nils-herrmann/clean_scirepeval huggingface dataset:
Five-year outcomes following a randomized trial of femorofemoral and femoropopliteal bypass grafting with heparin-bonded or standard polytetrafluoroethylene grafts.

Cohort studies suggest superior long-term patency of luminal heparin-bonded polytetrafluoroethylene (Hb-PTFE) bypass grafts compared with standard PTFE grafts. The aim of this study was to compare the outcomes of Hb-PTFE grafts with those of standard PTFE grafts 5 years after a randomized trial.



Patients with intermittent claudication or critical limb ischaemia requiring femorofemoral or femoropopliteal bypass grafting were randomized in a clinical trial of Hb-PTFE versus standard PTFE in 11 Scandinavian centres between 2005 and 2009. Patients were followed up for 5 years with clinical assessment and surveillance Duplex ultrasound imaging. The primary endpoint of this study was primary patency. Secondary endpoints included major amputation and mortality.



Overall, 569 patients were enrolled in the randomized trial. Some 552 had follow-up data available for analysis of the primary outcome. Use of Hb-PTFE significantly improved patency by 37 per cent at 2 years, but 5 years after randomization there was no difference in primary patency (adjusted hazard ratio (HR) 0·95, 95 per cent c.i. 0·71 to 1·28; P = 0·748). In patients with critical limb ischaemia the use of Hb-PTFE reduced the 5-year risk of loss of primary patency by 37 per cent (HR 0·63, 0·40 to 0·99; P = 0·049).



In this study there was no difference in primary graft patency between Hb-PTFE and standard PTFE grafts. Patients receiving Hb-PTFE grafts for critical limb ischaemia were more likely to have a patent graft at 5 years than those with standard PTFE grafts.
An Ad5-vectored HIV-1 vaccine elicits cell-mediated immunity but does not affect disease progression in HIV-1-infected male subjects: results from a randomized placebo-controlled trial (the Step study).

The Step study was a randomized trial to determine whether an adenovirus type 5 (Ad5) vector vaccine, which elicits T cell immunity, can lead to control of human immunodeficiency virus (HIV) replication in participants who became HIV-infected after vaccination.



We evaluated the effect of the vaccine on trends in HIV viral load, CD4+ T cell counts, time to initiation of antiretroviral therapy (ART), and AIDS-free survival in 87 male participants who became infected with HIV during the Step study and who had a median of 24 months of post-infection follow-up.



There was no overall effect of vaccine on mean log(10) viral load (estimated difference between groups, -0.11; P = .47). In a subset of subjects with protective HLA types (B27, B57, B58), mean HIV-1 RNA level over time was lower among vaccine recipients. There was no significant difference in CD4+ T cell counts, time to ART initiation, or in AIDS-free survival between HIV-1-infected subjects who received vaccine versus those who received placebo.



HIV RNA levels, CD4+ T cell counts, time to initiation of ART, and AIDS-free survival were similar in vaccine and placebo recipients. There may have been a favorable effect of vaccine on HIV-1 RNA levels in participants with HLA types associated with better control of HIV-1.
Pharmacokinetics of doxorubicin in children with acute lymphoblastic leukemia: multi-institutional collaborative study.

In adults, it has been shown that the pharmacokinetics of doxorubicin are highly variable, despite standardization of the dose based on body surface area (BSA). The purpose of this study was to determine the plasma concentrations of doxorubicin and its active metabolite doxorubicinol in children treated for acute lymphoblastic leukemia (ALL).



There was a more than 10-fold difference between patients in dose normalized plasma concentration of doxorubicin, median 62.8 ng/ml, range 22.6-334 ng/ml. The doxorubicin concentrations differed significantly between age groups (P = 0.003). Children aged 4-6 years had the highest doxorubicin concentrations, median 77.9 ng/ml, followed by 2-4-year-old children, median 64.3 ng/ml. Both younger and older children had median values of about 50 ng/ml. Patients with white blood cell (WBC) count > 50 x 10(9)/L at diagnosis had significantly lower doxorubicin concentrations, median 55.3 ng/ml, than those with WBC count < 10 x 10(9)/L, median 64.4 ng/ml (P = 0.015). There was no difference in doxorubicin concentration between boys and girls. No correlation was found between doxorubicin levels and serum aminotransferases or serum creatinine. The concentration of doxorubicinol was 13% (median value) of that of doxorubicin. Four infants, 7-9 months old, had plasma clearance between 350-431 ml/min/m(2), which is in the same range as in older children. A 3-month-old infant had a clearance of 181 ml/min/m(2).



