Iridium(III)-catalyzed photoredox cross-coupling of alkyl bromides with trialkyl amines: access to α-alkylated aldehydes.

A C(sp3)-C(sp3) cross coupling approach based on an iridium-photocatalytic radical process has been developed enabling the synthesis of various α-alkylated aldehydes from easily available/synthesized alkyl bromides and trialkyl amines under mild photocatalytic conditions. The synthesized aldehydes are also explored as a functional handle for various useful products such as carboxylic acid, alcohol and N-heterocycle synthesis.

Aromatic C(sp2 )-H Functionalization by Consecutive Paired Electrolysis: Dibromination of Aryl Amines with Dibromoethane at Room Temperature.

Herein, we disclose a facile and efficient electrochemical method for the dibromination of aryl amines by double functionalization of aromatic C(sp2 )-H (both para and ortho) under metal- and external oxidant-free conditions at room temperature for the first time. The reaction is demonstrated using 1,2-dibromoethane to dibrominate a wide range of N-substituted aryl amines in a simple setup with C(+)/Pt(-) electrodes under mild reaction conditions. This transformation proceeds smoothly with a broad substrate scope affording the valuable and versatile N-substituted 2,4-dibromoanilines in moderate to excellent yields with high regioselectivity. In this paired electrolysis, cathodic reduction of 1,2-DBE followed by anodic oxidation generates bromonium intermediates, which then couple with anilines to furnish the dibrominated products. It represents a distinctive approach to challenging redox-neutral reactions. The versatility of the electrochemical ortho-, para-dibromination was reflected by unique regioselectivities for challenging aryl amines and gram-scale electrosynthesis without the use of a stoichiometric oxidant or an activating agent.

Cost-effectiveness of implementing risk-based cardiovascular disease (CVD) management using updated WHO CVD risk prediction charts in India.

INTRODUCTION: The World Health Organization (WHO) has released the updated cardiovascular disease (CVD) risk prediction charts in 2019 for each of the 21 Global Burden of Disease regions. The WHO advocates countries to implement population-based CVD risk assessment and management using these updated charts for preventing and controlling CVDs. OBJECTIVE: To assess the cost-effectiveness of implementing risk-based CVD management using updated WHO CVD risk prediction charts in India. METHODS: We developed a decision tree combined with Markov Model to simulate implementing two community-based CVD risk screening strategies (interventions) compared with the current no-screening scenario. In the first strategy, the whole population is initially screened using the WHO non-lab-based CVD risk assessment method, and those with ≥10% CVD risk are subjected to WHO lab-based CVD risk assessment (two-stage screening). In the second strategy, the whole population is subjected only to the lab-based CVD risk assessment (single-stage screening). A mathematical cohort of those aged ≥40 years with no history of CVD events was simulated over a lifetime horizon with three months of cycle length. Data for the model were derived from a primary study and secondary sources. Incremental cost-effectiveness ratios (ICERs) were determined for the screening strategies and sensitivity analyses. RESULTS: The discounted Incremental cost-effectiveness ratio per QALY gained for both the two-stage (US$ 105; ₹ 8,656) and single-stage (US$ 1073; ₹ 88,588) screening strategies were cost-effective at an implementation effect of 40% when compared with no screening scenario. Implementing CVD screening strategies are estimated to cause substantial reduction in the number of CVD events in the population compared to the no screening scenario. CONCLUSION: In India, both CVD screening strategies would be cost-effective, and implementing the two-staged screening would be more cost-effective. Our findings support implementing population-based CVD screening in India. Future studies shall assess the budget impact of these strategies at different implementation coverage levels.

Comprehensive league table of cost-utility ratios: A systematic review of cost-effectiveness evidence for health policy decisions in India.

