EXPRESS: Learning from Data: An Empirics-First Approach to Relevant Knowledge Generation

A “theory-first” paradigm tends to be the dominant approach in much academic marketing research. In this approach, a theory is borrowed, refined, or developed and then tested empirically. In this challenging-the-boundaries article, we make a case for an “empirics-first” approach. Empirics-first refers to research that (i) is grounded in (originates from) a real-world marketing phenomenon, problem, or observation, (ii) involves obtaining and analyzing data, and (iii) produces valid marketing-relevant insights without necessarily developing or testing theory. The empirics-first approach is not antagonistic to theory but rather can serve as a stepping-stone to theory. The approach lends itself well to today’s data-rich environment, which can surface novel research questions untethered to theory. The present paper describes the underlying principles of an empirics-first approach, which consists of exploring a domain purposefully without preconceptions. Using a rich set of published examples, the present paper offers guidance on how to implement empirics-first research and how it can lead to valuable knowledge development. Advice is also offered to authors on how to report EF research and to reviewers and to editorial teams on how to evaluate it. Our ultimate objective is to pave a way for empirics-first to enter the mainstream of academic marketing research

Assessment of Lymph Node Metastases by Contrast-Enhanced MR Imaging in a Head and Neck Cancer Model

OBJECTIVE: We wanted to investigate the accuracy of contrast-enhanced MR imaging for the detection of lymph node metastases in a head and neck cancer rabbit model. MATERIALS AND METHODS: The metastatic lymph node model we used was created by inoculating VX2 tumors into the auricles of six New Zealand White rabbits. T1-weighted MR images were obtained before and after injecting gadopentetate dimeglumine at three weeks after tumor cell inoculation. The sizes, signal intensity ratios (i.e., the postcontrast signal intensities of the affected nodes relative to the adjacent muscle) and the enhancement patterns of 36 regional lymph nodes (parotid and caudal mandibular nodes) were evaluated on MR images and then compared with the histopathologic findings. RESULTS: No statistical difference was found between the sizes of 12 metastatic (10.5+/-3.2 mm) and 24 hyperplastic (8.0+/-3.6 mm) lymph nodes (p > 0.05). On the contrast-enhanced T1-weighted MR images, nine metastatic and four hyperplastic lymph nodes had peripheral high and central low signal intensity, whereas three metastatic and 20 hyperplastic lymph nodes had homogeneous high signal intensity. Using a signal intensity ratio less than one as a diagnostic criterion for a metastatic lymph node, the sensitivity, specificity and positive and negative predictive values of the enhanced MR images were 75% (9/12), 83% (20/24), 69% (9/13) and 87% (20/23), respectively, with areas under receiver-operating-characteristic curve values of 0.81. CONCLUSION: This experimental study confirms that metastatic and hyperplastic lymph nodes can be differentiated using MR images on the basis of the contrast uptake patterns, but that they cannot be differentiated using any particular size criteria

Discursive Equality and Everyday Talk Online: The Impact of “Superparticipants”

Empirical studies of online debate almost universally observe a “dominant” minority of posters. Informed by theories of deliberative democracy, these are typically framed negatively—yet research into their impact on debate is scant. To address this, a typology of what we call super-participation (super-posters, agenda-setters and facilitators) is developed and applied to the http://www.moneysavingexpert.com/ forum. Focusing on the first of these, we found 2,052 superposters (0.4%) contributing 47% of 25m+ posts. While superposters were quantitatively dominant, qualitative content analysis of the discursive practices of 25 superposters (n=40,044) found that most did not attempt to stop other users from posting (curbing) or attack them (flaming). In fact, in contradiction to the received wisdom, super-posters discursively performed a range of positive roles

The determinants of election to the United Nations Security Council

This is the author's accepted manuscript. The final publication is available at Springer via http://dx.doi.org/10.1007/s11127-013-0096-4.The United Nations Security Council (UNSC) is the foremost international body responsible for the maintenance of international peace and security. Members vote on issues of global importance and consequently receive perks—election to the UNSC predicts, for instance, World Bank and IMF loans. But who gets elected to the UNSC? Addressing this question empirically is not straightforward as it requires a model that allows for discrete choices at the regional and international levels; the former nominates candidates while the latter ratifies them. Using an original multiple discrete choice model to analyze a dataset of 180 elections from 1970 to 2005, we find that UNSC election appears to derive from a compromise between the demands of populous countries to win election more frequently and a norm of giving each country its turn. We also find evidence that richer countries from the developing world win election more often, while involvement in warfare lowers election probability. By contrast, development aid does not predict election

