Designing educational simulation for impact test machine

We report the simulation models for enhancing the metacognitive skills. Mechanical Engineering students of Babylon Institute in Iraq are chosen for case study. The design of model and Impact Test Simulations (ITS) for Metallurgy subject is addressed. The simulation software developed using Microsoft Studio 2010 includes tutorials to explain all necessary theoretical background and formulas. Step-by-step computerized procedures and numerical examples are rendered in a simple user-friendly, visual and interactive environment to enhance metacognitive skills and students' learning. Before starting the design process, objectives and the salient features of simulation are clearly identified. Subsequently, real laboratory experiments are conducted for collecting data and coding them in computer language. Despite the existence of numerous module embedded graphical simulation, the developed software package is expected to provide valuable tool for both students and instructors. Furthermore, the same package in the form of a bi-product can also be used as a "research tool" together with the application for engineering education

Treatment Outcomes of Treatment-Naïve Hepatitis C Patients co-infected with HIV: a systematic review and meta-analysis of observational cohorts

Co-infection with Hepatitis C (HCV) and HIV is common and HIV accelerates hepatic disease progression due to HCV. However, access to HCV treatment is limited and success rates are generally poor

Mechanism of mucosal permeability enhancement of CriticalSorb® (Solutol® HS15) investigated In Vitro in cell cultures.

Purpose CriticalSorb™, with the principal component Solutol® HS15, is a novel mucosal drug delivery system demonstrated to improve the bioavailability of selected biotherapeutics. The intention of this study is to elucidate mechanism(s) responsible for the enhancement of trans-mucosal absorption of biological drugs by Solutol® HS15. Methods Micelle size and CMC of Solutol® HS15 were determined in biologically relevant media. Polarised airway Calu-3 cell layers were used to measure the permeability of a panel of biological drugs, and to assess changes in TEER, tight junction and F-actin morphology. The rate of cell endocytosis was measured in vitro in the presence of Solutol® HS15 using a membrane probe, FM 2–10. Results This work initially confirms surfactant-like behaviour of Solutol® HS15 in aqueous media, while subsequent experiments demonstrate that the effect of Solutol® HS15 on epithelial tight junctions is different from a ‘classical’ tight junction opening agent and illustrate the effect of Solutol® HS15 on the cell membrane (endocytosis rate) and F-actin cytoskeleton. Conclusion Solutol® HS15 is the principle component of CriticalSorb™ that has shown an enhancement in permeability of medium sized biological drugs across epithelia. This study suggests that its mechanism of action arises primarily from effects on the cell membrane and consequent impacts on the cell cytoskeleton in terms of actin organisation and tight junction opening

Outcomes of clofazimine for the treatment of drug-resistant tuberculosis: a systematic review and meta-analysis

Background Current anti-tuberculosis therapeutics are not sufficiently effective against drug-resistant tuberculosis (DR-TB), and there is a need for new drugs and therapeutic approaches. It has been proposed that repurposing clofazimine for DR-TB treatment might be one way to increase therapeutic options. Methods We conducted a systematic review of studies reporting on the efficacy and safety of clofazimine as part of combination therapy for DR-TB. Six databases and six conference abstract sites were searched from inception until April 2012. All studies involving the use of clofazimine in the treatment of DR-TB were included. Results Twelve studies, comprising 3489 patients across 10 countries, were included in this review. Treatment success ranged from 16.5% (95% CI 2.7%-38.7%) to 87.8% (95% CI 76.8%-95.6%), with an overall pooled proportion of 61.96% achieving treatment success (95% CI 52.79%-71.12%) (τ2 0.07). Mortality, treatment interruptions, defaulting and adverse events were all in line with DR-TB treatment outcomes overall. The most commonly reported adverse events were gastrointestinal disturbances and skin pigmentation. Conclusions The available evidence to date suggests that clofazimine could be considered as an additional therapeutic option in the treatment of DR-TB. The optimal dose of clofazimine and duration of use require further investigatio

Efficacy of HIV Postexposure Prophylaxis: Systematic Review and Meta-analysis of Nonhuman Primate Studies

