Enhancing subsurface contamination assessment via ensemble prediction of ground electrical property: A Colorado AMD-impacted wetland case study.

Acid mine drainage (AMD) is recognized as a major environmental challenge in the Western United States, particularly in Colorado, leading to extreme subsurface contamination issue. Given Colorado's arid climate and dependence on groundwater, an accurate assessment of AMD-induced contamination is deemed crucial. While in past, machine learning (ML)-based inversion algorithms were used to reconstruct ground electrical properties (GEP) such as relative dielectric permittivity (RDP) from ground penetrating radar (GPR) data for contamination assessment, their inherent non-linear nature can introduce significant uncertainty and non-uniqueness into the reconstructed models. This is a challenge that traditional ML methods are not explicitly designed to address. In this study, a probabilistic hybrid technique has been introduced that combines the DeepLabv3+ architecture-based deep convolutional neural network (DCNN) with an ensemble prediction-based Monte Carlo (MC) dropout method. Different MC dropout rates (1%, 5%, and 10%) were initially evaluated using 1D and 2D synthetic GPR data for accurate and reliable RDP model prediction. The optimal rate was chosen based on minimal prediction uncertainty and the closest alignment of the mean or median model with the true RDP model. Notably, with the optimal MC dropout rate, prediction accuracy of over 95% for the 1D and 2D cases was achieved. Motivated by these results, the hybrid technique was applied to field GPR data collected over an AMD-impacted wetland near Silverton, Colorado. The field results underscored the hybrid technique's ability to predict an accurate subsurface RDP distribution for estimating the spatial extent of AMD-induced contamination. Notably, this technique not only provides a precise assessment of subsurface contamination but also ensures consistent interpretations of subsurface condition by different environmentalists examining the same GPR data. In conclusion, the hybrid technique presents a promising avenue for future environmental studies in regions affected by AMD or other contaminants that alter the natural distribution of GEP.

A large-scale retrospective study enabled deep-learning based pathological assessment of frozen procurement kidney biopsies to predict graft loss and guide organ utilization.

Lesion scores on procurement donor biopsies are commonly used to guide organ utilization for deceased-donor kidneys. However, frozen sections present challenges for histological scoring, leading to inter- and intra-observer variability and inappropriate discard. Therefore, we constructed deep-learning based models to recognize kidney tissue compartments in hematoxylin & eosin-stained sections from procurement needle biopsies performed nationwide in years 2011-2020. To do this, we extracted whole-slide abnormality features from 2431 kidneys and correlated with pathologists' scores and transplant outcomes. A Kidney Donor Quality Score (KDQS) was derived and used in combination with recipient demographic and peri-transplant characteristics to predict graft loss or assist organ utilization. The performance on wedge biopsies was additionally evaluated. Our model identified 96% and 91% of normal/sclerotic glomeruli respectively; 94% of arteries/arterial intimal fibrosis; 90% of tubules. Whole-slide features of Sclerotic Glomeruli (GS)%, Arterial Intimal Fibrosis (AIF)%, and Interstitial Space Abnormality (ISA)% demonstrated strong correlations with corresponding pathologists' scores of all 2431 kidneys, but had superior associations with post-transplant estimated glomerular filtration rates in 2033 and graft loss in 1560 kidneys. The combination of KDQS and other factors predicted one- and four-year graft loss in a discovery set of 520 kidneys and a validation set of 1040 kidneys. By using the composite KDQS of 398 discarded kidneys due to "biopsy findings", we suggest that if transplanted, 110 discarded kidneys could have had similar survival to that of other transplanted kidneys. Thus, our composite KDQS and survival prediction models may facilitate risk stratification and organ utilization while potentially reducing unnecessary organ discard.

Evaluation of impact of engaging federations of women groups to improve women's nutrition interventions- before, during and after pregnancy in social and economically backward geographies: Evidence from three eastern Indian States.

