Sequential autoencoders for feature engineering and pretraining in major depressive disorder risk prediction.

Objectives: We evaluated autoencoders as a feature engineering and pretraining technique to improve major depressive disorder (MDD) prognostic risk prediction. Autoencoders can represent temporal feature relationships not identified by aggregate features. The predictive performance of autoencoders of multiple sequential structures was evaluated as feature engineering and pretraining strategies on an array of prediction tasks and compared to a restricted Boltzmann machine (RBM) and random forests as a benchmark. Materials and Methods: We study MDD patients from Vanderbilt University Medical Center. Autoencoder models with Attention and long-short-term memory (LSTM) layers were trained to create latent representations of the input data. Predictive performance was evaluated temporally by fitting random forest models to predict future outcomes with engineered features as input and using autoencoder weights to initialize neural network layers. We evaluated area under the precision-recall curve (AUPRC) trends and variation over the study population's treatment course. Results: The pretrained LSTM model improved predictive performance over pretrained Attention models and benchmarks in 3 of 4 outcomes including self-harm/suicide attempt (AUPRCs, LSTM pretrained = 0.012, Attention pretrained = 0.010, RBM = 0.009, random forest = 0.005). The use of autoencoders for feature engineering had varied results, with benchmarks outperforming LSTM and Attention encodings on the self-harm/suicide attempt outcome (AUPRCs, LSTM encodings = 0.003, Attention encodings = 0.004, RBM = 0.009, random forest = 0.005). Discussion: Improvement in prediction resulting from pretraining has the potential for increased clinical impact of MDD risk models. We did not find evidence that the use of temporal feature encodings was additive to predictive performance in the study population. This suggests that predictive information retained by model weights may be lost during encoding. LSTM pretrained model predictive performance is shown to be clinically useful and improves over state-of-the-art predictors in the MDD phenotype. LSTM model performance warrants consideration of use in future related studies. Conclusion: LSTM models with pretrained weights from autoencoders were able to outperform the benchmark and a pretrained Attention model. Future researchers developing risk models in MDD may benefit from the use of LSTM autoencoder pretrained weights.

Movement behavior of swordfish provisions connectivity between the temperate and tropical southwest Pacific Ocean.

Swordfish (Xiphias gladius) are a widely distributed (45°N-45°S) large pelagic fish targeted by fisheries worldwide. Swordfish that occur at high latitudes tend to disproportionately be large adults, so their movements have implications for population dynamics and fisheries management. In the southwest Pacific, little is known about this subset of the stock and existing evidence suggests limited movement from the subtropics into cooler high latitude waters. Here, we capitalize on the recent emergence of a recreational swordfish fishery off temperate southeast Australia to characterize movements of swordfish caught in the fishery with pop-up satellite archival transmitting tags. Data were recovered from tags deployed for 56-250 days on 11 swordfish (50-350 kg) tagged between 38 and 43°S in the western Tasman Sea. Five swordfish entered the Coral Sea (< 30°S), with four reaching north to 11-24°S, up to 3275 km away from location of capture. Behavior modelling suggests these four individuals rapidly transited north until encountering 23-27 °C water, at which point they lingered in the area for several months, consistent with spawning-related partial migration. One migrating swordfish still carrying a tag after the spawning season returned to ~ 120 km of its release location, suggesting site fidelity. Movements toward the central south Pacific were confined to two individuals crossing 165°E. Swordfish predominantly underwent normal diel vertical migration, descending into the mesopelagic zone at dawn (median daytime depth 494.9 m, 95% CI 460.4-529.5 m). Light attenuation predicted daytime depth, with swordfish rising by up to 195 m in turbid water. At night, swordfish were deeper during the full moon, median night-time depth 45.8 m (37.8-55.5) m versus 18.0 m (14.9-21.8) m at new moon. Modelling fine-scale (10 min-1) swordfish depth revealed dynamic effects of moon phase varying predictably across time of night with implications for fisheries interactions. Studying highly migratory fishes near distribution limits allows characterization of the full range of movement phenotypes within a population, a key consideration for important fish stocks in changing oceans.

Peer Recovery Coaches Perceptions of Their Work and Their Implications for Training, Support and Personal Recovery.

