OBJECTIVETo summarize the clinical burden (cumulative incidence, prevalence, case fatality rate and length of stay) and economic burden (healthcare cost) of healthcare-associated infections (HAIs) due to multidrug-resistant organisms (MDROs) among patients in intensive care units (ICUs) in Southeast Asia.DESIGNSystematic review.METHODSWe conducted a comprehensive literature search in PubMed, EMBASE, CINAHL, EconLit, and the Cochrane Library databases from their inception through September 30, 2016. Clinical and economic burdens and study quality were assessed for each included study.RESULTSIn total, 41 studies met our inclusion criteria; together, 22,876 ICU patients from 7 Southeast Asian countries were included. The cumulative incidence of HAI caused by A. baumannii (AB) in Southeast Asia is substantially higher than has been reported in other regions, especially carbapenem-resistant AB (CRAB; 64.91%) and multidrug-resistant AB (MDR-AB) (58.51%). Evidence of a dose-response relationship between different degrees of drug resistance and excess mortality due to AB infections was observed. Adjusted odds ratios were 1.23 (95% confidence interval [CI], 0.51-3.00) for MDR-AB, 1.72 (95% CI, 0.77-3.80) for extensively drug-resistant AB (XDR-AB), and 1.82 (95% CI, 0.55-6.00) for pandrug-resistant AB (PDR-AB). There is, however, a paucity of published data on additional length of stay and costs attributable to MDROs.CONCLUSIONSThis review highlights the challenges in addressing MDROs in Southeast Asia, where HAIs caused by MDR gram-negative bacteria are abundant and have a strong impact on society. With our findings, we hope to draw the attention of clinicians and policy makers to the problem of antibiotic resistance and to issue a call for action in the management of MDROs.Infect Control Hosp Epidemiol 2018;39:525-533.
National immunization program of Pakistan does not include Influenza vaccines. The low rate of immunization might be attributed to the poor knowledge of influenza vaccination in Pakistan. Current study was aimed to assess the knowledge and attitude of influenza vaccination among parents. A questionnaire-based cross sectional study was conducted among randomly selected parents with at least one child aged >6 months. The responses were recorded against 27 items questionnaire assessing knowledge, perception, attitude and behaviours of parents. Data were analysed by using appropriate statistical methods. A total 532 responses were recorded with male gender preponderance (65%). Most of the parents (61.1%) reported that their children had received or planned to receive all recommended vaccines in Expanded Program on Immunization (EPI) of Pakistan. Only one third of the parents (24.4%) were aware of the availability of influenza vaccines in Pakistan, and very few (6.6%) reported vaccinating their child against influenza. Exploring the parents' attitudes regarding children vaccination, the top motivator was 'immunization is important to keep my children healthy' (relative index = 0.93, p < 0.000). However, substantial number of parents believed that influenza is not a serious disease (18.5%) and vaccines are accompanied by several side effects (24.6%). A positive attitude was reflected among parents who were aware of influenza vaccines in Pakistan. About 35% participants believed that influenza vaccines are not required for healthy children. Current study demonstrated very low vaccination rate against influenza. Awareness and health literacy regarding influenza vaccine is poor among parents. These findings necessitate the need to appropriately structured awareness programs regarding influenza vaccination among parents.
Streptomycetes remain as one of the important sources for bioactive products. Isolated from the mangrove forest, Streptomyces gilvigriseus MUSC 26T was previously characterised as a novel streptomycete. The high quality draft genome of MUSC 26T contained 5,213,277bp with G+C content of 73.0%. Through genome mining, several gene clusters associated with secondary metabolites production were revealed in the genome of MUSC 26T. These findings call for further investigations into the potential exploitation of the strain for production of pharmaceutically important compounds.
Objective: Association of various self-care activities on glycemic control of people with diabetes (PWD) in Pakistan is yet to be explored. The current study aimed to evaluate the association of various diabetes-related self-care activities with glycated hemoglobin (HbA1c) levels and to examine the predictive relationship of patients' demographic variables with their self-care activities.
Patients and methods: A cross-sectional study was conducted on adult PWD (N=218) who were diagnosed with type 2 diabetes mellitus of at least 1 year duration. Self-care activities were examined by using the Urdu version of Diabetes Self-management Questionnaire. Linear regression analysis was conducted to examine the significant predictors for diabetes-related self-care activities and glycemic control.
