Level of Effort and 3 Hour Rule Compliance.

OBJECTIVE: To determine if patients' level of effort (LOE) in therapy sessions during traumatic brain injury (TBI) rehabilitation modifies the effect of compliance with the 3-Hour Rule of the Centers for Medicare & Medicaid Services. DESIGN: Propensity score methodology applied to the TBI Practice-Based Evidence database, consisting of multisite, prospective, longitudinal observational data. SETTING: Acute inpatient rehabilitation facilities (IRF). PARTICIPANTS: Patients (N=1820) who received their first IRF admission for TBI in the United States and were enrolled for 3- and 9-month follow-up. MAIN OUTCOME MEASURES: Participation Assessment with Recombined Tools-Objective-17, FIM Motor and Cognitive scores, Satisfaction with Life Scale, and Patient Health Questionnaire-9. RESULTS: When the full cohort was examined, no strong main effect of compliance with the 3-Hour Rule was identified and LOE did not modify the effect of compliance with the 3-Hour Rule. In contrast, LOE had a strong positive main effect on all outcomes, except depression. When the sample was stratified by level of disability, LOE modified the effect of compliance, particularly on the outcomes of participants with less severe disability. For these patients, providing 3 hours of therapy for 50% or more of therapy days in the context of low effort resulted in poorer performance on select outcome measures at discharge and up to 9 months postdischarge compared to patients with <50% of 3-hour therapy days. CONCLUSIONS: LOE is an active ingredient in inpatient TBI rehabilitation, while compliance with the 3-Hour Rule was not found to have a substantive effect on the outcomes. The results support matching time in therapy during acute TBI rehabilitation to patients' LOE in order to optimize long-term benefits on outcomes.

Quality of primary care by advanced practice nurses: a systematic review.

PURPOSE: To conduct a systematic review of randomized controlled trials (RCTs) of the safety and effectiveness of primary care provided by advanced practice nurses (APNs) and evaluate the potential of their deployment to help alleviate primary care shortages. DATA SOURCES: PubMed, Medline and the Cumulative Index to Nursing and Allied Health Literature. STUDY SELECTION: RCTs and their follow-up reports that compared outcomes of care provided to adults by APNs and physicians in equivalent primary care provider roles were selected for inclusion. DATA EXTRACTION: Ten articles (seven RCTs, plus two economic evaluations and one 2-year follow-up study of included RCTs) met inclusion criteria. Data were extracted regarding study design, setting and outcomes across four common categories. RESULTS OF DATA SYNTHESIS: The seven RCTs include data for 10 911 patients who presented for ongoing primary care (four RCTs) or same-day consultations for acute conditions (three RCTs) in the primary care setting. Study follow-up ranged from 1 day to 2 years. APN groups demonstrated equal or better outcomes than physician groups for physiologic measures, patient satisfaction and cost. APNs generally had longer consultations compared with physicians; however, two studies reported that APN patients required fewer consultations over time. CONCLUSION: There were few differences in primary care provided by APNs and physicians; for some measures APN care was superior. While studies are needed to assess longer term outcomes, these data suggest that the APN workforce is well-positioned to provide safe and effective primary care.

Systematic evaluation of personal genome services for Japanese individuals.

Disease risk prediction (DRP) is one of the most important challenges in personal genome research. Although many direct-to-consumer genetic test (DTC) companies have begun to offer personal genome services for DRP, there is still no consensus on what constitutes a gold-standard service. Here, we systematically evaluated the distributions of DRPs from three DTC companies, that is, 23andMe, Navigenics and deCODEme, for 22 diseases using three Japanese samples. We systematically quantified and analyzed the differences between each DTC company's DRPs. Our independency test showed that the overall prediction results were correlated with each other, but not perfectly matched; less than onethird mismatching of the opposite direction occurred in eight diseases. Moreover, we found that the differences could mainly be attributed to four factors: (1) single nucleotide polymorphism (SNP) selection, (2) average risk estimation, (3) the disease risk calculation algorithm and (4) ethnicity adjustment. In particular, only 7.1% of SNPs over 22 diseases were reviewed by all three companies. Therefore, development of a universal core SNPs list for non-Caucasian samples will be important for achieving better prediction capacity for Japanese samples. This systematic methodology provides useful insights for improving the capacity of DRPs in future personal genome services.

