DeepCare: A Deep Dynamic Memory Model for Predictive Medicine

Personalized predictive medicine necessitates the modeling of patient illness and care processes, which inherently have long-term temporal dependencies. Healthcare observations, recorded in electronic medical records, are episodic and irregular in time. We introduce DeepCare, an end-to-end deep dynamic neural network that reads medical records, stores previous illness history, infers current illness states and predicts future medical outcomes. At the data level, DeepCare represents care episodes as vectors in space, models patient health state trajectories through explicit memory of historical records. Built on Long Short-Term Memory (LSTM), DeepCare introduces time parameterizations to handle irregular timed events by moderating the forgetting and consolidation of memory cells. DeepCare also incorporates medical interventions that change the course of illness and shape future medical risk. Moving up to the health state level, historical and present health states are then aggregated through multiscale temporal pooling, before passing through a neural network that estimates future outcomes. We demonstrate the efficacy of DeepCare for disease progression modeling, intervention recommendation, and future risk prediction. On two important cohorts with heavy social and economic burden -- diabetes and mental health -- the results show improved modeling and risk prediction accuracy.Comment: Accepted at JBI under the new name: "Predicting healthcare trajectories from medical records: A deep learning approach

Implementation of a distributed guideline-based decision support model within a patient-guidance framework

We report on new projection engine which was developed in order to implement a distributed guideline-based decision support system (DSS) within the European project MobiGuide.In this model, small portions of the guideline knowledge are projected, i.e. 'downloaded', from a central DSS server to a local DSS in the patient's mobile device, which then applies that knowledge using the mobile device’s local resources. Furthermore, the projection engine generates guideline projections which are adapted to the patient’s previously defined preferences and, implicitly, to the patient’s current context, which is embodied in the projected knowledge. We evaluated this distributed guideline application model for two complex guidelines: one for Gestational Diabetes Mellitus, and one for Atrial Fibrillation. We found that the initial specification of what we refer to as the customized guideline should be in the terms of the distributed DSS, i.e., include two levels: one for the central DSS, and one for the local DSS. In addition, we found significant differences between the customized, distributed versions of the two guidelines, indicating further research directions and possibly additional ways to analyze and characterize guidelines

Purified native and recombinant human alpha lymphotoxin [tumor necrosis factor (TNF)-beta] induces inflammatory reactions in normal skin

These studies report findings that demonstrate that human alpha lymphotoxin (LT) induces local, visible, and microscopic inflammatory reactions in normal skin. Skin sites in rabbits, when inoculated with a single injection of native or recombinant human alpha lymphotoxin, demonstrated erythema, swelling, and warmth within 5 hr. Erythema peaked between 24 and 48 hr had resolved by 72 hr. Histologic studies of skin sites injected with native LT revealed polymorphonuclear neutrophil (PMN) infiltration and edema beginning as early as 3 hr posttreatment. Individual skin sites that received three daily injections of native LT exhibited persistent erythema and swelling. Palpable induration was evident 24 hr after the second injection in the series. Histologic examination revealed the presence of many PMNs with associated focal dermal destruction, in the form of microabscesses, and scattered mononuclear cells. In contrast, control materials and recombinant human tumor necrosis factor (TNF-alpha) did not induce visible skin reactions in the rabbit. Several additional controls excluded endotoxin as being the agent responsible for the inflammatory skin reactions observed. The ability of LT to induce inflammation may have a role in its antitumor activity and it may be an important endogenous mediator in other immunologic reactions

Clinimetrics in rehabilitation medicine: current issues in developing and applying measurement instruments 1

Clinimetrics in rehabilitation medicine, i.e. the field of developing, evaluating and applying measurement instruments, has undergone considerable progress. Despite this progress, however, several issues remain. These include: (i) selection of an instrument out of the wide range available; (ii) using an instrument in a variety of diagnostic groups; (iii) using an instrument in individual patients, as opposed to a group of patients; and (iv) the use of instruments in clinical practice. This paper reviews these issues, as well as current attempts at resolving them. Illustrative examples are given. It is concluded that solutions seem to be available, but considerable research effort is required to make these a reality. Clinimetrics in rehabilitation medicine remains a field with challenging opportunities for researc

Placebo Adherence and Its Association with Morbidity and Mortality in the Studies of Left Ventricular Dysfunction

A provocative finding from several double-blind clinical trials has been the association between greater adherence to placebo study medication and better health outcomes. We used data from the Studies of Left Ventricular Dysfunction (SOLVD) Treatment Trial (SOLVD-TT) and the SOLVD Prevention Trial (SOLVD-PT) to examine whether such associations could be validated and to examine several sources of bias and potential confounding. Survival analytic methods were used to estimate the association between placebo adherence and several health outcomes, employing a number of modeling techniques to test for the existence of alternative explanations for the association. Higher adherence was defined as having taken ≥75% of prescribed study medication. Higher placebo adherence was associated with improved overall survival in both SOLVD-TT and SOLVD-PT [hazard ratio (HR) = 0.52, 95% confidence interval (CI): 0.35 to 0.79 and HR = 0.52, 95%CI: 0.38 to 0.71, respectively]. Associations were similar for fatal or non-fatal cardiovascular or coronary heart disease events. Adjustment for both modifiable and non-modifiable cardiac risk factors (including age, gender, diabetes, blood pressure, smoking, weight, alcohol use, and levels of education) had minimal effect on the strength of the association. Little evidence of bias was found as an explanation for this relationship. In these two trials, better adherence to placebo was associated with markedly superior health outcomes, including total in-study mortality and incident cardiovascular events. No important confounders were identified. These data suggest there may exist strong but unrecognized determinants of health outcomes for which placebo adherence is a marker

