Antithrombotic drugs for cardiovascular risk reduction in patients with lower limb peripheral arterial disease: protocol for a systematic review and network meta-analysis of randomised controlled trials.

INTRODUCTION: The optimal antithrombotic regimen to reduce the risk of vascular events in patients with peripheral arterial disease (PAD) is contentious. This systematic review and network meta-analysis (NMA) aims to define the relative efficacy and risks of previously investigated antithrombotic medication regimens in preventing major cardiovascular events, vascular limb events and mortality in patients with PAD. METHODS AND ANALYSIS: A peer-reviewed, systematic search will be executed in English on Medline, Embase, Cochrane (CENTRAL), Web of Science and Google Scholar databases in late 2022. The WHO International Clinical Trials Registry platform will also be searched for ongoing trials. Abstracts will be screened independently by two researchers for randomised controlled trials meeting the review criteria. All associated publications including the study protocol will be sought and evaluated together against prespecified inclusion/exclusion criteria. Two researchers will extract the data into a prepiloted extraction form. Risk-of-bias assessments will be performed using the Cochrane 'Risk-of-Bias V.2' criteria by individuals with domain expertise. All differences will be resolved by consensus or a third individual for ties.Included trials will be summarised. An NMA will be performed, subject to checks of assumptions. Both primary and secondary outcomes will be analysed on a whole network basis. Pairwise comparisons and league tables will be produced. Prespecified subgroup analyses will include sex, ethnicity, disease status, conservative versus interventional management and key comorbidities. The findings will be evaluated using the Grading of Recommendation Assessment, Development and Evaluation, informed by patient and public involvement work. ETHICS AND DISSEMINATION: This is a systematic review of data in the public domain and does not require ethical approval. Dissemination will include presentations to key vascular and patient organisations, publication in a peer-reviewed journal and an open-access repository of the study data. PROSPERO REGISTRATION NUMBER: CRD42023389262.

Health Systems' Resilience: COVID-19 Response in Trinidad and Tobago.

Trinidad and Tobago, a small island developing state, has been ranked as number one in a report published by the University of Oxford that assessed responses to COVID-19 based on four of the six WHO criteria for rolling back COVID-19 "lockdown" measures. The key mitigation and containment strategies implemented by the country were evidence-informed and demonstrated an "all-of-government" approach. The COVID-19 health system response of this country demonstrates that although developing countries face many health system challenges, political will, evidence-informed decision-making, respect for science, and timely, coordinated, collaborative actions can strengthen the resilience and response of the health system during a health emergency.

Use of amplified-fragment length polymorphism to study the ecology of Campylobacter jejuni in environmental water and to predict multilocus sequence typing clonal complexes.

We determined the genetic variability among water isolates of Campylobacter jejuni by using amplified-fragment length polymorphism (AFLP) and multilocus sequence typing (MLST). Across a highly diverse collection of isolates, AFLP clusters did not correlate with MLST clonal complexes, suggesting that AFLP is not reliable for deciphering population genetic relationships and may be problematic for larger epidemiologic analyses.

Determination of the optimal culture conditions for detecting thermophilic campylobacters in environmental water.

This study evaluated alternative protocols for culturing thermophilic campylobacters in environmental water. All samples were filtered through a sterile 0.45µm pore-size membrane, which was then incubated in Preston enrichment broth. Four variables were compared: water sample volume (2000mL vs. 500mL), enrichment broth volume (25mL vs. 100mL), enrichment incubation duration (24h vs. 48h), and number of enrichment passages (one vs. two). In addition, DNA extracts were prepared from all final broths and analyzed using three rRNA PCR assays. River water was collected at 3 sampling sites weekly for 9 weeks. Among these 27 collections, 25 (93%) yielded Campylobacter spp. under at least one of the 16 culture conditions. By univariate analysis, yields were significantly better for the 2000mL sample volume (68.5% vs. 43.0%, p<0.0001) and the 25mL enrichment broth volume (64.5% vs. 47.0%, p<0.0004). Neither of the enrichment period had a significant effect, although there was a trend in favor of 48h incubation (59.5% vs. 52.0%, p=0.13). The three PCR methods gave concordant results for 66 (33%) of the culture-negative samples and 103 (50%) of the culture-positive samples. Compared with culture results, Lubeck's 16S PCR assay had the best performance characteristics, with a sensitivity of 82% and a specificity of 94%. Of the 12 culture-negative samples positive by Lubeck's PCR assay, 11 (92%) samples were also positive by Denis' 16S PCR assay, suggesting that in these cases the culture might have been falsely negative. Based on our results, we conclude that the optimal conditions for detecting Campylobacter spp. in natural waters include 2000mL sample volume and a single enrichment broth of 25mL PB incubated for 48h.

Thermotolerant coliforms are not a good surrogate for Campylobacter spp. in environmental water.

This study aimed to assess the importance of quantitatively detecting Campylobacter spp. in environmental surface water. The prevalence and the quantity of Campylobacter spp., thermotolerant coliforms, and Escherichia coli in 2,471 samples collected weekly, over a 2-year period, from 13 rivers and 12 streams in the Eastern Townships, Québec, Canada, were determined. Overall, 1,071 (43%), 1,481 (60%), and 1,463 (59%) samples were positive for Campylobacter spp., thermotolerant coliforms, and E. coli, respectively. There were weak correlations between the weekly distributions of Campylobacter spp. and thermotolerant coliforms (Spearman's rho coefficient = 0.27; P = 0.008) and between the quantitative levels of the two classes of organisms (Kendall tau-b correlation coefficient = 0.233; P < 0.0001). Well water samples from the Eastern Townships were also tested. Five (10%) of 53 samples from private surface wells were positive for Campylobacter jejuni, of which only 2 were positive for thermotolerant coliforms. These findings suggest that microbial monitoring of raw water by using only fecal indicator organisms is not sufficient for assessing the occurrence or the load of thermophilic Campylobacter spp. Insights into the role of environmental water as sources for sporadic Campylobacter infection will require genus-specific monitoring techniques.