Complex regional pain syndrome: practical diagnostic and treatment guidelines, 4th edition.

OBJECTIVE: This is the fourth edition of diagnostic and treatment guidelines for complex regional pain syndrome (CRPS; aka reflex sympathetic dystrophy). METHODS: Expert practitioners in each discipline traditionally utilized in the treatment of CRPS systematically reviewed the available and relevant literature; due to the paucity of levels 1 and 2 studies, less rigorous, preliminary research reports were included. The literature review was supplemented with knowledge gained from extensive empirical clinical experience, particularly in areas where high-quality evidence to guide therapy is lacking. RESULTS: The research quality, clinical relevance, and "state of the art" of diagnostic criteria or treatment modalities are discussed, sometimes in considerable detail with an eye to the expert practitioner in each therapeutic area. Levels of evidence are mentioned when available, so that the practitioner can better assess and analyze the modality under discussion, and if desired, to personally consider the citations. Tables provide details on characteristics of studies in different subject domains described in the literature. CONCLUSIONS: In the humanitarian spirit of making the most of all current thinking in the area, balanced by a careful case-by-case analysis of the risk/cost vs benefit analysis, the authors offer these "practical" guidelines.

Crowdsourced health research studies: an important emerging complement to clinical trials in the public health research ecosystem.

BACKGROUND: Crowdsourced health research studies are the nexus of three contemporary trends: 1) citizen science (non-professionally trained individuals conducting science-related activities); 2) crowdsourcing (use of web-based technologies to recruit project participants); and 3) medicine 2.0 / health 2.0 (active participation of individuals in their health care particularly using web 2.0 technologies). Crowdsourced health research studies have arisen as a natural extension of the activities of health social networks (online health interest communities), and can be researcher-organized or participant-organized. In the last few years, professional researchers have been crowdsourcing cohorts from health social networks for the conduct of traditional studies. Participants have also begun to organize their own research studies through health social networks and health collaboration communities created especially for the purpose of self-experimentation and the investigation of health-related concerns. OBJECTIVE: The objective of this analysis is to undertake a comprehensive narrative review of crowdsourced health research studies. This review will assess the status, impact, and prospects of crowdsourced health research studies. METHODS: Crowdsourced health research studies were identified through a search of literature published from 2000 to 2011 and informal interviews conducted 2008-2011. Keyword terms related to crowdsourcing were sought in Medline/PubMed. Papers that presented results from human health studies that included crowdsourced populations were selected for inclusion. Crowdsourced health research studies not published in the scientific literature were identified by attending industry conferences and events, interviewing attendees, and reviewing related websites. RESULTS: Participatory health is a growing area with individuals using health social networks, crowdsourced studies, smartphone health applications, and personal health records to achieve positive outcomes for a variety of health conditions. PatientsLikeMe and 23andMe are the leading operators of researcher-organized, crowdsourced health research studies. These operators have published findings in the areas of disease research, drug response, user experience in crowdsourced studies, and genetic association. Quantified Self, Genomera, and DIYgenomics are communities of participant-organized health research studies where individuals conduct self-experimentation and group studies. Crowdsourced health research studies have a diversity of intended outcomes and levels of scientific rigor. CONCLUSIONS: Participatory health initiatives are becoming part of the public health ecosystem and their rapid growth is facilitated by Internet and social networking influences. Large-scale parameter-stratified cohorts have potential to facilitate a next-generation understanding of disease and drug response. Not only is the large size of crowdsourced cohorts an asset to medical discovery, too is the near-immediate speed at which medical findings might be tested and applied. Participatory health initiatives are expanding the scope of medicine from a traditional focus on disease cure to a personalized preventive approach. Crowdsourced health research studies are a promising complement and extension to traditional clinical trials as a model for the conduct of health research.

Multigenic condition risk assessment in direct-to-consumer genomic services.