Results: Mean age of the patients was 50.77±13.3 years. Poor glycemic control (HbA1c $7%) was observed in majority of the patients (83%). Linear regression analysis revealed that glucose management (β=-0.44; 95% CI -0.438, -0.209; P<0.001) was the strongest predictor for low levels of patients' HbA1c, followed by dietary control (β=-0.19; 95% CI -0.248, -0.018; P=0.024) and physical activity (β=-0.17; 95% CI -0.165, -0.023; P=0.010), respectively. Linear regression analysis showed that use of oral hypoglycemic agents only (β=-0.218; 95% CI -0.956, -0.200; P=0.003) and higher education level (β=0.204; 95% CI 0.138, 0.777; P=0.005) were significant predictors for higher scores of patients' self-care activities.
Conclusion: The findings support that PWD having better self-reported self-care activities achieve better glycemic control. Patients' self-care activities should be monitored on a regular basis, especially for those who are at risk of poor glycemic control.
Transcription factors are gene regulators that activate or repress target genes. One family of the transcription factors that have been extensively studied for their crucial role in regulating gene network in the immune system is the interferon regulatory factors (IRFs). IRFs possess a novel turn-helix turn motif that recognizes a specific DNA consensus found in the promoters of many genes that are involved in immune responses. IRF5, a member of IRFs has recently gained much attention for its role in regulating inflammatory responses and autoimmune diseases. Here, we discuss the role of IRF5 in regulating immune cells functions and how the dysregulation of IRF5 contributes to the pathogenesis of immune disorders. We also review the latest findings of potential IRF5 inhibitors that modulate IRF5 activity in the effort of developing therapeutic approaches for treating inflammatory disorders.
Background: Effectiveness of pharmacist-led educational interventions on self-care activities and glycemic control of type 2 diabetes mellitus (T2DM) patients is vague. The purpose of this review is to appraise the effect of pharmacist-led educational interventions on self-care activities and levels of glycated hemoglobin of T2DM patients.
Methods: Five electronic databases were searched from date of database inception to September 2017. Randomized clinical trials examining the effectiveness of pharmacist-led educational interventions, directed at T2DM patients only, were included for systematic review and meta-analysis. The protocol is available with PROSPERO (CRD42017078854).
Results: Eleven studies, involving n=1,544 T2DM patients, were included in this systematic review. Meta-analysis demonstrated that pharmacist-led interventions had a significant effect on lowering of the levels of glycated hemoglobin (-0.66; 95% CI [-0.83, -0.50]; I2=58.3%; P=0.008), in comparison to usual care. Self-care activities were assessed by using Summary of Diabetes Self-care Activities tool in eight studies. Overall meta-analysis of self-care activities for included studies demonstrated a significant effect of pharmacist-led interventions on improvement of self-monitoring of blood glucose (1.62; 95% CI [0.92, 2.32]; I2=70.5%; P=0.005), foot care (1.20; 95% CI [0.49, 1.90]; I2=95.0%; P<0.001), and overall diet (1.16; 95% CI [0.38, 1.93]; I2=64.2%; P=0.094).
Conclusion: The findings of this review demonstrate a significantly positive effect of pharmacist-led educational interventions on HbA1c levels and self-care practices among T2DM patients.
Background: Comparative efficacy of different pharmacist based interventions on glycemic control of type 2 diabetes patients is unclear. This review aimed to evaluate and compare the efficacy of different pharmacist based interventions on clinical outcomes of type 2 diabetes patients. Methods: A systematic search was conducted across five databases from date of database inception to September 2017. All randomized clinical trials evaluating the efficacy of pharmacist based interventions on type 2 diabetes patients were included for network meta-analysis (NMA). The protocol is available with PROSPERO (CRD42017078854). Results: A total of 43 studies, involving 6259 type 2 diabetes patients, were included. NMA demonstrated that all interventions significantly lowered glycosylated hemoglobin (HbA1c) levels compared to usual care, but there was no statistical evidence from this study that one intervention was significantly better than the other for reducing HbA1c levels. Pharmacist based diabetes education plus pharmaceutical care showed maximum efficacy for reducing HbA1c levels [-0.86, 95% CI -0.983, -0.727; p < 0.001]. Pharmacist based diabetes education plus pharmaceutical care was observed to be statistically significant in lowering levels of systolic blood pressure [-4.94; 95%CI -8.65, -1.23] and triglycerides levels [-0.26, 95%CI -0.51, -0.01], as compared to the interventions which involved diabetes education by pharmacist, and for body mass index (BMI) [-0.57; 95%CI -1.25, -0.12] in comparison to diabetes education by health care team involving pharmacist as member. Conclusion: The findings of this review demonstrate that all interventions had a significantly positive effect on HbA1c, but there was no statistical evidence from this study that one intervention was significantly better than the other for achieving glycemic control.Pharmacist based diabetes education plus pharmaceutical care showed maximum efficacy on HbA1c and rest of the clinical outcomes.
