Search

The application of machine learning to assess plaque risk phenotypes on cardiovascular CT angiography (CTA) is an area of active investigation. Studies using accepted histologic definitions of plaque risk as ground truth for machine learning models are uncommon. The aim was to evaluate the accuracy of a machine-learning software for determining plaque risk phenotype as compared to expert pathologists (histologic ground truth). Sections of atherosclerotic plaques paired with CTA were prospectively collected from patients undergoing carotid endarterectomy at two centers. Specimens were annotated for lipid-rich necrotic core, calcification, matrix, and intraplaque hemorrhage at 2 mm spacing and classified as minimal disease, stable plaque, or unstable plaque according to a modified American Heart Association histological definition. Phenotype is determined in two steps: plaque morphology is delineated according to histological tissue definitions, followed by a machine learning classifier. The performance in derivation and validation cohorts for plaque risk categorization and stenosis was compared to histologic ground truth at each matched cross-section. A total of 496 and 408 vessel cross-sections in the derivation and validation cohorts (from 30 and 23 patients, respectively). The software demonstrated excellent agreement in the validation cohort with histological ground truth plaque risk phenotypes with weighted kappa of 0.82 [0.78–0.86] and area under the receiver operating curve for correct identification of plaque type was 0.97 [0.96, 0.98], 0.95 [0.94, 0.97], 0.99 [0.99, 1.0] for unstable plaque, stable plaque, and minimal disease, respectively. Diameter stenosis correlated poorly to histologically defined plaque type; weighted kappa 0.25 in the validation cohort. A machine-learning software trained on histological ground-truth tissue inputs demonstrated high accuracy for identifying plaque stability phenotypes as compared to expert pathologists. [Display omitted] • Machine learning software based on histologically defined tissue characterization inputs demonstrated high accuracy for plaque risk phenotype determination compared to matched 2 mm tissue sample cross-sections: weighted kappa 0.82 and 0.70 in derivation and validation cohorts. • The area under the receiver operating curve for software correct identification of plaque type was 0.97, 0.95, 0.99 for unstable plaque, stable plaque, and minimal disease, respectively. • Percent lumen diameter stenosis per cross-section correlated poorly with plaque risk phenotypes. [ABSTRACT FROM AUTHOR]

Introduction: Abiraterone acetate plus prednisone (AA+P) has shown to significantly improve survival. COSMiC, a Canadian Observational Study in Metastatic Cancer of the Prostate, set out to prospectively amass real-world data on metastatic castrationresistant prostate cancer (mCRPC) patients managed with AA+P in Canada. Herein, we report their patient-reported outcomes (PROs). Methods: After a median followup of 67.1 weeks, 254 patients were enrolled across 39 sites. Functional Assessment of Cancer Therapy- Prostate (FACT-P), Montreal Cognitive Assessment (MoCA), Brief Pain Inventory-Short Form (BPI-SF), Brief Fatigue Inventory (BFI), and Current Health Satisfaction in Prostate Cancer (CHS-PCa) were evaluated at baseline, as well as at weeks 12, 24, 48, and 72 after AA+P initiation. Descriptive analysis was used with continuous variables. Changes from baseline were summarized using mean (standard deviation [SD]). Results: At a median age of 76.6 (8.94), baseline FACT-P total score was 111.3 (19.56) with no significant change in their functional status observed from baseline over time. The median baseline MoCA score was 25.2 (4.52), yet subsequent assessments showed an absence of cognitive decline while under treatment. Similarly, no meaningful changes were detected in BPI, BFI, and CHS-PCa during the 72-week study period, thus suggesting that patients' PROs were well-maintained throughout AA+P treatment. Prostatespecific antigen (PSA) response with >50% decline was 66.4%. Safety profile was consistent with the known side effect of AA+P. Conclusions: COSMiC represents the largest Canadian mCRPC cohort treated with AA+P with real-world, prospective evaluation of PROs. This data demonstrated the maintenance in quality of life and cognitive status over the course of the study and underscores the importance of PRO use in this complex patient population. [ABSTRACT FROM AUTHOR]

The possibility of obtaining potassium sulfate by converting calcium sulfate (phosphogypsum) and potassium chloride in an ammonia solution was investigated. The optimal conditions for the process at various concentrations of ammonia solution were determined. When using a 25% solution of NH3, the stirring time is 30–60 min, the consumption rate of KCl is 160% from stoichiometry. When using a 40% ammonia solution, the stirring time has practically no effect on the conversion, and the KCl consumption rate is only 120% from stoichiometry. The conversion temperature in both cases should be 15–20°C; the mass ratio of gypsum and ammonia should be 1 : (3–5). [ABSTRACT FROM AUTHOR]

Supporting families who have family members with intellectual and developmental disabilities (IDD) as they move through life is a critical need ( Reynolds, Palmer, & Gotto, 2018 ). The phrase, supporting families, juxtaposes the typical family support paradigm in response to the ongoing shrinkage of federal and state dollars and the recognition that parents and caregivers need services and supports to support their family member with IDD at home ( Amado, Stancliffe, McCarron, & McCallion, 2013 ). Within the family support movement, families are defined in the broadest terms, including those living in the same household, people who are affiliated by birth or choice, and others in the role of helping individuals with IDD succeed in life ( Reynolds et al., 2015 ; Turnbull, Turnbull, Erwin, Soodak, & Shogren, 2015 ). [ABSTRACT FROM AUTHOR]

Given its role in many biochemical processes essential to life, cholesterol remains a topic of intense research. Of all the plasma lipids, cholesterol is distinctive because it is a precursor to steroidogenic molecules, some of which regulate metabolism, and its blood concentration in the form of low- and high-density lipoprotein cholesterol (HDL-C) are positive and negative risk factors for atherosclerotic cardiovascular disease (ASCVD). New research, however, has challenged the widely held belief that high HDL-C levels are atheroprotective and is showing that both low and high plasma HDL-C levels confer an increased risk of ASCVD. Furthermore, it is disputing the widely cited mechanism involved in reverse cholesterol transport. This review explores the evolution of cholesterol research starting with the Gofman and Framingham studies, the development of traditional and emerging lipid-lowering therapies, and the role of reverse cholesterol transport in HDL cardioprotection. [ABSTRACT FROM AUTHOR]

