John, Mathew; Gopalakrishnan Unnikrishnan, Ambika; Kalra, Sanjay; Nair, Tiny
Since the time questions arose on cardiovascular safety of Rosiglitazone, FDA has suggested guidelines on conduct of studies on anti-diabetic drugs so as to prove that the cardiovascular risk is acceptable. Based on the cardiovascular risks of pre-approval clinical trials, guidelines have been made to conduct cardiovascular safety outcome trials (CVSOTs) prior to the drug approval or after the drug has been approved. Unlike the trials comparing the efficacy of antidiabetic agents, the CVSOTs examine the cardiovascular safety of a drug in comparison to standard of care. These trials are expensive aspects of drug development and are associated with various technical and operational challenges. More cost effective models of assessing cardiovascular safety like use of biomarkers, electronic medical records, pragmatic and factorial designs can be adopted. This article critically looks at the antidiabetic drug approval from a cardiovascular perspective by asking a few questions and arriving at answers. PMID:27543483
Fiorentino, Teresa Vanessa; Sesti, Giorgio
Previous trials of glucose-lowering strategies in subjects with type 2 diabetes have demonstrated a beneficial effect of intensive glycemic control on microvascular complications but failed to show a clear benefit on cardiovascular complications. The findings of meta-analyses of rosiglitazone trials suggesting that rosiglitazone might increase the risk of myocardial infarction have cast doubt on the cardiovascular safety of glucose-lowering drugs. In 2008, the US Food and Drug Administration has implemented rigorous criteria to approve new glucose-lowering drugs, requiring proof of cardiovascular safety. These regulatory requirements have led to a considerable increase in the number of cardiovascular outcome trials in type 2 diabetes to ensure that newer glucose-lowering drugs are not associated with increased cardiovascular risk. Incretin-based therapies including dipeptidyl peptidase 4 (DPP-4) inhibitors, and injectable glucagon-like peptide 1 (GLP-1) receptor agonists are novel treatment options for patients with inadequate glucose control. Although DPP-4 inhibitors have shown neutral effects on risk factors for cardiovascular diseases, it remains unclear whether treatment with these new glucose-lowering agents might be associated with a reduction in cardiovascular events. The results of the three cardiovascular outcome trials comparing DPP-4 inhibitors treatment to placebo in addition to other glucose-lowering drugs have been published. All the three DPP-4 inhibitor cardiovascular outcome trials have shown non-inferiority with regard to cardiovascular safety, compared with placebo, when added to usual care. In this review, we summarize cardiovascular outcome trials of DPP-4 inhibitors, and provide an overview of these trials and their limitations. PMID:26611248
Full Text Available BACKGROUND: Antioxidant vitamin (vitamin E, beta-carotene, and vitamin C are widely used for preventing major cardiovascular outcomes. However, the effect of antioxidant vitamin on cardiovascular events remains unclear. METHODOLOGY AND PRINCIPAL FINDINGS: We searched PubMed, EmBase, the Cochrane Central Register of Controlled Trials, and the proceedings of major conferences for relevant literature. Eligible studies were randomized controlled trials that reported on the effects of antioxidant vitamin on cardiovascular outcomes as compared to placebo. Outcomes analyzed were major cardiovascular events, myocardial infarction, stroke, cardiac death, total death, and any possible adverse events. We used the I(2 statistic to measure heterogeneity between trials and calculated risk estimates for cardiovascular outcomes with random-effect meta-analysis. Independent extraction was performed by two reviewers and consensus was reached. Of 293 identified studies, we included 15 trials reporting data on 188209 participants. These studies reported 12749 major cardiovascular events, 6699 myocardial infarction, 3749 strokes, 14122 total death, and 5980 cardiac deaths. Overall, antioxidant vitamin supplementation as compared to placebo had no effect on major cardiovascular events (RR, 1.00; 95%CI, 0.96-1.03, myocardial infarction (RR, 0.98; 95%CI, 0.92-1.04, stroke (RR, 0.99; 95%CI, 0.93-1.05, total death (RR, 1.03; 95%CI, 0.98-1.07, cardiac death (RR, 1.02; 95%CI, 0.97-1.07, revascularization (RR, 1.00; 95%CI, 0.95-1.05, total CHD (RR, 0.96; 95%CI, 0.87-1.05, angina (RR, 0.98; 95%CI, 0.90-1.07, and congestive heart failure (RR, 1.07; 95%CI, 0.96 to 1.19. CONCLUSION/SIGNIFICANCE: Antioxidant vitamin supplementation has no effect on the incidence of major cardiovascular events, myocardial infarction, stroke, total death, and cardiac death.
Avogaro, Angelo; Fadini, Gian Paolo; Sesti, Giorgio; Bonora, Enzo; Del Prato, Stefano
Diabetic patients suffer from a high rate of cardiovascular events and such risk increases with HbA1c. However, lowering HbA1c does not appear to yield the same benefit on macrovascular endpoints, as observed for microvascular endpoints. As the number of glucose-lowering medications increases, clinicians have to consider several open questions in the management of type 2 diabetes, one of which is the cardiovascular risk profile of each regimen. Recent placebo-controlled cardiovascular outcome trials (CVOTs) have responded to some of these questions, but careful interpretation is needed. After general disappointment around CVOTs assessing safety of DPP-4 inhibitors (SAVOR, TECOS, EXAMINE) and the GLP-1 receptor agonist lixisenatide (ELIXA), the EMPA-REG Outcome trial and the LEADER trial have shown superiority of the SGLT2-I empagliflozin and the GLP-1RA liraglutide, respectively, on the 3-point MACE outcome (cardiovascular death, non-fatal myocardial infarction or stroke) and cardiovascular, as well as all-cause mortality. While available mechanistic studies largely support a cardioprotective effect of GLP-1, the ability of SGLT2 inhibitor(s) to prevent cardiovascular death was unexpected and deserves future investigation. We herein review the results of completed CVOTs of glucose-lowering medications and suggest a possible treatment algorithm based on cardiac and renal co-morbidities to translate CVOT findings into clinical practice. PMID:27514514
Rydén, Lars; Shahim, Bahira; Mellbin, Linda
Cardiovascular disease is a major threat to people with diabetes. Attempts have long been made to lower cardiovascular risk by means of glucose-lowering treatment. Initially, it seemed that was an option, but subsequent trials could not verify the original observations and there was concern that some glucose-lowering drugs can actually cause cardiovascular harm. This led medical product agencies in the United States and Europe to require major outcomes trials before accepting new glucose-lowering drugs. The least requirement was noninferiority compared with existing treatment modalities. A large number of such trials have been performed or are ongoing, including >100,000 patients. The drug classes investigated are basal insulin, glucagon-like peptide-1 agonists, dipeptidyl peptidase 4 inhibitors, and sodium-glucose cotransporter-2 (SGLT2) inhibitors. This commentary discusses these trials and their outcomes, the reasons why several of them ended with neutral results (noninferiority), and that the likelihood for showing cardiovascular benefit was minor or even nonexistent. The surprising and highly rewarding impact of the SGLT2 inhibitor empagliflozin is described and potential mechanisms for cardiovascular benefits are discussed. PMID:27107734
Mannucci, Edoardo; Mosenzon, Ofri; Avogaro, Angelo
The U.S. Food and Drug Administration requires that the cardiovascular (CV) safety of all new drugs for diabetes be demonstrated through pooled analyses of phase III studies or specifically designed trials. This requirement prompted several placebo-controlled, noninferiority CV safety trials in high-risk patients; to date, all completed trials showed that dipeptidyl peptidase (DPP)-4 inhibitors do not increase or reduce the risk of major CV events. These results apparently contrast with those of pooled analyses and meta-analyses of previous, smaller trials with metabolic end points, which had suggested a reduction of risk. However, the design of CV trials, which were required to demonstrate safety, is not adequate (for duration, management of concurrent therapies, etc.) for the assessment of potential therapeutic benefits. In addition, CV safety trials enroll patients at high risk of CV events, who are different from those included in earlier trials with metabolic end points. Differences in characteristics of patients enrolled probably account for most of the discrepancy in CV outcomes between CV safety studies and earlier trials. The availability of several large-scale trials with longer duration provides the unique opportunity for assessment of the safety of DPP-4 inhibitors not only with respect to major CV events but also with reference to other safety issues. For example, CV safety trials can be a source of information for pancreatitis, cancer, or hypoglycemia. PMID:27440833
Inzucchi, Silvio E; Zinman, Bernard; Wanner, Christoph; Ferrari, Roberto; Fitchett, David; Hantel, Stefan; Espadero, Rosa-Maria; Woerle, Hans-Jürgen; Broedl, Uli C; Johansen, Odd Erik
Given the multi-faceted pathogenesis of atherosclerosis in type 2 diabetes mellitus (T2DM), it is likely that interventions to mitigate this risk must address cardiovascular (CV) risk factors beyond glucose itself. Sodium glucose cotransporter-2 (SGLT-2) inhibitors are newer antihyperglycaemic agents with apparent multiple effects. Inherent in their mode of action to decrease glucose reabsorption by the kidneys by increasing urinary glucose excretion, these agents improve glycaemic control independent of insulin secretion with a low risk of hypoglycaemia. In this review, we outline those CV risk factors that this class appears to influence and provide the design features and trial characteristics of six ongoing outcome trials involving more than 41,000 individuals with T2DM. Those risk factors beyond glucose that can potentially be modulated positively with SGLT-2 inhibitors include blood pressure, weight, visceral adiposity, hyperinsulinaemia, arterial stiffness, albuminuria, circulating uric acid levels and oxidative stress. On the other hand, small increases in low-density lipoprotein (LDL)-cholesterol levels have also been observed for the class, which theoretically might offset some of these benefits. The potential translational impact of these effects is being tested with outcome trials, also reviewed in this article, powered to assess both macrovascular as well as certain microvascular outcomes in T2DM. These are expected to begin to report in late 2015. PMID:25589482
Full Text Available BACKGROUND: Hormone replacement therapy (HRT is widely used to controlling menopausal symptoms and prevent adverse cardiovascular events. However, the benefit and risk of HRT on cardiovascular outcomes remains controversial. METHODOLOGY AND PRINCIPAL FINDINGS: We systematically searched the PubMed, EmBase, and Cochrane Central Register of Controlled Trials databases for obtaining relevant literature. All eligible trials reported on the effects of HRT on cardiovascular outcomes. We did a random effects meta-analysis to obtain summary effect estimates for the clinical outcomes with use of relative risks calculated from the raw data of included trials. Of 1903 identified studies, we included 10 trials reporting data on 38908 postmenopausal women. Overall, we noted that estrogen combined with medroxyprogesterone acetate therapy as compared to placebo had no effect on coronary events (RR, 1.07; 95%CI: 0.91-1.26; P = 0.41, myocardial infarction (RR, 1.09; 95%CI: 0.85-1.41; P = 0.48, stroke (RR, 1.21; 95%CI: 1.00-1.46; P = 0.06, cardiac death (RR, 1.19; 95%CI: 0.91-1.56; P = 0.21, total death (RR, 1.06; 95%CI: 0.81-1.39; P = 0.66, and revascularization (RR, 0.95; 95%CI: 0.83-1.08; P = 0.43. In addition, estrogen therapy alone had no effect on coronary events (RR, 0.93; 95%CI: 0.80-1.08; P = 0.33, myocardial infarction (RR, 0.95; 95%CI: 0.78-1.15; P = 0.57, cardiac death (RR, 0.86; 95%CI: 0.65-1.13; P = 0.27, total mortality (RR, 1.02; 95%CI: 0.89-1.18; P = 0.73, and revascularization (RR, 0.77; 95%CI: 0.45-1.31; P = 0.34, but associated with a 27% increased risk for incident stroke (RR, 1.27; 95%CI: 1.06-1.53; P = 0.01. CONCLUSION/SIGNIFICANCE: Hormone replacement therapy does not effect on the incidence of coronary events, myocardial infarction, cardiac death, total mortality or revascularization. However, it might contributed an important role on the risk of incident stroke.
Colivicchi F.; Sternhufvud C; Gandhi SK
Furio Colivicchi,1 Catarina Sternhufvud,2 Sanjay K Gandhi3 1Cardiology Division, Emergency Department, San Filippo Neri Hospital, ASL Roma E, Rome, Italy; 2Global Payer Evidence and Pricing, AstraZeneca R&D, Mölndal, Sweden; 3Global Health Economics and Outcomes Research, TEVA Pharmaceuticals, Frazer, PA, United States Objective: No clinical trials have been conducted to directly compare the effect of the two high-intensity statins, rosuvastatin and atorvastatin, on cardiovascular ou...
Kjøller, Erik; Hilden, Jørgen; Winkel, Per;
UNLABELLED: The objective of this study is to describe the agreement between randomized trial outcome assessment by committee and outcomes entirely identified through public registers. METHODS: In the CLARICOR trial, 4,372 patients with stable coronary heart disease received a short course...... of clarithromycin versus placebo and were followed up for 2.6 years. The pertinent hospital records and death certificates had originally been evaluated by the adjudication committee using common definitions of outcomes mapped into a 6-category list. We now mechanically converted the International Classification...... of Diseases-coded diagnoses of the public registries into the same categories. After cross-tabulation of the committee diagnoses with National Patient Register diagnoses and Register of Causes of Death, we calculate agreement and compare the estimated intervention effects of the 2 data sets. RESULTS...
Fitchett, David; Zinman, Bernard; Wanner, Christoph; Lachin, John M.; Hantel, Stefan; Salsali, Afshin; Johansen, Odd Erik; Woerle, Hans J.; Broedl, Uli C.; Inzucchi, Silvio E.
Aims We previously reported that in the EMPA-REG OUTCOME® trial, empagliflozin added to standard of care reduced the risk of 3-point major adverse cardiovascular events, cardiovascular and all-cause death, and hospitalization for heart failure in patients with type 2 diabetes and high cardiovascular risk. We have now further investigated heart failure outcomes in all patients and in subgroups, including patients with or without baseline heart failure. Methods and results Patients were randomi...
Full Text Available Furio Colivicchi,1 Catarina Sternhufvud,2 Sanjay K Gandhi3 1Cardiology Division, Emergency Department, San Filippo Neri Hospital, ASL Roma E, Rome, Italy; 2Global Payer Evidence and Pricing, AstraZeneca R&D, Mölndal, Sweden; 3Global Health Economics and Outcomes Research, TEVA Pharmaceuticals, Frazer, PA, United States Objective: No clinical trials have been conducted to directly compare the effect of the two high-intensity statins, rosuvastatin and atorvastatin, on cardiovascular outcomes. However, three such trials have been computer-simulated using the Archimedes model, an individual-based simulation of human physiology and behaviors, treatment interventions, and health care systems. The results are reviewed here.Methods: The first simulated trial assessed clinical outcomes in patients receiving available doses of the two drugs. The second assessed the impact of initial treatment decisions, while the third assessed the effect of switching from rosuvastatin to atorvastatin.Results: In the first simulated trial, treatment with rosuvastatin was estimated to result in greater reductions than treatment with atorvastatin in major adverse cardiac event (MACE rates at 5 years and 20 years at all doses examined (relative risk [RR]: 0.897, 0.888, and 0.930 at 5 years for rosuvastatin 20 mg vs atorvastatin 40 mg, rosuvastatin 40 mg vs atorvastatin 80 mg, and rosuvastatin 20 mg vs atorvastatin 80 mg, respectively; all P<0.05. In the second simulated trial, outcomes were significantly better in patients initially prescribed rosuvastatin than in those initially prescribed atorvastatin (RR of MACE at 5 years: 0.918; P<0.001. In the third simulated trial, risk of MACE was significantly greater in patients switching from rosuvastatin to atorvastatin than in those remaining on rosuvastatin (RR at 5 years: 1.109; P<0.001.Conclusion: The results of these simulated clinical trials suggest improved outcomes among patients receiving rosuvastatin relative to
Fiorentino, Teresa Vanessa; Sesti, Giorgio
Clinical trials of glucose-lowering strategies in patients with type 2 diabetes mellitus (T2DM) have shown a favorable effect of intensive glycemic control on microvascular complications but failed to show a clear benefit on cardiovascular events. In 2008, the US Food and Drug Administration (FDA) and European Medicines Agency (EMA) have required stringent criteria to approve new glucose-lowering drugs, demanding proof of cardiovascular safety. As a result of these regulatory requirements, a number of cardiovascular outcome trials in T2DM have been conducted examining the cardiovascular safety of novel glucose-lowering drugs. Dipeptidyl peptidase 4 (DPP4) inhibitors, analogs of glucagon-like peptide 1 (GLP-1), and inhibitors of the renal sodium-glucose linked transporter-2 (SGLT2) are new classes of glucose-lowering drugs for subjects with T2DM. The results of the cardiovascular outcome trials comparing the DPP4 inhibitors saxagliptin, alogliptin, and sitagliptin or the GLP-1 analog lixisenatide to placebo have demonstrated that these drugs are safe. The results of a cardiovascular outcome trial comparing the SGLT2 inhibitor empagliflozin to placebo have been published. Notably, empagliflozin treatment has been associated with a significant reduction in the primary composite cardiovascular outcome. Although the question regarding the positive effect of glycemic control on cardiovascular risk is still unanswered, current evidence suggests that a multifactorial approach aimed at treating not only hyperglycemia but also classical cardiovascular risk factors is necessary in order to reduce the risk of cardiovascular events in patients with T2DM. PMID:27030121
Weight and blood pressure response to weight management and sibutramine in diabetic and non-diabetic high-risk patients: an analysis from the 6-week lead-in period of the sibutramine cardiovascular outcomes (SCOUT) trial
Van Gaal, L F; Caterson, I D; Coutinho, W;
To assess treatment responses to sibutramine and weight management in diabetic patients during the lead-in period of the Sibutramine Cardiovascular OUTcomes (SCOUT) trial.......To assess treatment responses to sibutramine and weight management in diabetic patients during the lead-in period of the Sibutramine Cardiovascular OUTcomes (SCOUT) trial....
Schnell, Oliver; Standl, Eberhard; Catrinoiu, Doina; Genovese, Stefano; Lalic, Nebojsa; Skra, Jan; Valensi, Paul; Ceriello, Antonio
The 1st Cardiovascular Outcome Trial (CVOT) Summit of the Diabetes & Cardiovascular Disease (D&CVD) EASD Study Group was held during the annual meeting on 30 October 2015 in Munich. This summit was organized in light of recently published and numerous ongoing CVOTs on diabetes, which have emerged in response to the FDA and the EMA Guidelines. The CVOT Summit stands as a novel conference setup, with the aim of serving as a reference meeting for all topics related to CVOTs in diabetes. Members of the steering committee of the D&CVD EASD Study Group constitute the backbone of the summit. It included presentations of key results on DPP-4 inhibitors, GLP-1-Analogues, SGLT-2 inhibitors, acarbose and insulins. Diabetologists' and cardiologists' perspective on the potential need of new study designs were also highlighted. Furthermore, panel discussions on the design of CVOTs on diabetes were included in the program. The D&CVD EASD Study Group will continue its activity. In-depth discussions and presentations of new CVOTs like LEADER, will be resumed at the 2nd CVOT on diabetes of the D&CVD EASD Study Group, which will be held from 20-22 October 2016 in Munich ( http://www.dcvd.org). PMID:26892706
Caterson, I D; Finer, N; Coutinho, W;
Aim: The Sibutramine Cardiovascular OUTcomes trial showed that sibutramine produced greater mean weight loss than placebo but increased cardiovascular morbidity but not mortality. The relationship between 12-month weight loss and subsequent cardiovascular outcomes is explored. Methods: Overweight...... randomization to first occurrence of a primary outcome event (non-fatal myocardial infarction, non-fatal stroke, resuscitated cardiac arrest or cardiovascular death). Results: For the total population, mean weight change during Lead-in Period (sibutramine) was -2.54 kg. Post-randomization, mean total weight...... change to Month 12 was -4.18 kg (sibutramine) or -1.87 kg (placebo). Degree of weight loss during Lead-in Period or through Month 12 was associated with a progressive reduction in risk for the total population in primary outcome events and cardiovascular mortality over the 5-year assessment. Although...
Zinman, Bernard; Inzucchi, Silvio E.; Lachin, John M.; Wanner, Christoph; Ferrari, Roberto; Fitchett, David; Bluhmki, Erich; Hantel, Stefan; Kempthorne-Rawson, Joan; Newman, Jennifer; Johansen, Odd Erik; Woerle, Hans-Juergen; Broedl, Uli C.
Background Evidence concerning the importance of glucose lowering in the prevention of cardiovascular (CV) outcomes remains controversial. Given the multi-faceted pathogenesis of atherosclerosis in diabetes, it is likely that any intervention to mitigate this risk must address CV risk factors beyond glycemia alone. The SGLT-2 inhibitor empagliflozin improves glucose control, body weight and blood pressure when used as monotherapy or add-on to other antihyperglycemic agents in patients with ty...
Farkouh, M.E.; Kirshner, H.; Harrington, R.A.; Ruland, S.; Verheugt, F.W.A.; Schnitzer, T.J.; Burmester, G.R.; Mysler, E.; Hochberg, M.C.; Doherty, M.; Ehrsam, E.; Gitton, X.; Krammer, G.; Mellein, B.; Gimona, A.; Matchaba, P.; Hawkey, C.J.; Chesebro, J.H.
BACKGROUND: The potential for cyclo-oxygenase 2 (COX2)-selective inhibitors to increase the risk for myocardial infarction is controversial. The Therapeutic Arthritis Research and Gastrointestinal Event Trial (TARGET) aimed to assess gastrointestinal and cardiovascular safety of the COX2 inhibitor l
Zinman, Bernard; Inzucchi, Silvio E.; Lachin, John M.; Wanner, Christoph; Ferrari, Roberto; Fitchett, David; Bluhmki, Erich; Hantel, Stefan; Kempthorne-Rawson, Joan; Newman, Jennifer; Johansen, Odd Erik; Woerle, Hans-Juergen; Broedl, Uli C.
Background: Evidence concerning the importance of glucose lowering in the prevention of cardiovascular (CV) outcomes remains controversial. Given the multi-faceted pathogenesis of atherosclerosis in diabetes, it is likely that any intervention to mitigate this risk must address CV risk factors beyond glycemia alone. The SGLT-2 inhibitor empagliflozin improves glucose control, body weight and blood pressure when used as monotherapy or add-on to other antihyperglycemic agents in patients with t...
Padial, Luis Rodríguez
Ezetimibe is a drug that impairs intestinal cholesterol absorption and decreases blood cholesterol levels. It has been shown that added to statins it can achieve a further reduction of low-density lipoprotein-cholesterol of 18-20%, overcoming the increase in absorption that follow the reduction in cholesterol synthesis by statins. Four major outcome trials are underway to study the effect of ezetimibe plus simvastatin in different subsets of high-risk patients: familiar hypercholesterolemia, degenerative aortic stenosis, chronic kidney disease and acute coronary syndrome. Hopefully, in the next few years the information provided by these trials will allow us to further reduce the increasing burden of cardiovascular disease. PMID:18095904
Diederichsen, Axel Cosmus Pyndt; Rasmussen, Lars Melholt; Søgaard, Rikke;
to be 70 %. DISCUSSION: The primary aim of this so far stand-alone population-based, randomized trial will be to evaluate the health benefits and costeffectiveness of using non-contrast full truncus computer tomography (CT) scans (to measure coronary artery calcification (CAC) and identify aortic...... cardiovascular seven-faceted screening examinations at one of four locations. The screening will include: (1) low-dose non-contrast CT scan to detect coronary artery calcification and aortic/iliac aneurysms, (2) brachial and ankle blood pressure index to detect peripheral arterial disease and hypertension, (3) a...... events, and whether the possible health benefits are cost effective. OUTCOME: Registry-based follow-up on all cause death (primary outcome), and costs after 3, 5 and 10 years (secondary outcome). RANDOMIZATION: Each of the 45,000 individuals is, by EPIDATA, given a random number from 1-100. Those...
Schernthaner, Guntram; Schernthaner-Reiter, Marie Helene; Schernthaner, Gerit-Holger
During the last decade, the armamentarium for glucose-lowering drugs has increased enormously by the development of DPP-4 inhibitors, GLP-1 receptor agonists and SGLT2 inhibitors, allowing individualization of antidiabetic therapy for patients with type 2 diabetes (T2DM). Some combinations can now be used without an increased risk for severe hypoglycemia and weight gain. Following a request of the US Food and Drug Administration, many large cardiovascular (CV) outcome studies have been performed in patients with longstanding disease and established CV disease. In the majority of CV outcome studies, CV risk factors were well controlled and a high number of patients were already treated with ACE inhibitors/angiotensin receptor blockers, statins and antiplatelet drugs. Most studies with insulin glargine and newer glucose-lowering drugs (saxagliptin, alogliptin, sitagliptin, lixisenatide) demonstrated safety of newer glucose-lowering agents but did not show superiority in the CV outcomes compared with placebo. By contrast, in the EMPA-REG OUTCOME (Empagliflozin Cardiovascular Outcome Event Trial in Type 2 Diabetes Mellitus Patients) study, CV death, all-cause mortality, and hospitalization for heart failure were significantly decreased when empagliflozin was added instead of placebo to therapy for patients with high CV risk and T2DM already well treated with statins, glucose-lowering drugs, and blood pressure-lowering drugs as well as antiplatelet agents. In addition, renal endpoints including endstage renal disease were also significantly reduced when empagliflozin was added instead of placebo. Interestingly, the reduction of these clinically relevant end points was observed after a few months, making antiatherogenic effects an unlikely cause. The fact that the incidence of myocardial infarction (MI) and stroke were not reduced is in line with the hypothesis that hemodynamic factors in particular have contributed to the impressive improvement of the prognosis. To
Home, Philip D; Pocock, Stuart J; Beck-Nielsen, Henning;
BACKGROUND: Rosiglitazone is an insulin sensitiser used in combination with metformin, a sulfonylurea, or both, for lowering blood glucose in people with type 2 diabetes. We assessed cardiovascular outcomes after addition of rosiglitazone to either metformin or sulfonylurea compared with the comb...
An association between nonalcoholic fatty liver disease and cardiovascular disease has been repeatedly reported. Several studies have focused on levels of gamma-glutamyltransferase (GGT) and alanine aminotransferase (ALT) in relation to cardiovascular outcomes. Evidence indicates that GGT may have a potential role for cardiovascular risk stratification while the role of ALT for cardiac prognosis remains controversial. A conceptual framework that includes not only GGT and ALT but also markers ...
Braga Angelica F; Cecatti Jose G; Pereira Rosa I; Baciuk Erica P; Cavalcante Sergio R
Abstract Background To evaluate the association between water aerobics, maternal cardiovascular capacity during pregnancy, labor and neonatal outcomes. Methods A randomized, controlled clinical trial was carried out in which 34 pregnant women were allocated to a water aerobics group and 37 to a control group. All women were submitted to submaximal ergometric tests on a treadmill at 19, 25 and 35 weeks of pregnancy and were followed up until delivery. Oxygen consumption (VO2 max), cardiac outp...
Sattar, N.; McLaren, J; Kristensen, SL; Preiss, D; McMurray, JJ
While the modest reduction in the primary composite outcome of myocardial infarction, stroke or cardiovascular death in the EMPA-REG Outcomes trial was welcome, the 30–40% reductions in heart failure hospitalisation (HFH) and cardiovascular and all-cause deaths in patients treated with empagliflozin were highly impressive and unexpected. In this review, we discuss briefly why cardiovascular endpoint trials for new diabetes agents are required and describe the results of the first four such tr...
Sattar, Naveed; McLaren, James; Kristensen, Soren L.; Preiss, David; McMurray, John J V
While the modest reduction in the primary composite outcome of myocardial infarction, stroke or cardiovascular death in the EMPA-REG Outcomes trial was welcome, the 30–40% reductions in heart failure hospitalisation (HFH) and cardiovascular and all-cause deaths in patients treated with empagliflozin were highly impressive and unexpected. In this review, we discuss briefly why cardiovascular endpoint trials for new diabetes agents are required and describe the results of the first four such tr...
Andersson, Charlotte; Weeke, Peter; Fosbøl, Emil Loldrup;
Low levels of bilirubin are associated with an increased risk of cardiovascular adverse events. Weight reduction is known to reduce several cardiovascular risk factors, but effects on bilirubin levels have not been reported. We studied the response of weight loss therapy with sibutramine and life...
Theilade, S; Claggett, B; Hansen, T W;
Pulse pressure (PP) remains an elusive cardiovascular risk factor with inconsistent findings. We clarified the prognostic value in patients with type 2 diabetes, chronic kidney disease (CKD) and anemia in the Trial to Reduce cardiovascular Events with Aranesp (darbepoetin alfa) Therapy. In 4038...... with type 2 diabetes, CKD and anemia, PP did not independently predict cardiovascular events or ESRD. This may reflect confounding by aggressive antihypertensive treatment, or PP may be too rough a risk marker in these high-risk patients.Journal of Human Hypertension advance online publication, 26 March...
Forman, Daniel E; Alexander, Karen; Brindis, Ralph G; Curtis, Anne B; Maurer, Mathew; Rich, Michael W; Sperling, Laurence; Wenger, Nanette K
Longevity is increasing and the population of older adults is growing. The biology of aging is conducive to cardiovascular disease (CVD), such that prevalence of coronary artery disease, heart failure, valvular heart disease, arrhythmia and other disorders are increasing as more adults survive into old age. Furthermore, CVD in older adults is distinctive, with management issues predictably complicated by multimorbidity, polypharmacy, frailty and other complexities of care that increase management risks (e.g., bleeding, falls, and rehospitalization) and uncertainty of outcomes. In this review, state-of-the-art advances in heart failure, acute coronary syndromes, transcatheter aortic valve replacement, atrial fibrillation, amyloidosis, and CVD prevention are discussed. Conceptual benefits of treatments are considered in relation to the challenges and ambiguities inherent in their application to older patients. PMID:26918183
Sharma, A M; Caterson, I D; Coutinho, W;
cardiovascular event. During the 6-week lead-in period, 10,742 patients received sibutramine and weight management. Vital sign changes were assessed post hoc by initial blood pressure (mmHg) categorized as normal (<130/<85), high-normal (130 to <140/85 to <90) or hypertensive (>or=140/>or=90); weight change...... in the class of antihypertensive medication used and who did not report an increase in antihypertensive medication use were analysed. RESULTS: At entry, approximately 50% of patients were hypertensive and 26% were high-normal. In hypertensive patients, blood pressure changes (mmHg) decreased by...... categories (weight gain/no weight change, >0 to 2.5% weight loss, >2.5 to 5% weight loss and >5% weight loss) and current antihypertensive medication class use (none, one, or two or more). To assess the impact of sibutramine on blood pressure and pulse rate, only patients (N = 10,025) who reported no change...
Patel, Ravi B; Vaduganathan, Muthiah; Samman-Tahhan, Ayman; Kalogeropoulos, Andreas P; Georgiopoulou, Vasiliki V; Fonarow, Gregg C; Gheorghiade, Mihai; Butler, Javed
Surrogate endpoints facilitate trial efficiency but are variably linked to clinical outcomes, and limited data are available exploring their utilization in cardiovascular clinical trials over time. We abstracted data regarding primary clinical, intermediate, and surrogate endpoints from all phase II to IV cardiovascular clinical trials from 2001 to 2012 published in the 8 highest Web of Science impact factor journals. Two investigators independently classified the type of primary endpoint. Of the 1,224 trials evaluated, 677 (55.3%) primary endpoints were clinical, 165 (13.5%) intermediate, and 382 (31.2%) surrogate. The relative proportions of these endpoints remained constant over time (p = 0.98). Trials using surrogate endpoints were smaller (187 vs 1,028 patients) and enrolled patients more expeditiously (1.4 vs 0.9 patients per site per month) compared with trials using clinical endpoints (p <0.001 for both comparisons). Surrogate endpoint trials were independently more likely to meet their primary endpoint compared to trials with clinical endpoints (adjusted odds ratio 1.56, 95% CI 1.05 to 2.34; p = 0.03). Rates of positive results in clinical endpoint trials have decreased over time from 66.1% in 2001 to 2003 to 47.2% in 2010 to 2012 (p = 0.001), whereas these rates have remained stable over the same period for surrogate (72.0% to 69.3%, p = 0.27) and intermediate endpoints (74.4% to 71.4%, p = 0.98). In conclusion, approximately a third of contemporary cardiovascular trials use surrogate endpoints. These trials are completed more expeditiously and are more likely to meet their primary outcomes. The overall scientific contribution of these surrogate endpoint trials requires further attention given their variable association with definitive outcomes. PMID:27085935
Braga Angelica F
Full Text Available Abstract Background To evaluate the association between water aerobics, maternal cardiovascular capacity during pregnancy, labor and neonatal outcomes. Methods A randomized, controlled clinical trial was carried out in which 34 pregnant women were allocated to a water aerobics group and 37 to a control group. All women were submitted to submaximal ergometric tests on a treadmill at 19, 25 and 35 weeks of pregnancy and were followed up until delivery. Oxygen consumption (VO2 max, cardiac output (CO, physical fitness, skin temperature, data on labor and delivery, and neonate outcomes were evaluated. Frequency distributions of the baseline variables of both groups were initially performed and then analysis of the outcomes was carried out. Categorical data were compared using the chi-square test, and numerical using Student's t or Mann-Whitney tests. Wilk's Lambda or Friedman's analysis of repeat measurements were applied for comparison of physical capacity, cardiovascular outcomes and maternal temperature. Results VO2 max and physical fitness were higher in both groups in the second trimester, returning to basal levels in the third trimester. In both groups, CO increased as pregnancy progressed and peak exercise temperature was higher than resting temperature, increasing further after five minutes of recovery and remaining at this level until 15 minutes after exercise completion. There was no difference between the two groups regarding duration (457.9 ± SD 249.6 vs 428.9 ± SD 203.2 minutes or type of delivery. Labor analgesia was requested by significantly fewer women in the water aerobics group (27% vs 65%; RR = 0.42 95%CI 0.23–0.77. Neonatal results were similar in both groups. Conclusion The regular practice of moderate water aerobics by sedentary and low risk pregnant women was not detrimental to the health of the mother or the child. There was no influence on maternal cardiovascular capacity, duration of labor or type of delivery; however
M. V. Shestakova
Full Text Available The interdisciplinary interim experts’ council on March 3, 2016 in Moscow have considered the EMPA-REG OUTCOME trial results and suggested a number of propositions and recommendations on further empagliflozin’s cardiovascular effects investigation and its clinical application in patients with type 2 diabetes at high cardiovascular risk.