Mangrove derived microorganisms constitute a rich bioresource for bioprospecting of bioactive natural products. This study explored the antioxidant potentials of Streptomyces bacteria derived from mangrove soil. Based on 16S rRNA phylogenetic analysis, strain MUM292 was identified as the genus Streptomyces. Strain MUM292 showed the highest 16S rRNA gene sequence similarity of 99.54% with S. griseoruber NBRC12873T. Furthermore, strain MUM292 was also characterized and showed phenotypic characteristics consistent with Streptomyces bacteria. Fermentation and extraction were performed to obtain the MUM292 extract containing the secondary metabolites of strain MUM292. The extract displayed promising antioxidant activities, including DPPH, ABTS, and superoxide radical scavenging and also metal-chelating activities. The process of lipid peroxidation in lipid-rich product was also retarded by MUM292 extract and resulted in reduced MDA production. The potential bioactive constituents of MUM292 extract were investigated using GC-MS and preliminary detection showed the presence of pyrazine, pyrrole, cyclic dipeptides, and phenolic compound in MUM292 extract. This work demonstrates that Streptomyces MUM292 can be a potential antioxidant resource for food and pharmaceutical industries.
There are various studies that have addressed the use of Cyclosporine among patients with acute myocardial infarction (AMI). However, to date there is hardly any concise and systematically structured evidence that debate on the efficacy and safety of Cyclosporine in AMI patients. The aim of this review is to systematically summarize the overall evidence from published trials, and to conduct a meta-analysis in order to determine the efficacy and safety of Cyclosporine vs. placebo or control among patients with AMI. All randomized control trial (RCT) published in English language from January 2000 to August 2017 were included for the systematic review and meta-analysis. A total of six RCTs met the inclusion and were hence included in the systematic review and meta-analysis. Based on the performed meta-analysis, no significant difference was found between Cyclosporine and placebo in terms of left ventricular ejection fraction (LVEF) improvement (mean difference 1.88; 95% CI -0.99 to 4.74; P = 0.2), mortality rate (OR 1.01; 95% Cl 0.60 to 1.67, P = 0.98) and recurrent MI occurrence (OR 0.65; 95% Cl 0.29 to 1.45, P = 0.29), with no evidence of heterogeneity, when given to patients with AMI. Cyclosporine also did not significantly lessen the rate of rehospitalisation in AMI patients when compared to placebo (OR 0.91; 95% Cl 0.58 to 1.42, P = 0.68), with moderate heterogeneity (I2 = 46%). There was also no significant improvement in heart failure events between Cyclosporine and placebo in AMI patients (OR 0.63; 95% Cl 0.31 to 1.29, P = 0.21; I2 = 80%). No serious adverse events were reported in Cyclosporine group across all studies suggesting that Cyclosporine is well tolerated when given to patients with AMI. The use of Cyclosporine in this group of patients, however, did not result in better clinical outcomes vs. placebo at improving LVEF, mortality rate, recurrent MI, rehospitalisation and heart failure event.
Methicillin-resistant Staphylococcus aureus (MRSA) pose a significant health threat as they tend to cause severe infections in vulnerable populations and are difficult to treat due to a limited range of effective antibiotics and also their ability to form biofilm. These organisms were once limited to hospital acquired infections but are now widely present in the community and even in animals. Furthermore, these organisms are constantly evolving to develop resistance to more antibiotics. This results in a need for new clinically useful antibiotics and one potential source are the Streptomyces which have already been the source of several anti-MRSA drugs including vancomycin. There remain large numbers of Streptomyces potentially undiscovered in underexplored regions such as mangrove, deserts, marine, and freshwater environments as well as endophytes. Organisms from these regions also face significant challenges to survival which often result in the production of novel bioactive compounds, several of which have already shown promise in drug development. We review the various mechanisms of antibiotic resistance in MRSA and all the known compounds isolated from Streptomyces with anti-MRSA activity with a focus on those from underexplored regions. The isolation of the full array of compounds Streptomyces are potentially capable of producing in the laboratory has proven a challenge, we also review techniques that have been used to overcome this obstacle including genetic cluster analysis. Additionally, we review the in vivo work done thus far with promising compounds of Streptomyces origin as well as the animal models that could be used for this work.