Background and objectives: Although a relatively recent concept for developing countries, the developed world has been using League Tables as a policy guiding tool for a comprehensive assessment of health expenditures; country-specific "League tables" can be a very useful tool for national healthcare planning and budgeting. Presented herewith is a comprehensive league table of cost per Quality Adjusted Life Years (QALY) or Disability Adjusted Life Years (DALY) ratios derived from Health Technology Assessment (HTA) or economic evaluation studies reported from India through a systematic review. Methods: Economic evaluations and HTAs published from January 2003 to October 2019 were searched from various databases. We only included the studies reporting common outcomes (QALY/DALY) and methodology to increase the generalizability of league table findings. To opt for a uniform criterion, a reference case approach developed by Health Technology Assessment in India (HTAIn) was used for the reporting of the incremental cost-effectiveness ratio. However, as, most of the articles expressed the outcome as DALY, both (QALY and DALY) were used as outcome indicators for this review. Results: After the initial screening of 9,823 articles, 79 articles meeting the inclusion criteria were selected for the League table preparation. The spectrum of intervention was dominated by innovations for infectious diseases (33%), closely followed by maternal and child health (29%), and non-communicable diseases (20%). The remaining 18% of the interventions were on other groups of health issues, such as injuries, snake bites, and epilepsy. Most of the interventions (70%) reported DALY as an outcome indicator, and the rest (30%) reported QALY. Outcome and cost were discounted at the rate of 3 by 73% of the studies, at 5 by 4% of the studies, whereas 23% of the studies did not discount it. Budget impact and sensitivity analysis were reported by 18 and 73% of the studies, respectively. Interpretation and conclusions: The present review offers a reasonably coherent league table that reflects ICER values of a range of health conditions in India. It presents an update for decision-makers for making decisions about resource allocation.

Cost-effectiveness analysis of 'test and treat' policy for antiretroviral therapy among heterosexual HIV population in India.

Background & objectives: The World Health Organisation recommended immediate initiation of antiretroviral therapy (ART) in all adult human immunodeficiency virus (HIV) patients regardless of their CD4 cell count. This study was undertaken to ascertain the cost-effectiveness of implementation of these guidelines in India. Methods: A Markov model was developed to assess the lifetime costs and health outcomes of three scenarios for initiation of ART treatment at varying CD4 cell count <350/mm[3], <500/mm[3] and test and treat using health system perspective using life-time horizon. A few input parameters for this model namely, transition probabilities from one stage to another stage of HIV and incidence rates of TB were calculated from the data of Centre of Excellence for HIV treatment and care, Chandigarh; whereas, other parameters were obtained from the published literature. Total HIV-related deaths averted, HIV infections averted and incremental cost-effectiveness ratio per quality adjusted life years (QALYs) gained were calculated. Result: Test and treat intervention slowed down the progression of disease and averted 18,386 HIV-related deaths, over lifetime horizon. It also averted 16,105 new HIV infections and saved 343,172 QALYs as compared to the strategy of starting ART at CD4 cell count of 500/mm[3]. Incremental cost per QALY gained for the immediate initiation of ART as compared to ART at CD4 cell count of 500/mm[3] and 350/mm[3] was ₹ 46,599 and 80,050, respectively at reported rates of adherence to the therapy. Interpretation & conclusions: Immediate ART (test and treat) is highly cost-effective strategy over the past criteria of delayed therapy in India. Cost-effectiveness of this policy is largely because of reduction in the transmission of HIV.

Cost-effectiveness of incorporating Mycobacterium indicus pranii vaccine to multidrug therapy in newly diagnosed leprosy cases for better treatment outcomes & immunoprophylaxis in contacts as leprosy control measures for National Leprosy Eradication Programme in India.