PURPOSE: Gene carrier status and pharmacogenomic data may be detectable from single nucleotide polymorphisms (SNPs), but SNP-based research concerning multigenic common disease such as diabetes, cancers, and cardiovascular disease is an emerging field. The many SNPs and loci that may relate to common disease have not yet been comprehensively identified and understood scientifically. In the interim, direct-to-consumer (DTC) genomic companies have forged ahead in developing composite risk interpretations for multigenic conditions. It is useful to understand how variance in risk interpretation may arise. METHODS: A comprehensive study was conducted to analyze the 213 conditions covered by the 5 identifiable genome-wide DTC genomic companies, and the total SNPs (401) and loci (224) assessed in the 20 common disease conditions with the greatest overlapping coverage. RESULTS: Variance in multigenic condition risk interpretation can be explained by differences in the average lifetime risk assigned to similar underlying populations, the loci and SNPs selected for analysis, and the quantitative risk assignment methodologies used by DTC genomic companies. CONCLUSION: At present, multigenic condition analysis is a complicated process. DTC genomic companies have made laudable efforts to deliver risk predictions, but greater consistency is needed for the long-term validity, utility, and credibility of the sector.

Human Brain/Cloud Interface.

The Internet comprises a decentralized global system that serves humanity's collective effort to generate, process, and store data, most of which is handled by the rapidly expanding cloud. A stable, secure, real-time system may allow for interfacing the cloud with the human brain. One promising strategy for enabling such a system, denoted here as a "human brain/cloud interface" ("B/CI"), would be based on technologies referred to here as "neuralnanorobotics." Future neuralnanorobotics technologies are anticipated to facilitate accurate diagnoses and eventual cures for the ∼400 conditions that affect the human brain. Neuralnanorobotics may also enable a B/CI with controlled connectivity between neural activity and external data storage and processing, via the direct monitoring of the brain's ∼86 × 109 neurons and ∼2 × 1014 synapses. Subsequent to navigating the human vasculature, three species of neuralnanorobots (endoneurobots, gliabots, and synaptobots) could traverse the blood-brain barrier (BBB), enter the brain parenchyma, ingress into individual human brain cells, and autoposition themselves at the axon initial segments of neurons (endoneurobots), within glial cells (gliabots), and in intimate proximity to synapses (synaptobots). They would then wirelessly transmit up to ∼6 × 1016 bits per second of synaptically processed and encoded human-brain electrical information via auxiliary nanorobotic fiber optics (30 cm3) with the capacity to handle up to 1018 bits/sec and provide rapid data transfer to a cloud based supercomputer for real-time brain-state monitoring and data extraction. A neuralnanorobotically enabled human B/CI might serve as a personalized conduit, allowing persons to obtain direct, instantaneous access to virtually any facet of cumulative human knowledge. Other anticipated applications include myriad opportunities to improve education, intelligence, entertainment, traveling, and other interactive experiences. A specialized application might be the capacity to engage in fully immersive experiential/sensory experiences, including what is referred to here as "transparent shadowing" (TS). Through TS, individuals might experience episodic segments of the lives of other willing participants (locally or remote) to, hopefully, encourage and inspire improved understanding and tolerance among all members of the human family.

Treatment of complex regional pain syndrome: functional restoration.

In this review, the authors discuss the development of consensus-based treatment guidelines in 1997. They also synthesize the recommendations of a closed workshop held in Budapest in late 2004 that reexamined these treatment guidelines and made further and more detailed recommendations. They explore and develop the rationale for making functional restoration the pivotal treatment algorithm in the management of complex regional pain syndrome, around which all other treatments, such as psychotherapy, drugs, and interventions, revolve. The authors discuss in detail the process of functional restoration and the modalities appropriate to accomplishing that--specifically, the role of the occupational therapist, physical therapist, recreational therapist, and vocational rehabilitation specialist. Medications, interventions, and psychotherapy will be covered in other sections of this series.

Does diabetes self-management education in conjunction with primary care improve glycemic control in Hispanic patients? A systematic review and meta-analysis.

