nils-herrmann/clean_scirepeval huggingface dataset:
The striking effect of the Heart Outcomes Prevention Evaluation (HOPE) on ramipril prescribing in Ontario.

The Heart Outcomes Prevention Evaluation (HOPE), a Canadian-led, multicentre, randomized controlled trial, demonstrated the effectiveness of the ACE inhibitor ramipril in the secondary prevention of cardiovascular disease in patients who were at high risk for cardiovascular events but did not have left ventricular dysfunction or heart failure. We studied whether HOPE affected the prescribing of ACE inhibitors generally, and ramipril specifically, in Ontario, where the trial was coordinated.



We used linked administrative databases to examine prescribing patterns for ACE inhibitors in the 1.29 million to 1.54 million elderly (aged 66 and over) residents of Ontario during the study period and specifically those with diabetes or congestive heart failure. For all new prescriptions for these drugs filled between Jan. 1, 1993, and Mar. 31, 2001, we conducted time-series analyses to measure any association with the release of the HOPE results.



The monthly number of new prescriptions for ramipril from the time it was introduced in 1995 until HOPE's early termination, in April 1999, peaked at 58 per 100,000 elderly Ontario residents. The rate increased to 92/100,000 in May, coincident with newspaper coverage of the trial's early termination, then fell back to 63/100,000 in August. After HOPE's results were formally released, starting Aug. 31, the rate increased significantly; it peaked at 304/100,000 in May 2000 (p < 0.01). The market share of ramipril among ACE inhibitors also increased significantly (p < 0.01), both overall and among patients with diabetes or congestive heart failure.



HOPE led to a striking and unprecedented increase, over 400%, in ramipril prescribing to elderly Ontario residents, including those not eligible for the trial. Many physicians are now prescribing ramipril for patients with diabetes or congestive heart failure.
Virologic and immunologic responses in treatment-naive patients to ritonavir-boosted atazanavir or efavirenz with a common backbone.

Atazanavir boosted with ritonavir (ATV/r) and efavirenz (EFV) are both recommended as first-line therapies for HIV-infected patients. We compared the 2 therapies for virologic efficacy and immune recovery.



We included all treatment-naïve patients in the Swiss HIV Cohort Study starting therapy after May 2003 with either ATV/r or EFV and a backbone of tenofovir and either emtricitabine or lamivudine. We used Cox models to assess time to virologic failure and repeated measures models to assess the change in CD4 cell counts over time. All models were fit as marginal structural models using both point of treatment and censoring weights. Intent-to-treat and various as-treated analyses were carried out: In the latter, patients were censored at their last recorded measurement if they changed therapy or if they were no longer adherent to therapy.



Patients starting EFV (n = 1,097) and ATV/r (n = 384) were followed for a median of 35 and 37 months, respectively. During follow-up, 51% patients on EFV and 33% patients on ATV/r remained adherent and made no change to their first-line therapy. Although intent-to-treat analyses suggest virologic failure was more likely with ATV/r, there was no evidence for this disadvantage in patients who adhered to first-line therapy. Patients starting ATV/r had a greater increase in CD4 cell count during the first year of therapy, but this advantage disappeared after one year.



In this observational study, there was no good evidence of any intrinsic advantage for one therapy over the other, consistent with earlier clinical trials. Differences between therapies may arise in a clinical setting because of differences in adherence to therapy.
Beneficial effects of statins after percutaneous coronary intervention.

Evidence about the efficacy of statin treatment among patients after percutaneous coronary intervention (PCI) is very limited. The rapid advancement in PCI technology and near universal use of adjunctive cardioprotective medications make it necessary to formally assess the effect of statin therapy on cardiac events after PCI.



This was a multicenter prospective cohort study.



Patients who received stent implantation and survived to hospital discharge from the National Heart, Lung, and Blood Institute Dynamic Registry from 2004 to 2006 formed the study cohort. Patients with cardiogenic shock, in-hospital adverse events [including myocardial infarction and coronary artery bypass graft surgery (CABG)], liver disease, renal disease, alcoholism, or drug abuse were excluded. The occurrences of death, CABG, and repeat PCI, and repeat revascularization were collected over 1-year follow-up.