Background & objectives: The elimination goal for leprosy as a public health problem at the national level was achieved in 2005 in India. However, the number of new cases reporting annually remained nearly the same during the last 10-15 years. Moreover, a substantial number of these new cases reported disabilities for the first time. Therefore, besides multidrug therapy (MDT), newer strategies with focus on effectively decreasing the number of new cases, optimizing the treatment of detected cases, averting disabilities and arresting the transmission of the disease are required. So the objective of this study was to assess the cost-effectiveness of Mycobacterium indicus pranii (MIP) vaccine implementation in National Leprosy Eradication Programme (NLEP) for newly diagnosed leprosy patients as well as their contacts to arrest/decrease the transmission and occurrence of new cases. Methods: This was a model-based estimation of incremental costs, total quality-adjusted life years (QALYs) gained, new cases averted, deaths averted, incremental cost-effectiveness ratio (ICER) and budget impact of the vaccination intervention. This model included the addition of MIP treatment intervention to the newly detected leprosy patients as well as vaccination with MIP to their contacts. Results: Using the societal perspective, discounted ICER was estimated to be ₹73,790 per QALY gained over a five-year time period. Probabilistic sensitivity analysis (PSA) was assessed by varying the values of input parameters. Majority (96%) of simulations fell in North East quadrant of cost-effectiveness plane, which were all below the willingness to pay threshold. Interpretation & conclusions: Introduction of MIP vaccination in the NLEP appears to be a cost-effective strategy for India. Significant health gains were reduction in the number of new leprosy cases, decreased incidence and severity of reactions during treatment, and after release from treatment, prevention of disabilities, thus reducing the cost as well as stigma of the disease.

Cubic Lattice Structures of Ti6Al4V under Compressive Loading: Towards Assessing the Performance for Hard Tissue Implants Alternative.

Porous Lattice Structure (PLS) scaffolds have shown potential applications in the biomedical domain. These implants' structural designs can attain compatibility mechanobiologically, thereby avoiding challenges related to the stress shielding effect. Different unit cell structures have been explored with limited work on the fabrication and characterization of titanium-based PLS with cubic unit cell structures. Hence, in the present paper, Ti6Al4V (Ti64) cubic PLS scaffolds were analysed by finite element (FE) analysis and fabricated using selective laser melting (SLM) technique. PLS of the rectangular shape of width 10 mm and height 15 mm (ISO: 13314) with an average pore size of 600-1000 µm and structure porosity percentage of 40-70 were obtained. It has been found that the maximum ultimate compressive strength was found to be 119 MPa of PLS with a pore size of 600 µm and an overall relative density (RD) of 57%. Additionally, the structure's failure begins from the micro-porosity formed during the fabrication process due to the improper melting along a plane inclined at 45 degree.

Assessment of risk factors associated with prevalence of gastrointestinal parasites in poultry of central plain zone of Punjab, India.

BACKGROUND AND AIM: Parasitic diseases are an important hurdle to the economy for the developing poultry industry due to their deleterious effects resulting into malnutrition, diminished feed conversion ratio, weight loss, decreased egg production, and mortality in young birds. The aim of this study was to assess the prevalence and associated risk factors of gastrointestinal (GIT) parasites in poultry farms of central plain zone of Punjab. MATERIALS AND METHODS: A total of 490 pooled droppings and 351 intact intestines of poultry from slaughterhouses from seven districts of central plain zone of Punjab state, India, were collected and analyzed from September 2016 to May 2018 by qualitative and quantitative techniques. RESULTS: An overall prevalence of GIT parasites was 38.36% with significantly (p<0.01) highest (74.1%) in Ludhiana and lowest (12.0%) in Shri Fatehgarh Sahib. The most predominant (86.2%) infection was coccidia. The birds reared under a deep litter system were having a higher (p<0.01) fecal load of helminthic eggs and coccidian oocysts (54.4%) compared to the cage system (37.5%). Infection rate was apparently more (40%) in broilers than layers (35.7%). Prevalence of GIT parasites was higher (p<0.01) in monsoon season (58.5%) and lower in summer season (24.48%). The broilers in the age group of 0-2 weeks possessed a significant higher (p<0.05) level of GIT parasitic infection (57.5%), while in case of layers, a higher infection rate (46.66%) was observed in birds between 9 and 18 weeks of age as compared in other groups. Higher (p<0.05) infection rate of GIT parasites was seen in crossbred (45.55%) birds as compared to desi birds (20.00%). CONCLUSION: The study showed that coccidiosis was the predominant infection among all GIT parasites based on fecal and intestinal tract content analysis. The risk factors associated with the prevalence of GIT parasitic infections were geographical location, deep litter system, broilers, age, crossbred breeds, and monsoon season.

Economic evaluation of implementing a decentralised Hepatitis B virus diagnostic intervention under National Viral Hepatitis Control Programme in Tamil Nadu, South India.

