Grains of Sand to Clinical Pearls: Realizing the Potential of Wearable Data.

Despite the rapid growth of wearables as a consumer technology sector and a growing evidence base supporting their use, they have been slow to be adopted by the health system into clinical care. As regulatory, reimbursement, and technical barriers recede, a persistent challenge remains how to make wearable data actionable for clinicians-transforming disconnected grains of wearable data into meaningful clinical "pearls". In order to bridge this adoption gap, wearable data must become visible, interpretable, and actionable for the clinician. We showcase emerging trends and best practices that illustrate these 3 pillars, and offer some recommendations on how the ecosystem can move forward.

Metadata Correction: Direct Adherence Measurement Using an Ingestible Sensor Compared With Self-Reporting in High-Risk Cardiovascular Disease Patients Who Knew They Were Being Measured: Prospective Intervention.

[This corrects the article DOI: 10.2196/mhealth.6998.].

Reconfiguring Cardiac Rehabilitation to Achieve Panvascular Prevention: New Care Models for a New World.

Atherosclerotic cardiovascular disease (ASCVD) and its associated economic burden are increasing globally. Although cardiac rehabilitation is a vital component of secondary prevention with proven benefits, it is underutilized due to numerous barriers, especially in resource-limited settings. New care models for delivery of comprehensive prevention programs such as community-based, home-based, and "hybrid" models implementing m-health, e-health, and telemedicine need to be adopted. Such new care models should be offered to all patients with established ASCVD (coronary, cerebral, and peripheral) and additionally to those at high risk of developing ASCVD with multiple risk factors for panvascular prevention.

Direct Adherence Measurement Using an Ingestible Sensor Compared With Self-Reporting in High-Risk Cardiovascular Disease Patients Who Knew They Were Being Measured: A Prospective Intervention.

BACKGROUND: Use of appropriate cardioprotective medication is a cornerstone of cardiovascular disease prevention, but less-than-optimal patient adherence is common. Thus, strategies for improving adherence are recommended to adopt a multifaceted approach. OBJECTIVE: The objective of our study was to test a system comprising a biodegradable, ingestible sensor for direct measurement of medication ingestion in a group of patients at elevated cardiovascular risk attending a cardiac prevention and rehabilitation program. METHODS: In this prospective intervention trial in a single group of 21 patients running from April 2014 to June 2015, we measured adherence by self-report and adherence determined objectively by the system. The sensor emits a signal when it encounters the acidic environment of the stomach, detectable by an externally worn patch and linked software app. Longitudinal adherence data in the form of daily progress charts for sensed dosing events as compared with scheduled dosing are visible to patients on their tablet computer's medication dosing app, thus providing patients with continuous medication adherence feedback. We sought feedback on patient acceptability by questionnaire assessment. Participants used the system for the 12-week period of their cardiac prevention and rehabilitation program. RESULTS: Only 1 patient at initial assessment and 1 patient at end-of-program assessment reported often missing medication. The remaining patients reported never missing medication or had missing data. Only 12 (57%) of patients overall achieved system-determined adherence of 80% or more, and 3 patients had scores below 40%. Participants reported high levels of acceptability. CONCLUSIONS: This integrated system was well tolerated in a group of 21 patients over an appreciable time frame. Its ability to measure adherence reveals the sizeable disconnect between patient self-reported adherence and actual medication taking and has promising potential for clinical use as a tool to encourage better medication-taking behavior due to its ability to provide continuous patient-level feedback.

Can the Onset of Type 2 Diabetes Be Delayed by a Group-Based Lifestyle Intervention in Women with Prediabetes following Gestational Diabetes Mellitus (GDM)? Findings from a Randomized Control Mixed Methods Trial.