The peer recovery workforce, including individuals in sustained recovery from substance use, has grown rapidly in the previous decades. Peer recovery coaches represent a scalable, resource-efficient, and acceptable approach to increasing service delivery, specifically among individuals receiving substance use services in low-resource communities. Despite the potential to improve access to care in traditionally underserved settings, there are a number of barriers to successfully integrating peer recovery coaches in existing recovery services. The current study presents results from two focus groups composed of peer recovery coaches. Findings suggest that peer recovery coaches report discordance between their perceived role and their daily responsibilities and experience both inter- and intrapersonal challenges that impact their own recovery processes. These results point to several promising policy and structural changes that may support and enhance this growing workforce.

Optimizing warfarin dosing using deep reinforcement learning.

Warfarin is a widely used anticoagulant, and has a narrow therapeutic range. Dosing of warfarin should be individualized, since slight overdosing or underdosing can have catastrophic or even fatal consequences. Despite much research on warfarin dosing, current dosing protocols do not live up to expectations, especially for patients sensitive to warfarin. We propose a deep reinforcement learning-based dosing model for warfarin. To overcome the issue of relatively small sample sizes in dosing trials, we use a Pharmacokinetic/ Pharmacodynamic (PK/PD) model of warfarin to simulate dose-responses of virtual patients. Applying the proposed algorithm on virtual test patients shows that this model outperforms a set of clinically accepted dosing protocols by a wide margin. We tested the robustness of our dosing protocol on a second PK/PD model and showed that its performance is comparable to the set of baseline protocols.

Cathelicidin-3 Associated With Serum Extracellular Vesicles Enables Early Diagnosis of a Transmissible Cancer.

The identification of practical early diagnostic biomarkers is a cornerstone of improved prevention and treatment of cancers. Such a case is devil facial tumor disease (DFTD), a highly lethal transmissible cancer afflicting virtually an entire species, the Tasmanian devil (Sarcophilus harrisii). Despite a latent period that can exceed one year, to date DFTD diagnosis requires visual identification of tumor lesions. To enable earlier diagnosis, which is essential for the implementation of effective conservation strategies, we analyzed the extracellular vesicle (EV) proteome of 87 Tasmanian devil serum samples using data-independent acquisition mass spectrometry approaches. The antimicrobial peptide cathelicidin-3 (CATH3), released by innate immune cells, was enriched in serum EV samples of both devils with clinical DFTD (87.9% sensitivity and 94.1% specificity) and devils with latent infection (i.e., collected while overtly healthy, but 3-6 months before subsequent DFTD diagnosis; 93.8% sensitivity and 94.1% specificity). Although high expression of antimicrobial peptides has been mostly related to inflammatory diseases, our results suggest that they can be also used as accurate cancer biomarkers, suggesting a mechanistic role in tumorous processes. This EV-based approach to biomarker discovery is directly applicable to improving understanding and diagnosis of a broad range of diseases in other species, and these findings directly enhance the capacity of conservation strategies to ensure the viability of the imperiled Tasmanian devil population.

Using acoustic telemetry to quantify potential contaminant exposure of Vermilion Rockfish (Sebastes miniatus), Hornyhead Turbot (Pleuronichthys verticalis), and White Croaker (Genyonemus lineatus) at wastewater outfalls in southern California.

Contaminant Exposure Models (CEMs) were developed to predict population-level tissue contaminant concentrations in fishes by pairing sediment-bound contaminant concentrations (DDTs, PCBs) and fine-scale acoustic telemetry data from a habitat-associated species (Vermilion Rockfish, Sebastes miniatus), nomadic flatfish species (Hornyhead Turbot, Pleuronichthys verticalis), and nomadic benthic/midwater schooling species (White Croaker, Genyonemus lineatus) tagged near wastewater outfalls in southern California. Model results were compared to contaminant concentrations in tissue samples. The CEMs developed require further refinement before implementation into management efforts but may act as steppingstones to help shift primary monitoring methods away from the regular field collection of fish for tissue contaminant analyses and towards behavioral modeling and habitat mapping. We also developed Kernel Density Estimates that can be used by managers immediately to identify regions that contribute most to contaminant exposure in species of concern. Prioritizing remediation efforts in these areas are likely to be most effective at improving fish health.