Inflammation and lipid accumulation are two basic hallmarks of atherosclerosis as a chronic disease. Inflammation not only is a local response but can also be considered as a systemic process followed by an elevation of inflammatory mediators. Monocytes are a major source of proinflammatory species during atherogenesis. In atherosclerosis, modified low‐density lipoproteins (LDLs) are removed by macrophages; these are recruited in the vessel wall, inducing the release of inflammatory cytokines in inflamed tissue. Hence, inflammatory cholesterol ester‐loaded plaque is generated. High‐density lipoprotein‐cholesterol (HDL‐C) exhibits antiatherosclerotic effects by neutralizing the proinflammatory and pro‐oxidant effects of monocytes via inhibiting the migration of macrophages and LDL oxidation in addition to the efflux of cholesterol from these cells. Furthermore, HDL plays a role in suppressing the activation of monocytes and proliferation–differentiation of monocyte progenitor cells. Thus, accumulation of monocytes and reduction of HDL‐C may participate in atherosclerosis and cardiovascular diseases (CVD). Given that the relationship between the high number of monocytes and low HDL‐C levels has been reported in inflammatory disorders, this review focused on understanding whether the monocyte‐to‐HDL ratio could be a convenient marker to predict atherosclerosis development and progression, hallmarks of CV events, instead of the individual monocyte count or HDL‐C level. Monocytes are a major source of proinflammatory species during atherogenesis; in atherosclerosis, modified low‐density lipoproteins (LDLs) are removed by macrophages and these are recruited in the vessel wall, inducing the release of inflammatory cytokines in inflamed tissue generating inflammatory cholesterol ester‐loaded plaque. High‐density lipoprotein‐cholesterol (HDL‐C) exhibits antiatherosclerotic effects by neutralizing the proinflammatory and pro‐oxidant effects of monocytes via inhibiting the migration of macrophages and LDL oxidation in addition to the efflux of cholesterol from these cells; furthermore, HDL plays a role in suppressing the activation of monocytes and proliferation–differentiation of monocyte progenitor cells. Thus, accumulation of monocytes and reduction of HDL‐C may participate in atherosclerosis and cardiovascular diseases (CVD); given that the relationship between the high number of monocytes and low HDL‐C levels has been reported in inflammatory disorders, this review focused on understanding whether the monocyte‐to‐HDL ratio could be a convenient marker to predict atherosclerosis development and progression, hallmarks of CV events, instead of the individual monocyte count or HDL‐C level. [ABSTRACT FROM AUTHOR]

Aims To evaluate concordance, upgrades and downgrades from biopsy to prostatectomy, and associated clincopathological parameters, using the recently proposed Gleason grade groups/International Society of Urologic Pathology ( ISUP) grades. Methods and results We evaluated 2529 patients who underwent biopsy and prostatectomy in our institution from 2005 to 2014. A global grade group ( GR)/Gleason score ( GS) was used. Factors associated with GR1/ GS ≤6 upgrades and GR2/ GS3 + 4 downgrades were analysed by multivariable logistic regression. The final GR/ GS was identical with the biopsy GR/ GS in 59.3% of cases, with the highest concordance for GR2 and GR5 and lowest for GR4. In GR1-5, identical grades were found in GR: (i) 47.6%, (ii) 73.6%, (iii) 52.8%, (iv) 21.4% and (v) 68.3%, respectively. Final GR was upgraded in 32.3% cases; in GR1-4: (i) 52.4%, (ii) 19.0%, (iii) 16.4% and (iv) 32.9%. Most frequent upgrades occurred from biopsy GR1 to prostatectomy GR2. A final GR downgrade was found in 8.3% cases. For individual GR2-5 the downgrades were found in GR: (i) 7.4%, (ii) 30.8%, (iii) 45.7% and (iv) 31.7%. Upgrades of biopsy GR1 were associated with: age ≥60 years, PSA density ≥0.2, ≥2 positive cores, ≥5% core tissue involvement and perineural invasion [area under receiver operating characteristic ( ROC) curve 0.699]. Downgrades of biopsy GR2 correlated inversely with: age ≥60 years, PSA >10 ng/ml and ≥2 positive core (area under ROC curve 0.623). Conclusions We found highest concordance for GR2 and GR5 and lowest for GR4. The baseline clinical variables associated with GR1 upgrades and GR2 downgrades may play a role in clinical decision-making. [ABSTRACT FROM AUTHOR]

Background: High-density lipoprotein (HDL) cholesterol levels are a strong inverse predictor of cardiovascular events. However, it is not clear whether this association is maintained at very low levels of low-density lipoprotein (LDL) cholesterol.Methods: A post hoc analysis of the recently completed Treating to New Targets (TNT) study assessed the predictive value of HDL cholesterol levels in 9770 patients. The primary outcome measure was the time to a first major cardiovascular event, defined as death from coronary heart disease, nonfatal non-procedure-related myocardial infarction, resuscitation after cardiac arrest, or fatal or nonfatal stroke. The predictive relationship between HDL cholesterol levels at the third month of treatment with statins and the time to the first major cardiovascular event was assessed in univariate and multivariate analyses and was also assessed for specific LDL cholesterol strata, including subjects with LDL cholesterol levels below 70 mg per deciliter (1.8 mmol per liter).Results: The HDL cholesterol level in patients receiving statins was predictive of major cardiovascular events across the TNT study cohort, both when HDL cholesterol was considered as a continuous variable and when subjects were stratified according to quintiles of HDL cholesterol level. When the analysis was stratified according to LDL cholesterol level in patients receiving statins, the relationship between HDL cholesterol level and major cardiovascular events was of borderline significance (P=0.05). Even among study subjects with LDL cholesterol levels below 70 mg per deciliter, those in the highest quintile of HDL cholesterol level were at less risk for major cardiovascular events than those in the lowest quintile (P=0.03).Conclusions: In this post hoc analysis, HDL cholesterol levels were predictive of major cardiovascular events in patients treated with statins. This relationship was also observed among patients with LDL cholesterol levels below 70 mg per deciliter. (ClinicalTrials.gov number, NCT00327691 [ClinicalTrials.gov].). [ABSTRACT FROM AUTHOR]