PURPOSE: The purpose of this systematic review and meta-analysis is to evaluate the effectiveness of diabetes self-management education (DSME) interventions delivered in conjunction with primary care among Hispanic adults with type 2 diabetes mellitus (T2DM). METHODS: A systematic search of PubMed, Cochrane Library, and the Cumulative Index to Nursing and Allied Health Literature identified randomized controlled trials (RCT) that tested the effect of DSME interventions in Hispanic adults with T2DM. Studies reporting hemoglobin A1C (A1C) pre and post intervention or change in A1C were eligible for inclusion in the meta-analysis. RESULTS: Of 625 studies identified, 13 RCTs met criteria for inclusion in the systematic review; of these, 11 studies were included in the meta-analysis. The 13 RCTs represent data from 2784 adult Hispanic subjects. DSME interventions (individual, group, telephone/electronic, and multimodal sessions) varied in intensity from 1-time DSME sessions with phone follow-up to contact every 4 to 6 weeks over 5 years. At ≥6 months following intervention, pooled A1C reduction was -0.25 (95% CI, -0.42 to -0.07), favoring the intervention group. CONCLUSIONS: DSME in conjunction with primary care is effective in improving glycemic control in Hispanic adults with T2DM. Future comparative effectiveness research is needed to identify best delivery methods to optimize effectiveness of DSME delivered to the Hispanic population.

The Quantified Self: Fundamental Disruption in Big Data Science and Biological Discovery.

A key contemporary trend emerging in big data science is the quantified self (QS)-individuals engaged in the self-tracking of any kind of biological, physical, behavioral, or environmental information as n=1 individuals or in groups. There are opportunities for big data scientists to develop new models to support QS data collection, integration, and analysis, and also to lead in defining open-access database resources and privacy standards for how personal data is used. Next-generation QS applications could include tools for rendering QS data meaningful in behavior change, establishing baselines and variability in objective metrics, applying new kinds of pattern recognition techniques, and aggregating multiple self-tracking data streams from wearable electronics, biosensors, mobile phones, genomic data, and cloud-based services. The long-term vision of QS activity is that of a systemic monitoring approach where an individual's continuous personal information climate provides real-time performance optimization suggestions. There are some potential limitations related to QS activity-barriers to widespread adoption and a critique regarding scientific soundness-but these may be overcome. One interesting aspect of QS activity is that it is fundamentally a quantitative and qualitative phenomenon since it includes both the collection of objective metrics data and the subjective experience of the impact of these data. Some of this dynamic is being explored as the quantified self is becoming the qualified self in two new ways: by applying QS methods to the tracking of qualitative phenomena such as mood, and by understanding that QS data collection is just the first step in creating qualitative feedback loops for behavior change. In the long-term future, the quantified self may become additionally transformed into the extended exoself as data quantification and self-tracking enable the development of new sense capabilities that are not possible with ordinary senses. The individual body becomes a more knowable, calculable, and administrable object through QS activity, and individuals have an increasingly intimate relationship with data as it mediates the experience of reality.

Scaling crowdsourced health studies: the emergence of a new form of contract research organization.

Accessing crowdsourced cohorts for health studies is a significant emerging opportunity that could have a positive impact on public health research, particularly as outcomes shift to the personalized, preventive medicine of the future. Health social networks have grown to become some of the largest aggregate patient registries and offer cost and efficiency benefits for study recruitment and operation by both traditional researchers and citizen scientists. Here, a model is proposed for extending crowdsourced studies beyond small-group experimentation to large-scale intervention-based research studies that are professionally run and scientifically rigorous, in effect creating a new form of contract research organization.

Health 2050: The Realization of Personalized Medicine through Crowdsourcing, the Quantified Self, and the Participatory Biocitizen.

The concepts of health and health care are moving towards the notion of personalized preventive health maintenance and away from an exclusive focus on the cure of disease. This is against the backdrop of contemporary public health challenges that include increasing costs, worsening outcomes, 'diabesity' epidemics, and anticipated physician shortages. Personalized preventive medicine could be critical to solving public health challenges at their causal root. This paper sets forth a vision and plan for the realization of preventive medicine by 2050 and examines efforts already underway such as participatory health initiatives, the era of big health data, and qualitative shifts in mindset.