BACKGROUND: Undernutrition-before, during and after pregnancy endangers the health and well-being of the mother and contributes to sub-optimal fetal development and growth. A non-randomized controlled evaluation was undertaken to assess the impact of engaging federations of women's group on coverage of nutrition interventions and on nutrition status of women in the designated poverty pockets of three Indian states-Bihar, Chhattisgarh, and Odisha. METHOD: The impact evaluation is based on two rounds of cross-sectional data from 5 resource poor blocks across 3 States, assigning 162 villages to the intervention arm and 151 villages to the control arm. The cross-sectional baseline (2016-17) and endline survey (2021-22) covered a total of 10491 adolescent girls (10-19 years), 4271 pregnant women (15-49 years) and 13521 mothers of children under age two years (15-49 years). Exposure was defined based on participation in the participatory learning and action meetings, and fixed monthly health camps (Adolescent Health Days (AHDs) and Village Health Sanitation and Nutrition Days (VHSNDs)). Logistic regression models were applied to establish the association between exposure to programme activities and improvement in coverage of nutrition interventions and outcomes. RESULTS: In the intervention area at endline, 27-38% of women participated in the participatory learning and action meetings organized by women's groups. Pregnant women participating in programme activities were two times more likely to receive an antenatal care visit in the first trimester of pregnancy (Odds ratio: 2.55 95% CI-1.68-3.88), while mothers of children under 2 were 60% more likely to receive 4 ANC visits (Odds ratio: 1.61, 95% CI- 1.30-2.02). Odds of consuming a diversified diet was higher among both pregnant women (Odds ratio: 2.05, 95% CI- 1.41-2.99) and mother of children under 2 years of age (Odds ratio: 1.38, 95% CI- 1.08-1.77) among those participating in programme activities in the intervention arm. Access to commodities for WASH including safe sanitation services (Odds ratio: 1.80, 95% CI- 1.38-2.36) and sanitary pads (Odds ratio: 1.64, 95% CI- 1.20-2.22) was higher among adolescent girls participating in programme activities. CONCLUSION: Women's groups led participatory learning and action approaches coupled with strengthening of the supply side delivery mechanisms resulted in higher coverage of health and nutrition services. However, we found that frequency of participation was low and there was limited impact on the nutritional outcomes. Therefore, higher frequency of participation in programme activities is recommended to modify behaviour and achieve quick gains in nutritional outcomes.

Assessment of heavy metal contamination in street dust: concentrations, bioaccessibility, and human health risks in coal mine and thermal power plant complex.

Coal mining has also been associated with adverse environmental and health impacts including cancer and respiratory disorders, with the presence of thermal power plants exacerbating the problem of heavy metal pollution. Minimal studies have been conducted on the environmental impacts, health risks, and bioaccessibility of heavy metals in coal mine areas. Consequently, samples of street dust were collected from different locations in the Singrauli mine complex and analysed. Heavy metals (Cu, Ni, Zn, Cr, Co, As, and Mo) were found to be higher than the background concentration, with the maximum concentration was found in areas close to the Thermal Power Plants, like Near Vindyachal TPP, Near Shakti Nagar TPP, and Anpara. The highest geo-accumulation index value was found for Co, Mo, Zn, and As, indicating moderate to strong pollution levels. Health risk assessment (for both adults and children) revealed that Cr and Fe posed significantly higher Hazard Quotient and Hazard Index (HI) values, indicating significant non-carcinogenic threats. Moreover, Carcinogenic Risk (CR) values for Cd, Cr, and Ni indicated a risk of carcinogenicity to the public exposed to road dust. The study also examined the bioaccessibility of the metals, which showed that the gastric phase accumulated a higher percentage of Ni (42.52%), Pb (34.79%), Co (22.22%), As (20%) and Cu (15%) than the intestinal phase. Strong positive correlation was observed between metal concentration (Cu, Pb, Cr, Fe, Zn, and Mn), HI, and CR of adult and child, while bioaccessibility of intestinal phase was positively correlated with gastric phase of metals (Cu, Ni, Co, As, and Mn).

Qualitative and quantitative assessment of diatom deformities and protoplasmic condition under metal and metalloid stress.

Metals and metalloids are toxic, persistent, and non-biodegradable and can be biomagnified (e.g., Hg), and therefore pose a serious threat to the algal flora of aquatic ecosystems. This laboratory study tested the effects of metals (Zn, Fe, and Hg) and a metalloid (As) on the cell wall morphology and protoplasmic content of living cells of six widespread diatom genera over 28 days. Diatoms exposed to Zn and Fe had a higher frequency of deformed diatom frustules (> 1%) compared to the As, Hg, and control treatments (< 1%). Deformities in the valve outline and striae were found in all treatments, including the control, whereas deformed raphes and more than one type of deformity were more prevalent under Zn and Hg stress. The order of toxicity is as follows: Zn > Fe > Hg≈As. Deformities were more frequent in Achnanthes and Diploneis (adnate forms) than in the motile genera of Nitzschia and Navicula. The correlation between the % healthy diatoms and % deformities in all six genera showed a negative relationship with the integrity of protoplasmic content (i.e., greater alteration in protoplasmic content was associated with greater frustule deformation). We conclude that diatom deformities can be a good indicator of metal and metalloid stress in waterbodies and are very useful in the rapid biomonitoring of aquatic ecosystems.

