Efficacy and safety of different regimens in the treatment of patients with latent tuberculosis infection: a systematic review and network meta-analysis of randomized controlled trials.

BACKGROUND: Treatment of latent tuberculosis infection (LTBI) is effective in preventing progression to TB disease. This study aimed to synthesize available evidence on the efficacy, adherence, and safety of LTBI treatment in order to assist policymakers to design appropriate national treatment policies and treatment protocols. METHOD: The PRISMA-NMA was used to review and report this research. Randomized controlled trials which compared the efficacy and safety of LTBI treatments were included. A systematic literature search was done to identify relevant articles from online databases PubMed/ MEDLINE, Embase, and Cochrane Center for Clinical Trial database (CENTRAL). The network meta-analysis was done using R- studio Version 1.4.1103. RESULT: In this review, 42 studies were included, which enrolled 46,022 people who had recent contact with patients with active tuberculosis, evidence radiological of previous tuberculosis, tuberculin test equal or greater than 5 mm, radiographs that indicated inactive fibrotic or calcified parenchymal and/or lymph node lesions, had conversion to positive results on a tuberculin skin test, participants living with HIV, chronic Silicosis, immigrants, prisoners, old people, and pregnant women who were at risk for latent TB were included. The incidence of TB among people living with HIV who have taken 3RH as TPT was lower, followed by 48%,followed by 6H (41%). However, 3HP has also the potential to reduce the incidence of TB by 36% among HIV negative patients who had TB contact history. Patients' adherence to TPT was higher among patients who have taken 4R (RR 1.38 95% CI 1.0,1.89) followed by 3RH (34%). The proportion of subjects who permanently discontinued a study drug because of an adverse event were three times higher in the 3RH treatment group. Furthermore, the risk of grade 3 and 4 liver toxicity was significantly higher in 9H followed by 1HP, and 6H. CONCLUSION: From this review, it can be concluded 3RH and 6H has a significant impact on the reduction of TB incidence among PLWH and 3HP among HIV negative people who had TB contact history. However, combinations of rifampicin either with isoniazid were significantly associated with adverse events which resulted in permanent discontinuation among adult patients. Furthermore, grade 3 and 4 liver toxicity was more common in patents who have taken 9H, 1HP, and 6H. This may support the current recommended TPT regimen of 3HP, 3RH, and 6H.

Use of Xpert Contributes to Accurate Diagnosis, Timely Initiation, and Rational Use of Anti-TB Treatment Among Childhood Tuberculosis Cases in South Central Ethiopia.

BACKGROUND: Childhood tuberculosis (TB) was under-prioritized, and only 15% of childhood TB cases are microbiologically confirmed. Hence, most childhood TB diagnoses are made on a clinical basis and prone to over- or under-treatment. Xpert is a rapid method for the diagnosis of childhood TB with high sensitivity. OBJECTIVE: To assess the use of Xpert for accurate diagnosis, timely initiation, and rational use of anti-TB treatment among childhood TB. METHODS: In 2016, the hospital facilitated the installation of the Xpert machine. We reviewed data trends over four consecutive years; two years before the arrival of the machine and two years following the implementation of Xpert. Data were extracted retrospectively from electronically stored databases and medical records and entered to SPSS 21 for analysis. RESULTS: In the pre-intervention period (2014-2015), 404 cases of children presenting with symptoms or signs suggestive of TB ("presumptive TB") were evaluated using AFB microscopy. A total of 254 (62.8%) TB diagnoses were made, of which 54 (21.3%) were confirmed by smear AFB while 200 (78.7%) were treated as smear-negative TB cases. The mean waiting time to start anti-TB treatment was 6.95 days [95% CI (3.71-10.90)]. During the intervention period (2016-2017), 371 children with presumptive TB were evaluated using Xpert. A total of 199 (53.6%) childhood TB cases were notified, of which 88 (44.2%) were Xpert positive and 111 (55.8%) were treated as Xpert-negative probable TB cases. The tendency to initiate anti-TB treatment for unconfirmed TB cases was reduced by a third. Compared with smear AFB, Xpert improved accuracy of diagnosing pediatric TB cases two-fold. The average waiting time to start anti-TB treatment was 1.33 days [95% CI (0.95-1.71)]. There was a significant reduction in the waiting time to start anti-TB treatment, with a mean time difference before and during intervention of 5.62 days [95% CI (1.68-9.56)]. CONCLUSION: Xpert use was associated with a significant increase in the accuracy of identifying confirmed TB cases, reduced unnecessary anti-TB prescription, and shortened the time taken to start TB treatment.

