Cost-Effectiveness of Automated Digital Microscopy for Diagnosis of Active Tuberculosis.

BACKGROUND: Automated digital microscopy has the potential to improve the diagnosis of tuberculosis (TB), particularly in settings where molecular testing is too expensive to perform routinely. The cost-effectiveness of TB diagnostic algorithms using automated digital microscopy remains uncertain. METHODS: Using data from a demonstration study of an automated digital microscopy system (TBDx, Applied Visual Systems, Inc.), we performed an economic evaluation of TB diagnosis in South Africa from the health system perspective. The primary outcome was the incremental cost per new TB diagnosis made. We considered costs and effectiveness of different algorithms for automated digital microscopy, including as a stand-alone test and with confirmation of positive results with Xpert MTB/RIF ('Xpert', Cepheid, Inc.). Results were compared against both manual microscopy and universal Xpert testing. RESULTS: In settings willing to pay $2000 per incremental TB diagnosis, universal Xpert was the preferred strategy. However, where resources were not sufficient to support universal Xpert, and a testing volume of at least 30 specimens per day could be ensured, automated digital microscopy with Xpert confirmation of low-positive results could facilitate the diagnosis of 79-84$1280 per incremental TB diagnosis (95% uncertainty range, UR: $340-$3440) in the base case, but improved under conditions likely reflective of many settings in sub-Saharan Africa: $677 per diagnosis (95$450-$935) when sensitivity of manual smear microscopy was lowered to 0.5, and$956 per diagnosis (95% UR: $40-$2910) when the prevalence of multidrug-resistant TB was lowered to 1%. CONCLUSIONS: Although universal Xpert testing is the preferred algorithm for TB diagnosis when resources are sufficient, automated digital microscopy can identify the majority of cases and halve the cost of diagnosis and treatment when resources are more scarce and multidrug-resistant TB is not common

Effect of clopidogrel on the hydroxylation and sulfoxidation of omeprazole

Based upon the known potential interaction between omeprazole (OMP) and clopidogrel (CLOP), the current study was designed to evaluate the effect of CLOP on disposition of OMP and its two major metabolites, 5-hy- droxyomeprazole (5-OH-OMP) and omeprazole sulfone (OMP-S) in healthy clinical subjects. A randomized, open label, 2-period, crossover study was designed. Twelve volunteers were selected, of whom eight were extensive metabolizers (EM) of CYP2C19 and 4 were poor metabolizers (PM). They received single dose of OMP either alone or in combination with CLOP (single dose) and samples were collected periodically to calculate various pharmacokinetic parameters. Changes in most of the pharmacokinetic parameters of OMP, 5-OH-OMP and OMP- S were insignificant (P ˃ 0.05) both in EM and PM except for the maximum concentration (Cmax) of 5-OH-OMP and OMP-S in EM. The OMP Cmax and AUC0-∞ was increased both in EM and PM after concomitant administration of OMP with CLOP. The 5-OH-OMP Cmax was decreased in both EM and PM, demonstrating that CLOP inhibits hydroxylation of OMP. The OMP-S Cmax and AUC0-∞ were increased both in EM and PM showing that CLOP may induce sulfoxidation of OMP. It was concluded that CLOP may inhibit hydroxylation of OMP to a greater extent in EM than in PM, leading to higher OMP Cmax and AUC0-∞. Furthermore, the sulfoxidation of OMP may also be induced by CLOP. So, it is suggested that both these drugs should be carefull prescribed together to avoid any harm to the patients. (Application number13/EC/Pharm. Ref number 12/Pharm)

Comparison of the VersaTREK blood culture system against the Bactec9240 system in patients with suspected bloodstream infections

BACKGROUND: To evaluate the VersaTREK (TREK Diagnostic Systems, Cleveland, Ohio) blood culture system against the Bactec9240 (BD Microbiology, Cockeysville, MD), for the recovery of bloodstream pathogens. METHODS: Venous blood from patients with suspected bacterial sepsis was evenly distributed into bottles of each system. Positive signals were recorded and bottles processed onto standard media for organism recovery. False positive signals were regarded if no organisms were seen on Gram stain and no growth was observed. RESULTS: 177 bottles were available for analysis; the Bactec9240 system yielded 43 positive, 134 negative results and no false positive signals. The VersaTREK system had 58 positive signals with 14 being false positives. CONCLUSIONS: In our setting with high background burden of immuno-compromised patients, the VersaTREK system compared favourably with the Bactec9240 in recovering blood stream aerobic and facultative anaerobic pathogens from patients with suspected bacterial sepsis. A concern is the high false positivity rate. Due to its versatility to accommodate small and large workloads as well as using smaller volumes of blood, this system may establish itself as a useful alternative for the recovery of bloodstream pathogens

