Wastewater Surveillance of Antimicrobial Resistance in Human Populations: A Systematic Review

2020 ◽  
Author(s):  
Kevin Chau ◽  
Leanne Barker ◽  
Natalie Sims ◽  
Barbara Kasprzyk-Hordern ◽  
Eric Budgell ◽  
...  
Keyword(s):  
Antimicrobial Resistance ◽  
Longitudinal Studies ◽  
Study Design ◽  
Meta Analysis ◽  
Population Level ◽  
Human Populations ◽  
Grab Sampling ◽  
Culture Independent ◽  
Methodological Approaches ◽  
The Impact

Wastewater-based surveillance of antimicrobial resistance (AMR) may facilitate convenient monitoring of population-level AMR prevalence without the healthcare-associated bias and data collection restrictions inherent to clinically oriented systems. However, differences in study design and methodology likely contribute to differences in outcomes and interpretation, limiting reproducibility, reliability and meta-analysis. We therefore systematically reviewed studies using wastewater for AMR surveillance in human populations to identify optimal practices to detect wastewater-human AMR correlations. We evaluated 7,063 records and 174 full-text methods in a two-stage screen; 20 studies were included. Risk of bias assessment divided studies into high-risk (n=3), low-risk (n=3) and unclear-risk (n=14). Most studies detected wastewater-human AMR correlations (n=15) but only six studies identified statistically significant associations, most via culture-independent approaches (n=5). Genomic approaches also facilitated higher-resolution AMR monitoring whereas culture-based studies primarily undertook observational comparisons of specific organisms and phenotypic AMR profiles. Studies identifying wastewater-human AMR correlations were consistently associated with sampling wastewater influent irrespective of other methodological approaches. For longitudinal studies, a timeframe of >=6 months was similarly associated. Most influent studies identifying wastewater-human AMR correlations used composite (n=5) or flow-proportional wastewater sampling methods (n=4); however, grab sampling was commonest overall (n=6) and generally appeared similarly effective.Wastewater-based surveillance of AMR in human populations appears relatively robust, with most included studies reporting a correlation despite high diversity in study design and methodology. Our review supports sampling of wastewater influent using composite sampling (at a minimum) as a standard. Impacts of other methodological approaches are less clear; however, a minimum timeframe of six months for longitudinal studies, and increased sampling coverage for culture-independent studies to enable adequate biostatistical analyses appear sensible. As this relatively new field grows, more studies with clear wastewater-based population-level AMR surveillance aims are needed to better determine the impact of confounding features and validate comprehensive “best practice” protocols.

scholarly journals Evaluation of the impact of antimicrobial use protocols in PRRS virus infected swine on phenotypic antimicrobial resistance patterns

2021 ◽  
Author(s):  
Carissa A. Odland ◽  
Roy Edler ◽  
Noelle R. Noyes ◽  
Scott A. Dee ◽  
Joel Nerem ◽  
...  
Keyword(s):  
Antimicrobial Resistance ◽  
Longitudinal Studies ◽  
Bacterial Infections ◽  
Population Level ◽  
Control Group ◽  
Antimicrobial Use ◽  
Treatment Groups ◽  
Resistance Patterns ◽  
The Impact ◽  
Over Time

A longitudinal study was conducted to assess the impact of different antimicrobial exposures of nursery-phase pigs on patterns of phenotypic antimicrobial resistance in fecal indicator organisms throughout the growing phase. Based on practical approaches used to treat moderate to severe PRRSV-associated secondary bacterial infections, two antimicrobial protocols of differing intensity of exposure [44.1 and 181.5 animal-treatment days per 1000 animal days at risk (ATD)] were compared with a control group with minimal antimicrobial exposure (2.1 ATD). Litter-matched pigs (n = 108) with no prior antimicrobial exposure were assigned randomly to the treatment groups. Pen fecal samples were collected nine times during the wean-to-finish period and cultured for Escherichia coli and Enterococcus spp. Antimicrobial susceptibility testing was conducted using NARMS gram-negative and gram-positive antibiotic panels. Despite up to 65-fold difference in ATD, few and modest differences were observed between groups and over time. Resistant patterns at marketing overall remained similar to those observed at weaning, prior to any antimicrobial exposures. Those differences observed could not readily be reconciled with the patterns of antimicrobial exposure. Resistance of E. coli to streptomycin was higher in the group exposed to 44.1 ATD, but no aminoglycosides were used. In all instances where resistance differed between time points, the higher resistance occurred early in the trial prior to any antimicrobial exposures. These minimal impacts on AMR despite substantially different antimicrobial exposures point to the lack of understanding of the drivers of AMR at the population level and the likely importance of factors other than antimicrobial exposure. IMPORTANCE Despite a recognized need for more longitudinal studies to assess the effects of antimicrobial use on resistance in food animals, they remain sparse in the literature, and most longitudinal studies of pigs have been observational. The current experimental study had the advantages of greater control of potential confounding, precise measurement of antimicrobial exposures which varied markedly between groups and tracking of pigs until market age. Overall, resistance patterns were remarkably stable between the treatment groups over time, and the differences observed could not be readily reconciled with the antimicrobial exposures, indicating the likely importance of other determinants of AMR at the population level.

