Interplay of missed opportunity for vaccination and poor response to the vaccine led to measles outbreak in a slum area of Eastern Mumbai, India.

In the third week of September 2022, an outbreak of measles was reported from a slum in Eastern Mumbai, India. We sought to investigate whether failure to vaccinate or vaccine failure was the cause. We constructed an epidemic curve, drew a spot map, and calculated the attack rate and case-fatality ratio. We calculated vaccine effectiveness (VE) for one and two doses of measles vaccine in an unmatched case-control study and did stratified analysis by sex, availability of vaccination card, and migrant status. We identified 358 cases and four deaths with a 11.3% attack rate and 1.1% case fatality, both being highest among 0-24-month-old boys. The epidemic curve suggested a propagated mode of spread. The VE for two doses was 64% (95% confidence interval (CI): 23-73%) among under-5-year-old children and 70% (95% CI: 28-88%) among 5-15-year-old children. Failure to vaccinate, consequent to the COVID-19 pandemic, and vaccine hesitancy might have led to the accumulation of susceptible children in the community. Additionally, the occurrence of case-patients among vaccinated suggests reduced VE, which needs further investigation into humoral and cell-mediated immunity as well as contributory factors including nutritional status. Outbreak response immunization to complete immunization of missed and dropout children was carried out to control the outbreak.

Influence of tissue factor polymorphisms (603A>G and 5466A>G) on plasma tissue factor levels and their impact on deep vein thrombosis risk in young Indian population.

Deep vein thrombosis (DVT) is multifactorial disorder and well known to cause substantial morbidity and mortality. There is sparse data in the Asian population, particularly India regarding association of tissue factor (TF) gene single nucleotide polymorphisms (SNPs) with plasma TF levels in DVT. So, we analyzed the distribution of SNPs (603A>G and 5466A>G) in India, to evaluate their effect on TF levels in DVT patients. Plasma level and SNPs (603A>G and 5466A>G) of TF gene were screened in subjects (100 DVT patients and 100 controls). Patients had significantly higher TF levels than controls (patients: 84.95 ± 17.16 pg/ml, controls: 70.55 ± 15.87 pg/ml, p < 0.001). G allele of 603A>G polymorphism was significantly higher in patients than controls (patients: 40.5% controls: 27.5%, p = 0.004). Subjects with AG and GG genotype had significantly higher TF levels than AA genotype (p = 0.001). After multiple logistic regression analysis, risk of DVT was increased 1.398 fold (95% CI 0.738-2.651) and 4.41 fold (95% CI 1.404-13.884) with AG and GG genotype respectively. Allelic and genotypic frequencies of 5466A>G polymorphism was neither associated with TF levels nor with DVT. We found high TF level in patients with TF 603A>G polymorphism, which is an important predisposing factor in increasing risk of DVT in young Indians. Furthermore, GG genotype of 603A>G polymorphism augments the risk of thrombosis by 4.4 fold, thus highlighting the significance of this polymorphism in the development of DVT. So, we suggest that inclusion of 603A>G polymorphism in prothrombotic work-up may be helpful in making the treatment strategy in DVT patients.

Evaluation of role of FV, FVIII and APLAs in the pathogenesis of APCR in FV Leiden negative DVT patients: a study in India.

Resistance to APC (APCR) is a very important cause of thrombophilia and most frequently caused by the Leiden mutation. APCR is also seen in the absence of FV Leiden and associated with elevated levels of factor V (FV), factor VIII (FVIII) and antiphospholipid antibodies (APLAs). The aim of this prospective case control study was to find out the frequency and role of FV, FVIII and APLAs in the pathogenesis of APCR in FV Leiden negative deep vein thrombosis (DVT) patients in India. A total 30 APCR positive and FV Leiden negative patients with DVT and similar number of age and sex matched healthy controls were recruited. Significantly higher mean FVIII levels were observed in patients as compared to controls [patients: 132.3 ± 30.7 IU/ml, controls: 117.5 ± 17.7 IU/ml, p = 0.025]. A significant negative correlation was also observed between FVIII and APC ratio (Pearson correlation = 0.368, p = <0.001). Mean FV levels in patients [107.1 ± 13.1 IU/ml] and controls [102 ± 11.9 IU/ml] were not statistically significant (p = 0.119). Anti ß2 glycoprotein I (Anti-ß2-GPI, IgG) showed significant association with APCR phenotype (p = 0.050), unlike other factors such as protein C, protein S, lupus anticoagulant and anticardiolipin antibodies. The strong association of FVIII and anti-ß2 GPI (IgG) antibodies with APCR phenotype is suggestive of incorporation of these factors in APCR positive DVT patients in the absence of FV Leiden mutation in India. However more studies in large sample size are required for setting up the proper investigation protocol in these patients.