The age groups who had the highest doxorubicin concentrations, (2-) 4-6-year-old children, are known to make up a large proportion of standard risk ALL cases with good prognosis. The correlation between doxorubicin plasma levels and clinical effect needs further study. The influence of age, body composition, and tumor burden on the pharmacokinetics of antineoplastic drugs should also be further explored, aiming at improvements in the current dosing regimen based on BSA.
Uptake of smoking cessation aids by smokers with a mental illness

Psychiatric inpatient settings represent an opportunity to initiate the provision of tobacco cessation care to smokers with a mental illness. This study describes the use of evidence-based smoking cessation aids proactively and universally offered to a population of psychiatric inpatients upon discharge, and explores factors associated with their uptake. Data derived from the conduct of a randomised controlled trial were analysed in terms of the proportion of participants (N = 378) that utilised cessation aids including project delivered telephone smoking cessation counselling and nicotine replacement therapy (NRT), and Quitline support. Factors associated with uptake of cessation aids were explored using multivariable logistic regression analyses. A large proportion of smokers utilised project delivered cessation counselling calls (89 %) and NRT (79 %), while 11 % used the Quitline. The majority accepted more than seven project delivered telephone cessation counselling calls (52 %), and reported NRT use during more than half of their accepted calls (70 %). Older age, higher nicotine dependence, irregular smoking and seeing oneself as a non-smoker were associated with uptake of behavioural cessation aids. Higher nicotine dependence was similarly associated with use of pharmacological aids, as was NRT use whilst an inpatient. Most smokers with a mental illness took up a proactive offer of aids to support their stopping smoking. Consideration by service providers of factors associated with uptake may increase further the proportion of such smokers who use evidence-based cessation aids and consequently quit smoking successfully.
Early effects of raloxifene on clinical vertebral fractures at 12 months in postmenopausal women with osteoporosis.

Raloxifene hydrochloride therapy reduces the risk for vertebral fractures at 3 years, but the effects on clinical vertebral fractures in the first year are not known.



The Multiple Outcomes of Raloxifene Evaluation (MORE) Trial enrolled 7705 women with osteoporosis, defined by prevalent vertebral fractures and/or a bone mineral density (BMD) T score at or below -2.5, who were treated with placebo or raloxifene at a dosage of 60 or 120 mg/d for 3 years. New clinical vertebral fractures were defined as incident vertebral fractures associated with signs and symptoms suggestive of vertebral fractures, such as back pain, and were diagnosed by means of postbaseline adjudicated spinal radiographs. Scheduled spinal radiographs were obtained at baseline and at 2 and 3 years. In addition, unscheduled spinal radiographs were obtained in women who reported signs or symptoms suggestive of vertebral fracture, and these radiographs subsequently underwent adjudication. If an adjudicated fracture was identified, this was also considered a clinical fracture.



At 1 year, raloxifene, 60 mg/d, decreased the risk for new clinical vertebral fractures by 68% (95% confidence interval [CI], 20%-87%) compared with placebo in the overall study population, and by 66% (95% CI, 23%-89%) in women with prevalent vertebral fractures, who are at greater risk for subsequent fracture. The risk for clinical vertebral fractures in the raloxifene, 60 mg/d, group was decreased by 46% (95% CI, 14%-66%) at 2 years and by 41% (95% CI, 17%-59%) at 3 years. The cumulative incidence of new clinical vertebral fractures was lower in the group receiving raloxifene, 60 mg/d, compared with placebo (P<.001). We found no significant differences in the risk reductions for clinical vertebral fractures between the raloxifene groups at 1, 2, or 3 years.



The early risk reduction for new clinical vertebral fractures with 1 year of raloxifene treatment was similar to that reported with other antiresorptive agents.
Temporal trends in patient-reported angina at 1 year after percutaneous coronary revascularization in the stent era: a report from the National Heart, Lung, and Blood Institute-sponsored 1997-2006 dynamic registry.