BACKGROUND: There is a need for supports to promote self-determination in career development and employment that can be implemented by community support providers to address the poor employment outcomes of adults with disabilities. OBJECTIVE: The purpose of this study was to examine outcomes of implementation of the Self-Determined Career Development Model (SDCDM) when implemented in community-based support organizations by direct employment support providers. METHODS: Twenty-two community support provider organizations participated and were randomly assigned to a treatment (SDCDM) or control (business as usual) group; data were collected at three time points by facilitators on self-determination outcomes with 197 adults with disabilities. The data was analyzed using multilevel modeling and intraclass correlation coefficients were examined to determine the impact of the person with a disability, facilitator, and provider organization on outcomes. RESULTS AND CONCLUSIONS: Participants and the outcomes they experienced were influenced by multiple levels including each participant's own personal characteristics and experiences, as well as the characteristics of the facilitator they worked with and the organization that provided services. Autonomy showed greater change in the treatment group over time, compared to the control group. Implications for future research and practice are discussed. [ABSTRACT FROM AUTHOR]

Objective To assess the understanding of patients, who had previously undergone radical prostatectomy ( RP), about their postoperative sexual function, as clinical experience suggests that some RP patients have unrealistic expectations about their long-term sexual function. Patients and Methods Patients presenting within 3 months of their open RP or robot-assisted laparoscopic prostatectomy ( RALP) were questioned about the sexual function information that they had received preoperatively. Patients were questioned about erectile function ( EF), postoperative ejaculatory status, orgasm, and postoperative penile morphology changes. Statistical analyses were performed to assess for differences between patients who underwent open RP vs RALP. Results In all, 336 consecutive patients (from nine surgeons) with a mean ( SD) age of 64 (11) years had the survey instrument administered (216 underwent open RP and 120 underwent RALP). There were no significant differences in patient age or comorbidity profiles between the two groups. Only 38% of men had an accurate recollection of their nerve-sparing status. The mean ( SD) elapsed time after RP at the time of postoperative assessment was 3 (2) months. RALP patients expected a shorter EF recovery time (6 vs 12 months, P = 0.02), a higher likelihood of recovery back to baseline EF (75% vs 50%, P = 0.01), and a lower potential need for intracavernosal injection therapy (4% vs 20%, P = 0.01). Almost half of all patients were unaware that they were rendered anejaculatory by their surgery. None of the RALP patients and only 10% of open RP patients recalled being informed of the potential for penile length loss ( P < 0.01) and none were aware of the association between RP and Peyronie's disease. Conclusions Patients who have undergone RP have largely unrealistic expectations about their postoperative sexual function. [ABSTRACT FROM AUTHOR]

Research into the oxidation of lipoproteins has yielded many new insights into the pathogenesis of atherosclerosis. However, despite lipoprotein oxidation’s biologically plausible role in atherogenesis, several studies have reported inconsistent effects of antioxidants on clinical coronary end points, in sharp contrast with the studies of lipid modification with the 3-hydroxy-3-methylglutaryl coenzyme A inhibitors, or statins. There appears to be little support for the use of antioxidants in coronary prevention. However, the picture remains incomplete. What are the limitations of available antioxidant studies and the agents used? Until the picture can be clarified, lipid modification with strategies proved to reduce the risk for coronary events, such as statins or dietary changes in the style of the Mediterranean diet, should be better implemented in clinical practice. [Copyright &y& Elsevier]

Introduction: Despite high-level evidence of benefit, early repeat resection (ERR) among high-grade T1 bladder cancer (HGT1-BC) patients remains low in several non-Canadian jurisdictions and rates in Canada are largely unreported. We evaluated rates of ERR and trends over time in Alberta. We also examined factors associated with uptake of ERR. Methods: We conducted a retrospective review of data from all patients diagnosed with HGT1-BC from 2007 through 2011. Patients were identified from the Alberta Cancer Registry. Patients with a non-urothelial carcinoma of the bladder and those with invasion into the prostate or metastatic disease were excluded. We collected demographic and clinicopathologic information from patients' electronic medical records. Results: A total of 600 patients diagnosed with HCT1-BC were included. Overall, 1 67 patients (27.8%) received an ERR; however, the rate increased in a non-linear fashion from 27.4% in 2007 to 37.8% in 2011. Factors associated with ERR included age <80 years (p=0.021 ) and centre at which the initial transurethral resection of bladder tumour (TURBT) was performed (p=0.013). Median overall survival (OS) was not reached, but five-year OS was 72.7% (95% Cl 68.9, 76.5) for those who received an ERR and 55.3% (95% Cl 52.5, 58.1 ) for those who did not. Conclusions: Use of ERR in patients with HGT1-BC is improving over time. Regional variation in practice suggests the need for implementation strategies (i.e., provincial clinical care pathways) to standardize practice and set indicators for future measurement and reporting. Targeted interventions would require further investigation around the reasons for variation in practice. [ABSTRACT FROM AUTHOR]

The rapid growth in the understanding of the relation between cholesterol and coronary heart disease has introduced new challenges to the contemporary management of lipid disorders. The publication of the trials of the 3-hydroxy-3-methylglutaryl coenzyme-A inhibitors (statins) has invigorated support for the lipid hypothesis, and many advances have been made in understanding the mechanisms underlying atherosclerosis and the potential benefits of the statins. Several international groups have issued guidelines about desirable and undesirable lipid values to help clinical decision making. Despite the availability of such principles, there are many challenges to optimal management of lipid disorders. [ABSTRACT FROM AUTHOR]