M V Shestakova; S. A. Boytsov; O. M. Drapkina; T Yu Demidova; Drexel, H.; M B Antsiferov; N A Petunina; I. A. Chernikova; V. Yu. Kalashnikov; T P Bardymova; V. K. Protasov; A. Yu. Babenko; L. A. Ruyatkina; V V Klimontov; V. V. Salukhov
The interdisciplinary interim experts’ council on March 3, 2016 in Moscow have considered the EMPA-REG OUTCOME trial results and suggested a number of propositions and recommendations on further empagliflozin’s cardiovascular effects investigation and its clinical application in patients with type 2 diabetes at high cardiovascular risk.
Wong, AY; Root, A.; Douglas, IJ; Chui, CS; Chan, EW; Ghebremichael-Weldeselassie, Y.; Siu, CW; Smeeth, L; Wong, IC
STUDY QUESTION: What is the association between clarithromycin use and cardiovascular outcomes? METHODS: In this population based study the authors compared cardiovascular outcomes in adults aged 18 or more receiving oral clarithromycin or amoxicillin during 2005-09 in Hong Kong. Based on age within five years, sex, and calendar year at use, each clarithromycin user was matched to one or two amoxicillin users. The cohort analysis included patients who received clarithromycin (n=108 988) or ...
Holman, Rury R; Bethel, Mary Angelyn; George, Jyothis; Sourij, Harald; Doran, Zoë; Keenan, Joanne; Khurmi, Nardev S; Mentz, Robert J; Oulhaj, Abderrahim; Buse, John B; Chan, Juliana C; Iqbal, Nayyar; Kundu, Sudeep; Maggioni, Aldo P; Marso, Steven P; Öhman, Peter; Pencina, Michael J; Poulter, Neil; Porter, Lisa E; Ramachandran, Ambady; Zinman, Bernard; Hernandez, Adrian F
Exenatide once-weekly is an extended release formulation of exenatide, a glucagon-like peptide-1 receptor agonist, which can improve glycemic control, body weight, blood pressure, and lipid levels in patients with type 2 diabetes mellitus (T2DM). The EXenatide Study of Cardiovascular Event Lowering (EXSCEL) will compare the impact of adding exenatide once-weekly to usual care with usual care alone on major cardiovascular outcomes. EXSCEL is an academically led, phase III/IV, double-blind, pragmatic placebo-controlled, global trial conducted in 35 countries aiming to enrol 14,000 patients with T2DM and a broad range of cardiovascular risk over approximately 5 years. Participants will be randomized (1:1) to receive exenatide once-weekly 2 mg or matching placebo by subcutaneous injections. The trial will continue until 1,360 confirmed primary composite cardiovascular end points, defined as cardiovascular death, nonfatal myocardial infarction, or nonfatal stroke, have occurred. The primary efficacy hypothesis is that exenatide once-weekly is superior to usual care with respect to the primary composite cardiovascular end point. EXSCEL is powered to detect a 15% relative risk reduction in the exenatide once-weekly group, with 85% power and a 2-sided 5% alpha. The primary safety hypothesis is that exenatide once-weekly is noninferior to usual care with respect to the primary cardiovascular composite end point. Noninferiority will be concluded if the upper limit of the CI is <1.30. EXSCEL will assess whether exenatide once-weekly can reduce cardiovascular events in patients with T2DM with a broad range of cardiovascular risk. It will also provide long-term safety information on exenatide once-weekly in people with T2DM. ClinicalTrials.gov Identifier: NCT01144338. PMID:26995376
Full Text Available BACKGROUND: Folic acid is widely used to lower homocysteine concentrations and prevent adverse cardiovascular outcomes. However, the effect of folic acid on cardiovascular events is not clear at the present time. We carried out a comprehensive systematic review and meta-analysis to assess the effects of folic acid supplementation on cardiovascular outcomes. METHODOLOGY AND PRINCIPAL FINDINGS: We systematically searched Medline, EmBase, the Cochrane Central Register of Controlled Trials, reference lists of articles, and proceedings of major meetings for relevant literature. We included randomized placebo-controlled trials that reported on the effects of folic acid on cardiovascular events compared to placebo. Of 1594 identified studies, we included 16 trials reporting data on 44841 patients. These studies reported 8238 major cardiovascular events, 2001 strokes, 2917 myocardial infarctions, and 6314 deaths. Folic acid supplementation as compared to placebo had no effect on major cardiovascular events (RR, 0.98; 95% CI, 0.93-1.04, stroke (RR, 0.89; 95% CI,0.78-1.01, myocardial infarction (RR, 1.00; 95% CI, 0.93-1.07, or deaths from any cause (RR, 1.00;95% CI, 0.96-1.05. Moreover, folic acid as compared to placebo also had no effect on the following secondary outcomes: risk of revascularization (RR, 1.05; 95%CI, 0.95-1.16, acute coronary syndrome (RR, 1.06; 95%CI, 0.97-1.15, cancer (RR, 1.08; 95%CI, 0.98-1.21, vascular death (RR, 0.94; 95%CI,0.88-1.02, or non-vascular death (RR, 1.06; 95%CI, 0.97-1.15. CONCLUSION/SIGNIFICANCE: Folic acid supplementation does not effect on the incidence of major cardiovascular events, stroke, myocardial infarction or all cause mortality.
Forman, Daniel E.; Karen Alexander; Brindis, Ralph G.; Curtis, Anne B; Mathew Maurer; Rich, Michael W.; Laurence Sperling; Nanette K. Wenger
Longevity is increasing and the population of older adults is growing. The biology of aging is conducive to cardiovascular disease (CVD), such that prevalence of coronary artery disease, heart failure, valvular heart disease, arrhythmia and other disorders are increasing as more adults survive into old age. Furthermore, CVD in older adults is distinctive, with management issues predictably complicated by multimorbidity, polypharmacy, frailty and other complexities of care that increase manag...
Robert D. Chow
Full Text Available Background: To reduce the duration and overall costs of cardiovascular trials, use of the combined endpoints in trial design has become commonplace. Though this methodology may serve the needs of investigators and trial sponsors, the preferences of patients or potential trial subjects in the trial design process has not been studied. Objective: To determine the preferences of patients in the design of cardiovascular trials. Design: Participants were surveyed in a pilot study regarding preferences among various single endpoints commonly used in cardiovascular trials, preference for single vs. composite endpoints, and the likelihood of compliance with a heart medication if patients similar to them participated in the trial design process. Participants: One hundred adult English-speaking patients, 38% male, from a primary care ambulatory practice located in an urban setting. Key results: Among single endpoints, participants rated heart attack as significantly more important than death from other causes (4.53 vs. 3.69, p=0.004 on a scale of 1–6. Death from heart disease was rated as significantly more important than chest pain (4.73 vs. 2.47, p<0.001, angioplasty/PCI/CABG (4.73 vs. 2.43, p<0.001, and stroke (4.73 vs. 2.43, p<0.001. Participants also expressed a slight preference for combined endpoints over single endpoint (43% vs. 57%, incorporation of the opinions of the study patient population into the design of trials (48% vs. 41% for researchers, and a greater likelihood of medication compliance if patient preferences were considered during trial design (67% indicated a significant to major effect. Conclusions: Patients are able to make judgments and express preferences regarding trial design. They prefer that the opinions of the study population rather than the general population be incorporated into the design of the study. This novel approach to study design would not only incorporate patient preferences into medical decision making, but
Sever, Peter; Dahlöf, Björn; Poulter, Neil; Wedel, Hans; Beevers, Gareth; Caulfield, Mark; Collins, Rory; Kjeldsen, Sverre; Kristinsson, Arni; McInnes, Gordon; Mehlsen, Jesper; Nieminem, Markku; O'Brien, Eoin; Ostergren, Jan
A prespecified objective of the Anglo-Scandinavian Cardiac Outcomes Trial (ASCOT) was to assess whether any synergistic effects were apparent between the lipid-lowering and blood-pressure-lowering regimens in preventing cardiovascular events.......A prespecified objective of the Anglo-Scandinavian Cardiac Outcomes Trial (ASCOT) was to assess whether any synergistic effects were apparent between the lipid-lowering and blood-pressure-lowering regimens in preventing cardiovascular events....
Sever, Peter S; Poulter, Neil R; Dahlof, Bjorn;
-BPLA) compared two different antihypertensive treatment strategies on cardiovascular outcomes. ASCOT-LLA was a double-blind placebo-controlled trial of atorvastatin in those enrolled into ASCOT-BPLA with total cholesterol concentrations at baseline of <= 6.5 mmol/L. A total of 19 342 hypertensive patients were...... enrolled in ASCOT-BPLA and 10 305 were further assigned either atorvastatin, 10 mg, or placebo. ASCOT-LLA was stopped prematurely after a median 3.3 years follow-up because of substantial cardiovascular benefits in those assigned atorvastatin. Trial physicians were invited to offer atorvastatin to all...
Abstract The existence of effective therapies for most cardiovascular disease states, coupled with increased requirements that potential benefits of new drugs be evaluated on clinical rather than surrogate endpoints, makes it increasingly difficult to substantiate any incremental improvements in efficacy that these new drugs might offer. Compounding the problem is the highly controversial issue of comparing new agents with placebos rather than active pharmaceuticals in drug efficacy trials. D...
Prague : EuroMISE, 2004 - (Zvárová, J.; Hanzlíček, P.; Peleška, J.; Přečková, P.; Svátek, V.; Valenta, Z.). s. 28 ISBN 80-903431-0-4. [International Joint Meeting EuroMISE 2004. 12.04.2004-16.04.2004, Prague] R&D Projects: GA MŠk LN00B107 Keywords : atherosclerosis * clinical trials Subject RIV: FA - Cardiovascular Diseases incl. Cardiotharic Surgery
Andersson, C; van Gaal, L; Caterson, I D;
The optimal HbA(1c) concentration for prevention of macrovascular complications and deaths in obese cardiovascular high-risk patients with type 2 diabetes remains to be established and was therefore studied in this post hoc analysis of the Sibutramine Cardiovascular OUTcomes (SCOUT) trial, which...
Full Text Available Abstract Background Cardiovascular diseases (CVD are the leading cause of death and the third cause of disability in Europe. Prevention programmes should include interventions aimed at a reduction of medical risk factors (hypertension, hypercholesterol, hyperglycemia, overweight and obesity as well as behavioural risk factors (sedentary lifestyle, high fat intake and low fruit and vegetable intake, smoking. The aim of this study is to investigate the effects of a multifaceted, multidisciplinary electronic prevention programme on cardiovascular risk factors. Methods/Design In a randomized controlled trial, one group will receive a maximal intervention (= intervention group. The intervention group will be compared to the control group receiving a minimal intervention. An inclusion of 350 patients in total, with a follow-up of 3 years is foreseen. The inclusion criteria are age between 25–65 and insured by the Onderlinge Ziekenkas, insuring for guaranteed income in case of illness for self-employed. The maximal intervention group receives several prevention consultations by their general practitioner (GP using a new type of cardiovascular risk calculator with personalised feedback on behavioural risk factors. These patients receive a follow-up with intensive support of health behaviour change via different methods, i.e. a tailored website and personal advice of a multidisciplinary team (psychologist, physiotherapist and dietician. The aim of this strategy is to reduce cardiovascular risk factors according to the guidelines. The primary outcome measures will be cardiovascular risk factors. The secondary outcome measures are cardiovascular events, quality of life, costs and incremental cost effectiveness ratios. The control group receives prevention consultations using a new type of cardiovascular risk calculator and general feedback. Discussion This trial incorporates interventions by GPs and other health professionals aiming at a reduction of
Mehta, Puja K.; Minissian, Margo; Merz, C. Noel Bairey
Cardiovascular disease (CVD) is the leading health threat to American women. In addition to established risk factors for hypertension, hyperlipidemia, diabetes, smoking, and obesity, adverse pregnancy outcomes (APOs) including pre-eclampsia, eclampsia, and gestational diabetes are now recognized as factors that increase a woman’s risk for future CVD. CVD risk factor burden is disproportionately higher in those of low socioeconomic status and in ethnic/racial minority women. Since younger wome...
Ghosal, Samit; Sinha, Binayak
The issue related to macrovascular outcomes and intensive glycemic control was hotly debated after the publication of landmark trials like ACCORD, ADVANCE, and VADT. The only benefits seem to come from intervening early on in the disease process as indicated by the 10-year UKPDS follow-up. To complicate matters USFDA made it mandatory for modern drugs to conduct cardiovascular safety trials in high-risk populations after the 2008 rosiglitazone scare. This led to all the modern group of drugs designing cardiovascular safety trials (gliptins, GLP-1 agonists, and SGLT-2 inhibitors) to meet USFDA regulatory requirements. We saw publication of the first 2 randomized trials with gliptins published a year and a half back. On the face value SAVOR TIMI and EXAMINE satisfied the primary composite CV end-points. However, issues related to significant increase in heart failure and all-cause 7-day on-treatment mortality created a lot of confusion. FDA reanalysis of these data (especially SAVOR) raises a lot of doubts as far as CV safety of these groups of drugs was concerned. Hence, all eyes were on TECOS, which was published this year. We take a microscopic look at these trials trying to understand where we stand as from now on this issue. PMID:26649315
Full Text Available The issue related to macrovascular outcomes and intensive glycemic control was hotly debated after the publication of landmark trials like ACCORD, ADVANCE, and VADT. The only benefits seem to come from intervening early on in the disease process as indicated by the 10-year UKPDS follow-up. To complicate matters USFDA made it mandatory for modern drugs to conduct cardiovascular safety trials in high-risk populations after the 2008 rosiglitazone scare. This led to all the modern group of drugs designing cardiovascular safety trials (gliptins, GLP-1 agonists, and SGLT-2 inhibitors to meet USFDA regulatory requirements. We saw publication of the first 2 randomized trials with gliptins published a year and a half back. On the face value SAVOR TIMI and EXAMINE satisfied the primary composite CV end-points. However, issues related to significant increase in heart failure and all-cause 7-day on-treatment mortality created a lot of confusion. FDA reanalysis of these data (especially SAVOR raises a lot of doubts as far as CV safety of these groups of drugs was concerned. Hence, all eyes were on TECOS, which was published this year. We take a microscopic look at these trials trying to understand where we stand as from now on this issue.
Sattar, Naveed; McLaren, James; Kristensen, Søren L; Preiss, David; McMurray, John J
While the modest reduction in the primary composite outcome of myocardial infarction, stroke or cardiovascular death in the EMPA-REG Outcomes trial was welcome, the 30-40% reductions in heart failure hospitalisation (HFH) and cardiovascular and all-cause deaths in patients treated with empagliflozin were highly impressive and unexpected. In this review, we discuss briefly why cardiovascular endpoint trials for new diabetes agents are required and describe the results of the first four such trials to have reported, as a precursor to understanding why the EMPA-REG Outcomes results came as a surprise. Thereafter, we discuss potential mechanisms that could explain the EMPA-REG Outcomes results, concentrating on non-atherothrombotic effects. We suggest that the main driver of benefit may derive from the specific effects of sodium-glucose linked transporter-2 (SGLT2) inhibition on renal sodium and glucose handling, leading to both diuresis and improvements in diabetes-related maladaptive renal arteriolar responses. These haemodynamic and renal effects are likely to be beneficial in patients with clinical or subclinical cardiac dysfunction. The net result of these processes, we argue, is an improvement in cardiac systolic and diastolic function and, thereby, a lower risk of HFH and sudden cardiac death. We also discuss whether other drugs in this class are likely to show similar cardiovascular benefits. Finally, areas for future research are suggested to better understand the relevant mechanisms and to identify other groups who may benefit from SGLT2 inhibitor therapy. PMID:27112340
Hróbjartsson, Asbjørn; Thomsen, Ann Sofia Skou; Emanuelsson, Frida; Tendal, Britta; Hilden, Jørgen; Boutron, Isabelle; Ravaud, Philippe; Brorson, Stig
To evaluate the impact of non-blinded outcome assessment on estimated treatment effects in randomised clinical trials with binary outcomes.......To evaluate the impact of non-blinded outcome assessment on estimated treatment effects in randomised clinical trials with binary outcomes....
Ghosh, Raktim Kumar; Bandyopadhyay, Dhrubajyoti; Hajra, Adrija; Biswas, Monodeep; Gupta, Anjan
Diabetes is a leading cause of morbidity and mortality worldwide. Management of diabetes is changing at a rapid pace. Three new classes of antidiabetic drugs including GLP-1 (Glucagon-like peptide 1), DPP-IV (Dipeptidyl peptidase IV) and SGLT2 (Sodium glucose cotransporter 2) inhibitors have been approved in the last few years. Treating diabetes with the antidiabetic drug does not always reduce the cardiovascular complications of diabetes. On the contrary, there was a huge controversy regarding the effect of rosiglitazone on cardiovascular risk reduction a few years ago. Since then, submission of postmarketing cardiovascular outcome study data has been mandated by US FDA and other drug regulatory agencies for newer antidiabetic medications. This is to avoid further premature claims regarding cardiovascular harm or safety of the newer classes. We already have some cardiovascular safety data available on DPP-IV and GLP-1 groups of medications. Dapagliflozin, canagliflozin, and empagliflozin are currently approved SGLT2 inhibitors. We do not have sufficient cardiovascular outcome data available for this novel class. However, this group of drugs, which act by increasing renal glucose excretion, have also shown some non-glycemic benefits including weight reduction, blood pressure control, diuretic action, renal protection, decrease in arterial stiffness and uric acid reduction. Empagliflozin, a new member of SGLT2 class, showed significant cardiovascular morbidity and mortality benefit in recently published EMPA-REG OUTCOME trial. The authors summarize all the published clinical and preclinical cardiovascular outcome data of SGLT2 inhibitors, including recently completed and ongoing major clinical trials in this comprehensive review. PMID:27017118
Full Text Available Abstract The existence of effective therapies for most cardiovascular disease states, coupled with increased requirements that potential benefits of new drugs be evaluated on clinical rather than surrogate endpoints, makes it increasingly difficult to substantiate any incremental improvements in efficacy that these new drugs might offer. Compounding the problem is the highly controversial issue of comparing new agents with placebos rather than active pharmaceuticals in drug efficacy trials. Despite the recent consensus that placebos may be used ethically in well-defined, justifiable circumstances, the problem persists, in part because of increased scrutiny by ethics committees but also because of considerable lingering disagreement regarding the propriety and scientific value of placebo-controlled trials (and trials of antihypertensive drugs in particular. The disagreement also substantially affects the most viable alternative to placebo-controlled trials: actively controlled equivalence/noninferiority trials. To a great extent, this situation was prompted by numerous previous trials of this type that were marked by fundamental methodological flaws and consequent false claims, inconsistencies, and potential harm to patients. As the development and use of generic drugs continue to escalate, along with concurrent pressure to control medical costs by substituting less-expensive therapies for established ones, any claim that a new drug, intervention, or therapy is "equivalent" to another should not be accepted without close scrutiny. Adherence to proper methods in conducting studies of equivalence will help investigators to avoid false claims and inconsistencies. These matters will be addressed in the third article of this three-part series.
Naugle, Keith E.; Naugle, Kelly M.; Wikstrom, Erik A.
Naugle, KE, Naugle, KM, and Wikstrom, EA. Cardiovascular and affective outcomes of active gaming: Using the Nintendo Wii as a cardiovascular training tool. J Strength Cond Res 28(2): 443–451, 2014–Active-video gaming is purported to produce similar cardiovascular responses as aerobic fitness activities. This study compared the emotional and cardiovascular effects of Wii games with those of traditional exercise in college-aged adults with different exercise backgrounds. Specifically, the percentage of heart rate reserve, rate of perceived exertion (RPE), level of enjoyment, and Positive and Negative Affect Schedule scores were compared between subjects who reported exercising frequently at high intensities (high-intensity exerciser group: age = 20.18 years [0.87]; Height = 165.23 cm [9.97]; Mass = 62.37 kg [11.61]), N = 11 and those who exercise more often at lower intensities (low-intensity exercisers group: age = 20.72 years [1.19]; Height = 164.39 cm [8.05]; Mass = 68.04 kg [10.71]), N = 11. The subjects completed six 20-minute exercises sessions: treadmill walking, stationary cycling, and Wii's Tennis, Boxing, Cycling, and Step. The low-intensity exerciser group achieved a greater percentage of heart rate reserve (a) during traditional exercise compared with that during Wii boxing, (b) playing Wii boxing compared with that for Wii tennis, and (c) playing Wii boxing compared with that when the high-intensity exercisers group played any Wii games (p < 0.05). The RPE was greater for boxing and cycling compared with that for tennis and step (p < 0.05). Ratings of enjoyment and the increase in positive emotion were greater for boxing and for tennis compared with those for traditional exercises (p < 0.05). Results suggest that Wii boxing shows the greatest potential as a cardiovascular fitness tool among the Wii games, particularly for individuals who typically exercise at lower intensities. PMID:23660574
Jay, Kenneth; Frisch, Dennis; Hansen, Klaus;
The aim of this trial was to investigate the effectiveness of a worksite intervention using kettlebell training to improve musculoskeletal and cardiovascular health.......The aim of this trial was to investigate the effectiveness of a worksite intervention using kettlebell training to improve musculoskeletal and cardiovascular health....
Wirth, Sylvia; Avsar, Emin; Chiu, Cindy C.; Sharma, Varun; Smith, Anne C.; Emery N Brown; Suzuki, Wendy A.
In tasks of associative learning, animals establish new links between unrelated items by using information about trial outcome to strengthen correct/rewarded associations and modify incorrect/unrewarded ones. To study how hippocampal neurons convey information about reward and trial outcome during new associative learning, we recorded hippocampal neurons as monkeys learned novel object-place associations. A large population of hippocampal neurons (50%) signaled trial outcome by differentiatin...
Hermans, Michel; Bouenizabila, Evariste; Amoussou-guenou, Daniel K.; Ahn, Sylvie A; Rousseau, Michel
Background: Diabetes is a major cardiovascular risk factor. However, its influence on the rate of occurrence of cardiovascular (CV) events during a clinical trial that included a diabetes subgroup has not yet been quantified. Aims: To establish equations relating baseline diabetes prevalence and incident CV events, based on comparator arms data of major lipid-modifying trials. Methods: Meta-analysis of primary outcomes (PO) rates of key prospective trials, for which the baseline proportion of...
Full Text Available Abstract Background Cardiovascular disease (including coronary heart disease and stroke is a major cause of death and disability in the United Kingdom, and is to a large extent preventable, by lifestyle modification and drug therapy. The recent standardisation of electronic codes for cardiovascular risk variables through the United Kingdom's new General Practice contract provides an opportunity for the application of risk algorithms to identify high risk individuals. This randomised controlled trial will test the benefits of an automated system of alert messages and practice searches to identify those at highest risk of cardiovascular disease in primary care databases. Design Patients over 50 years old in practice databases will be randomised to the intervention group that will receive the alert messages and searches, and a control group who will continue to receive usual care. In addition to those at high estimated risk, potentially high risk patients will be identified who have insufficient data to allow a risk estimate to be made. Further groups identified will be those with possible undiagnosed diabetes, based either on elevated past recorded blood glucose measurements, or an absence of recent blood glucose measurement in those with established cardiovascular disease. Outcome measures The intervention will be applied for two years, and outcome data will be collected for a further year. The primary outcome measure will be the annual rate of cardiovascular events in the intervention and control arms of the study. Secondary measures include the proportion of patients at high estimated cardiovascular risk, the proportion of patients with missing data for a risk estimate, and the proportion with undefined diabetes status at the end of the trial.
Nataatmadja, Melissa; Cho, Yeoungjee; Fahim, Magid; Johnson, David W
As a consequence of both traditional and non-traditional risk factors, cardiovascular disease is over-represented, and the leading cause of mortality, among patients with Chronic Kidney Disease (CKD). Whilst recommendations for reducing cardiovascular risk in the general population exist, their applicability to the CKD population is questionable due to the exclusion of CKD patients from the majority of contemporary cardiovascular interventional studies. The aim of this review is to critically evaluate the literature regarding pharmacologic cardiovascular interventions in patients with CKD, with an emphasis on studies published since our 2008 review. Interventions discussed include erythropoiesis-stimulating agents (TREAT, U.S. Normal Hematocrit, CHOIR, CREATE, Palmer meta-analysis); statins (SHARP, AURORA, PPP, 4D, ALERT); Fibrates (VA-HIT); Folic Acid (ASFAST, US FOLIC acid trial, HOST); Antihypertensive Agents, Including Angiotensin-Converting Enzyme Inhibitors, angiotensin-receptor blockers, Beta-blockers and Combination therapy (Cice et al, FOSDIAL, Agarwal et al, ONTARGET); sevelamer (DCOR); Cinacalcet (ADVANCE, EVOLVE, Cunningham meta-analysis); Anti-oxidants (SPACE, HOPE, ATIC); Aspirin (HOT study re-analysis); vitamin D analogues (PRIMO); and multidisciplinary intervention (LANDMARK). Unfortunately, there remains a paucity of evidence in this area and a large number of methodologically poor quality studies with negative results. It is possible that these interventions do not have the same positive effect in CKD patients due to differences in the pathogenesis driving cardiovascular disease burden, such as altered bone metabolism and calcific vascular disease. Further well-designed studies with appropriately selected study populations and patient level outcomes are required. Until such time, physicians must consider on an individual patient basis the appropriateness of these interventions. PMID:26497837
Hróbjartsson, Asbjørn; Thomsen, Ann Sofia Skou; Emanuelsson, Frida;
BACKGROUND: Clinical trials are commonly done without blinded outcome assessors despite the risk of bias. We wanted to evaluate the effect of nonblinded outcome assessment on estimated effects in randomized clinical trials with outcomes that involved subjective measurement scales. METHODS: We...... conducted a systematic review of randomized clinical trials with both blinded and nonblinded assessment of the same measurement scale outcome. We searched PubMed, EMBASE, PsycINFO, CINAHL, Cochrane Central Register of Controlled Trials, HighWire Press and Google Scholar for relevant studies. Two...... investigators agreed on the inclusion of trials and the outcome scale. For each trial, we calculated the difference in effect size (i.e., standardized mean difference between nonblinded and blinded assessments). A difference in effect size of less than 0 suggested that nonblinded assessors generated more...
Herrmann, Sandra M S; Saad, Ahmed; Textor, Stephen C
Many patients with occlusive atherosclerotic renovascular disease (ARVD) may be managed effectively with medical therapy for several years without endovascular stenting, as demonstrated by randomized, prospective trials including the Cardiovascular Outcomes in Renal Atherosclerotic Lesions (CORAL) trial, the Angioplasty and Stenting for Renal Artery Lesions (ASTRAL) trial and the Stent Placement and Blood Pressure and Lipid-Lowering for the Prevention of Progression of Renal Dysfunction Caused by Atherosclerotic Ostial Stenosis of the Renal Artery (STAR) and ASTRAL. These trials share the limitation of excluding subsets of patients with high-risk clinical presentations, including episodic pulmonary edema and rapidly progressing renal failure and hypertension. Although hemodynamically significant, ARVD can reduce renal blood flow and glomerular filtration rate; adaptive mechanisms preserve both cortical and medullary oxygenation over a wide range of vascular occlusion. Progression of ARVD to severe vascular compromise eventually produces cortical hypoxia, however, associated with active inflammatory cytokine release and cellular infiltration of the renal parenchyma. In such cases ARVD produces a loss of glomerular filtration rate that no longer is reversible simply by restoring vessel patency with technically successful renal revascularization. Each of these trials reported adverse renal functional outcomes ranging between 16 and 22% over periods of 2-5 years of follow-up. Blood pressure control and medication adjustment may become more difficult with declining renal function and may prevent the use of angiotensin receptor blocker and angiotensin-converting enzyme inhibitors. The objective of this review is to evaluate the current management of ARVD for clinical nephrologists in the context of recent randomized clinical trials and experimental research. PMID:24723543
... various efficient and pragmatic clinical trial designs that are conducive to overcoming the challenges in... HUMAN SERVICES Food and Drug Administration Workshop on Optimizing Clinical Trial Design for the... ``Optimizing Clinical Trial Design for the Development of Pediatric Cardiovascular Devices.'' The topic to...
A randomised trial of the effect and cost-effectiveness of early intensive multifactorial therapy on 5-year cardiovascular outcomes in individuals with screen-detected type 2 diabetes: the Anglo-Danish-Dutch Study of Intensive Treatment in People with Screen-Detected Diabetes in Primary Care (ADDITION-Europe) study.
Simmons, Rebecca K; Borch-Johnsen, Knut; Lauritzen, Torsten; Rutten, Guy Ehm; Sandbæk, Annelli; van den Donk, Maureen; Black, James A; Tao, Libo; Wilson, Edward Cf; Davies, Melanie J; Khunti, Kamlesh; Sharp, Stephen J; Wareham, Nicholas J; Griffin, Simon J
BACKGROUND Intensive treatment (IT) of cardiovascular risk factors can halve mortality among people with established type 2 diabetes but the effects of treatment earlier in the disease trajectory are uncertain. OBJECTIVE To quantify the cost-effectiveness of intensive multifactorial treatment of screen-detected diabetes. DESIGN Pragmatic, multicentre, cluster-randomised, parallel-group trial. SETTING Three hundred and forty-three general practices in Denmark, the Netherlands, and Cambridge and Leicester, UK. PARTICIPANTS Individuals aged 40-69 years with screen-detected diabetes. INTERVENTIONS Screening plus routine care (RC) according to national guidelines or IT comprising screening and promotion of target-driven intensive management (medication and promotion of healthy lifestyles) of hyperglycaemia, blood pressure and cholesterol. MAIN OUTCOME MEASURES The primary end point was a composite of first cardiovascular event (cardiovascular mortality/morbidity, revascularisation and non-traumatic amputation) during a mean [standard deviation (SD)] follow-up of 5.3 (1.6) years. Secondary end points were (1) all-cause mortality; (2) microvascular outcomes (kidney function, retinopathy and peripheral neuropathy); and (3) patient-reported outcomes (health status, well-being, quality of life, treatment satisfaction). Economic analyses estimated mean costs (UK 2009/10 prices) and quality-adjusted life-years from an NHS perspective. We extrapolated data to 30 years using the UK Prospective Diabetes Study outcomes model [version 1.3; (©) Isis Innovation Ltd 2010; see www.dtu.ox.ac.uk/outcomesmodel (accessed 27 January 2016)]. RESULTS We included 3055 (RC, n = 1377; IT, n = 1678) of the 3057 recruited patients [mean (SD) age 60.3 (6.9) years] in intention-to-treat analyses. Prescription of glucose-lowering, antihypertensive and lipid-lowering medication increased in both groups, more so in the IT group than in the RC group. There were clinically important improvements
Moustgaard, Helene; Bello, Segun; Miller, Franklin G;
OBJECTIVES: The degree of bias in randomized clinical trials varies depending on whether the outcome is subjective or objective. Assessment of the risk of bias in a clinical trial will therefore often involve categorization of the type of outcome. Our primary aim was to examine how the concepts...... explicitly defined the terms. CONCLUSION: The terms "subjective" and "objective" are ambiguous when used to describe outcomes in randomized clinical trials. We suggest that the terms should be defined explicitly when used in connection with the assessment of risk of bias in a clinical trial...