Percutaneous coronary intervention (PCI) has witnessed rapid technological advancements, resulting in improved safety and effectiveness over time. Little, however, is known about the temporal impact on patient-reported symptoms and quality of life after PCI.



Temporal trends in post-PCI symptoms were analyzed using 8879 consecutive patients enrolled in the National Heart, Lung, and Blood Institute-sponsored Dynamic Registry (wave 1: 1997 [bare metal stents], wave 2: 1999 [uniform use of stents], wave 3: 2001 [brachytherapy], wave 4, 5: 2004, 2006 [drug eluting stents]). Patients undergoing PCI in the recent waves were older and more often reported comorbidities. However, fewer patients across the waves reported post-PCI angina at one year (wave 1 to 5: 24%, 23%, 18%, 20%, 20%; P(trend)<0.001). The lower risk of angina in recent waves was explained by patient characteristics including use of antianginal medications at discharge (relative risk [95% CI] for waves 2, 3, 4 versus 1: 1.0 [0.9 to 1.2], 0.9 [0.7 to 1.1], 1.0 [0.8 to 1.3], 0.9 [0.7 to 1.1]). Similar trend was seen in the average quality of life scores over time (adjusted mean score for waves 1 to 5: 6.2, 6.5, 6.6 and 6.6; P(trend)=0.01). Other factors associated with angina at 1 year included younger age, female gender, prior revascularization, need for repeat PCI, and hospitalization for myocardial infarction over 1 year.



Favorable temporal trends are seen in patient-reported symptoms after PCI in routine clinical practice. Specific subgroups, however, remain at risk for symptoms at 1 year and thus warrant closer attention.
Localization of the bronchodilator effect induced by type A natriuretic peptide in asthmatic subjects

A natriuretic peptide (CDD/ANP99-126) in its circulating form was analyzed with respect to the localization of its bronchodilating effects in asthmatic subjects in vivo. The intravenous infusion of 5.7, 11.4, and 17.1 pmol kg−1 min− CDD/ANP-99-126 caused a significant bronchodilation of both central and peripheral airways. While the localization of the bronchodilating effects was similar to β2-agonists, an improvement in lung function parameters comparable to these substances was not observed. But other members of the natriuretic peptide family may reveal a stronger bronchodilating potency.
Comment on: Gemifloxacin once daily for 5 days versus 7 days for the treatment of community-acquired pneumonia: a randomized, multicentre, double-blind study.

make. However, they go on to suggest that these relatively low concentrations of ertapenem will be ineffective against this strain. It is with this issue that we are concerned. In our article, we indicate that the emergence and spread of resistance are greatly enhanced at subinhibitory concentrations; however, resistance emergence is also a dynamic process of the progressive concentration of resistant strains within the clinical population, often by the same or related strains. In the individual case that Brink et al. describe, ertapenem did not select carbapenem-resistant P. aeruginosa; however, we are concerned with the much broader picture for, in the face of thousands or even millions of such challenges, we maintain that selection of resistant strains is likely to occur and progressively increases their concentration in the clinical setting. With regard to their later comment, the widespread dissemination of extended-spectrum b-lactamases (ESBLs) and transferable ampC b-lactamases does demonstrate that we have not used cephalosporins optimally. We do, though, have the benefit of hindsight and different strategies; in particular, the use of cephalosporins in combination with a b-lactamase inhibitor might have suppressed the huge problem of cephalosporin resistance that we now face. It should be possible to learn from experience that we must not take individual treatment cases in isolation as a model for drug strategy because, unless we consider the broader potential impact of using weaker drugs, we may well face a new ‘ESBL’ problem, but this time it will be carbapenemases.
Randomized trial of critical time intervention to prevent homelessness after hospital discharge.

This study assessed the effectiveness of a previously tested model, critical time intervention (CTI), in producing an enduring reduction in the risk of homelessness for persons with severe mental illness who were discharged from inpatient psychiatric treatment facilities.