This cost-consequences analysis of the Air Force/Texas Coronary Atherosclerosis Prevention Study compares the costs of lovastatin treatment with the costs of cardiovascular hospitalizations and procedures. The cost of lovastatin treatment was defined as the average retail price and the cost of drug safety monitoring and adverse experiences. Costs were determined by actual rates of hospitalizations and procedures. Within a trial, lovastatin treatment cost approximately $4,654/patient. Lovastatin treatment significantly reduced the cumulative rate of cardiovascular hospitalizations and procedures (p = 0.002). Over the duration of the study, the cumulative number of cardiovascular hospitalizations and related therapeutic procedures was significantly reduced by 29%. The time to first cardiovascular-related hospitalization or procedure was significantly extended by lovastatin (p = 0.002). Lovastatin reduced the frequency of cardiovascular hospitalization (28%), and cardiovascular therapeutic (32%) and diagnostic procedures (23%). Among therapeutic procedures, treatment reduced coronary artery bypass graft surgery by 19% and percutaneous transluminal coronary angioplasty by 37%. Total cardiovascular-related hospital days were reduced by 26% (p = 0.025). The between-group offset in direct medical costs was $524, which resulted in a 11% cost offset of lovastatin therapy over the mean study duration of 5.2 years. Lovastatin provides meaningful reductions in cardiovascular-related resource utilization and reductions in direct cardiovascular-related costs associated with the onset of coronary disease. [ABSTRACT FROM AUTHOR]

The article analysis cardiovascular outcomes in individuals with type 1 and type 2 diabetes and coronary disease. Topics discussed include risks of mortality and morbidity associated with the same; gender differences in symptoms of ischemic heart disease; and strategies for managing and preventing the same.

As a core unit of our society, the family provides support for all its members. Due to the nature of their disabilities, people with intellectual and developmental disabilities (IDD) often receive emotional, physical, and material support from their families across the life course. During the National Goals 2015 Conference, three goals were identified that will lead to a better understanding of families and maximize their capacity, strengths, and unique abilities to support, nurture, and facilitate opportunities for family members who have a disability. The three goals are to (1) develop a better understanding of the complex family structures in the United States and the best practices for supporting them; (2) extend our knowledge on how families are or might be supported by their natural communities, outside the purview of IDD systems; and (3) synthesize support practices, implementation strategies, and outcomes for supporting families. This article describes these three goals related to supporting families across the life course and provides a rationale, areas of research to address the goals, and implications for policy and practice for each goal. [ABSTRACT FROM AUTHOR]

More than 25 years of clinical trial data have established statins as first-line therapy for the prevention and treatment of atherosclerotic cardiovascular disease. With regard to low-density lipoprotein cholesterol, a wealth of evidence indicates that 'lower is better,' although recent guidelines from the American College of Cardiology and the American Heart Association take a different approach. A variety of approved and experimental lipid-lowering agents may be used as supplements or alternatives to statin therapy in patient subgroups, including those with familial hypercholesterolemia, mixed dyslipidemia or statin intolerance. Strategies to achieve further reductions in low-density lipoprotein cholesterol, target high-density lipoprotein cholesterol and triglycerides or reduce inflammation may help address residual cardiovascular risk, although early lifestyle interventions are crucial to prevention strategies. [ABSTRACT FROM AUTHOR]

In the more than 50 years since the founding of the National Heart, Lung, and Blood Institute and the American Heart Association, medical science has moved from an era in which hypercholesterolemia, as it is now defined, was not believed to be abnormal to one in which controlling hypercholesterolemia is known to reduce not only coronary artery disease morbidity and mortality but also total mortality. While the efforts and successes of many researchers involved in this evolution are impressive, atherosclerosis is still a major cause of death and disability in many developed nations, mostly in the form of myocardial infarction and stroke, and is an increasing cause of morbidity and mortality in developing nations. Many questions about the detailed pathogenesis of the disease remain. Elucidating the roles of high-density lipoprotein, other lipoproteins, and homocysteine, as well as the roles of cytokines and growth factors, will permit better understanding and treatment of atherosclerosis. With continuing support for research and encouragement of physicians and patients to follow recommended preventive regimens, further progress can be made against this major cause of death. [ABSTRACT FROM AUTHOR]

The data for an independent association between triglyceride concentrations and risk for coronary artery disease (CAD) are equivocal, unlike the data for low-density lipoprotein (LDL) cholesterol and high-density lipoprotein (HDL) cholesterol, which show strong, consistent, and opposing correlations with CAD risk. There is some evidence for triglyceride as an independent risk factor in certain subgroups, for example, women 50-69 years of age (Framingham Heart Study) and in patients with noninsulin-dependent diabetes. However, the evidence is stronger for triglyceride as a synergistic CAD risk factor. For example, patients with the "lipid triad" of high LDL cholesterol, low HDL cholesterol, and high triglyceride accounted for most of the event reduction with lipid-lowering therapy in the Helsinki Heart Study. An important confounder of the correlation between triglyceride and CAD risk is the heterogeneity of triglyceride-rich lipoproteins: the larger triglyceride-rich particles are thought not to be associated with CAD risk, whereas the smaller (and denser) particles are believed to be atherogenic. At present, measurement of fasting triglyceride levels and triglyceride assessment in conjunction with LDL cholesterol and HDL cholesterol concentrations are the most practical methods of evaluating hypertriglyceridemia in CAD risk, although postprandial lipemia may prove a better indicator of atherogenicity. Management of hypertriglyceridemia should initially focus on nonpharmacologic therapy (i.e., diet, exercise, weight control, and alcohol reduction). In diabetic patients, meticulous glycemic control is also important. However, if this approach proves inadequate, there are several pharmacologic options. Fibrates may be effective in decreasing triglyceride and increasing HDL cholesterol. Nicotinic acid (niacin) has been shown to decrease triglyceride, increase HDL cholesterol, lower LDL cholesterol, and decrease lipoprotein(a); it also decreases fibrinogen. The statins appear to be effective in decreasing triglyceride and LDL cholesterol in hypertriglyceridemia; however, they do not normalize metabolism of apolipoprotein B, and HDL cholesterol may remain low. Therefore, combination with a fibrate or niacin may be appropriate. Attention to hypertriglyceridemia with respect to increased CAD risk represents an important step in assessing global risk for CAD development. [ABSTRACT FROM AUTHOR]

