Post-market assessment of the quality of first line regimen fixed-dose combination antiretrovirals in South Africa

Magister Scientiae - MSc (Pharmaceutical Chemistry)The rapid increase in access to new antiretrovirals (ARVs) worldwide and, especially in sub-Saharan Africa, coupled with the well-documented problem of poor quality ARVs in developing countries has underscored the need for quality assessment of these medicines. South Africa has the worst human immunodeficiency virus (HIV) epidemic profile in the world; consequently, it has rolled out the world's largest antiretroviral ARV programme. With increasing market penetration of generic medicine in South Africa and especially ARVs, there is a call for stringent quality control mechanisms following the marketing approval (post-market quality control) of these medications. Unfortunately, evidence suggests that the World Health Organisation (WHO) recommendations for this aspect of quality assurance is not met by most Medicine Regulatory Authorities. In South Africa and many other countries this is attributed to a lack of physical and financial resources to enforce effective post-marketing surveillance (PMS) of all pharmaceuticals available in the country

Co-pyrolysis for bio-oil production via fixed bed reactor using date seeds and plastic waste as biomass.

The consumption of plastic bottles is relatively high in the United Arab Emirates (UAE). Therefore, in this study authors investigated the potential of combined plastic waste and locally available biomass (date seeds) to produce value-added products (bio-oil, bio-char and syngas) via pyrolysis process. The experiments were performed in a fixed bed pyrolizer, operated at different temperatures. Experimental results showed that 500 °C would be a better option for a higher bio-oil yield (59.16%), while lower temperatures (300 °C) produced more bio-char yields (24.97%). A plastic ratio of 70% gives the highest bio-oil content (62.57%), and lowest amounts of bio-char (12.14%). Experiment performed at 400 °C with a plastic waste ratio of 30% have the highest bio-oil density (1.020 g/cm3). The results obtained in this study showed that the co-pyrolysis of plastic waste and date seeds are suitable for bio-oil production as sustainable biofuel in UAE

Type 2 Diabetes : how informed are the general public? A cross-sectional study investigating disease awareness and barriers to communicating knowledge in high-risk populations in London

Abstract Background Preventing type 2 diabetes (T2DM) is one of the biggest health challenges currently facing the UK, with the NHS spending £14 billion each year on treating the disease and associated symptoms. Aims The aim of this study was to determine the public’s awareness about the symptoms, risk factors and lifestyle choices, commonly associated with T2DM. This study also aimed to determine whether the level of awareness varies if the questions are asked in different languages, primarily those spoken by ethnic minorities. Methods This was a cross sectional, multisite study conducted in London, UK, involving 399 participants, who were non-diabetic, aged between 25 and 74 years old and living in one of four selected London boroughs. Descriptive statistics, Chi square and Fisher’s Exact Tests were used to highlight and summarise the key findings of this study. Results A response rate of 23.7% (n = 399/1683) for the English questionnaire was achieved. Overall, 59.4% (n = 237/399) of the cohort were able to identify a minimum of three T2DM symptoms and thus, were considered to have adequate or good awareness. Whereas, 60.6% (n = 242/399) were able to identify a minimum of six T2DM risk factors and were considered to have adequate or good awareness. More participants could correctly identify that obesity was a risk factor of T2DM when they were asked the question in their spoken language, rather than English (p < 0.01). When participants were asked about their current lifestyle choices, there were high levels of inactivity, smoking and alcohol consumption reported. Conclusion Despite approximately half of participants demonstrating adequate or good awareness about the symptoms, risk factors and lifestyle choices commonly associated with T2DM, yet the study still highlights gaps in awareness among the remaining proportion of participants. Future prevention interventions should be tailored to address these existing gaps in awareness

ENHANCING THE ESTERIFICATION CONVERSION USING PERVAPORATION

Coupling of a pervaporation membrane unit with an esterification reactor has been undertaken with a view to improve the overall efficiency of the esterification process through removal of one of the products. The esterification reaction of acetic acid with methanol in the presence of two alternative heterogeneous catalysts Nafion resin (NR) and silica sulfuric acid (SSA) is investigated on the laboratory scale. The system consists of a batch reactor externally coupled with pervaparation (PV) module containing a Nafion membrane. The effect of different parameters on the esterification / pervaporation system is explored. The studied parameters include reactants molar ratio, temperature, and catalyst weight percent. The results show that the water diffusion through the PV membrane helps to break the thermodynamic equilibrium barrier of reversible esterification reaction and improve the reaction conversion. The maximum conversion reached 96.76 % after 60 min at 60 ºC, 3% silica sulfuric acid as catalyst, with a reactant to acid molar ratio of 8:1, and a membrane surface area to reactor volume of 1.3 cm-1.