A total of 150 previously homeless men and women with severe mental illness and who were discharged from inpatient psychiatric hospitalization to transitional residences on the hospital grounds were randomly assigned to receive usual care or usual care plus CTI at the point of discharge to the community. The nine-month intervention aims to gradually pass responsibility to community sources for providing ongoing support after the intervention ends, thereby leading to a durable reduction in risk of future homelessness. After participants were discharged from the transitional residence (length of stay six to 937 days), their housing status was assessed every six weeks for 18 months via participant self-report collected by interviewers blind to study condition.



In an intent-to-treat analysis, participants assigned to the CTI group had significantly less homelessness at the end of the follow-up period (the final three six-week intervals) than those assigned to the control group (odds ratio=.22, 95% confidence interval=.06-.88).



A relatively brief, focused intervention for persons with severe mental illness led to a reduction in the risk of homelessness that was evident nine months after the intervention ended. This work suggests that targeted, relatively short interventions applied at critical transition points may enhance the efficacy of long-term supports for persons with severe mental illness who are living in the community.
Influence of H. pylori infection on meal-stimulated gastric acid secretion and gastroesophageal acid reflux.

Gastric acid secretion, gastrin release, gastric emptying, and gastroesophageal acid reflux were measured in asymptomatic individuals before and after elimination of Helicobacter pylori gastritis. After basal gastric acid secretion and serum gastrin concentrations were measured, meal-stimulated gastric acid secretion and gastrin release were assessed during in vivo intragastric titration to pH 3. Experiments were repeated 4 wk after treatment with lansoprazole, amoxicillin, and clarithromycin. Esophageal pH was also monitored for 24 h before and after therapy. Basal gastric acidity increased approximately 20 mmol/l in subjects whose infection was eradicated (P < 0.05) but not in those with persistent infection. Basal and meal-stimulated gastric acid secretion did not change after H. pylori eradication, despite a 41% reduction in meal-stimulated gastrin release (P < 0.05). Gastroesophageal acid reflux increased two- to threefold after successful treatment (P < 0. 05) but did not change in subjects with persistent infection. Thus elimination of H. pylori gastritis increases gastric acidity, probably by reducing nonparietal alkaline secretion, and this may facilitate gastroesophageal acid reflux.
Barthel Index-Enhanced Feedback for Effective Cardiac Treatment (BI-EFFECT) Study: contribution of the Barthel Index to the Heart Failure Risk Scoring System model in elderly adults with acute heart failure in the emergency department.

To evaluate whether the Enhanced Feedback for Effective Cardiac Treatment (EFFECT) scale for 30-day prediction of mortality is applicable to elderly adults with acute heart failure (AHF) in emergency departments (EDs) and whether discriminatory power is added with the inclusion of the Barthel Index (BI) to this scale (BI-EFFECT scale).



BI-EFFECT is a multipurpose, nonintervention, multicenter cohort study.



Twenty EDs.



Individuals aged 65 and older with AHF.



Information on baseline and episode characteristics and 30-day mortality was collected, and participants were categorized according to the EFFECT scale. Baseline degree of functional dependence was measured using the BI. Receiver operating characteristic (ROC) curves were made of the EFFECT and BI-EFFECT scales to predict mortality.



One thousand sixty-eight participants were included. Thirty-day mortality was 5.1% and was directly and independently associated with high and very high risk categories of the EFFECT scale and with severe dependence. These two variables remained significant after adjustment of the model for both (OR = 4.5, 95% CI = 1.8-11.1 and OR = 2.9, 95% CI = 1.6-5.4, respectively). The EFFECT and the BI-EFFECT scales had significant ROC curves (area under the ROC curve (AUC) = 0.69, 95% CI = from 0.62 to 0.76; and AUC = 0.75, 95% CI = 0.69-0.81, respectively), and the difference in discriminatory power between the second and the first was also statistically significant (P = .02).



