieri Griseb.(GOG) flowers is quantitatively determined by a simple, precise and accurate HPLC method. HPLC assay was performed on reversed-phase C18 column and compound was detected at 210 nm with a flow rate of 1.0 ml/min. The mobile phase consisted of methanol (A) and 0.03 mol/L phosphate buffer, pH 2.9 (B) with a ratio of 85:15 (A: B v/v).The method showed good precision and accuracy with overall intra-day and inter-day variation of 0.36-1.33% and 0.43-1.15%, respectively, and overall recoveries of 99.32%. Application of these methods to determine the OA in Gentiana olivieri Griseb showed that the concentration of OA was found more in the flower as compared to the whole aerial part (average amount in flower 1.82 mg/g DW and 0.75 mg/g DW in whole aerial plant). A simple and accurate HPLC method has been developed for quantitative determination of OA in GOG flowers.