Bacterial foodborne pathogens are a significant health burden and the recent emergence of pathogenic resistant strains due to the excessive use of antibiotics makes it more difficult to effectively treat infections as a result of contaminated food. Awareness of this impending health crisis has spurred the search for alternative antimicrobials with natural plant antimicrobials being among the more promising candidates as these substances have good acceptability and likely low toxicity levels as they have long been used in traditional medicines. Resveratrol (3,5,4'-trihydroxystilbene) is a naturally occurring stilbenoid which has been gaining considerable attention in medical field due to its diverse biological activities - it has been reported to exhibit antioxidant, cardioprotective, anti-diabetic, anticancer, and antiaging properties. Given that resveratrol is phytoalexin, with increased synthesis in response to infection by phytopathogens, there has been interest in exploring its antimicrobial activity. This review aims to provide an overview of the published data on the antibacterial activity of resveratrol against foodborne pathogens, its mechanisms of action as well as its possible applications in food packing and processing; in addition we also summarize the current data on its potential synergism with known antibacterials and future research and applications.
Vibrio parahaemolyticus, a Gram-negative halophilic bacterium is often associated with fish and fishery products, thus causing gastroenteritis in humans upon ingestion of contaminated food. V. parahaemolyticus has become a globally well-known pathogen with yearly reported cases in many countries. This study aimed to discover the antibiotic resistance patterns of V. parahaemolyticus as well as detect Carbapenem resistant isolates from marine and freshwater fish in Selangor. A total of 240 freshwater and marine fish samples collected from wet market and supermarket in Selangor were tested for the presence of V. parahaemolyticus. All the fish samples were determined positive for V. parahaemolyticus using conventional microbiological culture-based method. The toxR gene were detected via polymerase chain reaction (PCR) in 165/240 (69%) isolates. The two-virulence factor of V. parahaemolyticus, thermostable direct hemolysin (tdh) and TDH-related hemolysin (trh) was screened via PCR. As such, four isolates were trh+and none were tdh+. Majority of the isolates presented high resistance to ampicillin (88%), amikacin (64%), and kanamycin (50%). In addition, this study identified 19-imipenem resistant isolates isolated from freshwater and marine fish samples. Further analysis of these 19-imipenem resistant isolates revealed that the resistance toward imipenem was plasmid mediated after plasmid curing assay. The multiple antibiotics resistance index was >0.2 for 70% of the isolates. In summary, the results confirm the presence of V. parahaemolyticus in freshwater and marine fish samples in Selangor, Malaysia. To our best knowledge, this is the first report discovering the antibiotic resistant patterns and Carbapenem-resistant isolates of V. parahaemolyticus isolated from marine and freshwater fish samples in Selangor.
As the largest genus in Actinobacteria family, Streptomyces species have the ability to synthesize numerous compounds of diverse structures with bioactivities. Streptomyces mangrovisoli MUSC 149T was previously isolated as a novel streptomycete from mangrove forest in east coast of Peninsular Malaysia. The high quality draft genome of MUSC 149T comprises 9,165,825bp with G+C content of 72.5%. Through bioinformatics analysis, 21 gene clusters identified in the genome were associated with the production of bioactive secondary metabolites. The presence of these biosynthetic gene clusters in MUSC 149T suggests the potential exploitation of the strain for production of medically important compounds.
Mangrove is a complex ecosystem that contains diverse microbial communities, including rare actinobacteria with great potential to produce bioactive compounds. To date, bioactive compounds extracted from mangrove rare actinobacteria have demonstrated diverse biological activities. The discovery of three novel rare actinobacteria by polyphasic approach, namely Microbacterium mangrovi MUSC 115T, Sinomonas humi MUSC 117T and Monashia flava MUSC 78T from mangrove soils at Tanjung Lumpur, Peninsular Malaysia have led to the screening on antibacterial, anticancer and neuroprotective activities. A total of ten different panels of bacteria such as Methicillin-resistant Staphylococcus aureus (MRSA) ATCC 43300, ATCC 70069, Pseudomonas aeruginosa NRBC 112582 and others were selected for antibacterial screening. Three different neuroprotective models (hypoxia, oxidative stress, dementia) were done using SHSY5Y neuronal cells while two human cancer cells lines, namely human colon cancer cell lines (HT-29) and human cervical carcinoma cell lines (Ca Ski) were utilized for anticancer activity. The result revealed that all extracts exhibited bacteriostatic effects on the bacteria tested. On the other hand, the neuroprotective studies demonstrated M. mangrovi MUSC 115T extract exhibited significant neuroprotective properties in oxidative stress and dementia model while the extract of strain M. flava MUSC 78T was able to protect the SHSY5Y neuronal cells in hypoxia model. Furthermore, the extracts of M. mangrovi MUSC 115T and M. flava MUSC 78T exhibited anticancer effect against Ca Ski cell line. The chemical analysis of the extracts through GC-MS revealed that the majority of the compounds present in all extracts are heterocyclic organic compound that could explain for the observed bioactivities. Therefore, the results obtained in this study suggested that rare actinobacteria discovered from mangrove environment could be potential sources of antibacterial, anticancer and neuroprotective agents.