Hróbjartsson, Asbjørn; Thomsen, Ann Sofia Skou; Emanuelsson, Frida;
BACKGROUND: Clinical trials are commonly done without blinded outcome assessors despite the risk of bias. We wanted to evaluate the effect of nonblinded outcome assessment on estimated effects in randomized clinical trials with outcomes that involved subjective measurement scales. METHODS: We...... conducted a systematic review of randomized clinical trials with both blinded and nonblinded assessment of the same measurement scale outcome. We searched PubMed, EMBASE, PsycINFO, CINAHL, Cochrane Central Register of Controlled Trials, HighWire Press and Google Scholar for relevant studies. Two...... optimistic estimates of effect. We pooled the differences in effect size using inverse variance random-effects meta-analysis and used metaregression to identify potential reasons for variation. RESULTS: We included 24 trials in our review. The main meta-analysis included 16 trials (involving 2854 patients...
The effect of a comprehensive lifestyle intervention on cardiovascular risk factors in pharmacologically treated patients with stable cardiovascular disease compared to usual care: a randomised controlled trial
Full Text Available Abstract Background The additional benefit of lifestyle interventions in patients receiving cardioprotective drug treatment to improve cardiovascular risk profile is not fully established. The objective was to evaluate the effectiveness of a target-driven multidisciplinary structured lifestyle intervention programme of 6 months duration aimed at maximum reduction of cardiovascular risk factors in patients with cardiovascular disease (CVD compared with usual care. Methods A single centre, two arm, parallel group randomised controlled trial was performed. Patients with stable established CVD and at least one lifestyle-related risk factor were recruited from the vascular and cardiology outpatient departments of the university hospital. Blocked randomisation was used to allocate patients to the intervention (n = 71 or control group (n = 75 using an on-site computer system combined with allocations in computer-generated tables of random numbers kept in a locked computer file. The intervention group received the comprehensive lifestyle intervention offered in a specialised outpatient clinic in addition to usual care. The control group continued to receive usual care. Outcome measures were the lifestyle-related cardiovascular risk factors: smoking, physical activity, physical fitness, diet, blood pressure, plasma total/HDL/LDL cholesterol concentrations, BMI, waist circumference, and changes in medication. Results The intervention led to increased physical activity/fitness levels and an improved cardiovascular risk factor profile (reduced BMI and waist circumference. In this setting, cardiovascular risk management for blood pressure and lipid levels by prophylactic treatment for CVD in usual care was already close to optimal as reflected in baseline levels. There was no significant improvement in any other risk factor. Conclusions Even in CVD patients receiving good clinical care and using cardioprotective drug treatment, a comprehensive
Full Text Available BACKGROUND: Landmark clinical trials have led to optimal treatment recommendations for patients with diabetes. Whether optimal treatment is actually delivered in practice is even more important than the efficacy of the drugs tested in trials. To this end, treatment quality indicators have been developed and tested against intermediate outcomes. No studies have tested whether these treatment quality indicators also predict hard patient outcomes. METHODS: A cohort study was conducted using data collected from >10.000 diabetes patients in the Groningen Initiative to Analyze Type 2 Treatment (GIANTT database and Dutch Hospital Data register. Included quality indicators measured glucose-, lipid-, blood pressure- and albuminuria-lowering treatment status and treatment intensification. Hard patient outcome was the composite of cardiovascular events and all-cause death. Associations were tested using Cox regression adjusting for confounding, reporting hazard ratios (HR with 95% confidence intervals. RESULTS: Lipid and albuminuria treatment status, but not blood pressure lowering treatment status, were associated with the composite outcome (HR = 0.77, 0.67-0.88; HR = 0.75, 0.59-0.94. Glucose lowering treatment status was associated with the composite outcome only in patients with an elevated HbA1c level (HR = 0.72, 0.56-0.93. Treatment intensification with glucose-lowering but not with lipid-, blood pressure- and albuminuria-lowering drugs was associated with the outcome (HR = 0.73, 0.60-0.89. CONCLUSION: Treatment quality indicators measuring lipid- and albuminuria-lowering treatment status are valid quality measures, since they predict a lower risk of cardiovascular events and mortality in patients with diabetes. The quality indicators for glucose-lowering treatment should only be used for restricted populations with elevated HbA1c levels. Intriguingly, the tested indicators for blood pressure-lowering treatment did not predict patient
Abdul-Ghani, Muhammad; Del Prato, Stefano; Chilton, Robert; DeFronzo, Ralph A
Although cardiovascular (CV) mortality is the principal cause of death in individuals with type 2 diabetes (T2DM), reduction of plasma glucose concentration has little effect on CV disease (CVD) risk. Thus, novel strategies to reduce CVD risk in T2DM patients are needed. The recently published BI 10773 (Empagliflozin) Cardiovascular Outcome Event Trial in Type 2 Diabetes Mellitus Patients (EMPA-REG OUTCOME) study demonstrated that in T2DM patients with high CVD risk empagliflozin reduced the primary major adverse cardiac event end point (CV death, nonfatal myocardial infarction, nonfatal stroke) by 14%. This beneficial effect was driven by a 38% reduction in CV mortality with no significant decrease in nonfatal myocardial infarction or stroke. Empagliflozin also caused a 35% reduction in hospitalization for heart failure without affecting hospitalization for unstable angina. Although sodium-glucose cotransporter 2 inhibitors exert multiple metabolic benefits (decreases in HbA1c, body weight, and blood pressure and an increase in HDL cholesterol), all of which could reduce CVD risk, it is unlikely that the reduction in CV mortality can be explained by empagliflozin's metabolic effects. More likely, hemodynamic effects, specifically reduced blood pressure and decreased extracellular volume, are responsible for the reduction in CV mortality and heart failure hospitalization. In this Perspective, we will discuss possible mechanisms for these beneficial effects of empagliflozin and their implications for the care of T2DM patients. PMID:27208375
Full Text Available BACKGROUND: With the increasing prevalence of chronic noncommunicable diseases, patient education is becoming important to strengthen disease prevention and control. We aimed to systematically determine the extent to which registered, ongoing randomized controlled trials (RCTs evaluated an educational intervention focus on patient-important outcomes (i.e., outcomes measuring patient health status and quality of life. METHODS: On May 6, 2009, we searched for all ongoing RCTs registered in the World Health Organization International Clinical Trials Registry platform. We used a standardized data extraction form to collect data and determined whether the outcomes assessed were 1 patient-important outcomes such as clinical events, functional status, pain, or quality of life or 2 surrogate outcomes, such as biological outcome, treatment adherence, or patient knowledge. PRINCIPAL FINDINGS: We selected 268 of the 642 potentially eligible studies and assessed a random sample of 150. Patient-important outcomes represented 54% (178 of 333 of all primary outcomes and 46% (286 of 623 of all secondary outcomes. Overall, 69% of trials (104 of 150 used at least one patient-important outcome as a primary outcome and 66% (99 of 150 as a secondary outcome. Finally, for 31% of trials (46 of 150, primary outcomes were only surrogate outcomes. The results varied by medical area. In neuropsychiatric disorders, patient important outcomes represented 84% (51 of 61 of primary outcomes, as compared with 54% (32 of 59 in malignant neoplasm and 18% (4 of 22 in diabetes mellitus trials. In addition, only 35% assessed the long-term impact of interventions (i.e., >6 months. CONCLUSIONS: There is a need to improve the relevance of outcomes and to assess the long term impact of educational interventions in RCTs.
Varvaki Rados, Dimitris; Catani Pinto, Lana; Reck Remonti, Luciana; Bauermann Leitão, Cristiane; Gross, Jorge Luiz
Background Sulfonylureas are an effective and inexpensive treatment for type 2 diabetes. There is conflicting data about the safety of these drugs regarding mortality and cardiovascular outcomes. The objective of the present study was to evaluate the safety of the sulfonylureas most frequently used and to use trial sequential analysis (TSA) to analyze whether the available sample was powered enough to support the results. Methods and Findings Electronic databases were reviewed from 1946 (Embase) or 1966 (MEDLINE) up to 31 December 2014. Randomized clinical trials (RCTs) of at least 52 wk in duration evaluating second- or third-generation sulfonylureas in the treatment of adults with type 2 diabetes and reporting outcomes of interest were included. Primary outcomes were all-cause and cardiovascular mortality. Additionally, myocardial infarction and stroke events were evaluated. Data were summarized with Peto odds ratios (ORs), and the reliability of the results was evaluated with TSA. Forty-seven RCTs with 37,650 patients and 890 deaths in total were included. Sulfonylureas were not associated with all-cause (OR 1.12 [95% CI 0.96 to 1.30]) or cardiovascular mortality (OR 1.12 [95% CI 0.87 to 1.42]). Sulfonylureas were also not associated with increased risk of myocardial infarction (OR 0.92 [95% CI 0.76 to 1.12]) or stroke (OR 1.16 [95% CI 0.81 to 1.66]). TSA could discard an absolute difference of 0.5% between the treatments, which was considered the minimal clinically significant difference. The major limitation of this review was the inclusion of studies not designed to evaluate safety outcomes. Conclusions Sulfonylureas are not associated with increased risk for all-cause mortality, cardiovascular mortality, myocardial infarction, or stroke. Current evidence supports the safety of sulfonylureas; an absolute risk of 0.5% could be firmly discarded. Review registration PROSPERO CRD42014004330 PMID:27071029
Pfeffer, Marc A.; Burdmann, Emmanuel A.; Chen, Chao-Yin; Cooper, Mark E.; de Zeeuw, Dick; Eckardt, Kai-Uwe; Ivanovich, Peter; Kewalramani, Reshma; Levey, Andrew S.; Lewis, Eldrin F.; McGill, Janet; McMurray, John J. V.; Parfrey, Patrick; Parving, Hans-Henrik; Remuzzi, Giuseppe; Singh, Ajay K.; Solomon, Scott D.; Toto, Robert; Uno, Hajime
Background: Anemia augments the already high rates of fatal and major nonfatal cardiovascular and renal events in individuals with type 2 diabetes. In 2004, we initiated the Trial to Reduce Cardiovascular Events With Aranesp Therapy (TREAT). This report presents the baseline characteristics and ther
Prevention of cardiovascular events with an antihypertensive regimen of amlodipine adding perindopril as required versus atenolol adding bendroflumethiazide as required, in the Anglo-Scandinavian Cardiac Outcomes Trial-Blood Pressure Lowering Arm (ASCOT-BPLA): a multicentre randomised controlled
Dahlöf, Björn; Sever, Peter S; Poulter, Neil R;
The apparent shortfall in prevention of coronary heart disease (CHD) noted in early hypertension trials has been attributed to disadvantages of the diuretics and beta blockers used. For a given reduction in blood pressure, some suggested that newer agents would confer advantages over diuretics an...... and beta blockers. Our aim, therefore, was to compare the effect on non-fatal myocardial infarction and fatal CHD of combinations of atenolol with a thiazide versus amlodipine with perindopril....
Schoos, Mikkel Malby; Sejersten, Maria; Baber, Usman;
Adequate health care is increasingly dependent on prehospital systems and cardiovascular (CV) disease remains the most common cause for hospital admission. However the prevalence of CV dispatches of emergency medical services (EMS) is not well reported and survival data described in clinical trials...... and registries are subject to selection biases. We aimed to describe the prevalence and prognosis of acute CV disease and the effect of invasive treatment, in an unselected and consecutive prehospital cohort of 3,410 patients calling the national emergency telephone number from 2005 to 2008 with...... follow-up in 2013. Individual-level data from national registries were linked to the dedicated EMS database of primary ambulance dispatches supported by physician-manned emergency units. Outcome data were obtained from the Central Population Registry, the National Patient Registry, and the National...
Lobraico, Jessika M; DiLello, Lauren C; Butler, Amber D; Cordisco, Marie Elena; Petrini, Joann R; Ahmadi, Ramin
Objective The purpose of this trial was to evaluate the effect of krill oil supplementation, a source of ω-3 fatty acids, on cardiovascular disease risk factors and blood glucose control among participants with type 2 diabetes. Research design and methods A randomized, double-blind controlled cross-over trial was employed. Outcomes assessed were: endothelial function, blood lipids, glucose, glycated hemoglobin, serum antioxidant level, C peptide, and calculated Homeostatic Model Assessment of...
Langefeld, Carl D.; Divers, Jasmin; Nicholas M. Pajewski; Hawfield, Amret T.; Reboussin, David M.; Bild, Diane E.; Kaysen, George A.; Kimmel, Paul L; Raj, Dominic; Ricardo, Ana C.; Wright, Jackson T; Sedor, John R.; Rocco, Michael V.; Freedman, Barry I.
Apolipoprotein L1 gene (APOL1) G1 and G2 coding variants are strongly associated with chronic kidney disease (CKD) in African Americans. Here APOL1 association was tested with baseline estimated glomerular filtration rate (eGFR), urine albumin:creatinine ratio (UACR), and prevalent cardiovascular disease (CVD) in 2,571 African Americans from the Systolic Blood Pressure Intervention Trial (SPRINT), a trial assessing effects of systolic blood pressure reduction on renal and CVD outcomes. Logist...
Ehimen C Aneni
Full Text Available CONTEXT: The internet is gaining popularity as a means of delivering employee-based cardiovascular (CV wellness interventions though little is known about the cardiovascular health outcomes of these programs. In this review, we examined the effectiveness of internet-based employee cardiovascular wellness and prevention programs. EVIDENCE ACQUISITION: We conducted a systematic review by searching PubMed, Web of Science and Cochrane library for all published studies on internet-based programs aimed at improving CV health among employees up to November 2012. We grouped the outcomes according to the American Heart Association (AHA indicators of cardiovascular wellbeing--weight, BP, lipids, smoking, physical activity, diet, and blood glucose. EVIDENCE SYNTHESIS: A total of 18 randomized trials and 11 follow-up studies met our inclusion/exclusion criteria. Follow-up duration ranged from 6-24 months. There were significant differences in intervention types and number of components in each intervention. Modest improvements were observed in more than half of the studies with weight related outcomes while no improvement was seen in virtually all the studies with physical activity outcome. In general, internet-based programs were more successful if the interventions also included some physical contact and environmental modification, and if they were targeted at specific disease entities such as hypertension. Only a few of the studies were conducted in persons at-risk for CVD, none in blue-collar workers or low-income earners. CONCLUSION: Internet based programs hold promise for improving the cardiovascular wellness among employees however much work is required to fully understand its utility and long term impact especially in special/at-risk populations.
Jani, Bhautesh Dinesh; Cavanagh, Jonathan; Barry, Sarah J. E.; Der, Geoff; Sattar, Naveed; Mair, Frances S.
We studied joint effect of blood pressure-BP and depression on risk of major adverse cardiovascular outcome in patients with existing cardiometabolic disease. A cohort of 35537 patients with coronary heart disease, diabetes or stroke underwent depression screening and BP was recorded concurrently. We used Cox’s proportional hazards to calculate risk of major adverse cardiovascular event-MACE (myocardial infarction/heart failure/stroke or cardiovascular death) over 4 years associated with ba...
Sturgeon, Kathleen M.; Ky, Bonnie; Libonati, Joseph R.; Schmitz, Kathryn H.
Asymptomatic cardiotoxicity following breast cancer treatment is a significant issue for many patients, as these patients typically face an increased risk of cardiovascular disease (CVD). Exercise has well established benefits to improve and maintain cardiovascular function across patients with and without CVD. However, there is a dearth of information on the effects of exercise on cardiovascular outcomes in breast cancer patients. While pre-clinical studies support the use of exercise in mit...
Reekie, J; Mocroft, A; J, Neaton; Lundgren, Jens Dilling
Since the introduction of combination antiretroviral therapy, there has been a decrease in both AIDS-defining illnesses and deaths. This decrease meant that performing clinical trials with clinical outcomes in HIV infection became more time consuming and hence costly. Improved understanding and...... the infection, so when treatment is started it is currently a lifelong commitment. Is it reasonable then that guidelines are based almost completely on short-term randomized trials and observational studies of surrogate markers, or is there still a need for trials with clinical outcomes?...
Kornerup, Henriette; Zwisler, Ann-Dorthe Olsen; Prescott, Eva
Anxiety and depression have been linked to adverse prognostic outcome in patients with cardiovascular disease (CVD) with mixed results. The timing of anxiety and depression measurement has received little attention so far.......Anxiety and depression have been linked to adverse prognostic outcome in patients with cardiovascular disease (CVD) with mixed results. The timing of anxiety and depression measurement has received little attention so far....
Full Text Available Abstract Background Androgen deprivation therapy leads to a number of adverse effects including deterioration of the musculoskeletal system and increased risk factors for cardiovascular and metabolic complications. The purpose of this study is to determine the effects, efficacy, retention and compliance of a physical exercise intervention in a large established cohort of prostate cancer patients from the Randomised Androgen Deprivation and Radiotherapy (RADAR study. Specifically, we aim to compare short- and long-term effects of a prostate cancer-specific supervised exercise program to a standard public health physical activity strategy utilizing printed resources on cardiovascular and metabolic risk factors. Our primary outcomes are cardiorespiratory capacity, abdominal obesity, and lipid and glycemic control, while secondary outcomes include self-reported physical activity, quality of life and psychological distress. Methods/Design Multi-site randomized controlled trial of 370 men from the RADAR study cohort undergoing treatment or previously treated for prostate cancer involving androgen deprivation therapy in the cities of Perth and Newcastle (Australia, and Wellington (New Zealand. Participants will be randomized to (1 supervised resistance/aerobic exercise or (2 printed material comprising general physical activity recommendations. Participants will then undergo progressive training for 6 months. Measurements for primary and secondary endpoints will take place at baseline, 6 months (end of intervention, and at 6 months follow-up. Discussion This study uses a large existent cohort of patients and will generate valuable information as to the continuing effects of exercise specifically targeting cardiovascular function and disease risk, insulin metabolism, abdominal obesity, physical function, quality of life and psychological distress. We expect dissemination of the knowledge gained from this project to reduce risk factors for the
Ghotbi, Adam Ali; Køber, Lars; Finer, Nick; James, W. Philip T.; Sharma, Arya M.; Caterson, Ian; Coutinho, Walmir; Van Gaal, Luc F.; Torp-Pedersen, Christian; Andersson, Charlotte
OBJECTIVE To assess the association of hypoglycemic treatment regimens with cardiovascular adverse events and mortality in a large population of type 2 diabetic patients at increased cardiovascular risk. RESEARCH DESIGN AND METHODS This analysis included 8,192 overweight patients with type 2 diabetes from the Sibutramine Cardiovascular Outcomes (SCOUT) trial randomized to lifestyle intervention with or without sibutramine for up to 6 years. Patients were grouped according to hypoglycemic treatment at baseline. The primary end point was the time from randomization to the first occurrence of a primary outcome event (POE), nonfatal myocardial infarction, nonfatal stroke, resuscitation after cardiac arrest, or cardiovascular death. Multivariable Cox proportional hazards regression models were used to assess the impact of antiglycemic treatment on POE and all-cause mortality. RESULTS Treatments for type 2 diabetes were as follows: diet alone (n = 1,394 subjects), metformin monotherapy (n = 1,631), insulin monotherapy (n = 1,116), sulfonylurea monotherapy (n = 1,083), metformin plus sulfonylurea (n = 1,565), and metformin plus insulin (n = 1,000); 905 subjects experienced a POE and 708 died. Metformin monotherapy was associated with lower risk of POE than insulin (hazard ratio [HR], 0.74; 95% CI, 0.57–0.95; P = 0.02). Diet alone also was associated with lower risk of POE (HR, 0.65; 95% CI, 0.48–0.87; P = 0.004). Metformin monotherapy also was associated with lower mortality (HR, 0.73; 95% CI, 0.54–0.99; P POE or all-cause mortality compared with insulin as monotherapy. CONCLUSIONS In obese patients with type 2 diabetes and high risk of cardiovascular disease, monotherapy with metformin or diet-only treatment was associated with lower risk of cardiovascular events than treatment with insulin. PMID:24089540
Weber, Michael A; Bloch, Michael; Bakris, George L; Weir, Matthew R; Zappe, Dion H; Dahlof, Bjorn; Velazquez, Eric J; Pitt, Bertram; Basile, Jan N; Jamerson, Kenneth; Hua, Tsushung A
To evaluate the effects of achieved systolic blood pressure (SBP) during treatment on cardiovascular (CV) outcomes, the authors measured event rates of a composite primary endpoint (CV death or nonfatal myocardial infarction or stroke) at on-treatment SBPs of ≥140 mm Hg and the 10 mm Hg intervals of <140 mm Hg, <130 mm Hg, and <120 mm Hg in 6459 patients with diabetes (mean age, 67) and 4246 patients without diabetes (mean age, 69) from the Avoiding Cardiovascular Events in Combination Therapy in Patients Living With Systolic Hypertension (ACCOMPLISH) trial. In the diabetic cohort, the primary endpoint was 49% lower (P<.001) at <140 mm Hg than at ≥140 mm Hg, and the separate components of this endpoint were also significantly reduced. Further SBP reductions did not improve outcomes, and at <120 mm Hg they were no longer different (except for stroke) from ≥140 mm Hg. In contrast, in the nondiabetic cohort, the primary endpoint event rate fell steadily (although not significantly) through the decreasing SBP categories until it was reduced by 45% (P=.0413) at <120 mm Hg. Total stroke rates for both the diabetic (-56%, P=.0120) and nondiabetic (-68%, P=.0067) cohorts were lowest at <120 mm Hg, and adverse renal events (serum creatinine increase ≥50%) were significantly lowest in the range of 130 mm Hg to 139 mm Hg for both cohorts. Diabetic patients (<140 mm Hg or <130 mm Hg) and nondiabetic patients (<120 mm Hg) may require different SBP targets for optimal CV protection, although stroke and renal considerations should also influence the selection of blood pressure targets. PMID:27060568
This paper introduces the latest research results of salt and cardiovascular outcomes , salt intake and cardiovascular outcome have the J shape relationship;low salt and high salt increased the risk of cardiovascular;the common salt reduction recommended is nonsupported .%介绍了食盐与心血管结局关系的最新研究结果，食盐摄入量与心血管结局之间呈J形关系；低盐和高盐都增加心血管危险；不支持普遍减盐推荐。
Full Text Available Abstract Background We examined female sedentary smokers' additional cardiovascular disease (CVD risk behaviors and their associations to smoking cessation. Methods This study was part of a randomized controlled trial testing the effectiveness of exercise and nicotine gum in smoking cessation. Included in the analyses were 148 participants. Dietary habits and alcohol consumption were measured as additional CVD risk behaviors. High-fat diet and heavy alcohol use were considered those risk behaviors. Nicotine dependence, length of the longest quit attempt, depressive symptoms, self-efficacy, and education were examined as other baseline variables. Abstinence from tobacco was recorded through 12 months. Results Diet was related to depressive symptoms at baseline. Alcohol use was related to nicotine dependence and education level. Heavy alcohol use alone and accumulation of two added risk behaviors predicted poorer smoking cessation outcome. Although diet alone was not associated with cessation outcome the high-fat diet interacted with depressive symptoms, such that the depressed women with high-fat diet were significantly more likely to relapse in their quit attempt compared to other subgroups. Conclusion Non-moderate alcohol use alone and accumulation of multiple CVD risk behaviors seem to be associated with lower success in smoking cessation.
Full Text Available Abstract Background We examined female sedentary smokers' additional cardiovascular disease (CVD risk behaviors and their associations to smoking cessation. Methods This study was part of a randomized controlled trial testing the effectiveness of exercise and nicotine gum in smoking cessation. Included in the analyses were 148 participants. Dietary habits and alcohol consumption were measured as additional CVD risk behaviors. High-fat diet and heavy alcohol use were considered those risk behaviors. Nicotine dependence, length of the longest quit attempt, depressive symptoms, self-efficacy, and education were examined as other baseline variables. Abstinence from tobacco was recorded through 12 months. Results Diet was related to depressive symptoms at baseline. Alcohol use was related to nicotine dependence and education level. Heavy alcohol use alone and accumulation of two added risk behaviors predicted poorer smoking cessation outcome. Although diet alone was not associated with cessation outcome the high-fat diet interacted with depressive symptoms, such that the depressed women with high-fat diet were significantly more likely to relapse in their quit attempt compared to other subgroups. Conclusion Non-moderate alcohol use alone and accumulation of multiple CVD risk behaviors seem to be associated with lower success in smoking cessation.
Younus, Adnan; Aneni, Ehimen C; Spatz, Erica S; Osondu, Chukwuemeka U; Roberson, Lara; Ogunmoroti, Oluseye; Malik, Rehan; Ali, Shozab S; Aziz, Muhammad; Feldman, Theodore; Virani, Salim S; Maziak, Wasim; Agatston, Arthur S; Veledar, Emir; Nasir, Khurram
Several population-based studies have examined the prevalence and trends of the American Heart Association's ideal cardiovascular health (CVH) metrics as well as its association with cardiovascular disease (CVD)-related morbidity and mortality and with non-CVD outcomes. However, no efforts have been made to aggregate these studies. Accordingly, we conducted a systematic review to synthesize available data on the distribution and outcomes associated with ideal CVH metrics in both US and non-US populations. We conducted a systematic search of relevant studies in the MEDLINE and CINAHL databases, as well as the Cochrane Register of Controlled Trials (CENTRAL). Search terms used included "life's simple 7", "AHA 2020" and "ideal cardiovascular health". We included articles published in English Language from January 1, 2010, to July 31, 2015. Of the 14 US cohorts, the prevalence of 6 to 7 ideal CVH metrics ranged from as low as 0.5% in a population of African Americans to 12% in workers in a South Florida health care organization. Outside the United States, the lowest prevalence was found in an Iranian study (0.3%) and the highest was found in a large Chinese corporation (15%). All 6 mortality studies reported a graded inverse association between the increasing number of ideal CVH metrics and the all-cause and CVD-related mortality risk. A similar relationship between ideal CVH metrics and incident cardiovascular events was found in 12 of 13 studies. Finally, an increasing number of ideal CVH metrics was associated with a lower prevalence and incidence of non-CVD outcomes such as cancer, depression, and cognitive impairment. The distribution of ideal CVH metrics in US and non-US populations is similar, with low proportions of persons achieving 6 or more ideal CVH metrics. Considering the strong association of CVH metrics with both CVD and non-CVD outcomes, a coordinated global effort for improving CVH should be considered a priority. PMID:27040086
Salisbury, Chris; O’Cathain, Alicia; Thomas, Clare; Edwards, Louisa; Gaunt, Daisy; Dixon, Padraig; Hollinghurst, Sandra; Nicholl, Jon; Large, Shirley; Yardley, Lucy; Fahey, Tom; Foster, Alexis; Garner, Katy; Horspool, Kimberley; Man, Mei-See
Objective To assess whether non-clinical staff can effectively manage people at high risk of cardiovascular disease using digital health technologies. Design Pragmatic, multicentre, randomised controlled trial. Setting 42 general practices in three areas of England. Participants Between 3 December 2012 and 23 July 2013 we recruited 641 adults aged 40 to 74 years with a 10 year cardiovascular disease risk of 20% or more, no previous cardiovascular event, at least one modifiable risk factor (sy...
Williamson Paula R
Full Text Available Abstract The selection of appropriate outcomes or domains is crucial when designing clinical trials in order to compare directly the effects of different interventions in ways that minimize bias. If the findings are to influence policy and practice then the chosen outcomes need to be relevant and important to key stakeholders including patients and the public, health care professionals and others making decisions about health care. There is a growing recognition that insufficient attention has been paid to the outcomes measured in clinical trials. These issues could be addressed through the development and use of an agreed standardized collection of outcomes, known as a core outcome set, which should be measured and reported, as a minimum, in all trials for a specific clinical area. Accumulating work in this area has identified the need for general guidance on the development of core outcome sets. Key issues to consider in the development of a core outcome set include its scope, the stakeholder groups to involve, choice of consensus method and the achievement of a consensus.
Lykke, Jacob Alexander; Langhoff-Roos, Jens; Young, Bradford;
Adverse pregnancy outcome refers to placenta-mediated complications that may share a common etiopathogenesis in some cases. Unraveling associations between prothrombotic genetic predispositions and these pregnancy disorders, namely recurrent fetal loss, stillbirth, severe preeclampsia, intrauteri...... pro-thrombotic and cardiovascular genetic polymorphisms. These studies are urgently needed to accurately assess the linkage between family history, presence of adverse pregnancy outcome, and long-term cardiovascular risk....... growth restriction, and placental abruption, requires rigorous epidemiological studies involving large cohorts of patients with sufficient numbers of the adverse pregnancy outcomes in question. Such is the case with the Denmark National Birth Cohort, which was initiated in 1996 and followed pregnant...
Hypertension is a public health problem, considering its high prevalence, low control rate and cardiovascular complications. Evaluate the control of blood pressure (BP) and cardiovascular outcomes in patients enrolled at the Reference Center for Hypertension and Diabetes, located in a medium-sized city in the Midwest Region of Brazil. Population-based study comparing patients enrolled in the service at the time of their admission and after an average follow-up of five years. Participants were aged ≥18 years and were regularly monitored at the Center up to 6 months before data collection. We assessed demographic variables, BP, body mass index, risk factors, and cardiovascular outcomes. We studied 1,298 individuals, predominantly women (60.9%), and with mean age of 56.7±13.1 years. Over time, there was a significant increase in physical inactivity, alcohol consumption, diabetes, dyslipidemia, and excessive weight. As for cardiovascular outcomes, we observed an increase in stroke and myocardial revascularization, and a lower frequency of chronic renal failure. During follow-up, there was significant improvement in the rate of BP control (from 29.6% to 39.6%; p = 0.001) and 72 deaths, 91.7% of which were due to cardiovascular diseases. Despite considerable improvements in the rate of BP control during follow-up, risk factors worsened and cardiovascular outcomes increased
Guimarães Filho, Gilberto Campos, E-mail: firstname.lastname@example.org; Sousa, Ana Luiza Lima; Jardim, Thiago de Souza Veiga; Souza, Weimar Sebba Barroso; Jardim, Paulo César Brandão Veiga [Liga de Hipertensão da Faculdade de Medicina da Universidade Federal de Goiânia, Goiás, GO (Brazil)
Hypertension is a public health problem, considering its high prevalence, low control rate and cardiovascular complications. Evaluate the control of blood pressure (BP) and cardiovascular outcomes in patients enrolled at the Reference Center for Hypertension and Diabetes, located in a medium-sized city in the Midwest Region of Brazil. Population-based study comparing patients enrolled in the service at the time of their admission and after an average follow-up of five years. Participants were aged ≥18 years and were regularly monitored at the Center up to 6 months before data collection. We assessed demographic variables, BP, body mass index, risk factors, and cardiovascular outcomes. We studied 1,298 individuals, predominantly women (60.9%), and with mean age of 56.7±13.1 years. Over time, there was a significant increase in physical inactivity, alcohol consumption, diabetes, dyslipidemia, and excessive weight. As for cardiovascular outcomes, we observed an increase in stroke and myocardial revascularization, and a lower frequency of chronic renal failure. During follow-up, there was significant improvement in the rate of BP control (from 29.6% to 39.6%; p = 0.001) and 72 deaths, 91.7% of which were due to cardiovascular diseases. Despite considerable improvements in the rate of BP control during follow-up, risk factors worsened and cardiovascular outcomes increased.
Pino, Cécile; Boutron, Isabelle; Ravaud, Philippe
Background With the increasing prevalence of chronic noncommunicable diseases, patient education is becoming important to strengthen disease prevention and control. We aimed to systematically determine the extent to which registered, ongoing randomized controlled trials (RCTs) evaluated an educational intervention focus on patient-important outcomes (i.e., outcomes measuring patient health status and quality of life). Methods On May 6, 2009, we searched for all ongoing RCTs registered in the ...
Hong, Jie; Zhang, Yifei; Lai, Shenghan; Lv, Ankang; Su, Qing; Dong, Yan; Zhou, Zhiguang; Tang, Weili; Zhao, Jiajun; Cui, Lianqun; Zou, Dajin; Wang, Dawang; Li, Hong; Liu, Chao; Wu, Guoting; Shen, Jie; Zhu, Dalong; Wang, Weiqing; Shen, Weifeng; Ning, Guang
OBJECTIVE The two major classes of antidiabetic drugs, sulfonylureas and metformin, may differentially affect macrovascular complications and mortality in diabetic patients. We compared the long-term effects of glipizide and metformin on the major cardiovascular events in type 2 diabetic patients who had a history of coronary artery disease (CAD). RESEARCH DESIGN AND METHODS This study is a multicenter, randomized, double-blind, placebo-controlled clinical trial. A total of 304 type 2 diabetic patients with CAD, mean age = 63.3 years (range, 36–80 years), were enrolled. Participants were randomly assigned to receive either glipizide (30 mg daily) or metformin (1.5 g daily) for 3 years. The primary end points were times to the composite of recurrent cardiovascular events, including death from a cardiovascular cause, death from any cause, nonfatal myocardial infarction, nonfatal stroke, or arterial revascularization. RESULTS At the end of study drug administration, both groups achieved a significant decrease in the level of glycated hemoglobin (7.1% in the glipizide group and 7.0% in the metformin group). At a median follow-up of 5.0 years, 91 participants had developed 103 primary end points. Intention-to-treat analysis showed an adjusted hazard ratio (HR) of 0.54 (95% CI 0.30–0.90; P = 0.026) for the composites of cardiovascular events among the patients that received metformin, compared with glipizide. The secondary end points and adverse events were not significantly different between the two groups. CONCLUSIONS Treatment with metformin for 3 years substantially reduced major cardiovascular events in a median follow-up of 5.0 years compared with glipizide. Our results indicated a potential benefit of metformin therapy on cardiovascular outcomes in high-risk patients. PMID:23230096
van Rijn, B.B.
