Pan-Indian Clinical Registry of Invasive Fungal Infections Among Patients in the Intensive Care Unit: Protocol for a Multicentric Prospective Study.

BACKGROUND: Fungal infections are now a great public health threat, especially in those with underlying risk factors such as neutropenia, diabetes, high-dose steroid treatment, cancer chemotherapy, prolonged intensive care unit stay, and so on, which can lead to mycoses with higher mortality rates. The rates of these infections have been steadily increasing over the past 2 decades due to the increasing population of patients who are immunocompromised. However, the data regarding the exact burden of such infection are still not available from India. Therefore, this registry was initiated to collate systematic data on invasive fungal infections (IFIs) across the country. OBJECTIVE: The primary aim of this study is to create a multicenter digital clinical registry and monitor trends of IFIs and emerging fungal diseases, as well as early signals of any potential fungal outbreak in any region. The registry will also capture information on the antifungal resistance patterns and the contribution of fungal infections on overall morbidity and inpatient mortality across various conditions. METHODS: This multicenter, prospective, noninterventional observational study will be conducted by the Indian Council of Medical Research through a web-based data collection method from 8 Advanced Mycology Diagnostic and Research Centers across the country. Data on age, gender, clinical signs and symptoms, date of admission, date of discharge or death, diagnostic tests performed, identified pathogen details, antifungal susceptibility testing, outcome, and so on will be obtained from hospital records. Descriptive and multivariate statistical methods will be applied to investigate clinical manifestations, risk variables, and treatment outcomes. RESULTS: These Advanced Mycology Diagnostic and Research Centers are expected to find the hidden cases of fungal infections in the intensive care unit setting. The study will facilitate the enhancement of the precision of fungal infection diagnosis and prompt treatment modalities in response to antifungal drug sensitivity tests. This registry will improve our understanding of IFIs, support evidence-based clinical decision-making ability, and encourage public health policies and actions. CONCLUSIONS: Fungal diseases are a neglected public health problem. Fewer diagnostic facilities, scanty published data, and increased vulnerable patient groups make the situation worse. This is the first systematic clinical registry of IFIs in India. Data generated from this registry will increase our understanding related to the diagnosis, treatment, and prevention of fungal diseases in India by addressing pertinent gaps in mycology. This initiative will ensure a visible impact on public health in the country. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/54672.

The Development of a Clinical Registry Digital Database on Invasive Fungal Infections in India: Advancing Epidemiological Understanding and Patient Care.

A well-structured digital database is essential for any national priority project as it can provide real-time data analysis and facilitate quick decision making. In recent times, particularly after the COVID-19 pandemic, invasive fungal infections (IFIs) have emerged as a significant public health challenge in India, affecting vulnerable population, including immunocompromised individuals. The lack of comprehensive and well-structured data on IFIs has hindered efforts to understand their true burden and optimize patient care. To address this critical knowledge gap, the ICMR has undertaken a Pan-India pioneer initiative to develop a network of Advanced Mycology Diagnostic research centres in different geographical zones of the country (ICMR-MycoNet). Under the aegis of this project, a clinical registry on IFIs in the ICUs is initiated. This process paper presents a detailed account of the steps involved in the establishment of a web-based data entering and monitoring platform to capture data electronically, ensuring robust and secure data collection and management. This system not only allows participating ICMR-MycoNet centres to enter patient information directly into the database using standardized Case Report Form (CRF) but also includes data validation checks to ensure the accuracy and completeness of entered data. It is complemented by a real-time, web-based, and adaptable data visualization platform. This registry aims to provide crucial epidemiological insights, promote evidence-based hospital infection control programs, and ultimately improve patient outcomes in the face of this formidable healthcare challenge.

Evaluation of methods for assigning causes of death from verbal autopsies in India.

Background: Physician-coded verbal autopsy (PCVA) is the most widely used method to determine causes of death (COD) in countries where medical certification of death is low. Computer-coded verbal autopsy (CCVA), an alternative method to PCVA for assigning the COD is considered to be efficient and cost-effective. However, the performance of CCVA as compared to PCVA is yet to be established in the Indian context. Methods: We evaluated the performance of PCVA and three CCVA methods i.e., InterVA 5, InSilico, and Tariff 2.0 on verbal autopsies done using the WHO 2016 VA tool on 2,120 reference standard cases developed from five tertiary care hospitals of Delhi. PCVA methodology involved dual independent review with adjudication, where required. Metrics to assess performance were Cause Specific Mortality Fraction (CSMF), sensitivity, positive predictive value (PPV), CSMF Accuracy, and Kappa statistic. Results: In terms of the measures of the overall performance of COD assignment methods, for CSMF Accuracy, the PCVA method achieved the highest score of 0.79, followed by 0.67 for Tariff_2.0, 0.66 for Inter-VA and 0.62 for InSilicoVA. The PCVA method also achieved the highest agreement (57%) and Kappa scores (0.54). The PCVA method showed the highest sensitivity for 15 out of 20 causes of death. Conclusion: Our study found that the PCVA method had the best performance out of all the four COD assignment methods that were tested in our study sample. In order to improve the performance of CCVA methods, multicentric studies with larger sample sizes need to be conducted using the WHO VA tool.

