Estimating the Causal Effects of Marketing Interventions Using Propensity Score Methodology

Propensity score methods were proposed by Rosenbaum and Rubin [Biometrika 70 (1983) 41--55] as central tools to help assess the causal effects of interventions. Since their introduction more than two decades ago, they have found wide application in a variety of areas, including medical research, economics, epidemiology and education, especially in those situations where randomized experiments are either difficult to perform, or raise ethical questions, or would require extensive delays before answers could be obtained. In the past few years, the number of published applications using propensity score methods to evaluate medical and epidemiological interventions has increased dramatically. Nevertheless, thus far, we believe that there have been few applications of propensity score methods to evaluate marketing interventions (e.g., advertising, promotions), where the tradition is to use generally inappropriate techniques, which focus on the prediction of an outcome from background characteristics and an indicator for the intervention using statistical tools such as least-squares regression, data mining, and so on. With these techniques, an estimated parameter in the model is used to estimate some global ``causal'' effect. This practice can generate grossly incorrect answers that can be self-perpetuating: polishing the Ferraris rather than the Jeeps ``causes'' them to continue to win more races than the Jeeps $\Leftrightarrow$ visiting the high-prescribing doctors rather than the low-prescribing doctors ``causes'' them to continue to write more prescriptions. This presentation will take ``causality'' seriously, not just as a casual concept implying some predictive association in a data set, and will illustrate why propensity score methods are generally superior in practice to the standard predictive approaches for estimating causal effects.Comment: Published at http://dx.doi.org/10.1214/088342306000000259 in the Statistical Science (http://www.imstat.org/sts/) by the Institute of Mathematical Statistics (http://www.imstat.org

Predictive value of Altmetric score on citation rates and bibliometric impact

Background Bibliometric and Altmetric analyses provide different perspectives regarding research impact. This study aimed to determine whether Altmetric score was associated with citation rate independent of established bibliometrics. Methods Citations related to a previous cohort of 100 most cited articles in surgery were collected and a 3-year interval citation gain calculated. Citation count, citation rate index, Altmetric score, 5-year impact factor, and Oxford Centre for Evidence-Based Medicine levels were used to estimate citation rate prospect. Results The median interval citation gain was 161 (i.q.r. 83–281); 74 and 62 articles had an increase in citation rate index (median increase 2.8 (i.q.r. –0.1 to 7.7)) and Altmetric score (median increase 3 (0–4)) respectively. Receiver operating characteristic (ROC) curve analysis revealed that citation rate index (area under the curve (AUC) 0.86, 95 per cent c.i. 0.79 to 0.93; P < 0.001) and Altmetric score (AUC 0.65, 0.55 to 0.76; P = 0.008) were associated with higher interval citation gain. An Altmetric score critical threshold of 2 or more was associated with a better interval citation gain when dichotomized at the interval citation gain median (odds ratio (OR) 4.94, 95 per cent c.i. 1.99 to 12.26; P = 0.001) or upper quartile (OR 4.13, 1.60 to 10.66; P = 0.003). Multivariable analysis revealed only citation rate index to be independently associated with interval citation gain when dichotomized at the median (OR 18.22, 6.70 to 49.55; P < 0.001) or upper quartile (OR 19.30, 4.23 to 88.15; P < 0.001). Conclusion Citation rate index and Altmetric score appear to be important predictors of interval citation gain, and better at predicting future citations than the historical and established impact factor and Oxford Centre for Evidence-Based Medicine quality descriptors

Extended haplotype association study in Crohn’s disease identifies a novel, Ashkenazi Jewish-specific missense mutation in the NF-κB pathway gene, HEATR3

The Ashkenazi Jewish population has a several-fold higher prevalence of Crohn’s disease compared to non-Jewish European ancestry populations and has a unique genetic history. Haplotype association is critical to Crohn’s disease etiology in this population, most notably at NOD2, in which three causal, uncommon, and conditionally independent NOD2 variants reside on a shared background haplotype. We present an analysis of extended haplotypes which showed significantly greater association to Crohn’s disease in the Ashkenazi Jewish population compared to a non-Jewish population (145 haplotypes and no haplotypes with P-value < 10−3, respectively). Two haplotype regions, one each on chromosomes 16 and 21, conferred increased disease risk within established Crohn’s disease loci. We performed exome sequencing of 55 Ashkenazi Jewish individuals and follow-up genotyping focused on variants in these two regions. We observed Ashkenazi Jewish-specific nominal association at R755C in TRPM2 on chromosome 21. Within the chromosome 16 region, R642S of HEATR3 and rs9922362 of BRD7 showed genome-wide significance. Expression studies of HEATR3 demonstrated a positive role in NOD2-mediated NF-κB signaling. The BRD7 signal showed conditional dependence with only the downstream rare Crohn’s disease-causal variants in NOD2, but not with the background haplotype; this elaborates NOD2 as a key illustration of synthetic association

FENETRE study: quality-assured follow-up of quiescent neovascular age-related macular degeneration by non-medical practitioners: study protocol and statistical analysis plan for a randomised controlled trial.