Effect of tacticity on the structure and glass transition temperature of polystyrene adsorbed onto solid surfaces.

We have carried out atomistic (all-atom) molecular dynamics simulations to investigate the effect of tacticity on the structure and glass transition temperature (Tg) of polystyrene (PS) thin films adsorbed on two distinct types of solid substrates. The systems consist of thin films made of atactic, isotactic, and syndiotactic PS chains supported by graphite or hydroxylated α-quartz substrates, which are known to be atomically flat but chemically and structurally different. We have observed a marked dependence of the film structure on substrate type as well as on tacticity. For instance, rings' orientation near substrate surfaces depends on substrate type for atactic PS and isotactic PS films, while no such dependence is observed for syndiotactic PS films whose interfacial structure seems to result from their propensity to adopt the trans conformation rather than their specific interaction with the substrates. Moreover, our results indicate that glass transition temperatures of substrate supported polystyrene films are higher compared to those of the corresponding free-standing films. More specifically, PS films on graphite exhibit larger Tg values than those on α-quartz, and we have noticed that syndiotactic PS has the largest Tg irrespective of the substrate type. Furthermore, the local Tg in the region of the film in contact with the substrates shows a strong tacticity and substrate dependence, whereas no dependencies were found for the local Tg in the middle of the film. Substrate-film interaction energy and chains' dynamics near substrate-film interfaces were subsequently investigated in order to substantiate the obtained Tgs, and it was found that films with higher Tgs are strongly adsorbed on the substrates and/or exhibit smaller interfacial chains' dynamics essentially due to steric hindrance.

Use of indicators of standards of care to improve tuberculosis program management in Ethiopia.

BACKGROUND: Systematic monitoring of health programs and on-site mentoring of health workers are essential for the success of health care. This operations research was designed to measure the effectiveness of a new mentorship and supervisory tool for supervisors. METHODS: In 2011 the Help Ethiopia Address the Low TB Performance (HEAL TB) Project used WHO or national TB indicators as standards of care (SOC) for baseline assessment, progress monitoring, gap identification, assessment of health workers' capacity-building needs, and data quality assurance. Cut-off points were selected for poor, average, and best performers for each indicator. In this analysis we present results from 10 zones (of 28) in which 1,165 health facilities were supported from 2011 through 2015. Other zones were excluded from the analysis because they entered the project later. The data were collected by trained mentors/supervisors and entered into Microsoft Excel. We used rates and ratios to show the impact of the intervention. RESULTS: The improvement in the median composite score of 13 selected major indicators (out of 22) over four years was significant (p = 0.000). The proportion of health facilities with 100% data accuracy for all forms of TB was 55.1% at baseline and reached 96.5%. In terms of program performance, the TB cure rate improved from 71% to 91.1%, while the treatment success rate increased from 88% to 95.3%. In the laboratory area, where there was previously no external quality assurance (EQA) for sputum microscopy, 1,165 health facilities now have quarterly EQA, and 96.1% of the facilities achieved a ≥ 95% concordance rate in blinded rechecking. CONCLUSION: The SOC approach for supervision was effective for measuring progress, enhancing quality of services, identifying capacity needs, and serving as a mentorship and an operational research tool.

Uptake of Isoniazid Preventive Therapy among Under-Five Children: TB Contact Investigation as an Entry Point.

