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Microneedle (MN) based electrochemical (bio)sensing has become a growing field within the discipline of analytical chemistry as a result of its unique capacity for continuous, decentralized health status monitoring. There are two significant advantages to this exclusive feature: i) the ability to directly analyze interstitial fluid (ISF), a body fluid with a similar enough composition to plasma (and blood) to be considered a plentiful source of information related to biologically relevant molecules and biomarkers; and ii) the capacity to overcome some of the major limitations of blood analysis including painful extraction, high interferant concentrations, and incompatibility with diagnosis of infants (and especially newborns). Recent publications have demonstrated important advancements in electrochemical MN sensor technology, among which are included new MN fabrication methods and various modification strategies, providing different architectures and allowing for the integration of electronics. This versatility highlights the undeniable need for interdisciplinary efforts towards tangible progress in the field. In a context evidently dominated by glucose sensing, which is slowly being expanded towards other analytes, the following crucial questions arise: to what extent are electrochemical MN (bio)sensors a reliable analytical tool for continuous ISF monitoring? Which is the best calibration protocol to be followed for in vivo assays? Which strategies can be employed to protect the sensing element during skin penetration? Is there an appropriate validation methodology to assess the accuracy of electrochemical MN (bio)sensors? How significant is the distinction between successful achievements in the laboratory and the real commercial feasibility of products? This paper aims to reflect on those previous questions while reviewing the progress of electrochemical MN (bio)sensors in the last decade with a focus on the analytical aspects. Overall, we describe the current state of electrochemical MN (bio)sensors, the benefits and challenges associated to ISF monitoring, as well as key features (and bottlenecks) regarding its implementation for in vivo assays.

As health care spending continues to strain government and household budgets, there is increasing interest in measuring whether the incremental dollar spent on health care is worth it. In studying this question, researchers often make two key assumptions: that health care intensity can be summarized by a single index such as average spending, and that samples of hospitals or regions are spatially independent: Manhattan and the Bronx are no more alike than are Manhattan and San Diego, for example. In this paper we relax both assumptions. Using detailed data on 897,008 elderly Medicare enrolees with acute myocardial infarction (or a heart attack) during 2007–11, we find first that the total level of health care spending has little impact on health outcomes; more important is how the money is spent. Same-day stenting, a treatment with proven effectiveness, positively predicts survival, while home health care spending does not. Second, there is strong evidence of spatial autocorrelation; without corrections this can lead to inefficient estimates and standard errors that are biased downward. Spatial autocorrelation in outcomes appears to be the consequence both of unmeasured health status and spatial correlation in new and effective technology.