OBJECTIVE: Management of age-related macular degeneration (AMD) places a high demand on already constrained hospital-based eye services. This study aims to assess the safety and quality of follow-up within the community led by suitably trained non-medical practitioners for the management of quiescent neovascular AMD (QnAMD). METHODS/DESIGN: This is a prospective, multisite, randomised clinical trial. 742 participants with QnAMD will be recruited and randomised to either continue hospital-based secondary care or to receive follow-up within a community setting. Participants in both groups will be monitored for disease reactivation over the course of 12 months and referred for treatment as necessary. Outcomes measures will assess the non-inferiority of primary care follow-up accounting for accuracy of the identification of disease reactivation, patient loss to follow-up and accrued costs and the budget impact to the National Health Service. ETHICS AND DISSEMINATION: Research ethics approval was obtained from the London Bloomsbury Ethics Committee. The results of this study will be disseminated through academic peer-reviewed publications, conferences and collaborations with eye charities to insure the findings reach the appropriate patient populations. TRIAL REGISTRATION NUMBER: NCT03893474

Diversity Strategies for Nuclear Power Plant Instrumentation and Control Systems

This report presents the technical basis for establishing acceptable mitigating strategies that resolve diversity and defense-in-depth (D3) assessment findings and conform to U.S. Nuclear Regulatory Commission (NRC) requirements. The research approach employed to establish appropriate diversity strategies involves investigation of available documentation on D3 methods and experience from nuclear power and nonnuclear industries, capture of expert knowledge and lessons learned, determination of best practices, and assessment of the nature of common-cause failures (CCFs) and compensating diversity attributes. The research described in this report does not provide guidance on how to determine the need for diversity in a safety system to mitigate the consequences of potential CCFs. Rather, the scope of this report provides guidance to the staff and nuclear industry after a licensee or applicant has performed a D3 assessment per NUREG/CR-6303 and determined that diversity in a safety system is needed for mitigating the consequences of potential CCFs identified in the evaluation of the safety system design features. Succinctly, the purpose of the research described in this report was to answer the question, 'If diversity is required in a safety system to mitigate the consequences of potential CCFs, how much diversity is enough?' The principal results of this research effort have identified and developed diversity strategies, which consist of combinations of diversity attributes and their associated criteria. Technology, which corresponds to design diversity, is chosen as the principal system characteristic by which diversity criteria are grouped to form strategies. The rationale for this classification framework involves consideration of the profound impact that technology-focused design diversity provides. Consequently, the diversity usage classification scheme involves three families of strategies: (1) different technologies, (2) different approaches within the same technology, and (3) different architectures within the same technology. Using this convention, the first diversity usage family, designated Strategy A, is characterized by fundamentally diverse technologies. Strategy A at the system or platform level is illustrated by the example of analog and digital implementations. The second diversity usage family, designated Strategy B, is achieved through the use of distinctly different technologies. Strategy B can be described in terms of different digital technologies, such as the distinct approaches represented by general-purpose microprocessors and field-programmable gate arrays. The third diversity usage family, designated Strategy C, involves the use of variations within a technology. An example of Strategy C involves different digital architectures within the same technology, such as that provided by different microprocessors (e.g., Pentium and Power PC). The grouping of diversity criteria combinations according to Strategies A, B, and C establishes baseline diversity usage and facilitates a systematic organization of strategic approaches for coping with CCF vulnerabilities. Effectively, these baseline sets of diversity criteria constitute appropriate CCF mitigating strategies for digital safety systems. The strategies represent guidance on acceptable diversity usage and can be applied directly to ensure that CCF vulnerabilities identified through a D3 assessment have been adequately resolved. Additionally, a framework has been generated for capturing practices regarding diversity usage and a tool has been developed for the systematic assessment of the comparative effect of proposed diversity strategies (see Appendix A)

Improving adherence to glaucoma medication: a randomised controlled trial of a patient-centred intervention (The Norwich Adherence Glaucoma Study)