OBJECTIVE: To evaluate a 12-week group-based lifestyle intervention programme for women with prediabetes following gestational diabetes (GDM). DESIGN: A two-group, mixed methods randomized controlled trial in which 50 women with a history of GDM and abnormal glucose tolerance postpartum were randomly assigned to intervention (n = 24) or wait control (n = 26) and postintervention qualitative interviews with participants. MAIN OUTCOME MEASURES: Modifiable biochemical, anthropometric, behavioural, and psychosocial risk factors associated with the development of type 2 diabetes. The primary outcome variable was the change in fasting plasma glucose (FPG) from study entry to one-year follow-up. RESULTS: At one-year follow-up, the intervention group showed significant improvements over the wait control group on stress, diet self-efficacy, and quality of life. There was no evidence of an effect of the intervention on measures of biochemistry or anthropometry; the effect on one health behaviour, diet adherence, was close to significance. CONCLUSIONS: Prevention programmes must tackle the barriers to participation faced by this population; home-based interventions should be investigated. Strategies for promoting long-term health self-management need to be developed and tested.

Reasons for participation and non-participation in a diabetes prevention trial among women with prior gestational diabetes mellitus (GDM).

BACKGROUND: Gestational diabetes mellitus (GDM) is a risk factor for the development of type 2 diabetes. Lifestyle intervention can prevent progression to type 2 diabetes in high risk populations. We designed a randomised controlled trial (RCT) to evaluate the effectiveness of an established lifestyle intervention compared to standard care for delaying diabetes onset in European women with recent GDM. Recruitment into the RCT was more challenging than anticipated with only 89 of 410 (22%) women agreeing to participate. This paper identifies factors that could enhance participation of the target population in future interventions. METHODS: We hypothesised that women who agreed to participate would have higher diabetes risk profiles than those who declined, and secondly that it would be possible to predict participation on the bases of those risk factors. To test our hypothesis, we identified the subset of women for whom we had comprehensive data on diabetes risks factors 3-5 years following GDM, reducing the sample to 43 participants and 73 decliners. We considered established diabetes risk factors: smoking, daily fruit and vegetable intake, participation in exercise, family history of diabetes, glucose values and BMI scores on post-partum re-screens, use of insulin during pregnancy, and age at delivery. We also analysed narrative data from 156 decliners to further understand barriers to and facilitators of participation. RESULTS: Two factors differentiated participants and decliners: age at delivery (with women older than 34 years being more likely to participate) and insulin use during pregnancy (with women requiring the use of insulin in pregnancy less likely to participate). Binary logistic regression confirmed that insulin use negatively affected the odds of participation. The most significant barriers to participation included the accessibility, affordability and practicality of the intervention. CONCLUSIONS: Women with recent GDM face multiple barriers to lifestyle change. Intervention designers should consider: (i) the practicalities of participation for this population, (ii) research designs that capitalise on motivational differences between participants, (iii) alleviating concerns about long-term diabetes management. We hope this work will support future researchers in developing interventions that are more relevant, effective and successful in recruiting the desired population. TRIAL REGISTRATION: Current Controlled Trials ISRCTN41202110.

Comparison of uptake and predictors of adherence in primary and secondary prevention of cardiovascular disease in a community-based cardiovascular prevention programme (MyAction Westminster).

BACKGROUND: Despite the benefits of cardiac rehabilitation, uptake and adherence remain suboptimal. With the advent of NHS Health Checks, primary prevention programmes have also been advocated, but little is known about uptake and adherence rates. This study examined rates and predictors of adherence amongst patients with cardiovascular disease (CVD) and those at high multifactorial risk (HRI) attending an innovative programme integrating primary and secondary prevention. METHODS: Comparison of rates of uptake and adherence and also predictors of adherence between 401 CVD patients and 483 HRI. The outcome was the number of sessions attended and predictor variables included clinical and psychosocial variables. Differences between groups were examined using t-tests and non-parametric tests. Multivariable regression analyses examined predictors of adherence. RESULTS: Uptake to the assessment (CVD: 97%, HRI: 88%) and the programme (CVD: 78%, HRI: 74%) were high for both groups. An average of 8/12 was attended in both groups. Beliefs about treatment predicted adherence for both groups (P < 0.01). The alcohol causal belief also predicted poorer adherence amongst CVD patients (P < 0.02). Older age also predicted better adherence amongst HRI (P < 0.001). CONCLUSIONS: Rates of uptake and adherence were high for both HRI and CVD patients. Further research is needed to examine whether interventions targeting predictor variables further improve adherence.

