nils-herrmann/clean_scirepeval huggingface dataset:
A phase Ib GOELAMS study of the mTOR inhibitor RAD001 in association with chemotherapy for AML patients in first relapse

The mTORC1 signaling pathway is constitutively activated in almost all acute myelogenous leukemia (AML) patients. We conducted a phase Ib trial combining RAD001 (everolimus), an allosteric inhibitor of mTORC1, and conventional chemotherapy, in AML patients under 65 years of age at first relapse (clinical trial NCT 01074086). Increasing doses of RAD001 from 10–70 mg were administrated orally on days 1 and 7 (d1 and d7) of a 3+7 daunorubicin+cytarabine conventional induction chemotherapy regimen. Twenty-eight patients were enrolled in this trial. The treatment was well tolerated with <10% toxicity, mainly involving the gastrointestinal tract and lungs. In this phase Ib trial, the RAD001 maximum tolerated dose was not reached at 70 mg. Sixty-eight percent of patients achieved CR, of which 14 received a double induction. Eight subsequently were intensified with allogeneic-stem cell transplant. Strong plasma inhibition of P-p70S6K was observed after RAD001 administration, still detectable at d7 (d7)at the 70 mg dosage. CR rates in patients with RAD001 areas under or above the curve median were 53% versus 85%. A 70 mg dose of RAD001 at d1 and d7 of an induction chemotherapy regimen for AML has acceptable toxicity and may improve treatment.
Cost-effectiveness of treatments for major depression in primary care practice.

This study augments a randomized controlled trial to analyze the cost-effectiveness of 2 standardized treatments for major depression relative to each other and to the "usual care" provided by primary care physicians.



A randomized controlled trial was conducted in which primary care patients meeting DSM-III-R criteria for current major depression were assigned to pharmacotherapy (where nortriptyline hydrochloride was given) or interpersonal psychotherapy provided in a standardized framework or a primary physician's usual care. Two outcome measures, depression-free days and quality-adjusted days, were developed using information on depressive symptoms over time. The costs of care were calculated. Cost-effectiveness ratios comparing the incremental outcomes with the incremental costs for the different treatments were estimated. Sensitivity analyses were performed.



In terms of both economic costs and quality-of-life outcomes, patients assigned to the pharmacotherapy group did slightly better than those assigned to interpersonal psychotherapy. Both standardized therapies provided better outcomes than primary physician's usual care, but each consumed more resources. No meaningful cost-offsets were found. The incremental direct cost per additional depression-free day for pharmacotherapy relative to usual care ranges from $12.66 to $16.87 which translates to direct cost per quality-adjusted year gained from $11270 to $19510.



Standardized treatments for depression lead to better outcomes than usual care but also lead to higher costs. However, the estimates of the cost per quality-of-life year gained for standardized pharmacotherapy are comparable with those found for other treatments provided in routine practice.
Anesthetic-induced improvement of the inflammatory response to one-lung ventilation.

Although one-lung ventilation (OLV) has become an established procedure during thoracic surgery, sparse data exist about inflammatory alterations in the deflated, reventilated lung. The aim of this study was to prospectively investigate the effect of OLV on the pulmonary inflammatory response and to assess possible immunomodulatory effects of the anesthetics propofol and sevoflurane.



Fifty-four adults undergoing thoracic surgery with OLV were randomly assigned to receive either anesthesia with intravenously applied propofol or the volatile anesthetic sevoflurane. A bronchoalveolar lavage was performed before and after OLV on the lung side undergoing surgery. Inflammatory mediators (tumor necrosis factor alpha, interleukin 1beta, interleukin 6, interleukin 8, monocyte chemoattractant protein 1) and cells were analyzed in lavage fluid as the primary endpoint. The clinical outcome determined by postoperative adverse events was assessed as the secondary endpoint.



The increase of inflammatory mediators on OLV was significantly less pronounced in the sevoflurane group. No difference in neutrophil recruitment was found between the groups. A positive correlation between neutrophils and mediators was demonstrated in the propofol group, whereas this correlation was missing in the sevoflurane group. The number of composite adverse events was significantly lower in the sevoflurane group.