The impact of dental Medicaid reform on dental care provider activity and market penetration of dental support organizations.

BACKGROUND: Medicaid state dental programs have experienced changes related to provider practice settings with the increased growth of dental support organizations (DSOs). The authors conducted this study to assess the impact of state Medicaid reform on the dental practice environment by examining provider activity and practice setting. METHODS: This was a retrospective cohort study of more than 13 million dental claims in the Virginia Medicaid program. It included children and dental care providers in the Virginia dental Medicaid program at some time during a 9-year period (fiscal years 2003-2011). The independent variable was the provider practice setting: private practice, DSO, and safety-net practice. The outcomes included annual measures of claims, patients, and payments per provider. The outcomes were examined over 3 phases of the study period: prereform (2003-2005), implementation phase (2006-2008), and postreform maturation (2009-2011). RESULTS: Provider activity increased after dental program reform, with private-practice providers delivering most of the dental care in the Medicaid program. There was a significant penetration of DSO providers in number of providers, claims per provider, and patients per provider (P < .001). Regression results found that providers in DSO settings had an increased number of patients and claims compared with private-practice providers. CONCLUSIONS: Medicaid reform has resulted in a significant increase in provider participation and growth of DSO-affiliated providers. PRACTICAL IMPLICATIONS: Areas of the state with more dense population had a higher penetrance of dentists practicing in DSO settings providing dental services to children enrolled in Medicaid.

Systemic Solutions for Addressing Non-Communicable Diseases in Low- and Middle-Income Countries.

Non-communicable diseases (NCDs) have been on the rise in low- and middle-income countries (LMICs) over the last few decades and represent a significant healthcare concern. Over 85% of "premature" deaths worldwide due to NCDs occur in the LMICs. NCDs are an economic burden on these countries, increasing their healthcare expenditure. However, targeting NCDs in LMICs is challenging due to evolving health systems and an emphasis on acute illness. The major issues include limitations with universal health coverage, regulations, funding, distribution and availability of the healthcare workforce, and availability of health data. Experts from across the health sector in LMICs formed a Think Tank to understand and examine the issues, and to offer potential opportunities that may address the rising burden of NCDs in these countries. This review presents the evidence and posits pragmatic solutions to combat NCDs.

Physiological mechanisms linking cold acclimation and the poleward distribution limit of a range-extending marine fish.

Extensions of species' geographical distributions, or range extensions, are among the primary ecological responses to climate change in the oceans. Considerable variation across the rates at which species' ranges change with temperature hinders our ability to forecast range extensions based on climate data alone. To better manage the consequences of ongoing and future range extensions for global marine biodiversity, more information is needed on the biological mechanisms that link temperatures to range limits. This is especially important at understudied, low relative temperatures relevant to poleward range extensions, which appear to outpace warm range edge contractions four times over. Here, we capitalized on the ongoing range extension of a teleost predator, the Australasian snapper Chrysophrys auratus, to examine multiple measures of ecologically relevant physiological performance at the population's poleward range extension front. Swim tunnel respirometry was used to determine how mid-range and poleward range edge winter acclimation temperatures affect metabolic rate, aerobic scope, swimming performance and efficiency and recovery from exercise. Relative to 'optimal' mid-range temperature acclimation, subsequent range edge minimum temperature acclimation resulted in absolute aerobic scope decreasing while factorial aerobic scope increased; efficiency of swimming increased while maximum sustainable swimming speed decreased; and recovery from exercise required a longer duration despite lower oxygen payback. Cold-acclimated swimming faster than 0.9 body lengths sec-1 required a greater proportion of aerobic scope despite decreased cost of transport. Reduced aerobic scope did not account for declines in recovery and lower maximum sustainable swimming speed. These results suggest that while performances decline at range edge minimum temperatures, cold-acclimated snapper are optimized for energy savings and range edge limitation may arise from suboptimal temperature exposure throughout the year rather than acute minimum temperature exposure. We propose incorporating performance data with in situ behaviour and environmental data in bioenergetic models to better understand how thermal tolerance determines range limits.

Estimated effect of US state syringe sale policy on source of last-used injection equipment.

