nils-herrmann/clean_scirepeval huggingface dataset:
Inspiratory capacity at inflation hold in ventilated newborns: a surrogate measure for static compliance of the respiratory system.

To study appropriateness of respiratory system compliance calculation using an inflation hold and compare it with ventilator readouts of pressure and tidal volume as well as with measurement of compliance of the respiratory system with the single-breath-single-occlusion technique gained with a standard lung function measurement.



Prospective clinical trial.



Level III neonatal unit of a university hospital.



Sixty-seven newborns, born prematurely or at term, ventilated for a variety of pathologic conditions.



A standardized sigh maneuver with a predefined peak inspiratory pressure of 30 cm H2O, termed inspiratory capacity at inflation hold, was applied. Using tidal volume, exhaled from inspiratory pause down to ambient pressure, as displayed by the ventilator, and predefined peak inspiratory pressure, compliance at inspiratory capacity at inflation hold conditions could be calculated as well as ratio of tidal volume and ventilator pressure using tidal volume and differential pressure at baseline ventilator settings: peak inspiratory pressure minus positive end-expiratory pressure.



For the whole cohort, the equation for the regression between tidal volume at inspiratory capacity at inflation hold and compliance of the respiratory system was: compliance of the respiratory system = 0.052 * tidal volume at inspiratory capacity at inflation hold - 0.113, and compliance at inspiratory capacity at inflation hold conditions was closely related to the standard lung function measurement method of compliance of the respiratory system (R = 0.958). In contrast, ratio of tidal volume and ventilator pressure per kilogram calculated from the ventilator readouts and displayed against compliance of the respiratory system per kilogram yielded a broad scatter throughout the whole range of compliance; both were only weakly correlated (R = 0.309) and also the regression line was significantly different from the line of identity (p < .05). Peak inspiratory pressure at study entry did not affect the correlation between compliance at inspiratory capacity at inflation hold conditions and compliance of the respiratory system.



After a standard sigh maneuver, inspiratory capacity at inflation hold and the derived quantity compliance at inspiratory capacity at inflation hold conditions can be regarded as a valid, accurate, and reliable surrogate measure for standard compliance of the respiratory system in contrast to ratio of tidal volume and ventilator pressure calculated from the ventilator readouts during ongoing mechanical ventilation at respective ventilator settings.
Facilitation of primary coronary angioplasty by early start of a glycoprotein 2b/3a inhibitor: results of the ongoing tirofiban in myocardial infarction evaluation (On-TIME) trial.

Although primary angioplasty is effective despite additional transportation delay, improved patency before PCI might be obtained by starting pharmacological pre-treatment before transportation.



From June 2001 to November 2002, 507 patients with acute myocardial infarction, who were transferred to a PCI centre, were randomised to early, pre-hospital initiation of Tirofiban (Early) or to initiation in the catheterisation laboratory (Late). The primary end-point was TIMI flow grade 3 of the infarct-related vessel (IRV) at initial angiography, as assessed by an independent core-lab. The effect of Tirofiban on each TIMI flow component, the presence of thrombus at initial angiography and pre-PCI myocardial blush grade were secondary end-points. A large proportion of patients (41%) was diagnosed and randomised in the ambulance, without intervention of a physician. In the Early group, Tirofiban was administered a median of 59 min (range 11-178 min) earlier than in the Late group. At initial angiography, TIMI 3 flow was present in 19% the Early group and in 15% in the Late group (P = 0.22). The combined incidence of TIMI 2 or 3 flow was present in 43% in the Early group and in 34% in the Late group, respectively (P = 0.04). Thrombus or a fresh occlusion was present in 60% and 73% in the Early and Late group, respectively (P = 0.002). A pre-PCI myocardial blush grades 2 or 3 was more often present in the Early group (30% vs. 22%, P = 0.04). However, no difference in TIMI 3 flow or myocardial blush grade was found between the groups, post-PCI. At one-year follow-up, the combined incidence of death or recurrent MI was not different between the groups (7.0% vs. 7.0%, P = 0.99).