The hidden transitions between stability, traffic intensity, and chaos of the non-stationary E_(-k) /M/1 queueing system

This research investigates the unexplored domain of negative k parameters within dynamic systems, focusing on their influence across stability, traffic intensity, and chaotic phases. Using an iterative computational framework, we examine the sigma function (σ) to characterize system responses under varying conditions of k and ρ. Visualizations and insights demonstrate transitions between phases for a first-time-ever exploration for negative values of the number of sets of phases, namely k, with novel findings extending foundational studies. This work establishes a baseline for further explorations of negative parameter spaces in complex systems. It is to be noted that the current work provides new contributions to Ismail’s Contemporary Pointwise Stationary  Fluid Approximation Theory by offering a comprehensive computational framework for exploring dynamic system behaviors across varying parameters

Isolation and purification of membrane-bound cytochrome c from Proteus mirabilis

In the present studies, respiratory chain pathogenic bacterium, Proteus mirabilis, was investigated. In the first phase, growth profile study was performed to optimize the P. mirabilis growth. Maximum bacterial growth could be obtained between 10 – 12 h of culturing time. Down-stream processing was performed by using sonication, ultracentrifugation and detergent solubilization techniques. Partially purified respiratory contents were analyzed spectrophotometrically. Pyridine-ferrochrome and redoxspectra showed the presence of heme-c

Drug-resistance mechanisms and tuberculosis drugs.

This publication presents independent research supported by the Health Innovation Challenge Fund (HICF-T5-342 and WT098600), a parallel funding partnership between the UK Department of Health and Wellcome Trust.This is the final version of the article. It first appeared at http://dx.doi.org/10.1016/S0140-6736(14)62450-8

Bedaquiline and clofazimine : successes and challenges

Bedaquiline, a novel therapeutic drug, and clofazimine, a re-purposed drug, are front-line therapies recommended by WHO to treat rifampicin-resistant or multidrugresistant tuberculosis. Both drugs have been in use in South Africa at least 10 years: bedaquiline since 2007 and clofazimine since 2010. The use of bedaquiline in programmatic settings in South Africa has reduced the risk of all-cause mortality threefold (hazard ratio 0·35, 95% CI 0·28–0·46)1 and achieved treatment success in at least 70% of patients.2 The inclusion of clofazimine in combination therapy has reduced treatment duration from 18–24 months to 9–12 months. South Africa has adopted both drugs extensively in the modified short and long regimens for rifampicin-resistant or multidrug-resistant tuberculosis. According to the electronic drug-resistant tuberculosis register, as of June 1, 2020, 29 193 individuals in South Africa have received bedaquiline, and 30 599 have received clofazimine. Emerging resistance and cross-resistance have been reported.http://www.thelancet.com/microbeam2021Medical Microbiolog

Bedaquiline and clofazimine : successes and challenges

Bedaquiline, a novel therapeutic drug, and clofazimine, a re-purposed drug, are front-line therapies recommended by WHO to treat rifampicin-resistant or multidrugresistant tuberculosis. Both drugs have been in use in South Africa at least 10 years: bedaquiline since 2007 and clofazimine since 2010. The use of bedaquiline in programmatic settings in South Africa has reduced the risk of all-cause mortality threefold (hazard ratio 0·35, 95% CI 0·28–0·46)1 and achieved treatment success in at least 70% of patients.2 The inclusion of clofazimine in combination therapy has reduced treatment duration from 18–24 months to 9–12 months. South Africa has adopted both drugs extensively in the modified short and long regimens for rifampicin-resistant or multidrug-resistant tuberculosis. According to the electronic drug-resistant tuberculosis register, as of June 1, 2020, 29 193 individuals in South Africa have received bedaquiline, and 30 599 have received clofazimine. Emerging resistance and cross-resistance have been reported.https://www.thelancet.com/microbeam2022Medical Microbiolog

Hindering and enabling factors towards ICT integration in schools: A developing country perspective

ICT in education has emerged as a widespread phenomenon and has been widely considered and explored. While remarkable achievement in ICT use in the teaching and learning process has been observed in the developed part of the world, schools in the developing countries still fail to do so. Pakistan, as a less developed country, has still been in its infancy stage of ICT integration in schools. The purpose of this paper was thus, to explore the existing state of affairs in relation to ICT integration in schools via reviewing both the hindering and enabling factors. The study employed a systemic review method to review the available research, conducted in Pakistan, in the last ten years. The results inform about several fundamental issues and provide a way forward towards effective ICT integration in the process of teaching and learning.