Of the 3227 patients evaluated, 2737 (85%) were prescribed a statin at discharge. By 1-year follow-up, incident events were 98 deaths, 44 CABG, 290 repeat PCI procedures, and 328 repeat revascularizations. After propensity score adjustment, postdischarge statin therapy was associated with lower risks of death [hazard ratio (HR): 0.58, 95% confidence interval (CI): 0.36-0.93, P = 0.02], CABG (HR: 0.49, 95% CI: 0.24-1.00, P = 0.05), and repeat revascularization (HR: 0.74, 95% CI: 0.56-1.00, P = 0.05).



These results support the routine use of statin therapy after PCI.
Health related quality of life outcomes for unresectable stage III or IV melanoma patients receiving ipilimumab treatment

In an international, randomized Phase III trial ipilimumab demonstrated a significant overall survival benefit in previously treated advanced melanoma patients. This report summarizes health-related quality of life (HRQL) outcomes for ipilimumab with/without gp100 vaccine compared to gp100 alone during the clinical trial's 12 week treatment induction period.



The Phase III clinical trial (MDX010-20) was a double-blind, fixed dose study in 676 previously treated advanced unresectable stage III or IV melanoma patients. Patients were randomized 3:1:1 to receive either ipilimumab (3 mg/kg q3w x 4 doses) + gp100 (peptide vaccine; 1 mg q3w x 4 doses; ipilimumab plus gp100, n = 403); gp100 vaccine + placebo (gp100 alone, n = 136); or ipilimumab + placebo (ipilimumab alone, n = 137). The European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) assessed HRQL. Baseline to Week 12 changes in EORTC QLQ-C30 function, global health status, and symptom scores were analyzed for ipilimumab with/without gp100 vaccine compared to gp100 alone. Mean change in scores were categorized "no change" (0-5), "a little" (5-10 points), "moderate" (10-20 points), and "very much" (>20).



In the ipilimumab plus gp100 and ipilimumab alone groups, mean changes from baseline to Week 12 generally indicated "no change" or "a little" impairment across EORTC QLQ-C30 global health status, function, and symptom subscales. Significant differences in constipation, favoring ipilimumab, were observed (p < 0.05). For ipilimumab alone arm, subscales with no or a little impairment were physical, emotional, cognitive, social function, global health, nausea, pain, dyspnea, constipation, and diarrhea subscales. For the gp100 alone group, the observed changes were moderate to large for global health, role function, fatigue, and for pain.



Ipilimumab with/without gp100 vaccine does not have a significant negative HRQL impact during the treatment induction phase relative to gp100 alone in stage III or IV melanoma patients.
Choice of New Oral Anticoagulant Agents Versus Vitamin K Antagonists in Atrial Fibrillation: FANTASIIA Study.

Atrial fibrillation (AF) is associated with an increased risk of thromboembolic events. Many patients with AF receive chronic anticoagulation, either with vitamin K antagonists (VKAs) or with non-VKA oral anticoagulants (NOACs). We sought to analyze variables associated with prescription of NOAC.



Patients with AF under anticoagulation treatment were prospectively recruited in this observational registry. The sample comprised 1290 patients under chronic anticoagulation for AF, 994 received VKA (77.1%) and 296 NOAC (22.9%). Univariate and multivariate analyses were performed to identify variables associated with use of NOAC.



Mean age was 73.8 ± 9.4 years, and 42.5% of the patients were women. The CHA2DS2-VASc score was 0 in 4.9% of the population, 1 in 24.1%, and ≥2 in 71% (median = 4, interquartile range = 2). Variables associated with NOAC treatment were major bleeding (odds ratio [OR] = 3.36; confidence interval [CI] 95%: 1.73-6.51; P < .001), hemorrhagic stroke (OR = 3.19; CI 95% 1.00-10.15, P = .049), university education (OR = 2.44; CI 95%: 1.55-3.84; P < .001), high diastolic blood pressure (OR = 1.02; CI 95%: 1.00-1.03; P = .006), and higher glomerular filtration rate (OR 1.01, CI 95% 1.00-1.01; P = .01). And variables associated with VKA use were history of cancer (OR = 0.46; CI 95%: 0.25-0.85; P = .013) and bradyarrhythmia (OR = 0.40; CI 95% 0.19-0.85; P = .020).