Response to pulmonary arterial hypertension drug therapies in patients with pulmonary arterial hypertension and cardiovascular risk factors.

The age at diagnosis of pulmonary arterial hypertension (PAH) and the prevalence of cardiovascular (CV) risk factors are increasing. We sought to determine whether the response to drug therapy was influenced by CV risk factors in PAH patients. We studied consecutive incident PAH patients (n = 146) between January 1, 2008, and July 15, 2011. Patients were divided into two groups: the PAH-No CV group included patients with no CV risk factors (obesity, systemic hypertension, type 2 diabetes mellitus, permanent atrial fibrillation, mitral and/or aortic valve disease, and coronary artery disease), and the PAH-CV group included patients with at least one. The response to PAH treatment was analyzed in all the patients who received PAH drug therapy. The PAH-No CV group included 43 patients, and the PAH-CV group included 69 patients. Patients in the PAH-No CV group were younger than those in the PAH-CV group (P < 0.0001). In the PAH-No CV group, 16 patients (37%) improved on treatment and 27 (63%) did not improve, compared with 11 (16%) and 58 (84%) in the PAH-CV group, respectively (P = 0.027 after adjustment for age). There was no difference in survival at 30 months (P = 0.218). In conclusion, in addition to older age, CV risk factors may predict a reduced response to PAH drug therapy in patients with PAH.

Transcriptome of hypertension-induced left ventricular hypertrophy and its regression by antihypertensive therapies.

Left ventricular hypertrophy (LVH), a common consequence of systemic hypertension associated with poor clinical outcome, is also a potentially reversible condition. Here, we probed the molecular pathways that underpin the development of LVH and their modulation by antihypertensive regimens that reversed LVH. Spontaneously hypertensive rats were studied at 12 (early LVH) and 48 weeks (late LVH), respectively, with normotensive Wistar-Kyoto rats as age-matched controls. Three treatment groups were maintained for 36 weeks on the following regimens: (1) quinapril, (2) doxazosin and quinapril combination, and (3) losartan. Gene expression profiling was performed with Affymetrix microarrays (GeneChip Rat-230A) and primary function-focused average linkage hierarchical cluster analysis. Of the 15 696 gene sequences expressed on the Affymetrix GeneChip Rat-230A, there was significant alteration in the expression of 295 (1.9%) of these transcripts in 'early' LVH and 143 (0.9%) in 'late' LVH. The predominant changes in gene expression were seen in metabolism, cell growth/proliferation, signal transduction, development and muscle contraction/cytoskeleton functional groups. Although sharing many effects on gene expression, the three treatments showed different expression profiles. Despite significant regression of LVH with treatment, 31 LVH-associated transcripts were unchanged by any of the treatment groups. Our data suggest that LVH regression does not normalize the LVH transcriptome. Therefore, regression of hypertension-induced LVH is associated with a distinct gene expression profile, suggesting the effect of both treatment and a previously unknown specific myocardial physiology after regression of LVH.

Sequential extracellular matrix-focused and baited-global cluster analysis of serial transcriptomic profiles identifies candidate modulators of renal tubulointerstitial fibrosis in murine adriamycin-induced nephropathy.

Transcriptome analysis using microarray technology represents a powerful unbiased approach for delineating pathogenic mechanisms in disease. Here molecular mechanisms of renal tubulointerstitial fibrosis (TIF) were probed by monitoring changes in the renal transcriptome in a glomerular disease-dependent model of TIF (adriamycin nephropathy) using Affymetrix (mu74av2) microarray coupled with sequential primary biological function-focused and secondary "baited"-global cluster analysis of gene expression profiles. Primary cluster analysis focused on mRNAs encoding matrix proteins and modulators of matrix turnover as classified by Onto-Compare and Gene Ontology and identified both molecules and pathways already implicated in the pathogenesis of TIF (e.g. transforming growth factor beta1-CTGF-fibronectin-1 pathway) and novel TIF-associated genes (e.g. SPARC and Matrilin-2). Specific gene expression patterns identified by primary extracellular matrix-focused cluster analysis were then used as bioinformatic bait in secondary global clustering, with which to search the renal transcriptome for novel modulators of TIF. Among the genes clustering with ECM proteins in the latter analysis were endoglin, clusterin, and gelsolin. In several notable cases (e.g. claudin-1 and meprin-1beta) the pattern of gene expression identified in adriamycin nephropathy in vivo was replicated during transdifferentiation of renal tubule epithelial cells to a fibroblast-like phenotype in vitro on exposure to transforming growth factor-beta and epidermal growth factor suggesting a role in fibrogenesis. The further exploration of these complex gene networks should shed light on the core molecular pathways that underpin TIF in renal disease.