This prospective, randomized clinical study suggests an immunomodulatory role for the volatile anesthetic sevoflurane in patients undergoing OLV for thoracic surgery with significant reduction of inflammatory mediators and a significantly better clinical outcome (defined by postoperative adverse events) during sevoflurane anesthesia.
Phase 1 trial of the antiangiogenic peptide ATN-161 (Ac-PHSCN-NH2), a beta integrin antagonist, in patients with solid tumours

To evaluate the toxicity, pharmacological and biological properties of ATN-161, a five –amino-acid peptide derived from the synergy region of fibronectin, adult patients with advanced solid tumours were enrolled in eight sequential dose cohorts (0.1–16 mg kg−1), receiving ATN-161 administered as a 10-min infusion thrice weekly. Pharmacokinetic sampling of blood and urine over 7 h was performed on Day 1. Twenty-six patients received from 1 to 14 4-week cycles of treatment. The total number of cycles administered to all patients was 86, without dose-limiting toxicities. At dose levels above 0.5 mg kg−1, mean total clearance and volume of distribution showed dose-independent pharmacokinetics (PKs). At 8.0 and 16.0 mg kg−1, clearance of ATN-161 was reduced, suggesting saturable PKs. Dose escalation was halted at 16 mg kg−1 when drug exposure (area under the curve) exceeded that associated with efficacy in animal models. There were no objective responses. Six patients received more than four cycles of treatment (>112 days). Three patients received 10 or more cycles (⩾280 days). ATN-161 was well tolerated at all dose levels. Approximately, 1/3 of the patients in the study manifested prolonged stable disease. These findings suggest that ATN-161 should be investigated further as an antiangiogenic and antimetastatic cancer agent alone or with chemotherapy.
Effect of high flow oxygen on mortality in chronic obstructive pulmonary disease patients in prehospital setting: randomised controlled trial

To compare standard high flow oxygen treatment with titrated oxygen treatment for patients with an acute exacerbation of chronic obstructive pulmonary disease in the prehospital setting.



Cluster randomised controlled parallel group trial.



Ambulance service in Hobart, Tasmania, Australia.



405 patients with a presumed acute exacerbation of chronic obstructive pulmonary disease who were treated by paramedics, transported, and admitted to the Royal Hobart Hospital during the trial period; 214 had a diagnosis of chronic obstructive pulmonary disease confirmed by lung function tests in the previous five years.



High flow oxygen treatment compared with titrated oxygen treatment in the prehospital (ambulance/paramedic) setting.



Prehospital or in-hospital mortality.



In an intention to treat analysis, the risk of death was significantly lower in the titrated oxygen arm compared with the high flow oxygen arm for all patients (high flow oxygen n=226; titrated oxygen n=179) and for the subgroup of patients with confirmed chronic obstructive pulmonary disease (high flow n=117; titrated n=97). Overall mortality was 9% (21 deaths) in the high flow oxygen arm compared with 4% (7 deaths) in the titrated oxygen arm; mortality in the subgroup with confirmed chronic obstructive pulmonary disease was 9% (11 deaths) in the high flow arm compared with 2% (2 deaths) in the titrated oxygen arm. Titrated oxygen treatment reduced mortality compared with high flow oxygen by 58% for all patients (relative risk 0.42, 95% confidence interval 0.20 to 0.89; P=0.02) and by 78% for the patients with confirmed chronic obstructive pulmonary disease (0.22, 0.05 to 0.91; P=0.04). Patients with chronic obstructive pulmonary disease who received titrated oxygen according to the protocol were significantly less likely to have respiratory acidosis (mean difference in pH 0.12 (SE 0.05); P=0.01; n=28) or hypercapnia (mean difference in arterial carbon dioxide pressure -33.6 (16.3) mm Hg; P=0.02; n=29) than were patients who received high flow oxygen.



