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Coronavirus disease (COVID-19) is an infectious disease caused by a newly discovered coronavirus. The disease is transmitted by inhalation or contact with infected droplets and the incubation period ranges from 2 to 14 days. The case fatality rate is estimated to range from 2 to 3%. As this virus spread very easily in dense places a lot emphasis has been laid down on preventing measures such as social distancing, isolation and quarantine, hand hygiene, respiratory etiquette, environment cleaning besides other measures to minimize the spread.In healthcare organizations, this distancing is achieved through proper layout and designing and through functional segregation of OPD, inpatients, diagnostic services and supportive services along with application of the principles of asepsis and hygiene.

This annual review is the sixth of its kind since 2016 (see references). Our objective is to explore and share articles which we deem influential and significant in the field of biotransformation and bioactivation. These fields are constantly evolving with new molecular structures and discoveries of corresponding pathways for metabolism that impact relevant drug development with respect to efficacy and safety. Based on the selected articles, we created three sections: (1) drug design, (2) metabolites and drug metabolizing enzymes, and (3) bioactivation and safety (Table 1). Unlike in years past, more biotransformation experts have joined and contributed to this effort while striving to maintain a balance of authors from academic and industry settings.[Table: see text]. ispartof: DRUG METABOLISM REVIEWS vol:53 issue:3 pages:384-433 ispartof: location:England status: published

The present study was undertaken to investigate epidemiological distribution, clinical manifestation, co morbid status, treatment strategy and case fatality index of emerging COVID-19 infection at SMS Medical College Hospital, Jaipur, Rajasthan. It also evaluated efficacy of hydroxychloroquine (HCQ) in treatment of patients and risk of serious adverse outcomes in patients with COVID-19 in relation to their co morbid status. The varied spectra of COVID-19 mostly affects young adult age group (third to fifth decades of life). Interestingly, early age group was also affected in significant proportion when compared with similar data from other countries. It was observed that male population seemed to be was more prone to getting infected. Majority of COVID-19 positive patients (nearly three-fourth) were asymptomatic (mostly in young age range) at the time of diagnosis, which poses a major challenge for health care workers. Fever, cough, sore throat and shortness of breath were major symptoms that could be detected in such COVID-19 patients. Symptomatic clinical manifestations were more common in old age population. Infectivity was higher in patients that had underlying co morbid disease, especially in patients with multiple co morbid conditions. Symptomatic presentation of COVID-19 was observed to be higher in patients with co morbid disease. Average recovery time from COVID-19 was 8 days with effective treatment. Mortality in COVID-19 was higher in old age population, male gender, symptomatic and co morbid patients as compared to other similarly matched group. Most of mortality was noted within first few days of admission, suggestive of early mortality due to the primary disease process. Treatment with HCQ had early recovery without effectively influencing the overall mortality.

BACKGROUND: TKM-130803 is a specific anti-EBOV therapeutic comprised of two small interfering RNAs (siRNA) siLpol-2 and siVP35-2. The pharmacokinetics (PK) of these siRNAs was defined in Ebola virus disease (EVD) patients, with reference to efficacy (ET) and toxicology thresholds (TT). The relationship between PK and patient survival was explored. METHODS: Pharmacokinetic (PK) and pharmacodynamic (PD) data were available for seven participants with EVD in Sierra Leone who received 0·3 mg/kg of TKM-130803 by intravenous infusion over 2 h daily for up to 7 days. Plasma concentration of siRNA was compared to survival at 14 days. PK data were fitted to two-compartment models then Monte Carlo simulated PK profiles were compared to ET (Cmax 0·04-0·57 ng/mL and mean concentration 1·43 ng/mL), and TT (3000 ng/mL). FINDINGS: Viral loads (VL) were not significantly different at treatment onset or during treatment (p = 0·1) in subjects who survived or died. siRNA was in quantitative excess of virus genomes throughout treatment, but the 95% percentile exceeded TT. The maximum AUC for which the 95% percentile remained under TT was a continuous infusion of 0·15 mg/kg/day. Plasma concentration of both siRNAs were higher in subjects who died compared to subjects who survived (p

Optimal control strategies for human infections are often investigated by computational approaches using individual-based models (IBMs). These typically track humans and evaluate the impact of control interventions in terms of human deaths, clinical cases averted, interruption of transmission etc. Genetic selection can be incorporated into these IBMs and used to track the spread of mutations whose origin and spread are often driven by the intervention, and which subsequently undermine the control strategy; for example, mutations which encode antimicrobial drug resistance or diagnosis- or vaccine-escape phenotypes. Basic population genetic descriptions of selection are based on infinite population sizes (so that chance fluctuations in allele frequency are absent) but IBMs track finite population sizes. We describe how the finite sizes of IBMs affect simulating the dynamics of genetic selection and how best to incorporate genetic selection into these models. We use the OpenMalaria IBM of malaria as an example, but the same principles apply to IBMs of other diseases. We identify four strategies to incorporate selection into IBMs and make the following four recommendations. Firstly, calculate and report the selection coefficients, s, of the advantageous allele as the key genetic parameter. Secondly, use these values of ‘s’ to calculate the wait-time until a mutation successful establishes itself in the population. The wait time for the mutation can be added to speed of selection, s, to calculate when the mutation will reach significant, operationally important levels. Thirdly, quantify the ability of the IBM to robustly estimate small selection coefficients. Fourthly, optimise computational efficacy: when ‘s’ is small it is plausible that fewer replicates of larger IBMs will be more efficient than a larger number of replicates of smaller size.