Early initiation of Tirofiban did not improve initial TIMI 3 flow of the IRV significantly. Despite a better patency (TIMI 2 or 3 flow), a lower prevalence of thrombus or fresh occlusion and a better myocardial perfusion in the infarct-related region pre-PCI, no beneficial effect on post-PCI angiographic or clinical outcome was found, as compared to initiation of Tirofiban in the catheterisation laboratory.
Visualization and dynamics of multidimensional health-related quality-of-life-adjusted overall survival: a new analytic approach

Vesnarinone Trial (VesT) was a three-armed, placebo-controlled, randomized clinical trial designed to study the effects of 30 mg or 60 mg/day vesnarinone. Certain contradictory results involving patient health-related quality-of-life (HRQOL) and overall survival (OS) have made a definitive and unified conclusion difficult. To reconcile these findings, we have focused on the HRQOL-adjusted OS, commonly known as quality-adjusted life years (QALYs). Currently, analyses of QALYs incorporate a single HRQOL subscale. However, the VesT HRQOL instrument had two subscales: physical (PHYS) and emotional (EMOT). We have developed new ways to visualize and compare EMOT- and PHYS-adjusted OS. In each VesT arm, there was an increased probability of superior EMOT-adjusted OS, compared to PHYS-adjusted OS. The magnitude of these findings was comparable across trial arms. Despite inferior survival and superior EMOT and PHYS scores, the 60-mg/day arm presents similar EMOT- and PHYS-adjusted OS compared to the placebo arm. We have provided a fresh perspective on the complex interactions between multiple HRQOL dimensions and OS. These novel methods address the burgeoning need for robust information on the interplay between OS and HRQOL from a patient, clinical care and public policy perspective.
Maximum Tolerated Dose Evaluation of the AMPA Modulator Org 26576 in Healthy Volunteers and Depressed Patients

A key challenge to dose selection in early central nervous system (CNS) clinical drug development is that patient tolerability profiles often differ from those of healthy volunteers (HVs), yet HVs are the modal population for determining doses to be investigated in phase II trials. Without clear tolerability data from the target patient population, first efficacy trials may include doses that are either too high or too low, creating undue risk for study participants and the development program overall. Bridging trials address this challenge by carefully investigating safety and tolerability in the target population prior to full-scale proof-of-concept trials.



Org 26576 is an alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA) receptor positive allosteric modulator that acts by modulating ionotropic AMPA-type glutamate receptors to enhance glutamatergic neurotransmission. In preparation for phase II efficacy trials in major depressive disorder (MDD), two separate phase I trials were conducted to evaluate safety, tolerability, and pharmacokinetics in HVs and in the target patient population.



Both trials were randomized and placebo controlled, and included multiple rising-dose cohorts (HV range 100-400 mg bid; MDD range 100-600 mg bid). HVs (n = 36) and patients with MDD (n = 54) were dosed under similarly controlled conditions in an inpatient facility, HVs for up to 14 days and MDD patients for up to 28 days. Safety, tolerability, and pharmacokinetics were assessed frequently.



Despite comparable pharmacokinetic profiles, the maximum tolerated dose (MTD) in depressed patients was 450 mg bid, twice the MTD established in HVs. No clinically relevant safety issues associated with Org 26576 were noted.



This article presents safety, tolerability, and pharmacokinetic data from two different populations examined under similar dosing conditions. The important implications of such bridging work in phase II dose selection are discussed, as are study design and data interpretation challenges.
Long-term cost-effectiveness of home versus clinic-based management of chronic heart failure: the WHICH? study.

The cost-effectiveness of a heart failure management intervention can be further informed by incorporating the expected benefits and costs of future survival.



This study compared the long-term costs per quality-adjusted life year (QALY) gained from home-based (HBI) vs specialist clinic-based intervention (CBI) among elderly patients (mean age = 71 years) with heart failure discharged home (mean intervention duration = 12 months). Cost-utility analysis was conducted from a government-funded health system perspective. A Markov cohort model was used to simulate disease progression over 15 years based on initial data from a randomized clinical trial (the WHICH? study). Time-dependent hazard functions were modeled using the Weibull function, and this was compared against an alternative model where the hazard was assumed to be constant over time. Deterministic and probabilistic sensitivity analyses were conducted to identify the key drivers of cost-effectiveness and quantify uncertainty in the results.