BACKGROUND: Many people who inject drugs (PWID) lack access to a new sterile syringe each time they inject, with increased risk of injection-related harms, including spread of communicable diseases. In the United States (US), restricted access is largely due to state laws and policies regulating syringe access. Our aim in this US-focused study is to estimate variations in syringe acquisition behavior in relation to state-level syringe sale policies, drawing upon self-identified PWID in a nationally representative sample survey. METHODS: Estimates were obtained on the source of the last used syringe from participants of the National Survey on Drug Use and Health (NSDUH) years 2002-2011. States were classified as having restricted syringe policies if they had any restriction on the sale of syringes during the study period (e.g., required a prescription or limited the number being sold). RESULTS: In states with unrestricted syringe sale policies, PWID were more likely to have obtained their most recently used syringe from a safe source (Difference (%) = 9.8, 95% CI: 1.9, 17.7). This difference was largely driven by a larger percent of injectors obtaining syringes from a pharmacy in unrestricted states (Difference = 20.4, 95% CI: 12.2, 28.6) but was partially offset by fewer injectors obtaining syringes from syringe exchange programs (Difference = -10.7, 95% CI: -16.1, -5.3). CONCLUSION: These new findings, taken with other evidence, should help promote removal of policy barriers that now thwart syringe acquisition from a safe source. We hope this additional evidence will provoke policy discussions and may influence regulations that promote public health and reduce the spread of communicable diseases.

In vivo tissue reaction within the outflow conduit in patients supported by HeartWare HVAD.

AIM: The frequency, extent, and nature of tissue ingrowth within the continuous-flow left ventricular assist device (cf-LVAD) outflow conduit has not been systematically assessed. We sought to characterize conduit histopathology at explantation in a cohort of patients with HeartWare ventricular assist device (HVAD) and assess the effect on pump performance. METHODS: Patients undergoing routine histopathological assessment of a HeartWare HVAD removed at transplantation or autopsy were assessed. Outflow conduits were examined macroscopically, and visible tissue was sectioned for microscopic evaluation. In patients who had undergone prior contrast-enhanced computerized tomography (CT) with HVAD in situ, the outflow conduit was measured at the aortic anastomosis and 5 cm proximal to the anastomosis, in the axial and sagittal planes. All patients had their pump flow, flow pulsatility, current, and speed determined from log files examined at 1, 3, 6, 9, and 12 months after LVAD implantation. RESULTS: Twenty-five consecutive patients were assessed (24 LVAD, 1 biventricular assist device (BiVAD)). Of the 26 outflow grafts assessed, there was evidence of tissue ingrowth reaction in 24 (92%) grafts. The most common site was the distal anastomosis (18/24, 75%), with the graft body involved in 14 of 24 (58%) grafts. Microscopic evaluation revealed acute inflammatory infiltrate in 4 of 24 grafts (17%), chronic inflammatory infiltrate in 14 of 24 (58%), neointima formation in 18 of 24 (75%) and fibrosis in 18 of 24 (75%) grafts. The median depth of tissue was 1 mm (range, 0-2 mm). The mean conduit diameter was 9.5 ± 0.6 mm at the aortic anastomosis compared with 11.1 ± 0.5 mm 5 cm proximal to the anastomosis (p < 0.0001). In patients with unchanged pump speed one month after implantation, analysis of log files revealed a significant (5.8 ± 8.6%) decrease in pump flow (4.65 ± 0.86 vs 4.38 ± 0.92 L/min, p = 0.01) and flow pulsatility (5.00 ± 1.10 vs 4.16 ± 1.05 L/min, p = 0.006). CONCLUSIONS: There is evidence of tissue formation within the HVAD outflow conduit in the vast majority of patients, most commonly located at the aortic anastomosis. This is associated with significantly decreased pump flow over time.

Development of tibulizumab, a tetravalent bispecific antibody targeting BAFF and IL-17A for the treatment of autoimmune disease.