Integrating an algorithmic and health systems thinking approach to improve the uptake of government antenatal nutrition services in Vidisha, Madhya Pradesh (India), 2018 to 2021.

In 2018, the Government of Madhya Pradesh initiated the feasibility testing of integrating an algorithmic approach (assess, give, counsel, treat) to strengthen antenatal nutrition services in routine government-funded programmes coupled with a health system thinking approach to strengthen the health service delivery platform. Implementation phases included (1) an evidence review and stakeholder consultations (April 2018) and (2) a health systems strengthening preparedness phase (May-December 2018), including pilot testing in Vidisha district (January-December 2019) covering ∼54 100 pregnant women with 237 antenatal contact points through 241 government auxiliary nurse midwives/staff nurses. During 2020-21, feasibility testing was expanded to an additional 7 districts. We used programme registers of the Auxiliary Nurse Midwives Registers (2019-21) and National Family Health Survey data for 2016 and 2021 to show changes in the Vidisha district and 7 expansion districts. We compare the performance of Vidisha district with Ashok Nagar district, where no such intervention occurred. Comparing 2016 and 2021 data, the Vidisha district showed improvements in receipt of antenatal care in the first trimester (29 to 85%) and in four antenatal visits (17 to 54%). Using the difference-in-difference approach, a 42% net increase in first-trimester antenatal check-ups in Vidisha as compared to Ashok Nagar is observed. There was also an improvement in the maternal nutrition budget of the state from USD 8.5 million to USD 17.8 million during this period. The Vidisha initiative offers several lessons in time-effective workflow to deliver all constituents of nutrition services at various antenatal contact points through and via routine government health systems. Continued execution of the algorithm for screening, with longitudinal data on the management of all nutrition risks, will be critical to show its long-term impact on maternal morbidities and birth outcomes.

Concepts of circular economy for sustainable management of electronic wastes: challenges and management options.

The electronic and electrical industrial sector is exponentially growing throughout the globe, and sometimes, these wastes are being disposed of and discarded with a faster rate in comparison to the past era due to technology advancements. As the application of electronic devices is increasing due to the digitalization of the world (IT sector, medical, domestic, etc.), a heap of discarded e-waste is also being generated. Per-capita e-waste generation is very high in developed countries as compared to developing countries. Expansion of the global population and advancement of technologies are mainly responsible to increase the e-waste volume in our surroundings. E-waste is responsible for environmental threats as it may contain dangerous and toxic substances like metals which may have harmful effects on the biodiversity and environment. Furthermore, the life span and types of e-waste determine their harmful effects on nature, and unscientific practices of their disposal may elevate the level of threats as observed in most developing countries like India, Nigeria, Pakistan, and China. In the present review paper, many possible approaches have been discussed for effective e-waste management, such as recycling, recovery of precious metals, adopting the concepts of circular economy, formulating relevant policies, and use of advance computational techniques. On the other hand, it may also provide potential secondary resources valuable/critical materials whose primary sources are at significant supply risk. Furthermore, the use of machine learning approaches can also be useful in the monitoring and treatment/processing of e-wastes. HIGHLIGHTS: In 2019, ~ 53.6 million tons of e-wastes generated worldwide. Discarded e-wastes may be hazardous in nature due to presence of heavy metal compositions. Precious metals like gold, silver, and copper can also be procured from e-wastes. Advance tools like artificial intelligence/machine learning can be useful in the management of e-wastes.

Assessment of masticatory function in older individuals with bimaxillary implant-supported fixed prostheses or with a natural dentition: A case-control study.