The aim of this study was to assess the effects on lipids and safety during a 12-week reversal period after 18 months of treatment with anacetrapib. The cholesteryl ester transfer protein inhibitor anacetrapib was previously shown to reduce low-density lipoprotein cholesterol by 39.8% (estimated using the Friedewald equation) and increase high-density lipoprotein (HDL) cholesterol by 138.1%, with an acceptable side-effect profile, in patients with or at high risk for coronary heart disease in the Determining the Efficacy and Tolerability of CETP Inhibition With Anacetrapib (DEFINE) trial. A total of 1,398 patients entered the 12-week reversal-phase study, either after completion of the active-treatment phase or after early discontinuation of the study medication. In patients allocated to anacetrapib, placeboadjusted mean percentage decreases from baseline were observed at 12 weeks off the study drug for Friedewald-calculated low-density lipoprotein cholesterol (18.6%), non-HDL cholesterol (17.6%), and apolipoprotein B (10.2%); placebo-adjusted mean percentage increases were observed for HDL cholesterol (73.0%) and apolipoprotein A-I (24.5%). Residual plasma anacetrapib levels (about 40% of on-treatment apparent steady-state trough levels) were also detected 12 weeks after cessation of anacetrapib. No clinically important elevations in liver enzymes, blood pressure, electrolytes, or adverse experiences were observed during the reversal phase. Preliminary data from a small cohort (n [ 30) revealed the presence of low concentrations of anacetrapib in plasma 2.5 to 4 years after the last anacetrapib dose. In conclusion, after the cessation of active treatment, anacetrapib plasma lipid changes and drug levels decreased to approximately 40% of on-treatment trough levels at 12 weeks after dosing, but modest HDL cholesterol elevations and low drug concentrations were still detectable 2 to 4 years after the last dosing. [ABSTRACT FROM AUTHOR]

Objectives: The purpose of this paper was to assess whether statins reduce all-cause mortality and cardiovascular (CV) events in elderly people without established CV disease. Background: Because of population aging, prevention of CV disease in the elderly is relevant. In elderly patients with previous CV events, the use of statins is recommended by guidelines, whereas the benefits of these drugs in elderly subjects without previous CV events are still debated. Methods: Randomized trials comparing statins versus placebo and reporting all-cause and CV mortality, myocardial infarction (MI), stroke, and new cancer onset in elderly subjects (age ≥65 years) without established CV disease were included. Results: Eight trials enrolling 24,674 subjects (42.7% females; mean age 73.0 ± 2.9 years; mean follow up 3.5 ± 1.5 years) were included in analyses. Statins, compared with placebo, significantly reduced the risk of MI by 39.4% (relative risk [RR]: 0.606 [95% confidence interval (CI): 0.434 to 0.847]; p = 0.003) and the risk of stroke by 23.8% (RR: 0.762 [95% CI: 0.626 to 0.926]; p = 0.006). In contrast, the risk of all-cause death (RR: 0.941 [95% CI: 0.856 to 1.035]; p = 0.210) and of CV death (RR: 0.907 [95% CI: 0.686 to 1.199]; p = 0.493) were not significantly reduced. New cancer onset did not differ between statin- and placebo-treated subjects (RR: 0.989 [95% CI: 0.851 to 1.151]; p = 0.890). Conclusions: In elderly subjects at high CV risk without established CV disease, statins significantly reduce the incidence of MI and stroke, but do not significantly prolong survival in the short-term. [ABSTRACT FROM AUTHOR]

The widespread clinical use of statins has contributed to significant reductions in the rate of cardiovascular morbidity and mortality over the past 3 decades, and statins are considered first-line therapy for the prevention and treatment of atherosclerotic vascular disease. Nevertheless, various other lipid-lowering agents can provide clinical benefit by supplementing or augmenting statin therapy in patients with severe hypercholesterolaemia or mixed dyslipidaemia, or by providing an alternative for patients who are intolerant to statins. Bile acid resins and niacin were prescribed for lipid modification for years before the introduction of the statins, and new data continue to emerge regarding their use in different patient groups and for specific conditions. Ezetimibe can be appropriate for patients whose primary lipid abnormality is an elevated LDL-cholesterol level, whereas the fibrates seem to be most beneficial in patients with low levels of HDL cholesterol and elevated triglycerides. At the end of 2012 and the beginning of 2013, the first microsomal triglyceride transfer protein inhibitor, Iomitapide, and the first antisense therapy to target apolipoprotein B, mipomersen, were approved for the treatment of individuals with extremely elevated LDL-cholesterol levels caused by homozygous familial hypercholesterolaemia. Although two agents in the experimental class of cholesteryl ester transfer protein inhibitors have failed to show a benefit in clinical trials, newer drugs in this class could provide an additional strategy to address residual cardiovascular risk in patients treated with statins. [ABSTRACT FROM AUTHOR]

The risk of suicide in the cancer population is real, and it requires nurses to be able to assess and manage such risk competently. This article supports the idea that oncology nurses need to be comfortable with identifying, assessing, and appropriately triaging depressed and possibly suicidal patients with cancer to appropriate specialists, given the increased risk of suicidal ideation and completion in the cancer population. The goal of this article is to help oncology nurses identify the specific risk factors for suicide in their patients with cancer, feel confident and prepared with an accurate assessment, and provide the necessary interventions. [ABSTRACT FROM AUTHOR]

Physicians regularly encounter suffering in patients who may be seriously or chronically ill, disabled, or dying. This article explores the question of why God allows suffering and considers the Book of Job in particular for insights on the role of faith in suffering. It examines how society has viewed disease as a manifestation of God across history and presents several perspectives on the relationship between disease, suffering, and religion, including potential implications for the contemporary practice of medicine and personal reflections. [ABSTRACT FROM PUBLISHER]