OBJECTIVE: To assess the cost-effectiveness of decentralised diagnostic programme for hepatitis B virus (HBV) implemented in Tamil Nadu, South India with specific focus on a selected key population at increased risk of HBV. METHODS: A combination of decision tree and Markov model was developed to compare cost-effectiveness of the new and standard strategy. Cost and health outcomes were calculated based on the proportion of cohort in each respective health state. Total costs, quality-adjusted life years (QALYs) and incremental cost-effectiveness ratio (ICER) of the intervention and comparator strategies were calculated. The model parameter uncertainties were evaluated by sensitivity analysis. RESULTS: Considering decentralised HBV diagnosis followed by early treatment and vaccination for negatives for a cohort of 1000 population resulted in 505 QALYs gained and incremental cost-saving of 180749 ($2620). The decentralised diagnostic strategy could avert 294 deaths, gain 293 life years and reduce out-of-pocket expenditure of 3274 ($47) per person for HBV management. CONCLUSION: Decentralised HBV diagnosis followed by early treatment and vaccination for negatives in Tamil Nadu can save lives and reduce out-of-pocket expenditures compared to standard strategy.

OBJECTIF: Evaluer le rapport coût-efficacité du programme de diagnostic décentralisé du virus de l'hépatite B (VHB) mis en œuvre au Tamil Nadu, dans le sud de l'Inde, avec un accent particulier sur une population clé sélectionnée à risque accru du VHB. MÉTHODES: Une combinaison d'arbre de décision et de modèle de Markov a été développée pour comparer la rentabilité de la stratégie nouvelle et standard. Les coûts et les résultats pour la santé ont été calculés sur base de la proportion de la cohorte dans chaque état de santé respectif. Les coûts totaux, les années de vie corrigées de la qualité (QALY), le rapport coût-efficacité supplémentaire de l'intervention et les stratégies de comparaison ont été calculés. Les incertitudes des paramètres du modèle ont été évaluées par analyse de sensibilité. RÉSULTATS: La prise en compte d'un diagnostic décentralisé du VHB suivi d'un traitement précoce et d'une vaccination des cas négatifs pour une cohorte de 1000 habitants a permis de gagner 505 QALY et d'économiser des coûts supplémentaires de ₹180.749 (2.620 USD). La stratégie de diagnostic décentralisée pourrait éviter 294 décès, gagner 293 années de vie et réduire les dépenses personnelles de ₹3274 (47 USD) par personne pour la prise en charge du VHB. CONCLUSION: Le diagnostic décentralisé du VHB suivi d'un traitement précoce et de la vaccination des cas négatifs au Tamil Nadu peut sauver des vies et réduire les dépenses personnelles par rapport à la stratégie standard.

Process evaluation of health system costing - Experience from CHSI study in India.

BACKGROUND: A national study, 'Costing of healthcare services in India' (CHSI) aimed at generating reliable healthcare cost estimates for health technology assessment and price-setting is being undertaken in India. CHSI sampled 52 public and 40 private hospitals in 13 states and used a mixed micro-costing approach. This paper aims to outline the process, challenges and critical lessons of cost data collection to feed methodological and quality improvement of data collection. METHODS: An exploratory survey with 3 components-an online semi-structured questionnaire, group discussion and review of monitoring data, was conducted amongst CHSI data collection teams. There were qualitative and quantitative components. Difficulty in obtaining individual data was rated on a Likert scale. RESULTS: Mean time taken to complete cost data collection in one department/speciality was 7.86(±0.51) months, majority of which was spent on data entry and data issues resolution. Data collection was most difficult for determination of equipment usage (mean difficulty score 6.59±0.52), consumables prices (6.09±0.58), equipment price(6.05±0.72), and furniture price(5.64±0.68). Human resources, drugs & consumables contributed to 78% of total cost and 31% of data collection time. However, furniture, overheads and equipment consumed 51% of time contributing only 9% of total cost. Seeking multiple permissions, absence of electronic records, multiple sources of data were key challenges causing delays. CONCLUSIONS: Micro-costing is time and resource intensive. Addressing key issues prior to data collection would ease the process of data collection, improve quality of estimates and aid priority setting. Electronic health records and availability of national cost data base would facilitate conducting costing studies.