Modification of the transcriptomic response to renal ischemia/reperfusion injury by lipoxin analog.

BACKGROUND: Lipoxins are lipoxygenase-derived eicosanoids with anti-inflammatory and proresolution bioactivities in vitro and in vivo. We have previously demonstrated that the stable synthetic LXA4 analog 15-epi-16-(FPhO)-LXA4-Me is renoprotective in murine renal ischemia/reperfusion injury, as gauged by lower serum creatinine, attenuated leukocyte infiltration, and reduced morphologic tubule injury. METHODS: We employed complementary oligonucleotide microarray and bioinformatic analyses to probe the transcriptomic events that underpin lipoxin renoprotection in this setting. RESULTS: Microarray-based analysis identified three broad categories of genes whose mRNA levels are altered in response to ischemia/reperfusion injury, including known genes previously implicated in the pathogenesis of ischemia/reperfusion injury [e.g., intercellular adhesion molecule-1 (ICAM-1), p21, KIM-1], known genes not previously associated with ischemia/reperfusion injury, and cDNAs representing yet uncharacterized genes. Characterization of expressed sequence tags (ESTs) displayed on microarrays represents a major challenge in studies of global gene expression. A bioinformatic annotation pipeline successfully annotated a large proportion of ESTs modulated during ischemia/reperfusion injury. The differential expression of a representative group of these ischemia/reperfusion injury-modulated genes was confirmed by real-time polymerase chain reaction. Prominent among the up-regulated genes were claudin-1, -3, and -7, and ADAM8. Interestingly, the former response was claudin-specific and was not observed with other claudins expressed by the kidney (e.g., claudin-8 and -6) or indeed with other components of the renal tight junctions (e.g., occludin and junctional adhesion molecule). Noteworthy among the down-regulated genes was a cluster of transport proteins (e.g., aquaporin-1) and the zinc metalloendopeptidase meprin-1 beta implicated in renal remodeling. CONCLUSION: Treatment with the lipoxin analog 15-epi-16-(FPhO)-LXA4-Me prior to injury modified the expression of many differentially expressed pathogenic mediators, including cytokines, growth factors, adhesion molecules, and proteases, suggesting a renoprotective action at the core of the pathophysiology of acute renal failure (ARF). Importantly, this lipoxin-modulated transcriptomic response included many genes expressed by renal parenchymal cells and was not merely a reflection of a reduced renal mRNA load resulting from attenuated leukocyte recruitment. The data presented herein suggest a framework for understanding drivers of kidney injury in ischemia/reperfusion and the molecular basis for renoprotection by lipoxins in this setting.

Transcriptome profiling and the pathogenesis of diabetic complications.

Diabetes is an escalating problem worldwide and a major cause of vascular disease, renal failure, and blindness, among other complications. The cellular mediators of high glucose-induced injury include activation of protein kinase C, accumulation of cell sorbitol from increased flux through the aldose reductase pathway, and generation of advanced glycosylation end products and reactive oxygen species, among others. Current strategies for preventing and slowing the progression of the macrovascular and microvascular complications of diabetes include optimization of glycemic control and BP, angiotensin-converting enzyme inhibitors and angiotensin II blockers, and HMG CoA reductase inhibitors. However, there is an urgent need to develop new therapeutic strategies, as these interventions, although they may slow, rarely halt the progression of diabetic complications. Central to this process is the elucidation of the molecular events that drive this complex disease and that are potential therapeutic targets. This review discusses the promise offered in this regard by global monitoring of cellular or tissue mRNA expression (so-called transcriptomics) and illustrates the potential of this approach by focusing on recent studies on the pathogenesis of diabetic nephropathy.