Medical and social variables were associated with prescription of NOAC. Major bleeding, hemorrhagic stroke, university education, and higher glomerular filtration rate were more frequent among patients under NOAC. On the contrary, patients with history of cancer or bradyarrhythmias more frequently received VKA.
The role of drinking restraint success in subsequent alcohol consumption.

Intentional self-restraint may play an important role in the control of potentially addictive behavior. Unfortunately, for some individuals, efforts to reduce substance use may prove not only temporary but to increase the likelihood of a later "binge." An experimental study examined the relationship between prior self-restraint efforts and drinking. Results indicated that successfully restrained drinkers (i.e., those individuals who reported exerting considerable effort toward drinking self-control, and who were normatively successful, that is, light drinkers) responded to the sudden availability of alcohol with increased levels of consumption, relative to unrestrained drinkers at a similar level of habitual drinking. There was no such effect among unsuccessfully restraining (i.e., heavy) drinkers. These results suggest that a period of successful drinking restraint which is initiated by the individual, may lead to heightened subsequent alcohol consumption.
The Impact of Accelerated HF-rTMS on the Subgenual Anterior Cingulate Cortex in Refractory Unipolar Major Depression: Insights From <ce:sup loc=pre>18</ce:sup>FDG PET Brain Imaging

Although one of the most frequent diagnosed mental illnesses worldwide, it appears to be challenging to successfully treat major depressive disorder (MDD). Although the phenomenon of treatment-resistant depression (TRD) still remains unclear, the subgenual anterior cingulate cortex (sgACC) has been put forward as a possible neurobiological marker to evaluate clinical effects of a variety of antidepressant treatments, including repetitive transcranial magnetic stimulation (rTMS). Accelerated high-frequency (HF)-rTMS may have the potential to rapidly result in beneficial clinical outcomes in TRD. No studies yet examined the clinical effects of such accelerated stimulation treatment paradigms on sgACC regional glucose metabolism (CMRglc), nor the predictive value of the latter for clinical outcome.



First, we investigated the predictive value of baseline sgACC metabolic activity for clinical outcome. Second, we hypothesized that in clinical responders only accelerated HF-rTMS treatment would result in significant metabolic decreases.



We recruited right-handed antidepressant-free unipolar melancholic TRD patients to participate in a two-week randomized sham-controlled crossover HF-rTMS treatment study. Stimulation was applied to the left dorsolateral prefrontal cortex (DLPFC). Fifteen patients underwent 18FDG PET (CMRglc) at baseline (T0), after the first week (T1) of accelerated HF-rTMS and at the end of the treatment after the second week (T2).



Higher baseline sgACC metabolic activity may indicate beneficial clinical outcome to this kind of accelerated HF-rTMS treatment. Moreover, clinical response resulted in a significant decrease in sgACC CMRglc. Non-response did not affect sgACC CMRglc.



Our results add to the sgACC as a specific neurobiological marker for anti-depressive response in accelerated HF-rTMS treatment paradigms. Such protocols may not only have the ability to result in fast clinical responses but they may also have potential to acutely modulate a dysfunctional sgACC.
Cholesterol-lowering effect of a theaflavin-enriched green tea extract: a randomized controlled trial.

Tea consumption has been associated with decreased cardiovascular risk, but potential mechanisms of benefit are ill-defined. While epidemiologic studies suggest that drinking multiple cups of tea per day lowers low-density lipoprotein cholesterol (LDL-C), previous trials of tea drinking and administration of green tea extract have failed to show any impact on lipids and lipoproteins in humans. Our objective was to study the impact of a theaflavin-enriched green tea extract on the lipids and lipoproteins of subjects with mild to moderate hypercholesterolemia.



Double-blind, randomized, placebo-controlled, parallel-group trial set in outpatient clinics in 6 urban hospitals in China. A total of 240 men and women 18 years or older on a low-fat diet with mild to moderate hypercholesterolemia were randomly assigned to receive a daily capsule containing theaflavin-enriched green tea extract (375 mg) or placebo for 12 weeks. Main outcome measures were mean percentage changes in total cholesterol, LDL-C, high-density lipoprotein cholesterol (HDL-C), and triglyceride levels compared with baseline.