Prognostic models for prediction of outcomes after traumatic brain injury based on patients admission characteristics.

OBJECTIVE: To identify the best performing prognostic model using admission characteristics to predict mortality at 30 days and functioning outcome at 6-months post-admission in patients with moderate or severe brain injury. METHODS: Using a retrospective database (n = 1466 patients) of a tertiary trauma care centre, three different models were developed using logistic regression methods for predicting mortality and functioning outcome. The performance of the models was assessed in terms of discrimination and calibration. The models were validated using split sample method. For facilitating clinical usefulness, score charts were derived from the regression models. RESULTS: The variables motor score, hypotension, pupillary reactivity, age, creatinine level, limb movement (hemiparesis), and tSAH/IVH were found to be the most predictive independent prognostic factors of both mortality and functioning outcome. For both the outcomes, discriminative ability of the three prognostic models was excellent in the development dataset (AUC = 0.845--0.905) as well as the validation data set (AUC = 0.836-0.880). Calibration in the validation data set for model-2 was good (H-L test p-value > 0.05); however, for model-1 and model-3, it was poor (H-L test p-value < 0.05). CONCLUSION: For clinical decision-making, model-2 is recommended on the basis of good performance in predicting outcomes in patients with moderate or severe TBI in India and other similar countries.

Level of Awareness of Various Aspects of Lung Cancer Among College Teachers in India: Impact of Cancer Awareness Programmes in Prevention and Early Detection.

Lung cancer is one of the most common causes of cancer mortality among men in India and incidence is increasing, but actually, they are largely preventable diseases. In India, advanced stage at the time of presentation is responsible for high mortality and morbidity and early detection is the only way to reduce it. The purpose of this study is to know the level of awareness of various aspects of lung cancer among college teachers and impact of awareness programmes in its prevention and early detection. This assessment was part of Pink Chain Campaign-a campaign on cancer awareness. During the cancer awareness events in 2011-2013 at various women colleges in different parts in India, pre-test related to lung cancer was followed by awareness programme. Post-test using the same questionnaire was conducted at the end of interactive session, at 6 months and 1 year. A total of 872 out of 985 teachers participated in the study (overall response rate was 88.5 %). Mean age of the study population was 41.6 years (range 26-59 years). There was a significant increase in the level of knowledge regarding lung cancer at 6 months, and this was sustained at 1 year. Among teachers who were just asked yes or no question, 117 teachers (13.4 %) were smokers and 241 teachers (27.6 %) were alcoholics. Magazines and newspapers were sources for knowledge in 50-60 % of teachers, whereas approximately 30 % of teachers were educated by TV and Internet regarding various aspects of lung cancer. Post awareness at 6 months and 1 year, Pink Chain Campaign was the major source of knowledge related to lung cancer in more than 90 % of teachers by continuous and timely update on subject. Post awareness at 6 months and 1 year, there was a significant change in alcohol and smoking habits. Major reasons for not going for check-up were ignorance (83.1 %), fear (30.1 %) and lethargic attitude (29.3 %) initially, but over time, lack of time, lethargic attitude and hesitation became important factors after knowing various aspects of lung cancer. Knowledge of lung cancer was very low among teachers. Overall awareness of risk factors, sign and symptoms, screening modalities of lung cancer has improved in a year along with practices related to smoking and alcohol, but there was not much improvement in people undergoing regular check-ups. To inculcate safe practices in the lifestyle of people, awareness programmes such as the Pink Chain Campaign should be conducted more widely and frequently.

Association of TNF-α-(308(GG)), IL-10(-819(TT)), IL-10(-1082(GG)) and IL-1R1(+1970(CC)) genotypes with the susceptibility and progression of leprosy in North Indian population.

Leprosy is an infectious disease caused by M. leprae. We analyzed 48 cytokine polymorphisms in 13 (pro as well as anti-inflammatory) cytokine genes using PCR-SSP assay in 102 leprosy patients and 120 healthy controls with intent to find out a link between cytokine polymorphisms and disease susceptibility. TNF-α (-308) GG, IL-10 (-819) TT, IL-10 (-1082) GG and IL1R (+1970) CC genotypes are found to be predominant (p=0.01, p=0.02, p=0.0001 and p=0.001, respectively) in both tuberculoid as well as lepromatous leprosy patients. This observation suggests these genotypes as play the central role(s) in the progression of disease. CBA assay demonstrates the varied serum concentration of these cytokines with respect to their genotypes. The above genotypes appeared as high producer genotypes in our study. Even in presence of high produce genotypes, TNF-α level are found to be affected/masked by the presence of IL-10 in leprosy patients. Expressional masking of TNF-α is associated with the expression of IL-10 in these patients. This is one the negative impact of SNP-SNP interaction in leprosy patients. Therefore, we can conclude that cytokine gene polymorphisms determine the predisposition to the leprosy progression.