scholarly journals ‘Disperse abroad in the land’: the role of wildlife in the dissemination of antimicrobial resistance

2016 ◽  
Vol 12 (8) ◽  
pp. 20160137 ◽  
Author(s):  
Kathryn E. Arnold ◽  
Nicola J. Williams ◽  
Malcolm Bennett
Keyword(s):  
Antimicrobial Resistance ◽  
Natural Environment ◽  
High Throughput Sequencing ◽  
Small Scale ◽  
Human Populations ◽  
Long Distance ◽  
Antimicrobial Drugs ◽  
Clinical Resistance ◽  
Wildlife Populations ◽  
The Impact

Antimicrobial resistance (AMR) has been detected in the microbiota of many wildlife species, including long-distance migrants. Inadequately treated wastes from humans and livestock dosed with antimicrobial drugs are often assumed to be the main sources of AMR to wildlife. While wildlife populations closely associated with human populations are more likely to harbour clinically important AMR related to that found in local humans and livestock, AMR is still common in remote wildlife populations with little direct human influence. Most reports of AMR in wildlife are survey based and/or small scale, so researchers can only speculate on possible sources and sinks of AMR or the impact of wildlife AMR on clinical resistance. This lack of quantitative data on the flow of AMR genes and AMR bacteria across the natural environment could reflect the numerous AMR sources and amplifiers in the populated world. Ecosystems with relatively simple and well-characterized potential inputs of AMR can provide tractable, but realistic, systems for studying AMR in the natural environment. New tools, such as animal tracking technologies and high-throughput sequencing of resistance genes and mobilomes, should be integrated with existing methodologies to understand how wildlife maintains and disperses AMR.

scholarly journals Strength of functional signature correlates with effect size in autism

2016 ◽  
Author(s):  
Sara Ballouz ◽  
Jesse Gillis
Keyword(s):  
Study Design ◽  
Effect Size ◽  
Statistical Power ◽  
Fragile X ◽  
Meta Analysis ◽  
Autism Spectrum ◽  
Protein Interaction Data ◽  
Functional Convergence ◽  
Study Designs ◽  
The Impact

AbstractBackgroundDisagreements over genetic signatures associated with disease have been particularly prominent in the field of psychiatric genetics, creating a sharp divide between disease burdens attributed to common and rare variation, with study designs independently targeting each. Meta-analysis within each of these study designs is routine, whether using raw data or summary statistics, but combining results across study designs is atypical. However, tests of functional convergence are used across all study designs, where candidate gene sets are assessed for overlaps with previously known properties. This suggests one possible avenue for combining not study data, but the functional conclusions that they reach.MethodIn this work, we test for functional convergence in autism spectrum disorder (ASD) across different study types, and specifically whether the degree to which a gene is implicated in autism is correlated with the degree to which it drives functional convergence. Because different study designs are distinguishable by their differences in effect size, this also provides a unified means of incorporating the impact of study design into the analysis of convergence.ResultsWe detected remarkably significant positive trends in aggregate (p < 2.2e-16) with 14 individually significant properties (FDR<0.01), many in areas researchers have targeted based on different reasoning, such as the fragile X mental retardation protein (FMRP) interactor enrichment (FDR 0.003). We are also able to detect novel technical effects and we see that network enrichment from protein-protein interaction data is heavily confounded with study design, arising readily in control data.ConclusionsWe see a convergent functional signal for a subset of known and novel functions in ASD from all sources of genetic variation. Meta-analytic approaches explicitly accounting for different study designs can be adapted to other diseases to discover novel functional associations and increase statistical power.

