The Cochrane Collaboration: institutional analysis of a knowledge commons

Cochrane is an international network that produces and updates new knowledge through systematic reviews for the health sector. Knowledge is a shared resource, and can be viewed as a commons. As Cochrane has been in existence for 25 years, we used Elinor Ostrom's theory of the commons and Institutional Analysis and Development Framework to appraise the organisation. Our aim was to provide insight into one particular knowledge commons, and to reflect on how this analysis may help Cochrane and its funders improve their strategy and development. An assessment of Cochrane product showed extensive production of systematic reviews, although assuring consistent quality of these reviews is an enduring challenge; there is some restriction of access to the reviews, open access is not yet implemented; and, while permanence of the record is an emerging problem, it has not yet been widely discussed. The assessment of the process showed that the resource, community, and rules-in-use are complex, vary between different groups within Cochrane, and are not well understood. Many of the rules have been informal, and the underlying ethos of volunteerism where reviews get done are important features and constraints to the organisation. Like all collective efforts, Cochrane is subject to collective action problems, particularly free-riding and variable commitment, and the under-production of public goods and internal processes, such as surveillance of product quality and procedures for transparent resolution of conflicts

The effectiveness of continuous quality improvement for developing professional practice and improving health care outcomes: a systematic review

Efforts to improve the quality, safety, and efficiency of health care provision have often focused on changing approaches to the way services are organized and delivered. Continuous quality improvement (CQI), an approach used extensively in industrial and manufacturing sectors, has been used in the health sector. Despite the attention given to CQI, uncertainties remain as to its effectiveness given the complex and diverse nature of health systems. This review assesses the effectiveness of CQI across different health care settings, investigating the importance of different components of the approach. We searched 11 electronic databases: MEDLINE, CINAHL, EMBASE, AMED, Academic Search Complete, HMIC, Web of Science, PsycINFO, Cochrane Central Register of Controlled Trials, LISTA, and NHS EED to February 2019. Also, we searched reference lists of included studies and systematic reviews, as well as checking published protocols for linked papers. We selected randomized controlled trials (RCTs) within health care settings involving teams of health professionals, evaluating the effectiveness of CQI. Comparators included current usual practice or different strategies to manage organizational change. Outcomes were health care professional performance or patient outcomes. Studies were published in English. Twenty-eight RCTs assessed the effectiveness of different approaches to CQI with a non-CQI comparator in various settings, with interventions differing in terms of the approaches used, their duration, meetings held, people involved, and training provided. All RCTs were considered at risk of bias, undermining their results. Findings suggested that the benefits of CQI compared to a non-CQI comparator on clinical process, patient, and other outcomes were limited, with less than half of RCTs showing any effect. Where benefits were evident, it was usually on clinical process measures, with the model used (i.e., Plan-Do-Study-Act, Model of Improvement), the meeting type (i.e., involving leaders discussing implementation) and their frequency (i.e., weekly) having an effect. None considered socio-economic health inequalities. Current evidence suggests the benefits of CQI in improving health care are uncertain, reflecting both the poor quality of evaluations and the complexities of health services themselves. Further mixed-methods evaluations are needed to understand how the health service can use this proven approach. Protocol registered on PROSPERO (CRD42018088309)

Maintaining relevance in HIV systematic reviews: an evaluation of Cochrane reviews

Background Research turnover in the HIV field is rapid, and as a result, maintaining high-quality, up-to-date, and relevant systematic reviews is a challenge. One approach is to frequently update published reviews. Methods We evaluated the methods and relevance of all HIV systematic reviews and protocols published in the Cochrane Library over a 16-year period (2000–2016) to determine the need to update published reviews or complete of reviews in progress. Results Of 148 published reviews and protocols, 129 (87%) were identified as not for updating or progression to publication, mostly due to research questions which were either entirely outdated or addressed questions in an outdated manner (N = 89; 60%); this was anticipated for older reviews, but was found also to be the case for recent publications. Some research questions were also inadequately conceptualized, particularly when complex pragmatic trials or behavioral interventions were included. Conclusions We suggest that authors clearly characterize interventions and synthesis approaches in their review protocols. In research fields, such as HIV, where questions change frequently, systematic reviews and protocols should be regularly re-evaluated to ensure relevance to current questions. This process of re-evaluation should be incorporated into the methods of living systematic reviews