Cerebral oximetry during cardiac arrest : a multicenter study of neurologic outcomes and survival

OBJECTIVES Cardiac arrest is associated with morbidity and mortality because of cerebral ischemia. Therefore, we tested the hypothesis that higher regional cerebral oxygenation during resuscitation is associated with improved return of spontaneous circulation, survival, and neurologic outcomes at hospital discharge. We further examined the validity of regional cerebral oxygenation as a test to predict these outcomes. DESIGN Multicenter prospective study of in-hospital cardiac arrest. SETTING Five medical centers in the United States and the United Kingdom. PATIENTS Inclusion criteria are as follows: in-hospital cardiac arrest, age 18 years old or older, and prolonged cardiopulmonary resuscitation greater than or equal to 5 minutes. Patients were recruited consecutively during working hours between August 2011 and September 2014. Survival with a favorable neurologic outcome was defined as a cerebral performance category 1-2. INTERVENTIONS Cerebral oximetry monitoring. MEASUREMENTS AND MAIN RESULTS Among 504 in-hospital cardiac arrest events, 183 (36%) met inclusion criteria. Overall, 62 of 183 (33.9%) achieved return of spontaneous circulation, whereas 13 of 183 (7.1%) achieved cerebral performance category 1-2 at discharge. Higher mean ± SD regional cerebral oxygenation was associated with return of spontaneous circulation versus no return of spontaneous circulation (51.8% ± 11.2% vs 40.9% ± 12.3%) and cerebral performance category 1-2 versus cerebral performance category 3-5 (56.1% ± 10.0% vs 43.8% ± 12.8%) (both p < 0.001). Mean regional cerebral oxygenation during the last 5 minutes of cardiopulmonary resuscitation best predicted the return of spontaneous circulation (area under the curve, 0.76; 95% CI, 0.69-0.83); regional cerebral oxygenation greater than or equal to 25% provided 100% sensitivity (95% CI, 94-100) and 100% negative predictive value (95% CI, 79-100); regional cerebral oxygenation greater than or equal to 65% provided 99% specificity (95% CI, 95-100) and 93% positive predictive value (95% CI, 66-100) for return of spontaneous circulation. Time with regional cerebral oxygenation greater than 50% during cardiopulmonary resuscitation best predicted cerebral performance category 1-2 (area under the curve, 0.79; 95% CI, 0.70-0.88). Specifically, greater than or equal to 60% cardiopulmonary resuscitation time with regional cerebral oxygenation greater than 50% provided 77% sensitivity (95% CI,:46-95), 72% specificity (95% CI, 65-79), and 98% negative predictive value (95% CI, 93-100) for cerebral performance category 1-2. CONCLUSIONS Cerebral oximetry allows real-time, noninvasive cerebral oxygenation monitoring during cardiopulmonary resuscitation. Higher cerebral oxygenation during cardiopulmonary resuscitation is associated with return of spontaneous circulation and neurologically favorable survival to hospital discharge. Achieving higher regional cerebral oxygenation during resuscitation may optimize the chances of cardiac arrest favorable outcomes

Adverse events in people taking macrolide antibiotics versus placebo for any indication