Satellite Epidemic of Covid-19 Associated Mucormycosis in India: A Multi-Site Observational Study.

BACKGROUND: Sudden upsurge in cases of COVID-19 Associated Mucormycosis (CAM) following the second wave of the COVID-19 pandemic was recorded in India. This study describes the clinical characteristics, management and outcomes of CAM cases, and factors associated with mortality. METHODS: Microbiologically confirmed CAM cases were enrolled from April 2021 to September 2021 from ten diverse geographical locations in India. Data were collected using a structured questionnaire and entered into a web portal designed specifically for this investigation. Bivariate analyses and logistic regression were conducted using R version 4.0.2. RESULTS: A total of 336 CAM patients were enrolled; the majority were male (n = 232, 69.1%), literate (n = 261, 77.7%), and employed (n = 224, 66.7%). The commonest presenting symptoms in our cohort of patients were oro-facial and ophthalmological in nature. The median (Interquartile Range; IQR) interval between COVID diagnosis and admission due to mucormycosis was 31 (18, 47) days, whereas the median duration of symptoms of CAM before hospitalization was 10 (5, 20) days. All CAM cases received antifungal treatment, and debridement (either surgical or endoscopic or both) was carried out in the majority of them (326, 97.02%). Twenty-three (6.9%) of the enrolled CAM cases expired. The odds of death in CAM patients increased with an increase in HbA1c level (aOR: 1.34, 95%CI: 1.05, 1.72) following adjustment for age, gender, education and employment status. CONCLUSION: A longer vigil of around 4-6 weeks post-COVID-19 diagnosis is suggested for earlier diagnosis of CAM. Better glycemic control may avert mortality in admitted CAM cases.

Smokeless Tobacco Use and Cessation Attempts during COVID-19 Lockdown: A Qualitative Study.

BACKGROUND: Smokeless tobacco (SLT) use among women is widely prevalent in Manipur state accounting for 45% users as per Global Adult Tobacco Survey (GATS)-2 India. Studies from India and elsewhere indicate changes in the way people used SLT during COVID-19 lockdown. This study explores individual and economic influences on SLT consumption and cessation attempts by tribal women in Manipur during the first COVID-19 lockdown (March-June, 2020) in India. METHODS: Twenty in-depth interviews, both in-person and telephonically, were conducted among tribal women from Imphal west, Manipur, India, who used any SLT, from April to September 2020. Objective of the study was to understand the use, factors associated with consumption, purchasing behaviors, and cessation attempts of SLT during the lockdown. Thematic content analysis was used to identify core themes and codes. RESULTS: Study participants reported of changes in current SLT use during restrictions imposed to contain COVID-19 pandemic in India. Majority reported of reduction or quit attempts in SLT use. Reasons included inaccessibility due to travel restrictions, limited availability and price rise of SLT products, fear of COVID-19, and disposable income for purchase of SLT products. However, a few women reported of increased consumption due to bulk purchasing, or switching to other SLT products as a result of unavailability or price rise of preferred products or to cope up with social isolation caused by the lockdown. CONCLUSION: Study findings on factors influencing quit attempts and strategies used for reducing SLT use by tribal women in Imphal, Manipur provide valuable insights for development of appropriate intervention for prevention of SLT use among women.

Expedited diagnosis of pediatric tuberculosis using Truenat MTB-Rif Dx and GeneXpert MTB/RIF.

Rapid, cost-effective, and sensitive diagnostic assays are essential for global tuberculosis (TB) control, especially in high TB burden, resource-limited settings. The current study was designed to evaluate diagnostic accuracy of Truenat MTB-Rif Dx (MolBio) in children less than 18 years of age, with symptoms suggestive of TB. Gastric aspirate, induced sputum, and broncho-alveolar lavage samples were subjected simultaneously to AFB-smear, GeneXpert MTB/RIF, liquid culture (MGIT-960) and Truenat MTB-Rif Dx. The index-test results were evaluated against microbiological reference standards (MRS). Truenat MTB-Rif Dx had a sensitivity of 57.1%, specificity of 92% against MRS. The sensitivity and specificity of the Truenat MTB-RIF Dx compared with liquid culture was 58.7% and 87.5% while GeneXpert MTB/RIF was 56% and 91.4%. The performance of both GeneXpert MTB/RIF and Truenat MTB-Rif Dx are comparable. Result of our study demonstrates that Truenat MTB-Rif can aid in early and efficient diagnosis of TB in children.

Age adjusted Charlson comorbidity index (a-CCI) AS a tool to predict 30-day post-operative outcome in general surgery patients.