Lymphocele is the most common complication of pelvic lymphadenectomy (PLND). We sought to determine predictors of symptomatic lymphocele after radical prostatectomy (RP) and PLND, and in particular, to determine if the number of drains placed represents an independent predictor. Between January 1999 and June 2007, 4173 consecutive patients underwent bilateral PLND at the time of either open or laparoscopic RP. Lymphoceles were identified in patients undergoing imaging as a result of symptoms suspicious for lymphocele, such as fever, abdominal pain or lower extremity swelling. Routine postoperative imaging was not carried out. Cox proportional hazards analysis was carried out using forced variable entry to obtain maximum likelihood estimates of the hazard ratios and 95% confidence intervals using the number of drains placed, number of nodes removed, RP approach and use of prophylactic low-molecular-weight heparin (LMWH) as predictors of symptomatic lymphocele. There were 164 patients (4%) with a symptomatic lymphocele on follow up, with a median time to presentation of 19 days. The primary presenting complaints were fever in 47%, abdominal pain in 40%, lower extremity swelling in 37%, genital swelling in 25%, groin pain in 22%, abdominal swelling in 9%, and back and flank pain in 6% and 5%, respectively. Median lymphocele diameter was 5 cm. Significant predictors of symptomatic lymphocele on multivariate analysis included number of nodes removed and use of LMWH, but not number of drains placed. Use of prophylactic LMWH and a higher node count are predictive of a higher incidence of symptomatic lymphocele after RP and PLND. [ABSTRACT FROM AUTHOR]

Objective: The objective of this study was to assess the characteristics of publications by members of the Canadian Urological Association (CUA) over a 10-year period. Methods: All publications by active CUA members during the periods January 1993-December 1994 and January 2003-December 2004 were reviewed. Results: Of the 487 active members in 1993-1994, 130 (26.7%) were authors a total of 649 times in 641 publications. External funding was acknowledged in 195 (30.4%). There were 131 observational studies (20.4%), 127 review articles (19.8%), 58 case reports (9.0%), 37 case series (5.8%), and 21 randomized controlled trials (RCTs) (3.3%). Of the 454 active member in 2003-2004, 139 (30.6%) were authors a total of 748 times in 705 publications. External funding was acknowledged in 237 (33.6%). There were 153 observational studies (21.7%), 124 review articles (17.6%), 52 case reports (7.4%), 49 case series (7.0%), and 46 RCTs (6.5%). There were significantly more RCTs and clinical trials in 2003-2004. The most common journal was The Journal of Urology in both eras. There were significantly more publications in The Canadian Journal of Urology, the British Journal of Urology International and the Journal of Endourology in 2003-2004. There were significantly more publications acknowledging industry funding and more publications citing more than 1 CUA member in 2003-2004. Publication intensity increased significantly from 0.67 to 0.82 publications per member, per year for the CUA as a whole. Interpretation: Scholarly activity has remained robust over the last decade with over 30% of active CUA members contributing to peer-reviewed literature. Higher levels of evidence are now observed with a greater number of RCTs. CUA members should be proud of their academic productivity. [ABSTRACT FROM AUTHOR]

This article presents findings from two early intervention agencies examining how administrative structures affect providers' ability to serve families of young children with disabilities. Based on previous research identifying three administrative structures (i.e., vision/leadership, organizational climate, and resources), this article illustrates the relationship between administrative structures, provider practices, and family supports and services. Findings include (a) the role of administrators' knowledge and vision influencing provider practices, (b) the importance of organizational climates that foster partnership and peer support for implementing and evaluating practices, (c) the effects of resource allocation decisions on family supports and services, and (d) the need for accountability to ensure effective practices and family supports and services. [ABSTRACT FROM AUTHOR]

Background: High-density lipoprotein (HDL) cholesterol levels are a strong inverse predictor of cardiovascular events. However, it is not clear whether this association is maintained at very low levels of low-density lipoprotein (LDL) cholesterol. Methods: A post hoc analysis of the recently completed Treating to New Targets (TNT) study assessed the predictive value of HDL cholesterol levels in 9770 patients. The primary outcome measure was the time to a first major cardiovascular event, defined as death from coronary heart disease, nonfatal non–procedure-related myocardial infarction, resuscitation after cardiac arrest, or fatal or nonfatal stroke. The predictive relationship between HDL cholesterol levels at the third month of treatment with statins and the time to the first major cardiovascular event was assessed in univariate and multivariate analyses and was also assessed for specific LDL cholesterol strata, including subjects with LDL cholesterol levels below 70 mg per deciliter (1.8 mmol per liter). Results: The HDL cholesterol level in patients receiving statins was predictive of major cardiovascular events across the TNT study cohort, both when HDL cholesterol was considered as a continuous variable and when subjects were stratified according to quintiles of HDL cholesterol level. When the analysis was stratified according to LDL cholesterol level in patients receiving statins, the relationship between HDL cholesterol level and major cardiovascular events was of borderline significance (P=0.05). Even among study subjects with LDL cholesterol levels below 70 mg per deciliter, those in the highest quintile of HDL cholesterol level were at less risk for major cardiovascular events than those in the lowest quintile (P=0.03). Conclusions: In this post hoc analysis, HDL cholesterol levels were predictive of major cardiovascular events in patients treated with statins. This relationship was also observed among patients with LDL cholesterol levels below 70 mg per deciliter. (ClinicalTrials.gov number, NCT00327691.) N Engl J Med 2007;357:1301-10. [ABSTRACT FROM AUTHOR]

Abstract: AFCAPS/TexCAPS was the first prevention trial of a statin conducted in a low-to-moderate—risk cohort that included men (≥45 years) and women (≥55 years) with no evidence of atherosclerotic cardiovascular disease. At study entry, LDL-C had to be 130–190mg/dL and HDL-C ≤45mg/dL for men and ≤47mg/dL for women. Participants were randomized to either lovastatin 20–40mg/day (n =3304) or placebo (n =3301) for a mean follow-up period of 5.2 years. At 1 year, in the lovastatin group TC, LDL-C, and TG were reduced by 18.4%, 25.0%, and 15%, respectively. HDL-C increased by 6.0%. At 5 years, there was a 37% decrease in the relative risk for having a first acute coronary event in the lovastatin versus placebo group. Women showed similar relative risk reduction as men. Older individuals benefited as much as younger ones from lovastatin. Subjects with ≥2 risk factors benefited more from statin than those with <2 risk factors. At baseline, HDL-C but not TC or LDL-C was determined a significant predictor of risk. On treatment, ApoB and ApoA1 were the best predictors. Based on AFCAPS/TexCAPS, a simple heuristic could be that individuals with “age plus one other risk factor” may benefit from statin therapy in primary prevention. [Copyright &y& Elsevier]