STATEMENT OF PROBLEM: A clinical assessment of the masticatory performance of edentulous people treated with bimaxillary implant-supported fixed prostheses is lacking. PURPOSE: The purpose of this case-control study was to compare the masticatory performance of edentulous people treated with bimaxillary implant-supported fixed prostheses to that of those with a natural dentition by using a simplified comminution test with hard viscoelastic test food and a mixing ability test. MATERIAL AND METHODS: Thirty-six participants were recruited and divided into 2 equal groups (n=18) based on their dental status. The experimental group (7 women, mean ±standard deviation age=69.8 ±7.5 years) had bimaxillary implant-supported fixed prostheses, and the control group (9 women, mean ±standard deviation age=68.3 ±5.6 years) had a natural dentition. A hard viscoelastic food comminution test and a mixing ability test with 2-colored chewing gum were performed in both groups. The number and total area of the particles during the comminution test and the variance of hue during the mixing ability test were measured. The data were analyzed with the parametric (paired t test) and nonparametric (Mann-Whitney U) tests to assess differences between the groups (α=.05). RESULTS: The experimental group exhibited significantly fewer pieces in the food comminution test than the control group (P=.001). The experimental group also showed significantly higher variance of hue values than the control group (P<.001). CONCLUSIONS: Patients treated with bimaxillary implant-supported prostheses had reduced masticatory performance in comparison to those with a natural dentition, despite having been provided with satisfactory and well-functioning prostheses.

Digital Inequalities in Cancer Care Delivery in India: An Overview of the Current Landscape and Recommendations for Large-Scale Adoption.

Introduction: COVID-19 pandemic has caused major disruptions to delivery of various cancer care services as efforts were put to control the outbreak of the pandemic. Although the pandemic has highlighted the inadequacies of the system but has also led to emergence of a new cancer care delivery model which relies heavily on digital mediums. Digital health is not only restricted to virtual dissemination of information and consultation but has provided additional benefits ranging from support to cancer screening, early and more accurate diagnosis to increasing access to specialized care. This paper evaluates the challenges in the adoption of digital technologies to deliver cancer care services and provides recommendation for large-scale adoption in the Indian healthcare context. Methods: We performed a search of PubMed and Google Scholar for numerous terms related to adoption of digital health technologies for cancer care during pandemic. We also analyze various socio-ecological challenges-from individual to community, provider and systematic level-for digital adoption of cancer care service which have existed prior to pandemic and lead to digital inequalities. Results: Despite encouraging benefits accruing from the adoption of digital health key challenges remain for large scale adoption. With respect to user the socio-economic characteristics such as age, literacy and socio-cultural norms are the major barriers. The key challenges faced by providers include regulatory issues, data security and the inconvenience associated with transition to a new system. Policy Summary: For equitable digital healthcare, the need is to have a participatory approach of all stakeholders and urgently addressing the digital divide adequately. Sharing of health data of public and private hospitals, within the framework of the Indian regulations and Data Protection Act, is critical to the development of digital health in India and it can go a long way in better forecasting and managing cancer burden.

Mechanical characterization and adhesive properties of a dental adhesive modified with a polymer antibiotic conjugate.

This study is a follow up investigation on recent work by our group demonstrating synthesis, release and strong antibacterial character of resins modified with penicillin V (PV)-based polymer-antibiotic conjugates (PACs). Here, we aimed to evaluate the mechanical, bonding, and other relevant biomedical properties of a commercial adhesive resin modified with PV-PAC. Single Bond Plus (SB+) was modified with PAC containing 1.8 wt% conjugated PV. Adhesive resins were bonded to dentin from extracted human molars and restorative resin added. Beams of cross-sectional area of 0.9 ± 0.1 mm (Kutsch and Young, 2011) (n = 20) were obtained from the molars and tested for micro-tensile bond strength (µTBS) at 24 h and 4 months. For cohesive strength, hourglass beams (10 × 2 × 1 mm; n = 10) were assessed for ultimate tensile strength (UTS), beam-shaped specimens (25x2x2 mm; n = 10) evaluated for flexural strength and modulus (FS/FM) via three-point bending, and cylindrical specimens (3 × 2 mm; n = 10) assessed for ultimate compressive strength (UCS). For surface micro-hardness (MH), cylindrical specimens (3 × 2 mm; n = 6) were assessed before and after an EtOH challenge. The degree of conversion (DC) (5 × 1 mm; n = 6) was determined based on changes in absorbance ratio between peaks at ∼1637 cm-1 and ∼1608 cm-1 before and after curing of adhesive resins using attenuated total reflectance Fourier transform infrared (ATR-FTIR) spectroscopy. To monitor water uptake and diffusion kinetics over a 28-day period, specimens (5 × 1mm) were desiccated, weighed and stored in deionized water. Control and PV-PAC modified adhesive resins demonstrated similar µTBS at 24 h and 4 months; both showing decrease in values after 4 months (p = 0.001 and 0.004). No significant differences between adhesive resins were shown in UTS, FS/FM or UCS (p<0.05). MH of PV-PAC adhesive resin was significantly reduced relative to the control (p<0.001). The DC values of the adhesive resins were not significantly different. While sorption and solubility were no different between materials, the diffusion coefficient of PV-PAC modified adhesive resin was higher than the control (p<0.001). We conclude that incorporation of PV-PAC with 1.8 wt% PV into an adhesive resin does not adversely affect its mechanical, bonding, and physical properties, thus providing a promising option for materials with long-term antibacterial character and on-demand release.