We describe a bispecific dual-antagonist antibody against human B cell activating factor (BAFF) and interleukin 17A (IL-17). An anti-IL-17 single-chain variable fragment (scFv) derived from ixekizumab (Taltz®) was fused via a glycine-rich linker to anti-BAFF tabalumab. The IgG-scFv bound both BAFF and IL-17 simultaneously with identical stoichiometry as the parental mAbs. Stability studies of the initial IgG-scFv revealed chemical degradation and aggregation not observed in either parental antibody. The anti-IL-17 scFv showed a high melting temperature (Tm) by differential scanning calorimetry (73.1°C), but also concentration-dependent, initially reversible, protein self-association. To engineer scFv stability, three parallel approaches were taken: labile complementary-determining region (CDR) residues were replaced by stable, affinity-neutral amino acids, CDR charge distribution was balanced, and a H44-L100 interface disulfide bond was introduced. The Tm of the disulfide-stabilized scFv was largely unperturbed, yet it remained monodispersed at high protein concentration. Fluorescent dye binding titrations indicated reduced solvent exposure of hydrophobic residues and decreased proteolytic susceptibility was observed, both indicative of enhanced conformational stability. Superimposition of the H44-L100 scFv (PDB id: 6NOU) and ixekizumab antigen-binding fragment (PDB id: 6NOV) crystal structures revealed nearly identical orientation of the frameworks and CDR loops. The stabilized bispecific molecule LY3090106 (tibulizumab) potently antagonized both BAFF and IL-17 in cell-based and in vivo mouse models. In cynomolgus monkey, it suppressed B cell development and survival and remained functionally intact in circulation, with a prolonged half-life. In summary, we engineered a potent bispecific antibody targeting two key cytokines involved in human autoimmunity amenable to clinical development.

Relationship of Inter-Individual Blood Pressure Variability and the Risk for Recurrent Stroke.

Background Evidence suggests that patients with higher blood pressure variability ( BPV ) have a higher risk for stroke, but any link between BPV and stroke recurrence is unknown among those who had a stroke or transient ischemic attack ( TIA ). Methods and Results Data for patients with a history of stroke or TIA at enrollment were extracted from the ASCOT (Anglo Scandinavian Cardiac Outcomes Trial) and the ALLHAT (Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial). BPV was defined as the within-subject standard deviation or coefficient of variation of systolic blood pressure across visits from 12 weeks poststroke or TIA onward. BPV was significantly higher in patients with a history of stroke or TIA than those without. BPV was a predictor of recurrent stroke in the pooled analysis. In the ASCOT study, 252 patients (12.3%) had a recurrent stroke among 2046 with a history of stroke. Incidence of recurrent stroke was significantly higher in the highest BPV quartile (17.8%) compared with the lowest quartile (10.5%); by treatment arm, this reached significance for the amlodipine-arm only (high- BPV : 18.7% versus low- BPV : 12.9%; P=0.029). Of the 2173 patients from the ALLHAT with a history of stroke or TIA , patients with the highest quartile of BPV had a higher incidence of recurrent stroke (9.6%) compared with the lowest quartile BPV (5.5%); by treatment arm, this reached significance for the chlorthalidone-arm only (high- BPV : 12.1% versus low- BPV : 5.4%; P=0.007). Conclusions Visit-to-visit BPV is a predictor of recurrent stroke in patients with a history of stroke or TIA on antihypertensive treatment. Considering BPV following a stroke may be important to reduce the risk for a recurrent stroke.

Get the Lead off Our Backs!

Many interventionalists face physical challenges almost daily for years or decades. The burden of assuming awkward positions while carrying extra weight can take its toll on the musculoskeletal system to such an extent that the career is ended or modified to exclude procedural aspects. The proliferation of lighter aprons has unfortunately resulted in reduced protection with poor correlation of protection to labeling due to the inadequacies of testing methods for nonlead materials. The protective quality of the non-leads is not superior to lead-containing composites on a weight basis, and the user no longer knows how well they are protected unless buying aprons containing lead. Various useful methods and shields that may reduce radiation exposure are supported by the floor, ceiling, table, or patient. The suspended personal radiation protection system is a recent development which provides substantially greater radiation protection than conventional lead aprons combined with other shields, while also taking all of the weight off of the operator. It is composed of an expansive and thick (1mm Pb equiv) apron with a large face-shield to protect the neck, head, and eyes, and is suspended overhead to provide motion in the x, y, and z planes. Exposures may also be substantially reduced by leaving the area during acquisition sequences and use of power injectors.