BACKGROUND: Macrolide antibiotics (macrolides) are among the most commonly prescribed antibiotics worldwide and are used for a wide range of infections. However, macrolides also expose people to the risk of adverse events. The current understanding of adverse events is mostly derived from observational studies, which are subject to bias because it is hard to distinguish events caused by antibiotics from events caused by the diseases being treated. Because adverse events are treatment-specific, rather than disease-specific, it is possible to increase the number of adverse events available for analysis by combining randomised controlled trials (RCTs) of the same treatment across different diseases. OBJECTIVES:To quantify the incidences of reported adverse events in people taking macrolide antibiotics compared to placebo for any indication. SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL), which includes the Cochrane Acute Respiratory Infections Group Specialised Register (2018, Issue 4); MEDLINE (Ovid, from 1946 to 8 May 2018); Embase (from 2010 to 8 May 2018); CINAHL (from 1981 to 8 May 2018); LILACS (from 1982 to 8 May 2018); and Web of Science (from 1955 to 8 May 2018). We searched clinical trial registries for current and completed trials (9 May 2018) and checked the reference lists of included studies and of previous Cochrane Reviews on macrolides. SELECTION CRITERIA: We included RCTs that compared a macrolide antibiotic to placebo for any indication. We included trials using any of the four most commonly used macrolide antibiotics: azithromycin, clarithromycin, erythromycin, or roxithromycin. Macrolides could be administered by any route. Concomitant medications were permitted provided they were equally available to both treatment and comparison groups. DATA COLLECTION AND ANALYSIS: Two review authors independently extracted and collected data. We assessed the risk of bias of all included studies and the quality of evidence for each outcome of interest. We analysed specific adverse events, deaths, and subsequent carriage of macrolide-resistant bacteria separately. The study participant was the unit of analysis for each adverse event. Any specific adverse events that occurred in 5% or more of any group were reported. We undertook a meta-analysis when three or more included studies reported a specific adverse event. MAIN RESULTS: We included 183 studies with a total of 252,886 participants (range 40 to 190,238). The indications for macrolide antibiotics varied greatly, with most studies using macrolides for the treatment or prevention of either acute respiratory tract infections, cardiovascular diseases, chronic respiratory diseases, gastrointestinal conditions, or urogynaecological problems. Most trials were conducted in secondary care settings. Azithromycin and erythromycin were more commonly studied than clarithromycin and roxithromycin.Most studies (89%) reported some adverse events or at least stated that no adverse events were observed.Gastrointestinal adverse events were the most commonly reported type of adverse event. Compared to placebo, macrolides caused more diarrhoea (odds ratio (OR) 1.70, 95% confidence interval (CI) 1.34 to 2.16; low-quality evidence); more abdominal pain (OR 1.66, 95% CI 1.22 to 2.26; low-quality evidence); and more nausea (OR 1.61, 95% CI 1.37 to 1.90; moderate-quality evidence). Vomiting (OR 1.27, 95% CI 1.04 to 1.56; moderate-quality evidence) and gastrointestinal disorders not otherwise specified (NOS) (OR 2.16, 95% CI 1.56 to 3.00; moderate-quality evidence) were also reported more often in participants taking macrolides compared to placebo.The number of additional people (absolute difference in risk) who experienced adverse events from macrolides was: gastrointestinal disorders NOS 85/1000; diarrhoea 72/1000; abdominal pain 62/1000; nausea 47/1000; and vomiting 23/1000.The number needed to treat for an additional harmful outcome (NNTH) ranged from 12 (95% CI 8 to 23) for gastrointestinal disorders NOS to 17 (9 to 47) for abdominal pain; 19 (12 to 33) for diarrhoea; 19 (13 to 30) for nausea; and 45 (22 to 295) for vomiting.There was no clear consistent difference in gastrointestinal adverse events between different types of macrolides or route of administration.Taste disturbances were reported more often by participants taking macrolide antibiotics, although there were wide confidence intervals and moderate heterogeneity (OR 4.95, 95% CI 1.64 to 14.93; Iand#178; = 46%; low-quality evidence).Compared with participants taking placebo, those taking macrolides experienced hearing loss more often, however only four studies reported this outcome (OR 1.30, 95% CI 1.00 to 1.70; Iand#178; = 0%; low-quality evidence).We did not find any evidence that macrolides caused more cardiac disorders (OR 0.87, 95% CI 0.54 to 1.40; very low-quality evidence); hepatobiliary disorders (OR 1.04, 95% CI 0.27 to 4.09; very low-quality evidence); or changes in liver enzymes (OR 1.56, 95% CI 0.73 to 3.37; very low-quality evidence) compared to placebo.We did not find any evidence that appetite loss, dizziness, headache, respiratory symptoms, blood infections, skin and soft tissue infections, itching, or rashes were reported more often by participants treated with macrolides compared to placebo.Macrolides caused less cough (OR 0.57, 95% CI 0.40 to 0.80; moderate-quality evidence) and fewer respiratory tract infections (OR 0.70, 95% CI 0.62 to 0.80; moderate-quality evidence) compared to placebo, probably because these are not adverse events, but rather characteristics of the indications for the antibiotics. Less fever (OR 0.73, 95% 0.54 to 1.00; moderate-quality evidence) was also reported by participants taking macrolides compared to placebo, although these findings were non-significant.There was no increase in mortality in participants taking macrolides compared with placebo (OR 0.96, 95% 0.87 to 1.06; Iand#178; = 11%; low-quality evidence).Only 24 studies (13%) provided useful data on macrolide-resistant bacteria. Macrolide-resistant bacteria were more commonly identified among participants immediately after exposure to the antibiotic. However, differences in resistance thereafter were inconsistent.Pharmaceutical companies supplied the trial medication or funding, or both, for 91 trials. AUTHORS' CONCLUSIONS: The macrolides as a group clearly increased rates of gastrointestinal adverse events. Most trials made at least some statement about adverse events, such as "none were observed". However, few trials clearly listed adverse events as outcomes, reported on the methods used for eliciting adverse events, or even detailed the numbers of people who experienced adverse events in both the intervention and placebo group. This was especially true for the adverse event of bacterial resistance.</p