Background. The efficacy of antiretrovirals as postexposure prophylaxis (PEP) to prevent viral acquisition was demonstrated in nonhuman primate models of human immunodeficiency virus (HIV) in the early 1990s. To complement the evidence base for efficacy of HIV PEP in humans, we systematically reviewed the published data on PEP efficacy across animal studies. Methods. PubMed, Web of Science, and Embase were searched from inception to 31 May 2014 for randomized and nonrandomized studies reporting seroconversions among uninfected animals exposed to HIV or simian immunodeficiency virus, irrespective of route of exposure. Seroconversion risk data were pooled using random-effects models, and associations explored through meta-regression. Results. Twenty-five studies (408 primates) were included for review. The risk of serconversion was 89% lower among animals exposed to PEP compared with those that did not receive PEP (odds ratio, 0.11 [95% confidence interval, .05-.23]). Heterogeneity was low (I2 = 0.0%). In meta-regression, a significant association was found between timing of PEP and seroconversion and the use of tenofovir compared with other drugs. Conclusions. This review provides further evidence of the protective benefit of PEP in preventing HIV acquisition, and the importance of initiating PEP as early as possible following virus exposur

CD4 Cell Count Threshold for Cryptococcal Antigen Screening of HIV-Infected Individuals: A Systematic Review and Meta-analysis.

Background: Current guidelines recommend screening all people living with human immunodeficiency virus (PLHIV) who have a CD4 count ≤100 cells/µL for cryptococcal antigen (CrAg) to identify those patients who could benefit from preemptive fluconazole treatment prior to the onset of meningitis. We conducted a systematic review to assess the prevalence of CrAg positivity at different CD4 cell counts. Methods: We searched 4 databases and abstracts from 3 conferences up to 1 September 2017 for studies reporting prevalence of CrAg positivity according to CD4 cell count strata. Prevalence estimates were pooled using random effects models. Results: Sixty studies met our inclusion criteria. The pooled prevalence of cryptococcal antigenemia was 6.5% (95% confidence interval [CI], 5.7%-7.3%; 54 studies) among patients with CD4 count ≤100 cells/µL and 2.0% (95% CI, 1.2%-2.7%; 21 studies) among patients with CD4 count 101-200 cells/µL. Twenty-one studies provided sufficient information to compare CrAg prevalence per strata; overall, 18.6% (95% CI, 15.4%-22.2%) of the CrAg-positive cases identified at ≤200 cells/µL (n = 11823) were identified among individuals with a CD4 count 101-200 cells/µL. CrAg prevalence was higher among inpatients (9.8% [95% CI, 4.0%-15.5%]) compared with outpatients (6.3% [95% CI, 5.3%-7.4%]). Conclusions: The findings of this review support current recommendations to screen all PLHIV who have a CD4 count ≤100 cells/µL for CrAg and suggest that screening may be considered at CD4 cell count ≤200 cells/µL

Patient-reported barriers to adherence to antiretroviral therapy : a systematic review and meta-analysis