Uncovering treatment burden as a key concept for stroke care: a systematic review of qualitative research

<b>Background</b> Patients with chronic disease may experience complicated management plans requiring significant personal investment. This has been termed ‘treatment burden’ and has been associated with unfavourable outcomes. The aim of this systematic review is to examine the qualitative literature on treatment burden in stroke from the patient perspective.<p></p> <b>Methods and findings</b> The search strategy centred on: stroke, treatment burden, patient experience, and qualitative methods. We searched: Scopus, CINAHL, Embase, Medline, and PsycINFO. We tracked references, footnotes, and citations. Restrictions included: English language, date of publication January 2000 until February 2013. Two reviewers independently carried out the following: paper screening, data extraction, and data analysis. Data were analysed using framework synthesis, as informed by Normalization Process Theory. Sixty-nine papers were included. Treatment burden includes: (1) making sense of stroke management and planning care, (2) interacting with others, (3) enacting management strategies, and (4) reflecting on management. Health care is fragmented, with poor communication between patient and health care providers. Patients report inadequate information provision. Inpatient care is unsatisfactory, with a perceived lack of empathy from professionals and a shortage of stimulating activities on the ward. Discharge services are poorly coordinated, and accessing health and social care in the community is difficult. The study has potential limitations because it was restricted to studies published in English only and data from low-income countries were scarce.<p></p> <b>Conclusions</b> Stroke management is extremely demanding for patients, and treatment burden is influenced by micro and macro organisation of health services. Knowledge deficits mean patients are ill equipped to organise their care and develop coping strategies, making adherence less likely. There is a need to transform the approach to care provision so that services are configured to prioritise patient needs rather than those of health care systems

Enrichment and characterization of ammonia-oxidizing archaea from the open ocean : phylogeny, physiology and stable isotope fractionation

Author Posting. © The Author(s), 2011. This is the author's version of the work. It is posted here by permission of Nature Publishing Group for personal use, not for redistribution. The definitive version was published in The ISME Journal 5 (2011): 1796–1808, doi:10.1038/ismej.2011.58.Archaeal genes for ammonia oxidation are widespread in the marine environment, but direct physiological evidence for ammonia oxidation by marine archaea is limited. We report the enrichment and characterization of three strains of pelagic ammonia-oxidizing archaea (AOA) from the north Pacific Ocean that have been maintained in laboratory culture for over three years. Phylogenetic analyses indicate the three strains belong to a previously identified clade of water column-associated AOA and possess 16S rRNA genes and ammonia monooxygenase subunit a (amoA) genes highly similar (98-99% identity) to those recovered in DNA and cDNA clone libraries from the open ocean. The strains grow in natural seawater-based liquid medium while stoichiometrically converting ammonium (NH4 +) to nitrite (NO2 -). Ammonia oxidation by the enrichments is only partially inhibited by allylthiourea at concentrations known to inhibit cultivated ammonia-oxidizing bacteria. The three strains were used to determine the nitrogen stable isotope effect (15εNH3) during archaeal ammonia oxidation, an important parameter for interpreting stable isotope ratios in the environment. Archaeal 15εNH3 ranged from 13- 41‰, within the range of that previously reported for ammonia-oxidizing bacteria. Despite low amino acid identity between the archaeal and bacterial Amo proteins, their functional diversity as captured by 15εNH3 is similar.This work was supported by a Woods Hole Oceanographic Institution (WHOI) Postdoctoral Scholar fellowship to AES and the WHOI Ocean Life Institute

Comparing the Functional Independence Measure and the interRAI/MDS for use in the functional assessment of older adults: a review of the literature

<p>Abstract</p> <p>Background</p> <p>The rehabilitation of older persons is often complicated by increased frailty and medical complexity - these in turn present challenges for the development of health information systems. Objective investigation and comparison of the effectiveness of geriatric rehabilitation services requires information systems that are comprehensive, reliable, valid, and sensitive to clinically relevant changes in older persons. The Functional Independence Measure is widely used in rehabilitation settings - in Canada this is used as the central component of the National Rehabilitation Reporting System of the Canadian Institute of Health Information. An alternative system has been developed by the interRAI consortium. We conducted a literature review to compare the development and measurement properties of these two systems.</p> <p>Methods</p> <p>English language literature published between 1983 (initial development of the FIM) and 2008 was searched using Medline and CINAHL databases, and the reference lists of retrieved articles. Relevant articles were summarized and charted using the criteria proposed by Streiner. Additionally, attention was paid to the ability of the two systems to address issues particularly relevant to older rehabilitation clients, such as medical complexity, comorbidity, and responsiveness to small but clinically meaningful improvements.</p> <p>Results</p> <p>In total, 66 articles were found that met the inclusion criteria. The majority of FIM articles studied inpatient rehabilitation settings; while the majority of interRAI/MDS articles focused on nursing home settings. There is evidence supporting the reliability of both instruments. There were few articles that investigated the construct validity of the interRAI/MDS.</p> <p>Conclusion</p> <p><b>A</b>dditional psychometric research is needed on both the FIM and MDS, especially with regard to their use in different settings and with different client groups.</p