In this thesis, maternal constitutional factors related to long-term cardiovascular health and subsequent pregnancy outcome in women with early-onset preeclampsia is addressed. Aims of the thesis: To evaluate subsequent pregnancy outcome in women with a first pregnancy complicated by early-onset preeclampsia and to study risk factors for recurrence of preeclampsia and preterm delivery; To evaluate subsequent pregnancy outcome in women with a first pregnancy complicated by intrauterine growth ...
Lin, Pin; Rhew, Elisa; Ness, Roberta B.; PEACEMAN, Alan; Dyer, Alan; McPherson, David; Kondos, George T.; Edmundowicz, Daniel; Sutton-Tyrrell, Kim; Thompson, Trina; Ramsey-Goldman, Rosalind
Background/objective Patients with systemic lupus erythematosus (SLE) are at increased risk for adverse pregnancy outcomes and cardiovascular disease (CVD). The objective of this exploratory study was to investigate the association between a history of adverse pregnancy outcomes and subsequent risk of subclinical CVD assessed by imaging studies and verified clinical CVD events in 129 women with SLE. Methods The occurrence of adverse pregnancy outcomes, specifically pre-eclampsia, preterm birt...
Lykke, Jacob Alexander; Langhoff-Roos, Jens; Young, Bradford;
Adverse pregnancy outcome refers to placenta-mediated complications that may share a common etiopathogenesis in some cases. Unraveling associations between prothrombotic genetic predispositions and these pregnancy disorders, namely recurrent fetal loss, stillbirth, severe preeclampsia, intrauterine...... study focuses on pro-thrombotic and cardiovascular genetic polymorphisms in a nested-case control study comparing pregnancies with and without an adverse pregnancy outcome in the index pregnancy. This study will be adequately powered to determine the relationship between adverse pregnancy outcome and...
Androgen deprivation therapy leads to a number of adverse effects including deterioration of the musculoskeletal system and increased risk factors for cardiovascular and metabolic complications. The purpose of this study is to determine the effects, efficacy, retention and compliance of a physical exercise intervention in a large established cohort of prostate cancer patients from the Randomised Androgen Deprivation and Radiotherapy (RADAR) study. Specifically, we aim to compare short- and long-term effects of a prostate cancer-specific supervised exercise program to a standard public health physical activity strategy utilizing printed resources on cardiovascular and metabolic risk factors. Our primary outcomes are cardiorespiratory capacity, abdominal obesity, and lipid and glycemic control, while secondary outcomes include self-reported physical activity, quality of life and psychological distress. Multi-site randomized controlled trial of 370 men from the RADAR study cohort undergoing treatment or previously treated for prostate cancer involving androgen deprivation therapy in the cities of Perth and Newcastle (Australia), and Wellington (New Zealand). Participants will be randomized to (1) supervised resistance/aerobic exercise or (2) printed material comprising general physical activity recommendations. Participants will then undergo progressive training for 6 months. Measurements for primary and secondary endpoints will take place at baseline, 6 months (end of intervention), and at 6 months follow-up. This study uses a large existent cohort of patients and will generate valuable information as to the continuing effects of exercise specifically targeting cardiovascular function and disease risk, insulin metabolism, abdominal obesity, physical function, quality of life and psychological distress. We expect dissemination of the knowledge gained from this project to reduce risk factors for the development of co-morbid diseases commonly associated with androgen
Coster, Wendy J.
Selecting an appropriate outcome measure is a critical step in designing valid and useful clinical trials and outcome studies. This selection process needs to extend beyond examining basic psychometric properties to consider additional features of instruments that may affect their validity and utility for the study’s purpose. This article discusses these additional factors and their potential impact on outcome measurement. Guidelines are proposed to help clinical researchers and consumers of ...
Reekie, J; Mocroft, A; J, Neaton;
Since the introduction of combination antiretroviral therapy, there has been a decrease in both AIDS-defining illnesses and deaths. This decrease meant that performing clinical trials with clinical outcomes in HIV infection became more time consuming and hence costly. Improved understanding and k...
Arrigo FG Cicero
Full Text Available Arrigo FG Cicero1, Sibel Ertek21Internal Medicine, Aging and Kidney Diseases Department, Sant’Orsola-Malpighi Hospital, University of Bologna, Bologna, Italy; 2Ufuk University, Medical Faculty, Dr Ridvan Ege Hospital, Department of Endocrinology and Metabolic Diseases, Ankara, TurkeyAbstract: Berberine is a plant alkaloid with numerous biological activities. A large body of preclinical in vitro and in vivo studies support different pharmacological actions of berberine that could be potentially useful in the management of metabolic diseases associated with high cardiovascular disease risk, such as mixed hyperlipidemia, insulin resistance, metabolic syndrome, and type 2 diabetes. Moreover, it seems that berberine also exerts anti-inflammatory and antiproliferative effects that could play a role in the development of atherosclerosis and its clinical consequences. Recently, the metabolic effects of berberine have been demonstrated in humans, opening new perspectives for the use of this molecule in patient therapy. Larger and longer clinical studies need to be carried out to implement the definition of the therapeutic role of berberine in humans.Keywords: berberine, cardiovascular disease, diabetes, cholesterol
Full Text Available Abstract Background The global burden of the major vascular diseases is projected to rise and to remain the dominant non-communicable disease cluster well into the twenty first century. The Department of Health in England has developed the NHS Health Check service as a policy initiative to reduce population vascular disease risk. The aims of this study were to monitor population changes in cardiovascular disease (CVD risk factors over the first year of the new service and to assess the value of tailored lifestyle support, including motivational interview with ongoing support and referral to other services. Methods Randomised trial comparing NHS Health Check service only with NHS Health Check service plus additional lifestyle support in Stoke on Trent, England. Thirty eight general practices and 601 (365 usual care, 236 additional lifestyle support patients were recruited and randomised independently between September 2009 and February 2010. Changes in population CVD risk between baseline and one year follow-up were compared, using intention-to-treat analysis. The primary outcome was the Framingham 10 year CVD risk score. Secondary outcomes included individual modifiable risk measures and prevalence of individual risk categories. Additional lifestyle support included referral to a lifestyle coach and free sessions as needed for: weight management, physical activity, cook and eat and positive thinking. Results Average population CVD risk decreased from 32.9% to 29.4% (p Conclusions The NHS Health Check service in Stoke on Trent resulted in significant reduction in estimated population CVD risk. There was no evidence of further benefit of the additional lifestyle support services in terms of absolute CVD risk reduction.
Full Text Available Cardiovascular diseases are common in renal transplant recipients and renal insuf-ficiency has been shown to be a risk factor for cardiovascular disease. Some studies have reported that cardiovascular risk factors may contribute to the outcome of renal transplantation. This study was performed to determine the impact of cardiovascular risk factors on the outcome of renal transplantation in Iranian subjects. This is a retrospective, observational study including patients of 20-85 years of age who had undergone renal transplantation. Parameters documented and analyzed included demographics, cardiovascular risk factors, past medical history, date of last transplan-tation, the outcome of transplant, last measured serum creatinine, cause of graft failure, rejection, and death. A total of 192 patients were analyzed including 152 in the case group (with identifiable cardiovascular risk factors and 40 controls (transplant recipients without identifiable risk factors. The mean serum creatinine in the case and control groups were 1.33 ± 0.13 and 1.29 ± 0.36 mg/dL respectively (P= 0.493. Response to transplantation was categorized based on a report from the World Health Organization. Complete response to grafting occurred in the control group more than the case group (P= 0.009, while frequency of partial response to grafting was higher in the case group (0.008. A history of chronic obstructive pulmonary diseases (COPD could significantly predict the outcome of grafting (P= 0.008 as could the occurrence of renal failure (P= 0.022. Results were consistently reproduced using multivariate cumulative log it model. Our study indicates that the measured cardiovascular risk factors do not significantly influence the outcome of renal transplantation.
De Berardis, Giorgia; Sacco, Michele; Strippoli, Giovanni F.M.; Pellegrini, Fabio; Graziano, Giusi; Tognoni, Gianni; Nicolucci, Antonio
Objective To evaluate the benefits and harms of low dose aspirin in people with diabetes and no cardiovascular disease. Design Meta-analysis of randomised controlled trials. Data sources Medline (1966-November 2008), the Cochrane central register of controlled trials (Cochrane Library 2008;issue 4), and reference lists of retrieved articles. Review methods Randomised trials of aspirin compared with placebo or no aspirin in people with diabetes and no pre-existing cardiovascular disease were e...
Bansal, Nisha; Carpenter, Myra A; Weiner, Daniel E; Levey, Andrew S; Pfeffer, Marc; Kusek, John W; Cai, Jianwen; Hunsicker, Lawrence G; Park, Meyeon; Bennett, Michael; Liu, Kathleen D; Hsu, Chi-Yuan
Recipients of kidney transplants (KTR) are at increased risk for cardiovascular events, graft failure, and death. It is unknown whether urine kidney injury biomarkers are associated with poor outcomes among KTRs. We conducted a post hoc analysis of the Folic Acid for Vascular Outcome Reduction in Transplantation (FAVORIT) Trial using a case-cohort study design, selecting participants with adjudicated cardiovascular events, graft failure, or death. Urine neutrophil gelatinase-associated lipocalin (NGAL), kidney injury molecule-1 (KIM-1), IL-18, and liver-type fatty acid binding protein (L-FABP) were measured in spot urine samples and standardized to urine creatinine concentration. We adjusted for demographics, cardiovascular risk factors, eGFR, and urine albumin-to-creatinine ratio. Patients had 291 cardiovascular events, 257 graft failure events, and 359 deaths. Each log increase in urine NGAL/creatinine independently associated with a 24% greater risk of cardiovascular events (adjusted hazard ratio [aHR], 1.24; 95% confidence interval [95% CI], 1.06 to 1.45), a 40% greater risk of graft failure (aHR, 1.40; 95% CI, 1.16 to 1.68), and a 44% greater risk of death (aHR, 1.44; 95% CI, 1.26 to 1.65). Urine KIM-1/creatinine and IL-18/creatinine independently associated with greater risk of death (aHR, 1.29; 95% CI, 1.03 to 1.61 and aHR, 1.25; 95% CI, 1.04 to 1.49 per log increase, respectively) but not with risk of cardiovascular events or graft failure. Urine L-FABP did not associate with any study outcomes. In conclusion, among prevalent KTRs, higher urine NGAL, KIM-1, and IL-18 levels independently and differentially associated with greater risk of adverse outcomes. PMID:26538631
Rankinen, Tuomo; Sarzynski, Mark A; Ghosh, Sujoy; Bouchard, Claude
Clustering of obesity, coronary artery disease, and cardiovascular disease risk factors is observed in epidemiological studies and clinical settings. Twin and family studies have provided some supporting evidence for the clustering hypothesis. Loci nearest a lead single nucleotide polymorphism (SNP) showing genome-wide significant associations with coronary artery disease, body mass index, C-reactive protein, blood pressure, lipids, and type 2 diabetes mellitus were selected for pathway and n...
Anavekar, Nagesh S; McMurray, John J V; Velazquez, Eric J;
in Acute Myocardial Infarction Trial (VALIANT), we identified 14,527 patients with acute myocardial infarction complicated by clinical or radiologic signs of heart failure, left ventricular dysfunction, or both, and a documented serum creatinine measurement. Patients were randomly assigned to receive...
Full Text Available OBJECTIVES: Russia faces a high burden of cardiovascular disease. Prevalence of all cardiovascular risk factors, especially hypertension, is high. Elevated blood pressure is generally poorly controlled and medication usage is suboptimal. With a disease-model simulation, we forecast how various treatment programs aimed at increasing blood pressure control would affect cardiovascular outcomes. In addition, we investigated what additional benefit adding lipid control and smoking cessation to blood pressure control would generate in terms of reduced cardiovascular events. Finally, we estimated the direct health care costs saved by treating fewer cardiovascular events. METHODS: The Archimedes Model, a detailed computer model of human physiology, disease progression, and health care delivery was adapted to the Russian setting. Intervention scenarios of achieving systolic blood pressure control rates (defined as systolic blood pressure <140 mmHg of 40% and 60% were simulated by modifying adherence rates of an antihypertensive medication combination and compared with current care (23.9% blood pressure control rate. Outcomes of major adverse cardiovascular events; cerebrovascular event (stroke, myocardial infarction, and cardiovascular death over a 10-year time horizon were reported. Direct health care costs of strokes and myocardial infarctions were derived from official Russian statistics and tariff lists. RESULTS: To achieve systolic blood pressure control rates of 40% and 60%, adherence rates to the antihypertensive treatment program were 29.4% and 65.9%. Cardiovascular death relative risk reductions were 13.2%, and 29.6%, respectively. For the current estimated 43,855,000-person Russian hypertensive population, each control-rate scenario resulted in an absolute reduction of 1.0 million and 2.4 million cardiovascular deaths, and a reduction of 1.2 million and 2.7 million stroke/myocardial infarction diagnoses, respectively. Averted direct costs from
White, William B; Wilson, Craig A; Bakris, George L; Bergenstal, Richard M; Cannon, Christopher P; Cushman, William C; Heller, Simon K; Mehta, Cyrus R; Nissen, Steven E; Zannad, Faiez; Kupfer, Stuart
Activation of the sympathetic nervous system when there is dipeptidyl peptidase 4 inhibition in the presence of high-dose angiotensin-converting enzyme (ACE) inhibition has led to concerns of potential increases in cardiovascular events when the 2 classes of drugs are coadministered. We evaluated cardiovascular outcomes from the EXAMINE (Examination of Cardiovascular Outcomes With Alogliptin versus Standard of Care) trial according to ACE inhibitor use. Patients with type 2 diabetes mellitus and a recent acute coronary syndrome were randomly assigned to receive the dipeptidyl peptidase 4 inhibitor alogliptin or placebo added to existing antihyperglycemic and cardiovascular prophylactic therapies. Risks of adjudicated cardiovascular death, nonfatal myocardial infarction and stroke, and hospitalized heart failure were analyzed using a Cox proportional hazards model in patients according to ACE inhibitor use and dose. There were 3323 (62%) EXAMINE patients treated with an ACE inhibitor (1681 on alogliptin and 1642 on placebo). The composite rates of cardiovascular death, nonfatal myocardial infarction, and nonfatal stroke were comparable for alogliptin and placebo with ACE inhibitor (11.4% versus 11.8%; hazard ratio, 0.97; 95% confidence interval, 0.79-1.19; P=0.76) and without ACE inhibitor use (11.2% versus 11.9%; hazard ratio, 0.94; 95% confidence interval, 0.73-1.21; P=0.62). Composite rates for cardiovascular death and heart failure in patients on ACE inhibitor occurred in 6.8% of patients on alogliptin versus 7.2% on placebo (hazard ratio, 0.93; 95% confidence interval, 0.72-1.2; P=0.57). There were no differences for these end points nor for blood pressure or heart rate in patients on higher doses of ACE inhibitor. Cardiovascular outcomes were similar for alogliptin and placebo in patients with type 2 diabetes mellitus and coronary disease treated with ACE inhibitors. PMID:27480840
Richard, Edo; Jongstra, Susan; Soininen, Hilkka; Brayne, Carol; Moll van Charante, Eric P; Meiller, Yannick; van der Groep, Bram; Beishuizen, Cathrien R L; Mangialasche, Francesca; Barbera, Mariagnese; Ngandu, Tiia; Coley, Nicola; Guillemont, Juliette; Savy, Stéphanie; Dijkgraaf, Marcel G W; Peters, Ron J G; van Gool, Willem A; Kivipelto, Miia; Andrieu, Sandrine
Introduction Cardiovascular disease and dementia share a number of risk factors including hypertension, hypercholesterolaemia, smoking, obesity, diabetes and physical inactivity. The rise of eHealth has led to increasing opportunities for large-scale delivery of prevention programmes encouraging self-management. The aim of this study is to investigate whether a multidomain intervention to optimise self-management of cardiovascular risk factors in older individuals, delivered through an coach-supported interactive internet platform, can improve the cardiovascular risk profile and reduce the risk of cardiovascular disease and cognitive decline. Methods and analysis HATICE is a multinational, multicentre, prospective, randomised, open-label blinded end point (PROBE) trial with 18 months intervention. Recruitment of 2600 older people (≥65 years) at increased risk of cardiovascular disease will take place in the Netherlands, Finland and France. Participants randomised to the intervention condition will have access to an interactive internet platform, stimulating self-management of vascular risk factors, with remote support by a coach. Participants in the control group will have access to a static internet platform with basic health information. The primary outcome is a composite score based on the average z-score of the difference between baseline and 18 months follow-up values of systolic blood pressure, low-density-lipoprotein and body mass index. Main secondary outcomes include the effect on the individual components of the primary outcome, the effect on lifestyle-related risk factors, incident cardiovascular disease, mortality, cognitive functioning, mood and cost-effectiveness. Ethics and dissemination The study was approved by the medical ethics committee of the Academic Medical Center in Amsterdam, the Comité de Protection des Personnes Sud Ouest et Outre Mer in France and the Northern Savo Hospital District Research Ethics Committee in Finland. We
Klupp, Nerida L; Kiat, Hosen; Bensoussan, Alan; Steiner, Genevieve Z; Chang, Dennis H
This study aimed to evaluate the efficacy and safety of Ganoderma lucidum for the treatment of hyperglycaemia and other cardiovascular risk components of metabolic syndrome using a prospective, double-blind, randomised, placebo-controlled trial. Eighty-four participants with type 2 diabetes mellitus and metabolic syndrome were randomised to one of three intervention groups: Ganoderma lucidum, Ganoderma lucidum with Cordyceps sinensis, or placebo. The dosage was 3 g/day of Ganoderma lucidum, with or without Cordyceps sinensis, for 16 weeks. The primary outcome measure was blood glucose (glycosylated haemoglobin [HbA1c] and fasting plasma glucose [FPG]); a number of secondary outcome measures were also tested. Data from the two intervention groups were combined. The combined intervention had no effect on any of the primary (baseline-adjusted difference in means: HbA1c = 0.13%, 95% CI [-0.35, 0.60], p = 0.60; FPG = 0.03 mmol/L, 95% CI [-0.90, 0.96], p = 0.95) or secondary outcome measures over the course of the 16-week trial, and no overall increased risk of adverse events with either active treatment. Evidence from this randomised clinical trial does not support the use of Ganoderma lucidum for treatment of cardiovascular risk factors in people with diabetes mellitus or metabolic syndrome. This Clinical Trial was registered with the Australian New Zealand Clinical Trials Registry on November 23, 2006. Trial ID: ACTRN12606000485538 and can be accessed here: https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=81705. PMID:27511742
Full Text Available BACKGROUND: The systematic use of aspirin and statins in patients with diabetes and no previous cardiovascular events is controversial. We sought to assess the effects of aspirin and statins on the thrombotic risk assessed by thrombin generation (TG among patients with type II diabetes mellitus and no previous cardiovascular events. METHODOLOGY/PRINCIPAL FINDINGS: Prospective, randomized, open, blinded to events evaluation, controlled, 2×2 factorial clinical trial including 30 patients randomly allocated to aspirin 100 mg/d, atorvastatin 40 mg/d, both or none. Outcome measurements included changes in TG levels after treatment (8 to 10 weeks, assessed by a calibrated automated thrombogram. At baseline all groups had similar clinical and biochemical profiles, including TG levels. There was no interaction between aspirin and atorvastatin. Atorvastatin significantly reduced TG measured as peak TG with saline (85.09±55.34 nmol vs 153.26±75.55 nmol for atorvastatin and control groups, respectively; p = 0.018. On the other hand, aspirin had no effect on TG (121.51±81.83 nmol vs 116.85±67.66 nmol, for aspirin and control groups, respectively; p = 0.716. The effects of treatments on measurements of TG using other agonists were consistent. CONCLUSIONS/SIGNIFICANCE: While waiting for data from ongoing large clinical randomized trials to definitively outline the role of aspirin in primary prevention, our study shows that among diabetic patients without previous vascular events, statins but not aspirin reduce thrombotic risk assessed by TG. TRIAL REGISTRATION: ClinicalTrials.gov NCT00793754.
Thabane, Lehana; Kaczorowski, Janusz; Dolovich, Lisa; Larry W. Chambers; Mbuagbaw, Lawrence; ,
Abstract Knowledge translation (KT) involves implementation of evidence-based strategies and guidelines into practice to improve the process of care and health outcomes for patients. Findings from pragmatic trials may be used in KT to provide patients, healthcare providers and policymakers with information to optimize healthcare decisions based on how a given strategy or intervention performs under the real world conditions. However, pragmatic trials have been criticized for having the follow...
Rankinen, Tuomo; Sarzynski, Mark A.; Ghosh, Sujoy; Bouchard, Claude
Clustering of obesity, coronary artery disease, and cardiovascular disease risk factors is observed in epidemiological studies and clinical settings. Twin and family studies have provided some supporting evidence for the clustering hypothesis. Loci nearest a lead single nucleotide polymorphism (SNP) showing genome-wide significant associations with coronary artery disease, body mass index, C-reactive protein, blood pressure, lipids, and type 2 diabetes mellitus were selected for pathway and network analyses. Eighty-seven autosomal regions (181 SNPs), mapping to 56 genes, were found to be pleiotropic. Most pleiotropic regions contained genes associated with coronary artery disease and plasma lipids, whereas some exhibited coaggregation between obesity and cardiovascular disease risk factors. We observed enrichment for liver X receptor (LXR)/retinoid X receptor (RXR) and farnesoid X receptor/RXR nuclear receptor signaling among pleiotropic genes and for signatures of coronary artery disease and hepatic steatosis. In the search for functionally interacting networks, we found that 43 pleiotropic genes were interacting in a network with an additional 24 linker genes. ENCODE (Encyclopedia of DNA Elements) data were queried for distribution of pleiotropic SNPs among regulatory elements and coding sequence variations. Of the 181 SNPs, 136 were annotated to ≥1 regulatory feature. An enrichment analysis found over-representation of enhancers and DNAse hypersensitive regions when compared against all SNPs of the 1000 Genomes pilot project. In summary, there are genomic regions exerting pleiotropic effects on cardiovascular disease risk factors, although only a few included obesity. Further studies are needed to resolve the clustering in terms of DNA variants, genes, pathways, and actionable targets. PMID:25722444
Lin, Steven C.; Ang, Brandon; Hernandez, Carolyn; Bettencourt, Ricki; Jain, Rashmi; Salotti, Joanie; Richards, Lisa; Kono, Yuko; Bhatt, Archana; Aryafar, Hamed; Lin, Grace Y.; Valasek, Mark A.; Sirlin, Claude B.; Brouha, Sharon; Loomba, Rohit
Background: Nonalcoholic steatohepatitis (NASH) is associated with increased cardiovascular risk and mortality. No US Food and Drug Administration (FDA) approved therapies for NASH are available; clinical trials to date have not yet systematically assessed for changes in cardiovascular risk. This study examines the prospective utility of cardiovascular risk assessments, the Framingham risk score (FRS) and coronary artery calcium (CAC) score, as endpoints in a NASH randomized clinical trial, and assesses whether histologic improvements lead to lower cardiovascular risk. Methods: Secondary analysis of a 24-week randomized, double-blind, placebo-controlled trial (MOZART) in which 50 biopsy-proven NASH patients received oral ezetimibe 10 mg daily (n = 25) versus placebo (n = 25). Biochemical profiling, FRS, CAC scores, liver biopsies were obtained at baseline and endpoint. Results: Ezetimibe improved FRS whereas placebo did not (4.4 ± 6.2 to 2.9 ± 4.8, p = 0.038; 3.0 ± 4.4 to 2.9 ± 4.2, p = 0.794). CAC scores did not change with ezetimibe or placebo (180.4 ± 577.2 to 194.1 ± 623.9, p = 0.293; 151.4 ± 448.9 to 183.3 ± 555.7, p = 0.256). Ezetimibe improved FRS and CAC scores in more patients than placebo (48% versus 23%, p = 0.079, and 21% versus 0%, p = 0.090, respectively), though not significantly. No differences were noted in cardiovascular risk scores among histologic responders versus nonresponders. Conclusions: Ezetimibe improved FRS whereas placebo did not. FRS and CAC scores improved in a greater proportion of patients with ezetimibe; this trend did not reach significance. These findings indicate the utility and feasibility of monitoring cardiovascular risk in a NASH trial. The utility of CAC scores may be higher in trials of longer duration (⩾52 weeks) and with older patients (age ⩾45). ClinicalTrials.gov registration: NCT01766713. PMID:26929777
Naugle, Keith E; Naugle, Kelly M; Wikstrom, Erik A
Active-video gaming is purported to produce similar cardiovascular responses as aerobic fitness activities. This study compared the emotional and cardiovascular effects of Wii games with those of traditional exercise in college-aged adults with different exercise backgrounds. Specifically, the percentage of heart rate reserve, rate of perceived exertion (RPE), level of enjoyment, and Positive and Negative Affect Schedule scores were compared between subjects who reported exercising frequently at high intensities (high-intensity exerciser group: age = 20.18 years [0.87]; Height = 165.23 cm [9.97]; Mass = 62.37 kg [11.61]), N = 11 and those who exercise more often at lower intensities (low-intensity exercisers group: age = 20.72 years [1.19]; Height = 164.39 cm [8.05]; Mass = 68.04 kg [10.71]), N = 11. The subjects completed six 20-minute exercises sessions: treadmill walking, stationary cycling, and Wii's Tennis, Boxing, Cycling, and Step. The low-intensity exerciser group achieved a greater percentage of heart rate reserve (a) during traditional exercise compared with that during Wii boxing, (b) playing Wii boxing compared with that for Wii tennis, and (c) playing Wii boxing compared with that when the high-intensity exercisers group played any Wii games (p positive emotion were greater for boxing and for tennis compared with those for traditional exercises (p games, particularly for individuals who typically exercise at lower intensities. PMID:23660574
Cohen, Jeffrey A; Reingold, Stephen C; Polman, Chris H;
Many of the available disability outcome measures used in clinical trials of multiple sclerosis are insensitive to change over time, inadequately validated, or insensitive to patient-perceived health status or quality of life. Increasing focus on therapies that slow or reverse disability...... progression makes it essential to refine existing measures or to develop new tools. Major changes to the expanded disability status scale should be avoided to prevent the loss of acceptance by regulators as a measure for primary outcomes in trials that provide substantial evidence of effectiveness. Rather, we......, and measurement of biomarkers, show promise as adjuncts to the current disability measures, but are insufficiently validated to serve as substitutes. A collaborative approach that involves academic experts, regulators, industry representitives, and funding agencies is needed to most effectively develop disability...
Full Text Available Confidence that randomized controlled trial (RCT results accurately reflect intervention effectiveness depends on proper trial conduct and the accuracy and completeness of published trial reports. The Journal of Consulting and Clinical Psychology (JCCP is the primary trials journal amongst American Psychological Association (APA journals. The objectives of this study were to review RCTs recently published in JCCP to evaluate (1 adequacy of primary outcome analysis definitions; (2 registration status; and, (3 among registered trials, adequacy of outcome registrations. Additionally, we compared results from JCCP to findings from a recent study of top psychosomatic and behavioral medicine journals.Eligible RCTs were published in JCCP in 2013-2014. For each RCT, two investigators independently extracted data on (1 adequacy of outcome analysis definitions in the published report, (2 whether the RCT was registered prior to enrolling patients, and (3 adequacy of outcome registration.Of 70 RCTs reviewed, 12 (17.1% adequately defined primary or secondary outcome analyses, whereas 58 (82.3% had multiple primary outcome analyses without statistical adjustment or undefined outcome analyses. There were 39 (55.7% registered trials. Only two trials registered prior to patient enrollment with a single primary outcome variable and time point of assessment. However, in one of the two trials, registered and published outcomes were discrepant. No studies were adequately registered as per Standard Protocol Items: Recommendation for Interventional Trials guidelines. Compared to psychosomatic and behavioral medicine journals, the proportion of published trials with adequate outcome analysis declarations was significantly lower in JCCP (17.1% versus 32.9%; p = 0.029. The proportion of registered trials in JCCP (55.7% was comparable to behavioral medicine journals (52.6%; p = 0.709.The quality of published outcome analysis definitions and trial registrations in JCCP is
Annapureddy, N; Devilliers, H; Jolly, M
Therapeutic advances in systemic lupus erythematosus (SLE) are greatly needed. Despite advances in our knowledge of pathogenesis of the disease and targets, treatment remains a significant challenge. Finding effective and relatively safe medications remains one of the top priorities. SLE significantly impairs quality of life (QoL), and patient-reported outcomes (PROs) measure a unique aspect of the disease not captured by disease activity. Inclusion of PRO measurements is encouraged in SLE clinical trials, as they allow capturing benefits of a proposed intervention in language patients can relate to and in areas deemed pertinent and important to and by patients. Availability of patient-reported and patient-centric clinical trials data may facilitate patients in informed and shared decision making, and allow for comparative cost-effectiveness evaluation for future resource allocation and reimbursements. Herein we review clinical trials with biologic therapies wherein PRO tools were included in the study design. PMID:27497256
Cluster randomized trials (CRTs) are increasingly used in many fields including public health and medicine. We consider two-arm CRTs with binary outcomes with possibly unequal intraclass correlations coefficients (ICCs) in the two arms. The efficacy of the intervention may be measured in terms of the risk difference (RD), relative risk (RR) or odds ratio (OR). We define cost efficiency (CE) as the ratio of the precision of the efficacy measure to the study cost and develop optimal allocations...
... same title was announced in the Federal Register on March 13, 2008 (73 FR 13546), and Docket No. FDA... HUMAN SERVICES Food and Drug Administration Guidance for Industry on Hypertension Indication: Drug... for industry entitled ``Hypertension Indication: Drug Labeling for Cardiovascular Outcome...
Kwak, Jin Sook; Kim, Ji Yeon; Paek, Ju Eun; Lee, You Jin; Kim, Haeng-Ran; Park, Dong-Sik; Kwon, Oran
BACKGROUND/OBJECTIVES Although preclinical studies suggest that garlic has potential preventive effects on cardiovascular disease (CVD) risk factors, clinical trials and reports from systematic reviews or meta-analyses present inconsistent results. The contradiction might be attributed to variations in the manufacturing process that can markedly influence the composition of garlic products. To investigate this issue further, we performed a meta-analysis of the effects of garlic powder on CVD ...
Stolarz-Skrzypek, Katarzyna; Thijs, Lutgarde; Richart, Tom;
Ambulatory blood pressure (BP) monitoring provides information not only on the BP level but also on the diurnal changes in BP. In the present review, we summarized the main findings of the International Database on Ambulatory BP in relation to Cardiovascular Outcome (IDACO) with regard to risk.......1%. In conclusion, the IDACO observations support the concept that BP variability adds to risk stratification, but above all highlight that 24-h ambulatory BP level remains the main predictor to be considered in clinical practice....
