The use of artificial intelligence, and the deep-learning subtype in particular, has been enabled by the use of labeled big data, along with markedly enhanced computing power and cloud storage, across all sectors. In medicine, this is beginning to have an impact at three levels: for clinicians, predominantly via rapid, accurate image interpretation; for health systems, by improving workflow and the potential for reducing medical errors; and for patients, by enabling them to process their own data to promote health. The current limitations, including bias, privacy and security, and lack of transparency, along with the future directions of these applications will be discussed in this article. Over time, marked improvements in accuracy, productivity, and workflow will likely be actualized, but whether that will be used to improve the patient-doctor relationship or facilitate its erosion remains to be seen.

High-performance medicine: the convergence of human and artificial intelligence

Introduction to stochastic programming

Artificial intelligence (AI) is gradually changing medical practice. With recent progress in digitized data acquisition, machine learning and computing infrastructure, AI applications are expanding into areas that were previously thought to be only the province of human experts. In this Review Article, we outline recent breakthroughs in AI technologies and their biomedical applications, identify the challenges for further progress in medical AI systems, and summarize the economic, legal and social implications of AI in healthcare.

Artificial Intelligence in Healthcare

Medical Image Computing and Computer-Assisted Intervention

The paper proposes Metropolis adjusted Langevin and Hamiltonian Monte Carlo sampling methods defined on the Riemann manifold to resolve the shortcomings of existing Monte Carlo algorithms when sampling from target densities that may be high dimensional and exhibit strong correlations. The methods provide fully automated adaptation mechanisms that circumvent the costly pilot runs that are required to tune proposal densities for Metropolis-Hastings or indeed Hamiltonian Monte Carlo and Metropolis adjusted Langevin algorithms. This allows for highly efficient sampling even in very high dimensions where different scalings may be required for the transient and stationary phases of the Markov chain. The methodology proposed exploits the Riemann geometry of the parameter space of statistical models and thus automatically adapts to the local structure when simulating paths across this manifold, providing highly efficient convergence and exploration of the target density. The performance of these Riemann manifold Monte Carlo methods is rigorously assessed by performing inference on logistic regression models, log-Gaussian Cox point processes, stochastic volatility models and Bayesian estimation of dynamic systems described by non-linear differential equations. Substantial improvements in the time-normalized effective sample size are reported when compared with alternative sampling approaches. MATLAB code that is available from http://www.ucl.ac.uk/statistics/research/rmhmc allows replication of all the results reported.

Riemann manifold Langevin and Hamiltonian Monte Carlo methods

Nearly all aspects of modern life are in some way being changed by big data and machine learning. Netflix knows what movies people like to watch and Google knows what people want to know based on their search histories. Indeed, Google has recently begun to replace much of its existing non–machine learning technology with machine learning algorithms, and there is great optimism that these techniques can provide similar improvements across many sectors. It isnosurprisethenthatmedicineisawashwithclaims of revolution from the application of machine learning to big health care data. Recent examples have demonstrated that big data and machine learning can create algorithms that perform on par with human physicians.1 Though machine learning and big data may seem mysterious at first, they are in fact deeply related to traditional statistical models that are recognizable to most clinicians. It is our hope that elucidating these connections will demystify these techniques and provide a set of reasonable expectations for the role of machine learning and big data in health care. Machine learning was originally described as a program that learns to perform a task or make a decision automatically from data, rather than having the behavior explicitlyprogrammed.However,thisdefinitionisverybroad and could cover nearly any form of data-driven approach. For instance, consider the Framingham cardiovascular risk score,whichassignspointstovariousfactorsandproduces a number that predicts 10-year cardiovascular risk. Should this be considered an example of machine learning? The answer might obviously seem to be no. Closer inspection oftheFraminghamriskscorerevealsthattheanswermight not be as obvious as it first seems. The score was originally created2 by fitting a proportional hazards model to data frommorethan5300patients,andsothe“rule”wasinfact learnedentirelyfromdata.Designatingariskscoreasamachine learning algorithm might seem a strange notion, but this example reveals the uncertain nature of the original definition of machine learning. It is perhaps more useful to imagine an algorithm as existing along a continuum between fully human-guided vs fully machine-guided data analysis. To understand the degree to which a predictive or diagnostic algorithm can said to be an instance of machine learning requires understanding how much of its structure or parameters were predetermined by humans. The trade-off between human specificationofapredictivealgorithm’spropertiesvslearning those properties from data is what is known as the machine learning spectrum. Returning to the Framingham study, to create the original risk score statisticians and clinical experts worked together to make many important decisions, such as which variables to include in the model, therelationshipbetweenthedependentandindependent variables, and variable transformations and interactions. Since considerable human effort was used to define these properties, it would place low on the machine learning spectrum (#19 in the Figure and Supplement). Many evidence-based clinical practices are based on a statistical model of this sort, and so many clinical decisions in fact exist on the machine learning spectrum (middle left of Figure). On the extreme low end of the machine learning spectrum would be heuristics and rules of thumb that do not directly involve the use of any rules or models explicitly derived from data (bottom left of Figure). Suppose a new cardiovascular risk score is created that includes possible extensions to the original model. For example, it could be that risk factors should not be added but instead should be multiplied or divided, or perhaps a particularly important risk factor should square the entire score if it is present. Moreover, if it is not known in advance which variables will be important, but thousands of individual measurements have been collected, how should a good model be identified from among the infinite possibilities? This is precisely what a machine learning algorithm attempts to do. As humans impose fewer assumptions on the algorithm, it moves further up the machine learning spectrum. However, there is never a specific threshold wherein a model suddenly becomes “machine learning”; rather, all of these approaches exist along a continuum, determined by how many human assumptions are placed onto the algorithm. An example of an approach high on the machine learning spectrum has recently emerged in the form of so-called deep learning models. Deep learning models are stunningly complex networks of artificial neurons that were designed expressly to create accurate models directly from raw data. Researchers recently demonstrated a deep learning algorithm capable of detecting diabetic retinopathy (#4 in the Figure, top center) from retinal photographs at a sensitivity equal to or greater than that of ophthalmologists.1 This model learned the diagnosis procedure directly from the raw pixels of the images with no human intervention outside of a team of ophthalmologists who annotated each image with the correct diagnosis. Because they are able to learn the task with little human instruction or prior assumptions, these deep learning algorithms rank very high on the machine learning spectrum (Figure, light blue circles). Though they require less human guidance, deep learning algorithms for image recognition require enormous amounts of data to capture the full complexity, variety, and nuance inherent to real-world images. Consequently, these algorithms often require hundreds of thousands of examples to extract the salient image features that are correlated with the outcome of interest. Higher placement on the machine learning spectrum does not imply superiority, because different tasks require different levels of human involvement. While algorithms high on the spectrum are often very flexible and can learn many tasks, they are often uninterpretable VIEWPOINT