Evaluating two oral health video interventions with early head start families.

Poor oral health in early childhood can have long-term consequences, and parents often are unaware of the importance of preventive measures for infants and toddlers. Children in rural, low-income families suffer disproportionately from the effects of poor oral health. Participants were 91 parents of infants and toddlers enrolled in Early Head Start (EHS) living in rural Hawai'i, USA. In this quasi-experimental design, EHS home visitors were assigned to use either a didactic or family-centered video with parents they served. Home visitors reviewed short segments of the assigned videos with parents over an eight-week period. Both groups showed significant prepost gains on knowledge and attitudes/behaviors relating to early oral health as well as self-reported changes in family oral health routines at a six-week followup. Controlling for pretest levels, parents in the family-centered video group showed larger changes in attitudes/behaviors at posttest and a higher number of positive changes in family oral health routines at followup. Results suggest that family-centered educational videos are a promising method for providing anticipatory guidance to parents regarding early childhood oral health. Furthermore, establishing partnerships between dental care, early childhood education, and maternal health systems offers a model that broadens potential reach with minimal cost.

Comparison of the effectiveness of 0.5% tea, 2% neem and 0.2% chlorhexidine mouthwashes on oral health: a randomized control trial.

BACKGROUND: The aim of this study was to evaluate and compare the effectiveness of 0.5% tea, 2% neem, and 0.2% chlorhexidine mouthwashes on oral health. MATERIALS AND METHODS: A randomized blinded controlled trial with 30 healthy human volunteers of age group 18-25 years was carried out. The subjects were randomly assigned to 3 groups i.e., group A - 0.2% chlorhexidine gluconate (bench mark control), Group B - 2% neem, and group C - 0.5% tea of 10 subjects per group. Plaque accumulation and gingival condition were recorded using plaque index and gingival index. Oral hygiene was assessed by simplified oral hygiene index (OHIS). Salivary pH was assessed by indikrom pH strips. Plaque, gingival, and simplified OHI scores as well as salivary pH were recorded at baseline, immediately after 1 st rinse, after 1 week, 2 nd week, and 3 rd week. The 3 rd week was skipped for group A. RESULTS: Mean plaque and gingival scores were reduced over the 3 week trial period for experimental and control groups. Anti-plaque effectiveness was observed in all groups and the highest being in group C (P < 0.05). Neem and tea showed comparative effectiveness on gingiva better than chlorhexidine (P < 0.05). The salivary pH rise was sustained and significant in Group B and C compared to Group A. Oral hygiene improvement was better appreciated in Group B and Group C. CONCLUSION: The effectiveness of 0.5% tea was more compared to 2% neem and 0.2% chlorhexidine mouth rinse.

Expression analyses of zebrafish transferrin, ifabp, and elastaseB mRNAs as differentiation markers for the three major endodermal organs: liver, intestine, and exocrine pancreas.

In the present work, three zebrafish cDNA clones encoding transferrin, intestinal fatty acid binding protein (IFABP), and elastaseB were cloned and their expression patterns in early zebrafish development were characterized as differentiation markers for the three major endoderm organs: liver, intestine, and exocrine pancreas. transferrin and ifabp mRNAs exhibit a biphasic expression pattern during early development. transferrin mRNAs were first expressed at approximately 7 hours postfertilization (hpf) in the yolk syncytial layer (YSL) and later in the liver rudiment (from approximately 48 hpf) and in the esophagus transiently (72-96 hpf). Ifabp mRNAs were initially expressed in the YSL at the ventral side during late epiboly (8-9 hpf), spread throughout the YSL of later stage embryos, and appeared in the intestine rudiment at approximately 36 hpf. In contrast to the transferrin and ifabp mRNAs, elastaseB mRNAs were not expressed in the yolk sac or YSL, and these transcripts were detected exclusively in the exocrine pancreas after approximately 56 hpf.