Anomaly detection in elderly daily behavior in ambient sensing environments

Current ubiquitous computing applications for smart homes aim to enhance people’s daily living respecting age span. Among the target groups of people, elderly are a population eager for “choices for living arrangements”, which would allow them to continue living in their homes but at the same time provide the health care they need. Given the growing elderly population, there is a need for statistical models able to capture the recurring patterns of daily activity life and reason based on this information. We present an analysis of real-life sensor data collected from 40 different households of elderly people, using motion, door and pressure sensors. Our objective is to automatically observe and model the daily behavior of the elderly and detect anomalies that could occur in the sensor data. For this purpose, we first introduce an abstraction layer to create a common ground for home sensor configurations. Next, we build a probabilistic spatio-temporal model to summarize daily behavior. Anomalies are then defined as significant changes from the learned behavioral model and detected using a cross-entropy measure. We have compared the detected anomalies with manually collected annotations and the results show that the presented approach is able to detect significant behavioral changes of the elderly

Elective surgery cancellations due to the COVID-19 pandemic: global predictive modelling to inform surgical recovery plans.

BACKGROUND: The COVID-19 pandemic has disrupted routine hospital services globally. This study estimated the total number of adult elective operations that would be cancelled worldwide during the 12 weeks of peak disruption due to COVID-19. METHODS: A global expert response study was conducted to elicit projections for the proportion of elective surgery that would be cancelled or postponed during the 12 weeks of peak disruption. A Bayesian β-regression model was used to estimate 12-week cancellation rates for 190 countries. Elective surgical case-mix data, stratified by specialty and indication (surgery for cancer versus benign disease), were determined. This case mix was applied to country-level surgical volumes. The 12-week cancellation rates were then applied to these figures to calculate the total number of cancelled operations. RESULTS: The best estimate was that 28 404 603 operations would be cancelled or postponed during the peak 12 weeks of disruption due to COVID-19 (2 367 050 operations per week). Most would be operations for benign disease (90·2 per cent, 25 638 922 of 28 404 603). The overall 12-week cancellation rate would be 72·3 per cent. Globally, 81·7 per cent of operations for benign conditions (25 638 922 of 31 378 062), 37·7 per cent of cancer operations (2 324 070 of 6 162 311) and 25·4 per cent of elective caesarean sections (441 611 of 1 735 483) would be cancelled or postponed. If countries increased their normal surgical volume by 20 per cent after the pandemic, it would take a median of 45 weeks to clear the backlog of operations resulting from COVID-19 disruption. CONCLUSION: A very large number of operations will be cancelled or postponed owing to disruption caused by COVID-19. Governments should mitigate against this major burden on patients by developing recovery plans and implementing strategies to restore surgical activity safely

A simplified (modified) Duke Activity Status Index (M-DASI) to characterise functional capacity: A secondary analysis of the Measurement of Exercise Tolerance before Surgery (METS) study

Background Accurate assessment of functional capacity, a predictor of postoperative morbidity and mortality, is essential to improving surgical planning and outcomes. We assessed if all 12 items of the Duke Activity Status Index (DASI) were equally important in reflecting exercise capacity. Methods In this secondary cross-sectional analysis of the international, multicentre Measurement of Exercise Tolerance before Surgery (METS) study, we assessed cardiopulmonary exercise testing and DASI data from 1455 participants. Multivariable regression analyses were used to revise the DASI model in predicting an anaerobic threshold (AT) >11 ml kg −1 min −1 and peak oxygen consumption (VO 2 peak) >16 ml kg −1 min −1, cut-points that represent a reduced risk of postoperative complications. Results Five questions were identified to have dominance in predicting AT>11 ml kg −1 min −1 and VO 2 peak>16 ml.kg −1min −1. These items were included in the M-DASI-5Q and retained utility in predicting AT>11 ml.kg −1.min −1 (area under the receiver-operating-characteristic [AUROC]-AT: M-DASI-5Q=0.67 vs original 12-question DASI=0.66) and VO 2 peak (AUROC-VO2 peak: M-DASI-5Q 0.73 vs original 12-question DASI 0.71). Conversely, in a sensitivity analysis we removed one potentially sensitive question related to the ability to have sexual relations, and the ability of the remaining four questions (M-DASI-4Q) to predict an adequate functional threshold remained no worse than the original 12-question DASI model. Adding a dynamic component to the M-DASI-4Q by assessing the chronotropic response to exercise improved its ability to discriminate between those with VO 2 peak>16 ml.kg −1.min −1 and VO 2 peak<16 ml.kg −1.min −1. Conclusions The M-DASI provides a simple screening tool for further preoperative evaluation, including with cardiopulmonary exercise testing, to guide perioperative management