Given the limitations of current risk assessment strategies, adjunctive markers are needed to improve the prediction of a first coronary event. Research into the inflammatory nature of atherosclerosis suggests that inflammatory-response proteins may serve as potential predictors of clinical events. One in particular, C-reactive protein, has been the focus of much attention. Epidemiologic studies have shown a fairly consistent independent association between high-sensitivity C-reactive protein (hs-CRP) elevations and coronary risk, although a causal relation has not yet been established. Given this association, current guidelines recommend the optional use of hs-CRP to predict enhanced absolute risk in selected patients. The use of a marker in general clinical practice should be based on statistical measures that show incremental benefit over established risk factors and on randomized clinical trials in which therapy initiated as a result of marker screening improves patient outcomes. Thus far, statistical evidence concerning the incremental benefit of hs-CRP is not conclusive. Justification for the Use of Statins in Primary Prevention: An Intervention Trial Evaluating Rosuvastatin (JUPITER) is now being conducted to compare the efficacy of statin therapy versus placebo in subjects considered to be at increased risk on the basis of hs-CRP elevations, despite low to normal levels of low-density lipoprotein cholesterol. In conclusion, although epidemiologic studies suggest that low-grade C-reactive protein elevations are independently associated with coronary risk, more complete evidence is needed to validate the use of hs-CRP as a risk assessment tool in general practice and as a target for therapy in individual patients. [Copyright &y& Elsevier]

A social worker and a psychologist, working with troubled youth in a day treatment setting, describe unique ways to use the concepts of Positive Peer Culture (PPC) to facilitate groups from the elementary to high school levels. The authors have adapted the well-known PPC concepts and incorporated them into their strength-based program, SPLASH, to promote problem solving (Heckenlaible-Gotto & Roggow, in development). [ABSTRACT FROM AUTHOR]

This article describes an evaluation conducted with a juvenile who was facing transfer into the adult system after an encounter with law enforcement officers. Adopted at age one from an Eastern European orphanage, Andrei experienced conflict, bringing him into contact with special education, mental health, and juvenile authorities. While there were bright spots in his school and work history, a common theme in diagnostic records was a focus on deficits which obscured his strengths and resilience. Facing a court hearing, Andrei's family secured an independent evaluation. This Developmental Audit® provided a strikingly different view of the boy who was little known beyond his large box of case files documenting failed interventions. [ABSTRACT FROM AUTHOR]

Restoration of anti-viral immune response may be a requisite for sustained virological response to treatment in chronic hepatitis B patients. Over a 13-month period, we examined the dynamics of hepatitis B virus (HBV)-specific CD8+ cells in six human leucocyte antigen (HLA)-A2+ hepatitis B e antigen (HBeAg)+ ‘immunotolerant’ chronic hepatitis B patients treated sequentially with corticosteroid and lamivudine. Our results show that the combination treatment did not result in a sustained restoration of anti-viral specific CD8+ cells in five of the six patients studied. However, HBV-specific CD8+ cells, despite being severely compromised, were not totally deleted. Paradoxically, steroid treatment was not associated with inhibition but with a minimal increase of the HBV-specific CD8 response, and we observed that nucleocapsid-specific CD8 responses were not rescued by stable and prolonged inhibition but became detectable after rapid rebounds of HBV replication. In most patients, the transient and minimal restoration of HBV-specific immunity was not associated with clinical benefits. Our results describe a dynamic relationship between HBV-specific CD8+ cells and HBV-DNA values, that could potentially be used for a better design of HBV treatment in HBeAg+ ‘immunotolerant’ chronic hepatitis B patients. [ABSTRACT FROM AUTHOR]

Abstract: Cardiovascular disease (CVD) is the leading cause of death in Europe and the US. This paper reviews the evolution of the Joint European Societies’ guidelines with respect to their lipid recommendations. We stress the importance of lowering lipid levels to, or below, the currently recommended goals and argue that patients’ global risk for CVD, rather than baseline lipid levels, should direct the intensity of lipid-lowering treatment. However, the emphasis on near-term (i.e., in the next 10 years) global risk estimation may under-emphasize the importance of considering lifetime cardiovascular risk in treatment decisions. Although various guidelines’ thresholds for treatment initiation and recommended goals differ, they are similar in the theme of treating global risk. Most clinical trials have not identified a threshold of cholesterol level beyond which lowering cholesterol levels no longer provides cardiovascular benefit. An urgent call for action is needed to improve goal attainment in patients with or at risk for CVD. Improving access to risk-reducing treatments should be a priority. [Copyright &y& Elsevier]

There are overwhelming data in favor of cholesterol as a modifiable risk factor for coronary artery disease (CAD). Lifestyle modifications are considered first-line treatments for lowering cholesterol, but drug therapies are recommended in at-risk groups. Trials published before the National Cholesterol Education Program (NCEP) Adult Treatment Panel (ATP) III reports have helped statins emerge at the forefront of lipid therapies, and more recent trials have shed light on high-risk prevention. Although 6 statins are currently available, large clinical trials reported thus far have mainly evaluated atorvastatin, lovastatin, pravastatin, and simvastatin in the prevention of CAD and other cardiovascular events. A few small end point trials have evaluated fluvastatin, whereas rosuvastatin trials are only in their early days. [Copyright &y& Elsevier]

Hepatitis C is a hepatotropic RNA virus with a propensity to cause chronic infection, causing a worldwide burden of chronic hepatitis, cirrhosis and hepatocellular carcinoma. Both viral elimination and hepatocellular damage are thought to be immune mediated with T-helper and cytotoxic T-lymphocytes central to these events. A delay in the onset of adaptive immunity following infection indicates that a defect in the innate immune response may lead to viral persistence with a combination of other mechanisms subsequently contributing. Antiviral therapy based on interferon-α leads to resolution of disease in approximately 50% of patients. Specific anti-hepatitis C anti-viral drugs are being developed. [Copyright &y& Elsevier]