INTRODUCTION: Age adjusted Charlson comorbidity index (a-CCI) is an established scoring system to predict long-term mortality. However, its role in predicting 30-day post-operative outcome in general surgery patients is not well elucidated. METHODS: This was a prospective observational study. Consecutive patients operated under general anaesthesia between January 2019 and December 2020 were enrolled. Their a-CCI was calculated and stratified as Grade 0 comorbidities (a-CCI score = 0), Grade A comorbidities (a-CCI score = 1 and 2) and Grade B comorbidities (a-CCI score ≥ 3). Post-operative complications were graded according to Clavien Dindo (CD) grading system and classified as minor complications (CD Grades I and II), major complications (CD Grades III-IV) and mortality (CD Grade V). Binary logistic regression and multi-nominal logistic regression analysis were done and relative risk ratios were calculated. RESULT: A total of 925 patients were enrolled. The mean age was 42.75 (14-85 ± 10) years. 31% of our patients had complications within 30 days of surgery which included mortality in 2.7%. Compared with patients with Grade 0 comorbidities, the odds of getting complications is 1.2 times more in patients with Grade A comorbidities and 1.84 times more in patients with Grade B comorbidities (P = 0.205, 0.001 respectively). In comparison to patients with Grade 0 co-morbidities, risk of mortality is 3 and 17.86 times more in patients with Grade A and Grade B comorbidities (P = 0.121 and < 0.001 respectively). CONCLUSION: a-CCI has clinical relevance in general surgical patients and can predict early post-operative outcome. It should be a part of our armamentarium for pre-operative assessment of surgical patients.

A case control investigation of COVID-19 associated mucormycosis in India.

BACKGROUND: Increased occurrence of mucormycosis during the second wave of COVID-19 pandemic in early 2021 in India prompted us to undertake a multi-site case-control investigation. The objectives were to examine the monthly trend of COVID-19 Associated Mucormycosis (CAM) cases among in-patients and to identify factors associated with development of CAM. METHODS: Eleven study sites were involved across India; archived records since 1st January 2021 till 30th September 2021 were used for trend analysis. The cases and controls were enrolled during 15th June 2021 to 30th September 2021. Data were collected using a semi-structured questionnaire. Among 1211 enrolled participants, 336 were CAM cases and 875 were COVID-19 positive non-mucormycosis controls. RESULTS: CAM-case admissions reached their peak in May 2021 like a satellite epidemic after a month of in-patient admission peak recorded due to COVID-19. The odds of developing CAM increased with the history of working in a dusty environment (adjusted odds ratio; aOR 3.24, 95% CI 1.34, 7.82), diabetes mellitus (aOR: 31.83, 95% CI 13.96, 72.63), longer duration of hospital stay (aOR: 1.06, 95% CI 1.02, 1.11) and use of methylprednisolone (aOR: 2.71, 95% CI 1.37, 5.37) following adjustment for age, gender, occupation, education, type of houses used for living, requirement of ventilatory support and route of steroid administration. Higher proportion of CAM cases required supplemental oxygen compared to the controls; use of non-rebreather mask (NRBM) was associated as a protective factor against mucormycosis compared to face masks (aOR: 0.18, 95% CI 0.08, 0.41). Genomic sequencing of archived respiratory samples revealed similar occurrences of Delta and Delta derivates of SARS-CoV-2 infection in both cases and controls. CONCLUSIONS: Appropriate management of hyperglycemia, judicious use of steroids and use of NRBM during oxygen supplementation among COVID-19 patients have the potential to reduce the risk of occurrence of mucormycosis. Avoiding exposure to dusty environment would add to such prevention efforts.

Predictors of smokeless tobacco use among the adult population of north-east India during 2009-2017: A decomposition analysis.

Background & objectives: Contrary to overall declining trend in smokeless tobacco (SLT) use in India, an increase is observed in north-east (NE) India. This study examined the predictors of daily SLT use by gender and assessed the demographic and socio-economic characteristics that contribute to gender differences in SLT use in NE India. Methods: Data collected from 15,259 and 13,574 adults in the two rounds of Global Tobacco Adult Survey 1 and 2 for NE India during 2009-2010 and 2016-2017 were analyzed. Relative change, multivariable binary logistic regression and Blinder-Oaxaca decomposition analysis were used for analysis. Results: The findings suggest that among women in NE India, the daily SLT use significantly increased by 58 per cent between 2009-2010 to 2016-2017. Women residing in Nagaland, Manipur, Mizoram and Tripura were 3.5 and 2.5 times, respectively more likely to be daily SLT users compared to those in Assam. While age, education and wealth were the significant predictors of SLT use in both women and men, increased odds of SLT use were observed with women's type of occupation and the State of residence. The majority of the gender differences in daily SLT use was explained by differences in work status (44%), age (26%), education (14%) and wealth status (9%) between men and women. Interpretation & conclusions: Increasing prevalence of SLT use amongst women in the NE States necessitates integration of gender-specific messages on harmful effects of SLT in the ongoing tobacco control programmes and development of culturally appropriate community-based interventions for cessation of SLT use.