Continuous and Synoptic Assessment of Indian Inland Waters for Harmful Algae Blooms.

Cyanobacterial Harmful Algal Blooms (CyanoHABs) are progressively becoming a major water quality, socioeconomic, and health hazard worldwide. In India, there are frequent episodes of severe CyanoHABs, which are left untreated due to a lack of awareness and monitoring infrastructure, affecting the economy of the country gravely. In this study, for the first time, we present a country-wide analysis of CyanoHABs in India by developing a novel interactive cloud-based dashboard called "CyanoKhoj" in Google Earth Engine (GEE) which uses Sentinel-3 Ocean and Land Colour Instrument (OLCI) remotely sensed datasets. The main goal of this study was to showcase the utility of CyanoKhoj for rapid monitoring and discuss the widespread CyanoHABs problems across India. We demonstrate the utility of Cyanokhoj by including select case studies of lakes and reservoirs geographically spread across five states: Bargi and Gandhisagar Dams in Madhya Pradesh, Hirakud Reservoir in Odisha, Ukai Dam in Gujarat, Linganamakki Reservoir in Karnataka, and Pulicat Lake in Tamil Nadu. These sites were studied from September to November 2018 using CyanoKhoj, which is capable of near-real-time monitoring and country-wide assessment of CyanoHABs. We used CyanoKhoj to prepare spatiotemporal maps of Chlorophyll-a (Chl-a) content and Cyanobacterial Cell Density (CCD) to study the local spread of the CyanoHABs and their phenology in these waterbodies. A first-ever all-India CCD map is also presented for the year 2018, which highlights the spatial spread of CyanoHABs throughout the country (32 large waterbodies across India with severe bloom: CCD>2,500,000). Results indicate that CyanoHABs are most prevalent in nutrient-rich waterbodies prone to industrial and other nutrient-rich discharges. A clear temporal evolution of the blooms showed that they are dominant during the post-monsoon season (September-October) when the nutrient concentrations in the waterbodies are at their peak, and they begin to decline towards winter (November-December). CyanoKhoj is an open-source tool that can have a significant broader impact in mapping CyanoHABs not only throughout cyanobacteria data-scarce India, but on a global level using archived and future Sentinel-3A/B OLCI data.

Assessment of ideal serum dilution for screening of antinuclear antibodies by an indirect immunofluorescence method in diagnosis of autoimmune disorders.

BACKGROUND: Time and cost constraints lead to majority of clinical laboratories deviating away from an ideal practice of checking for antinuclear antibodies (ANAs) by indirect immunofluorescence (IIF) at multiple dilutions. Usage of screening dilution of 1:40 recommended by most manufacturers of commercial ANA kits results in numerous false positive-tests and misdiagnosis of connective tissue disorders (CTDs). We sought to study the ideal screening dilution for ANA by IIF for a diagnosis of ANA-related CTDs. METHODS: Serum samples of patients with ANA-related conditions (n = 233) and healthy controls (n = 154) were evaluated by IIF using Immuno Concepts Hep-2000 ® ANA kits at dilutions from 1:40 to 1:640. Accuracy for diagnosis of CTDs for each serum dilution was assessed by receiver operating curve (ROC) analysis. RESULTS: Antinuclear antibodies (ANA) positivity was observed in 19.5%, 10.4%, 4.55%, 0.65%, and 0% of healthy controls at dilutions of 1:40, 1:80, 1:160, 1:320, and 1:640, respectively. ANA positivity at 1:40 dilution was observed among 26.4% cases with mimics of CTDs. Prevalence of ANA positivity in ANA-related CTDs was 97.3%, 96.4%, 89.3%, 83.9%, and 71.4% at dilutions of 1:40, 1:80, 1:160, 1:320, and 1:640, respectively. ROC analysis revealed best test performance for distinction between healthy and ANA-related CTD populations at a serum dilution of 1 in 80. CONCLUSIONS: Antinuclear antibodies (ANA) positivity at low titers (1:40) is highly prevalent in healthy population (19.5%) as well as amongst mimics of CTD (26.4%). Our study suggests a higher screening dilution of 1:80 for ANA by IIF for diagnosis of CTD maybe better. Combination of 1:80 and 1:160 dilutions provides optimum sensitivity and specificity for diagnosis of ANA-related disorders.