Polymorphisms in factor V and antithrombin III gene in recurrent pregnancy loss: a case-control study in Indian population.

Recurrent pregnancy loss (RPL) can be caused due to diverse factors with thrombophilia being one of them. The association of various thrombophilic risk factors with RPL is inconsistent in different studies and the frequency of these risk factors in Indian population is obscure. Five hundred and eighty patients with either recurrent early miscarriage or a history of at least one late miscarriage were screened for deficiency of protein C (PC), protein S (PS), antithrombin III (AT), APC resistance and prothrombin 20210G > A mutation. APC resistance positive patients were typed for the factor V Leiden, factor V Hong Kong/Cambridge mutations, and HR2 haplotype. PstI and rs2227589 AT mutations were detected by direct sequencing. APC resistance (13.4 %) was detected to be most common in Indian RPL patients followed by PS (10.6 %), PC (9.8 %) and AT deficiency (4.31 %.). FV Leiden was shown to be associated with APC resistance while HR2 haplotype was not associated with APC resistance (p values: 0.0001 and 0.327 respectively) and the increased risk of RPL. PstI and rs2227589 polymorphisms were similar in patients and controls and not associated with AT deficiency in RPL. Our study emphasizes the presence of other contributory factors towards APC resistance rather than FV Leiden alone. This is the first Indian study where HR2 haplotype and rs2227589 are observed to be present in RPL population. Although not significant, occurrence of rs2227589 and FV HR2 in homozygous condition necessitates the study of these polymorphisms in a larger sample size.

Assessment of Bone Thickness at the Infra Zygomatic Crest Region for Various Orthodontic Miniscrew Implant (OMSI) Insertion Angles: A Cone-Beam Computed Tomographic Study.

Objective: To evaluate the infrazygomatic crest (IZC) bone and develop guidelines for the optimum placement of orthodontic miniscrew implants (OMSIs) along the distobuccal root of the permanent maxillary first molar. Methods: Bone thickness of the IZC region of 50 young adults (25 males and 25 females) aged 18-30 years were evaluated using cone-beam computed tomography images. The infrazygomatic bone thickness along the distobuccal root of the permanent maxillary first molar was assessed at various insertion angles (40° to 75° i.r.t the maxillary occlusal plane) with an increment of 5°. Student's t-test was used to compare the IZC bone thickness and height at the orthodontic miniscrew insertion site for males and females on the right and left sides. Results: The bone thickness of the IZC region above the distobuccal root of the permanent maxillary first molar was estimated between 4.39±0.25 mm and 9.03±0.45 mm for insertion angles from 40° to 75° to the maxillary occlusal plane. The corresponding OMSI insertion heights were 17.71±0.61 mm to 13.69±0.75 mm, respectively, above the maxillary occlusal plane. There were statistically significant gender and side-wise variations in bone thickness at the IZC area and insertion height. Conclusion: The safe position for OMSI placement at the IZC was 13.69-16 mm from the maxillary occlusal plane with an insertion angle between 55° and 75°. These parameters provide the optimum placement of OMSIs along the distobuccal root of the permanent maxillary first molar.

Does the use of platelet-rich fibrin enhance the rate of orthodontic tooth movement? A systematic review and meta-analysis.

Introduction: This review synthesizes the available evidence pertinent to the effect of platelet-rich fibrin on the rate of orthodontic tooth movement during comprehensive orthodontic treatment. Method: This review followed the Preferred Reporting Items for Systematic Review and Meta-Analysis guidelines. Nine electronic databases were searched until January 2024 without restrictions, followed by a hand search of the reference lists. Controlled randomized split-mouth human studies assessing the effect of platelet-rich fibrin on the rate of orthodontic tooth movement were included. All relevant data from the included studies were extracted and pooled for qualitative and quantitative analysis. Risk-of-Bias was assessed using the Cochrane Risk of Bias tool. The certainty of the evidence was graded using the Grading of Recommendations, Assessment, Development, and Evaluation tool. Results: From 515 studies, eleven randomized clinical trials were included for qualitative analysis and nine for quantitative analysis. The certainty of the evidence for these studies was low to moderate. The overall risk of bias for most studies was of some concern. The pooled estimate of the data from ten studies has a mean revealed difference of 1.31 (0.13-2.48) at a 95 % confidence interval with significant heterogeneity. Conclusions: This systematic review suggest that platelet-rich fibrin enhances the orthodontic tooth movement rate, but the evidence quality was moderate. Further, based on the currently available evidence, the effectiveness of platelet-rich fibrin on the acceleration of orthodontic tooth movement could not be fully established. Trial registration: PROSPERO: (CRD42021261836).