Clinical data show that a 1% increase in serum concentrations of high-density lipoprotein cholesterol (HDL-C) can decrease cardiovascular risk by 2% to 3%. Therefore, mechanisms affecting the level and functionality of high-density lipoprotein (HDL) and its constituents are being investigated as targets for the rational development of drugs to prevent or treat cardiovascular disease. High-density lipoprotein-related research may also increase our understanding of the link between atherosclerosis and metabolic disorders. This report and update of the HDL Working Group discusses HDL metabolism and reverse cholesterol transport, impaired HDL as a marker and a cause of proatherogenic states, and experimental and current approaches to HDL-related therapy. [Copyright &y& Elsevier]

Objective: To document the needs and resources of indigenous people with disabilities. Study Design: An analysis of 5 descriptive studies. Setting: Oaxaca City and various rural and remote areas of Oaxaca, Mexico. Research Participants: Individuals with disabilities and their families, both urban and rural, representing a wide age span. Main Outcome Measures: Interview protocols developed through participatory research procedures involving persons with disabilities. Results: Across populations, the need for centers of education, training, and support was identified; however, medical intervention was the primary need. Conclusions: The Vecinos project demonstrates the successes of cooperative research efforts between university-based researchers and grassroots leaders with disabilities, with implications for change in public policy and practice to accommodate indigenous people with disabilities. [ABSTRACT FROM AUTHOR]

Atherosclerosis is a form of arterial disease that manifests in the coronary circulation as coronary artery disease (CAD), in the carotid arteries as cerebrovascular disease, and in the aorta and lower extremity arteries as peripheral arterial disease (PAD). The systemic nature of the disease is reflected in the fact that individuals with PAD or carotid artery disease are more likely to have CAD than those without. Since individuals with PAD are at markedly increased risk of cardiovascular ischemic events, early identification of this population and more aggressive medical interventions could substantially improve both morbidity and survival. The incidence of PAD in the general population is high, and currently affects 8–10 million Americans. The risk of developing PAD is predicted by both age and common atherosclerosis risk factors (e.g., smoking and diabetes). Efficient office-based PAD detection depends on the application of objective techniques to establish this diagnosis. Objective noninvasive tests, such as measurement of the ankle–brachial index (ABI), are known to be more sensitive than traditional clinical assessments. Since the major threat to patients with PAD is from secondary cardiovascular ischemic events, a primary therapeutic goal is to modify atherosclerotic risk factors. While national recommendations mandate aggressive lowering of serum low-density lipoprotein cholesterol (LDL-C) levels as a primary treatment goal in all patients with overt atherosclerosis, as 'coronary heart disease risk equivalent' syndromes, individuals with PAD are less intensively treated than those with CAD. Statins are the most effective of current treatments in lowering LDL-C, and have proven efficacy in secondary prevention among patients with established CAD. The use of statin medications in high-risk groups such as PAD patients could prove particularly beneficial in reducing cardiovascular morbidity and mortality and therefore merits prospective clinical investigation. [ABSTRACT FROM AUTHOR]

Focuses on the clinical trials of statin therapy in different populations. Clinical and surrogate endpoint trials on elderly patients; Clinical trials on patients with diabetes mellitus; Clinical and surrogate endpoint trials on women; Effect of statins on lipid lowering to prevent ischemic events.

Discusses the data from the Air Force/Texas Coronary Atherosclerosis Prevention Study, which involved patients with average cholesterol levels and reduced high-density lipoprotein cholesterol. Effects of statin therapy on coronary artery disease events; Importance of on-treatment values of apolipoproteins B and A-1; Challenges for future treatment guidelines.

Reports on therapeutic options for the management of dyslipidemia for patients at risk for coronary artery disease. Approximation of the population; Identification of over-the-counter (OTC)-type subgroup; Reduction in the incidence of myocardial infarction; Treatment effects in the OTC-type subgroup; Safety and tolerability of treatment.

Assesses therapeutic benefits of statin treatment in an over-the-counter (OTC)-like population. Use of Air Force/Texas Coronary Atherosclerosis Prevention Study; Treatment of the respondents with either lovastatin or placebo; Decrease incidence of heart diseases upon statin treatment; Implications for the identification and treatment of persons at risk for coronary disease.

ABSTRACT Background Methods Results Conclusions Androgen‐deprivation therapy (ADT) remains a cornerstone in treatment for patients with advanced prostate cancer. ADT is associated with several adverse effects, including osteoporosis, metabolic syndrome, and cardiovascular events, leading to guidelines recommending routine testing to monitor for these toxicities. There is a lack of data assessing adherence to these recommendations.The authors conducted a retrospective cohort study using administrative data from Ontario, Canada between 2008 and 2021. They identified all older men (aged 65 years and older) who received ADT for prostate cancer using comprehensive provincial health databases. The primary outcomes were the use of testing for lipids, dysglycemia (glucose), bone health serum, and bone density between 6 weeks before and 1 year after the initiation of ADT.In total, 29,097 patients were examined, of whom 52.8% were prescribed ADT by urologists, 37.9% were prescribed ADT by radiation oncologists, 2.8% were prescribed ADT by medical oncologists, and 2.4% were prescribed ADT by other physicians. Adherence to guidelines was low: only 21.3% of patients received a bone density scan, 41.2% underwent bone health–related serum tests, 51.3% completed a lipid profile, and 65.9% underwent dysglycemia testing within 1 year of diagnosis. Overall, only 11.9% of patients received all of the recommended investigations. Adherence to testing did not appear to improve over time (2008–2021) or with guideline publication. Patient (age) and physician (specialty) factors had important associations with adherence to testing.Most patients receiving ADT for prostate cancer do not receive recommended testing to monitor for treatment‐related toxicity. Further study is required to address barriers to therapeutic monitoring of men on ADT and to reduce treatment‐associated adverse events. [ABSTRACT FROM AUTHOR]