Protocols, policies and practices for antimicrobial stewardship in hospitalized patients in least-developed and low-income countries: a systematic review.

BACKGROUND: We aimed to identify interventions used to implement antimicrobial stewardship practices among hospitalized patients in least-developed countries. METHODS: The research team searched PubMed, EMBASE, and Cochrane Central Register of Controlled Trials for studies of AMS interventions in the least developed and low-income countries, published between 2000 and 2023. Included studies had a population of hospitalized patients of all age groups in least-developed countries, implemented an AMS intervention, and reported its impact on prescription practices, clinical outcomes, or microbiological results. The risk of bias was assessed using the integrated quality criteria for review of multiple study designs. A total of 443 articles were identified, 386 articles were screened, 16 full-text papers were reviewed, and 10 studies were included in the analysis. RESULTS: The ten studies included three controlled before and after, two qualitative, one controlled interrupted time series, two non-controlled interrupted time series, one quasi-experimental study, and one randomized controlled trial. Three studies implemented either enabling, persuasive, or structural interventions respectively. The rest used bundled strategies, including a combination of persuasive, enabling, structural, and restrictive interventions. Bundled interventions using enabling and persuasive strategies were the most common. These involved creating a prescription guideline, training prescribers on updated methods, and subsequent review and feedback of patient files by members of an AMS team. Improved microbiological surveillance was important to most studies but, sustained improvement in appropriate prescriptions was dependent on enabling or persuasive efforts. Studies noted significant improvements in appropriate prescriptions and savings on the costs of antibiotics. None evaluated the impact of AMS on AMR. CONCLUSION: AMS practices generally involve multiple strategies to improve prescription practices. In the setting of least-developed countries, enabling and persuasive interventions are popular AMS measures. However, measured outcomes are heterogeneous, and we suggest that further studies assessing the impact of AMS should report changes in AMR patterns (microbiological outcomes), patient length of stay and mortality (patient outcomes), and changes in prescription practices (prescription outcomes). Reporting on these as outcomes of AMS interventions could make it easier for policymakers to compare which interventions have desirable outcomes that can be generalized to similar settings.

Antimicrobial stewardship interventions in least developed and low-income countries: a systematic review protocol.

INTRODUCTION: Antimicrobial resistance (AMR) is increasing in low resource settings. It complicates the management of infectious diseases and is an increasing cause of death. This is due to, among other things, lack of health resources for appropriate diagnosis and unregulated access to antimicrobials in the public sphere. Developing context-specific interventions that enable judicious use of antimicrobials is important to curb this problem. METHODS: We will conduct a systematic review of antimicrobial stewardship (AMS) approaches in Development Assistance Committee in least developed and low-income countries. The inclusion criteria are antimicrobial stewardship interventions in hospitalised patients of all age groups and exclusion criteria are community-based trials and studies that solely focus on viral, fungal or parasite infections. Antimicrobial stewardship interventions will be classified as structural, enabling, persuasive, restrictive or combined. Outcomes of included studies will be classified as clinical, microbiological or behavioural outcomes. The studies to be included will be randomised controlled trials, controlled before-after studies, interrupted time series trials, cohort and qualitative studies. Data will be extracted using forms adapted from the Cochrane collaboration data collection form. This systematic review will be conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines and risk of bias will be done according to the Integrated quality Criteria for Review of Multiple Study Designs. ETHICS AND DISSEMINATION: Our findings will be presented to clinicians and policymakers, to support developing AMS protocols for low resource settings. We will publish our results in peer-reviewed journals. TRIAL REGISTRATION NUMBER: CRD42020210634.

Predictive role of heterozygous p.R4810K of RNF213 in the phenotype of Chinese moyamoya disease.

OBJECTIVE: Precise genetic analyses were conducted with ring finger protein 213 (RNF213) in relation to a particular clinical phenotype in Chinese patients with moyamoya disease (MMD) to determine whether heterozygosity is responsible for the early-onset and severe form of this disease. METHODS: A case-control study for RNF213 p.R4810K involving 1,385 Chinese patients with MMD and 2,903 normal control participants was performed. Correlation analyses between genotype and phenotype or different clinical features were also statistically explored. RESULTS: An obvious trend was observed: the carrying rate of RNF213 p.R4810K gradually decreased when moving from coastal cities in northeast, north, and east China to southern cities or inland areas. Higher frequencies of p.R4810K were observed in patients with MMD compared with control participants (odds ratio, 48.1; 95% confidence interval, 29.1-79.6; p = 1.6 × 10-141). In addition, the onset age of all patients with the GA and AA genotypes were lower than with the GG genotype, and the median onset age was 40.0, 36.0, and 11.5 years with GG, GA, and AA, respectively, thereby confirming that those with GA or AA could acquire MMD during early life stages. Patients with MMD with the GA genotype were more susceptible to posterior cerebral artery (PCA) involvement compared to those with the GG genotype (38.4% vs 23.3%, p = 8.3 × 10-7). CONCLUSIONS: Strong evidence suggests that the carrying rate of RNF213 p.R4810K is closely related MMD risk in China and has given rise to an earlier onset age and more severe PCA involvement.