During the trial, mortality was the highest within 30 days of discharge and decreased thereafter in both groups, although the declining rate of mortality was slower in CBI than HBI. At 15 years (extrapolated), HBI was associated with slightly better health outcomes (mean of 0.59 QALYs gained) and mean additional costs of AU$13,876 per patient. The incremental cost-utility ratio and the incremental net monetary benefit (vs CBI) were AU$23,352 per QALY gained and AU$15,835, respectively. The uncertainty was driven by variability in the costs and probabilities of readmissions. Probabilistic sensitivity analysis showed HBI had a 68% probability of being cost-effective at a willingness-to-pay threshold of AU$50,000 per QALY.



Compared with CBI (outpatient specialized HF clinic-based intervention), HBI (home-based predominantly, but not exclusively) could potentially be cost-effective over the long-term in elderly patients with heart failure at a willingness-to-pay threshold of AU$50,000/QALY, albeit with large uncertainty.
Effect of synbiotic in constipated adult women - a randomized, double-blind, placebo-controlled study of clinical response.

Synbiotic intake may selectively change microbiota composition, restore microbial balance in the gut and improve gastrointestinal functions. We have assessed the clinical response of chronically constipated women to a commercially available synbiotic, combining fructooligosaccharides with Lactobacillus and Bifidobacterium strains (LACTOFOS®).



Following 1 week of non-interventional clinical observation, 100 constipated adult women, diagnosed by ROME III criteria, were randomized to receive two daily doses (6 g) of synbiotic or maltodextrin (placebo group), for 30 days. Treatment response was evaluated by patient's daily record of evacuation (stool frequency, consistency and shape, according to Bristol scale), abdominal symptoms (abdominal pain, bloating and flatulence) and constipation intensity (Constipation Scoring System AGACHAN).



Patients treated with synbiotic had increased frequency of evacuation, as well as stool consistency and shape nearer normal parameters than the placebo group, with significant benefits starting during the second and third weeks, respectively (interaction group/time, P<0.0001). There were no significant differences in abdominal symptoms, but AGACHAN score was better in the synbiotic than in the placebo group.



Dietary supplementation with a synbiotic composed of fructooligosaccharides with Lactobacillus and Bifidobacterium improved evacuation parameters and constipation intensity of chronically constipated women, without influencing abdominal symptoms.
Clinical studies on the treatment of cancer cachexia with megestrol acetate plus thalidomide.

The management of cancer-related anorexia/cachexia syndrome (CACS) is a great challenge in clinical practice. To date, practice guidelines for the prevention and treatment of CACS are lacking. The authors conducted a randomized study to confirm the effectiveness and safety of treatment of CACS utilizing megestrol acetate (MA) plus thalidomide.



One hundred and two candidates with CACS were randomly assigned to two treatment groups (trial group and control group): the trial group received MA (160 mg po, bid) plus thalidomide (50 mg po, bid), while the control group received MA (160 mg po, bid) alone. Treatment duration was 8 weeks.



Analysis of the trial group demonstrated a significant increase from baseline in body weight (<0.01), quality of life (p = 0.02), appetite (p = 0.01), and grip strength (p = 0.01), and a significant decrease in fatigue, Glasgow Prognostic Score (p = 0.05), Eastern Cooperative Oncology Group performance status (p = 0.03), IL-6 (p < 0.01), and tumor necrosis factor-α (p = 0.02). In contrast, in the control group, endpoints with a significant improvement from baseline included body weight (p < 0.02) and appetite (p = 0.02). The mean changes in the endpoints from baseline in the trial group were significantly greater compared with the control group: in the primary endpoints, body weight (p = 0.05), fatigue (p < 0.01) and quality of life (p = 0.01), and in the secondary endpoints, grip strength (p = 0.05), Glasgow Prognostic Score (p = 0.02), Eastern Cooperative Oncology Group performance status (p = 0.02), IL-6 (p < 0.01) and tumor necrosis factor-α (p = 0.01). Toxicity was found to be relatively negligible in both groups.



A combination regimen of MA and thalidomide is more effective than MA alone in the treatment of CACS.
Breast imaging: is the sonographic descriptor of orientation valid for magnetic resonance imaging?

To evaluate if the Breast Imaging Reporting and Data System (BI-RADS) ultrasound descriptor of orientation can be used in magnetic resonance imaging (MRI).



We conducted a retrospective study to evaluate breast mass lesions identified by MRI from 2008 to 2010 who had ultrasound (US) and histopathologic confirmation. Lesions were measured in the craniocaudal (CC), anteroposterior (AP), and transverse (T) axes and classified as having a nonparallel orientation, longest axis perpendicular to Cooper's ligaments, or in a parallel orientation when the longest axis is parallel to Cooper's ligaments. The MR image data were correlated with the US orientation according to BI-RADS and histopathological diagnosis.