Assessment of knowledge of obstetric danger signs and its associated factors among pregnant women attending antenatal clinic of rural health training centre of a medical college: A cross-sectional study from Rajasthan.

Background and Objectives: Women and newborns are most vulnerable during and immediately after childbirth. The majority of maternal and newborn deaths occurring in developing countries can be attributed to inabilities to access health services, illiteracy, social stigmas, and gender inequalities. Women should be made aware of the danger signs so that health care services can be assessed on time, thus reducing maternal mortality. The objectives of this study were to assess the knowledge about obstetric danger signs and to find out various factors associated with them among pregnant women attending antenatal care (ANC) clinic at the Rural Health Training Centre (RHTC) attached to a Medical College. Methodology: This cross-sectional study was conducted at the ANC clinic of the RHTC attached to a medical college of Rajasthan for a period of 4 months and included 353 pregnant women. A pre-designed and pre-tested schedule was used. Mean knowledge scores were computed and knowledge was classified into adequate and inadequate. Descriptive statistics were used and the Pearson Chi-square test was used as a test of significance, taking a P value of < 0.05 as statistically significant. Results: Educational status of pregnant women, antenatal check-up status and gravid status had significant associations with the knowledge of obstetric danger signs. Conclusions: About half of the respondents had adequate knowledge about the obstetrics danger signs. Therefore, there is a strong need of creating awareness in the community by improving access to health care.

Financial uncertainty and interest rate movements: is Asian bond market volatility different?

The COVID-19 pandemic has given rise to a spike in financial market volatility. In this paper, we attempt to assess the effects of financial & news-driven uncertainty shocks in growing Asian economies, using country-specific bond volatility shocks as a measure of local interest rate uncertainty. Also, we contrast the effects of local uncertainty with global stock market uncertainty. Using bond market data from nine Asian markets, we uncover a transmission mechanism of uncertainty shocks via the bond market. The mechanism works as a crowding-out effect due to government-led excessive market borrowing with supply-side consequences for the private sector, as opposed to economic policy or global stock market uncertainty which works more like a demand shock as in the literature. We conclude that countries with growing fiscal deficits that entail a larger government bond market or higher current account deficits, tend to experience an increase in the cost of borrowing due to this bond market volatility or interest rate uncertainty shocks.

Assessment of Periodontal Status and Treatment Needs among Beedi Factory Workers.

INTRODUCTION: Periodontal disease is considered to be one of the most common oral conditions in human population sharing an equal prevalence rate in both developed and developing countries. It is observed that in India, more than 800 million beedis are sold every year; hence, beedi making is a big industry involving approximately 4.4 million workers, and 76% of these workers are women. OBJECTIVES: The objectives of this study were to assess the frequency of gingival and periodontal disease and to evaluate the treatment needs in labors working in a beedi factory. MATERIALS AND METHODS: A cross-sectional study was conducted on 1000 daily wage labors working in a beedi factory resided at Patna, Bihar. Subjects aged between 19 and 60 years were randomly selected for the study. The community periodontal index of treatment needs (CPITN) index with CPTIN probe along with the demographic data was recorded in daylight. RESULTS: None of the study subjects was found to fall in category community periodontal index-1 (CPI-1), 67.2% of the study population was found to be in CPI-2, 12.3% were found to be in CPI-3, and 9.7% of the study subjects scored CPI-4. For the treatment needs, majority of the subjects were in TN2 category; however, with advancing age, there was increase in the percentage of population requiring TN3 treatment needs. CONCLUSION: CPITN index along with the demographic data was recorded in daylight. The high prevalence rate of periodontal disease in these beedi factory workers was found, which increased with advancing age. The treatment need index also showed rise in the requirement of complex procedures with advancing age, suggesting the role of dental education and regular checkups in these population groups.