Prevalence and risk factors associated with undiagnosed diabetes in India: Insights from NFHS-5 national survey.

Background: Undiagnosed diabetes is a significant public health concern in India, considering the accumulative burden of diabetes and its long-term complications. We have estimated the prevalence and factors associated with undiagnosed diabetes in India. Methods: We used data from the fifth round of the National Family Health Survey (NFHS-5, 2019-21) to estimate undiagnosed diabetes prevalence aged under 50 (15-49) years. A log-binomial model with survey-adjusted Poisson regression was used to estimate the prevalence risk ratio (PR) between undiagnosed diabetes and various factors. Multinomial logistic regression analysis was performed to examine the factors associated with diagnosed diabetes (vs. healthy) and undiagnosed diabetes (vs. healthy). All the analyses were survey-weighted and stratified by gender and reported with 95% confidence intervals. Results: The prevalence of diabetes for individuals aged 15-49 years was found to be 4.90% (4.80 to 5.00%) from the NFHS-5. Among them, the proportion of individuals with undiagnosed diabetes was 24.82% (24.07 to 25.59%), with higher among males (28.82% (26.45 to 31.30%)) than females (24.22% (23.44 to 25.01%)). The overall prevalence of undiagnosed diabetes was 1.22% (1.18 to 1.26%), with a higher prevalence among males (1.60% (1.46 to 1.76%)) than females (1.17% (1.13 to 1.21%)). Individuals who are middle-aged (45-49), have a higher body mass index (BMI), and are in a lower wealth index group, or live in the southern regions of India are at a higher risk of being undiagnosed for diabetes. Conclusion: One in every four having diabetes is undiagnosed. The study highlights the need for public health interventions to improve diabetes screening and access to health care, particularly among middle-aged individuals, and those with higher BMI, as well as addressing lifestyle and dietary factors. The findings also reveal disparities in diabetes burden among population subgroups in India, underscoring the need for targeted efforts.

Safety and immunogenicity of the Rotavac and Rotasiil rotavirus vaccines administered in an interchangeable dosing schedule among healthy Indian infants: a multicentre, open-label, randomised, controlled, phase 4, non-inferiority trial.

BACKGROUND: Rotavirus is the leading cause of severe dehydrating gastroenteritis among children younger than 5 years in low-income and middle-income countries. Two vaccines-Rotavac and Rotasiil-are used in routine immunisation in India. The safety and immunogenicity of these vaccines administered in a mixed regimen is not documented. We therefore aimed to compare the safety and seroresponse of recipients of a mixed regimen versus a single regimen. METHODS: We did a multicentre, open-label, randomised, controlled, phase 4, non-inferiority trial at two sites in India. We recruited healthy infants aged 6-8 weeks. Infants with systemic disorders, weight-for-height Z scores of less than minus three SDs, or a history of persistent diarrhoea were excluded. Eligible infants were randomly allocated to six groups in equal numbers to receive either the single vaccine regimen (ie, Rotavac-Rotavac-Rotavac [group 1] or Rotasiil-Rotasiil-Rotasiil [group 2]) or the mixed vaccine regimen (ie, Rotavac-Rotasiil-Rotavac [group 3], Rotasiil-Rotavac-Rotasiil [group 4], Rotavac-Rotasiil-Rotasiil [group 5], or Rotasiil-Rotavac-Rotavac [group 6]). Randomisation was done using an online software by site in blocks of at least 12. The primary outcome was seroresponse to rotavirus vaccine, measured using rotavirus-specific serum IgA antibodies 4 weeks after the third dose. The seroresponse rates were compared between recipients of the four mixed vaccine regimens (consisting of various combinations of Rotavac and Rotasiil) with recipients of the single vaccine regimens (consisting of Rotavac or Rotasiil only for all three doses). The non-inferiority margin was set at 10%. Safety follow-ups were done for the duration of study participation. This trial was registered with the Clinical Trials Registry India, number CTRI/2018/08/015317. FINDINGS: Between March 25, 2019, and Jan 15, 2020, a total of 1979 eligible infants were randomly assigned to receive a single vaccine regimen (n=659; 329 in group 1 and 330 in group 2) or a mixed vaccine regimen (n=1320; 329 each in groups 3 and 4, and 331 each in groups 5 and 6). All eligible participants received the first dose, 1925 (97·3%) of 1979 received the second dose, and 1894 (95·7%) received all three doses of vaccine. 1852 (93·6%) of 1979 participants completed the follow-up. The immunogenicity analysis consisted of 1839 infants (1238 [67·3%] in the mixed vaccine regimen and 601 [32·7%] in the single vaccine regimen; 13 samples were insufficient in quantity) who completed vaccination and provided post-vaccination sera. The seroresponse rate in the mixed vaccine regimen group (33·5% [95% CI 30·9-36·2]) was non-inferior compared with the single vaccine regimen group (29·6% [26·1-33·4]); the seroresponse rate difference was 3·9% (95% CI -0·7 to 8·3). The proportion of participants with any type of solicited adverse events was 90·9% (95% CI 88·4-93·0) in the single vaccine regimen group and 91·1% (89·5-92·6) in the mixed vaccine regimen group. No vaccine-related serious adverse events or intussusception were reported during the study. INTERPRETATION: Rotavac and Rotasiil can be safely used in an interchangeable manner for routine immunisation since the seroresponse was non-inferior in the mixed vaccine regimen compared with the single vaccine regimen. These results allow for flexibility in administering the vaccines, helping to overcome vaccine shortages and supply chain issues, and targeting migrant populations easily. FUNDING: Ministry of Health and Family Welfare, Government of India. TRANSLATION: For the Hindi translation of the abstract see Supplementary Materials section.