Wang, Rui; Won, Sara; Haviland, Miriam J.; Bargen, Emily Von; Hacker, Michele R.; Li, Janet
Introduction and hypothesis Our aim was to identify predictors of postoperative voiding trial failure among patients who had a pelvic floor repair without a concurrent incontinence procedure in order to identify low-risk patients in whom postoperative voiding trials may be modified. Methods We conducted a retrospective cohort study of women who underwent pelvic floor repair without concurrent incontinence procedures at two institutions from 1 November 2011 through 13 October 2013 after abstracting demographic and clinical data from medical records. The primary outcome was postoperative retrograde voiding trial failure. We used modified Poisson regression to calculate the risk ratio (RR) and 95 % confidence interval (CI). Results Of the 371 women who met eligibility criteria, 294 (79.2 %) had complete data on the variables of interest. Forty nine (16.7%) failed the trial, and those women were less likely to be white (p = 0.04), more likely to have had an anterior colporrhaphy (p = 0.001), and more likely to have had a preoperative postvoid residual (PVR) ≥150 ml (p = 0.001). After adjusting for race, women were more likely to fail their voiding trial if they had a preoperative PVR of ≥150 ml (RR: 1.9; 95 % CI: 1.1–3.2); institution also was associated with voiding trial failure (RR: 3.0; 95 % CI: 1.6–5.4). Conclusions Among our cohort, postoperative voiding trial failure was associated with a PVR of ≥150 ml and institution at which the surgery was performed. PMID:26886553
Prevention of cardiovascular events with an antihypertensive regimen of amlodipine adding perindopril as required versus atenolol adding bendroflumethiazide as required, in the Anglo-Scandinavian Cardiac Outcomes Trial-Blood Pressure Lowering Arm (ASCOT-BPLA): a multicentre randomised controlled trial
Dahlöf, Björn; Sever, Peter S; Poulter, Neil R;
The apparent shortfall in prevention of coronary heart disease (CHD) noted in early hypertension trials has been attributed to disadvantages of the diuretics and beta blockers used. For a given reduction in blood pressure, some suggested that newer agents would confer advantages over diuretics an...
van Herick A
Full Text Available Andrew van Herick,1 C Andy Schuetz,1 Peter Alperin,1 Michael Bullano,2 Sanjeev Balu,2 Sanjay Gandhi21Archimedes, Inc, San Francisco, CA, USA; 2AstraZeneca Pharmaceuticals LP, Wilmington, DE, USAPurpose: Many patients treated for dyslipidemia do not achieve recommended cholesterol goals despite the widespread availability of effective statins. Pharmaceutical claims show a strong tendency for patients to remain on their initially assigned treatment. With computer simulations, the impact of initial statin treatment decisions on medium- and long-term cardiovascular outcomes were examined.Patients and methods: Using the Archimedes Model, three treatment scenarios were simulated. Patients initiated treatment with simvastatin (20, 40, or 80 mg, atorvastatin (10, 20, 40, or 80 mg, or rosuvastatin (10, 20, or 40 mg, and periodically intensified treatment. The simulated population consisted of 50,025 patients, aged 45–70 years, with low-density lipoprotein cholesterol exceeding goal. The proportion of patients initiating each dose was calibrated to United States pharmacy claims. Patients not reaching goal intensified the dose of their current statin or switched to an appropriate dose of rosuvastatin at rates matching pharmacy claims. Biomarkers and major adverse cardiovascular events (MACE were tracked for 10 years and several high-risk subpopulations were analyzed. Statin models used biomarker effects from the STELLAR (Statin Therapies for Elevated Lipid Levels Compared Across Doses to Rosuvastatin trial and outcomes data from various trials.Results: Initiating therapy with rosuvastatin reduced MACE more than simvastatin or atorvastatin. The 5- year relative risk of MACE was 0.906 (95% confidence interval: 0.888–0.923; P < 0.001 for initial treatment with atorvastatin rather than simvastatin, 0.831 (0.812–0.850; P < 0.001 for rosuvastatin rather than simvastatin, and 0.918 (0.898–0.938; P < 0.001 for rosuvastatin rather than atorvastatin
Krum, Henry; McMurray, John J V; Abraham, William T; Dickstein, Kenneth; Køber, Lars; Desai, Akshay S; Solomon, Scott D; Chiang, Yanntong; Gimpelewicz, Claudio; Reimund, Bernard; Ali, M Atif; Tarnesby, Georgia; Massie, Barry M
ATMOSPHERE with those in the Prospective comparison of Angiotensin Receptor neprilysin inhibitors with Angiotensin converting enzyme inhibitors to Determine Impact on Global Mortality and morbidity in Heart Failure trial (PARADIGM-HF); and (iii) compare the characteristics of patients with and without...... dysfunction, and were treated with a mineralocorticoid receptor antagonist. In ATMOSPHERE, patients with diabetes differed in numerous ways from those without. Patients with diabetes were older and had worse heart failure status but a similar left ventricular ejection fraction (mean 28%); they had a higher...
DiazOrdaz, K; Kenward, M G; Gomes, M; Grieve, R
Missing observations are common in cluster randomised trials. The problem is exacerbated when modelling bivariate outcomes jointly, as the proportion of complete cases is often considerably smaller than the proportion having either of the outcomes fully observed. Approaches taken to handling such missing data include the following: complete case analysis, single-level multiple imputation that ignores the clustering, multiple imputation with a fixed effect for each cluster and multilevel multiple imputation. We contrasted the alternative approaches to handling missing data in a cost-effectiveness analysis that uses data from a cluster randomised trial to evaluate an exercise intervention for care home residents. We then conducted a simulation study to assess the performance of these approaches on bivariate continuous outcomes, in terms of confidence interval coverage and empirical bias in the estimated treatment effects. Missing-at-random clustered data scenarios were simulated following a full-factorial design. Across all the missing data mechanisms considered, the multiple imputation methods provided estimators with negligible bias, while complete case analysis resulted in biased treatment effect estimates in scenarios where the randomised treatment arm was associated with missingness. Confidence interval coverage was generally in excess of nominal levels (up to 99.8%) following fixed-effects multiple imputation and too low following single-level multiple imputation. Multilevel multiple imputation led to coverage levels of approximately 95% throughout. © 2016 The Authors. Statistics in Medicine Published by John Wiley & Sons Ltd. PMID:26990655
Gilbert, Mark R; Rubinstein, Lawrence; Lesser, Glenn
Clinical outcome assessments (COAs) are increasingly being used in determining the efficacy of new treatment regimens. This was typified in the recent use of a symptom-based instrument combined with an organ-based measure of response for the approval of ruxolitinib in myelofibrosis. There are challenges in incorporating these COAs into clinical trials, including designating the level of priority, incorporating these measures into a combined or composite endpoint, and dealing with issues related to compliance and interpretation of results accounting for missing data. This article describes the results of a recent panel discussion that attempted to address these issues and provide guidance to the incorporation of COAs into clinical trials, including novel statistical designs, so that the testing of new treatments in patients with cancers of the central nervous system can incorporate these important clinical endpoints. PMID:26989129
Froud, Robert; Eldridge, Sandra; Kovacs, Francisco;
trials. METHODS: We presented experts with clinicians' views on different reporting methods and asked them to rate and comment on the suitability reporting methods for inclusion in a standardized set. Panellists developed a statement of recommendation over three online rounds. We used a modified Delphi......BACKGROUND: Low back pain is a common and expensive health complaint. Many low back pain trials have been conducted, but these are reported in a variety of ways and are often difficult to interpret. AIM: To facilitate consensus on a statement recommending reporting methods for future low back pain...... process and the RAND/UCLA appropriateness method as a formal framework for establishing appropriateness and quantifying panel disagreement. RESULTS: A group of 63 experts from 14 countries participated. Consensus was reached on a statement recommending that the continuous patient-reported outcomes...
Zheng, Jia; Cheng, Jing; Zhang, Qian; Qi, Cuijuan; Wang, Tong; Xiao, Xinhua
Glycosylated hemoglobin (HbA1c) is a critical measure of glycemic control, which may be a reliable predictor of complications after percutaneous coronary intervention (PCI). This systematic review and meta-analysis evaluates the association between HbA1c levels and clinical outcomes in diabetic patients after PCI.Pubmed, Embase, and Cochrane Library databases (dated to December 2015) were screened for relevant studies. Appropriate diabetic cases and controls, assessed using blood HbA1c levels, were extracted, and statistical analysis was conducted using RevMan 5.3 software. Summary odds ratios (ORs) with 95% confidence intervals (CIs) were used to calculate the associations between HbA1c levels and clinical outcomes in diabetic patients after PCI. Ethics review and approval was not necessary because this systematic meta-analysis did not involve any direct human trials or animal experiments.Eight studies that reported HbA1c levels for a total of 3290 diabetic subjects after PCI were included in this meta-analysis. Comprehensive integration and analysis revealed a significant correlation between higher HbA1c levels and the risk of target vessel revascularization progression (OR 1.36, 95% CI 1.03-1.82) and nonfatal myocardial infarction after PCI (OR 2.47, 95% CI 1.38-4.44). However, no significant association was found between HbA1c levels and major adverse cardiovascular events (OR 1.02, 95% CI 0.83-1.27), all-cause mortality (OR 0.73, 95% CI 0.52-1.02), cardiac death (OR 1.12, 95% CI 0.62-2.03), or in-stent thrombosis (OR 0.65, 95% CI 0.23-1.87) among diabetic patients after PCI. Sensitivity analysis indicated a statistically robust result and revealed no publication bias.Our meta-analysis demonstrated that blood HbA1c levels might be associated with higher risks of target vessel revascularization progression and nonfatal myocardial infarction among diabetic patients after PCI. However, further studies with larger sample sizes are required to verify the association
Miller, Justin B; Banks, Sarah J; Léger, Gabriel C; Cummings, Jeffrey L
Progress has been made in understanding the genetics and molecular biology of frontotemporal dementia (FTD). Targets for intervention have been identified, therapies are being developed, and clinical trials are advancing. A major challenge for FTD research is that multiple underlying pathologies can be associated with heterogeneous phenotypes. The neuropsychological profiles associated with FTD spectrum disorders often include executive dysfunction, language impairments and behavioral disturbance. Behavioral variant FTD is characterized by an initial presentation of changes in personality, behavior and/or emotion, which are often difficult to objectively capture using traditional neuropsychological measures. The two principal language variants of FTD are Progressive Nonfluent Aphasia (PNFA) with predominant agrammatic/non-fluent impairments and Semantic Dementia (SD) with semantic impairments and visual agnosia. Selection of appropriate endpoints for clinical trials is critical to ensure that the measures are adequately sensitive to detect change, yet specific enough to isolate signal from noise, and acceptable to regulatory agencies. Given the anticipated potential for small effect sizes, measures must be able to identify small incremental changes over time. It is also imperative that the measures provide adequate coverage of the constructs or behaviors of interest. Selected outcome measures should be suitable for repeat administration, yet relatively robust to practice effects to ensure that observed changes reflect true signal variance and not residual effects due to repeated measurement or poor reliability. To facilitate widespread adoption as an endpoint, measures should be readily accessible. We provide several examples of potential global, composite, and individual cognitive measures, as well as behavioral measures promising for FTD trials. Development and application of appropriate trial outcomes is critically important to success in advancing new
Mark B Zimering
Full Text Available Aim: Cardiovascular disease is a leading cause of morbidity and mortality in adults with type 2 diabetes mellitus. The aim of the present study was to test whether plasma basic fibroblast growth factor (bFGF levels predict future cardiovascular disease (CVD occurrence in adults from the Veterans Affairs Diabetes Trial. Methods: Nearly four- hundred veterans, 40 years of age or older, having a mean baseline diabetes duration of 11.4 years were recruited from outpatient clinics at six geographically distributed sites in the Veterans Affairs Diabetes Trial (VADT. Within the VADT, they were randomly assigned to intensive or standard glycemic treatment, with follow-up as much as seven and one-half years. Cardiovascular disease occurrence was examined at baseline in the patient population and during randomized treatment. Plasma bFGF was determined with a sensitive, specific two-site enzyme-linked immunoassay at the baseline study visit in all 399 subjects. Results: One hundred-five first cardiovascular events occurred in these 399 subjects. The best fit model of risk factors associated with the time to first cardiovascular disease occurrence (in the study over a seven and one-half year period had as significant predictors: prior cardiovascular event, (hazard ratio [HR] 3.378; 95% confidence intervals [CI] 3.079- 3.807; P < .0001, baseline plasma bFGF (HR 1.008; 95% CI 1.002-1.014; P =.01, age, (HR 1.027; 95% CI 1.004-1.051; P =.019, baseline plasma triglycerides, (HR 1.001; 95% CI 1.000-1.002; P =.02 and diabetes duration-treatment interaction (P =.03. Intensive glucose-lowering was associated with significantly decreased hazard ratios for CVD occurrence (0.38-0.63 in patients with known diabetes duration of 0-10 years, and non-significantly increased hazard ratios for CVD occurrence (0.82-1.78 in patients with longer diabetes duration. Conclusion: High level ofplasma basic fibroblast growth factor is a predictive biomarker of future cardiovascular
Luis Miguel Ruilope
Full Text Available Luis Miguel Ruilope1, Josep Redón2, Roland Schmieder31Servicio de Nefrologia, Unidad de Hipertension Hospital, 12 de Octubre, Madrid, Spain; 2Department of Internal Medicine, Hospital Clinico University of Valencia, Valencia, Spain; 3Department of Nephrology and Hypertension, Friedrich-Alexander-Universitat, Erlangen-Nurnberg, GermanyAbstract: Endothelial dysfunction is the initial pathophysiological step in a progression of vascular damage that leads to overt cardiovascular and chronic kidney disease. Angiotensin II, the primary agent of the renin–angiotensin system (RAS, has a central role in endothelial dysfunction. Therefore, RAS blockade with an angiotensin receptor blocker (ARB and/or angiotensin-converting enzyme (ACE inhibitor provides a rational approach to reverse endothelial dysfunction, reduce microalbuminuria, and, thus, improves cardiovascular and renal prognosis. ARBs and ACE inhibitors act at different points in the RAS pathway and recent evidence suggests that there are differences regarding their effects on endothelial dysfunction. In addition to blood pressure lowering, studies have shown that ARBs reduce target-organ damage, including improvements in endothelial dysfunction, arterial stiffness, the progression of renal dysfunction in patients with type 2 diabetes, proteinuria, and left ventricular hypertrophy. The ONgoing Telmisartan Alone in combination with Ramipril Global Endpoint Trial (ONTARGET Programme is expected to provide the ultimate evidence of whether improved endothelial func tion translates into reduced cardiovascular and renal events in high-risk patients, and to assess possible differential outcomes with telmisartan, the ACE inhibitor ramipril, or a combination of both (dual RAS blockade. Completion of ONTARGET is expected in 2008. Keywords: angiotensin-converting enzyme inhibitor, angiotensin receptor blocker, endothelial dysfunction, ONTARGET, renin–angiotensin system, telmisartan
Petrie, John R.; Marso, Steven P.; Bain, Stephen C.; Franek, Edward; Jacob, Stephan; Masmiquel, Luis; Leiter, Lawrence A.; Haluzik, Martin; Satman, Ilhan; Omar, Mohamed; Shestakova, Marina; Van Gaal, Luc; Mann, Johannes F.; Baeres, Florian M.M.; Zinman, Bernard; Poulter, Neil R.
Objective: As glucagon-like peptide-1 receptor agonists lower blood pressure (BP) in type 2 diabetes mellitus (T2DM), we examined BP control in relation to targets set by international bodies prior to randomization in the Liraglutide Effect and Action in Diabetes: Evaluation of cardiovascular outcome Results (LEADER) trial. Methods: We analyzed baseline data from LEADER (NCT01179048), an ongoing phase 3B, randomized, double-blind, placebo-controlled cardiovascular outcomes trial examining the cardiovascular safety of the glucagon-like peptide-1 receptor agonist liraglutide in 9340 people with T2DM from 32 countries [age (all mean ± SD) 64 ± 7.2 years, BMI 32.5 ± 6.3 kg/m2, duration of diabetes 12.7 ± 8.0 years], all of whom were at high risk for cardiovascular disease (CVD). Results: A total of 81% (n = 7592) of participants had prior CVD and 90% (n = 8408) had a prior history of hypertension. Despite prescription of multiple antihypertensive agents at baseline, only 51% were treated to a target BP of less than 140/85 mmHg and only 26% to the recommended baseline BP target of less than 130/80 mmHg. In univariate analyses, those with prior CVD were prescribed more agents (P < 0.001) and had lower BP than those without (137 ± 18.8/78 ± 10.6 mmHg versus 140 ± 17.7/80 ± 9.9 mmHg; P < 0.001). In logistic regression analyses, residency in North America (64% treated to <140/85 mmHg; 38% treated to <130/80 mmHg) was the strongest predictor of BP control. Conclusion: These contemporary data confirm that BP remains insufficiently controlled in a large proportion of individuals with T2DM at high cardiovascular risk, particularly outside North America. Longitudinal data from the LEADER trial may provide further insights into BP control in relation to cardiovascular outcomes in this condition. PMID:26855018
Lammi, Matthew R.; Baughman, Robert P.; Birring, Surinder S.; Russell, Anne-Marie; Ryu, Jay H.; Scholand, Marybeth; Distler, Oliver; LeSage, Daphne; Sarver, Catherine; Antoniou, Katerina; Highland, Kristin B.; Kowal-Bielecka, Otylia; Lasky, Joseph A.; Wells, Athol U.; Saketkoo, Lesley Ann
The chronic fibrosing idiopathic interstitial pneumonias (IIPs) are a group of heterogeneous pulmonary parenchymal disorders described by radiologic and histological patterns termed usual interstitial pneumonia (UIP) and non-specific interstitial pneumonia (NSIP). These include idiopathic pulmonary fibrosis (IPF) and those related to connective tissue disease (CTD) and are associated with substantial morbidity and mortality. Beyond the importance of establishing an appropriate diagnosis, designing optimal clinical trials for IIPs has been fraught with difficulties in consistency of clinical endpoints making power analyses, and the establishment of efficacy and interpretation of results across trials challenging. Preliminary recommendations, developed by rigorous consensus methods, proposed a minimum set of outcome measures, a ‘core set’, to be incorporated into future clinical trials (Saketkoo et al, THORAX. 2014.). This paper sets out to examine the candidate instruments for each domain (Dyspnea, Cough, Health Related Quality of Life, Imaging, Lung Physiology and Function, Mortality). Candidate measures that were not selected as well as measures that were not available for examination at the time of the consensus process will also be discussed. PMID:27019654
Full Text Available Abstract Background Patients with sepsis syndromes in comparison to general intensive care patients can have worse outcomes for physical function, quality of life and survival. Early intensive care rehabilitation can improve the outcome in general Intensive Care Unit (ICU patients, however no investigations have specifically looked at patients with sepsis syndromes. The 'i-PERFORM Trial' will investigate if early targeted rehabilitation is both safe and effective in patients with sepsis syndromes admitted to ICU. Methods/Design A single-centred blinded randomized controlled trial will be conducted in Brisbane, Australia. Participants (n = 252 will include those ≥ 18 years, mechanically ventilated for ≥ 48 hours and diagnosed with a sepsis syndrome. Participants will be randomised to an intervention arm which will undergo an early targeted rehabilitation program according to the level of arousal, strength and cardiovascular stability and a control group which will receive normal care. The primary outcome measures will be physical function tests on discharge from ICU (The Acute Care Index of Function and The Physical Function ICU Test. Health-related quality of life will be measured using the Short Form-36 and the psychological component will be tested using The Hospital Anxiety and Depression Scale. Secondary measures will include inflammatory biomarkers; Interleukin-6, Interleukin-10 and Tumour Necrosis Factor-α, peripheral blood mitochondrial DNA content and lactate, fat free muscle mass, tissue oxygenation and microcirculatory flow. Discussion The 'i-PERFORM Trial' will determine whether early rehabilitation for patients with sepsis is effective at improving patient outcomes with functional and physiological parameters reflecting long and short-term effects of early exercise and the safety in its application in critical illness. Trial Registration Australia and New Zealand Clinical Trials Register (ANZCTR: ACTRN12610000808044
Core Outcome Measures in Effectiveness Trials (COMET) initiative: protocol for an international Delphi study to achieve consensus on how to select outcome measurement instruments for outcomes included in a ‘core outcome set’
Prinsen, Cecilia A C; Vohra, Sunita; Rose, Michael R.; King-Jones, Susanne; Ishaque, Sana; Bhaloo, Zafira; Adams, Denise; Terwee, Caroline B
Background The Core Outcome Measures in Effectiveness Trials (COMET) initiative aims to facilitate the development and application of ‘core outcome sets’ (COS). A COS is an agreed minimum set of outcomes that should be measured and reported in all clinical trials of a specific disease or trial population. The overall aim of the Core Outcome Measurement Instrument Selection (COMIS) project is to develop a guideline on how to select outcome measurement instruments for outcomes included in a COS...
Full Text Available Abstract Background The future risk of heart disease can be predicted with increasing precision. However, more research is needed into how this risk is conveyed and presented. The aim of this study is to compare the effects of presenting cardiovascular risk in different formats on individuals' intention to change behaviour to reduce risk, understanding of risk information and emotional affect. Methods/design A randomised controlled trial comprising four arms, with a between subjects design will be performed. There will be two intervention groups and two control groups. The first control comprises a pre-intervention questionnaire and presents risk in a bar graph format. The second control presents risk in a bar graph format without pre-intervention questionnaire. These two control groups are to account for the potential Hawthorne effect of thinking about cardiovascular risk before viewing actual risk. The two intervention groups comprise presenting risk in either a pictogram or metonym format (image depicting seriousness of having a myocardial infarction. 800 individuals' aged between 45 and 64 years, who have not been previously diagnosed with heart disease and have access to a computer with internet, will be given a link to a website comprising a risk calculator and electronic questionnaires. 10-year risk of having a coronary heart disease event will be assessed and presented in one of the three formats. A post-intervention questionnaire will be completed after viewing the risk format. Main outcome measures are (i intention to change behaviour, (ii understanding of risk information, (iii emotional affect and (iv worry about future heart disease. Secondary outcomes are the sub-components of the theory of planned behaviour: attitudes, perceived behavioural control and subjective norms. Discussion Having reviewed the literature, we are not aware of any other studies which have used the assessment of actual risk, in a trial to compare different
Matsushita, Kunihiro; Coresh, Josef; Sang, Yingying; Chalmers, John; Fox, Caroline; Guallar, Eliseo; Jafar, Tazeen; Jassal, Simerjot K.; Landman, Gijs W. D.; Muntner, Paul; Roderick, Paul; Sairenchi, Toshimi; Schoettker, Ben; Shankar, Anoop; Shlipak, Michael; Tonelli, Marcello; Townend, Jonathan; van Zuilen, Arjan; Yamagishi, Kazumasa; Yamashita, Kentaro; Gansevoort, Ron; Sarnak, Mark; Warnock, David G.; Woodward, Mark; Arnlov, Johan; de Zeeuw, Dick
Background The usefulness of estimated glomerular filtration rate (eGFR) and albuminuria for prediction of cardiovascular outcomes is controversial. We aimed to assess the addition of creatinine-based eGFR and albuminuria to traditional risk factors for prediction of cardiovascular risk with a meta-
Matsushita, K.; Coresh, J.; Sang, Y.; Chalmers, J.; Fox, C.; Guallar, E.; Jafar, T.; Jassal, S.K.; Landman, G.W.; Muntner, P.; Roderick, P.; Sairenchi, T.; Schottker, B.; Shankar, A.; Shlipak, M.; Tonelli, M.; Townend, J.; Zuilen, A. van; Yamagishi, K.; Yamashita, K.; Gansevoort, R.; Sarnak, M.; Warnock, D.G.; Woodward, M.; Arnlov, J.; Wetzels, J.F.M.
BACKGROUND: The usefulness of estimated glomerular filtration rate (eGFR) and albuminuria for prediction of cardiovascular outcomes is controversial. We aimed to assess the addition of creatinine-based eGFR and albuminuria to traditional risk factors for prediction of cardiovascular risk with a meta
O'Donoghue, Michelle L; Glaser, Ruchira; Cavender, Matthew A;
IMPORTANCE: p38 Mitogen-activated protein kinase (MAPK)-stimulated inflammation is implicated in atherogenesis, plaque destabilization, and maladaptive processes in myocardial infarction (MI). Pilot data in a phase 2 trial in non-ST elevation MI indicated that the p38 MAPK inhibitor losmapimod...... potentially eligible for enrollment if they had been hospitalized with an acute MI and had at least 1 additional predictor of cardiovascular risk. INTERVENTIONS: Patients were randomized to either twice-daily losmapimod (7.5 mg; n = 1738) or matching placebo (n = 1765) on a background of guideline-recommended...
Griffo, Raffaele; Ambrosetti, Marco; Furgi, Giuseppe; Carlon, Roberto; Chieffo, Carmine; Favretto, Giuseppe; Febo, Oreste; Corrà, Ugo; Fattirolli, Francesco; Giannuzzi, Pantaleo; Greco, Cesare; Piepoli, Massimo F; Temporelli, Pier Luigi; Tramarin, Roberto; Urbinati, Stefano
Despite major improvements in diagnostics and interventional therapies, cardiovascular diseases remain a major health care and socio-economic problem in Italy. Costs and resources required are increasing in close correlation to both the improved quality of care and to the population ageing. There is an overwhelming evidence of the efficacy of cardiac rehabilitation (CR) in terms of reduction in morbidity and mortality after acute cardiac events. CR services are by definition multi-factorial and comprehensive. Furthermore, systematic analysis and monitoring of the process of delivery and outcomes is of paramount importance. The aim of this position paper promoted by the Italian Association for Cardiovascular Prevention and Rehabilitation (GICR-IACPR) is to provide specific recommendations to assist CR staff in the design, evaluation and development of their care delivery organization. The position paper should also assist health care providers, insurers, policy makers and consumers in the recognition of the quality of care requirements, standards and outcome measure, quality and performance indicators, and professional competence involved in such organization and programs. The position paper i) include comprehensive CR definition and indications, ii) describes priority criteria based on the clinical risk for admission to both inpatient or outpatient CR, and iii) defines components and technological, structural and organizing requirements for inpatient or outpatient CR services, with specific indicators and standards, performance measures and required professional skills. A specific chapter is dedicated to the requirements for highly specialized CR services for patients with more advanced cardiovascular diseases. PMID:23659104
Kunadian, Vijay; Neely, R Dermot G; Sinclair, Hannah; Batty, Jonathan A; Veerasamy, Murugapathy; Ford, Gary A; Qiu, Weiliang
Introduction The ICON1 study (a study to Improve Cardiovascular Outcomes in high-risk older patieNts with acute coronary syndrome) is a prospective observational study of older patients (≥75 years old) with non-ST-elevation acute coronary syndrome managed by contemporary treatment (pharmacological and invasive). The aim of the study was to determine the predictors of poor cardiovascular outcomes in this age group and to generate a risk prediction tool. Methods and analysis Participants are recruited from 2 tertiary hospitals in the UK. Baseline evaluation includes frailty, comorbidity, cognition and quality-of-life measures, inflammatory status assessed by a biomarker panel, including microRNAs, senescence assessed by telomere length and telomerase activity, cardiovascular status assessed by arterial stiffness, endothelial function, carotid intima media thickness and left ventricular systolic and diastolic function, and coronary plaque assessed by virtual histology intravascular ultrasound and optical coherence tomography. The patients are followed-up at 30 days and at 1 year for primary outcome measures of death, myocardial infarction, stroke, unplanned revascularisation, bleeding and rehospitalisation. Ethics and dissemination The study has been approved by the regional ethics committee (REC 12/NE/016). Findings of the study will be presented in scientific sessions and will be published in peer-reviewed journals. Trial registration number NCT01933581: Pre-results. PMID:27554105
Cordoba Currea, Gloria Cristina; Schwartz, Lisa; Woloshin, Steven; Bae, Harold; Gøtzsche, Peter
admission. Other major problems were change in the definition of the composite outcome between the abstract, methods, and results sections (13 trials); missing, ambiguous, or uninterpretable data (9 trials); and post hoc construction of composite outcomes (4 trials). Only 24 trials (60%) provided reliable...... also to the most important component. CONCLUSIONS: The use of composite outcomes in trials is problematic. Components are often unreasonably combined, inconsistently defined, and inadequately reported. These problems will leave many readers confused, often with an exaggerated perception of how well...
Sofi, Francesco; Dinu, Monica; Pagliai, Giuditta; Cesari, Francesca; Marcucci, Rossella; Casini, Alessandro
Background Nutrition is able to alter the cardiovascular health of the general population. However, the optimal dietary strategy for cardiovascular disease prevention is still far from being defined. Mediterranean and vegetarian diets are those reporting the greatest grade of evidence in the literature, but no experimental studies comparing these two dietary patterns are available. Methods/design This is an open randomized crossover clinical trial including healthy subjects with a low-to-medi...
Guo-Shuang Feng; Harry HX Xia; Ji-You Li; Shiu Kum Lam; Wei-Cheng You; Jun-Ling Ma; Benjamin CY Wong; Lian Zhang; Wei-Dong Liu; Kai-Feng Pan; Lin Shen; Xiao-Dong Zhang; Jie Li
AIM: To evaluate the long-term risk of gastroduodenal ulcer and cardiovascular events induced by celecoxib in a population-based, randomized, double-blind,placebo-controlled study.METHODS: From 2004 to 2006, a total of 1024 Chinese patients (aged 35 to 64 years) with severe chronic atrophic gastritis, intestinal metaplasia or dysplasia were randomly assigned to receive 200 mg of celecoxib twice daily or placebo in Linqu County (Shandong Province, China), a high-risk area of gastric cancer. All gastroduodenal ulcer and cardiovascular events occurred were recorded and the patients were followed up for 1.5 years after treatment. At the end of the trial, a systematic interview survey about other adverse events was conducted.RESULTS: Gastroduodenal ulcer was detected in 19 of 463 (3.72%) patients who Received: celecoxib and 17 of 473 (3.31%) patients who Received placebo,respectively (odds ratio = 1.13, 95% CI = 0.58-2.19).Cardiovascular (CV) events occurred in 4 patients who received celecoxib and in 5 patients who received placebo,respectively.Compared with those who received placebo,patients who received celecoxib had no significant increase in occurrence of Cvevents (hazard ratio = 0.84,95% CI =0.23-3.15).Among the adverse events acquired by interview survey,only the frequency of bloating was significantly higher in patients treated with celecoxib than in those treated with placebo.CONCLUSION:Treatment of gastric cancer with celecoxib is not associated with increased risk of gastroduodenal ulcer and cardiovascular events.
Full Text Available David Feldman1, Terry S Elton2, Doron M Menachemi3, Randy K Wexler41Heart Failure/Transplant and VAD Programs, Minneapolis Heart Institute, Minneapolis, Minnesota, USA; 2Division of Pharmacology, College of Pharmacology, The Ohio State University, Columbus, Ohio, USA; 3Heart Failure Services, Edith Wolfson Medical Center, The Heart Institute, Sakler School of Medicine, Tel-Aviv University, Holon, Israel; 4Department of Clinical Family Medicine, The Ohio State University, Columbus, Ohio, USAAbstract: The sympathetic nervous system is involved in regulating various cardiovascular parameters including heart rate (HR and HR variability. Aberrant sympathetic nervous system expression may result in elevated HR or decreased HR variability, and both are independent risk factors for development of cardiovascular disease, including heart failure, myocardial infarction, and hypertension. Epidemiologic studies have established that impaired HR control is linked to increased cardiovascular morbidity and mortality. One successful way of decreasing HR and cardiovascular mortality has been by utilizing β-blockers, because their ability to alter cell signaling at the receptor level has been shown to mitigate the pathogenic effects of sympathetic nervous system hyperactivation. Numerous clinical studies have demonstrated that β-blocker-mediated HR control improvements are associated with decreased mortality in postinfarct and heart failure patients. Although improved HR control benefits have yet to be established in hypertension, both traditional and vasodilating β-blockers exert positive HR control effects in this patient population. However, differences exist between traditional and vasodilating β-blockers; the latter reduce peripheral vascular resistance and exert neutral or positive effects on important metabolic parameters. Clinical evidence suggests that attainment of HR control is an important treatment objective for patients with cardiovascular
McMullan, Ciaran J; Lambers Heerspink, Hiddo J; Parving, Hans-Henrik;
(Reduction of End Points in Non-Insulin-Dependent Diabetes With the Angiotensin II Antagonist Losartan) Study. SETTING & PARTICIPANTS: 2,739 participants with type 2 diabetes and nephropathy with at least 1 year of blood pressure measurements available. PREDICTORS: Systolic blood pressure visit......BACKGROUND: Increased systolic blood pressure variability between outpatient visits is associated with increased incidence of cardiovascular end points. However, few studies have examined the association of visit-to-visit variability in systolic blood pressure with clinically relevant kidney...... disease outcomes. We analyzed the association of systolic blood pressure visit-to-visit variability with renal and cardiovascular morbidity and mortality among individuals with diabetes and nephropathy. STUDY DESIGN: Observational analysis of IDNT (Irbesartan Diabetic Nephropathy Trial) and the RENAAL...
Full Text Available Abstract Background This paper describes a methodology for comparing the effects of an eduentertainment strategy involving a music concert, and a participatory class experience involving the description and making of a healthy breakfast, as educational vehicles for delivering obesity-preventing/cardiovascular health messages to children aged 7–8 years. Methods/design This study will involve a cluster-randomised trial with blinded assessment. The study subjects will be children aged 7–8 years of both sexes attending public primary schools in the Madrid Region. The participating schools (n=30 will be randomly assigned to one of two groups: 1 Group MC, in which the children will attend a music concert that delivers obesity-preventing/cardiovascular health messages, or 2 Group HB, in which the children will attend a participatory class providing the same information but involving the description and making of a healthy breakfast. The main outcome measured will be the increase in the number of correct answers scored on a knowledge questionnaire and in an attitudes test administered before and after the above interventions. The secondary outcome recorded will be the reduction in BMI percentile among children deemed overweight/obese prior to the interventions. The required sample size (number of children was calculated for a comparison of proportions with an α of 0.05 and a β of 0.20, assuming that the Group MC subjects would show values for the measured variables at least 10% higher than those recorded for the subjects of Group HB. Corrections were made for the design effect and assuming a loss to follow-up of 10%. The maximum sample size required will be 2107 children. Data will be analysed using summary measurements for each cluster, both for making estimates and for hypothesis testing. All analyses will be made on an intention-to-treat basis. Discussion The intervention providing the best results could be recommended as part of health
Li, Fuzhong; Harmer, Peter; Liu, Yu; Eckstrom, Elizabeth; Fitzgerald, Kathleen; Stock, Ronald; Chou, Li-Shan
A previous randomized, controlled trial of tai chi showed improvements in objectively measured balance and other motor-related outcomes in patients with Parkinson's disease. This study evaluated whether patient-reported outcomes could be improved through exercise interventions and whether improvements were associated with clinical outcomes and exercise adherence. In a secondary analysis of the tai chi trial, patient-reported and clinical outcomes and exercise adherence measures were compared ...