https://jamanetwork.com/journals/JAMA/articlepdf/2675024/jvp170174supp1_prod.pdf

Big Data and Machine Learning in Health Care.

Emerging vulnerabilities demand new conversations With public and academic attention increasingly focused on the new role of machine learning in the health information economy, an unusual and no-longer-esoteric category of vulnerabilities in machine-learning systems could prove important. These vulnerabilities allow a small, carefully designed change in how inputs are presented to a system to completely alter its output, causing it to confidently arrive at manifestly wrong conclusions. These advanced techniques to subvert otherwise-reliable machine-learning systems—so-called adversarial attacks—have, to date, been of interest primarily to computer science researchers (1). However, the landscape of often-competing interests within health care, and billions of dollars at stake in systems' outputs, implies considerable problems. We outline motivations that various players in the health care system may have to use adversarial attacks and begin a discussion of what to do about them. Far from discouraging continued innovation with medical machine learning, we call for active engagement of medical, technical, legal, and ethical experts in pursuit of efficient, broadly available, and effective health care that machine learning will enable.

https://science.sciencemag.org/content/sci/363/6433/1287.full.pdf

Adversarial attacks on medical machine learning

Objective To quantify the effects of varying opioid prescribing patterns after surgery on dependence, overdose, or abuse in an opioid naive population. Design Retrospective cohort study. Setting Surgical claims from a linked medical and pharmacy administrative database of 37 651 619 commercially insured patients between 2008 and 2016. Participants 1 015 116 opioid naive patients undergoing surgery. Main outcome measures Use of oral opioids after discharge as defined by refills and total dosage and duration of use. The primary outcome was a composite of misuse identified by a diagnostic code for opioid dependence, abuse, or overdose. Results 568 612 (56.0%) patients received postoperative opioids, and a code for abuse was identified for 5906 patients (0.6%, 183 per 100 000 person years). Total duration of opioid use was the strongest predictor of misuse, with each refill and additional week of opioid use associated with an adjusted increase in the rate of misuse of 44.0% (95% confidence interval 40.8% to 47.2%, P Conclusions Each refill and week of opioid prescription is associated with a large increase in opioid misuse among opioid naive patients. The data from this study suggest that duration of the prescription rather than dosage is more strongly associated with ultimate misuse in the early postsurgical period. The analysis quantifies the association of prescribing choices on opioid misuse and identifies levers for possible impact.

https://www.bmj.com/content/bmj/360/bmj.j5790.full.pdf

Andrew L. Beam

Papers

Artificial Intelligence in Healthcare

Big Data and Machine Learning in Health Care.

Adversarial attacks on medical machine learning

Postsurgical prescriptions for opioid naive patients and association with overdose and misuse: retrospective cohort study.

Zebrafish developmental screening of the ToxCast™ Phase I chemical library.