Cost-effectiveness of Nivolumab-Ipilimumab Combination Therapy for the Treatment of Advanced Non-Small Cell Lung Cancer.

Importance: Treatment with nivolumab-ipilimumab combination therapy was found to improve overall survival compared with chemotherapy among patients with advanced non-small cell lung cancer (NSCLC) in the CheckMate 227 clinical trial. However, these drugs are substantially more expensive than chemotherapy and, given the high incidence of advanced NSCLC, the incorporation of dual immune checkpoint inhibitors into the standard of care could have substantial economic consequences. Objective: To assess whether nivolumab-ipilimumab combination therapy is a cost-effective first-line treatment for patients with advanced NSCLC. Design, Setting, and Participants: This economic evaluation designed a Markov model to compare the cost-effectiveness of nivolumab-ipilimumab combination therapy with platinum-doublet chemotherapy as first-line treatment for patients with advanced NSCLC. The Markov model was created to simulate patients with advanced NSCLC who were receiving either nivolumab-ipilimumab combination therapy or platinum-doublet chemotherapy. Transition probabilities, including disease progression, survival, and treatment toxic effects, were derived using data from the CheckMate 227 clinical trial. Costs and health utilities were obtained from published literature. Data analyses were conducted from November 2019 to September 2020. Exposures: Nivolumab-ipilimumab combination therapy. Main Outcomes and Measures: The primary study outcomes were quality-adjusted life-years (QALYs) and cost in 2020 US dollars. Cost-effectiveness was measured using an incremental cost-effectiveness ratio (ICER), with an ICER less than $100 000 per QALY considered cost-effective. Model uncertainty was assessed with 1-way and probabilistic sensitivity analyses. Results: Treatment with nivolumab-ipilimumab combination therapy was associated with an increase in overall cost of $201 900 and improved effectiveness of 0.50 QALYs compared with chemotherapy, yielding an ICER of $401 700 per QALY. The study model was sensitive to the cost and duration of immunotherapy. Treatment with nivolumab-ipilimumab combination therapy became cost-effective when monthly treatment costs were reduced from $26 425 to $5058 (80.9% reduction) or when the maximum duration of immunotherapy was reduced from 24.0 months to 1.4 months. The model was not sensitive to assumptions about survival or programmed cell death 1 ligand 1 status. A probabilistic sensitivity analysis indicated that, at a willingness-to-pay threshold of $100 000 per QALY, nivolumab-ipilimumab combination therapy was less cost-effective than chemotherapy 99.9% of the time. Conclusions and Relevance: In this study, first-line treatment with nivolumab-ipilimumab combination therapy was not found to be cost-effective at current prices despite clinical trial data indicating that this regimen increases overall survival among patients with advanced NSCLC.

In vivo assessment of a single adenine mutation in 5'UTR of Endothelin-1 gene in paediatric cases with severe pulmonary hypertension: an observational study.

OBJECTIVE: Endothelin-1 plays an important role in the pathogenesis of severe pulmonary hypertension. The + 139 'A', adenine insertion variant in 5'UTR of edn1 gene has been reported to be associated with increased expression of Endothelin-1 in vitro. The aim of present study was to explore the association of this variant with the circulating levels of Endothelin-1 in vivo using archived DNA and plasma samples from 38 paediatric congenital heart disease (cyanotic and acyanotic) patients with severe pulmonary hypertension. RESULTS: The plasma Endothelin-1 levels were highly varied ranging from 1.63 to75.16 pg/ml. The + 139 'A' insertion variant in 5'UTR of edn1 was seen in 8 out of 38 cases with only one acyanotic sample demonstrating homozygosity of inserted 'A' allele at + 139 site (4A/4A genotype). The plasma Endothelin-1 levels in children with homozygous variant 3A/3A genotype were comparable in cyanotic and acyanotic groups. Lone 4A/4A acyanotic sample had ET-1 levels similar to the median value of ET-1 associated with 3A/3A genotype and was absent in cyanotic group presumably due to deleterious higher ET-1 levels. The discussed observations, limited by the small sample size, are suggestive of homozygous adenine insertion variant posing a risk in cyanotic babies with Severe Pulmonary Hypertension.

