Dapsone for paediatric chronic immune thrombocytopenia: Short report from a tertiary centre in South India.

Immune thrombocytopenia (ITP) resolves in most children within 3-12 months of diagnosis. Chronic ITP affects 10%-20% of patients, some of whom require treatment. Several second-line agents are efficacious in this group of patients. This paper describes our experience of using dapsone as a single second-line agent in children with chronic ITP. One hundred and three children with chronic ITP were seen at our centre from January 2012 to December 2016. Forty-five children met the inclusion criteria and received dapsone; 17 (37.8%) were boys; and 28 (62.2%) were girls. Early response to dapsone was seen in 37.8% of patients. The median duration of long-term follow-up was 50 months, and at least a partial response was seen in 64.4% of the patients. Dapsone offers good initial response rates and sustained remission in paediatric chronic ITP, comparable to other therapeutic agents available.

Nutritional Prescription in ICU Patients: Does it Matter?

Background: The nutritional status of the patients before critical illness and nutrition support given during the critical illness play an important role in the recovery. We aimed to evaluate the nutritional prescription and its effect on ICU mortality. Materials and methods: This was a prospective observational study conducted after institutional ethical committee approval (IEC 94/2018, CTRI/2018/06/014625) in a case-mixed (medical and surgical) ICU. Patients admitted to the ICU were enrolled within 24 hours of admission. The amount of calories and proteins prescribed and received by the patients was collected for 7 days. The primary outcome was ICU mortality. Results: A total of 100 patients were included. The mean age was 48.63 (16.25) years, and 62% were males. The acute physiology and chronic health evaluation (APACHE II), sequential organ failure assessment (SOFA), and modified Nutric (mNUTRIC) scores were comparable between the two groups. The ICU mortality was 30%. The calorie and protein deficits were comparable between survivors and non-survivors. Among the secondary outcomes, a significant time effect (p = 0.013) and interaction effect (p = 0.004) were noted for maximum glucose levels. The glucose variability calculated by coefficient of variation (CV) was significantly higher in non-survivors than survivors (p = 0.031). Conclusion: The calorie and protein deficits did not affect ICU mortality. The maximum glucose variability and CV were significant parameters associated with ICU mortality. How to cite this article: Havaldar AA, Selvam S. Nutritional Prescription in ICU Patients: Does it Matter? Indian J Crit Care Med 2024;28(7):657-661.

Estimation of the effect of vaccination in critically ill COVID-19 patients, analysis using propensity score matching.

BACKGROUND: Vaccination helped in reducing mortality and disease severity due to COVID-19. Some patients can develop breakthrough infections. The effect of vaccination in critically ill patients admitted with breakthrough infections is not well studied. We designed a study to estimate the effect of vaccination on ICU mortality in critically ill COVID-19 patients by using propensity score matching. METHODS: We included patients from 15th June 2020 to 31st December 2021. Inclusion criteria were unvaccinated and vaccinated COVID-19 patients requiring intensive care unit (ICU) admission. The institutional ethics committee approval was obtained (institutional ethics committee, IEC 08/2023, Clinical trial registry, India CTRI/2023/01/049142). The primary outcome was ICU mortality. The secondary outcomes were the length of ICU stay and duration of mechanical ventilation. We used multivariable logistic regression (MLR) and propensity score matching (PSM) for the statistical analysis. RESULTS: Total of 667 patients (79.31%) were unvaccinated and 174 (20.68%) vaccinated. The mean age was 57.11 [standard deviation (SD) 15.13], and 70.27% were males. The ICU mortality was 56.60% [95% confidence interval (CI) 53.24-60%]. The results of MLR and PSM method showed that vaccinated patients were less likely to be associated with mortality [adjusted odds ratio (AOR), 95% CI using logistic regression: 0.52 (0.29, 0.94), and by propensity score matching: 0.83 (0.77, 0.91)]. CONCLUSION: The findings of this study support COVID-19 vaccination as an effective method for reducing case fatality not only in the general population but also in critically ill patients, and it has important public health implications.

Development and evaluation of the Indian Sleepiness Scale to assess excessive daytime sleepiness in patients with Obstructive Sleep Apnea.