Efficacy of Naltrexone/Bupropion in Treatment of Binge Eating: A Systematic Review and Meta-Analysis

Background: As the most widespread eating disorder in the world now, binge eating disorder (BED) is a mental condition characterized by recurrent periods of excessive food consumption and an inability to regulate one’s portion sizes. The utilization of a bupropion–naltrexone (NB) combination has been suggested as a potential therapeutic approach for BED. Assessing the effectiveness of NB in the treatment of BED and its accompanying obesity is the purpose of this research. Methods: A comprehensive search was conducted in order to obtain any pertinent articles. PubMed, Scopus, Web of Science, and Cochrane Clinical Trials were consulted against in the databases that were searched. In our final meta-analysis, we incorporated interventional or observational studies that documented the effects of NB therapy for binge eating in adults. We also examined the difference in the mean change between the NB and placebo groups, as well as the disparity in outcomes before and after treatment. Results: This study shows that the use of an NB combination is associated with a statistically significant reduction in the weight, BMI, and Binge Eating Scale (BES) of the patients compared to their weight before treatment with MD: −8.52 (95% CI: −10.01–−6.94, p &lt; 0.00001), MD: −4.95 (95%CI: −9.72–−0.17, p = 0.04), and MD: −7.66 (95%CI: −14.36–0.96, p = 0.02), respectively. The absolute mean change was statistically significantly higher in the drug combination group compared to the placebo group. Conclusions: NB showed efficacy in the improvement of the weight and psychiatric symptoms associated with BED and this provides a promising treatment option

Altered Regulation of the Glucose Transporter GLUT3 in PRDX1 Null Cells Caused Hypersensitivity to Arsenite

Targeting tumour metabolism through glucose transporters is an attractive approach. However, the role these transporters play through interaction with other signalling proteins is not yet defined. The glucose transporter SLC2A3 (GLUT3) is a member of the solute carrier transporter proteins. GLUT3 has a high affinity for D-glucose and regulates glucose uptake in the neurons, as well as other tissues. Herein, we show that GLUT3 is involved in the uptake of arsenite, and its level is regulated by peroxiredoxin 1 (PRDX1). In the absence of PRDX1, GLUT3 mRNA and protein expression levels are low, but they are increased upon arsenite treatment, correlating with an increased uptake of glucose. The downregulation of GLUT3 by siRNA or deletion of the gene by CRISPR cas-9 confers resistance to arsenite. Additionally, the overexpression of GLUT3 sensitises the cells to arsenite. We further show that GLUT3 interacts with PRDX1, and it forms nuclear foci, which are redistributed upon arsenite exposure, as revealed by immunofluorescence analysis. We propose that GLUT3 plays a role in mediating the uptake of arsenite into cells, and its homeostatic and redox states are tightly regulated by PRDX1. As such, GLUT3 and PRDX1 are likely to be novel targets for arsenite-based cancer therapy

Tutors, The Valuable Resource to Enhance Medical Students’ Motivation.

Background: Students’ academic performance is largely affected by their motivation. Moreover, health professions’ education needs motivated students who are keen to tolerate the burden of clinical work along with the academic excellence to graduate competently. This study assessed the effect of tutors on students’ motivation. Method: A cross-sectional, institution-based study of the first-year medical students at University of Khartoum, Sudan was conducted. A self-administered questionnaire was used comprising a modified Motivated Strategies for Learning Questionnaire (MSLQ) with students’ evaluation of their tutors after semester one community medicine course. A total of 237 out of 324 students responded. Pearson productmoment correlation coefficient was used to test the relationship between motivation and evaluation. Hierarchical multiple regression model tested the ability of evaluation factors to predict motivation score. Results: There was a significant association between tutor’s characteristics regarding creativity in conducting the sessions, igniting discussion, and adequacy of knowledge about the course contents and the motivation score (p-value = 0.001). There was a strong, positive correlation between the perceived evaluation score and perceived motivation score (r = 0.505, n = 206, p &lt; 0.0005). After controlling age, gender, paternal educational levels, and scores of Sudanese certificate upon entry, R squared change = 0.28, F change (9.181) = 8.416, p &lt;0.001. In the final model, the content of the course was statistically significant, standardized Beta = 0.285, indicating that content uniquely explains 5.7% of the variance in total perceived motivation score. Conclusion: The evaluation score explained 28% of the variance in student motivation. Students’ motivation issignificantly associated with tutor’s teaching skills concerning knowledge, creativity, students’ involvement, and attractiveness in conducting the tutorials. Improving course content can enhance students’ motivation toward community medicine

