Likelihood‐based methods for regression analysis with binary exposure status assessed by pooling

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/93644/1/sim4426.pd

Molecular testing for Lynch syndrome in people with colorectal cancer: systematic reviews and economic evaluation

This is the final version of the article. Available from the publisher via the DOI in this record.BACKGROUND: Inherited mutations in deoxyribonucleic acid (DNA) mismatch repair (MMR) genes lead to an increased risk of colorectal cancer (CRC), gynaecological cancers and other cancers, known as Lynch syndrome (LS). Risk-reducing interventions can be offered to individuals with known LS-causing mutations. The mutations can be identified by comprehensive testing of the MMR genes, but this would be prohibitively expensive in the general population. Tumour-based tests - microsatellite instability (MSI) and MMR immunohistochemistry (IHC) - are used in CRC patients to identify individuals at high risk of LS for genetic testing. MLH1 (MutL homologue 1) promoter methylation and BRAF V600E testing can be conducted on tumour material to rule out certain sporadic cancers. OBJECTIVES: To investigate whether testing for LS in CRC patients using MSI or IHC (with or without MLH1 promoter methylation testing and BRAF V600E testing) is clinically effective (in terms of identifying Lynch syndrome and improving outcomes for patients) and represents a cost-effective use of NHS resources. REVIEW METHODS: Systematic reviews were conducted of the published literature on diagnostic test accuracy studies of MSI and/or IHC testing for LS, end-to-end studies of screening for LS in CRC patients and economic evaluations of screening for LS in CRC patients. A model-based economic evaluation was conducted to extrapolate long-term outcomes from the results of the diagnostic test accuracy review. The model was extended from a model previously developed by the authors. RESULTS: Ten studies were identified that evaluated the diagnostic test accuracy of MSI and/or IHC testing for identifying LS in CRC patients. For MSI testing, sensitivity ranged from 66.7% to 100.0% and specificity ranged from 61.1% to 92.5%. For IHC, sensitivity ranged from 80.8% to 100.0% and specificity ranged from 80.5% to 91.9%. When tumours showing low levels of MSI were treated as a positive result, the sensitivity of MSI testing increased but specificity fell. No end-to-end studies of screening for LS in CRC patients were identified. Nine economic evaluations of screening for LS in CRC were identified. None of the included studies fully matched the decision problem and hence a new economic evaluation was required. The base-case results in the economic evaluation suggest that screening for LS in CRC patients using IHC, BRAF V600E and MLH1 promoter methylation testing would be cost-effective at a threshold of £20,000 per quality-adjusted life-year (QALY). The incremental cost-effectiveness ratio for this strategy was £11,008 per QALY compared with no screening. Screening without tumour tests is not predicted to be cost-effective. LIMITATIONS: Most of the diagnostic test accuracy studies identified were rated as having a risk of bias or were conducted in unrepresentative samples. There was no direct evidence that screening improves long-term outcomes. No probabilistic sensitivity analysis was conducted. CONCLUSIONS: Systematic review evidence suggests that MSI- and IHC-based testing can be used to identify LS in CRC patients, although there was heterogeneity in the methods used in the studies identified and the results of the studies. There was no high-quality empirical evidence that screening improves long-term outcomes and so an evidence linkage approach using modelling was necessary. Key determinants of whether or not screening is cost-effective are the accuracy of tumour-based tests, CRC risk without surveillance, the number of relatives identified for cascade testing, colonoscopic surveillance effectiveness and the acceptance of genetic testing. Future work should investigate screening for more causes of hereditary CRC and screening for LS in endometrial cancer patients. STUDY REGISTRATION: This study is registered as PROSPERO CRD42016033879. FUNDING: The National Institute for Health Research Health Technology Assessment programme.Funding for this study was provided by the Health Technology Assessment programme of the National Institute for Health Researc

The Library as Safe Space

Purpose: This chapter will explain how libraries define safe space through policies, procedures, and professional codes of ethics. The chapter will generate a history of the concept of libraries as safe space, will explain how libraries attempt to create safe spaces in physical and online environments, and will show how library practices both help and harm patrons in need of safe space. Design/methodology/approach: This chapter provides a review of the literature that illustrates how libraries provide safe space—or not—for their patrons. The author will deconstruct the ALA Code of Ethics and Bill of Rights to demonstrate how libraries remain heteronormative institutions that do not recognize the existence of diverse patrons or employees, and how this phenomenon manifests in libraries. Findings: Libraries, either through their physical construction or through policies and procedures, have become spaces for illegal activities and discrimination. Populations who would be most likely to use libraries often report barriers to access. Practical Implications: Libraries should revisit their policies and procedures, as well as assess their physical and online spaces, to determine whether or not they truly provide safe space for their patrons. While libraries can become safer spaces, they should clearly communicate what types of safety they actually provide. Originality/value: This chapter offers a critique of libraries as safe spaces, which will challenge popular opinions of libraries, and compel the profession to improve

A systematic review and meta-analysis of haematological malignancies in residents living near petrochemical facilities

Background The petrochemical industry is a major source of hazardous and toxic air pollutants that are recognised to have mutagenic and carcinogenic properties. A wealth of occupational epidemiology literature exists around the petrochemical industry, with adverse haematological effects identified in employees exposed to ‘low’ concentrations of aromatic hydrocarbons (benzene, toluene, ethylbenzene, and xylene). Releases from the petrochemical industry are also thought to increase the risk of cancer incidence in fenceline communities. However, this emerging and at times inconclusive evidence base remains fragmented. The present study’s aim was to conduct a systematic review and meta-analysis of epidemiological studies investigating the association between incidences of haematological malignancy and residential exposure to the petrochemical industry. Methods Epidemiological studies reporting the risk of haematological malignancies (Leukaemia, Hodgkin’s lymphoma, Non-Hodgkin’s lymphoma, and Multiple myeloma) were included where the following criteria were met: (i) Cancer incidence is diagnosed by a medical professional and coded in accordance to the International Classification of Diseases; (ii) A clear definition of fenceline communities is provided, indicating the proximity between exposed residents and petrochemical activities; and (iii) Exposure is representative of normal operating conditions, not emergency events. Two investigators independently extracted information on study characteristics and outcomes in accordance with PRISMA and MOOSE guidelines. Relative risks and their 95% confidence intervals were pooled across studies for the four categories of haematological malignancy, using a random effects meta-analysis. Results The systematic review identified 16 unique studies, which collectively record the incidence of haematological malignancies across 187,585 residents living close to a petrochemical operation. Residents from fenceline communities, less than 5 km from a petrochemical facility (refinery or manufacturer of commercial chemicals), had a 30% higher risk of developing Leukaemia than residents from communities with no petrochemical activity. Meanwhile, the association between exposure and rarer forms of haematological malignancy remains uncertain, with further research required. Conclusions The risk of developing Leukaemia appears higher in individuals living near a petrochemical facility. This highlights the need for further policy to regulate the release of carcinogens by industry

Beyond the Votes: A European Perspective on the Use of Public Relations to Legitimize Authority in Obama’s Campaign

In political campaigns in Western society, there are many examples of public relations being behind opinion leaders in getting grassroots committed to a candidate; Obama’s campaign was one example. Grassroots communication has been a major public relations activity that has harnessed local community involvement (from nongovernmental organizations, social and cultural communities, companies, and individuals) in the United States as well as in Europe. Since the 2008 U.S. presidential campaign, third-party engagement is now considered a valid way to legitimize the authority of politicians all over the world. In this research, the authors point out that public opinion support, even outside the United States, can result in greater authority and greater acceptance of U.S. government policies