Cruz Lemini, Mónica Cristina
Most risk factors leading to cardiovascular disease are already present in childhood and the importance of early identification of pediatric cardiovascular risk factors is now well recognized. Hypertension in the child has been associated with substantial long-term health risks and considered an indication for lifestyle modifications. Current clinical guidelines contemplate screening for hypertension in children over 3 years of age, in order to provide strategies for promoting cardiovascular ...
Inglis, Sally C.; McMurray, John J. V.; Boehm, Michael; Schaufelberger, Maria; van Veldhuisen, Dirk J.; Lindberg, Magnus; Dunselman, Peter; Hjalmarson, Ake; Kjekshus, John; Waagstein, Finn; Wedel, Hans; Wikstrand, John
To examine the relationship between baseline intermittent claudication and outcomes in patients enrolled in the Controlled Rosuvastatin Multinational Trial in Heart Failure trial (CORONA). Intermittent claudication is an independent predictor of worse outcome in coronary heart disease, but its progn
Rationale and design of the Kanyini guidelines adherence with the polypill (Kanyini-GAP study: a randomised controlled trial of a polypill-based strategy amongst Indigenous and non Indigenous people at high cardiovascular risk
Full Text Available Abstract Background The Kanyini Guidelines Adherence with the Polypill (Kanyini-GAP Study aims to examine whether a polypill-based strategy (using a single capsule containing aspirin, a statin and two blood pressure-lowering agents amongst Indigenous and non-Indigenous people at high risk of experiencing a cardiovascular event will improve adherence to guideline-indicated therapies, and lower blood pressure and cholesterol levels. Methods/Design The study is an open, randomised, controlled, multi-centre trial involving 1000 participants at high risk of cardiovascular events recruited from mainstream general practices and Aboriginal Medical Services, followed for an average of 18 months. The participants will be randomised to one of two versions of the polypill, the version chosen by the treating health professional according to clinical features of the patient, or to usual care. The primary study outcomes will be changes, from baseline measures, in serum cholesterol and systolic blood pressure and self-reported current use of aspirin, a statin and at least two blood pressure lowering agents. Secondary study outcomes include cardiovascular events, renal outcomes, self-reported barriers to indicated therapy, prescription of indicated therapy, occurrence of serious adverse events and changes in quality-of-life. The trial will be supplemented by formal economic and process evaluations. Discussion The Kanyini-GAP trial will provide new evidence as to whether or not a polypill-based strategy improves adherence to effective cardiovascular medications amongst individuals in whom these treatments are indicated. Trial Registration This trial is registered with the Australian New Zealand Clinical Trial Registry ACTRN126080005833347.
Arce Roger M
Full Text Available Abstract Background Periodontal disease (PD is an infectious clinical entity characterized by the destruction of supporting tissues of the teeth as the result of a chronic inflammatory response in a susceptible host. It has been proposed that PD as subclinical infection may contribute to the etiology and to the pathogenesis of several systemic diseases including Atherosclerosis. A number of epidemiological studies link periodontal disease/edentulism as independent risk factor for acute myocardial infarction, peripheral vascular disease, and cerebrovascular disease. Moreover, new randomized controlled clinical trials have shown an improvement on cardiovascular surrogate markers (endothelial function, sICAM, hsPCR level, fibrinogen after periodontal treatment. Nonetheless, such trials are still limited in terms of external validity, periodontal treatment strategies, CONSORT-based design and results consistency/extrapolation. The current study is designed to evaluate if periodontal treatment with scaling and root planning plus local delivered chlorhexidine improves endothelial function and other biomarkers of cardiovascular disease in subjects with moderate to severe periodontitis. Methods/Design This randomized, single-blind clinical trial will be performed at two health centers and will include two periodontal treatment strategies. After medical/periodontal screening, a baseline endothelium-dependent brachial artery flow-mediated dilatation (FMD and other systemic surrogate markers will be obtained from all recruited subjects. Patients then will be randomized to receive either supragingival/subgingival plaque cleaning and calculus removal plus chlorhexidine (treatment group or supragingival plaque removal only (control group. A second and third FMD will be obtained after 24 hours and 12 weeks in both treatment arms. Each group will consist of 49 patients (n = 98 and all patients will be followed-up for secondary outcomes and will be monitored
Heiligenhaus, Arnd; Foeldvari, Ivan; Edelsten, Clive;
To develop a set of core outcome measures for use in randomized controlled trials (RCTs) and longitudinal observational studies in juvenile idiopathic arthritis (JIA)-associated uveitis.......To develop a set of core outcome measures for use in randomized controlled trials (RCTs) and longitudinal observational studies in juvenile idiopathic arthritis (JIA)-associated uveitis....
Ainsworth, Hannah; Hewitt, Catherine E.; Higgins, Steve; Wiggins, Andy; Torgerson, David J.; Torgerson, Carole J.
Randomised controlled trials (RCTs) can be at risk of bias. Using data from a RCT, we considered the impact of post-randomisation bias. We compared the trial primary outcome, which was administered blindly, with the secondary outcome, which was not administered blindly. From 44 schools, 522 children were randomised to receive a one-to-one maths…
La Cour, Jeppe Lerche; Brok, Jesper; Gøtzsche, Peter C
To assess if authors of randomised clinical trials convey the fact that they have used surrogate outcomes and discussed their validity.......To assess if authors of randomised clinical trials convey the fact that they have used surrogate outcomes and discussed their validity....
Aydin, Mesut; Yildiz, Abdulkadir; Kaya, Zeynettin; Kaya, Zekeriya; Basarir, Ahmet Ozgur; Cakmak, Nazmiye; Donmez, Ibrahim; Morrad, Baktash; Avci, Ahmet; Demir, Kenan; Cagliyan, Emre Caglar; Yuksel, Murat; Elbey, Mehmet Ali; Kayan, Fethullah; Ozaydogdu, Necdet; Islamoglu, Yahya; Cayli, Murat; Alan, Said; Ulgen, Mehmet Siddik; Ozhan, Hakan
Infection is one of the most devastating outcomes of cardiovascular implantable electronic device (CIED) implantation and is related to significant morbidity and mortality. In our country, there is no evaluation about CIED infection. Therefore, our aim was to investigate clinical characteristics and outcome of patients who had infection related to CIED implantation or replacement. The study included 144 consecutive patients with CIED infection treated at 11 major hospitals in Turkey from 2005 to 2014 retrospectively. We analyzed the medical files of all patients hospitalized with the diagnosis of CIED infection. Inclusion criteria were definite infection related to CIED implantation, replacement, or revision. Generator pocket infection, with or without bacteremia, was the most common clinical presentation, followed by CIED-related endocarditis. Coagulase-negative staphylococci and Staphylococcus aureus were the leading causative agents of CIED infection. Multivariate analysis showed that infective endocarditis and ejection fraction were the strongest predictors of in-hospital mortality. PMID:25589093
Dixon, Padraig; Edwards, Louisa; Thomas, Clare; Gaunt, Daisy; Foster, Alexis; Large, Shirley; Montgomery, Alan A
Objectives To investigate the cost-effectiveness of a telehealth intervention for primary care patients with raised cardiovascular disease (CVD) risk. Design A prospective within-trial patient-level economic evaluation conducted alongside a randomised controlled trial. Setting Patients recruited through primary care, and intervention delivered via telehealth service. Participants Adults with a 10-year CVD risk ≥20%, as measured by the QRISK2 algorithm, with at least 1 modifiable risk factor. Intervention A series of up to 13 scripted, theory-led telehealth encounters with healthcare advisors, who supported participants to make behaviour change, use online resources, optimise medication and improve adherence. Participants in the control arm received usual care. Primary and secondary outcome measures Cost-effectiveness measured by net monetary benefit at the end of 12 months of follow-up, calculated from incremental cost and incremental quality-adjusted life years (QALYs). Productivity impacts, participant out-of-pocket expenditure and the clinical outcome were presented in a cost-consequences framework. Results 641 participants were randomised—325 to receive the telehealth intervention in addition to usual care and 316 to receive only usual care. 18% of participants had missing data on either costs, utilities or both. Multiple imputation was used for the base case results. The intervention was associated with incremental mean per-patient National Health Service (NHS) costs of £138 (95% CI 66 to 211) and an incremental QALY gain of 0.012 (95% CI −0.001 to 0.026). The incremental cost-effectiveness ratio was £10 859. Net monetary benefit at a cost-effectiveness threshold of £20 000 per QALY was £116 (95% CI −58 to 291), and the probability that the intervention was cost-effective at this threshold value was 0.77. Similar results were obtained from a complete case analysis. Conclusions There is evidence to suggest that the Healthlines telehealth
Molecular sources of residual cardiovascular risk, clinical signals, and innovative solutions: relationship with subclinical disease, undertreatment, and poor adherence: implications of new evidence upon optimizing cardiovascular patient outcomes
would be cardioprotective. When LDL cholesterol is aggressively lowered to targets, low HDL cholesterol levels are still inversely related to MCVE. The efflux capacity, or ability to relocate cholesterol out of macrophages, is believed to be a major antiatherogenic mechanism responsible for reduction in MCVE mediated in part by healthy HDL. HDL cholesterol is a complex molecule with antioxidative, anti-inflammatory, antithrombotic, antiplatelet, and vasodilatory properties, among which is protection of LDL from oxidation. HDL-associated paraoxonase-1 has a major effect on endothelial function. Further, HDL promotes endothelial repair and progenitor cell health, and supports production of nitric oxide. HDL from patients with cardiovascular disease, diabetes, and autoimmune disease may fail to protect or even become proinflammatory or pro-oxidant. Mendelian randomization and other clinical studies in which raising HDL cholesterol has not been beneficial suggest that high plasma levels do not necessarily reduce cardiovascular risk. These data, coupled with extensive preclinical information about the functional heterogeneity of HDL, challenge the “HDL hypothesis”, ie, raising HDL cholesterol per se will reduce MCVE. After the equivocal AIM-HIGH (Atherothrombosis Intervention in Metabolic Syndrome With Low HDL/High Triglycerides: Impact on Global Health Outcomes study and withdrawal of two major cholesteryl ester transfer protein compounds, one for off-target adverse effects and the other for lack of efficacy, development continues for two other agents, ie, anacetrapib and evacetrapib, both of which lower LDL cholesterol substantially. The negative but controversial HPS2-THRIVE (the Heart Protection Study 2-Treatment of HDL to Reduce the Incidence of Vascular Events trial casts further doubt on the HDL cholesterol hypothesis. The growing impression that HDL functionality, rather than abundance, is clinically important is supported by experimental evidence highlighting
Kwok, Chun Shing; Muhammad RASHID; Beynon, Rhys; Barker, Diane; Patwala, Ashish; Morley-Davies, Adrian; Satchithananda, Duwarakan; Nolan, James; Myint, Phyo K; Buchan, Iain; Loke, Yoon K.; Mamas, Mamas A.
Objective: First-degree atrioventricular block is frequently encountered in clinical practice and is generally considered a benign process. However, there is emerging evidence that prolonged PR interval may be associated with adverse outcomes. This study aims to determine if prolonged PR interval is associated with adverse cardiovascular outcomes and mortality. Methods: We searched MEDLINE and EMBASE for studies that evaluated clinical outcomes associated with prolonged and normal PR interval...
Chaugai, Sandip; Sherpa, Lhamo Yanchang; Sepehry, Amir A; Arima, Hisatomi; Wang, Dao Wen
Recent studies have demonstrated that atrial fibrillation significantly increases the risk of adverse clinical outcomes in high cardiovascular disease risk subjects. Application of renin-angiotensin-aldosterone system blockers for prevention of recurrence of atrial fibrillation and adverse clinical outcomes in subjects with atrial fibrillation is a theoretically appealing concept. However, results of clinical trials evaluating the effect of renin-angiotensin-aldosterone blockers on adverse clinical outcomes in high cardiovascular disease risk subjects with atrial fibrillation remain inconclusive.A pooled study of 6 randomized controlled trials assessing the efficacy of renin-angiotensin-aldosterone blockers on subjects with atrial fibrillation was performed.A total of 6 randomized controlled trials enrolled a total of 53,510 patients followed for 1 to 5 years. RAAS blockade therapy was associated with 14% reduction in the incidence of heart failure (OR: 0.86, [95%CI: 0.76- 0.97], P=0.018) and 17% reduction in the incidence of CVE (OR: 0.83, [95%CI: 0.70-0.99], P = 0.038). The corresponding decline in absolute risk against heart failure (ARR: 1.4%, [95%CI: 0.2-2.6%], P = 0.018) and CVE (ARR: 3.5%, [95%CI: 0.0-6.9%], P = 0.045) in the AF group was much higher than the non-AF group for heart failure (ARR: 0.4%, [95%CI: 0.0-0.7%], P = 0.057) and CVE (ARR: 1.6%, [95%CI: -0.1% to 3.3%], P = 0.071). No significant effect was noted on all-cause or cardiovascular mortality, stroke, or myocardial infarction.This study suggests that RAAS blockade offers protection against heart failure and cardiovascular events in high cardiovascular disease risk subjects with atrial fibrillation. PMID:27368043
Andreas D Meid
Full Text Available Cardiovascular disease is a leading cause of death in older people, and the impact of being exposed or not exposed to preventive cardiovascular medicines is accordingly high. Underutilization of beneficial drugs is common, but prevalence estimates differ across settings, knowledge on predictors is limited, and clinical consequences are rarely investigated.Using data from a prospective population-based cohort study, we assessed the prevalence, determinants, and outcomes of medication underuse based on cardiovascular criteria from Screening Tool To Alert to Right Treatment (START.Medication underuse was present in 69.1% of 1454 included participants (mean age 71.1 ± 6.1 years and was significantly associated with frailty (odds ratio: 2.11 [95% confidence interval: 1.24-3.63], body mass index (1.03 [1.01-1.07] per kg/m2, and inversely with the number of prescribed drugs (0.84 [0.79-0.88] per drug. Using this information for adjustment in a follow-up evaluation (mean follow-up time 2.24 years on cardiovascular and competing outcomes, we found no association of medication underuse with cardiovascular events (fatal and non-fatal (hazard ratio: 1.00 [0.65-1.56], but observed a significant association of medication underuse with competing deaths from non-cardiovascular causes (2.52 [1.01-6.30].Medication underuse was associated with frailty and adverse non-cardiovascular clinical outcomes. This may suggest that cardiovascular drugs were withheld because of serious co-morbidity or that concurrent illness can preclude benefit from cardiovascular prevention. In the latter case, adapted prescribing criteria should be developed and evaluated in those patients.
Rationale and design of the ADDITION-Leicester study, a systematic screening programme and Randomised Controlled Trial of multi-factorial cardiovascular risk intervention in people with Type 2 Diabetes Mellitus detected by screening
Farooqi A; Hiles S; Henson J; Barnett J; Campbell S; Taub N; Gray LJ; Srinivasan B; Khunti K.; Webb DR; Griffin SJ; Wareham NJ; Davies MJ
Abstract Background Earlier diagnosis followed by multi-factorial cardiovascular risk intervention may improve outcomes in Type 2 Diabetes Mellitus (T2DM). Latent phase identification through screening requires structured, appropriately targeted population-based approaches. Providers responsible for implementing screening policy await evidence of clinical and cost effectiveness from randomised intervention trials in screen-detected T2DM cases. UK South Asians are at particularly high risk of ...
Pillutla, Priya; Nguyen, Tina; Markovic, Daniela; Canobbio, Mary; Koos, Brian J; Aboulhosn, Jamil A
Congenital heart disease (CHD) increases the risk of adverse maternal and neonatal outcomes. However, previous studies have included mainly women with low-risk features. A single-center, retrospective analysis of pregnant women with CHD was performed. Inclusion criteria were the following high-risk congenital lesions and co-morbidities: maternal cyanosis; New York Heart Association (NHYA) functional class >II; severe ventricular dysfunction; maternal arrhythmia, single ventricle (SV) physiology, severe left-sided heart obstruction and severe pulmonary arterial hypertension. Multivariate analyses for predictors of adverse maternal cardiovascular and neonatal outcomes were performed. Forty-three women reported 61 pregnancies. There were no maternal or neonatal deaths. Maternal cardiac (31%) and neonatal (54%) complications were frequent. The most frequent cardiac events were pulmonary edema, arrhythmia, and reduced NYHA class. Previous arrhythmia conferred a 12-fold increase in the odds of experiencing at least one major cardiac complication. Maternal SV physiology was an independent risk factor for low birth weight, risk of neonatal intensive care unit admission and lower gestational age. Maternal cyanosis and severe pulmonary arterial hypertension also predicted adverse neonatal outcomes. In conclusion, mothers without antepartum arrhythmia or functional incapacity are unlikely to experience arrhythmias or a decrease in NYHA class during pregnancy. In addition, SV physiology is a robust predictor of neonatal complications. Antepartum counseling and assessment of maternal fitness are crucial for the woman with CHD. PMID:27055756
Golyadkina, Anastasiya A.; Kalinin, Aleksey A.; Kirillova, Irina V.; Kossovich, Elena L.; Kossovich, Leonid Y.; Menishova, Liyana R.; Polienko, Asel V.
Object of study: Improvement of life quality of patients with high stroke risk ia the main goal for development of system for patient-specific modeling of cardiovascular system. This work is dedicated at increase of safety outcomes for surgical treatment of brain blood supply alterations. The objects of study are common carotid artery, internal and external carotid arteries and bulb. Methods: We estimated mechanical properties of carotid arteries tissues and patching materials utilized at angioplasty. We studied angioarchitecture features of arteries. We developed and clinically adapted computer biomechanical models, which are characterized by geometrical, physical and mechanical similarity with carotid artery in norm and with pathology (atherosclerosis, pathological tortuosity, and their combination). Results: Collaboration of practicing cardiovascular surgeons and specialists in the area of Mathematics and Mechanics allowed to successfully conduct finite-element modeling of surgical treatment taking into account various features of operation techniques and patching materials for a specific patient. Numerical experiment allowed to reveal factors leading to brain blood supply decrease and atherosclerosis development. Modeling of carotid artery reconstruction surgery for a specific patient on the basis of the constructed biomechanical model demonstrated the possibility of its application in clinical practice at approximation of numerical experiment to the real conditions.
Daniel E. Forman
Full Text Available Longevity is increasing and the population of older adults is growing. The biology of aging is conducive to cardiovascular disease (CVD, such that prevalence of coronary artery disease, heart failure, valvular heart disease, arrhythmia and other disorders are increasing as more adults survive into old age. Furthermore, CVD in older adults is distinctive, with management issues predictably complicated by multimorbidity, polypharmacy, frailty and other complexities of care that increase management risks (e.g., bleeding, falls, and rehospitalization and uncertainty of outcomes. In this review, state-of-the-art advances in heart failure, acute coronary syndromes, transcatheter aortic valve replacement, atrial fibrillation, amyloidosis, and CVD prevention are discussed. Conceptual benefits of treatments are considered in relation to the challenges and ambiguities inherent in their application to older patients.
Full Text Available Abstract Background Pre- and postconditioning describe mechanisms whereby short ischemic periods protect an organ against a longer period of ischemia. Interestingly, short ischemic periods of a limb, in itself harmless, may increase the ischemia tolerance of remote organs, e.g. the heart (remote conditioning, RC. Although several studies have shown reduced biomarker release by RC, a reduction of complications and improvement of patient outcome still has to be demonstrated. Atrial fibrillation (AF is one of the most common complications after coronary artery bypass graft surgery (CABG, affecting 27-46% of patients. It is associated with increased mortality, adverse cardiovascular events, and prolonged in-hospital stay. We hypothesize that remote ischemic pre- and/or post-conditioning reduce the incidence of AF following CABG, and improve patient outcome. Methods/design This study is a randomized, controlled, patient and investigator blinded multicenter trial. Elective CABG patients are randomized to one of the following four groups: 1 control, 2 remote ischemic preconditioning, 3 remote ischemic postconditioning, or 4 remote ischemic pre- and postconditioning. Remote conditioning is applied at the arm by 3 cycles of 5 minutes of ischemia and reperfusion. Primary endpoint is the incidence AF in the first 72 hours after surgery, detected using a Holter-monitor. Secondary endpoints include length-of-stay on the intensive care unit and in-hospital, and the occurrence of major adverse cardiovascular events at 30 days, 3 months and 1 year. Based on an expected incidence in the control group of 27%, 195 patients per group are needed to detect with 80% power a reduction by 45% following either pre- or postconditioning, while allowing for a 10% dropout and at an alpha of 0.05. With the combined intervention expected to be stronger, we need 75 patients in this group to detect a reduction in incidence of AF of 60%. Discussion The RICO-trial (the effect of
Rogozinska, E; Fen, Y; Molyneaux, E; Khan, K S; Thangaratinam, S
Obesity is a growing threat to women of childbearing age. Increased maternal weight or excessive weight gain in pregnancy is associated with adverse pregnancy outcomes. Interventions based on diet and physical activity minimise gestational weight gain with varied effect on a number of clinical outcomes. There is no consensus amongst the trialists on the core outcomes that need to be reported to inform the clinical care of pregnant women. The aim of this systematic review is to evaluate variation in the type and quality of outcomes reported in systematic reviews and randomised controlled trials on diet and lifestyle interventions on maternal and fetal outcomes. We will assess the correlation between the type of outcome, the quality of the studies and journal impact factor. We searched the major databases from the inception to October 2013 without language restrictions. We used current recommendations for quality of outcome reporting using a 6-point scale. The quality assessment of systematic reviews and RCTs was performed using the AMSTAR and Jadad scoring systems. Additionally we obtained journals' impact factor in the year of publication. We calculated Spearman rank coefficient to assess the correlation between the type of outcome, and study quality. An overview of outcome reporting will show the current attitude of the researchers towards outcomes of importance when conducting trials on diet and lifestyle management in pregnancy. If our abstract is accepted, we will provide the details of the results. PMID:26104628
Margareta K Eriksson
Full Text Available BACKGROUND: Successfully transferring the findings of expensive and tightly controlled programmes of intensive lifestyle modification to the primary care setting is necessary if such knowledge is to be of clinical utility. The objective of this study was to test whether intensive lifestyle modification, shown previously in tightly-controlled clinical trials to be efficacious for diabetes risk-reduction among high-risk individuals, can reduce cardiovascular risk factor levels in the primary care setting. METHODOLOGY / PRINCIPAL FINDINGS: The Swedish Björknäs study was a randomized controlled trial conducted from 2003 to 2006 with follow-up on cardiovascular risk factors at 3, 12, 24 and 36 months. A total of 151 middle-aged men and women at moderate- to high-risk of cardiovascular disease from northern Sweden were randomly assigned to either an intensive lifestyle intervention (n = 75 or control (n = 76 group. The intervention was based broadly on the protocol of the Diabetes Prevention Program. The three-month intervention period was administered in the primary care setting and consisted of supervised exercise sessions and diet counselling, followed by regular group meetings during three years. The control group was given general advice about diet and exercise and received standard clinical care. Outcomes were changes in anthropometrics, aerobic fitness, self-reported physical activity, blood pressure, and metabolic traits. At 36 months post-randomisation, intensive lifestyle modification reduced waist circumference (-2.2 cm: p = 0.001, waist-hip ratio (-0.02: p<0.0001, systolic blood pressure (-4.9 mmHg: p = 0.036, and diastolic blood pressure (-1.6 mmHg: p = 0.005, and improved aerobic fitness (5%; p = 0.038. Changes in lipid or glucose values did not differ statistically between groups. At 36 months, self-reported time spent exercising and total physical activity had increased more in the intervention group than in the control group (p<0
Sinha, Ian; Jones, Leanne; Smyth, Rosalind L; Williamson, Paula R
Background In clinical trials the selection of appropriate outcomes is crucial to the assessment of whether one intervention is better than another. Selection of inappropriate outcomes can compromise the utility of a trial. However, the process of selecting the most suitable outcomes to include can be complex. Our aim was to systematically review studies that address the process of selecting outcomes or outcome domains to measure in clinical trials in children. Methods and Findings We searche...
Cox, Jafna; Johnstone, David; Nemis-White, Joanna; Montague, Terrence
Disease management is increasingly considered a valid strategy in the chronic care of our aging patient populations with multiple diseases. The Improving Cardiovascular Outcomes in Nova Scotia (ICONS) project examined whether a community-oriented health management partnership would lead to enhanced care and improved outcomes across an entire healthcare system. ICONS was a prospective cohort study, with baseline and repeated measurements of care and outcomes fed back to all project partners, along with other interventions aimed at optimizing care; preceding interval cohorts served as controls to post-intervention cohorts. The setting was the province of Nova Scotia, whose population is approximately 950,000. All 34,060 consecutive adult patients hospitalized in Nova Scotia with acute myocardial infarction (AMI), unstable angina (UA) or congestive heart failure (CHF) October 1997-March 2002 were included. Interventions were a combination of serial audits and feedbacks of practices and outcomes, web-based publication of findings, newsletter-based education and reminders, physician small-group workshops, pharmacy monitoring and compliance programs, care maps, algorithms, discharge forms and patient information cards. Rates of use of evidence-based marker therapies were the primary outcome measure. Secondary measures included one-year, all-cause mortality and re-hospitalization. Evidence-based prescription practices, for all target diseases, continuously and markedly improved over time. At the population level, there were no changes in one-year mortality for any disease state, although use of proven therapies predicted survival at the individual level throughout the five-year period for all disease states. Rates of re-hospitalization decreased significantly for all disease states over the course of ICONS; but most traditional positive and negative predictors of this outcome, like advanced age and use of proven therapies, respectively, were not predictive. ICONS
Full Text Available Background The instability of cardiovascular indices and anxiety disorders are common among patients undergoing coronary artery bypass graft (CABG and could interfere with their recovery. Therefore, improving the cardiovascular indices and anxiety is essential. Objectives This study aimed to investigate the effect of music therapy on anxiety and cardiovascular indices in patients undergoing CABG. Patients and Methods In this randomized controlled trial, 60 patients hospitalized in the cardiovascular surgical intensive care unit of Shahid Beheshti Hospital in Qom city, Iran, in 2013 were selected using a consecutive sampling method and randomly allocated into the experimental and control groups. In the experimental group, patients received 30 minutes of light music, whereas in the control group, patients had 30 minutes of rest in bed. The cardiovascular indices and anxiety were measured immediately before, immediately after and half an hour after the study. Data were analyzed using the chi-square test and repeated measures analysis of variance. Results Compared to the immediately before intervention, the mean anxiety scores immediately after and 30 minutes after the intervention were significantly lower in the experimental group (P 0.05. Conclusions Music therapy is effective in decreasing anxiety among patients undergoing CABG. However, the intervention was not effective on cardiovascular indices. Music can effectively be used as a non-pharmacological method to manage anxiety after CABG.
Fassett, Robert G; Coombes, Jeff S
Oxidative stress and inflammation are established processes contributing to cardiovascular disease caused by atherosclerosis. However, antioxidant therapies tested in cardiovascular disease such as vitamin E, C and β-carotene have proved unsuccessful at reducing cardiovascular events and mortality. Although these outcomes may reflect limitations in trial design, new, more potent antioxidant therapies are being pursued. Astaxanthin, a carotenoid found in microalgae, fungi, complex plants, seaf...
McDuffie, Roberta; Summerson, John; Reilly, Patricia; Blackwell, Caroline; Goff, David; Kimel, Angela R.; Crago, Lenore; Fonseca, Vivian
Hurricane Katrina was one of the most catastrophic natural disasters to hit the United States. It had a major impact on health care in New Orleans, LA and the surrounding region, not only in relation to acute illness but also chronic disease. When Hurricane Katrina struck New Orleans on August 29, 2005, there were 193 participants being followed in the Action to Control Cardiovascular Risk in Diabetes (ACCORD) Trial at Tulane University Health Sciences Center. In the immediate aftermath of th...
Hróbjartsson, Asbjørn; Thomsen, Ann Sofia Skou; Emanuelsson, Frida;
of trials and outcomes. We compared hazard ratios based on nonblinded and blinded assessments. A ratio of hazard ratios (RHR).... Eleven trials (1969 patients) with subjective outcomes provided hazard ratios, RHR 0.88 (0.69 to 1.12), (I2=44%, P=0.06), but unconditional pooling was problematic because of qualitative heterogeneity. Four atypical cytomegalovirus retinitis trials compared experimental oral administration with control......-treatment or active control, resulting in bias favouring the experimental intervention, RHR 0.73 (0.57 to 0.93), indicating an average exaggeration of nonblinded hazard ratios by 27% (7% to 43%). CONCLUSIONS: Lack of blinded outcome assessors in randomized trials with subjective time-to-event outcomes causes high...
BACKGROUND: Conducting a pragmatic randomised trial in primary care is often accompanied by practical problems. Such problems are seldom reported and may constitute useful lessons for researchers planning future trials. AIM: To address the difficulties involved in patient recruitment and to present measures to minimise bias during outcome assessment. METHOD: A recently conducted trial comparing the effects of corticosteroid injections and physiotherapy for painful stiff shoulder was used to i...
Antel, Jochen; Albayrak, Özgür; Heusch, Gerd; Banaschewski, Tobias; Hebebrand, Johannes
With the recent approval of methylphenidate (MPH) for treating attention-deficit/hyperactivity disorder (ADHD) in adults, the number of patients exposed will increase tremendously. The ongoing debate on the cardiovascular safety of MPH has triggered two large retrospective cohort studies in children and adolescents as well as in young to middle-aged adults. These studies looked into serious cardiovascular events (sudden cardiac death, acute myocardial infarction and stroke) as primary endpoints and concluded that MPH was safe after a mean duration of 2.1 years of follow-up in children and adolescents and mean duration of 0.33 years of current use in adults. The results are encouraging with respect to the short- and medium-term use of MPH. Without the inherent limitations of retrospective cohort studies, a prospective randomized, double-blind, placebo-controlled, multicenter trial in individuals stratified for cardiovascular risk factors would allow for an optimized risk assessment. With many millions of patients treated per year and drawing parallels to the lately discovered risks of sibutramine, another sympathomimetic with an overlapping mode of action and similar side effects on heart rate and blood pressure, we hypothesize that such a trial might be a dedicated risk mitigation strategy for public health. A critical assessment of cardiovascular side effects of MPH appears particularly warranted, because ADHD is associated with obesity, smoking and poor health in general. We summarize recent findings with the focus on cardiovascular risks of MPH in humans; we additionally analyze the limited number of rodent studies that have addressed cardiovascular risks of MPH. PMID:25149468
Welschen, Laura M. C.; Bot, Sandra D M; Kostense, Piet J.; Dekker, Jacqueline M; Timmermans, Daniëlle R.M.; van der Weijden, Trudy; Nijpels, Giel
OBJECTIVE Patients with type 2 diabetes mellitus (T2DM) underestimate their risk of developing severe complications, and they do not always understand the risk communication by their caregivers. The aim of this study was to investigate the effects of an intervention focused on the communication of the absolute 10-year risk of developing cardiovascular disease (CVD) in patients with T2DM. RESEARCH DESIGN AND METHODS A randomized controlled trial was performed in T2DM patients newly referred to...
Full Text Available BACKGROUND: At the end of the past century there were multiple concerns regarding lack of transparency in the conduct of clinical trials as well as some ethical and scientific issues affecting the trials' design and reporting. In 2000 ClinicalTrials.gov data repository was developed and deployed to serve public and scientific communities with valid data on clinical trials. Later in order to increase deposited data completeness and transparency of medical research a set of restrains had been imposed making the results deposition compulsory for multiple cases. METHODS: We investigated efficiency of the results deposition and outcome reporting as well as what factors make positive impact on providing information of interest and what makes it more difficult, whether efficiency depends on what kind of institution was a trial sponsor. Data from the ClinicalTrials.gov repository has been classified based on what kind of institution a trial sponsor was. The odds ratio was calculated for results and outcome reporting by different sponsors' class. RESULTS: As of 01/01/2012 118,602 clinical trials data deposits were made to the depository. They came from 9068 different sources. 35344 (29.8% of them are assigned as FDA regulated and 25151 (21.2% as Section 801 controlled substances. Despite multiple regulatory requirements, only about 35% of trials had clinical study results deposited, the maximum 55.56% of trials with the results, was observed for trials completed in 2008. CONCLUSIONS: The most positive impact on depositing results, the imposed restrains made for hospitals and clinics. Health care companies showed much higher efficiency than other investigated classes both in higher fraction of trials with results and in providing at least one outcome for their trials. They also more often than others deposit results when it is not strictly required, particularly, in the case of non-interventional studies.