Maintaining high levels of adherence to antiretroviral therapy (ART) is a challenge across settings and populations. Understanding the relative importance of different barriers to adherence will help inform the targeting of different interventions and future research priorities.; We searched MEDLINE via PubMed, Embase, Web of Science, and PsychINFO from 01 January 1997 to 31 March 2016 for studies reporting barriers to adherence to ART. We calculated pooled proportions of reported barriers to adherence per age group (adults, adolescents, and children). We included data from 125 studies that provided information about adherence barriers for 17,061 adults, 1,099 children, and 856 adolescents. We assessed differences according to geographical location and level of economic development. The most frequently reported individual barriers included forgetting (adults 41.4%, 95% CI 37.3%-45.4%; adolescents 63.1%, 95% CI 46.3%-80.0%; children/caregivers 29.2%, 95% CI 20.1%-38.4%), being away from home (adults 30.4%, 95% CI 25.5%-35.2%; adolescents 40.7%, 95% CI 25.7%-55.6%; children/caregivers 18.5%, 95% CI 10.3%-26.8%), and a change to daily routine (adults 28.0%, 95% CI 20.9%-35.0%; adolescents 32.4%, 95% CI 0%-75.0%; children/caregivers 26.3%, 95% CI 15.3%-37.4%). Depression was reported as a barrier to adherence by more than 15% of patients across all age categories (adults 15.5%, 95% CI 12.8%-18.3%; adolescents 25.7%, 95% CI 17.7%-33.6%; children 15.1%, 95% CI 3.9%-26.3%), while alcohol/substance misuse was commonly reported by adults (12.9%, 95% CI 9.7%-16.1%) and adolescents (28.8%, 95% CI 11.8%-45.8%). Secrecy/stigma was a commonly cited barrier to adherence, reported by more than 10% of adults and children across all regions (adults 13.6%, 95% CI 11.9%-15.3%; children/caregivers 22.3%, 95% CI 10.2%-34.5%). Among adults, feeling sick (15.9%, 95% CI 13.0%-18.8%) was a more commonly cited barrier to adherence than feeling well (9.3%, 95% CI 7.2%-11.4%). Health service-related barriers, including distance to clinic (adults 17.5%, 95% CI 13.0%-21.9%) and stock outs (adults 16.1%, 95% CI 11.7%-20.4%), were also frequently reported. Limitations of this review relate to the fact that included studies differed in approaches to assessing adherence barriers and included variable durations of follow up. Studies that report self-reported adherence will likely underestimate the frequency of non-adherence. For children, barriers were mainly reported by caregivers, which may not correspond to the most important barriers faced by children.; Patients on ART face multiple barriers to adherence, and no single intervention will be sufficient to ensure that high levels of adherence to treatment and virological suppression are sustained. For maximum efficacy, health providers should consider a more triaged approach that first identifies patients at risk of poor adherence and then seeks to establish the support that is needed to overcome the most important barriers to adherence

Choice of Antiretroviral Drugs for Postexposure Prophylaxis for Adults and Adolescents: A Systematic Review

Background. The choice of preferred regimens for human immunodeficiency virus postexposure prophylaxis (PEP) has evolved over the last 2 decades as more data have become available regarding the safety and tolerability of newer antiretroviral drugs. We undertook a systematic review to assess the safety and efficacy of antiretroviral options for PEP to inform the World Health Organization guideline revision process. Methods. Four databases were searched up to 1 June 2014 for studies reporting outcomes associated with specific PEP regimens. Data on PEP completion and discontinuation due to adverse events was extracted and pooled estimates were obtained using random-effects meta-analyses. Results. Fifteen studies (1830 PEP initiations) provided evaluable information on 2-drug regimens (zidovudine [ZDV]- or tenofovir [TDF]-based regimens), and 10 studies (1755 initiations) provided evaluable information on the third drug, which was usually a protease inhibitor. The overall quality of the evidence was rated as very low. For the 2-drug regimen, PEP completion rates were 78.4% (95% confidence interval [CI], 66.1%-90.7%) for people receiving a TDF-based regimen and 58.8% (95% CI, 47.2%-70.4%) for a ZDV-based regimen; the rate of PEP discontinuation due to an adverse event was lower among people taking TDF-based PEP (0.3%; 95% CI, 0%-1.1%) vs a ZDV-based regimen (3.2%; 95% CI, 1.5%-4.9%). For the 3-drug comparison, PEP completion rates were highest for the TDF-based regimens (TDF+emtricitabine [FTC]+lopinavir/ritonavir [LPV/r], 71.1%; 95% CI, 43.6%-98.6%; TDF+FTC+raltegravir [RAL], 74.7%; 95% CI, 41.4%-100%; TDF+FTC+ boosted darunavir [DRV/r], 93.9%; 95% CI, 90.2%-97.7%) and lowest for ZDV+ lamivudine [3TC]+LPV/r (59.1%; 95% CI, 36.2%-82.0%). Discontinuations due to adverse drug reactions were lowest for TDF+FTC+RAL (1.9%; 95% CI, 0%-3.8%) and highest for ZDV+3TC+boosted atazanavir (21.2%; 95% CI, 13.5%-30.0%). Conclusions. The findings of this review provide evidence supporting the use of coformulated TDF and 3TC/FTC as preferred backbone drugs for PEP. Choice of third drug will depend on setting; for resource-limited settings, LPV/r is a reasonable choice, pending the improved availability of better-tolerated drugs with less potential for drug-drug interaction