The EFFECT scale may be applied in the elderly population, and inclusion of functional status according to the BI in the new BI-EFFECT scale significantly improves the model for the prediction of 30-day mortality.
Diltiazem maintains renal vasodilation without hyperfiltration in hypertension: Studies in essential hypertensive man and the spontaneously hypertensive rat

The systemic and renal hemodynamic effects of diltiazem were determined in patients with mild to moderately severe essential hypertension and in rats with spontaneous hypertension (SHR). Seven patients were treated for one full year (300 mg/day, average dose) and 10 SHR and 10 normotensive Wistar-Kyoto (WKY) rats received 1 and 2 mg/ kg, intravenously. In both man and rat with genetic hypertension, arterial pressure was reduced through a fall in total peripheral resistance without associated reflexive increases in heart rate and cardiac index; and the patients demonstrated no change in plasma volume. In both man and the SHR: renal blood flow increased (in SHR not statistically significant) as arterial pressure and renal vascular resistance fell; glomerular filtration rate (GFR) remained unchanged and the filtration fraction (FF) significantly fell; and calculated intrarenal hemodynamic indices (using the Gomez formulae) demonstrated falls in afferent and efferent glomerular arteriolar pressures and resistances and in intraglomerular pressures, thereby explaining the unchanged GFRs and the decline in FF. These findings in both hypertensive man and rat are in contrast with those of the normotensive WKY that only demonstrated a fall in afferent glomerular arteriolar resistance. Thus, these data demonstrate that diltiazem controlled arterial pressure in both forms of genetic hypertension associated with falls in systemic and renal arteriolar resistances and with improved intrarenal hemodynamics without glomerular hyperfiltration.
Phase I pharmacokinetic and pharmacodynamic study of Carboplatin and topotecan administered intravenously every 28 days to patients with malignant solid tumors.

Preclinical studies have shown that the combination of topotecan and carboplatin is synergistic. To evaluate the schedule dependency of this interaction, the following phase I trial was designed to determine the safety and maximum tolerated dose (MTD), pharmacokinetics, and pharmacodynamics of carboplatin and topotecan in patients with malignant solid tumors.



In part 1, patients received carboplatin on day 1 and topotecan on days 1, 2, and 3 (C-->T schedule). In part 2, topotecan was administered on days 1, 2, and 3, followed by carboplatin on day 3 (T-->C schedule). Pharmacokinetics were determined in plasma and DNA topoisomerase I catalytic activity and Pt-DNA adducts in WBC and tumor tissue.



Forty-one patients were included. Dose-limiting toxicities during the C-->T schedule were grade 4 thrombocytopenia and febrile neutropenia (MTD: carboplatin target area under the free carboplatin plasma concentration versus time curve, 4 min mg/mL; topotecan, 0.5 mg/m(2)/d). Dose-limiting toxicities during the T-->C schedule included grade 4 neutropenia, thrombocytopenia, neutropenic fever, and grade 4 nausea and vomiting (MTD: carboplatin target area under the free carboplatin plasma concentration versus time curve, 6 min mg/mL; topotecan, 0.9 mg/m(2)/d). One complete response and five partial responses were observed. The clearance of and exposure to carboplatin and topotecan did not depend on the sequence of drug administration. No schedule-dependent effects were seen in Pt-DNA levels and DNA topoisomerase I catalytic activity in WBC and tumor tissue. However, myelotoxicity was clearly more evident in the C-->T schedule.



The T-->C schedule was better tolerated because both hematologic and nonhematologic toxicities were milder. Other pharmacodynamic factors than the ones investigated must explain the schedule-dependent differences in toxicities.
Adding hydrocortisone as 1st line of inotropic treatment for hypotension in very low birth weight infants.

In this pilot study the authors demonstrate the feasibility, effectiveness and safety of the combined early treatment with hydrocortisone and dopamine for refractory hypotension in preterm newborns. Very low birth weight infants born at gestational age < 30 wk or birth weight < 1250 g in the first 48 h of life with hypotension after receiving 10-20 mL/kg bolus of normal saline, were randomized to receive concurrently with the initiation of dopamine, intravenous hydrocortisone (11 infants) or an equivalent volume of placebo (11 infants). Despite no significant clinical difference between the groups including gestational age, birth weight, prevalence of chorioamnionitis, prenatal steroid treatment, cord PH, baseline cortisol level, there was a trend towards lower incidence of bronchopulmonary dysplasia (BPD), and higher survival without BPD rate in the hydrocortisone group. In this very sick small group of infants, hydrocortisone was not associated with more adverse effects, but rather showed a trend toward association with better outcome, including survival without BPD.