scholarly journals ART initiations following community-based distribution of HIV self-tests: meta-analysis and meta-regression of STAR Initiative data

2021 ◽  
Vol 6 (Suppl 4) ◽  
pp. e004986
Author(s):  
Melissa Neuman ◽  
Katherine L Fielding ◽  
Helen Ayles ◽  
Frances M Cowan ◽  
Bernadette Hensen ◽  
...  
Keyword(s):  
Meta Analysis ◽  
National Level ◽  
Population Level ◽  
Hiv Care ◽  
People Living With Hiv ◽  
Community Based ◽  
Variable Effect ◽  
Standard Testing ◽  
Meta Regression ◽  
The Impact

IntroductionMeasuring linkage after community-based testing, particularly HIV self-testing (HIVST), is challenging. Here, we use data from studies of community-based HIVST distribution, conducted within the STAR Initiative, to assess initiation of antiretroviral therapy (ART) and factors driving differences in linkage rates.MethodsFive STAR studies evaluated HIVST implementation in Malawi, Zambia and Zimbabwe. New ART initiations during the months of intervention at clinics in HIVST and comparison areas were presented graphically, and study effects combined using meta-analysis. Meta-regression was used to estimate associations between the impact of community-based HIVST distribution and indicators of implementation context, intensity and reach. Effect size estimates used (1) prespecified trial definitions of ART timing and comparator facilities and (2) exploratory definitions accounting for unexpected diffusion of HIVST into comparison areas and periods with less distribution of HIVST than was expected.ResultsCompared with arms with standard testing only, ART initiations were higher in clinics in HIVST distribution areas in 4/5 studies. The prespecified meta-analysis found positive but variable effects of HIVST on facility ART initiations (RR: 1.14, 95% CI 0.93 to 1.40; p=0.21). The exploratory meta-analysis found a stronger impact of HIVST distribution on ART initiations (RR: 1.29, 95% CI 1.08 to 1.55, p=0.02).ART initiations were higher in studies with greater self-reported population-level intensity of HIVST use (RR: 1.12; 95% CI 1.04 to 1.21; p=0.02.), but did not differ by national-level indicators of ART use among people living with HIV, number of HIVST kits distributed per 1000 population, or self-reported knowledge of how to link to care after a reactive HIVST.ConclusionCommunity-based HIVST distribution has variable effect on ART initiations compared with standard testing service alone. Optimising both support for and approach to measurement of effective and timely linkage or relinkage to HIV care and prevention following HIVST is needed to maximise impact and guide implementation strategies.

scholarly journals The Impact of Protein Supplementation on Appetite and Energy Intake in Healthy Older Adults: A Systematic Review with Meta-Analysis

2020 ◽  
Author(s):  
Sana Ben-Harchache ◽  
Helen M Roche ◽  
Clare A Corish ◽  
Katy M Horner
Keyword(s):  
Systematic Review ◽  
Older Adults ◽  
Longitudinal Studies ◽  
Energy Intake ◽  
Energy Content ◽  
Meta Analysis ◽  
Protein Supplementation ◽  
Cochrane Library ◽  
Healthy Older Adults ◽  
The Impact

ABSTRACT Protein supplementation is an attractive strategy to prevent loss of muscle mass in older adults. However, it could be counterproductive due to adverse effects on appetite. This systematic review and meta-analysis aimed to determine the effects of protein supplementation on appetite and/or energy intake (EI) in healthy older adults. MEDLINE, The Cochrane Library, CINAHL, and Web of Science were searched up to June 2020. Acute and longitudinal studies in healthy adults ≥60 y of age that reported effects of protein supplementation (through supplements or whole foods) compared with control and/or preintervention (for longitudinal studies) on appetite ratings, appetite-related peptides, and/or EI were included. Random-effects model meta-analysis was performed on EI, with other outcomes qualitatively reviewed. Twenty-two studies (9 acute, 13 longitudinal) were included, involving 857 participants (331 males, 526 females). In acute studies (n = 8), appetite ratings were suppressed in 7 out of 24 protein arms. For acute studies reporting EI (n = 7, n = 22 protein arms), test meal EI was reduced following protein preload compared with control [mean difference (MD): −164 kJ; 95% CI: −299, −29 kJ; P  = 0.02]. However, when energy content of the supplement was accounted for, total EI was greater with protein compared with control (MD: 649 kJ; 95% CI: 438, 861 kJ; P &lt; 0.00001). Longitudinal studies (n = 12 protein arms) showed a higher protein intake (MD: 0.29 g ⋅ kg−1 ⋅ d−1; 95% CI: 0.14, 0.45 g ⋅ kg−1 ⋅ d−1; P &lt; 0.001) and no difference in daily EI between protein and control groups at the end of trials (MD: −54 kJ/d; 95% CI: −300, 193 kJ/d; P  = 0.67). While appetite ratings may be suppressed with acute protein supplementation, there is either a positive effect or no effect on total EI in acute and longitudinal studies, respectively. Therefore, protein supplementation may represent an effective solution to increase protein intakes in healthy older adults without compromising EI through appetite suppression. This trial was registered at PROSPERO as https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42019125771 (CRD42019125771).