Rosen, Raymond C.; Wing, Rena R.; Schneider, Stephen; Wadden, Thomas A.; Foster, Gary D.; West, Delia Smith; Kitabchi, Abbas E.; Brancati, Frederick L.; Maschak-Carey, Barbara J.; Bahnson, Judy L.; Lewis, Cora E.; Gendrano, Isaias N.
Introduction Determinants of erectile dysfunction in diabetic men have not been adequately investigated as potential mediators of change. Aim To determine the prevalence and correlates of erectile dysfunction (ED) in overweight men with type 2 diabetes in the multicenter, Look AHEAD trial (Action for Health in Diabetes). Main Outcome Measures International Index of Erectile Function (IIEF), self-reported use of phosphodiesterase type 5 inhibitors, laboratory measures of adiposity, cardiometabolic parameters, and exercise fitness. Methods Male participants aged 45–75 in the Look AHEAD trial in a committed relationship were recruited for an ongoing study of sexual function and diabetes. Eligible participants completed the IIEF questionnaire and provided updated information on use of medical treatments for sexual dysfunction. Baseline sexual function results for participants in the male ancillary study are reported here; intervention data and results for female participants are presented elsewhere. Results A total of 373 eligible male participants completed all sexual function questionnaires, of whom 263 (68.7%) were sexually active at the time of the study. Almost half (49.8%) of the men reported mild or moderate degrees of ED, and 24.8% had complete ED. Among sexually active participants, 42.6% had sought medical help for their problem, and 39.7% reported use of ED medications. ED was significantly associated with age (odds ratio [OR] = 1.05; confidence interval [CI]: 1.01–1.10) baseline HbA1c (OR = 1.31; CI: 1.05–1.63), hypertension history (OR = 2.41; CI: 1.34–4.36), and metabolic syndrome (OR = 3.05, CI: 1.31–7.11). Of note, cardiorespiratory fitness was found to be protective of ED in a multivariable analysis (OR = 0.61; P < 0.001). Conclusions ED is prevalent in this sample of obese, type 2 diabetic men in the Look AHEAD study. Cardiovascular risk factors were highly associated with ED in this population, and cardiorespiratory fitness was protective
Brown, Eric C.; Low, Sabina; Smith, Brian H.; Haggerty, Kevin P.
This study reports the outcomes of a randomized controlled trial of Steps to Respect: A Bullying Prevention Program conducted in 33 California elementary schools. Schools were matched on school demographic characteristics and assigned randomly to intervention or waitlisted control conditions. Outcome measures were obtained from (a) all school…
Harris-Hayes, Marcie; McDonough, Christine M; Leunig, Michael;
Patient-reported outcome measures are an important component of outcomes assessment in clinical trials to assess the treatment of femoroacetabular impingement (FAI). This review of disease-specific measures and instruments used to assess the generic quality of life and physical activity levels of...
The CHANGE trial: no superiority of lifestyle coaching plus care coordination plus treatment as usual compared to treatment as usual alone in reducing risk of cardiovascular disease in adults with schizophrenia spectrum disorders and abdominal obesity.
Speyer, Helene; Christian Brix Nørgaard, Hans; Birk, Merete; Karlsen, Mette; Storch Jakobsen, Ane; Pedersen, Kamilla; Hjorthøj, Carsten; Pisinger, Charlotta; Gluud, Christian; Mors, Ole; Krogh, Jesper; Nordentoft, Merete
Life expectancy in patients with schizophrenia is reduced by 20 years for men and 15 years for women compared to the general population. About 60% of the excess mortality is due to physical illnesses, with cardiovascular disease being dominant. CHANGE was a randomized, parallel-group, superiority, multi-centre trial with blinded outcome assessment, testing the efficacy of an intervention aimed to improve cardiovascular risk profile and hereby potentially reduce mortality. A total of 428 patients with schizophrenia spectrum disorders and abdominal obesity were recruited and centrally randomized 1:1:1 to 12 months of lifestyle coaching plus care coordination plus treatment as usual (N=138), or care coordination plus treatment as usual (N=142), or treatment as usual alone (N=148). The primary outcome was 10-year risk of cardiovascular disease assessed post-treatment and standardized to age 60. At follow-up, the mean 10-year risk of cardiovascular disease was 8.4 ± 6.7% in the group receiving lifestyle coaching, 8.5 ± 7.5% in the care coordination group, and 8.0 ± 6.5% in the treatment as usual group (p=0.41). We found no intervention effects for any secondary or exploratory outcomes, including cardiorespiratory fitness, physical activity, weight, diet and smoking. In conclusion, the CHANGE trial did not support superiority of individual lifestyle coaching or care coordination compared to treatment as usual in reducing cardiovascular risk in patients with schizophrenia spectrum disorders and abdominal obesity. PMID:27265706
The CHANGE trial: no superiority of lifestyle coaching plus care coordination plus treatment as usual compared to treatment as usual alone in reducing risk of cardiovascular disease in adults with schizophrenia spectrum disorders and abdominal obesity
Speyer, Helene; Christian Brix Nørgaard, Hans; Birk, Merete; Karlsen, Mette; Storch Jakobsen, Ane; Pedersen, Kamilla; Hjorthøj, Carsten; Pisinger, Charlotta; Gluud, Christian; Mors, Ole; Krogh, Jesper; Nordentoft, Merete
Life expectancy in patients with schizophrenia is reduced by 20 years for men and 15 years for women compared to the general population. About 60% of the excess mortality is due to physical illnesses, with cardiovascular disease being dominant. CHANGE was a randomized, parallel‐group, superiority, multi‐centre trial with blinded outcome assessment, testing the efficacy of an intervention aimed to improve cardiovascular risk profile and hereby potentially reduce mortality. A total of 428 patients with schizophrenia spectrum disorders and abdominal obesity were recruited and centrally randomized 1:1:1 to 12 months of lifestyle coaching plus care coordination plus treatment as usual (N=138), or care coordination plus treatment as usual (N=142), or treatment as usual alone (N=148). The primary outcome was 10‐year risk of cardiovascular disease assessed post‐treatment and standardized to age 60. At follow‐up, the mean 10‐year risk of cardiovascular disease was 8.4 ± 6.7% in the group receiving lifestyle coaching, 8.5 ± 7.5% in the care coordination group, and 8.0 ± 6.5% in the treatment as usual group (p=0.41). We found no intervention effects for any secondary or exploratory outcomes, including cardiorespiratory fitness, physical activity, weight, diet and smoking. In conclusion, the CHANGE trial did not support superiority of individual lifestyle coaching or care coordination compared to treatment as usual in reducing cardiovascular risk in patients with schizophrenia spectrum disorders and abdominal obesity. PMID:27265706
Full Text Available Abstract Background Depression, cardiovascular disease (CVD risk factors and cognitive impairment are important causes of disability and poor health outcomes. In combination they lead to an even worse prognosis. Internet or web-based interventions have been shown to deliver efficacious psychological intervention programs for depression on a large scale, yet no published studies have evaluated their impact among patients with co-existing physical conditions. The aims of this randomised controlled trial are to determine the effects of an evidence-based internet intervention program for depression on depressive mood symptoms, cognitive function and treatment adherence in patients at risk of CVD. Methods/Design This study is an internet-based, double-blind, parallel group randomised controlled trial. The trial will compare the effectiveness of online cognitive behavioural therapy with an online attention control placebo. The trial will consist of a 12-week intervention phase with a 40-week follow-up. It will be conducted in urban and rural New South Wales, Australia and will recruit a community-based sample of adults aged 45 to 75 years. Recruitment, intervention, cognitive testing and follow-up data collection will all be internet-based and automated. The primary outcome is a change in severity of depressive symptoms from baseline to three-months. Secondary outcomes are changes in cognitive function and adherence to treatment for CVD from baseline to three, six and 12-months. Discussion Prior studies of depression amongst patients with CVD have targeted those with previous vascular events and major depression. The potential for intervening earlier in these disease states appears to have significant potential and has yet to be tested. Scalable psychological programs using web-based interventions could deliver care to large numbers in a cost effective way if efficacy were proved. This study will determine the effects of a web-based intervention on
McDuffie, Roberta; Summerson, John; Reilly, Patricia; Blackwell, Caroline; Goff, David; Kimel, Angela R; Crago, Lenore; Fonseca, Vivian
Hurricane Katrina was one of the most catastrophic natural disasters to hit the United States. It had a major impact on health care in New Orleans, LA and the surrounding region, not only in relation to acute illness but also chronic disease. When Hurricane Katrina struck New Orleans on August 29, 2005, there were 193 participants being followed in the Action to Control Cardiovascular Risk in Diabetes (ACCORD) Trial at Tulane University Health Sciences Center. In the immediate aftermath of the storm, the Tulane University ACCORD Study site, in collaboration with the Study Coordinating Center and the Southeast Clinical Center Network office of the trial at Wake Forest University Health Sciences in North Carolina, took several actions in order to locate the participants, ensure their safety, and maintain the scientific integrity of the trial. We describe the actions taken and the relative success/failure of such actions. PMID:18577469
Hong, Jie; Zhang, Yifei; Lai, Shenghan; Lv, Ankang; Su, Qing; Dong, Yan; Zhou, Zhiguang; Tang, Weili; Zhao, Jiajun; CUI, LIANQUN; Zou, Dajin; Wang, Dawang; Li, Hong; Liu, Chao; Wu, Guoting
OBJECTIVE The two major classes of antidiabetic drugs, sulfonylureas and metformin, may differentially affect macrovascular complications and mortality in diabetic patients. We compared the long-term effects of glipizide and metformin on the major cardiovascular events in type 2 diabetic patients who had a history of coronary artery disease (CAD). RESEARCH DESIGN AND METHODS This study is a multicenter, randomized, double-blind, placebo-controlled clinical trial. A total of 304 type 2 diabeti...
Wang, Henry E; Prince, David K; Stephens, Shannon W; Herren, Heather; Daya, Mohamud; Richmond, Neal; Carlson, Jestin; Warden, Craig; Colella, M Riccardo; Brienza, Ashley; Aufderheide, Tom P; Idris, Ahamed H; Schmicker, Robert; May, Susanne; Nichol, Graham
Airway management is an important component of resuscitation from out-of-hospital cardiac arrest (OHCA). The optimal approach to advanced airway management is unknown. The Pragmatic Airway Resuscitation Trial (PART) will compare the effectiveness of endotracheal intubation (ETI) and Laryngeal Tube (LT) insertion upon 72-h survival in adult OHCA. Encompassing United States Emergency Medical Services agencies affiliated with the Resuscitation Outcomes Consortium (ROC), PART will use a cluster-crossover randomized design. Participating subjects will include adult, non-traumatic OHCA requiring bag-valve-mask ventilation. Trial interventions will include (1) initial airway management with ETI and (2) initial airway management with LT. The primary and secondary trial outcomes are 72-h survival and return of spontaneous circulation. Additional clinical outcomes will include airway management process and adverse events. The trial will enroll a total of 3000 subjects. Results of PART may guide the selection of advanced airway management strategies in OHCA. PMID:26851059
Devereaux PJ; Thabane Lehana; Pogue Janice; Yusuf Salim
Abstract Background Investigators designing clinical trials often use composite outcomes to overcome many statistical issues. Trialists want to maximize power to show a statistically significant treatment effect and avoid inflation of Type I error rate due to evaluation of multiple individual clinical outcomes. However, if the treatment effect is not similar among the components of this composite outcome, we are left not knowing how to interpret the treatment effect on the composite itself. G...
Improving patient adherence to lifestyle advice (IMPALA: a cluster-randomised controlled trial on the implementation of a nurse-led intervention for cardiovascular risk management in primary care (protocol
Full Text Available Abstract Background Many patients at high risk of cardiovascular diseases are managed and monitored in general practice. Recommendations for cardiovascular risk management, including lifestyle change, are clearly described in the Dutch national guideline. Although lifestyle interventions, such as advice on diet, physical exercise, smoking and alcohol, have moderate, but potentially relevant effects in these patients, adherence to lifestyle advice in general practice is not optimal. The IMPALA study intends to improve adherence to lifestyle advice by involving patients in decision making on cardiovascular prevention by nurse-led clinics. The aim of this paper is to describe the design and methods of a study to evaluate an intervention aimed at involving patients in cardiovascular risk management. Methods A cluster-randomised controlled trial in 20 general practices, 10 practices in the intervention arm and 10 in the control arm, starting on October 2005. A total of 720 patients without existing cardiovascular diseases but eligible for cardiovascular risk assessment will be recruited. In both arms, the general practitioners and nurses will be trained to apply the national guideline for cardiovascular risk management. Nurses in the intervention arm will receive an extended training in risk assessment, risk communication, the use of a decision aid and adapted motivational interviewing. This communication technique will be used to support the shared decision-making process about risk reduction. The intervention comprises 2 consultations and 1 follow-up telephone call. The nurses in the control arm will give usual care after the risk estimation, according to the national guideline. Primary outcome measures are self-reported adherence to lifestyle advice and drug treatment. Secondary outcome measures are the patients' perception of risk and their motivation to change their behaviour. The measurements will take place at baseline and after 12 and 52
Miller, Justin B; Banks, Sarah J; Léger, Gabriel C; Cummings, Jeffrey L.
Progress has been made in understanding the genetics and molecular biology of frontotemporal dementia (FTD). Targets for intervention have been identified, therapies are being developed, and clinical trials are advancing. A major challenge for FTD research is that multiple underlying pathologies can be associated with heterogeneous phenotypes. The neuropsychological profiles associated with FTD spectrum disorders often include executive dysfunction, language impairments and behavioral disturb...
Topping, K. J.; Miller, D.; Murray, P.; Henderson, S.; Fortuna, C.; Conlin, N.
Background: Large-scale randomised controlled trials (RCT) are relatively rare in education. The present study was an attempt to scale up previous small peer tutoring projects, while investing only modestly in continuing professional development for teachers. Purpose: A two-year RCT of peer tutoring in mathematics was undertaken in one local…
Ridker, P.M.; Genest, J.; Boekholdt, S.M.;
Background HDL-cholesterol concentrations are inversely associated with occurrence of cardiovascular events. We addressed, using the JUPITER trial cohort, whether this association remains when LDL-cholesterol concentrations are reduced to the very low ranges with high-dose statin treatment. Methods...... Participants in the randomised placebo-controlled JUPITER trial were adults without diabetes or previous cardiovascular disease, and had baseline concentrations of LDL cholesterol of less than 3.37 mmol/L and high-sensitivity C-reactive protein of 2 mg/L or more. Participants were randomly allocated by a...... quartiles and the JUPITER primary endpoint of first non-fatal myocardial infarction or stroke, hospitalisation for unstable angina, arterial revascularisation, or cardiovascular death. This trial is registered with ClinicalTrials.gov, number NCT00239681. Findings For 17802 patients in the JUPITER trial...
Chan, Aileen W K; Sit, Janet W H; Chair, Sek Ying; Leung, Doris Y P; Lee, Diana T F; Wong, Eliza M L; Fung, Lawrence C W
Physical inactivity is one of the major modifiable lifestyle risk factors for cardiovascular disease (CVD). This protocol aims to evaluate the effectiveness of Tai Chi versus brisk walking in reducing CVD risk factors. This is a randomized controlled trial with three arms, namely, Tai Chi group, walking group, and control group. The Tai Chi group will receive Tai Chi training, which consists of two 60-min sessions each week for three months, and self-practice for 30 min every day. The walking group will perform brisk walking for 30 min every day. The control group will receive their usual care. 246 subjects with CVD risk factors will be recruited from two outpatient clinics. The primary outcome is blood pressure. Secondary outcomes include fasting blood for lipid profile, sugar and glycated haemoglobin (HbA1c); body mass index, waist circumference, body fat percentage; perceived stress level and quality of life. Data collections will be conducted at baseline, 3-month, 6-month and 9-month. Generalized estimating equations model will be used to compare the changes in outcomes across time between groups. It is expected that both the Tai Chi and walking groups could maintain better health and have improved quality of life, and that Tai Chi will be more effective than brisk walking in reducing CVD risk factors. PMID:27399735
Aileen W. K. Chan
Full Text Available Physical inactivity is one of the major modifiable lifestyle risk factors for cardiovascular disease (CVD. This protocol aims to evaluate the effectiveness of Tai Chi versus brisk walking in reducing CVD risk factors. This is a randomized controlled trial with three arms, namely, Tai Chi group, walking group, and control group. The Tai Chi group will receive Tai Chi training, which consists of two 60-min sessions each week for three months, and self-practice for 30 min every day. The walking group will perform brisk walking for 30 min every day. The control group will receive their usual care. 246 subjects with CVD risk factors will be recruited from two outpatient clinics. The primary outcome is blood pressure. Secondary outcomes include fasting blood for lipid profile, sugar and glycated haemoglobin (HbA1c; body mass index, waist circumference, body fat percentage; perceived stress level and quality of life. Data collections will be conducted at baseline, 3-month, 6-month and 9-month. Generalized estimating equations model will be used to compare the changes in outcomes across time between groups. It is expected that both the Tai Chi and walking groups could maintain better health and have improved quality of life, and that Tai Chi will be more effective than brisk walking in reducing CVD risk factors.
Hyang Mo Koo
Full Text Available BACKGROUND: The prognostic importance of anemia for cardiovascular (CV events and mortality has been extensively investigated. However, little is known about the impact of transferrin saturation (TSAT, a marker reflecting the availability of iron for erythropoiesis, on clinical outcome in dialysis patients. METHODS: A total of 879 anemic incident dialysis patients were recruited from the Clinical Research Center for End-Stage Renal Disease in Korea and were divided into 3 groups according to baseline TSAT of ≤20%, 20-40%, and >40%. RESULTS: There were no differences in hemoglobin levels and the proportion of patients on erythropoiesis-stimulating agents or iron supplements among the 3 groups. During a mean follow-up duration of 19.3 months, 51 (5.8% patients died. CV composite (11.71 vs. 5.55 events/100 patient-years, P = 0.001 and all-cause mortality rates (5.38 vs. 2.31 events/100 patient-years, P = 0.016 were significantly higher in patients with TSAT ≤20% compared to those with TSAT 20-40% (reference group. Cox regression analysis revealed that patients with TSAT ≤20% had 1.62- and 2.19-fold higher risks for CV composite outcome (P = 0.046 and all-cause mortality (P = 0.030. Moreover, TSAT ≤20% was significantly associated with left ventricular hypertrophy [odds ratio (OR = 1.46], high-sensitivity C-reactive protein ≥3 mg/dL (OR = 2.09, N-terminal pro B-type natriuretic peptide ≥10000 pg/mL (OR = 2.04, and troponin-T≥0.1 ng/mL (OR = 2.02, on logistic regression analysis. CONCLUSIONS: Low TSAT was a significant independent risk factor for adverse clinical outcome in incident dialysis patients with anemia, which may be partly attributed to cardiac dysfunction and inflammation.
Schwendicke, Falk; Karimbux, Nadeem; Allareddy, Veerasathpurush; Gluud, Christian
Objectives Periodontal treatment might reduce adverse pregnancy outcomes. The efficacy of periodontal treatment to prevent preterm birth, low birth weight, and perinatal mortality was evaluated using meta-analysis and trial sequential analysis. Methods An existing systematic review was updated and meta-analyses performed. Risk of bias, heterogeneity, and publication bias were evaluated, and meta-regression performed. Subgroup analysis was used to compare different studies with low and high risk of bias and different populations, i.e., risk groups. Trial sequential analysis was used to assess risk of random errors. Results Thirteen randomized clinical trials evaluating 6283 pregnant women were meta-analyzed. Four and nine trials had low and high risk of bias, respectively. Overall, periodontal treatment had no significant effect on preterm birth (odds ratio [95% confidence interval] 0.79 [0.57-1.10]) or low birth weight (0.69 [0.43-1.13]). Trial sequential analysis demonstrated that futility was not reached for any of the outcomes. For populations with moderate occurrence (<20%) of preterm birth or low birth weight, periodontal treatment was not efficacious for any of the outcomes, and trial sequential analyses indicated that further trials might be futile. For populations with high occurrence (≥20%) of preterm birth and low birth weight, periodontal treatment seemed to reduce the risk of preterm birth (0.42 [0.24-0.73]) and low birth weight (0.32 [0.15-0.67]), but trial sequential analyses showed that firm evidence was not reached. Periodontal treatment did not significantly affect perinatal mortality, and firm evidence was not reached. Risk of bias, but not publication bias or patients’ age modified the effect estimates. Conclusions Providing periodontal treatment to pregnant women could potentially reduce the risks of perinatal outcomes, especially in mothers with high risks. Conclusive evidence could not be reached due to risks of bias, risks of random
Norman Jane E
Full Text Available Abstract Background Preterm birth is a global problem, with a prevalence of 8 to 12% depending on location. Several large trials and systematic reviews have shown progestogens to be effective in preventing or delaying preterm birth in selected high risk women with a singleton pregnancy (including those with a short cervix or previous preterm birth. Although an improvement in short term neonatal outcomes has been shown in some trials these have not consistently been confirmed in meta-analyses. Additionally data on longer term outcomes is limited to a single trial where no difference in outcomes was demonstrated at four years of age of the child, despite those in the “progesterone” group having a lower incidence of preterm birth. Methods/Design The OPPTIMUM study is a double blind randomized placebo controlled trial to determine whether progesterone prophylaxis to prevent preterm birth has long term neonatal or infant benefit. Specifically it will study whether, in women with singleton pregnancy and at high risk of preterm labour, prophylactic vaginal natural progesterone, 200 mg daily from 22 – 34 weeks gestation, compared to placebo, improves obstetric outcome by lengthening pregnancy thus reducing the incidence of preterm delivery (before 34 weeks, improves neonatal outcome by reducing a composite of death and major morbidity, and leads to improved childhood cognitive and neurosensory outcomes at two years of age. Recruitment began in 2009 and is scheduled to close in Spring 2013. As of May 2012, over 800 women had been randomized in 60 sites. Discussion OPPTIMUM will provide further evidence on the effectiveness of vaginal progesterone for prevention of preterm birth and improvement of neonatal outcomes in selected groups of women with singleton pregnancy at high risk of preterm birth. Additionally it will determine whether any reduction in the incidence of preterm birth is accompanied by improved childhood outcome. Trial
Kramer Barnett S
Full Text Available Abstract Background Randomized trials stochastically answer the question. "What would be the effect of treatment on outcome if one turned back the clock and switched treatments in the given population?" Generalizations to other subjects are reliable only if the particular trial is performed on a random sample of the target population. By considering an unobserved binary variable, we graphically investigate how randomized trials can also stochastically answer the question, "What would be the effect of treatment on outcome in a population with a possibly different distribution of an unobserved binary baseline variable that does not interact with treatment in its effect on outcome?" Method For three different outcome measures, absolute difference (DIF, relative risk (RR, and odds ratio (OR, we constructed a modified BK-Plot under the assumption that treatment has the same effect on outcome if either all or no subjects had a given level of the unobserved binary variable. (A BK-Plot shows the effect of an unobserved binary covariate on a binary outcome in two treatment groups; it was originally developed to explain Simpsons's paradox. Results For DIF and RR, but not OR, the BK-Plot shows that the estimated treatment effect is invariant to the fraction of subjects with an unobserved binary variable at a given level. Conclusion The BK-Plot provides a simple method to understand generalizability in randomized trials. Meta-analyses of randomized trials with a binary outcome that are based on DIF or RR, but not OR, will avoid bias from an unobserved covariate that does not interact with treatment in its effect on outcome.
Ioana R. Preston
Full Text Available The past two decades have seen significant improvements in the management of patients with pulmonary arterial hypertension (PAH. Although outcome has improved, long-term prognosis remains unsatisfactory. The development of new treatment options is clearly important. Equally important is testing new agents in trials designed to provide robust evidence for sustained clinical benefits enabling clinicians to determine the optimal treatment strategy for individual patients. End-points such as the change in 6-min walk distance (6MWD have been pivotal in the registration trials of currently available PAH-specific therapies. However, as current clinical trials enrol patients with milder disease, many already on background therapy, there is growing evidence that change from baseline in 6MWD is a weak surrogate of outcome in PAH. In addition, while short-term trials allowed for the rapid approval of PAH therapies in the past, there is increasing recognition that clinical trials for new agents must provide evidence of long-term benefits. Clinical trials need to evolve to provide the long-term, clinically relevant data required to appropriately assess new therapies. Event-driven long-term morbidity and mortality trials are currently underway, and will provide robust data on the frequency and timing of events, and are likely to reflect the future of clinical trial design in PAH.
Full Text Available Abstract Background Much attention has been drawn to the deleterious effects of adding progestins to estrogen as hormone therapy (HT in postmenopausal women. Some widely prescribed progestins have been shown to partially oppose the beneficial effects of estrogens on surrogate markers of cardiovascular disease (CVD risk. Progestins with higher androgenic activity may interfere with lipid profile and glucose tolerance, and could affect mechanisms of estrogen-induced C-reactive protein (CRP stimulation. Recent data have shown that norpregnane derivatives, but not micronized progesterone, increase the risk of venous thromboembolism among transdermal estrogens users. The aim of the present study was to assess the effects of combining micronized progesterone with non-oral estrogen therapy on lipid profile and cardiovascular risk factors in a sample of early postmenopausal women. Methods Clinical trial including 40 women receiving intranasal 17β estradiol 3 mg/day for two months and 46 women receiving percutaneous 17β estradiol gel 1.5 mg/day for three months (E2. Both groups received an additional 200 mg/day of micronized progesterone by vaginal route 14 days/month (E2+P. Outcome measures included body weight, waist circumference, body mass index (BMI, lipid profile and ultra-sensitive C-reactive protein (usCRP at baseline and during the E2 or E2+P portions of treatment. Results Mean age was 51±3 years. Mean time since menopause was 22.2±10 months. Most participants were overweight; HT did not change BMI. E2 and E2+P did not affect waist circumference and weight. Menopausal symptoms improved after HT. The effects of intranasal and percutaneous estradiol were similar, regardless of the addition of progesterone. Similarly, for the overall group of 86 women, micronized progesterone did not alter the response to E2. Blood pressure, glucose, insulin, HDL-c, triglycerides, and usCRP remained constant with or without micronized progesterone. Total
Caille, Agnès; Leyrat, Clémence; Giraudeau, Bruno
In cluster randomized trials, clusters of subjects are randomized rather than subjects themselves, and missing outcomes are a concern as in individual randomized trials. We assessed strategies for handling missing data when analysing cluster randomized trials with a binary outcome; strategies included complete case, adjusted complete case, and simple and multiple imputation approaches. We performed a simulation study to assess bias and coverage rate of the population-averaged intervention-effect estimate. Both multiple imputation with a random-effects logistic regression model or classical logistic regression provided unbiased estimates of the intervention effect. Both strategies also showed good coverage properties, even slightly better for multiple imputation with a random-effects logistic regression approach. Finally, this latter approach led to a slightly negatively biased intracluster correlation coefficient estimate but less than that with a classical logistic regression model strategy. We applied these strategies to a real trial randomizing households and comparing ivermectin and malathion to treat head lice. PMID:24713160
Mihos, Christos G; Krishna, Rama K; Kherada, Nisharahmed; Larrauri-Reyes, Maiteder; Tolentino, Alfonso; Santana, Orlando
Ranolazine has characteristic properties of a selective inhibitor of the inward sodium current. It is primarily indicated as an anti-anginal agent in patients with coronary artery disease and chronic stable angina. Recently, ranolazine has been noted to possibly impart beneficial effects in various other cardiac conditions, including new-onset, paroxysmal, and chronic atrial fibrillation, post-operative atrial fibrillation, ventricular arrhythmias, post-revascularization coronary artery disease, chemotherapeutic cardiotoxicity, and diastolic and microvascular dysfunction. Herein, we present a review of the current clinical evidence describing the adjunctive or synergistic effects of ranolazine in non-angina related cardiovascular disorders, and include a discussion of the ongoing randomized trials investigating the therapeutic potential of ranolazine in a variety of cardiovascular diseases. PMID:26546970
Cockayne, Sarah; Hewitt, Catherine; Hashmi, Farina; Hicks, Kate; Concannon, Michael; McIntosh, Caroline; Thomas, Kim; Hall, Jill; Watson, Judith; Torgerson, David; Watt, Ian
Background Trials using inadequate levels of blinding may report larger effect sizes than blinded studies. It has been suggested that blinded outcome assessment in open trials may in some cases be undertaken by assessments of photographs. The aim of this paper is to explore the effect of using different methods to assess the primary outcome in the EVerT (Effective Verruca Treatments) trial. It also aims to give an overview of the experiences of using digital photographs within the trial. Meth...
Full Text Available Evidence suggests there are inconsistencies in patient-reported outcome (PRO assessment and reporting in clinical trials, which may limit the use of these data to inform patient care. For trials with a PRO endpoint, routine inclusion of key PRO information in the protocol may help improve trial conduct and the reporting and appraisal of PRO results; however, it is currently unclear exactly what PRO-specific information should be included. The aim of this review was to summarize the current PRO-specific guidance for clinical trial protocol developers.We searched the MEDLINE, EMBASE, CINHAL and Cochrane Library databases (inception to February 2013 for PRO-specific guidance regarding trial protocol development. Further guidance documents were identified via Google, Google scholar, requests to members of the UK Clinical Research Collaboration registered clinical trials units and international experts. Two independent investigators undertook title/abstract screening, full text review and data extraction, with a third involved in the event of disagreement. 21,175 citations were screened and 54 met the inclusion criteria. Guidance documents were difficult to access: electronic database searches identified just 8 documents, with the remaining 46 sourced elsewhere (5 from citation tracking, 27 from hand searching, 7 from the grey literature review and 7 from experts. 162 unique PRO-specific protocol recommendations were extracted from included documents. A further 10 PRO recommendations were identified relating to supporting trial documentation. Only 5/162 (3% recommendations appeared in ≥50% of guidance documents reviewed, indicating a lack of consistency.PRO-specific protocol guidelines were difficult to access, lacked consistency and may be challenging to implement in practice. There is a need to develop easily accessible consensus-driven PRO protocol guidance. Guidance should be aimed at ensuring key PRO information is routinely included in
Full Text Available Background: Patients presenting with chest pain and evidence of functional ischemia by myocardial perfusion imaging (MPI, but lacking commensurate angiographic disease pose a diagnostic and therapeutic dilemma. They are often dismissed as having ′false-positive MPI′. Moreover, a majority of the available long-term outcome data for it has been derived from homogenous female populations. In this study, we sought to evaluate the long-term outcomes of this presentation in a multiethnic male-predominant cohort. Materials and Methods: We retrospectively identified 47 patients who presented to our institution between 2002 and 2005 with chest pain and evidence of ischemia on MPI, but with no significant angiographic disease on subsequent cardiac catheterization (cases. The occurrence of adverse cardiovascular outcomes (chest pain, congestive heart failure, acute myocardial infarction and stroke post-index coronary angiogram was tracked. Similar data was collected for 37 patients who also presented with chest pain, but normal MPI over the same period (controls. Overall average follow-up was over 22 months. Results: Fifty-three percent (26/47 of the cases had one or more of the adverse outcomes as compared with 22% (8/37 of controls (P < 0.01. Of these, 13 (50.0% and 3 (37.5% were males, respectively. Conclusions: Ischemia on MPI is predictive of long-term adverse cardiovascular outcomes despite normal (′false-negative′ coronary angiography. This appears to be gender-neutral.
Kiberd, Bryce; Panek, Romuald
Background and objectives: Cardiovascular disease is an important cause of morbidity and death in kidney transplant recipients. This study examines the Framingham risk score's ability to predict cardiac and stroke events. Because cyclosporine and tacrolimus have different cardiovascular risk profiles, these agents were also examined.
textabstractPhase III clinical trials to assess the clinical benefit of new treatment options often require large patient numbers and long follow-up, in particular in diseases with a long natural history, such as prostate cancer. In this thesis, we argue that in order to improve the efficiency of phase III prostate cancer clinical trials, a thorough understanding of prognostic factors of outcome is needed, as well as an exploration of potential predictive factors that might affect treatment b...
Stutchfield, Peter Roy; Whitaker, Rhiannon; Gliddon, Angela E; Hobson, Lucie; Kotecha, Sailesh; Doull, Iolo J M
Objectives To determine whether antenatal betamethasone prior to elective term caesarean section (CS) affects long term behavioural, cognitive or developmental outcome, and whether the risk of asthma or atopic disease is reduced. Design A questionnaire based follow-up of a multicentre randomised controlled trial (Antenatal Steroids for Term Elective Caesarean Section, BMJ 2005). Setting Four UK study centres from the original trial. Participants 862 participants from the four largest recruiti...
Ahlehoff, O; Skov, L; Gislason, Gunnar Hilmar;
BACKGROUND: Psoriasis is a common disease and is associated with cardiovascular diseases. Systemic anti-inflammatory drugs may reduce risk of cardiovascular events. We therefore examined the rate of cardiovascular events, i.e. cardiovascular death, myocardial infarction and stroke, in patients with...... severe psoriasis treated with systemic anti-inflammatory drugs. METHODS: Individual-level linkage of administrative registries was used to perform a longitudinal nationwide cohort study. Time-dependent multivariable adjusted Cox regression was used to estimate hazard ratios (HRs) with 95% confidence...... factor inhibitors (HR 0.46; CI 0.22-0.98) were linked to reduced event rates, whereas the interleukin-12/23 inhibitor ustekinumab (HR 1.52; CI 0.47-4.94) was not. CONCLUSION: Systemic anti-inflammatory treatment with methotrexate was associated with significantly lower rates of cardiovascular events...
