BackgroundClinical quality registries (CQRs) are playing an increasingly important role in improving health outcomes and reducing health care costs. CQRs are established with the purpose of monitoring quality of care, providing feedback, benchmarking performance, describing pattern of treatment, reducing variation and as a tool for conducting research.ObjectivesTo synthesise the impact of clinical quality registries (CQRs) as an ‘intervention’ on (I) mortality/survival; (II) measures of outcome that reflect a process or outcome of health care; (III) health care utilisation; and (IV) healthcare-related costs.MethodsThe following electronic databases were searched: MEDLINE, EMBASE, CENTRAL, CINAHL and Google Scholar. In addition, a review of the grey literature and a reference check of citations and reference lists within articles was undertaken to identify relevant studies in English covering the period January 1980 to December 2016. The PRISMA-P methodology, checklist and standard search strategy using pre-defined inclusion and exclusion criteria and structured data extraction tools were used. Data on study design and methods, participant characteristics attributes of included registries and impact of the registry on outcome measures and/or processes of care were extracted.ResultsWe identified 30102 abstracts from which 75 full text articles were assessed and finally 17 articles were selected for synthesis. Out of 17 studies, six focused on diabetes care, two on cardiac diseases, two on lung diseases and others on organ transplantations, rheumatoid arthritis, ulcer healing, surgical complications and kidney disease. The majority of studies were “before after” design (#11) followed by cohort design (#2), randomised controlled trial (#2), experimental non randomised study and one cross sectional comparison. The measures of impact of registries were multifarious and included change in processes of care, quality of care, treatment outcomes, adherence to guidelines and survival. Sixteen of 17 studies demonstrated positive findings in their outcomes after implementation of the registry.ConclusionsDespite the large number of published articles using data derived from CQRs, few have rigorously evaluated the impact of the registry as an intervention on improving health outcomes. Those that have evaluated this impact have mostly found a positive impact on healthcare processes and outcomes.Trial registrationPROSPERO CRD42015017319

Predation by bacteriophages can significantly influence the population structure of bacterial communities. Vibrio cholerae the causative agent of cholera epidemics interacts with numerous phages in the aquatic ecosystem, and in the intestine of cholera patients. Seasonal epidemics of cholera reportedly collapse due to predation of the pathogen by phages. However, it is not clear how sufficient number of the bacteria survive to seed the environment in the subsequent epidemic season. We found that bacterial cell density-dependent gene expression termed “quorum sensing” which is regulated by signal molecules called autoinducers (AIs) can protect V. cholerae against predatory phages. V. cholerae mutant strains carrying inactivated AI synthase genes were significantly more susceptible to multiple phages compared to the parent bacteria. Likewise when mixed cultures of phage and bacteria were supplemented with exogenous autoinducers CAI-1 or AI-2 produced by recombinant strains carrying cloned AI synthase genes, increased survival of V. cholerae and a decrease in phage titer was observed. Mutational analyses suggested that the observed effects of autoinducers are mediated in part through the quorum sensing-dependent production of haemaglutinin protease, and partly through downregulation of phage receptors. These results have implication in developing strategies for phage mediated control of cholera.

CRISPR-Cas (clustered regularly interspersed short palindromic repeats-CRISPR-associated proteins) are microbial nuclease systems involved in defense against phages. Bacteria also resist phages by hosting phage-inducible chromosomal islands (PICI) which prevent phage reproduction. Vibrio cholerae which causes cholera epidemics, interacts with numerous phages in the environment and in cholera patients. Although CRISPR-Cas systems are usually carried by bacteria and archea, recently V. cholerae specific ICP1 phages were found to host a CRISPR-Cas system that inactivates PICI-like elements (PLE) in V. cholerae. We analyzed a collection of phages and V. cholerae isolated during seasonal cholera epidemics in Bangladesh, to study the distribution, and recent evolution of the phage-encoded CRISPR-Cas system. Five distinct but related phages carrying the CRISPR-Cas system, and possible CRISPR-Cas negative progenitor phages were identified. Furthermore, CRISPR arrays in the phages were found to have evolved by acquisition of new spacers targeting diverse regions of PLEs carried by the V. cholerae strains, enabling the phages to efficiently grow on PLE positive strains. Our results demonstrate a continuing arms-race involving genetic determinants of phage-resistance in V. cholerae, and the phage-encoded CRISPR-Cas system in the co-evolution of V. cholerae and its phages, presumably fostered by their enhanced interactions during seasonal epidemics of cholera.

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