After 12 weeks, the mean +/- SEM changes from baseline in total cholesterol, LDL-C, HDL-C, and triglyceride levels were -11.3% +/- 0.9% (P =.01), -16.4% +/- 1.1% (P =.01), 2.3% +/- 2.1% (P =.27), and 2.6% +/- 3.5% (P =.47), respectively, in the tea extract group. The mean levels of total cholesterol, LDL-C, HDL-C, and triglycerides did not change significantly in the placebo group. No significant adverse events were observed.



The theaflavin-enriched green tea extract we studied is an effective adjunct to a low-saturated-fat diet to reduce LDL-C in hypercholesterolemic adults and is well tolerated.
Novel Approaches in Primary Cardiovascular Disease Prevention: The HOPE-3 Trial Rationale, Design, and Participants' Baseline Characteristics.

Cholesterol and blood pressure (BP) can be effectively and safely lowered with statin drugs and BP-lowering drugs, reducing major cardiovascular (CV) events by 20%-30% within 5 years in high-risk individuals. However, there are limited data in lower-risk populations. The Heart Outcomes Prevention Evaluation-3 (HOPE-3) trial is evaluating whether cholesterol lowering with a statin drug, BP lowering with low doses of 2 antihypertensive agents, and their combination safely reduce major CV events in individuals at intermediate risk who have had no previous vascular events and have average cholesterol and BP levels.



A total of 12,705 women 65 years or older and men 55 years or older with at least 1 CV risk factor, no known CV disease, and without any clear indication or contraindication to the study drugs were randomized to rosuvastatin 10 mg/d or placebo and to candesartan/hydrochlorothiazide 16/12.5 mg/d or placebo (2 × 2 factorial design) and will be followed for a mean of 5.8 years. The coprimary study outcomes are the composite of CV death, nonfatal myocardial infarction (MI), and nonfatal stroke and the composite of CV death, nonfatal MI, nonfatal stroke, resuscitated cardiac arrest, heart failure, and arterial revascularization.



Participants were recruited from 21 countries in North America, South America, Europe, Asia, and Australia. Mean age at randomization was 66 years and 46% were women.



The HOPE-3 trial will provide new information on cholesterol and BP lowering in intermediate-risk populations with average cholesterol and BP levels and is expected to inform approaches to primary prevention worldwide (HOPE-3 ClinicalTrials.gov NCT00468923).
Effects of Inspiratory Muscle Training and Calisthenics-and-Breathing Exercises in COPD With and Without Respiratory Muscle Weakness.

Patients with COPD may experience respiratory muscle weakness. Two therapeutic approaches to the respiratory muscles are inspiratory muscle training and calisthenics-and-breathing exercises. The aims of the study are to compare the effects of inspiratory muscle training and calisthenics-and-breathing exercises associated with physical training in subjects with COPD as an additional benefit of strength and endurance of the inspiratory muscles, thoracoabdominal mobility, physical exercise capacity, and reduction in dyspnea on exertion. In addition, these gains were compared between subjects with and without respiratory muscle weakness.



25 subjects completed the study: 13 composed the inspiratory muscle training group, and 12 composed the calisthenics-and-breathing exercises group. Subjects were assessed before and after training by spirometry, measurements of respiratory muscle strength and test of inspiratory muscle endurance, thoracoabdominal excursion measurements, and the 6-min walk test. Moreover, scores for the Modified Medical Research Council dyspnea scale were reported.



After intervention, there was a significant improvement in both groups of respiratory muscle strength and endurance, thoracoabdominal mobility, and walking distance in the 6-min walk test. Additionally, there was a decrease of dyspnea in the 6-min walk test peak. A difference was found between groups, with higher values of respiratory muscle strength and thoracoabdominal mobility and lower values of dyspnea in the 6-min walk test peak and the Modified Medical Research Council dyspnea scale in the inspiratory muscle training group. In the inspiratory muscle training group, subjects with respiratory muscle weakness had greater gains in inspiratory muscle strength and endurance.



Both interventions increased exercise capacity and decreased dyspnea during physical effort. However, inspiratory muscle training was more effective in increasing inspiratory muscle strength and endurance, which could result in a decreased sensation of dyspnea. In addition, subjects with respiratory muscle weakness that performed inspiratory muscle training had higher gains in inspiratory muscle strength and endurance but not of dyspnea and submaximal exercise capacity.
A double-blind, placebo-controlled, randomized trial to evaluate the safety and efficacy of Cerebrolysin in patients with acute ischaemic stroke in Asia--CASTA.