We evaluated 71 lesions in 64 patients. On MRI, 27 lesions (38.0%) were nonparallel (8 benign and 19 malignant), and 44 lesions (62.0%) were parallel (33 benign and 11 malignant). There was significant agreement between the lesion orientation on US and MRI (kappa value = 0.901). The positive predictive values (PPV) for parallel orientation malignancy on MR and US imaging were 70.4% and 73.1%, respectively.



A descriptor of orientation for breast lesions can be used on MRI with PPV for malignant lesions similar to US.
Oestrogen therapy for prevention of reinfarction in postmenopausal women: a randomised placebo controlled trial.

Results of observational studies suggest that hormone replacement therapy (HRT) could reduce the risk of coronary heart disease (CHD), but those of randomised trials do not indicate a lower risk in women who use oestrogen plus progestagen. The aim of this study was to ascertain whether or not unopposed oestrogen reduces the risk of further cardiac events in postmenopausal women who survive a first myocardial infarction.



The study was a randomised, blinded, placebo controlled, secondary prevention trial of postmenopausal women, age 50-69 years (n=1017) who had survived a first myocardial infarction. Individuals were recruited from 35 hospitals in England and Wales. Women received either one tablet of oestradiol valerate (2 mg; n=513) or placebo (n=504), daily for 2 years. Primary outcomes were reinfarction or cardiac death, and all-cause mortality. Analyses were by intention-to-treat. Secondary outcomes were uterine bleeding, endometrial cancer, stroke or other embolic events, and fractures.



Frequency of reinfarction or cardiac death did not differ between treatment groups at 24 months (rate ratio 0.99, 95% CI 0.70-1.41, p=0.97). Similarly, the reduction in all-cause mortality between those who took oestrogen and those on placebo was not significant (0.79, 0.50-1.27, p=0.34). The relative risk of any death (0.56, 0.23-1.33) and cardiac death (0.33, 0.11-1.01) was lowest at 3 months post-recruitment.



Oestradiol valerate does not reduce the overall risk of further cardiac events in postmenopausal women who have survived a myocardial infarction.
Laparoscopic hyperthermic intraperitoneal peroperative chemotherapy (HIPEC) in the management of refractory malignant ascites: A multi-institutional retrospective analysis in 52 patients.

Malignant ascites is a debilitating condition affecting cancer patients in their terminal stage of disease. Recently, laparoscopic hyperthermic intraperitoneal peroperative chemotherapy (HIPEC) was introduced as a new approach. From September 2001 to August 2008, 52 patients were treated with this new modality. No treatment-related mortality was observed. Median survival was 98 days. One patient developed a clinical recurrence. Laparoscopic HIPEC is a safe and effective method for palliating malignant ascites.
Continuous sodium vaiproate or phenobarbitone in the prevention of ' simple ' febrile convulsions Comparison by a double-blind trial

Of the 265 children aged between 6 and 18 months admitted to hospital in a 26-month period each with his first febrile convulsion, there were 64 who satisfied our criteria for a simple febrile convulsion. Ofthese, 43 (random) were entered into a double-blind trial of continuous sodium valproate versus phenobarbitone, and 21 were untreated. The dosage was phenobarbitone 3-6 mg/kg per day; sodium valproate 30-60 mg/kg per day. 39 completed treatment (21 phenobarbitone, 18 sodium valproate), 2 in each group being withdrawn because of unacceptable side effects. Close supervision and random serum drug estimations showed compliance to be good. After a mean treatment period of 12 months (mean age 25 months) there had been one recurrence in the sodium valproate group compared with 7 in the untreated group (P<0 .05), and 4 recurrences in the phenobarbitone group. The difference between treatment and no treatment was significant (P<0 .05). These results suggest that in simple febrile convulsions occurring between 6 and 18 months of age sodium valproate is as effective as phenobarbitone in preventing recurrence and that either treatmenis better than none.
Interferon alfa-2b and chlorambucil in the treatment of non-Hodgkin's lymphoma

