A route to access imidazol[1,5-a]indole-1,3-diones and pyrrolo[1,2-c]imidazole-1,3-diones.

A novel and practical route to synthesize imidazol[1,5-a]indoles and pyrrolo[1,2-c]imidazoles via N-H functionalization has been developed. Indole-2-carboxylic acid or pyrrole-2-carboxylic acid with diverse aniline groups and carbonyldiimidazole (CDI), in the presence of a base under microwave conditions, resulted in imidazol[1,5-a]indoles and pyrrolo[1,2-c]imidazoles, respectively. The present method is free of work-up and no need for column chromatography. Both title scaffolds can serve as useful heterocyclic scaffolds in medicinal chemistry as such, or they can be used as building blocks to construct different classes of useful compounds.

Brønsted acid-mediated cyclization-dehydrosulfonylation/reduction sequences: An easy access to pyrazinoisoquinolines and pyridopyrazines.

An efficient and alternative synthetic approach has been developed to prepare various N-(arylethyl)piperazine-2,6-diones from 4-benzenesulfonyliminodiacetic acid and primary amines using carbonyldiimidazole in the presence of a catalytic amount of DMAP at ambient temperature. Piperazine-2,6-diones are successfully transformed to pharmaceutically useful pyridopyrazines or pyrazinoisoquinolines and ene-diamides via an imide carbonyl group activation strategy using a Brønsted acid. Subsequent dehydrosulfonylation reactions of the ene-diamides, in a one pot manner, smoothly transformed them to substituted pyrazinones. A concise synthesis of praziquantel (1) has also been achieved through this method.

Scalable Synthesis of Silacyclohexanones and Ready Access to Silicon Building Blocks.

A simple and efficient two-step method for the synthesis of silacyclohexanones starting from bis(bromoethylsilanes) using TosMIC is presented. The prepared silacyclohexanones were transformed to nine different heterocycles with silicon incorporation. In addition, the developed methodology was used for the synthesis of a sila analogue of the HDAC6 inhibitor tubastatin A.

Utility of prehospital call center ambulance dispatch data for COVID-19 cluster surveillance: A retrospective analysis.

INTRODUCTION: Cluster surveillance, identification, and containment are primary outbreak management techniques; however, adapting these for low- and middle-income countries is an ongoing challenge. We aimed to evaluate the utility of prehospital call center ambulance dispatch (CCAD) data for surveillance by examining the correlation between influenza-like illness (ILI)-related dispatch calls and COVID-19 cases. METHODS: We performed a retrospective analysis of state-level CCAD and COVID-19 data recorded between January 1 and April 30, 2020, in Telangana, India. The primary outcome was a time series correlation between ILI calls in CCAD and COVID-19 case counts. Secondarily, we looked for a year-to-year correlation of ILI calls in the same period over 2018, 2019, and 2020. RESULTS: On average, ILI calls comprised 12.9% (95% CI 11.7%-14.1%) of total daily calls in 2020, compared to 7.8% (95% CI 7.6%-8.0%) in 2018, and 7.7% (95% CI 7.5%-7.7%) in 2019. ILI call counts from 2018, 2019, and 2020 aligned closely until March 19, when 2020 ILI calls increased, representing 16% of all calls by March 23 and 27.5% by April 7. In contrast to the significant correlation observed between 2020 and previous years' January-February calls (2020 and 2019-Durbin-Watson test statistic [DW] = 0.749, p < 0.001; 2020 and 2018-DW = 1.232, p < 0.001), no correlation was observed for March-April calls (2020 and 2019-DW = 2.012, p = 0.476; 2020 and 2018-DW = 1.820, p = 0.208). In March-April 2020, the daily reported COVID-19 cases by time series significantly correlated with the ILI calls (DW = 0.977, p < 0.001). The ILI calls on a specific day significantly correlated with the COVID-19 cases reported 6 days prior and up to 14 days after (cross-correlation > 0.251, the 95% upper confidence limit). CONCLUSIONS: The statistically significant time series correlation between ILI calls and COVID-19 cases suggests prehospital CCAD can be part of early warning systems aiding outbreak cluster surveillance, identification, and containment.

International multi-center real world implementation trial to increase out-of-hospital cardiac arrest survival with a dispatcher-assisted cardio-pulmonary resuscitation package (Pan-Asian resuscitation outcomes study phase 2).

BACKGROUND: Dispatcher-assisted CPR (DA-CPR) has the potential to deliver early bystander CPR (BCPR) and improve out-of-hospital cardiac arrest (OHCA) survival. This study in the Asia-Pacific evaluated the impact of a DA-CPR program on BCPR rates and survival. METHODS: This was a three-arm, prospective, multi-national, population-based, community-level, implementation trial. Cases between January 2009 and June 2018 from the Pan-Asian Resuscitation Outcomes Study were included. Sites either implemented a comprehensive (with quality improvement tool) or a basic DA-CPR package, or served as controls. Primary outcome was survival-to-discharge/30th day post-arrest. Secondary outcomes were BCPR and favorable neurological outcome. A before-after comparison was made within each country; this before-after change was then compared across the three groups using logistic regression. RESULTS: 170,687 cases were analyzed. Before-after comparison showed that survival to discharge was higher in the 'implementation' period in all three groups: comprehensive odds ratio (OR) 1.09, 95% confidence interval (CI; [1.0-1.19]); basic OR 1.14, 95% CI (1.08-1.2); and control OR 1.25, 95% CI (1.02-1.53). Comparing between groups, the comprehensive group had significantly higher change in BCPR (comprehensive vs control ratio of OR 1.86, 95% CI [1.66-2.09]; basic vs control ratio of OR 0.94, 95% CI [0.85-1.05]; and comprehensive vs basic ratio of OR 1.97, 95% CI [1.87-2.08]) and survival with favorable neurological outcome (comprehensive vs basic ratio of OR 1.2, 95% CI [1.04-1.39]). CONCLUSION: We evaluated the impact of a DA-CPR program across heterogeneous EMS systems and demonstrated that a comprehensive DA-CPR program had the most impact on BCPR and favorable neurological outcome.

Estimating the spatial distribution of acute undifferentiated fever (AUF) and associated risk factors using emergency call data in India. A symptom-based approach for public health surveillance.

The System for Early-warning based on Emergency Data (SEED) is a pilot project to evaluate the use of emergency call data with the main complaint acute undifferentiated fever (AUF) for syndromic surveillance in India. While spatio-temporal methods provide signals to detect potential disease outbreaks, additional information about socio-ecological exposure factors and the main population at risk is necessary for evidence-based public health interventions and future preparedness strategies. The goal of this study is to investigate whether a spatial epidemiological analysis at the ecological level provides information on urban-rural inequalities, socio-ecological exposure factors and the main population at risk for AUF. Our results displayed higher risks in rural areas with strong local variation. Household industries and proximity to forests were the main socio-ecological exposure factors and scheduled tribes were the main population at risk for AUF. These results provide additional information for syndromic surveillance and could be used for evidence-based public health interventions and future preparedness strategies.