Prescription practices and availability of artemisinin monotherapy in India: where do we stand?

BACKGROUND: The World Health Organization has urged all member states to deploy artemisinin-based combination therapy and progressively withdraw oral artemisinin monotherapies from the market due to their high recrudescence rates and to reduce the risk of drug resistance. Prescription practices by physicians and the availability of oral artemisinin monotherapies with pharmacists directly affect the pattern of their use. Thus, treatment practices for malaria, with special reference to artemisinin monotherapy prescription, in selected states of India were evaluated. METHODS: Structured, tested questionnaires were used to conduct convenience surveys of physicians and pharmacists in eleven purposively selected districts across six states in 2008. In addition, exit interviews of patients with a diagnosis of uncomplicated malaria or a prescription for an anti-malarial drug were also performed. Logistic regression was used to determine patient clinical care, and institutional factors associated with artemisinin monotherapy prescription. RESULTS: Five hundred and eleven physicians from 196 health facilities, 530 pharmacists, and 1,832 patients were interviewed. Artemisinin monotherapy was available in 72.6% of pharmacies and was prescribed by physicians for uncomplicated malaria in all study states. Exit interviews among patients confirmed the high rate of use of artemisinin monotherapy with 14.8% receiving such a prescription. Case management, i.e. method of diagnosis and overall treatment, varied by state and public or private sector. Treatment in the private sector (OR 8.0, 95%CI: 3.8, 17) was the strongest predictor of artemisinin monotherapy prescription when accounting for other factors. Use of the combination therapy recommended by the national drug policy, artesunate + sulphadoxine-pyrimethamine, was minimal (4.9%), with the exception of one state. CONCLUSIONS: Artemisinin monotherapy use was widespread across India in 2008. The accessible sale of oral artemisinin monotherapy in retail market and an inadequate supply of recommended drugs in the public sector health facilities promoted its prescription. This study resulted in notifications to all state drug controllers in India to withdraw the oral artemisinin formulations from the market. In 2010, artesunate + sulphadoxine-pyrimethamine became the universal first-line treatment for confirmed Plasmodium falciparum malaria and was deployed at full scale.

Development and temporal external validation of a simple risk score tool for prediction of outcomes after severe head injury based on admission characteristics from level-1 trauma centre of India using retrospectively collected data.