Hemorrhagic and thrombotic events in oncology patients treated with antiangiogenic therapy: Impact of study design on the results assessed by meta-analysis.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e14058-e14058
Author(s):  
Jane-Chloe Trone ◽  
Céline Chapelle ◽  
Edouard Ollier ◽  
Laurent Bertoletti ◽  
Michel Cucherat ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Cancer Patients ◽  
Study Design ◽  
Fixed Effects ◽  
Meta Analysis ◽  
Antiangiogenic Therapy ◽  
Solid Cancer ◽  
Increasing Risk ◽  
Meta Analyses ◽  
The Impact

e14058 Background: Antiangiogenic (AA) therapies emerge as a new cornerstone for cancer treatment, but carry their own particular risk profile. Several previous meta-analyses have showed increasing risk of bleeding and paradoxically thrombosis in cancer patients receiving antiangiogenic. The aim of the meta-analysis is to investigate the impact of studies design (open or double blind (DB)), on the incidence and the occurrence of bleeding, venous thrombotic events (VTE) and arterial thrombotic events (ATE) in cancer patients treated by AA therapies. Methods: We searched Medline, Cochrane, ClinicalTrial databases, meeting abstracts of the American Society of Clinical Oncology and the European Society of Medical Oncology for relevant clinical trials. We included prospective phase II and III clinical trials that randomly assigned patients with solid cancer to AA therapy or control. Statistical analyses were conducted to calculate the summary incidence, ORs, and 95% CIs, using random-effects or fixed-effects models based on the heterogeneity of included studies. Results: A total of 166 trials (72,024 patients) were included. For bleeding events, comparison on AA treatment versus control yielded an OR of 2.41 (95% CI 2.07 to 2.71; p < 0.001) with an exaggeration of treatment effects by 68% (95% CI, 33 to 113) in open-label studies compared with DB trials. Concerning VTE, an OR of 1.18 (95% CI 1.04 to 1.35; p = 0.0115) was noted, with a significant enhancement of 53% (95% CI, 19 to 96) of treatment side effects with open trials compared with DB trials. AA don’t increase significantly the frequency of VTE when considering only DB trials. For ATE, an OR of 1.59 (95% CI 1.30 to 1.94; p < 0.001) was observed, associated with a significant exaggeration of 65% (95% CI, 13 to 143) with open trials compared with DB trials. Conclusions: The present meta-analysis showed a significant interaction of study design for the tolerance assessment in the AA therapies in cancers. The increasing risk of hemorrhagic events, VTE and ATE appear to have been overestimated in the previous meta-analyses. In the future, meta-analyses should be restricted to DB trials for analysis of toxicity profile.

P–014 Effect of microsurgical varicocelectomy on fertility outcome and treatment plans of patients with severe oligozoospermia: An original report and meta-analysis

2021 ◽  
Vol 36 (Supplement_1) ◽  
Author(s):  
A Majzoub ◽  
H Elbardisi ◽  
A Almalki ◽  
S Alsaid ◽  
M Arafa
Keyword(s):  
Pregnancy Rate ◽  
Study Design ◽  
Meta Analysis ◽  
Original Study ◽  
Pregnancy Rates ◽  
Semen Parameters ◽  
Q Value ◽  
Severe Oligozoospermia ◽  
Original Report ◽  
The Impact