Association of single nucleotide polymorphisms of MTHFR, TCN2, RNF213 with susceptibility to hypertension and blood pressure.

Methylenetetrahydrofolate reductase gene (MTHFR), transcobalaminII (TCN2) and ring finger protein 213 (RNF213) are related to homocysteine (Hcy) level and are of great significance for hypertension. We aimed to evaluate the associations of MTHFR (rs1801133, rs1801131, rs9651118), TCN2 (rs117353193) and RNF213 (rs9916351) with hypertension and blood pressure (BP). A total of 953 patients with hypertension and 1103 controls were enrolled. Genotyping was performed by Taqman. Logistic regression analysis indicated that A allele of TCN2 rs117353193 under the dominant model had a significantly protective effect (P=0.045) after adjustment, which showed that AA+GA genotype has a lower risk than GG. Additionally, the average diastolic BP (DBP) (P=0.044) and mean arterial pressure (MAP) (P=0.035) levels were significantly different between genotypes of RNF213 rs9916351. Further pairwise comparison showed that the average systolic BP (SBP) level of the TT genotype carriers were significantly higher than in CC (P=0.024), and the average DBP and MAP levels of the TT genotype carriers were higher than in CT (P=0.044, P=0.012, respectively) and CC (P=0.048, P=0.010, respectively). In the recessive model, the average SBP (P=0.043), DBP (P=0.018) and MAP (P=0.017) levels with the TT genotype carriers were significantly higher than in CT+CC. Multiple linear regression analysis suggested that RNF213 rs9916351 in the recessive model had significant effects on SBP (P=0.025), DBP (P=0.017) and MAP (P=0.010) as a risk factor. However, no associations were observed between MTHFR and hypertension. TCN2 rs117353193 might serve as a protective factor in hypertension, and RNF213 rs9916351 might be a risk factor that is linked to increase BP level in Northeast Chinese population.

The Play of Genes and Non-genetic Factors on Type 2 Diabetes.

Diabetes has been a disease of public health concern for a number of decades. It was in the 1930s when scientists made an interesting discovery that the disease is actually divided into two types as some patients were insensitive to insulin treatment then. Type 2 Diabetes which happens to be the non-insulin dependent one is the most common form of the disease and is caused by the interaction between genetic and non-genetic factors. Despite conflicting results, numerous studies have identified genetic and non-genetic factors associated with this common type of diabetes. This review has summarized literature on some genes and non-genetic factors which have been identified to be associated with Type 2 diabetes. It has sourced literature from PubMed, Web of Science and Medline without any limitation to regions, publication types, or languages. The paper has started with the introduction, the play of non-genetic factors, the impact of genes in general, and ended with the interaction between some genes and environmental factors.

Association between ADIPOQ G276T and C11377G polymorphisms and the risk of non-alcoholic fatty liver disease: An updated meta-analysis.

BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) is a significant contributor to global hepatic disorders. ADIPOQ gene single-nucleotide polymorphisms have been associated with NAFLD susceptibility, but with inconsistent results across the studies. This study aimed to investigate the association between ADIPOQ polymorphisms (+276G>T, rs1501299 and -11377C>G, rs266729) and the risk of NAFLD. METHODS: PubMed, Embase, Wanfang, Web of Science, and China National Knowledge Infrastructure databases were used to identify the relevant published literature. Statistical analyses were calculated with STATA 11.0 software and RevMan 5.2. Summary odds ratios (OR) and 95% confidence intervals (CIs) were generated to assess the strength of the associations. RESULTS: Eleven relevant articles with a total of 3,644 participants (1,847 cases/1,797 controls) were included. Our meta-analysis results revealed that ADIPOQ gene +276G>T polymorphism was not associated with NAFLD under various genetic models (allele model: OR = 0.99, 95% CI [0.69, 1.41]; dominant model: OR = 1.06, 95% CI [0.71, 1.58]; recessive model: OR = 0.83, 95% CI [0.42, 1.65]; homozygous model: OR = 0.86, 95% CI [0.38, 1.95]; heterozygous model: OR = 1.10, 95% CI [0.80, 1.53]; respectively). Moreover, no statistical significant association was found between +276G>T and NAFLD risk in the subgroups. ADIPOQ gene -11377C>G polymorphism significantly increased the risk of NAFLD (allele model: OR = 1.49, 95% CI [1.28, 1.75]; dominant model: OR = 1.64, 95% CI [1.35, 1.99]; recessive model: OR = 1.77, 95% CI [1.16, 2.70]; homozygous model: OR = 2.13, 95% CI [1.38, 3.28]; heterozygous model: OR = 1.58, 95% CI [1.29, 1.93]; respectively). CONCLUSION: ADIPOQ gene -11377C>G may be a risk factor for NAFLD, while there was no association between ADIPOQ gene +276G>T polymorphism and the risk of NAFLD. Further studies are needed to detect the relationship between these ADIPOQ polymorphisms and NAFLD.

A Meta-Analysis of the Association between Microrna-196A2 and Risk of Ischemic Stroke and Coronary Artery Disease in Asian Population.

OBJECT: Single nucleotide polymorphisms (SNPs) of small non-coding RNAs (sncRNAs) that affect the sncRNA function and target gene expression to mediate the risk of certain diseases. The association between the miR-196a2 rs11614913 and ischemic stroke (IS) and coronary artery disease (CAD) is still conflicting and inconclusive. This meta-analysis aimed at analysing studies which have been done so far to get a more precise assessment of the association between the mutation and these two diseases. METHODS: Electronic databases dated up to April 2018 were searched, retrieved and used. Revman 5.2 software and STATA version 12.0 were used for statistical analysis. Odds ratios (ORs) and 95% confidence intervals (CIs) were used to identify any potential associations. Heterogeneity, publication bias and sensitivity analysis were conducted to measure the robustness of our findings. RESULTS: The overall meta-analysis results showed that miR-196a2 rs11614913 T > C polymorphism was significantly associated with CAD risk in certain genetic models, as well as in subgroup analysis (CC versus TT, OR = .43, 95%CI = .39-.47, P < .00001). However, no significant association was detected between the miR-196a2 rs11614913 T > C and IS risk in all genetic models. CONCLUSIONS: Our study suggests that miR-196a2 rs11614913 T > C may contribute to CAD susceptibility but further well-designed studies with larger sample size and comprehensive data are needed to confirm our findings and provide a profound conclusion.

RNF213 p.R4810K Polymorphism and the Risk of Moyamoya Disease, Intracranial Major Artery Stenosis/Occlusion, and Quasi-Moyamoya Disease: A Meta-Analysis.

BACKGROUND: Accumulating studies have reported that there is an association between the Ring finger protein 213 (RNF213) p.R4810K (rs112735431, c.14576G>A) single nucleotide polymorphism and the predisposition of moyamoya disease (MMD), intracranial major artery stenosis/occlusion (ICASO), quasi-moyamoya disease (quasi-MMD), and other vascular diseases. However, to this day, analyses about this association have remained scarce in the literature. We attempted to conduct a meta-analysis to systematically summarize and clarify the issue. METHODS: Electronic databases dated up to January 2018 were searched, retrieved, and used. Revman 5.2 software and STATA version 12.0 were used for statistical analysis. The association between RNF213 p.R4810K and MMD, ICASO, and quasi-MMD were assessed by odds ratios and 95% confidence intervals using fixed effects models. Between-study heterogeneity was evaluated by I-squared (I2) statistics and sensitivity analysis was performed by omitting 1 study at a time. A funnel plot and Begg's test were used to assess the potential publication bias. RESULTS: The outcomes showed a statistically significant association between RNF213 p.R4810K and MMD, ICASO, and quasi-MMD, especially in the dominant model. Apart from the first 2 diseases, no significant association was identified under the recessive, the homozygote, and the heterozygote models in ICASO. CONCLUSIONS: RNF213 p.R4810K was associated with MMD, ICASO, and quasi-MMD in different genetic models. Subgroup analysis indicated highly significantly higher risk in the Japanese patients. However, further well-designed studies with larger sample size and comprehensive data are needed to confirm our findings and provide a profound conclusion.