Adalimumab, etanercept, infliximab, certolizumab pegol, golimumab, tocilizumab and abatacept for the treatment of rheumatoid arthritis not previously treated with disease-modifying antirheumatic drugs and after the failure of conventional disease-modifying antirheumatic drugs only: systematic review and economic evaluation.

OBJECTIVES: Rheumatoid arthritis (RA) is a chronic inflammatory disease associated with increasing disability, reduced quality of life and substantial costs (as a result of both intervention acquisition and hospitalisation). The objective was to assess the clinical effectiveness and cost-effectiveness of seven biologic disease-modifying antirheumatic drugs (bDMARDs) compared with each other and conventional disease-modifying antirheumatic drugs (cDMARDs). The decision problem was divided into those patients who were cDMARD naive and those who were cDMARD experienced; whether a patient had severe or moderate to severe disease; and whether or not an individual could tolerate methotrexate (MTX). DATA SOURCES: The following databases were searched: MEDLINE from 1948 to July 2013; EMBASE from 1980 to July 2013; Cochrane Database of Systematic Reviews from 1996 to May 2013; Cochrane Central Register of Controlled Trials from 1898 to May 2013; Health Technology Assessment Database from 1995 to May 2013; Database of Abstracts of Reviews of Effects from 1995 to May 2013; Cumulative Index to Nursing and Allied Health Literature from 1982 to April 2013; and TOXLINE from 1840 to July 2013. Studies were eligible for inclusion if they evaluated the impact of a bDMARD used within licensed indications on an outcome of interest compared against an appropriate comparator in one of the stated population subgroups within a randomised controlled trial (RCT). Outcomes of interest included American College of Rheumatology (ACR) scores and European League Against Rheumatism (EULAR) response. Interrogation of Early Rheumatoid Arthritis Study (ERAS) data was undertaken to assess the Health Assessment Questionnaire (HAQ) progression while on cDMARDs. METHODS: Network meta-analyses (NMAs) were undertaken for patients who were cDMARD naive and for those who were cDMARD experienced. These were undertaken separately for EULAR and ACR data. Sensitivity analyses were undertaken to explore the impact of including RCTs with a small proportion of bDMARD experienced patients and where MTX exposure was deemed insufficient. A mathematical model was constructed to simulate the experiences of hypothetical patients. The model was based on EULAR response as this is commonly used in clinical practice in England. Observational databases, published literature and NMA results were used to populate the model. The outcome measure was cost per quality-adjusted life-year (QALY) gained. RESULTS: Sixty RCTs met the review inclusion criteria for clinical effectiveness, 38 of these trials provided ACR and/or EULAR response data for the NMA. Fourteen additional trials contributed data to sensitivity analyses. There was uncertainty in the relative effectiveness of the interventions. It was not clear whether or not formal ranking of interventions would result in clinically meaningful differences. Results from the analysis of ERAS data indicated that historical assumptions regarding HAQ progression had been pessimistic. The typical incremental cost per QALY of bDMARDs compared with cDMARDs alone for those with severe RA is > £40,000. This increases for those who cannot tolerate MTX (£50,000) and is > £60,000 per QALY when bDMARDs were used prior to cDMARDs. Values for individuals with moderate to severe RA were higher than those with severe RA. Results produced using EULAR and ACR data were similar. The key parameter that affected the results is the assumed HAQ progression while on cDMARDs. When historic assumptions were used typical incremental cost per QALY values fell to £38,000 for those with severe disease who could tolerate MTX. CONCLUSIONS: bDMARDs appear to have cost per QALY values greater than the thresholds stated by the National Institute for Health and Care Excellence for interventions to be cost-effective. Future research priorities include: the evaluation of the long-term HAQ trajectory while on cDMARDs; the relationship between HAQ direct medical costs; and whether or not bDMARDs could be stopped once a patient has achieved a stated target (e.g. remission). STUDY REGISTRATION: This study is registered as PROSPERO CRD42012003386. FUNDING: The National Institute for Health Research Health Technology Assessment programme