Barriers and facilitators to deprescribing in primary care: a systematic review

Background Managing polypharmacy is a challenge for healthcare systems globally. It is also a health inequality concern as it can expose some of the most vulnerable in society to unnecessary medications and adverse drug-related events. Care for most patients with multimorbidity and polypharmacy occurs in primary care. Safe deprescribing interventions can reduce exposure to inappropriate polypharmacy. However, these are not fully accepted or routinely implemented. Aim To identify barriers and facilitators to safe deprescribing interventions for adults with multimorbidity and polypharmacy in primary care. Design and setting Systematic review of studies published from 2000, examining safe deprescribing interventions for adults with multimorbidity and polypharmacy (PROSPERO: CRD42019121848). Method A search of electronic databases: Medline, Embase, CINHAL, Cochrane and HMIC (26.02.19) using an agreed search strategy; supplemented by handsearching of relevant journals, and screening of reference lists and citations of included studies. Results Forty studies from 14 countries were identified. Cultural and organisational barriers included a culture of diagnosis and prescribing; evidence-based guidance focused on single diseases; a lack of evidence-based guidance for the care of older people with multimorbidities; and a lack of shared communication, decision-making systems, tools and resources. Interpersonal and individual-level barriers included professional etiquette; fragmented care; prescribers’ and patients’ uncertainties; and gaps in tailored support. Facilitators included prudent prescribing; greater availability and acceptability of non-pharmacological alternatives; resources; improved communication, collaboration, knowledge and understanding; patient-centred care; and shared decision-making. Conclusion A whole systems patient-centred approach to safe deprescribing interventions is required, involving key decision-makers, healthcare professionals, patients and carers

De novo mutations of KIAA2022 in females cause intellectual disability and intractable epilepsy

Background Mutations in the KIAA2022 gene have been reported in male patients with X-linked intellectual disability, and related female carriers were unaffected. Here, we report 14 female patients who carry a heterozygous de novo KIAA2022 mutation and share a phenotype characterised by intellectual disability and epilepsy. Methods Reported females were selected for genetic testing because of substantial developmental problems and/or epilepsy. X-inactivation and expression studies were performed when possible. Results All mutations were predicted to result in a frameshift or premature stop. 12 out of 14 patients had intractable epilepsy with myoclonic and/or absence seizures, and generalised in 11. Thirteen patients had mild to severe intellectual disability. This female phenotype partially overlaps with the reported male phenotype which consists of more severe intellectual disability, microcephaly, growth retardation, facial dysmorphisms and, less frequently, epilepsy. One female patient showed completely skewed X-inactivation, complete absence of RNA expression in blood and a phenotype similar to male patients. In the six other tested patients, X-inactivation was random, confirmed by a non-significant twofold to threefold decrease of RNA expression in blood, consistent with the expected mosaicism between cells expressing mutant or normal KIAA2022 alleles. Conclusions Heterozygous loss of KIAA2022 expression is a cause of intellectual disability in females. Compared with its hemizygous male counterpart, the heterozygous female disease has less severe intellectual disability, but is more often associated with a severe and intractable myoclonic epilepsy

Genome-wide identification and phenotypic characterization of seizure-associated copy number variations in 741,075 individuals

Copy number variants (CNV) are established risk factors for neurodevelopmental disorders with seizures or epilepsy. With the hypothesis that seizure disorders share genetic risk factors, we pooled CNV data from 10,590 individuals with seizure disorders, 16,109 individuals with clinically validated epilepsy, and 492,324 population controls and identified 25 genome-wide significant loci, 22 of which are novel for seizure disorders, such as deletions at 1p36.33, 1q44, 2p21-p16.3, 3q29, 8p23.3-p23.2, 9p24.3, 10q26.3, 15q11.2, 15q12-q13.1, 16p12.2, 17q21.31, duplications at 2q13, 9q34.3, 16p13.3, 17q12, 19p13.3, 20q13.33, and reciprocal CNVs at 16p11.2, and 22q11.21. Using genetic data from additional 248,751 individuals with 23 neuropsychiatric phenotypes, we explored the pleiotropy of these 25 loci. Finally, in a subset of individuals with epilepsy and detailed clinical data available, we performed phenome-wide association analyses between individual CNVs and clinical annotations categorized through the Human Phenotype Ontology (HPO). For six CNVs, we identified 19 significant associations with specific HPO terms and generated, for all CNVs, phenotype signatures across 17 clinical categories relevant for epileptologists. This is the most comprehensive investigation of CNVs in epilepsy and related seizure disorders, with potential implications for clinical practice