Zannad, F.; Stough, W.G.; Pitt, B.;
Specific criteria have been established to define the occurrence of myocardial infarction (MI) and stroke in cardiovascular clinical trials, but there is not a consistent definition for heart failure. Heart failure events appear to occur at a rate that is similar to stroke and MI in trials...... of hypertension, hyperlipidaemia, diabetes, and coronary heart disease, yet a consistent approach to defining heart failure events has not yet been realized. The wide range of definitions used in clinical trials makes it difficult to interpret new data in the context of existing literature. This inconsistency has...... led to challenges in determining the incidence of heart failure in cardiovascular studies and the effects of interventions on these endpoints. This paper examines issues related to defining heart failure events in cardiovascular clinical trials and presents a definition to formally address this issue...
Orange juice–derived flavanone and phenolic metabolites do not acutely affect cardiovascular risk biomarkers: a randomized, placebo-controlled, crossover trial in men at moderate risk of cardiovascular disease
Schar, Manuel; Curtis, Peter; Hazim, Sara; Ostertag, Luisa; Kay, Colin; Potter, John; Cassidy, Aedin
Background: Epidemiologic data suggest inverse associations between citrus flavanone intake and cardiovascular disease (CVD) risk. However, insufficient randomized controlled trial data limit our understanding of the mechanisms by which flavanones and their metabolites potentially reduce cardiovascular risk factors. Objective: We examined the effects of orange juice or a dose-matched hesperidin supplement on plasma concentrations of established and novel flavanone metabolites and their effect...
NN, NN; Yusuf, S; Teo, K;
BACKGROUND: Angiotensin-converting enzyme (ACE) inhibitors reduce major cardiovascular events, but are not tolerated by about 20% of patients. We therefore assessed whether the angiotensin-receptor blocker telmisartan would be effective in patients intolerant to ACE inhibitors with cardiovascular...... group). INTERPRETATION: Telmisartan was well tolerated in patients unable to tolerate ACE inhibitors. Although the drug had no significant effect on the primary outcome of this study, which included hospitalisations for heart failure, it modestly reduced the risk of the composite outcome...
Pedersen, Susan H; Lokkegaard, Ellen; Ottesen, Bent
cardiovascular outcomes. Recent, large-scale, randomized clinical studies did not confirm a beneficial cardiovascular effect of HT. On the contrary, an increased risk was found with continuous combined estrogen-progestagen regimens. The progestagen used in these trials was medroxyprogesterone acetate and other...
Bangalore, Sripal; Makani, Harikrishna; Radford, Martha; Thakur, Kamia; Toklu, Bora; Katz, Stuart D; DiNicolantonio, James J; Devereaux, P J; Alexander, Karen P; Wetterslev, Jorn; Messerli, Franz H
patients. The primary outcome was all-cause mortality. Analysis was performed stratifying trials into reperfusion era (>50% undergoing reperfusion and/or receiving aspirin/statin) or pre-reperfusion era trials. RESULTS: Sixty trials with 102003 patients satisfied the inclusion criteria. In the acute......BACKGROUND: Debate exists regarding the efficacy of â-blockers in myocardial infarction and their required duration of usage in contemporary practice. METHODS: We conducted a MEDLINE/EMBASE/CENTRAL search for randomized trials evaluating â-blockers in myocardial infarction enrolling at least 100...... myocardial infarction trials, a significant interaction (Pinteraction=0.02) was noted such that â-blockers reduced mortality in the pre-reperfusion[Incident Rate Ratio (IRR)=0.86, 95% CI 0.79-0.94] but not in the reperfusion era(IRR=0.98, 95% CI 0.92-1.05). In the pre-reperfusion era, â-blockers reduced...
Full Text Available Abstract Good quality clinical trials are essential to inform the best cystic fibrosis (CF management and care, by determining and comparing the effectiveness of new and existing therapies and drug delivery systems. The formal inclusion of quality of life (QoL as an outcome measure in CF clinical trials is becoming more common. Both an appropriate QoL measure and sound methodology are required in order to draw valid inferences about treatments and QoL. A review was undertaken of randomised controlled trials in cystic fibrosis where QoL was measured. EMBASE, MEDLINE and ISI Web of Science were searched to locate all full papers in the English language reporting randomised controlled trials in cystic fibrosis, published between January 1991 and December 2004. All Cochrane reviews published before December 2004 were hand searched. Papers were included if the authors had reported that they had measured QoL or well being in the trial. 16 trials were identified. The interventions investigated were: antibiotics (4; home versus hospital administration of antibiotics (1; steroids (1; mucolytic therapies (6; exercise (3 and pancreatic enzymes (1. Not one trial evaluated in this review provided conclusive results concerning QoL. This review highlights many of the pitfalls of QoL measurement in CF clinical trials and provides constructive information concerning the design and reporting of trials measuring QoL.
Heather Ann Hausenblas; Kacey Heekin; Heather Lee Mutchie; Stephen Anton
BACKGROUND: Throughout the past three decades, increased scientiifc attention has been given to examining saffron’s (Crocus sativusL.) use as a potential therapeutic or preventive agent for a number of health conditions, including cancer, cardiovascular disease, and depression. OBJECTIVE: The purpose of this systematic review is to examine and categorize the current state of scientiifc evidence from randomized controled trials (RCTs) regarding the efifcacy of saffron on psychological/behavioral outcomes. SEARCH STRATEGY: Electronic and non-electronic systematic searches were conducted to identify al relevant human clinical research on saffron. The search strategy was extensive and was designed according to the “Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA).” Reference lists of articles that met the inclusion criteria were searched. Only English language studies were reviewed. INCLUSION CRITERIA:Saffron trials in combination with other substances and saffron safety studies were considered, in accordance with the PRISMA statement. Included studies must have a control group. Included studies must measure a physiological and/or a behavioral outcome. DATA EXTRACTION AND ANALYSIS:The methodological quality of al included studies was independently evaluated by two reviewers using the Jadad score. Mean scores andP-values of measures were compared both inter- and intra-study for each parameter (i.e., depression). RESULTS:Twelve studies met our inclusion criteria. These studies examined the effects of saffron on psychological/behavioral outcomes of: major depressive disorder (n = 6), premenstrual syndrome (n = 1), sexual dysfunction and infertility (n = 4), and weight loss/snacking behaviors (n = 1). The data from these studies support the efifcacy of saffron as compared to placebo in improving the folowing conditions:depressive symptoms (compared to anti-depressants and placebo), premenstrual symptoms, and sexual dysfunction. In addition
Full Text Available Midlife cardiovascular risk factors, including diabetes, hypertension, dyslipemia, and an unhealthy lifestyle, have been linked to subsequent incidence, delay of onset, and progression rate of Alzheimer disease and vascular dementia. Conversely, optimal treatment of cardiovascular risk factors prevents and slows down age-related cognitive disorders. The impact of antihypertensive therapy on cognitive outcome in patients with hypertension was assessed in large trials which demonstrated a reduction in progression of MRI white matter hyperintensities, in cognitive decline and in incidence of dementia. Large-scale database correlated statin use and reduction in the incidence of dementia, mainly in patients with documented atherosclerosis, but clinical trials failed to reach similar conclusions. Whether a multitargeted intervention would substantially improve protection, quality of life, and reduce medical cost expenditures in patients with lower risk profile has not been ascertained. This would require appropriately designed trials targeting large populations and focusing on cognitive decline as a primary outcome endpoint.
Bosch, Jackie; Gerstein, Hertzel C; Dagenais, Gilles R; Díaz, Rafael; Dyal, Leanne; Jung, Hyejung; Maggiono, Aldo P; Probstfield, Jeffrey; Ramachandran, Ambady; Riddle, Matthew C; Rydén, Lars E; Yusuf, Salim; Krarup, Thure; Perrild, Hans Jørgen Duckert; Torp-Pedersen, Christian Tobias
The use of n-3 fatty acids may prevent cardiovascular events in patients with recent myocardial infarction or heart failure. Their effects in patients with (or at risk for) type 2 diabetes mellitus are unknown....
Rowland, Melisa D.; Chapman, Jason E.; Henggeler, Scott W.
This study examined the substance use and delinquency outcomes for the nearest age siblings of substance abusing and delinquent adolescents that participated in a randomized clinical trial evaluating the effectiveness of integrating evidence-based practices into juvenile drug court. The sample of 70 siblings averaged 14.4 years of age, 50% were…
Ferrer-Wreder, Laura; Cadely, Hans Saint-Eloi; Domitrovich, Celene E.; Small, Meg L.; Caldwell, Linda L.; Cleveland, Michael J.
Two evidence-based interventions, Life Skills Training and TimeWise, were combined in an effectiveness trial. Participants were predominately African American youth (N = 715; M[subscript age] = 12). The study authors provide an empirical demonstration of the implications of incorporating dosage information in intervention outcome analyses. Study…
Friis, Henrik; Michaelsen, Kim F.; Wells, Jonathan C
There is a need for trials on the effects of food aid products for children with moderate acute malnutrition, to identify how best to restore body tissues and function. The choice of control intervention is a major challenge, with both ethical and scientific implications. While randomized trials...... understand what components of health might be impacted by public health programs, or the underlying mechanisms whereby improved nutritional status might benefit short- and long-term health. Measurement of body composition, specific growth markers and functional outcomes may provide greater insight into the...... are needed, special designs, such as cluster-randomized, stepped-wedged or factorial designs may offer advantages. Anthropometry is widely used as the primary outcome in such trials, but anthropometric traits do not refer directly to specific organs, tissues, or functions. Thus, it is difficult to...
Køber, Lars; Rustom, Rana; Wiedmann, Jonas; Kappelgaard, Anne-Marie; El Nahas, Meguid; Feldt-Rasmussen, Bo
The high morbidity and mortality rates in hemodialysis (HD) patients are due, at least in part, to their increased risk for cardiovascular diseases (CVD). This prospective study evaluated the effect of growth hormone (GH) on a number of CVD risk markers in adult patients on HD.......The high morbidity and mortality rates in hemodialysis (HD) patients are due, at least in part, to their increased risk for cardiovascular diseases (CVD). This prospective study evaluated the effect of growth hormone (GH) on a number of CVD risk markers in adult patients on HD....
Verheijden, Marieke; Bakx, J Carel; Akkermans, Reinier; van den Hoogen, Henk; Godwin, N Marshall; Rosser, Walter; Staveren, Wija; van Weel, Chris
Background Using the Internet may prove useful in providing nutrition counselling and social support for patients with chronic diseases. Objective We evaluated the impact of Web-based nutrition counselling and social support on social support measures, anthropometry, blood pressure, and serum cholesterol in patients at increased cardiovascular risk. Methods We conducted a randomized controlled trial among patients with increased cardiovascular risk in Canadian family practices. During 8 month...
M. N. Mamedov; M. B. Stroeva
Primary prevention of diabetes in persons with high cardiovascular risk is an actual problem. Results of DREAM trial are discussed. Influence of ACE inhibitor, ramipril, on risk of diabetes onset in patients with pre-diabetes and low cardiovascular risk is focused. Metabolic effects of other groups of antihypertensive drugs and their ability to prevent diabetes onset are compared. Ramipril three years therapy resulted in normalization in glucose level but did not have effect on frequency of d...
Sasaki, Nobuo; Ozono, Ryoji; Edahiro, Yoshinobu; Ishii, Kiyomi; Seto, Ayako; Okita, Tomomi; Teramen, Kazushi; Fujiwara, Saeko; Kihara, Yasuki
Obstructive sleep apnea syndrome (OSAS) is a risk factor for cardiovascular events. However, it is unclear how OSAS contributes to the events. We investigated the impact of non-dipping on the incidence of cardiovascular events in a retrospective cohort study comprising 251 patients with OSAS. OSAS was diagnosed by overnight polysomnography and all patients underwent 24-h ambulatory blood pressure monitoring. Non-dipping was diagnosed when reduction in sleep blood pressure was <10% of awake blood pressure. Over a mean 43-month follow-up period, 15 patients (6.0%) developed cardiovascular events including stroke, heart failure, and ischemic heart disease. Significantly higher cardiovascular events were observed in the non-dipping group than those without it by Kaplan-Meier analyses. Cox regression analysis revealed that the presence of non-dipping was significantly and independently associated with the incidence of cardiovascular events (hazard ratio, 3.88; 95% confidence interval, 1.19-17.41; p < 0.05), after adjusting for severity of OSAS, and CPAP therapy. Thus, non-dipping was a marker for a poor prognosis in patients with OSAS. PMID:26395950
Maraldo, Maja V.; Giusti, Francesco; Vogelius, Ivan R.;
BACKGROUND: Cardiovascular disease after treatment is an important concern in cancer survivors. However, knowledge of cardiotoxicity is limited by the retrospective nature of data, which often does not contain details of treatment exposure. To facilitate individual risk counselling of patients, w...
Maraldo, Maja V.; Giusti, Francesco; Vogelius, Ivan R.; Lundemann, Michael; van der Kaaij, Marleen A. E.; Ramadan, Safaa; Meulemans, Bart; Henry-Amar, Michel; Aleman, Berthe M. P.; Raemaekers, John; Meijnders, Paul; Moser, Elisabeth C.; Kluin-Nelemans, Hanneke C.; Feugier, Pierre; Casasnovas, Olivier; Fortpied, Catherine; Specht, Lena
Background Cardiovascular disease after treatment is an important concern in cancer survivors. However, knowledge of cardiotoxicity is limited by the retrospective nature of data, which often does not contain details of treatment exposure. To facilitate individual risk counselling of patients, we ai
Effects of the Multidisciplinary Risk Assessment and Management Program for Patients with Diabetes Mellitus (RAMP-DM) on biomedical outcomes, observed cardiovascular events and cardiovascular risks in primary care: a longitudinal comparative study
Jiao, Fang Fang; Fung, Colman Siu Cheung; Wong, Carlos King Ho; Wan, Yuk Fai; Dai, Daisy; Kwok, Ruby; Lam, Cindy Lo Kuen
Background To assess whether the Multidisciplinary Risk Assessment and Management Program for Patients with Diabetes Mellitus (RAMP-DM) led to improvements in biomedical outcomes, observed cardiovascular events and predicted cardiovascular risks after 12-month intervention in the primary care setting. Methods A random sample of 1,248 people with diabetes enrolled to RAMP-DM for at least 12 months was selected and 1,248 people with diabetes under the usual primary care were matched by age, sex...
Full Text Available Venkata Narla, Michael J Blaha, Roger S Blumenthal, Erin D MichosThe Ciccarone Preventive Cardiology Center, Division of Cardiology, Johns Hopkins University School of Medicine, Baltimore, MD, USAAbstract: Statins have emerged at the forefront of preventive cardiology and have significantly reduced cardiovascular events and mortality. Nonetheless, cardiovascular disease remains the leading cause of death in the United States and in other developed countries, as well as the etiology of significant morbidity and health-care expenditure. In an attempt to reduce potentially missed opportunities for instituting preventive therapy, the JUPITER study (Justification for the Use of Statins in Prevention: an Intervention Trial Evaluating Rosuvastatin and the AURORA study (A Study to Evaluate the Use of Rosuvastatin in Subjects on Regular Hemodialysis: An Assessment of Survival and Cardiovascular Events examined the effect of statins in two specific patient populations who currently do not meet the guidelines for statin treatment, but nonetheless, are at high cardiovascular risk. This review outlines the JUPITER and AURORA trials, interprets the data and significance of the results, analyses the drawbacks and impact of both trials and delineates the potential for further clinical trials.Keywords: JUPITER, AURORA, rosuvastatin, cardiovascular disease
Jian-Bing Wang; Jin-Hu Fan; Dawsey, Sanford M.; Rashmi Sinha; Freedman, Neal D.; Taylor, Philip R.; You-Lin Qiao; Abnet, Christian C.
Although previous studies have shown that dietary consumption of certain food groups is associated with a lower risk of cancer, heart disease and stroke mortality in western populations, limited prospective data are available from China. We prospectively examined the association between dietary intake of different food groups at baseline and risk of total, cancer, heart disease and stroke mortality outcomes in the Linxian Nutrition Intervention Trials(NIT) cohort. In 1984–1991, 2445 subjects ...
Caille, Agnès; Leyrat, Clémence; Giraudeau, Bruno
In cluster randomized trials (CRTs), clusters of individuals are randomized rather than the individuals themselves. For such trials, power depends in part on the degree of similarity among responses within a cluster, which is quantified by the intaclass correlation coefficient (ICC). Thus, for a fixed sample size, power decreases with increasing ICC. In reliability studies with two observers, dichotomizing a continuous outcome variable has been shown to reduce the ICC. We checked (by a simulation study) that this property still applies to CRTs, in which cluster sizes are variable and usually greater than in reliability studies and observations (within clusters) are exchangeable. Then, in a CRT, dichotomizing a continuous outcome actually induces two antagonistic effects: decreased power because of loss of information and increased power induced by attenuation of the ICC. Therefore, we aimed to assess the impact of dichotomizing a continuous outcome on power in a CRT. We derived an analytical formula for power based on a generalized estimating equation approach after dichotomizing a continuous outcome. This theoretical result was obtained by considering equal cluster sizes, and we then assessed its accuracy (by a simulation study) in the more realistic situation of varying cluster sizes. We showed that dichotomization is associated with decreased power: attenuation of the ICC does not compensate for the loss of power induced by loss of information. Loss of power is reduced with increased initial continuous-outcome ICC and/or prevalence of success for the dichotomized outcome approaching 50%. PMID:22733454
Mix, TCH; Brenner, RM; Cooper, ME; de Zeeuw, D; Ivanovich, P; Levey, AS; McGill, JB; McMurray, JJV; Parfrey, PS; Parving, HH; Pereira, BJG; Remuzzi, G; Singh, AK; Solomon, SD; Stehman-Breen, C; Toto, RD; Pfeffer, MA
Background Patients with chronic kidney disease (CKD) have a high burden of mortality and cardiovascular morbidity. Additional strategies to modulate cardiovascular risk in this population are needed. Data suggest that anemia is a potent and potentially modifiable risk factor for cardiovascular dise
Central review of radiation therapy (RT) delivery within multicenter clinical trials was initiated in the early 1970s in the United States. Early quality assurance publications often focused on metrics related to process, logistics, and timing. Our objective was to review the available evidence supporting correlation of RT quality with clinical outcomes within cooperative group trials. A MEDLINE search was performed to identify multicenter studies that described central subjective assessment of RT protocol compliance (quality). Data abstracted included method of central review, definition of deviations, and clinical outcomes. Seventeen multicenter studies (1980-2012) were identified, plus one Patterns of Care Study. Disease sites were hematologic, head and neck, lung, breast, and pancreas. Between 0 and 97% of treatment plans received an overall grade of acceptable. In 7 trials, failure rates were significantly higher after inadequate versus adequate RT. Five of 9 and 2 of 5 trials reported significantly worse overall and progression-free survival after poor-quality RT, respectively. One reported a significant correlation, and 2 reported nonsignificant trends toward increased toxicity with noncompliant RT. Although more data are required, protocol-compliant RT may decrease failure rates and increase overall survival and likely contributes to the ability of collected data to answer the central trial question
Sidorenkov, Grigory; Voorham, Jaco; de Zeeuw, Dick; Haaijer-Ruskamp, Flora M.; Denig, Petra
Background: Landmark clinical trials have led to optimal treatment recommendations for patients with diabetes. Whether optimal treatment is actually delivered in practice is even more important than the efficacy of the drugs tested in trials. To this end, treatment quality indicators have been devel
Usefulness of Doppler echocardiographic left ventricular diastolic function and peak exercise oxygen consumption to predict cardiovascular outcomes in patients with systolic heart failure (from HF-ACTION).
Gardin, Julius M; Leifer, Eric S; Kitzman, Dalane W; Cohen, Gerald; Landzberg, Joel S; Cotts, William; Wolfel, Eugene E; Safford, Robert E; Bess, Renee L; Fleg, Jerome L
Heart Failure: A Controlled Trial Investigating Outcomes of Exercise Training (HF-ACTION) was a multicenter, randomized controlled trial designed to examine the safety and efficacy of aerobic exercise training versus usual care in 2,331 patients with systolic heart failure (HF). In HF-ACTION patients with rest transthoracic echocardiographic measurements, the predictive value of 8 Doppler echocardiographic measurements-left ventricular (LV) diastolic dimension, mass, systolic (ejection fraction) and diastolic (mitral valve peak early diastolic/peak late diastolic [E/A] ratio, peak mitral valve early diastolic velocity/tissue Doppler peak early diastolic myocardial velocity [E/E'] ratio, and deceleration time) function, left atrial dimension, and mitral regurgitation severity-was examined for a primary end point of all-cause death or hospitalization and a secondary end point of cardiovascular disease death or HF hospitalization. Also compared was the prognostic value of echocardiographic variables versus peak oxygen consumption (Vo(2)). Mitral valve E/A and E/E' ratios were more powerful independent predictors of clinical end points than the LV ejection fraction but less powerful than peak Vo(2). In multivariate analyses for predicting the primary end point, adding E/A ratio to a basic demographic and clinical model increased the C-index from 0.61 to 0.62, compared with 0.64 after adding peak Vo(2). For the secondary end point, 6 echocardiographic variables, but not the LV ejection fraction or left atrial dimension, provided independent predictive power over the basic model. The addition of E/E' or E/A to the basic model increased the C-index from 0.70 to 0.72 and 0.73, respectively (all p values <0.0001). Simultaneously adding E/A ratio and peak Vo(2) to the basic model increased the C-index to 0.75 (p <0.0005). No echocardiographic variable was significantly related to the change from baseline to 3 months in exercise peak Vo(2). In conclusion, the addition of
Pegelow Halvorsen, Cecilia
Background Fetal environment has become a subject for increasing interest when studying health and disease in adults. Monozygous (MZ) twins, especially gestations complicated with twin - twin transfusion syndrome (TTTS), offer a unique opportunity to study adverse developmental programming of the cardiovascular system. TTTS affects about 10% of pregnancies with a common placenta because of unbalanced blood flow across deep arteriovenous connecting vessels . ...
Farkouh, M.E.; Greenberg, J.D.; Jeger, R.V.; Ramanathan, K.; Verheugt, F.W.A.; Chesebro, J.H.; Kirshner, H.; Hochman, J.S.; Lay, C.L.; Ruland, S.; Mellein, B.; Matchaba, P.; Fuster, V.; Abramson, S.B.
BACKGROUND: Evidence suggests that both selective cyclooxygenase (COX)-2 inhibitors and non-selective non-steroidal anti-inflammatory drugs (NSAIDs) increase the risk of cardiovascular events. However, evidence from prospective studies of currently available COX-2 inhibitors and non-selective NSAIDs
Friedlander, M; Mercieca-Bebber, R L; King, M T
Despite increased recognition of the value of including patient-reported outcomes (PROs) as important end points in phase III clinical trials, there has been a lack of pre-specified PRO hypotheses and shortcomings with the analyses and interpretation of PROs in many ovarian cancer trials. This paper discusses and provides examples of the so-called lost opportunities in ovarian cancer trials. These include: (i) no clear pre-specified PRO hypotheses; (ii) PRO end points not included; (iii) insensitive PRO end point selection; (iv) collection of poor-quality PRO data not suitable for analysis; (v) differences in PROs between treatment arms ignored; and (vi) poor reporting quality. We can learn from the past and with relatively little additional effort, improve the collection and interpretation of PRO data in future ovarian cancer trials. The importance of doing so is underpinned by recent initiatives to improve the standard and usefulness of PRO data in clinical trials. These include the Food and Drug Administration (FDA) Guidance for PROs to support labelling claims, the European Society for Medical Oncology Magnitude of Clinical Benefit Scale (ESMO MCBS), the International Society for Quality-of-Life Research PRO reporting guidance and the Consolidated Standards of Reporting Clinical Trials (CONSORT)-PRO-extension statement which includes a checklist of recommended items to include in PRO sections of trial protocols. Promoting the importance of hypothesis-driven PROs in ovarian cancer clinical trials will lead to improvements in the design of these trials and the interpretation of their results. PMID:27141076
Tully, Phillip J; Turnbull, Deborah A; Horowitz, John D; Beltrame, John F.; Selkow, Terina; Baune, Bernhard T; Markwick, Elizabeth; Sauer-Zavala, Shannon; Baumeister, Harald; Cosh, Suzanne; Gary A Wittert
Background Previous psychological and pharmacological interventions have primarily focused on depression disorders in populations with cardiovascular diseases (CVDs) and the efficacy of anxiety disorder interventions is only more recently being explored. Transdiagnostic interventions address common emotional processes and the full range of anxiety and depression disorders often observed in populations with CVDs. The aim of CHAMPS is to evaluate the feasibility of a unified protocol (UP) for t...
Ong Lai Teik, Derek; Lee, Xiao Shiang; Lim, Chu Jian; Low, Chia Mei; Muslima, Mariyam; Aquili, Luca
Background There is some evidence to suggest that ginseng and Ginkgo biloba can improve cognitive performance, however, very little is known about the mechanisms associated with such improvement. Here, we tested whether cardiovascular reactivity to a task is associated with cognitive improvement. Methodology/Principal findings Using a double-blind, placebo controlled, crossover design, participants (N = 24) received two doses of Panax Ginseng (500, 1000 mg) or Ginkgo Biloba (120, 240 mg) (N =...
Full Text Available Habibollah Saadat¹, Hossein Shiri², Zahra Salarpour², Tahereh Ashktorab² , Hamid Alavi Majd², Zahra Saadat¹, Hosein Vakili¹ 1Cardiovascular Research Center, Modarres Hospital, Shaheed Beheshti University of Medical Sciences, Tehran; 2Nursing School, Shaheed Beheshti University of Medical Sciences, Tehran, Iran Background: Most patients who present to medical centers due to chest pain do not suffer from acute coronary syndromes and do not need to be hospitalized in coronary care units (CCUs. This study was done to determine exploitation of resources and cardiovascular outcomes in low-risk patients with chest pain hospitalized in CCUs of educational hospitals affiliated with a major medical university. Methods: Over a 4-month period, 550 patients with chest pain who were hospitalized in the CCUs belonging to six hospitals affiliated to the authors' medical university were recruited by census method. Using Thrombolysis in Myocardial Infarction risk score, 95 patients (17.27% were categorized as low-risk patients. This group was evaluated with respect to demographics, bed occupancy rate, mean hospitalization period, expenses during admission, and cardiovascular outcomes in the 30-day period postdischarge. Results: Mean (± standard deviation hospitalization duration was 3.04 (±0.71 days. No significant difference was seen between the six surveyed hospitals regarding hospitalization duration (P = 0.602. The highest bed occupancy rate was seen in Taleghani and Shohada Tajrish hospitals and the lowest was in Modarres Hospital. The mean paid treatment expenses by low-risk patients was IRR 2,050,000 (US$205. Mean total hospitalization expenses was US$205. No significant difference was seen between the six surveyed hospitals (P = 0.699. Of the patients studied, 89.5% did not show any cardiovascular complications in 1 month and no deaths occurred. Conclusion: Given the high bed-occupancy rate by low-risk patients, associated high hospitalization
Aryangat, Ajikumar V; Gerich, John E.
Ajikumar V Aryangat, John E GerichUniversity of Rochester, Rochester, New York, USAAbstract: Hyperglycemia is a major risk factor for both the microvascular and macrovascular complications in patients with type 2 diabetes. This review summarizes the cardiovascular results of large outcomes trials in diabetes and presents new evidence on the role of hyperglycemia, with particular emphasis on postprandial hyperglycemia, in adverse cardiovascular outcomes in patients with type 2 diabet...
Goldman, Myla D.; Motl, Robert W.; Rudick, Richard A.
Multiple sclerosis (MS) is a chronic inflammatory and neurodegenerative disease with both clinical and pathological heterogeneity. The complexity of the MS population has offered challenges to the measurement of MS disease progression in therapeutic trials. The current standard clinical outcome measures are relapse rate, Expanded Disability Severity Scale (EDSS), and the MS Functional Composite (MSFC). These measures each have strengths and some weakness. Two additional measures, the six-minute walk and accelerometry, show promise in augmenting current measures. MS therapeutics is a quickly advancing field which requires sensitive clinical outcome measures that can detect small changes in disability that reliably reflect long-term changes in sustained disease progression in a complex population. A single clinical outcome measure of sustained disease progression may remain elusive. Rather, an integration of current and new outcome measures may be most appropriate and utilization of different measures depending on the MS population and stage of the disease may be preferred. PMID:21179614
Niiranen, T. J.; Asayama, K.; Thijs, L; Johansson, J K; Ohkubo, T.; Kikuya, M; Boggia, J.; Hozawa, A.; Sandoya, E.; Stergiou, G. S.; Tsuji, I; Jula, A. M.; Imai, Y.; Staessen, J. A.
The lack of outcome-driven operational thresholds limits the clinical application of home blood pressure (BP) measurement. Our objective was to determine an outcome-driven reference frame for home BP measurement. We measured home and clinic BP in 6470 participants (mean age, 59.3 years; 56.9% women; 22.4% on antihypertensive treatment) recruited in Ohasama, Japan (n=2520); Montevideo, Uruguay (n=399); Tsurugaya, Japan (n=811); Didima, Greece (n=665); and nationwide in Finland (n=2075). In mul...
The VITamin D and OmegA-3 TriaL (VITAL): Rationale and Design of a Large Randomized Controlled Trial of Vitamin D and Marine Omega-3 Fatty Acid Supplements for the Primary Prevention of Cancer and Cardiovascular Disease
Manson, JoAnn E.; Bassuk, Shari S.; Lee, I-Min; Cook, Nancy R.; Albert, Michelle A.; Gordon, David; Zaharris, Elaine; MacFadyen, Jean G.; Danielson, Eleanor; Lin, Jennifer; Zhang, Shumin M.; Buring, Julie E
Data from laboratory studies, observational research, and/or secondary prevention trials suggest that vitamin D and marine omega-3 fatty acids may reduce risk for cancer or cardiovascular disease (CVD), but primary prevention trials with adequate dosing in general populations (i.e., unselected for disease risk) are lacking. The ongoing VITamin D and OmegA-3 TriaL (VITAL) is a large randomized, double-blind, placebo-controlled, 2×2 factorial trial of vitamin D (in the form of vitamin D3 [chole...
Full Text Available Hsuan-Li Huang,1 Jyh-Ming Jimmy Juang,2 Hsin-Hua Chou,1,3 Chien-An Hsieh,1 Shih-Jung Jang,1 Shih-Tsung Cheng,1,3 Yu-Lin Ko1,3 1Division of Cardiology, Department of Internal Medicine, Taipei Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, New Taipei City, 2Cardiovascular Center and Division of Cardiology, Department of Internal Medicine, National Taiwan University Hospital, National Taiwan University College of Medicine, Taipei, 3School of Medicine, Tzu Chi University, Hualien, Taiwan Purpose: To investigate the clinical outcomes of endovascular therapy (EVT in octogenarians and nonoctogenarians with peripheral arterial disease. Methods: A retrospective analysis of 511 patients (654 affected legs who underwent EVT between July 2005 and December 2013 was conducted in a prospectively maintained database. Immediate results and long-term vascular outcomes were analyzed and compared between octogenarians and nonoctogenarians. Results: Octogenarians were more likely to be female and have atrial fibrillation (AF, whereas nonoctogenarians had higher rates of obesity, claudication, and medical comorbidities. There were no differences in the rates of EVT success, 30-day major adverse vascular events, and 6-month functional improvement between groups. Over the 10-year follow-up period, the rates of 3-year limb salvage, sustained clinical success, freedom from major cerebrovascular and cardiovascular events, and composite vascular events were similar between groups, but the survival rate was better in nonoctogenarians than in octogenarians (73% vs 63%, respectively, P=0.004. In Cox regression analysis, dependence on dialysis and AF were significant predictors of death (odds ratio [OR] 4.44 in dialyzed and 2.83 in AF patients, major cerebrovascular and cardiovascular events (OR 3.49 and 2.45, and composite vascular events (OR 3.14 and 2.25. Conclusion: EVT in octogenarians was feasible, without an increased risk of periprocedural complications. The
Dworkin, R.H.; Turk, D.C.; Wyrwich, K.W.;
IMMPACT for 4 core chronic pain outcome domains: (1) Pain intensity, assessed by a 0 to 10 numerical rating scale; (2) physical functioning, assessed by the Multidimensional Pain Inventory and Brief Pain Inventory interference scales; (3) emotional functioning, assessed by the Beck Depression Inventory...... and Profile of Mood States; and (4) participant ratings of overall improvement, assessed by the Patient Global Impression of Change scale. It is recommended that 2 or more different methods be used to evaluate the clinical importance of improvement or worsening for chronic pain clinical trial outcome...