Titrated oxygen treatment significantly reduced mortality, hypercapnia, and respiratory acidosis compared with high flow oxygen in acute exacerbations of chronic obstructive pulmonary disease. These results provide strong evidence to recommend the routine use of titrated oxygen treatment in patients with breathlessness and a history or clinical likelihood of chronic obstructive pulmonary disease in the prehospital setting.
Changes in smoking status affect women more than men: results of the Lung Health Study.

Lung Health Study participants were smokers aged 35-60 years with mild lung function impairment who participated in a 5-year, 10-center (nine in the United States, one in Canada) clinical trial in 1986-1994. The authors compared the relation of randomized treatment assignments and of smoking history during the study with changes in lung function between men and women. Spirometry was performed annually, and 3,348 men and 1,998 women attended the follow-up clinic visit that included spirometry at year 5. This paper reports on an analysis of changes in lung function by gender, treatment group, and three smoking history categories: sustained quitters, intermittent quitters, and continuing smokers. Among participants who quit smoking in the first year, mean forced expiratory volume in 1 second (FEV(1)) expressed as a percentage of the predicted value of FEV(1 )given the person's age, height, gender, and race (FEV(1)%) increased more in women (3.7% of predicted) than in men (1.6% of predicted) (p < 0.001). Across the 5-year follow-up period, among sustained quitters, women gained more in FEV(1)% of predicted than did men. Methacholine reactivity was more strongly related to rates of decline in women than in men (p < 0.001). Therefore, among persons at risk for chronic obstructive pulmonary disease, smoking cessation has an even clearer advantage for women than it does for men.
Interaction paradigms in technology-enhanced social spaces: a case study in museums

This paper investigates, through a case study, the interaction paradigms that can be adopted in a museum exhibition involving hybrid interactive artifacts, i.e., installations that support visitors manipulating and interacting with physical and digital exhibits [6], . We discuss the design principles and solutions we adopted in a temporary exhibition titled "The Fire and The Mountain", where we integrated technological and physical artifacts within a multi-sensory exhibition space to foster enjoyment, engagement, and, ultimately, learning, and to promote a variety of social behaviors among visitors interacting together and with hybrid exhibits. We also discuss a field study we carried on to evaluate the user experience in "The Fire and the Mountain", and the lessons we learnt.
Feasibility of institutional registry-based recruitment for enrolling newly diagnosed breast cancer patients in an exercise trial.

The purpose of this study was to determine the feasibility of using a tumor registry to recruit newly diagnosed survivors into a randomized controlled exercise trial and to discuss issues related to this recruitment strategy.



A tumor registry-based rapid ascertainment system was used to recruit breast cancer survivors into a 6-month home-based, telephone-administered intervention of moderate-to-vigorous intensity exercise or a usual care group.



468 newly diagnosed cases were identified. Of these, 50 women (15.4% of those for which screening calls were made) were enrolled in the study. Women were randomized, on average, 11 weeks after diagnosis (SD = 4.8). Sixty-four percent were randomized before beginning treatment or within the first week of treatment. Time required to obtain physician consent was the primary determinant of diagnosis-to-randomization latency. Enrolled women were more likely than nonenrolled women to be non-Hispanic White and to have a college degree (P < .05).



Tumor registries present a feasible means of recruiting breast cancer survivors before or early in adjuvant treatment. The success of recruiting survivors promptly after diagnosis is largely dependent on ability to rapidly obtain physician consent. Specific effort is needed to counteract self-selection effects that may lead to under-representation of minorities.
Physical activity intervention (Movi-Kids) on improving academic achievement and adiposity in preschoolers with or without attention deficit hyperactivity disorder: study protocol for a randomized controlled trial

The prevention of obesity and improvement of academic achievement in children are concerns of industrialized societies. Obesity has been associated with psychological disorders, including attention deficit hyperactivity disorder, whose prevalence has been estimated at 6.8 % in Spanish children and adolescents. It is known that physical activity is positively related to academic achievement and negatively related to the risk of obesity in children. However, studies to test the effectiveness of physical activity interventions in improving academic achievement in preschool children are scarce and have some weaknesses that threaten their validity. Moreover, very few studies have examined their effectiveness in improving symptoms of attention deficit hyperactivity disorder. This paper outlines a two-year multidimensional preschool intervention (Movi-Kids) aimed at preventing obesity and improving academic achievement in children with or without attention deficit hyperactivity disorder.