Relationship Between Visit-to-Visit Blood Pressure Variability (BPV) and Kidney Function in Patients with Hypertension.

BACKGROUND/AIMS: To investigate the impact of kidney function (using estimated glomerular filtration rate, [eGFR]) on blood pressure variability (BPV) via a retrospective post hoc analysis of patients with hypertension enrolled in two large clinical trials. METHODS: Subject-level data were extracted from ASCOT (N=18,852) and ALLHAT (N=26,441) databases; both were randomized, active controlled studies, with treatment duration for hypertension ≥4 years. Visit-to-visit BPV was assessed using the square root of the coefficient of variation of systolic blood pressure (SBP) across visits from 12 weeks onwards. Baseline GFR, estimated by the simplified Modification of Diet in Renal Disease equation, was stratified into ≤60, 61-90, and >90 mL/min/1.73 m2. The relationship between baseline eGFR and systolic BPV was analyzed using an analysis of covariance, with baseline factors considered as covariates. Studies were pooled and analyzed individually. RESULTS: Patient characteristics were largely consistent between studies. In the pooled population (n=38,133) there were 19.1%, 62.9%, and 18.0% patients, with eGFR ≤60, 61-90, and > 90 mL/min/1.73 m2, respectively. Patients with lower baseline eGFR had higher systolic BPV, in the pooled population and the individual analyses. Other baseline predictors of high systolic BPV included high SBP and age, being male, and a smoker. An amlodipine-based regimen was a negative predictor of high systolic BPV, vs. other antihypertensives, regardless of eGFR. CONCLUSIONS: Patients with declining renal function tended to have higher systolic BPV vs. those without, even after adjusting for risk factors. Amlodipine-based therapy reduced BPV more than other antihypertensive agents, regardless of level of eGFR.

Predictors of visit-to-visit blood pressure variability in patients with hypertension: an analysis of trials with an amlodipine treatment arm.

We conducted a post hoc analysis of blood pressure (BP) data from long-term antihypertensive trials to identify predictors of visit-to-visit BP variability (BPV). BPV was defined as the within-subject coefficient of variation in systolic BP from week 12 onward. BP data from the Anglo-Scandinavian Cardiac Outcomes Trial-Blood Pressure Lowering Arm, Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial, Comparison of Amlodipine Versus Enalapril to Limit Occurrences of Thrombosis, NY92011, and R-0510 trials were pooled and dichotomized into top 25th and bottom 75th percentiles because of positive skew. Significant (P < .001) predictors of BPV within the top 25th percentile were identified using logistic regression. The baseline characteristics of the pooled cohort (n = 47,558) were similar between patients who received amlodipine (n = 17,499) versus other antihypertensive drugs (n = 29,491). BPV in the top 25th percentile was lower with amlodipine versus other treatments (13.7 ± 3.2 vs. 14.3 ± 3.5), with single-study analyses of Anglo-Scandinavian Cardiac Outcomes Trial-Blood Pressure Lowering Arm, Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial, and Comparison of Amlodipine Versus Enalapril to Limit Occurrences of Thrombosis all showing BPV was the lowest with amlodipine. Baseline diastolic BP, estimated glomerular filtration rate, and smoking were predictors of BPV, with significant two-way interactions between smoking and both age and body mass index and between systolic BP or diastolic BP and being randomized to treatment other than amlodipine. In conclusion, analysis of BPV required transformation of BP data. After transformation, a number of baseline variables and combinations of variables were predictors of BPV.

Effect of inter-individual blood pressure variability on the progression of atherosclerosis in carotid and coronary arteries: a post hoc analysis of the NORMALISE and PREVENT studies.