Antimicrobial resistance among migrants in Europe: a systematic review and meta-analysis

BACKGROUND: Rates of antimicrobial resistance (AMR) are rising globally and there is concern that increased migration is contributing to the burden of antibiotic resistance in Europe. However, the effect of migration on the burden of AMR in Europe has not yet been comprehensively examined. Therefore, we did a systematic review and meta-analysis to identify and synthesise data for AMR carriage or infection in migrants to Europe to examine differences in patterns of AMR across migrant groups and in different settings. METHODS: For this systematic review and meta-analysis, we searched MEDLINE, Embase, PubMed, and Scopus with no language restrictions from Jan 1, 2000, to Jan 18, 2017, for primary data from observational studies reporting antibacterial resistance in common bacterial pathogens among migrants to 21 European Union-15 and European Economic Area countries. To be eligible for inclusion, studies had to report data on carriage or infection with laboratory-confirmed antibiotic-resistant organisms in migrant populations. We extracted data from eligible studies and assessed quality using piloted, standardised forms. We did not examine drug resistance in tuberculosis and excluded articles solely reporting on this parameter. We also excluded articles in which migrant status was determined by ethnicity, country of birth of participants' parents, or was not defined, and articles in which data were not disaggregated by migrant status. Outcomes were carriage of or infection with antibiotic-resistant organisms. We used random-effects models to calculate the pooled prevalence of each outcome. The study protocol is registered with PROSPERO, number CRD42016043681. FINDINGS: We identified 2274 articles, of which 23 observational studies reporting on antibiotic resistance in 2319 migrants were included. The pooled prevalence of any AMR carriage or AMR infection in migrants was 25·4% (95% CI 19·1-31·8; I2 =98%), including meticillin-resistant Staphylococcus aureus (7·8%, 4·8-10·7; I2 =92%) and antibiotic-resistant Gram-negative bacteria (27·2%, 17·6-36·8; I2 =94%). The pooled prevalence of any AMR carriage or infection was higher in refugees and asylum seekers (33·0%, 18·3-47·6; I2 =98%) than in other migrant groups (6·6%, 1·8-11·3; I2 =92%). The pooled prevalence of antibiotic-resistant organisms was slightly higher in high-migrant community settings (33·1%, 11·1-55·1; I2 =96%) than in migrants in hospitals (24·3%, 16·1-32·6; I2 =98%). We did not find evidence of high rates of transmission of AMR from migrant to host populations. INTERPRETATION: Migrants are exposed to conditions favouring the emergence of drug resistance during transit and in host countries in Europe. Increased antibiotic resistance among refugees and asylum seekers and in high-migrant community settings (such as refugee camps and detention facilities) highlights the need for improved living conditions, access to health care, and initiatives to facilitate detection of and appropriate high-quality treatment for antibiotic-resistant infections during transit and in host countries. Protocols for the prevention and control of infection and for antibiotic surveillance need to be integrated in all aspects of health care, which should be accessible for all migrant groups, and should target determinants of AMR before, during, and after migration. FUNDING: UK National Institute for Health Research Imperial Biomedical Research Centre, Imperial College Healthcare Charity, the Wellcome Trust, and UK National Institute for Health Research Health Protection Research Unit in Healthcare-associated Infections and Antimictobial Resistance at Imperial College London

Impact of opioid-free analgesia on pain severity and patient satisfaction after discharge from surgery: multispecialty, prospective cohort study in 25 countries