The orthogonality of cat and displaced cat states, underlying Heisenberg limited measurement in quantum metrology, is studied in the limit of large number of states. The mesoscopic superposition of the generalized cat state is correlated with the corresponding state overlap function, controlled by the sub-Planck structures arising from phase space interference. The asymptotic expression of this overlap function is evaluated and the validity of large phase space support and distinguishability of the constituent states, in which context the asymptotic limit is achieved, are discussed in detail. For large number of coherent states, uniformly located on a circle, the overlap function significantly matches with the diffraction pattern for a circular ring source with uniform angular strength. This is in accordance with the van Cittert-Zernike theorem, where the overlap function, similar to the mutual coherence function, matches with a diffraction pattern. The physical situation under consideration is delineated in phase space by utilizing Husimi-Q function., Comment: 6 pages, 5 figures. arXiv admin note: substantial text overlap with arXiv:1008.0630

This research was undertaken to understand gender issues on the distribution of, access to, and control over major assets of rice-farming households as well as the effects of technologies promoted by an Agricultural Research for Development (AR4D) project in selected villages in eastern Uttar Pradesh (EUP), India.

The orthogonality of cat and displaced cat states, underlying Heisenberg limited measurement in quantum metrology, is studied in the limit of large number of states. The asymptotic expression for the corresponding state overlap function, controlled by the sub-Planck structures arising from phase space interference, is obtained exactly. The validity of large phase space support, in which context the asymptotic limit is achieved, is discussed in detail. For large number of coherent states, uniformly located on a circle, it identically matches with the diffraction pattern for a circular ring with uniform angular source strength. This is in accordance with the van Cittert-Zernike theorem, where the overlap function, similar to the mutual coherence function matches with a diffraction pattern., Comment: 5 pages, 3 figures

Resistance to broad spectrum β lactams, mediated by extended spectrum beta lactamase (ESβL) and AmpC βL enzymes is an increasing problem worldwide. Presence of these in clinical infections can result in treatment failure if one of the second or third generation cephalosporins is used. Therefore, it is recommended that any ESβL-producing organism according to the National Committee for Clinical Laboratory Standards (NCCLS) criteria can be reported as resistant to all extended spectrum β lactam antibiotics regardless of the susceptibility test results. In this study, a total of 250 Escherichia coli (E. coli) isolates were subjected to Double disc test and AmpC disc test for the detection of ESβL- and AmpC βL-producing strains, respectively. Prevalence of ESβL- and AmpC βL-producing strains among E. coli isolates, over a 3-month-period in the hospital-based population of Jaipur, was 64.80% (162/250). AmpC βL producers were 24.00% (60/250) and co-existence of ESβL and AmpC βL was detected in 8.00% (20/250) of the isolates.

Objectives The objective of this study was to describe the population pharmacokinetics of cefazolin in plasma and the interstitial fluid of subcutaneous tissue of post-trauma critically ill patients and provide clinically relevant dosing recommendations that result in optimal concentrations at the target site. Patients and methods This was a pharmacokinetic study in a tertiary referral ICU. We recruited 30 post-trauma critically ill adult patients and collected serial total and unbound plasma cefazolin concentrations. Interstitial fluid concentrations were determined using in vivo microdialysis. Population pharmacokinetic analysis and Monte Carlo simulations were undertaken with Pmetrics®. Fractional target attainment against an MIC distribution for Staphylococcus aureus isolates was calculated. Results The mean (SD) age, weight, APACHE II score and CLCR were 37.0 (14.1) years, 86.8 (22.7) kg, 16.9 (5.3) and 163 (44) mL/min, respectively. A three-compartment linear population pharmacokinetic model was most appropriate. Covariates included in the model were CLCR on drug clearance and serum albumin concentration and body weight on the volume of the central compartment. The fractional target attainment for a 1 g intravenous 8-hourly dose for a CLCR of 50 mL/min was 88%, whereas for a patient with a CLCR of 215 mL/min, a dose of 2 g 6-hourly achieved 84% fractional target attainment. Conclusions Clinicians should be mindful of the effects of elevated CLCR and serum albumin concentrations on dosing requirements for post-trauma critically ill patients.