Background: Excessive daytime sleepiness (EDS), a cardinal symptom of obstructive sleep apnea (OSA) is assessed using Epworth Sleepiness Scale (ESS). Some limitations of ESS include graded responses, inapplicable situations and equal scores for active and passive situations. To overcome these limitations, we developed a novel sleepiness scale and evaluated its performance in patients with OSA. Methods: The study was executed in multiple phases. After determining applicability of items in the ESS, a 6-item questionnaire was developed comprising OSA symptoms and self-reported 'sleepy' situations, dichotomized responses and weighted scoring. After content and face validation by experts, the scale was tested for applicability and its performance was compared with ESS in patients with suspected OSA. Results: In phase I, applicability of ESS was tested in 189 participants, of whom 98 (51.8 %) participants found multiple items inapplicable.In phase II, 34 self-reported sleepy situations from 200 participants were narrowed down to a 6-item questionnaire, based on expert validation. This scale was named the Indian Sleepiness Scale (ISS) and was tested for applicability in phase III in 226 participants from diverse literacy backgrounds, who found all situations applicable.In phase IV, ISS and ESS were administered to 335 patients with suspected OSA. OSA was confirmed on polysomnography in 294 (87.7 %) patients. A cut-off score of ≥6 was derived for ISS; at this cut-off score, the ISS which was more sensitive than ESS (71.1 % vs 43.2 %). Conclusions: The Indian Sleepiness Scale was found to be widely applicable and more sensitive than ESS for sleepiness evaluation in patients with OSA.

Exploratory clinical subgroup clustering in systemic sclerosis: Results from the Indian Progressive Systemic Sclerosis Registry.

Objective: To conduct an exploratory cluster analysis of systemic sclerosis patients from the baseline data of the Indian systemic sclerosis registry. Methods: Patients satisfying American College of Rheumatology-European League Against Rheumatism classification criteria for systemic sclerosis were included. The clusters formed using clinical and immunological parameters were compared. Results: Of the 564 systemic sclerosis registry participants, 404 patients were included. We derived four clusters of which three were anti-topoisomerase I predominant and one was anti-centromere antibody 2 dominant. Cluster 1 (n-82 (20.3%)) had diffuse cutaneous systemic sclerosis patients with the most severe skin disease, anti-topoisomerase I positivity, males, younger age of onset and high prevalence of musculoskeletal, vasculopathic and gastrointestinal features. Cluster 2 (n-141 (34.9%)) was also diffuse cutaneous systemic sclerosis and anti-topoisomerase I predominant but with less severe skin phenotype than cluster 1 and a lesser prevalence of musculoskeletal, vasculopathic and gastrointestinal features. Cluster 3 (n-119 (29.5%)) had limited cutaneous systemic sclerosis patients with anti-topoisomerase I positivity along with other antibodies. The proximal muscle weakness was higher and digital pitting scars were lower, while other organ involvement was similar between clusters 2 and 3. Cluster 4 (n-62 (15.30%)) was the least severe group with limited cutaneous systemic sclerosis and anti-centromere antibody predominance. Age of onset was higher with low musculoskeletal disease and a higher presence of upper gastrointestinal features. The prevalence of interstitial lung disease was similar in the three anti-topoisomerase I predominant clusters. Conclusion: With exploratory cluster analysis, we confirmed the possibility of subclassification of systemic sclerosis along a spectrum based on clinical and immunological characteristics. We also corroborated the presence of anti-topoisomerase I in limited cutaneous systemic sclerosis and the association of interstitial lung disease with anti-topoisomerase I.

Nutritional Status and Body Composition at Diagnosis, of South Indian Children with Acute Lymphoblastic Leukaemia (ALL).