This systematic review aimed to assess the clinical benefits of green tea consumption on the progression and prevention of prostate cancer (PCa). A systematic search was performed across the following databases: PubMed, Excerpta Medica dataBASE, Database of Abstracts of Reviews of Effects, Current Nursing and Allied Health Literature, Allied and Complementary Medicine Database, Cochrane Database of Systematic Reviews, and Cochrane Central Register of Controlled Trials. We included studies from database inception to September 2015. Studies must report on the effect of green tea consumption on PCa. The quality of observational studies was assessed using the Newcastle-Ottawa Scale (NOS), while randomized controlled trials (RCTs) were assessed for quality using the Jadad scale. A total of 15 articles were included, with 11 reporting on the effect of green tea consumption on PCa prevention, and four reporting on the effect of green tea on treatment. Mean NOS for observational studies was 7.4 (SD±1.3), with a range from 6 to 9, while all three RCTs scored 5 on the Jadad scale. Findings demonstrate that green tea appears to be an effective chemopreventive agent, particularly in those with high-grade prostate intraepithelial neoplasia. However, evidence of efficacy in the treatment of PCa is currently lacking. Given the limitations in current studies, more well-designed RCTs should be undertaken to determine if green tea indeed has a role in the prevention and treatment of PCa.
Particle Swarm Optimization (PSO) is a popular metaheuristic for deterministic optimization. Originated in the interpretations of the movement of individuals in a bird flock or fish school, PSO introduces the concept of personal best and global best to simulate the pattern of searching for food by flocking and successfully translate the natural phenomena to the optimization of complex functions. Many real-life applications of PSO cope with stochastic problems. To solve a stochastic problem using PSO, a straightforward approach is to equally allocate computational effort among all particles and obtain the same number of samples of fitness values. This is not an efficient use of computational budget and leaves considerable room for improvement. This paper proposes a seamless integration of the concept of optimal computing budget allocation (OCBA) into PSO to improve the computational efficiency of PSO for stochastic optimization problems. We derive an asymptotically optimal allocation rule to intelligently determine the number of samples for all particles such that the PSO algorithm can efficiently select the personal best and global best when there is stochastic estimation noise in fitness values. We also propose an easy-to-implement sequential procedure. Numerical tests show that our new approach can obtain much better results using the same amount of computational effort.
The Asian venous thromboembolism (VTE) prophylaxis guidelines were first published in 2012. Since its first edition, the Asian Venous Thrombosis Forum (AVTF) working group have updated the Asian VTE epidemiology and reviewed issues that were not addressed in the previous guidelines. The authors noted that the rising incidence of VTE across Asia may be attributable to aging population, dietary changes, and increasing incidence of obesity and diabetes. The new additions in the guideline include role of thrombophilia in VTE, bleeding risk in Asians, individual risk assessment, updates in the prevention of VTE in medically ill, bariatric surgery, cancer, orthopedic and trauma patients. The influence of primary thrombophilia in perioperative VTE is still unclear. The secondary risk factors, however, are similar between Asians and Caucasians. The group found no evidence of increased risk of bleeding while using pharmacological agents, including the use of novel anti-coagulants. At present, Caprini risk assessment model is widely used for individual risk assessment. Further validation of this model is needed in Asia. In medically ill patients, pharmacological agents are preferred if there is no bleeding risk. Intermittent pneumatic compression device (IPC) is recommended in patients with bleeding risk but we do not recommend using graduated compressive stockings. In bariatric patients, data on VTE is lacking in Asia. We recommend following current international guidelines. A high index of suspicion should be maintained during postbariatric surgery to detect and promptly treat portomesenteric venous thrombosis. Different cancer types have different thrombotic risks and the types of surgery influence to a large extent the overall VTE risk. Cancer patients should receive further risk assessment. In patients with higher thrombotic risk, either due to predisposing risk or concomitant surgery, low molecular weight heparin is indicated. Different countries appear to have different incidence of VTE following trauma and major orthopedic surgery. We recommend mechanical prophylaxis using IPC as the main method and additional pharmacological prophylaxis if the thrombotic risk is high. As for obstetric practice, we propose adherence to the UK Greentop guideline that is widely accepted and utilized across Asia. To improve VTE thromboprophylaxis implementation in the region, we propose that there should be better health education, establishment of hospital-based guidelines and multidisciplinary collaboration.