nils-herrmann/clean_scirepeval huggingface dataset:
MRI perfusion maps in acute stroke validated with 15O-water positron emission tomography.

Perfusion-weighted imaging maps are used to identify hypoperfusion in acute ischemic stroke. We evaluated maps of cerebral blood flow (CBF), cerebral blood volume, mean transit time, and time to peak (TTP) in acute stroke by comparison with positron emission tomography.



Perfusion-weighted imaging and positron emission tomography were performed in 26 patients with acute ischemic stroke (median 18.5 hours after stroke onset, 65 minutes between MRI and positron emission tomography). The perfusion-weighted imaging-derived maps of CBF, cerebral blood volume, mean transit time, and TTP delay were compared with quantitative positron emission tomography CBF. A receiver-operating characteristic curve analysis identified the best perfusion-weighted imaging map and threshold to identify hypoperfusion <20 mL/100 g/min, a widely used measure of penumbral flow.



Individual regression analysis of positron emission tomography CBF and perfusion-weighted imaging values were strong for CBF and TTP delay and weaker for mean transit time and cerebral blood volume, but the pooled analysis showed a large variance. Receiver-operating characteristic curve analysis identified TTP and CBF maps as most predictive (median area under the curve=0.94 and 0.93). Penumbral flow thresholds were <21.7 mL/100 g/min (CBF), <1.5 mL/100 g (cerebral blood volume), >5.3 seconds (mean transit time), and >4.2 seconds (TTP). TTP and CBF maps reached sensitivity/specificity values of 91%/82% and 89%/87%.



In our sample, maps of CBF, TTP, and mean transit time yielded a good estimate of penumbral flow. The performance of TTP maps was equivalent to deconvolution techniques using an arterial input function. For all maps, the application of a predefined threshold is mandatory and calibration studies will enhance their use in acute stroke therapy as well as in clinical stroke trials.
Evaluation of a pharmacist intervention on patients initiating pharmacological treatment for depression: A randomized controlled superiority trial

Major depression is associated with high burden, disability and costs. Non-adherence limits the effectiveness of antidepressants. Community pharmacists (CP) are in a privileged position to help patients cope with antidepressant treatment. The aim of the study was to evaluate the impact of a CP intervention on primary care patients who had initiated antidepressant treatment. Newly diagnosed primary care patients were randomised to usual care (UC) (92) or pharmacist intervention (87). Patients were followed up at 6 months and evaluated three times (Baseline, and at 3 and 6 months). Outcome measurements included clinical severity of depression (PHQ-9), health-related quality of life (HRQOL) (Euroqol-5D) and satisfaction with pharmacy care. Adherence was continuously registered from the computerised pharmacy records. Non-adherence was defined as refilling less than 80% of doses or having a medication-free gap of more than 1 month. Patients in the intervention group were more likely to remain adherent at 3 and 6 months follow-up but the difference was not statistically significant. Patients in the intervention group showed greater statistically significant improvement in HRQOL compared with UC patients both in the main analysis and PP analyses. No statistically significant differences were observed in clinical symptoms or satisfaction with the pharmacy service. The results of our study indicate that a brief intervention in community pharmacies does not improve depressed patients' adherence or clinical symptoms. This intervention helped patients to improve their HRQOL, which is an overall measure of patient status.
Infusional mitoxantrone plus bolus melphalan as a stem cell transplant conditioning regimen for multiple myeloma.

This study combined infusional mitoxantrone with bolus melphalan as a transplant preparative regimen for multiple myeloma. Mitoxantrone was infused over 6 hr on days 6 and 5. Melphalan was given as a 15 min bolus on day 1 followed by autologous transplant on day 0. Thirty-five patients were enrolled; 57% of enrollees had received ≥ 2 prior treatments. The median overall survival was 5 years and 8 months, with 37% of the subjects alive >7 years posttransplantation. Myelosuppression and mucositis were the most frequent adverse events. This regimen is well tolerated and the survival compares well to other transplant trials.
Are Open-Fit Hearing Aids a Possible Alternative to Bone-Anchored Hearing Devices in Patients with Mild to Severe Hearing Loss? A Preliminary Trial