Background: Balancing opioid stewardship and the need for adequate analgesia following discharge after surgery is challenging. This study aimed to compare the outcomes for patients discharged with opioid versus opioid-free analgesia after common surgical procedures.Methods: This international, multicentre, prospective cohort study collected data from patients undergoing common acute and elective general surgical, urological, gynaecological, and orthopaedic procedures. The primary outcomes were patient-reported time in severe pain measured on a numerical analogue scale from 0 to 100% and patient-reported satisfaction with pain relief during the first week following discharge. Data were collected by in-hospital chart review and patient telephone interview 1 week after discharge.Results: The study recruited 4273 patients from 144 centres in 25 countries; 1311 patients (30.7%) were prescribed opioid analgesia at discharge. Patients reported being in severe pain for 10 (i.q.r. 1-30)% of the first week after discharge and rated satisfaction with analgesia as 90 (i.q.r. 80-100) of 100. After adjustment for confounders, opioid analgesia on discharge was independently associated with increased pain severity (risk ratio 1.52, 95% c.i. 1.31 to 1.76; P &lt; 0.001) and re-presentation to healthcare providers owing to side-effects of medication (OR 2.38, 95% c.i. 1.36 to 4.17; P = 0.004), but not with satisfaction with analgesia (beta coefficient 0.92, 95% c.i. -1.52 to 3.36; P = 0.468) compared with opioid-free analgesia. Although opioid prescribing varied greatly between high-income and low- and middle-income countries, patient-reported outcomes did not.Conclusion: Opioid analgesia prescription on surgical discharge is associated with a higher risk of re-presentation owing to side-effects of medication and increased patient-reported pain, but not with changes in patient-reported satisfaction. Opioid-free discharge analgesia should be adopted routinely

Surgical site infection after gastrointestinal surgery in high-income, middle-income, and low-income countries: a prospective, international, multicentre cohort study

Background: Surgical site infection (SSI) is one of the most common infections associated with health care, but its importance as a global health priority is not fully understood. We quantified the burden of SSI after gastrointestinal surgery in countries in all parts of the world. Methods: This international, prospective, multicentre cohort study included consecutive patients undergoing elective or emergency gastrointestinal resection within 2-week time periods at any health-care facility in any country. Countries with participating centres were stratified into high-income, middle-income, and low-income groups according to the UN's Human Development Index (HDI). Data variables from the GlobalSurg 1 study and other studies that have been found to affect the likelihood of SSI were entered into risk adjustment models. The primary outcome measure was the 30-day SSI incidence (defined by US Centers for Disease Control and Prevention criteria for superficial and deep incisional SSI). Relationships with explanatory variables were examined using Bayesian multilevel logistic regression models. This trial is registered with ClinicalTrials.gov, number NCT02662231. Findings: Between Jan 4, 2016, and July 31, 2016, 13 265 records were submitted for analysis. 12 539 patients from 343 hospitals in 66 countries were included. 7339 (58·5%) patient were from high-HDI countries (193 hospitals in 30 countries), 3918 (31·2%) patients were from middle-HDI countries (82 hospitals in 18 countries), and 1282 (10·2%) patients were from low-HDI countries (68 hospitals in 18 countries). In total, 1538 (12·3%) patients had SSI within 30 days of surgery. The incidence of SSI varied between countries with high (691 [9·4%] of 7339 patients), middle (549 [14·0%] of 3918 patients), and low (298 [23·2%] of 1282) HDI (p < 0·001). The highest SSI incidence in each HDI group was after dirty surgery (102 [17·8%] of 574 patients in high-HDI countries; 74 [31·4%] of 236 patients in middle-HDI countries; 72 [39·8%] of 181 patients in low-HDI countries). Following risk factor adjustment, patients in low-HDI countries were at greatest risk of SSI (adjusted odds ratio 1·60, 95% credible interval 1·05–2·37; p=0·030). 132 (21·6%) of 610 patients with an SSI and a microbiology culture result had an infection that was resistant to the prophylactic antibiotic used. Resistant infections were detected in 49 (16·6%) of 295 patients in high-HDI countries, in 37 (19·8%) of 187 patients in middle-HDI countries, and in 46 (35·9%) of 128 patients in low-HDI countries (p < 0·001). Interpretation: Countries with a low HDI carry a disproportionately greater burden of SSI than countries with a middle or high HDI and might have higher rates of antibiotic resistance. In view of WHO recommendations on SSI prevention that highlight the absence of high-quality interventional research, urgent, pragmatic, randomised trials based in LMICs are needed to assess measures aiming to reduce this preventable complication