Twenty-one schools from Ciudad Real and Cuenca, Spain, were randomized to intervention and control groups. In the first academic year, children in the third grade of preschool and the first grade of primary school in the intervention group received the Movi-Kids intervention. In the second academic year, schools were crossed over to the other group. The intervention included children, parents and teachers, and the school environment, and consisted of: (i) three hour-long sessions of recreational non-competitive physical activity after school, weekly, (ii) educational materials for parents and teachers addressing sedentary lifestyle risks and (iii) playground modifications to promote physical activity during breaks. Primary outcome measures of this study were academic achievement (intelligence, cognition, memory, attention and perception), assessed by the Battery of General and Differential Aptitudes, and adiposity measures (body mass index, waist circumference, triceps skinfold thickness and body fat percentage). Secondary outcome measures were: attention deficit hyperactivity disorder risk, motor skills, health-related quality of life and sleep quality. These variables will all be measured in both groups at baseline and at the end of the first and second academic years.



It seems reasonable that an intervention to promote physical activity based on playground games will be useful for simultaneously improving academic achievement and controlling obesity.
Assessment of metabolic brain damage and recovery following mild traumatic brain injury: a multicentre, proton magnetic resonance spectroscopic study in concussed patients.

Concussive head injury opens a temporary window of brain vulnerability due to the impairment of cellular energetic metabolism. As experimentally demonstrated, a second mild injury occurring during this period can lead to severe brain damage, a condition clinically described as the second impact syndrome. To corroborate the validity of proton magnetic resonance spectroscopy in monitoring cerebral metabolic changes following mild traumatic brain injury, apart from the magnetic field strength (1.5 or 3.0 T) and mode of acquisition, we undertook a multicentre prospective study in which a cohort of 40 athletes suffering from concussion and a group of 30 control healthy subjects were admitted. Athletes (aged 16-35 years) were recruited and examined at three different institutions between September 2007 and June 2009. They underwent assessment of brain metabolism at 3, 15, 22 and 30 days post-injury through proton magnetic resonance spectroscopy for the determination of N-acetylaspartate, creatine and choline-containing compounds. Values of these representative brain metabolites were compared with those observed in the group of non-injured controls. Comparison of spectroscopic data, obtained in controls using different field strength and/or mode of acquisition, did not show any difference in the brain metabolite ratios. Athletes with concussion exhibited the most significant alteration of metabolite ratios at Day 3 post-injury (N-acetylaspartate/creatine: -17.6%, N-acetylaspartate/choline: -21.4%; P < 0.001 with respect to controls). On average, metabolic disturbance gradually recovered, initially in a slow fashion and, following Day 15, more rapidly. At 30 days post-injury, all athletes showed complete recovery, having metabolite ratios returned to values detected in controls. Athletes self-declared symptom clearance between 3 and 15 days after concussion. Results indicate that N-acetylaspartate determination by proton magnetic resonance spectroscopy represents a non-invasive tool to accurately measure changes in cerebral energy metabolism occurring in mild traumatic brain injury. In particular, this metabolic evaluation may significantly improve, along with other clinical assessments, the management of athletes suffering from concussion. Further studies to verify the effects of a second concussive event occurring at different time points of the recovery curve of brain metabolism are needed.
Is there a role for renin profiling in selecting chronic heart failure patients for ACE inhibitor treatment?

It remains uncertain whether angiotensin converting enzyme (ACE) inhibitors benefit all heart failure patients or just those with renin-angiotensin-aldosterone system (RAAS) activation.



To determine whether the response to an ACE inhibitor, assessed by urine sodium excretion, was different in patients with low renin versus those with high renin.