Open-fit hearing aids (OFHAs) may be of benefit for some individuals with chronic outer and middle ear conditions for which boneanchored hearing devices (BAHDs) are normally recommended. The purpose of this study was to compare performance between OFHAs and BAHDs. A Starkey Destiny 800 OFHA was fit on eight adult BAHD users and speech perception measures in quiet and in background noise were compared under two different test conditions: i) BAHD only and ii) OFHA only. Equivalent outcome measure performance between these two conditions suggests that the OFHA was able to provide sufficient amplification for mild to moderate degrees of hearing loss (pure-tone averages (PTAs) less than 47 dB HL). The improved speech perception performances and increased loudness ratings observed for several of the participants with moderately-severe to severe degrees of hearing loss (PTAs of 47 dB HL or greater) in the BAHD only condition suggest that the OFHA did not provide sufficient amplification for these individuals. Therefore, OFHAs may be a successful alternative to the BAHD for individuals with no more than a moderate conductive hearing loss who are unable or unwilling to undergo implant surgery or unable to wear conventional hearing aids due to allergies, irritation, or chronic infection associated with the ear being blocked with a shell or earmold.
The effect of dofetilide on ventricular defibrillation thresholds.

High defibrillation threshold (DFT) with an inadequate defibrillation safety margin remains an infrequent but troubling problem associated with defibrillator implantation. Dofetilide is a selective class III antiarrhythmic drug that reduces DFTs in a canine model. We hypothesized that dofetilide would reduce DFTs in humans, obviating the need for complex lead systems.



Sixteen consecutive patients with DFTs > or =20 J delivered energy at implant-received dofetilide therapy and underwent follow-up DFT testing acutely following drug loading and/or chronically (128 +/- 94 days). Amiodarone was discontinued in four patients at implantation. With dofetilide, DFTs decreased from 28 +/- 4 J to 19 +/- 7 J (P < 0.0001), resulting in a safety margin of 15 +/- 8 J for the implanted devices. Five patients subsequently had spontaneous arrhythmias terminated successfully with shocks.



Dofetilide reduces DFTs sufficiently to prevent the need for more complex lead systems. This strategy should be considered when an inadequate defibrillation safety margin is present.
Hemoglobin targets and blood transfusions in hemodialysis patients without symptomatic cardiac disease receiving erythropoietin therapy.

Optimal hemoglobin targets for chronic kidney disease patients receiving erythropoiesis-stimulating agents remain controversial. The effects of different hemoglobin targets on blood transfusion requirements have not been well characterized, despite their relevance to clinical decision-making.



Five hundred ninety-six incident hemodialysis patients without symptomatic cardiac disease were randomly assigned to hemoglobin targets of 9.5 to 11.5 g/dl or 13.5 to 14.5 g/dl for 96 wk using epoetin alfa as primary therapy and changes in left ventricular structure as the primary outcome (previously reported). Patients were masked to treatment assignment. Blood transfusion data were prospectively collected at 4-wk intervals.



The mean age and prior duration of dialysis therapy of the study population were 50.8 and 0.8 yr, respectively. Previously reported mortality was similar in low and high-target subjects, at 4.7 (95% confidence interval 3.0, 7.3) and 3.1 (1.8, 5.4) per hundred patient years, respectively. Transfusion rates were 0.66 (0.59, 0.74) units of blood per year in low and 0.26 (0.22, 0.32) in high-target subjects (P < 0.0001). Hemoglobin level at transfusion (7.7 [7.5, 7.9]) versus 8.1 [7.6, 8.5] g/dl) were similar with both groups. High hemoglobin target was a significant predictor of time to first transfusion independent of baseline associations (hazard ratio = 0.42; 95% confidence interval = 0.26-0.67).



In hemodialysis patients with comparatively low mortality risks, normal hemoglobin targets may reduce the need for transfusions.
Effects of the direct renin inhibitor aliskiren and atenolol alone or in combination in patients with hypertension.

Aliskiren is the first in a new class of direct renin inhibitors to be approved for the treatment of hypertension.