Background Improving adherence to ocular hypertension (OH)/glaucoma therapy is highly likely to prevent or reduce progression of optic nerve damage. The present study used a behaviour change counselling intervention to determine whether education and support was beneficial and cost-effective in improving adherence with glaucoma therapy. Methods A randomised controlled trial with a 13-month recruitment and 8-month follow-up period was conducted. Patients with OH/glaucoma attending a glaucoma clinic and starting treatment with travoprost were approached. Participants were randomised into two groups and adherence was measured over 8 months, using an electronic monitoring device (Travalert® dosing aid, TDA). The control group received standard clinical care, and the intervention group received a novel glaucoma education and motivational support package using behaviour change counselling. Cost-effectiveness framework analysis was used to estimate any potential cost benefit of improving adherence. Results Two hundred and eight patients were recruited (102 intervention, 106 control). No significant difference in mean adherence over the monitoring period was identified with 77.2% (CI, 73.0, 81.4) for the control group and 74.8% (CI, 69.7, 79.9) for the intervention group (p = 0.47). Similarly, there was no significant difference in percentage intraocular pressure reduction; 27.6% (CI, 23.5, 31.7) for the control group and 25.3% (CI, 21.06, 29.54) for the intervention group (p = 0.45). Participants in the intervention group were more satisfied with information about glaucoma medication with a mean score of 14.47/17 (CI, 13.85, 15.0) compared with control group which was 8.51 (CI, 7.72, 9.30). The mean intervention cost per patient was GB£10.35 (<US$16) and not cost-effective. Conclusions Adherence with travoprost was high and not further increased by the intervention. Nevertheless, the study demonstrated that provision of information, tailored to the individual, was inexpensive and able to achieve high patient satisfaction with respect to information about glaucoma medication. Measurement of adherence remains problematic since awareness of study participation may cause a change in participant behaviour

Is short-term-variation of fetal-heart-rate a better predictor of fetal acidaemia in labour? A feasibility study

Background Continuous intrapartum fetal monitoring is challenging and its clinical benefits are debated. The project evaluated whether short-term-variation (STV) and other computerised fetal heart rate (FHR) parameters (baseline FHR, long-term-variation, accelerations and decelerations) predicted acidaemia at birth. The aims of the study were to assess the changes in FHR pattern during labour and determine the feasibility of undertaking a definitive trial by reporting the practicalities of using the monitoring device, participant recruitment, data collection and staff training. Methods 200 high-risk women carrying a term singleton, non-anomalous fetus, requiring continuous FHR monitoring in labour were consented to participate from the Jessop Wing maternity unit, Sheffield, UK. The trans-abdominal fetal ECG monitor was placed as per clinical protocol. During the monitoring session, clinicians were blinded to the computerised FHR parameters. We analysed the last hour of the FHR and its ability to predict umbilical arterial blood pH <7.20 using receiver operator characteristics (ROC) curves. Results Of 200 women, 137 cases were excluded as either the monitor did not work from the onset of labour (n = 30), clinical staff did not return or used the monitor on another patient (n = 37), umbilical cord blood not obtained (n = 25), FHR data not recorded within an hour of birth (n = 34) and other reasons (n = 11). In 63 cases included in the final analysis, the computer-derived FHR parameters did not show significant correlation with umbilical artery cord pH <7.20. Labour was associated with a significant increase in short and long term variation of FHR and number of deceleration (P<0.001). However, baseline FHR decreased significantly before delivery (P<0.001). Conclusions The project encountered a number of challenges, with learning points crucial to informing the design of a large study to evaluate the potential place of intrapartum computerised FHR parameters, using abdominal fetal ECG monitor before its clinical utility and more widespread adoption can be ascertained

Antimicrobial resistance among migrants in Europe: a systematic review and meta-analysis