A child's risk of developing tuberculosis (TB) can be reduced by nearly 60% with administration of 6 months course of isoniazid preventive therapy (IPT). However, uptake of IPT by national TB programs is low, and IPT delivery is a challenge in many resource-limited high TB-burden settings. Routinely collected program data was analyzed to determine the coverage and outcome of implementation of IPT for eligible under-five year old children in 28 health facilities in two regions of Ethiopia. A total of 504 index smear-positive pulmonary TB (SS+) cases were reported between October 2013 and June 2014 in the 28 health facilities. There were 282 under-five children registered as household contacts of these SS+ TB index cases, accounting for 17.9% of all household contacts. Of these, 237 (84%) were screened for TB symptoms, and presumptive TB was identified in 16 (6.8%) children. TB was confirmed in 5 children, producing an overall yield of 2.11% (95% confidence interval, 0.76-4.08%). Of 221 children eligible for IPT, 64.3% (142) received IPT, 80.3% (114) of whom successfully completed six months of therapy. No child developed active TB while on IPT. Contact screening is a good entry point for delivery of IPT to at risk children and should be routine practice as recommended by the WHO despite the implementation challenges.

Decentralization of Acid Fast Bacilli (AFB) External Quality Assurance Using Blind Rechecking for Sputum Smear Microscopy in Ethiopia.

INTRODUCTION: Ethiopia achieved a rapid expansion of TB microscopic centers for acid fast bacilli (AFB). However, external quality assurance (EQA) services were, until recently, limited to few regional and sub-regional laboratories. In this paper, we describe the decentralization experience and the result of EQA using random blinded rechecking. MATERIALS AND METHODS: The routine EQA quarterly report was compiled and analyzed. A positive result by the microscopic center while the EQA center reported negative result is categorized as false positive (FP). A negative result by the microscopic center while the EQA center reported positive is considered false negative (FN). The reading of EQA centers was considered a gold standard to compute the sensitivity, specificity, positive predictive (PPV) and negative predictive values (NPV) of the readings of microscopic centers. RESULTS: We decentralized sputum smear AFB EQA from 4 Regional Laboratories (RRLs) to 82 EQA centers and enrolled 956 health facilities in EQA schemes. Enrollment of HFs in EQA was gradual because it required training and mentoring laboratory professionals, institutionalizing internal QA measures, equipping all HFs to perform diagnosis, and establishing more EQA centers. From 2012 to 2014 (Phase I), the FP rate declined from 0.6% to 0.2% and FN fell from as high as 7.6% to 1.6% in supported health facilities (HFs). In HFs that joined in Phase II, FN rates ranged from 5.6 to 7.3%. The proportion of HFs without errors has increased from 77.9% to 90.5% in Phase I HFs and from 82.9% to 86.9% in Phase II HFs. Overall sensitivity and specificity were 95.0% and 99.7%, respectively. PPV and NPV were 93.3% and 99.7%, respectively. CONCLUSION: Decentralizing blinded rechecking of sputum smear microscopy is feasible in low-income settings. While a comprehensive laboratory improvement strategy enhanced the quality of microscopy, laboratory professionals' capacity in slide reading and smear quality requires continued support.

Differences in public and private sector adoption of telemedicine: Indian case study for sectoral adoption.

Telemedicine is the use of communication networks to exchange medical information for providing healthcare services and medical education from one site to another. The application of telemedicine is more promising in economically developing countries with agrarian societies. The American Telemedicine Association (ATA) identifies three healthcare services: clinical medical services, health and medical education, and consumer health information. However, it is not clear how these services can be adopted by different sectors: public and private. This paper looks at four Indian case studies, two each in public and private sectors to understand two research questions: Are there differences in telemedicine adoption between public and private hospitals. If there are differences: What are the differences in telemedicine adoption between public and private sectors? Authors have used the extant literature in telemedicine and healthcare to frame theoretical background, describe the research setting, present the case studies, and provide discussion and conclusions about their findings. Authors believe that as India continues to develop its telemedicine infrastructures, especially with continued government support through subsidies to private telemedicine initiatives, its upward trend in healthcare will continue. This is expected to put India on the path to increase its life expectancy rates, especially for it rural community which constitute over 70% of its populace.