Meeting report: American Aging Association 40th Annual Meeting, Raleigh, North Carolina, June 3-6, 2011.

The focus of the 2011 American Aging Association meeting was emerging concepts in the mechanisms of aging. Many of the usual topics in aging were covered, such as dietary restriction (DR), inflammation, stress resistance, homeostasis and proteasome activity, sarcopenia, and neural degeneration. There was also discussion of newer methods, such as microRNAs and genome sequencing, that have been employed to investigate gene expression variance with aging and genetic signatures of longevity. Aging as a field continues to mature, including the following areas: Using a systems approach to tracing conserved pathways across organisms; sharpening definitions of sarcopenia, frailty, and health span; and distinguishing interventions by age tier (early-onset versus late-onset). A preconference session on late-onset intervention concluded that there are numerous benefits to deriving such interventions. Conference talks applied the biology of aging in a translational manner to intervention development. Using an individual's own stem cells to regenerate organs for transplantation and as a cell source for cellular therapies could be a powerful near-term solution to disease. Several proposed interventions were pharmaceutical, myostatin inhibition, losartan, Janus kinase (JAK) pathway inhibitors, and enalapril for frailty and sarcopenia, and metformin to promote the Nrf2 antiinflammation response. In DR, protein restriction was found to be better than general calorie restriction. Short-term fasting may be helpful in chemotherapy, surgery, and acute stress, simultaneously increasing the killing of cancer cells by chemotherapy, while improving the survival of normal cells. Immune system interventions remain elusive, although statins may help to improve cellular senescence promoted bacterial infection. Engineered enzymes may be useful in lysosomal catabolism. Dietary restriction mimetics, most promisingly involving target of rapamycin (TOR; TORC1 inhibition and rapamycin), may be more feasible than dietary restriction.

Steady advance of stem cell therapies: report from the 2011 World Stem Cell Summit, Pasadena, California, October 3-5.

Stem cell research and related therapies (including regenerative medicine and cellular therapies) could have a significant near-term impact on worldwide public health and aging. One reason is the industry's strong linkage between policy, science, industry, and patient advocacy, as was clear in the attendance and programming at the 7(th) annual World Stem Cell Summit held in Pasadena, California, October 3-5, 2011. A special conference session sponsored by the SENS Foundation discussed how stem cell therapies are being used to extend healthy life span. Stem cells are useful not only in cell-replacement therapies, but also in disease modeling, drug discovery, and drug toxicity screening. Stem cell therapies are currently being applied to over 50 diseases, including heart, lung, neurodegenerative, and eye disease, cancer, and human immunodeficiency virus (HIV)/acquired immunodeficiency syndrome (AIDS). Dozens of companies are developing therapeutic solutions that are in different stages of clinical use and clinical trials. Some high-profile therapies include Dendreon's Provenge for prostate cancer, Geron's first-ever embryonic stem cell trials for spinal cord injury, Fibrocell's laViv cellular therapy for wrinkles, and well-established commercial skin substitutes (Organogenesis' Apligraf and Advanced BioHealing's Dermagraft). Stem cell policy issues under consideration include medical tourism, standards for large-scale stem cell manufacturing, and lingering ethical debates over the use of embryonic stem cells. Contemporary stem cell science advances include a focus on techniques for the direct reprogramming of cells from one lineage to another without returning to pluripotency as an intermediary step, improved means of generating and characterizing induced pluripotent cells, and progress in approaches to neurodegenerative disease.

Emerging patient-driven health care models: an examination of health social networks, consumer personalized medicine and quantified self-tracking.

A new class of patient-driven health care services is emerging to supplement and extend traditional health care delivery models and empower patient self-care. Patient-driven health care can be characterized as having an increased level of information flow, transparency, customization, collaboration and patient choice and responsibility-taking, as well as quantitative, predictive and preventive aspects. The potential exists to both improve traditional health care systems and expand the concept of health care though new services. This paper examines three categories of novel health services: health social networks, consumer personalized medicine and quantified self-tracking.