BACKGROUND: Rates of antimicrobial resistance (AMR) are rising globally and there is concern that increased migration is contributing to the burden of antibiotic resistance in Europe. However, the effect of migration on the burden of AMR in Europe has not yet been comprehensively examined. Therefore, we did a systematic review and meta-analysis to identify and synthesise data for AMR carriage or infection in migrants to Europe to examine differences in patterns of AMR across migrant groups and in different settings. METHODS: For this systematic review and meta-analysis, we searched MEDLINE, Embase, PubMed, and Scopus with no language restrictions from Jan 1, 2000, to Jan 18, 2017, for primary data from observational studies reporting antibacterial resistance in common bacterial pathogens among migrants to 21 European Union-15 and European Economic Area countries. To be eligible for inclusion, studies had to report data on carriage or infection with laboratory-confirmed antibiotic-resistant organisms in migrant populations. We extracted data from eligible studies and assessed quality using piloted, standardised forms. We did not examine drug resistance in tuberculosis and excluded articles solely reporting on this parameter. We also excluded articles in which migrant status was determined by ethnicity, country of birth of participants' parents, or was not defined, and articles in which data were not disaggregated by migrant status. Outcomes were carriage of or infection with antibiotic-resistant organisms. We used random-effects models to calculate the pooled prevalence of each outcome. The study protocol is registered with PROSPERO, number CRD42016043681. FINDINGS: We identified 2274 articles, of which 23 observational studies reporting on antibiotic resistance in 2319 migrants were included. The pooled prevalence of any AMR carriage or AMR infection in migrants was 25·4% (95% CI 19·1-31·8; I2 =98%), including meticillin-resistant Staphylococcus aureus (7·8%, 4·8-10·7; I2 =92%) and antibiotic-resistant Gram-negative bacteria (27·2%, 17·6-36·8; I2 =94%). The pooled prevalence of any AMR carriage or infection was higher in refugees and asylum seekers (33·0%, 18·3-47·6; I2 =98%) than in other migrant groups (6·6%, 1·8-11·3; I2 =92%). The pooled prevalence of antibiotic-resistant organisms was slightly higher in high-migrant community settings (33·1%, 11·1-55·1; I2 =96%) than in migrants in hospitals (24·3%, 16·1-32·6; I2 =98%). We did not find evidence of high rates of transmission of AMR from migrant to host populations. INTERPRETATION: Migrants are exposed to conditions favouring the emergence of drug resistance during transit and in host countries in Europe. Increased antibiotic resistance among refugees and asylum seekers and in high-migrant community settings (such as refugee camps and detention facilities) highlights the need for improved living conditions, access to health care, and initiatives to facilitate detection of and appropriate high-quality treatment for antibiotic-resistant infections during transit and in host countries. Protocols for the prevention and control of infection and for antibiotic surveillance need to be integrated in all aspects of health care, which should be accessible for all migrant groups, and should target determinants of AMR before, during, and after migration. FUNDING: UK National Institute for Health Research Imperial Biomedical Research Centre, Imperial College Healthcare Charity, the Wellcome Trust, and UK National Institute for Health Research Health Protection Research Unit in Healthcare-associated Infections and Antimictobial Resistance at Imperial College London

Globalisation from Above? Corporate Social Responsibility, the Workers' Party and the Origins of the World Social Forum

In its assessment of the origins and early development of the World Social Forum this article challenges traditional understandings of the Forum as representing ‘globalisation from below’. By tracing the intricate relations among elements of business, civil society, and the Workers’ Party in the first years of the Forum, this article reveals the major role played by a corporate movement stemming from the Brazilian democratisation process in the 1980s, and how this combined with the transformed agenda of the Workers’ Party as it gained higher political offices to constrain the Forum’s activities from the outset. In so doing, this article challenges not only widespread conceptions of the Forum as a counter‐hegemonic alternative but also current critiques concerning its subsequent limitations. Furthermore, it reveals how traditional understandings of the World Social Forum and of global civil society are underpinned by flawed assumptions which typecast political activities in the global ‘South’

Effects of Reproductive Status, Social Rank, Sex and Group Size on Vigilance Patterns in Przewalski's Gazelle

Quantifying vigilance and exploring the underlying mechanisms has been the subject of numerous studies. Less attention has focused on the complex interplay between contributing factors such as reproductive status, social rank, sex and group size. Reproductive status and social rank are of particular interest due to their association with mating behavior. Mating activities in rutting season may interfere with typical patterns of vigilance and possibly interact with social rank. In addition, balancing the tradeoff between vigilance and life maintenance may represent a challenge for gregarious ungulate species rutting under harsh winter conditions. We studied vigilance patterns in the endangered Przewalski's gazelle (Procapra przewalskii) during both the rutting and non-rutting seasons to examine these issues.Field observations were carried out with focal sampling during rutting and non-rutting season in 2008-2009. Results indicated a complex interplay between reproductive status, social rank, sex and group size in determining vigilance in this species. Vigilance decreased with group size in female but not in male gazelles. Males scanned more frequently and thus spent more time vigilant than females. Compared to non-rutting season, gazelles increased time spent scanning at the expense of bedding in rutting season. During the rutting season, territorial males spent a large proportion of time on rutting activities and were less vigilant than non-territorial males. Although territorial males may share collective risk detection with harem females, we suggest that they are probably more vulnerable to predation because they seemed reluctant to leave rut stands under threats.Vigilance behavior in Przewalski's gazelle was significantly affected by reproductive status, social rank, sex, group size and their complex interactions. These findings shed light on the mechanisms underlying vigilance patterns and the tradeoff between vigilance and other crucial activities