OBJECTIVE: To develop and validate a simple risk scores chart to estimate the probability of poor outcomes in patients with severe head injury (HI). DESIGN: Retrospective. SETTING: Level-1, government-funded trauma centre, India. PARTICIPANTS: Patients with severe HI admitted to the neurosurgery intensive care unit during 19 May 2010-31 December 2011 (n=946) for the model development and further, data from same centre with same inclusion criteria from 1 January 2012 to 31 July 2012 (n=284) for the external validation of the model. OUTCOMES: In-hospital mortality and unfavourable outcome at 6 months. RESULTS: A total of 39.5% and 70.7% had in-hospital mortality and unfavourable outcome, respectively, in the development data set. The multivariable logistic regression analysis of routinely collected admission characteristics revealed that for in-hospital mortality, age (51-60, >60 years), motor score (1, 2, 4), pupillary reactivity (none), presence of hypotension, basal cistern effaced, traumatic subarachnoid haemorrhage/intraventricular haematoma and for unfavourable outcome, age (41-50, 51-60, >60 years), motor score (1-4), pupillary reactivity (none, one), unequal limb movement, presence of hypotension were the independent predictors as its 95% confidence interval (CI) of odds ratio (OR)_did not contain one. The discriminative ability (area under the receiver operating characteristic curve (95% CI)) of the score chart for in-hospital mortality and 6 months outcome was excellent in the development data set (0.890 (0.867 to 912) and 0.894 (0.869 to 0.918), respectively), internal validation data set using bootstrap resampling method (0.889 (0.867 to 909) and 0.893 (0.867 to 0.915), respectively) and external validation data set (0.871 (0.825 to 916) and 0.887 (0.842 to 0.932), respectively). Calibration showed good agreement between observed outcome rates and predicted risks in development and external validation data set (p>0.05). CONCLUSION: For clinical decision making, we can use of these score charts in predicting outcomes in new patients with severe HI in India and similar settings.

IKZF1 Deletion Subtyping and Outcome Analysis in BCR-ABL1-Negative Pediatric B-Cell Acute Lymphoblastic Leukemia: A Single-Institution Experience from North India.

BACKGROUND: IKZF1 deletions are associated with adverse outcomes in B-cell acute lymphoblastic leukemia (B-ALL). We assessed the prevalence and clinical impact of functional subtypes of IKZF1 deletions in pediatric BCR-ABL1-negative B-ALL. PATIENTS AND METHODS: This retrospective study of IKZF1 deletions was done in cases of pediatric BCR-ABL1-negative B-ALL. The genomic DNA of cases, over a 53-month period, was analyzed using multiplex ligation-dependent probe amplification and multiplex fluorescent polymerase chain reaction. The deletions were divided into functional subgroups: (1) loss-of-function/haploinsufficiency, (2) dominant-negative, and (3) a combination of both types of deletion. The post-induction remission status, event-free survival (EFS), and overall survival (OS) were noted. RESULTS: Out of 320 cases, 47 (14.7%) had IKZF1 deletions. Thirty-six of the 47 (77%) had loss-of-function deletions, 10 (21%) had dominant-negative deletions, and one (2%) had a combination of both types. The post-induction remission rates in cases with loss-of-function deletions (22/30, 73%; P = .060) and dominant-negative deletions (4/5, 80%; P = .517) were lower compared with those without deletions (215/248, 86.7%). These cases also had worse median EFS: 21.1 months (P = .006) for loss-of-function and 15.4 months (P = .156) for dominant-negative deletions, compared with 46.4 months in cases without IKZF1 deletions. They also had worse median OS: 23.4 months (P = .012) for loss-of-function deletions and 15.7 months (P = .233) for dominant-negative deletions, compared with median not reached in cases without IKZF1 deletions. CONCLUSION: The IKZF1 deletions were seen in 14.7% of BCR-ABL1-negative pediatric B-ALL. Most of these deletions (77%) were loss-of-function type. The cases with loss-of-function deletions had lower remission rates and poor EFS and OS compared with cases without IKZF1 deletions. A similar trend of poor outcome was seen in the few cases with dominant-negative IKZF1 deletions.

Proposal and clinical application of molecular genetic risk scoring system, "MRplus", for BCR-ABL1 negative pediatric B-cell acute lymphoblastic leukemia- report from a single centre.