BACKGROUND: Accurate estimation of body composition, particularly, Body Cell Mass (BCM), which is independent of hydration status is important in children with cancer. This study aimed to accurately measure the anthropometry and body composition of children with Acute Lymphoblastic Leukaemia (ALL) at diagnosis and compare them with healthy children from South India. METHODS: This was a cross-sectional study in children aged 2 to 8 y with ALL from St. John's Medical College Hospital, Bengaluru, and age and sex-matched, normal-weight children recruited as controls from communities. Anthropometry (weight, height, circumferences), skinfolds and body composition measurements using a whole-body potassium counter were performed. Body mass index-for-age, weight and height for age z-scores were calculated using WHO child growth standards. Biochemical markers, dietary intake and physical activity details were recorded. Categorical and continuous variables were analyzed by chi-square and independent t-tests respectively.     Results: The mean age of the children with ALL (n = 39) was 4.6±1.9 y and control group (n=39) was 4.7±1.9 y; 61.5% were boys. The prevalence of underweight, overweight/obesity and stunting were 17.9%, 7.7%, and 10.3% respectively. The mean weight and height, of children with ALL and children in the control group were 16.8±6.2 kg and 16.4±4.1 kg, 104.3±14.9 cm and 105.1±12.2 cm, respectively with no statistical difference. Children with ALL showed lower body cell mass index kg/m2 (4.6± 0.8), compared to children in the control group (4.7±0.9) p=0.527, but higher fat mass index kg/m2 (3.6±1.1 vs. 3.4±0.8) p=0.276. CONCLUSION: At diagnosis, anthropometric and body composition measurements were similar between children with ALL and children in the control group. The BCM showed a non-significant trend of being lower in children with ALL, which requires close monitoring during treatment. Evaluating early-stage nutritional status and body composition can help in planning appropriate interventions during treatment to prevent long term non-communicable diseases.

Two by Two Factorial Design using Metformin and Curcumin for Second Primary Head and Neck Cancer Prevention Trial.

OBJECTIVE: The 2x2 factorial design is an effective method that allows for multiple comparisons, especially in the context of interactions between different interventions, without substantially increasing the required sample size. In view of the considerable preclinical evidence for Curcumin and Metformin in preventing the development and progression of head and neck squamous cell carcinoma (HNSCC), this study describes the protocol of the clinical trial towards applying the drug combination in prevention of second primary tumors. METHODS: We have applied the trial design to a large phase IIB/III double-blind, multi-centric, placebo-controlled, randomized clinical trial to determine the safety and efficacy of Metformin and Curcumin in the prevention of second primary tumours (SPT) of the aerodigestive tract following treatment of HNSCC (n=1,500) [Clinical Registry of India, CTRI/2018/03/012274]. Patients recruited in this trial will receive Metformin (with placebo), Curcumin (with placebo), Metformin, and Curcumin or placebo alone for a period of 36 months. The primary endpoint of this trial is the development of SPT, while the secondary endpoints are toxicities associated with the agents, incidence of recurrence, and identifying potential biomarkers. In this article, we discuss the 2x2 factorial design and how it applies to the head and neck cancer chemoprevention trial. CONCLUSION: 2x2 factorial design is an effective trial design for chemoprevention clinical trials where the effectiveness of multiple interventions needs to be tested parallelly.

A Study of the Profile and the Impact of Diabetes, Steroid and Stress Hyperglycaemia on COVID-19 Outcomes.

Background: Diabetes Mellitus (DM) and hyperglycaemia (HG) have been identified as risk factors for morbidity and mortality in coronavirus disease 19 (COVID-19) infection. However, a detailed study of various categories of HG and the impacts and characteristics of each of these on COVID-19 was considered important to address this metabolic disorder in COVID-19. Aims: This study aimed to describe the patterns of HG and its impact on the clinical outcomes in hospitalised patients with COVID-19 infection. Methodology: Data on 1000 consecutive patients with COVID-19 were analysed using Statistical Package for Social Sciences (SPSS) version 20.0 software (SPSS Inc., Chicago, IL, USA). Results: A total of 1000 patients were included for analysis The overall mean age of the study group was 52.77 + 19.71 with 636 (63.6%) male patients; 261 had mild, 317 moderate, and 422 severe infections; and 601 had HG (New-onset DM 66, known DM 386, steroid-induced HG 133 and stress HG 16). The HG group has significantly higher levels of inflammatory markers and worse outcomes. Blood glucose levels were higher in patients with known DM. The ROC cut-off of total steroids to predict mortality in the HG group was 84 mg versus 60 mg in the normoglycaemia group. The ROC cut-off of FBS to predict mortality in the overall HG group was 165, with AUC 0.58 (95% CI 0.52, 0.63, P = 0.005), whereas that for pre-existing DM and steroid HG were 232 and 166, which were also significant. There was a wide variation in mean glucose levels against time. Conclusion: HG is an independent predictor of mortality, with the highest significance in the steroid-induced category. COVID-19 morbidity and mortality can be minimised by identifying the blood glucose range for best results and instituting appropriate treatment guidelines.