Twenty-two patients with non-Hodgkin's lymphoma (NHL) were treated with a combined regimen of interferon alfa-2b (Intron A; Schering-Plough) and chlorambucil to evaluate the response and efficacy in pre-treated or relapsed patients. Ten patients were classified as having follicular lymphoma and 12 diffuse lymphoma. The treatment schedule consisted of interferon alfa-2b 3 × 106 IU/m2 thrice-weekly and chlorambucil 10 mg daily for three weeks, with a week's rest between each cycle. Treatment continued for upto six cycles. We obtained two complete remissions (CR), 12 good partial remissions (GPR), seven no remissions (NR) and one stable disease. On histologic examination we observed a response in 8 of 10 patients with follicular lymphoma (2 CR and 6 GPR); three of five patients with diffuse mixed lymphoma, and three of seven patients with diffuse lymphoma showed GPR. The major toxicity consisted of fever and nausea and, in one case, lethargy. In one patient the treatment was stopped at the second cycle because of poor compliance. Hematologic toxicity was generally mild and occurred between the third and fourth cycle. We observed hepatic toxicity i.e. a transient increase of transaminase levels, in three patients. We consider this regimen to be effective in the treatment of relapsed or resistant NHL and no more toxic than single agent therapy. A randomized study to verify this therapeutic approach versus conventional therapy with chlorambucil alone in first-line treatment is recommended.
Arterial blood pressure as a predictor of the response to fluid administration in euvolemic nonhypotensive or hypotensive isoflurane-anesthetized dogs.

To determine the effects of rapid small-volume fluid administration on arterial blood pressure measurements and associated hemodynamic variables in isoflurane-anesthetized euvolemic dogs with or without experimentally induced hypotension.



Prospective, randomized, controlled study.



13 healthy dogs.


PROCEDURES
Isoflurane-anesthetized dogs were randomly assigned to conditions of nonhypotension or hypotension (mean arterial blood pressure, 45 to 50 mm Hg) and treatment with lactated Ringer's solution (LRS) or hetastarch (3 or 10 mL/kg [1.4 or 4.5 mL/lb] dose in a 5-minute period or 3 mL/kg dose in a 1-minute period [4 or 5 dogs/treatment; ≥ 10-day interval between treatments]). Hemodynamic variables were recorded before and for up to 45 minutes after fluid administration.



IV administration of 10 mL/kg doses of LRS or hetastarch in a 5-minute period increased right atrial and pulmonary arterial pressures and cardiac output (CO) when dogs were nonhypotensive or hypotensive, compared with findings before fluid administration; durations of these effects were greater after hetastarch administration. Intravenous administration of 3 mL of hetastarch/kg in a 5-minute period resulted in an increase in CO when dogs were nonhypotensive. Intravenous administration of 3 mL/kg doses of LRS or hetastarch in a 1-minute period increased right atrial pressure and CO when dogs were nonhypotensive or hypotensive.



Administration of LRS or hetastarch (3 or 10 mL/kg dose in a 5-minute period or 3 mL/kg dose in a 1-minute period) improved CO in isoflurane-anesthetized euvolemic dogs with or without hypotension. Overall, arterial blood pressure measurements were a poor predictor of the hemodynamic response to fluid administration.
Psychometric Evaluation of the Chinese Version of the Pittsburgh Sleep Quality Index (CPSQI) in Primary Insomnia and Control Subjects

In order to effectively study the population experiencing insomnia, it is important to identify reliable and valid tools to measure sleep that can be administered in the home setting. The purpose of this study was to assess psychometric properties for the Chinese version of the Pittsburgh Sleep Quality Index (CPSQI) in community-dwelling adults with primary insomnia. The CPSQI had an overall reliability coefficient of 0.82 –0.83 for all subjects. ‘Subjective sleep quality’ was the component most highly correlated with the global score. Overall, the CPSQI showed acceptable test–retest reliability over a 14- to 21-day interval with a coefficient of 0.85 for all subjects and 0.77 for primary insomniacs. The two contrasting groups had significantly different global and component scores. A CPSQI of greater than 5 yielded a sensitivity and specificity of 98 and 55% in primary insomniacs vs. controls. A CPSQI of greater than 6 resulted in a sensitivity and specificity of 90 and 67%. Results suggest that the CPSQI is a psychometrically sound measure of sleep quality and disturbance for patients with primary insomnia. It may not be an effective screening tool because of its low specificity, but it can be a sensitive, reliable, and valid outcome assessment tool for use in community-based studies of primary insomnia