Plasma renin activity (PRA) was measured in 38 patients with stable chronic heart failure (21 male, 17 female; mean (SD) age 71 (6) years, range 59-82 years) on chronic diuretic treatment alone. They were divided into three groups: low (PRA </= 1.5 ng/ml/h, n = 11); normal (1.5 < PRA < 5, n = 14); and high (PRA > 5, n = 13). The effect of ACE inhibition was then assessed on diuretic induced natriuresis with respect to renin status.



There were no significant differences in age and sex distribution between the groups. Plasma angiotensin II and aldosterone increased serially from low to high renin groups, while 24 h urinary sodium concentrations fell from low to high renin groups (low PRA, 96.7 (39.5); normal PRA, 90.4 (26.7); high PRA, 66. 3 (18.9) mmol/l; p = 0.033), despite a higher diuretic dose in the high renin group. This blunted natriuretic effect of loop diuretics was caused by RAAS activation, which could partly be reversed by ACE inhibition. ACE inhibitors increased natriuresis by 22% in the high renin group (p = 0.029), but had no effect in the normal and low renin groups. Within the low renin group, five of the 11 patients had persistently low renin levels despite ACE inhibition. There was a non-significant reduction in natriuresis (-9.6%, p = 0.335) following ACE inhibition in this subgroup of patients.



About one third of heart failure patients in our study had low renin status and a non-activated RAAS, despite diuretic treatment. ACE inhibitors did not alter natriuresis significantly in this subgroup of patients, and enhanced natriuresis only in patients with high renin. There is thus tentative support for renin profiling in targeting ACE inhibitors to the most deserving, by showing that short term sodium retention does not occur in low renin patients if ACE inhibitors are withdrawn.
Multilevel analysis of HIV related risk behaviors among heroin users in a low prevalence community

Injecting drug users (IDU) are at increased risk of human immunodeficiency virus (HIV) infection. Their HIV prevalence however varies from place to place and may not be directly linked with the level of individual risk. This study explores the relative importance of individual and community level characteristics in the practice of HIV-related risk behaviors in IDU in Hong Kong where the HIV prevalence has remained low at below 1%.



Methadone clinics were used as the channel for accessing drug users in Hong Kong. HIV-related risk factors in drug users attending these clinics were retrieved from a questionnaire routinely administered to newly admitted and readmitted clients, and assessed using logistic regression and multilevel analyses.



Between 1999 and 2005, a total of 41,196 person-admissions were recorded by 20 methadone clinics. Male gender, older age and new admissions in bigger clinics located in districts with older median age were more likely to have engaged in HIV related risk behaviors including heroin injection, needle sharing, unprotected sex and having multiple sex partners (p < 0.05).



Multilevel analysis is a useful adjunct for determining the association between risk behaviors and both individual and community factors in IDUs, which can be demonstrated even in low HIV prevalence settings.
Three-year extension study of lanthanum carbonate therapy in Japanese hemodialysis patients

Lanthanum carbonate is a non-aluminum, non-calcium phosphate binder. Its efficacy and its safety profile up to 1 year have been reported in Japanese hemodialysis patients. The present study was an extension of the earlier study. One hundred and forty-five patients were enrolled in the original 1 year observational Phase III study. After 1 year of treatment, 63 patients continued with further lanthanum treatment. Lanthanum carbonate was administered at 750–4,500 mg/day for up to 156 weeks (3 years). The reduction in serum phosphate was used to evaluate efficacy, and laboratory markers of bone turnover were monitored. The serum phosphate level was maintained at a significantly lower level (P < 0.05) than the baseline level during the 3-year study period. Most of the drug-related adverse events were mild and were mainly gastrointestinal disorders. The safety profile of lanthanum during 3 years of treatment was similar to that seen in the previous study. There were no clinically relevant changes in vital signs or the electrocardiogram. Bone turnover markers, such as osteocalcin, bone-specific alkaline phosphatase, and crosslinked N-telopeptide of type I collagen, showed no clinically relevant changes. Lanthanum therapy was able to reduce and maintain the serum phosphate level within the K/DOQI and JSDT guideline ranges in Japanese dialysis patients for 3 years.