INTRODUCTION: We propose "MRplus", a molecular genetic risk score and check its clinical application in the risk-stratification of pediatric B-ALL. METHODS: The genomic DNA of untreated pediatricBCR-ABL1 negative B-ALL patients was analyzed for deletions of IKZF1, PAX5, CDKN2A/B, BTG1, RB1, ETV6, EBF1, ERG, pseudoautosomal region(PAR) genes using multiplex ligation-dependent probe amplification, along with the routine genetic work-up. The patients were assigned an 'M'score- 0 (M0) for low and 1 (M1) for high genetic-risk as per the criteria by Moorman et al., and another score "IKplus"-1 (IKplus1) for IKZF1plus as per the criteria by Stanulla et al., and 0 (IKplus0) for other patients. The final "MRplus" risk-score of 0 (MRplus0), 1 (MRplus1) or 2 (MRplus2) was obtained by adding both these scores. The association of risk scores with overall survival (OS) and event free survival(EFS) was seen using Cox proportion hazard model. The overall goodness of fit of the model was done using Cox-Snell residuals. RESULTS: The median age of 320 patients was 6 years (1-18 years). The patients with score M1 were 139 (43.4 %), M0-181 (56.6 %); IKplus1-32 (10 %) and IKplus0-288 (90 %). The final "MRplus" score of 0,1,or 2 was obtained in 181(56.6 %), 107(33.4 %) and 32(10 %) patients respectively. The post-induction remission rate was 90.7 %, 77.8 %, 73.9 % (p = 0.004); 4-year OS 67 %, 48 %, 27 % (p < 0.001); and 4-year EFS 56 %, 34 %, 19 %(p < 0.001) in patients with "MRplus" score 0,1,and 2 respectively. CONCLUSIONS: The proposed "MRplus" scoring at baseline could identify three distinct risk groups-good (MRplus0), intermediate (MRplus1) and poor (MRplus2), with different outcomes; in pediatricBCR-ABL1 negative B-ALL. This may help in better risk-stratification and selection of patients for alternative treatment approaches.

Determinants of severity among hospitalised COVID-19 patients: Hospital-based case-control study, India, 2020.

BACKGROUND: Risk factors for the development of severe COVID-19 disease and death have been widely reported across several studies. Knowledge about the determinants of severe disease and mortality in the Indian context can guide early clinical management. METHODS: We conducted a hospital-based case control study across nine sites in India to identify the determinants of severe and critical COVID-19 disease. FINDINGS: We identified age above 60 years, duration before admission >5 days, chronic kidney disease, leucocytosis, prothrombin time > 14 sec, serum ferritin >250 ng/mL, d-dimer >0.5 ng/mL, pro-calcitonin >0.15 µg/L, fibrin degradation products >5 µg/mL, C-reactive protein >5 mg/L, lactate dehydrogenase >150 U/L, interleukin-6 >25 pg/mL, NLR ≥3, and deranged liver function, renal function and serum electrolytes as significant factors associated with severe COVID-19 disease. INTERPRETATION: We have identified a set of parameters that can help in characterising severe COVID-19 cases in India. These parameters are part of routinely available investigations within Indian hospital settings, both public and private. Study findings have the potential to inform clinical management protocols and identify patients at high risk of severe outcomes at an early stage.

Global impact of environmental temperature and BCG vaccination coverage on the transmissibility and fatality rate of COVID-19.

The 2019-Coronavirus (COVID-19) pandemic has had a global impact. The effect of environmental temperature on transmissibility and fatality rate of COVID-19 and protective efficacy of Bacillus Calmette-Guérin (BCG) vaccination towards COVID-19 remains ambiguous. Therefore, we explored the global impact of environmental temperature and neonatal BCG vaccination coverage on transmissibility and fatality rate of COVID-19. The COVID-19 data for reported cases, deaths and global temperature were collected from 31st December 2020 to 3rd April 2020 for 67 countries. Temperature data were split into quartiles for all three categories (minimum temperature, maximum temperature and mean temperature). The impact of three types of temperature data and policy of BCG vaccination on COVID-19 infection was determined by applying the multivariable two-level negative binomial regression analysis keeping daily new cases and daily mortality as outcome. The highest number of cases fell in the temperature categories as following: mean temperature in the second quartile (6°C to 10.5°C), median 26, interquartile range (IQR) 237; minimum temperature in the first quartile (-26°C to 1°C), median 23, IQR 173; maximum temperature in the second quartile (10°C to 16°C), median 27.5, IQR 219. For the minimum temperature category, 28% statistically significant lower incidence was noted for new cases from the countries falling in the second quartile (2°C to 6°C) compared with countries falling in the first quartile (-26°C to 1°C) (incidence rate ratio [IRR] 0.72, 95% confidence interval [CI] 0.57 to 0.93). However, no statistically significant difference in incidence rate was observed for mean temperature categories in comparison to the first quartile. Countries with BCG vaccination policy had 58% less mortality as compared with countries without BCG coverage (IRR 0.42; 95% CI 0.18 to 0.95). Our exploratory study provides evidence that high temperature might not be associated with low transmissibility and countries having neonatal BCG vaccination policy had a low fatality rate of COVID-19.

Dual partial arc volumetric-modulated arc therapy: The game changer for accelerated hypofractionated whole-breast radiotherapy with simultaneous integrated tumor cavity boost in early breast cancer - A comparative dosimetric study with single partial arc volumetric-modulated arc therapy.