In this double-blind, multicentre trial, 694 patients with hypertension (mean sitting diastolic blood pressure [BP] > or = 95 and < 110 mmHg) were randomised to once-daily aliskiren 150 mg (n=231), atenolol 50 mg (n=231) or the combination (150/50 mg; n=232) for six weeks, followed by a further six weeks on double the initial doses of aliskiren and atenolol. Efficacy (reduction from baseline in mean sitting systolic and diastolic BP) and tolerability of study treatments were assessed; plasma renin activity (PRA) was measured in a subset of patients.



At Week 12 endpoint, aliskiren, atenolol and aliskiren/atenolol lowered systolic and diastolic BP from baseline by 14.3/11.3, 14.3/13.7 and 17.3/14.1 mmHg, respectively. Systolic BP reductions with aliskiren/atenolol were significantly greater than those with aliskiren (p=0.039) or atenolol (p=0.034) alone, and diastolic BP reductions were greater than with aliskiren alone (p<0.001). Diastolic BP changes were larger with atenolol than with aliskiren (p=0.003, correlating with the large reductions in pulse rate (> 10 bpm) observed with atenolol. Aliskiren, atenolol and aliskiren/atenolol reduced geometric mean PRA from baseline by 65%, 52% and 61%, respectively. In patients with moderate or high baseline PRA (> or = 0.65 ng/ml/hour), PRA was reduced to low levels (< 0.65 ng/ml/hour) at Week 12 endpoint in a greater proportion of patients receiving aliskiren (11/15 patients, 73.3%) or aliskiren/atenolol (18/23, 78.3%) than with atenolol (10/21, 47.6%). Aliskiren treatment was associated with numerically lower rates of adverse events and discontinuations due to adverse events compared with atenolol or combination treatment, and unlike atenolol was not associated with bradycardia.



Direct renin inhibition with aliskiren may be an appropriate substitute for beta-blocker treatment in patients with uncomplicated hypertension. Aliskiren also represents an attractive option for dual therapy with atenolol to improve systolic BP/pulse pressure reductions and BP control with maintained tolerability compared with atenolol alone.
A Randomized, Double-Blind, Double-Dummy Study to Evaluate the Intranasal Human Abuse Potential and Pharmacokinetics of a Novel Extended-Release Abuse-Deterrent Formulation of Oxycodone

Evaluate the human abuse potential (HAP) of an experimental, microsphere-in-capsule formulation of extended-release oxycodone (oxycodone DETERx®) (herein "DETERx").



Randomized, double-blind, double-dummy, positive- and placebo-controlled, single-dose, four-phase, four-treatment, crossover study.



Clinical research site.



There were 39 qualifying subjects (72% male, 85% white, mean age of 27 years) with 36 completing all four Double-blind Treatment Periods.



The four phases encompassed: 1) Screening; 2) Drug Discrimination; 3) Double-blind Treatment; and 4) Follow-up. Drug Discrimination tests ensured that subjects could distinguish placebo from opioid. The four Double-blind Treatments compared DETERx-administered as either a crushed intranasal (IN) or an intact oral (PO) preparation-with immediate-release oxycodone IN (OXY-IR IN) and with an intact IN and PO placebo DETERx control.



For primary pharmacokinetic (PK) assessments, abuse quotient (Cmax/Tmax) was lower with DETERx IN than DETERx PO; both treatments were substantially lower than OXY-IR IN (6.24, 8.60, and 69.6 ng/mL/h, respectively). For drug liking, the primary subjective pharmacodynamic (PD) endpoint, both DETERx IN and DETERx PO produced significantly lower scores than OXY-IR IN (P ≤ 0.0001 for each); DETERx IN was less liked than DETERx PO (P ≤ 0.05), mirroring the PK relationships. Objectively assessed pupillometry corroborated the more rapid and significantly greater effect of OXY-IR IN than either DETERx IN or DETERx PO (P ≤ 0.007 for each). Overall safety profiles of DETERx and OXY-IR were comparable and both were well tolerated.



Pharmacokinetic and pharmacodynamic outcomes suggest that DETERx IN has relatively low HAP; continued research in larger populations is suggested.
Nedocromil sodium: a new drug for the management of bronchial asthma.