Abstract Study question Does microsurgical subinguinal varicocelectomy (MSV) improve semen parameters and fertility outcomes of patients with severe oligozoospermia (SO) and clinical varicocele? Summary answer MSV significantly improves semen parameters of patients with SO and can broaden their fertility treatment options. What is known already: Varicocele ligation has been proven to restore semen parameters and improve pregnancy rates in men with clinically palpable disease. However, its effect in men with SO is less clearly elucidated. Patients with SO are candidates for in vitro fertilization and intracytoplasmic sperm injection. Improvements in semen quality following varicocele ligation in this patient population may broaden their fertility options. While few studies indicate an improvement in semen parameters, reports revealing a negative outcome following surgery in this patient group were also published. Study design, size, duration This original report and meta-analysis examined the impact of MSV on semen parameters and fertility outcomes of men with SO. A retrospective chart review of 85 patients was conducted on patients with SO who underwent MSV. A literature search was carried out according to the PRISMA guidelines using the key words “severe oligozoospermia” and “varicocele”. 8 scientific articles (including the current study) reporting the impact of MSV on men with SO were included. Participants/materials, setting, methods Changes in semen parameters postoperatively were compared with pre-operative results. The reported natural pregnancy rates were also calculated. The Wilcoxon signed-rank test was used to compare semen and hormone values before and after varicocelectomy. The Chi-squared test was used to assess the changes in TMSC groups after surgery. The meta-analysis was performed using comprehensive meta-analysis software (Biostat, Englewood, NJ, USA). Statistical significance was set at α = 0.05. The random-effects model was used to adjust for heterogeneity. Main results and the role of chance The original study reported significant improvements in sperm concentration (p &lt; 0.001), total motility (p = 0.003), progressive motility (p = 0.002) and TMSC (p &lt; 0.001) was following the surgery. in semen parameters following surgery. 78 patients had a pre-operative TMSC &lt; 5 million. Following surgery, 9 (11.5%) patients had a TMSC between 5–9 million, while 14 (17.9%) patients had a TMSC &gt; 9 million. The meta-analysis shows a statistically significant increase in sperm count following surgery (MD 5.64, 95% CI, 4.195–7.090, p = 0.00) with an acceptable degree of heterogeneity (Q value= 8.75, p = 0.188, I²= 31.5%). Similarly, the total motility significantly increased by 7.77% (p = 0.001) following surgery (95% CI, 3.248–12.297), however, with considerable heterogeneity among the reported results (Q value= 34.4, p &lt; 0.001). TMSC was assessed by three studies, including ours. The meta-analysis shows a significant increase in TMSC following surgery (MD 8.44 million sperm, 95% CI, 4.648–12.228, p &lt; 0.001) (Q Value= 2.53, p = 283, I²=20.7%). A total of 6 studies reported the natural pregnancy rate of patients with SO who underwent surgery. Out of 530 patients with preoperative SO, 146 patients achieved natural pregnancy following surgery indicating that the reported pregnancy rate was 27.5%. Limitations, reasons for caution One limitation to the original study is its relatively small sample size. However, this was compensated by conducting a meta-analysis and reporting the outcome of 601 patients with SO who underwent varicocele ligation. Another limitation is the retrospective nature of the study design. Wider implications of the findings: 29.5% of SO patients in the original study became eligible for IUI following varicocelectomy. Meta-analysis showed that 27.5% of patients achieved natural conception following surgery. Such information is beneficial during patient counselling and needs to be measured against the financial and clinical implications in order to make sound treatment decisions. Trial registration number NA

scholarly journals Antimicrobial resistance in human populations: challenges and opportunities

2017 ◽  
Vol 2 ◽  
Author(s):  
S. Allcock ◽  
E. H. Young ◽  
M. Holmes ◽  
D. Gurdasani ◽  
G. Dougan ◽  
...  
Keyword(s):  
Antimicrobial Resistance ◽  
Sustainable Use ◽  
Population Level ◽  
Population Based ◽  
Human Populations ◽  
Antimicrobial Use ◽  
Global Public Health ◽  
Burden Distribution ◽  
Public Health Threat ◽  
Challenges And Opportunities

AbstractAntimicrobial resistance (AMR) is a global public health threat. Emergence of AMR occurs naturally, but can also be selected for by antimicrobial exposure in clinical and veterinary medicine. Despite growing worldwide attention to AMR, there are substantial limitations in our understanding of the burden, distribution and determinants of AMR at the population level. We highlight the importance of population-based approaches to assess the association between antimicrobial use and AMR in humans and animals. Such approaches are needed to improve our understanding of the development and spread of AMR in order to inform strategies for the prevention, detection and management of AMR, and to support the sustainable use of antimicrobials in healthcare.

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