INTRODUCTION: In a previous study, we demonstrated clinical and dosimetric feasibility of single partial arc volumetric modulated arc therapy (VMAT) for accelerated hypofractionated whole breast radiotherapy with simultaneous integrated boost (SIB) to lumpectomy cavity for early breast cancer. In this dosimetric study, we compared dual partial arcs versus single arc. PATIENTS AND METHODS: Fifteen consecutive patients for treatment with hypofractionated accelerated radiotherapy with SIB using VMAT were planned with single partial arc in an earlier study, initial result of which is published elsewhere. The comparative dosimetric plan was created using two partial arcs. Skewness and kurtosis test, Paired Student's t-test, and Wilcoxon signed-rank test were applied for statistical analysis. P < 0.05 was considered statistically significant. RESULTS: Most planning targets are better achieved with dual arc technique. Coverage of planning target volume (PTV) whole breast (PTVWB) and PTV lumpectomy cavity (PTVBOOST) was significantly improved with dual partial arc without significant difference in conformity index and homogeneity index. Dual arc improved dosimetric parameter significantly. Mean dose (Dmean) and maximum dose (Dmax) of whole breast PTV as well as Dmax of PTVBOOST; ipsilateral and contralateral lung Dmean, Dmax, 5 Gy volume (V5); contralateral lung Dmean, Dmax, V5; Heart V25 and V18; Dmean of 5 mm thickness skin; Dmean and Dmax of ribs; and Dmean and Dmax of contralateral breast were improved with dual arc. CONCLUSION: This is first of its kind study establishing the advantage of dual partial arcs in the current context. Dual partial arcs improved dosimetry over single partial arc. Significant dose reduction can be achieved for multiple crucial organs at risk.

Molecular genetic profile in BCR-ABL1 negative pediatric B-cell acute lymphoblastic leukemia can further refine outcome prediction in addition to that by end-induction minimal residual disease detection.

The recently proposed molecular genetic criteria promise improved risk-prediction in B-cell acute lymphoblastic leukemia (B-ALL). This study assesses their utility in BCR-ABL1 negative pediatric B-ALL, particularly with respect to end-induction minimal residual disease (MRD). The DNA was analyzed for copy number alterations in CDKN2A/B, PAX5, IKZF1, and other genes. Seventy-six cases with median age 7 years (2 months-18 years) included MRD-positive (24; 32%), and MRD negative-standard (20; 26%), intermediate (20; 26%), & high risk (12;16%) cases. The risk classification was based on age, initial total leukocyte count, central nervous system involvement, cytogenetics, day 8 prednisolone response and MRD status after induction chemotherapy. The genetic profile based on Moorman's criteria identified two subgroups with different event free survival (EFS) (0.77 vs. 0.38; p = .045) and overall survival (OS) (0.90 vs. 0.30; p = .037) in the MRD-negative intermediate-risk group. The genetic profile also separated two subgroups with different EFS (0.75 vs. 0.41; p = .036) in the MRD-positive group, however the OS was not different (0.75 vs. 0.57; p = .293).

Impact of Cancer Awareness Drive on Generating Awareness of and Improving Screening for Cervical Cancer: A Study Among Schoolteachers in India.

PURPOSE: Cervical cancer is the second most common cancer in India. Our study assessed the level and impact of awareness programs in the adoption of safe practices in prevention and early detection. METHODS: This assessment was part of a Pink Chain Campaign, the mission of which is to fight cancer. During cancer awareness events from 2013 to 2015 at various women's colleges in different parts in India, a pretest related to cervical cancer was followed by an awareness program. A post-test was conducted 6 months and 1 year later. RESULTS: A total of 872 of 985 teachers participated in the study, for a response rate of 88.5%. Mean age of the population was 42.4 years. There was a significant increase in the level of knowledge regarding cervical cancer at 6 months, which was sustained at 1 year. Regarding cervical cancer screening, knowledge and practice of the Papanicolaou (Pap) test as a screening test for cervical cancer among teachers were changed significantly at 6 months and 1 year. More than 75% of teachers were educated by physicians about the Pap test. At the time of the post-test, there was a significant change in alcohol and smoking habits. The main reasons for not undergoing a screening test were ignorance (50%), lethargic attitude (44.8%), and lack of time (34.6%). CONCLUSION: The level of knowledge of cervical cancer was poor. A significant increase in the level of knowledge of cervical cancer among the population was found after this study. To inculcate safe lifestyle practices, awareness programs should be conducted more widely and frequently.