Cerebrolysin has exhibited neuroprotective as well as neurotrophic properties in various animal models of cerebral ischaemia and has shown clinical efficacy and good safety in several small controlled clinical studies in ischaemic stroke. Therefore, a large double-blind placebo-controlled randomized clinical trial was launched in Asia to prove the validity of this treatment strategy. In the more than 50 participating centres patients with acute ischemic hemispheric stroke are randomized within 12 hours of symptoms onset to treatment (30 ml Cerebrolysin diluted in physiologic saline) or placebo (saline) given as intravenous infusion once daily added to standard care for 10 days. The patients are followed with regular visits for 90 days. Efficacy is evaluated on day 90 by three outcome scales - modified Rankin Scale, Barthel Index and NIH Stroke Scale - combined to single global directional test. Additionally, adverse events are documented to prove safety. In this study a total of 1060 patients will be included and analysis of data will be completed in 2010. If positive, this trial will add an effective strategy to the treatment of acute ischaemic stroke.
Neighborhood Socioeconomic Status, Depression, and Health Status in the Look AHEAD (Action for Health in Diabetes) Study

Depression and diminished health status are common in adults with diabetes, but few studies have investigated associations with socio-economic environment. The objective of this manuscript was to evaluate the relationship between neighborhood-level SES and health status and depression.



Individual-level data on 1010 participants at baseline in Look AHEAD (Action for Health in Diabetes), a trial of long-term weight loss among adults with type 2 diabetes, were linked to neighborhood-level SES (% living below poverty) from the 2000 US Census (tracts). Dependent variables included depression (Beck Inventory), and health status (Medical Outcomes Study (SF-36) scale). Multi-level regression models were used to account simultaneously for individual-level age, sex, race, education, personal yearly income and neighborhood-level SES.



Overall, the % living in poverty in the participants' neighborhoods varied, mean =11% (range 0-67%). Compared to their counterparts in the lowest tertile of neighborhood poverty (least poverty), those in the highest tertile (most poverty) had significantly lower scores on the role-limitations(physical), role limitations(emotional), physical functioning, social functioning, mental health, and vitality sub-scales of the SF-36 scale. When evaluating SF-36 composite scores, those living in neighborhoods with more poverty had significantly lower scores on the physical health (beta-coefficient [beta]= -1.90 units, 95% CI: -3.40,-0.039), mental health (beta= -2.92 units, -4.31,-1.53) and global health (beta= -2.77 units, -4.21,-1.33) composite scores.



In this selected group of weight loss trial participants, lower neighborhood SES was significantly associated with poorer health status. Whether these associations might influence response to the Look AHEAD weight loss intervention requires further investigation.
Chromosome 1q21 gains confer inferior outcomes in multiple myeloma treated with bortezomib but copy number variation and percentage of plasma cells involved have no additional prognostic value.

Chromosome 1q21 aberrations have not been yet been made part of routine clinical tests and their effect in multiple myeloma is still under investigation. The prognostic value of copy number variation and percentage of plasma cells involved have remained unclear. In the present study, we analyzed the prognostic value of 1q21 in a series of 290 cases of newly diagnosed multiple myeloma treated in a prospective, non-randomized clinical trial (BDH 2008/02). We found that incidence of 1q21 aberration increased at relapse, but its copy numbers and proportion of cells involved did not change. Gains of 1q21 had no impact on survival in patients receiving thalidomide-based treatment but conferred a significantly inferior prognosis in patients under bortezomib-based chemotherapy and was an independent adverse prognostic factor for progression free survival (HR 3.831; 95%CI: 2.125-6.907; P<0.001) and overall survival (HR 3.245; 95%CI: 1.555-6.773; P=0.002). Strikingly, our results showed that the copy number variation and clone size harboring 1q21 gains carried no additional prognostic value and patients with 1q21 gains did not benefit significantly from regimens incorporating bortezomib. Our results indicate that three copies of 1q21 and 20% of plasma cells with this abnormality were enough to confer bortezomib resistance. Therefore, chromosome 1q21 gains should be considered a high-risk feature in multiple myeloma receiving bortezomib therapy.