Aims: To investigate the relationship between visit-to-visit blood pressure variability (BPV) and the progression of both carotid and coronary artery disease (CAD). Methods and results: Data from two cardiovascular endpoint studies [Norvasc for Regression of Manifest Atherosclerotic Lesions by Intravascular Sonographic Evaluation (NORMALISE) and Prospective Randomized Evaluation of the Vascular Effects of Norvasc Trial (PREVENT)] were analysed separately. Systolic BPV was assessed as within-subject standard deviation of systolic BP across visits from 12-weeks onwards. Follow-up was 24 months (NORMALISE) or 36 months (PREVENT). Any association between BPV and progression of atherosclerosis was assessed using quantitative coronary angiography (QCA), intravascular ultrasound (IVUS), or B-mode ultrasound (depending on study). Patients from NORMALISE (n = 261) and PREVENT (n = 688 for QCA; n = 364 for ultrasound) were stratified within study according to median systolic BPV. No significant difference in change of minimal luminal diameter (by QCA in PREVENT) or change in percent atheroma volume or normalized total atheroma volume (by IVUS in NORMALISE) was detected for subjects with low BPV (BPV < median) compared with high BPV (BPV ≥ median), regardless of treatment. In PREVENT, a significantly greater reduction in maximum carotid intima-media thickness (IMT) (left and right common carotid artery far wall) was observed for patients with BPV < median compared with those with BPV ≥ median [least squares mean difference 0.06 (95% confidence interval 0.01, 0.11); P = 0.0271], after adjusting for treatment, carotid artery segment (left or right), baseline maximum carotid IMT, and other baseline and cardiovascular risk factors/covariates. Conclusions: In patients with existing CAD and well-controlled BP, visit-to-visit BPV was not associated with progression of coronary atherosclerosis; however, a significantly greater reduction in maximum carotid IMT was observed for patients with low BPV.

Efficacy of Calcium Channel Blockers Versus Other Classes of Antihypertensive Medication in the Treatment of Hypertensive Patients With Previous Stroke and/or Coronary Artery Disease: A Systematic Review and Meta-Analysis.

Hypertensive patients, such as those with established coronary artery disease (CAD) or those who have suffered a stroke, are at increased risk of morbidity and mortality. This systematic literature review and meta-analysis assesses the long-term effects of calcium channel blockers (CCBs) compared with other classes of antihypertensive medications on major cardiovascular (CV) outcomes in these high-risk subgroups of hypertensive patients. Randomized, active controlled parallel group trials were included if they compared CCBs with α-blockers, ß-blockers, angiotensin II receptor blockers, angiotensin-converting enzyme inhibitors, or diuretics, had a follow-up of ≥6 months, and had assessments of blood pressure (BP) and CV events [all-cause death, CV death, major CV events (myocardial infarction, MI; congestive heart failure, CHF; stroke; and CV death), MI, stroke, or CHF] in patients with baseline systolic/diastolic BP ≥140/≥90 mm Hg with either concomitant previous stroke and/or CAD. The final dataset included 19 publications reporting on 7 unique trials. In hypertensive patients with previous stroke, there was no difference between CCBs and comparators for any CV outcome. In those with CAD, there was no difference for all-cause death, CV death, major CV events, and MI for CCBs relative to comparators; however, a reduction in the risk of stroke and an increase in the risk of CHF were seen. For BP lowering, CCBs were at least as efficacious as comparators. The findings of our systematic review and analysis add to the body of evidence for the use of CCBs for the long-term treatment of hypertension in difficult-to-treat high CV risk populations.

Effect of visit-to-visit blood pressure variability on cardiovascular events in patients with coronary artery disease and well-controlled blood pressure.

This post hoc analysis of CAMELOT and PREVENT analyzed the impact of blood pressure variability (BPV, assessed as within-subject standard deviation of SBP from 12 weeks onward) on the incidence of major adverse cardiovascular events (MACE, defined according to original studies). Patients (n = 1677 CAMELOT; n = 776 PREVENT) were stratified by BPV quartile. Regardless of study, BPV was significantly lower for amlodipine versus other treatments. In CAMELOT, a significant association between BPV quartile and MACE was observed with amlodipine treatment. Significant associations between BPV quartile and MACE were observed for both studies, when analyzed overall (adjusting for treatment). In CAMELOT, with amlodipine treatment, an increased risk for MACE was observed with high (BPV ≥ Q3) versus low BPV (< Q1; adjusting for characteristics and risk factors). In both studies, increased risk for MACE was observed for BPV ≥ Q3 versus BPV < Q1 (analyzed overall, adjusting for treatment and covariates). For both studies, BPV, but not mean SBP, was associated with cardiovascular events. BPV was associated with cardiovascular outcomes in patients with CAD and well-controlled BP.