Cost-Effectiveness Analysis of Stereotactic Ablative Radiation Therapy in Patients With Oligometastatic Cancer.

PURPOSE: The Stereotactic Ablative Radiation therapy for Comprehensive Treatment of Oligometastatic Tumors phase 2 randomized clinical trial found that stereotactic ablative radiation therapy (SABR) improved outcomes among cancer patients with oligometastatic disease. Yet, the cost of SABR along with the large number of patients with oligometastatic disease raises the important question of value. This study sought to evaluate the cost-effectiveness of the addition of SABR compared with standard therapy alone among cancer patients with oligometastatic disease. METHODS AND MATERIALS: We constructed a Markov model to simulate treatment with stereotactic ablative radiation therapy or standard therapy among patients with oligometastatic cancers. The model derived transition probabilities from Stereotactic Ablative Radiation therapy for Comprehensive Treatment of Oligometastatic Tumors clinical trial data to estimate risks of toxicity, disease progression and survival. Health care costs and health utilities were estimated from the literature. Probabilistic and one-way sensitivity analyses evaluate model uncertainty. Cost-effectiveness was estimated from both the health care sector and societal perspectives with an incremental cost-effectiveness ratio (ICER) defined as dollars per quality-adjusted life year (QALY). An ICER less than $100,000/QALY was considered cost-effective. One-way and probabilistic sensitivity analyses were used to examine model uncertainty. RESULTS: The addition of SABR increased total costs by $54,260 (health care sector perspective) or $72,799 (societal perspective) and improved effectiveness by 1.88 QALYs compared with standard therapy, leading to an ICER of $28,906/QALY (health care sector perspective) or $38,783/QALY (societal perspective). The model was modestly sensitive to assumptions about tumor progression, although the model was not sensitive to assumptions about survival or cost of treatment. Probabilistic sensitivity analyses demonstrated that SABR was the cost-effective treatment option 99.8% (health care sector perspective) or 98.7% (societal perspective) of the time. CONCLUSIONS: The addition of SABR increased costs and improved quality adjusted survival, overall leading to a cost-effective treatment strategy for patients with oligometastatic cancer.

Cost-effectiveness Analysis of Genetic Testing and Tailored First-Line Therapy for Patients With Metastatic Gastrointestinal Stromal Tumors.

Importance: Gastrointestinal stromal tumor (GIST) is frequently driven by oncogenic KIT variations. Imatinib targeting of KIT marked a new era in GIST treatment and ushered in precision oncological treatment for all solid malignant neoplasms. However, studies on the molecular biological traits of GIST have found that tumors respond differentially to imatinib dosage based on the KIT exon with variation. Despite this knowledge, few patients undergo genetic testing at diagnosis, and empirical imatinib therapy remains routine. Barriers to genetic profiling include concerns about the cost and utility of testing. Objective: To determine whether targeted gene testing (TGT) is a cost-effective diagnostic for patients with metastatic GIST from the US payer perspective. Design, Setting, and Participants: This economic evaluation developed a Markov model to compare the cost-effectiveness of TGT and tailored first-line therapy compared with empirical imatinib therapy among patients with a new diagnosis of metastatic GIST. The main health outcome, quality-adjusted life years (QALYs), and costs were obtained from the literature, and transitional probabilities were modeled from disease progression and survival estimates from randomized clinical trials of patients with metastatic GIST. Data analyses were conducted October 2019 to January 2020. Exposure: TGT and tailored first-line therapy. Main Outcomes and Measures: The primary outcome was QALYs and cost. Cost-effectiveness was defined using an incremental cost-effectiveness ratio, with an incremental cost-effectiveness ratio less than $100 000/QALY considered cost-effective. One-way and probabilistic sensitivity analyses were conducted to assess model stability. Results: Therapy directed by TGT was associated with an increase of 0.10 QALYs at a cost of $9513 compared with the empirical imatinib approach, leading to an incremental cost-effectiveness ratio of $92 100. These findings were sensitive to the costs of TGT, drugs, and health utility model inputs. Therapy directed by TGT remained cost-effective for genetic testing costs up to $3730. Probabilistic sensitivity analysis found that TGT-directed therapy was considered cost-effective 70% of the time. Conclusions and Relevance: These findings suggest that using genetic testing to match treatment of KIT variations to imatinib dosing is a cost-effective approach compared with empirical imatinib.