Nedocromil sodium (FPL 59002) is a pyranoquinoline dicarboxylic acid that has been developed for the management of bronchial asthma. We report the results of a double blind group comparative trial in which the disodium salt of nedocromil delivered by pressurised aerosol and a placebo were compared in the management of patients with a diagnosis of bronchial asthma who entered the double blind period on a minimum dose of beclomethasone dipropionate. In almost all the assessments of clinical activity nedocromil sodium was shown to be more effective than placebo. These include improvements in diary card symptom scores, reduction in concomitant use of a bronchodilator aerosol, and patients' and investigators' assessments of efficacy. Unwanted effects were few and mild. No patients were withdrawn from the trial.
A pilot study of systolic dyssynchrony index by real time three-dimensional echocardiography and Doppler tissue imaging parameters predicting the hemodynamic response to biventricular pacing in the early postoperative period after cardiac surgery.

To evaluate systolic dyssynchrony index (SDI) measured by real time three-dimensional echocardiography (RT3DE) and Doppler tissue imaging (DTI) dyssynchrony parameters in predicting the hemodynamic response to biventricular (BIV) pacing in the early postoperative period after cardiac surgery. To compare right ventricular (RV) and BIV pacing using invasively measured hemodynamic values.



A prospective randomized clinical study enrolling 11 patients with ischemic heart disease, concomitant valvular heart disease, and left ventricular ejection fraction (LVEF) ≤ 35% comparing preoperative SDI by RT3DE and DTI LV dyssynchrony parameters to hemodynamic values obtained during RV or BIV sequential (DDD) epicardial pacing in the first 72 hours after cardiac surgery.



BIV pacing produced a statistically significant higher cardiac output (CO) (6.27 ± 1.55 L/min) and cardiac index (CI) (3.44 ± 0.93 L/min per m(2) ) than RV pacing (CO 5.44 ± 0.97 L/min, CI 3.03 ± 0.83 L/min per m(2) , P < 0.05). We found a statistically moderate correlation between preoperative SDI by RT3DE and CO (r = 0.596, P < 0.05) and a nonsignificant correlation to CI (r = 0.535, P < 0.10) during BIV pacing. No correlation was observed between DTI dyssynchrony parameters and measured hemodynamic values. BIV pacing reduced the ICU stay and inotropic support requirements of patients after heart surgery.



SDI measured preoperatively using RT3DE can predict CO during BIV pacing in the early postoperative period after cardiac surgery. BIV pacing is more hemodynamically effective than RV pacing in patients with LV dysfunction after coronary artery bypass grafting with or without a valve procedure.
Association between single nucleotide polymorphism-genotype and outcome of patients with chronic lymphocytic leukemia in a randomized chemotherapy trial.

There is variability in the outcome of patients with chronic lymphocytic leukemia with apparently the same stage of disease. Identifying genetic variants that influence patients' outcome and response to treatment may provide important insights into the biology of the disease.



We investigated the possibility that genetic variation influences outcome by conducting a genome-wide analysis of 346,831 single nucleotide polymorphisms in 356 patients entered into a phase III trial comparing the efficacy of fludarabine, chlorambucil, and fludarabine with cyclophosphamide as first-line treatment. Genotypes were linked to individual patients' outcome data and response to chemotherapy. The association between genotype and progression-free survival was assessed by Cox regression analysis adjusting for treatment and clinicopathology.



The strongest associations were shown for rs1949733 (ACOX3; P=8.22x10-7), rs1342899 (P=7.72×10(-7)) and rs11158493 (PPP2R5E; P=8.50×10(-7)). In addition, the 52 single nucleotide polymorphisms associated at P<10(-4) included rs438034 (CENPF; P=4.86×10(-6)), previously correlated with cancer progression, and rs2255235 (B2M; P=3.10×10(-5)) and rs2064501 (IL22RA2; P=4.81×10(-5)) which map to B-cell genes.



Our findings provide evidence that genetic variation is a determinant of progression-free survival of patients with chronic lymphocytic leukemia. Specific associations warrant further analyses.
Itolizumab in combination with methotrexate modulates active rheumatoid arthritis: safety and efficacy from a phase 2, randomized, open-label, parallel-group, dose-ranging study

The objective of this study was to assess the safety and efficacy of itolizumab with methotrexate in active rheumatoid arthritis (RA) patients who had inadequate response to methotrexate. In this open-label, phase 2 study, 70 patients fulfilling American College of Rheumatology (ACR) criteria and negative for latent tuberculosis were randomized to four arms: 0.2, 0.4, or 0.8 mg/kg itolizumab weekly combined with oral methotrexate, and methotrexate alone (2:2:2:1). Patients were treated for 12 weeks, followed by 12 weeks of methotrexate alone during follow-up. Twelve weeks of itolizumab therapy was well tolerated. Forty-four patients reported adverse events (AEs); except for six severe AEs, all others were mild or moderate. Infusion-related reactions mainly occurred after the first infusion, and none were reported after the 11th infusion. No serum anti-itolizumab antibodies were detected. In the full analysis set, all itolizumab doses showed evidence of efficacy. At 12 weeks, 50 % of the patients achieved ACR20, and 58.3 % moderate or good 28-joint count Disease Activity Score (DAS-28) response; at week 24, these responses were seen in 22 and 31 patients. Significant improvements were seen in Short Form-36 Health Survey and Health Assessment Questionnaire Disability Index scores. Overall, itolizumab in combination with methotrexate was well tolerated and efficacious in RA for 12 weeks, with efficacy persisting for the entire 24-week evaluation period.
Short- and long-term outcomes of endoscopic submucosal dissection for early gastric cancer in elderly patients aged 75 years and older

Only a few studies have reported long-term outcomes for endoscopic submucosal dissection (ESD) of early gastric cancer (EGC) in elderly patients. The aim of this study was to evaluate the efficacy of ESD for EGC in elderly patients ≥75 years with respect to both short- and long-term outcomes. We reviewed the clinical data of elderly patients ≥75 years who had undergone ESD for EGC at Tonan Hospital from January 2003 to May 2010. A total of 177 consecutive patients, including 145 with curative resection (CR) and 32 with noncurative resection (non-CR), were examined. Of the 32 patients with non-CR, 15 underwent additional surgery, and lymph node metastases were found in 3 patients. The remaining 17 patients were followed without additional surgery because of advanced age or poor general condition. Procedure-related complications, such as post-ESD bleeding, perforation and pneumonia, were within the acceptable range. The 5-year survival rates of patients with CR, those with additional surgery after non-CR, and those without additional surgery after non-CR were 84.6, 73.3, and 58.8 %, respectively. No deaths were attributable to the original gastric cancer; patients succumbed to other illnesses, including malignancy and respiratory disease. In elderly patients, ESD is an acceptable treatment for EGC in terms of both short- and long-term outcomes. Careful clinical assessment of elderly patients is necessary before ESD. After ESD, medical follow-up is important so that other malignancies and diseases that affect the elderly are not overlooked.
Control of esophageal and intragastric pH with compounded and manufactured omeprazole in patients with reflux esophagitis: a pilot study.

Proton pump inhibitors (PPI) are the drugs of choice for treatment of gastroesophageal reflux disease (GERD). Omeprazole, the first PPI commercialized, is now available in different formulations.



To compare the efficacy of different omeprazole formulations on gastric acid secretion measured by intragastric and esophageal pH monitoring in patients with reflux esophagitis.



Prospective, open, randomized clinical trial involving H. pylori negative patients with typical symptoms of GERD. Patients were submitted to 24-h intragastric and esophageal pH studies during use of six different formulations of compounded and manufactured omeprazole.



Thirty patients, 19 female, median age 55 years were studied. The intragastric pH was maintained below 4.0 for a median of 36.7% of total time in compounded group and 47.7% in manufactured group (p>0.05). There was also no statistical difference between the median percentage of time of pH below 4.0 in orthostatic and supine position in compounded and manufactured groups (30.1% and 49.6% and 28.8% and 55.2%, respectively). The esophageal pH was maintained below 4.0 for a median of 0.1% of total time in compounded group and 0.4% in manufactured group (p>0.05). In orthostatic position the median percentage of time of esophageal pH below 4.0 was 0.0% in both groups (p>0.05). In supine position, the median percentage of time of esophageal pH below 4.0 was 0.1% and 0.3% in compounded and manufactured groups, respectively (p>0.05).



The omeprazole formulations studied (compounded and manufactured) showed similar control of gastric acid secretion and esophageal acid exposure in patients with reflux esophagitis.