nils-herrmann/clean_scirepeval huggingface dataset:
Effects of exenatide combined with lifestyle modification in patients with type 2 diabetes.

To determine the effect of a lifestyle modification program plus exenatide versus lifestyle modification program plus placebo on weight loss in overweight or obese participants with type 2 diabetes treated with metformin and/or sulfonylurea.



In this 24-week, multicenter, randomized, double-blind, placebo-controlled study, 194 patients participated in a lifestyle modification program, consisting of goals of 600 kcal/day deficit and physical activity of at least 2.5 hours/week. Participants were randomized to 5 microg exenatide twice daily injection + lifestyle modification program (n = 96) or placebo + lifestyle modification program (n = 98), and after 4 weeks increased their exenatide dose to 10 microg twice daily or volume equivalent of placebo.



Baseline characteristics: (mean +/- standard deviation) age, 54.8 +/- 9.5 years; weight, 95.5 +/- 16.0 kg; hemoglobin A(1c), 7.6 +/- 0.8%. At 24 weeks (least squares mean +/- standard error), treatments showed similar decreases in caloric intake (-378 +/- 58 vs -295 +/- 58 kcal/day, exenatide + lifestyle modification program vs placebo + lifestyle modification program, P = .27) and increases in exercise-derived energy expenditure. Exenatide + lifestyle modification program showed greater change in weight (-6.16 +/- 0.54 kg vs -3.97 +/- 0.52 kg, P = .003), hemoglobin A(1c) (-1.21 +/- 0.09% vs -0.73 +/- 0.09%, P <.0001), systolic (-9.44 +/- 1.40 vs -1.97 +/- 1.40 mm Hg, P <.001) and diastolic blood pressure (-2.22 +/- 1.00 vs 0.47 +/- 0.99 mm Hg, P = .04). Nausea was reported more for exenatide + lifestyle modification program than placebo + lifestyle modification program (44.8% vs 19.4%, respectively, P <.001), with no difference in withdrawal rates due to adverse events (4.2% vs 5.1%, respectively, P = 1.0) or rates of hypoglycemia.



When combined with lifestyle modification, exenatide treatment led to significant weight loss, improved glycemic control, and decreased blood pressure compared with lifestyle modification alone in overweight or obese participants with type 2 diabetes on metformin and/or sulfonylurea treatment.
The effect of nebulised magnesium sulphate in the management of childhood moderate asthma exacerbations as adjuvant treatment.

After the bronchodilator effect of magnesium was shown, the use of magnesium in treatment of asthma exacerbations became common. With the results of recent studies, the use of intravenous magnesium in severe asthma exacerbations took its place. We aimed to examine the effects of adding isotonic magnesium sulphate instead of isotonic saline into nebulised salbutamol on the Modified Pulmonary Index Score (MPIS) and the hospitalisation rate in moderate asthma exacerbations.



Our study population included 100 children age between 3 and 15 years with asthma admitted to emergency department due to moderate asthma exacerbations. The patients were randomised to placebo or magnesium, with 50 patients in each arm. All patients received 1mg/kg of systemic methylprednisolone at the beginning of treatment and thereafter received either nebulised salbutamol (0.15mg/kg/dose) and 1ml magnesium sulphate (15%)+1.5ml isotonic saline on three occasions at roughly 20min intervals (Magnesium group) or nebulised salbutamol (0.15mg/kg/dose) and 2.5ml isotonic saline mixture on three occasions at roughly 20min intervals (Placebo group). The MPIS of patients on 0th min, 20th min, 40th and 120th min were calculated and compared. The primary outcome was to compare MPIS values at the end of 120th min.



Both groups have similar demographic, allergic characteristics and baseline MPIS scores. When the MPIS scores in the 120th min and admission rates in the 200th min, there was no significant difference between the two groups.



The use of nebulised magnesium sulphate in moderate asthma exacerbation as adjuvant treatment showed no benefit to standard treatment in our study.
Comparison of Coagulation Parameters, Anticoagulation, and Need for Transfusion in Patients on Interventional Lung Assist or Veno-Venous Extracorporeal Membrane Oxygenation.

Clinical data on anticoagulation needs of modern extracorporeal membrane oxygenation (ECMO) and its impact on coagulation are scarce. Therefore, we analyzed coagulation-related parameters, need for transfusion, and management of anticoagulation in adult patients with severe acute respiratory failure during treatment with either pumpless interventional lung assist (iLA) or veno-venous ECMO (vv-ECMO). Sixty-three patients treated with iLA and 192 patients treated with vv-ECMO at Regensburg University Hospital between January 2005 and May 2011 were analyzed. Data related to anticoagulation, transfusion, and coagulation parameters were collected prospectively by the Regensburg ECMO registry. Except for a higher, sequential organ failure assessment (SOFA) score in the ECMO group (12 [9-15] vs. 11 [7-14], P = 0.007), a better oxygenation, and a lower dosage of vasopressors in the iLA patients, both groups had similar baseline characteristics. No difference was noted in terms of outcome and overall transfusion requirements. Factors of the plasmatic coagulation system were only marginally altered over time and did not differ between groups. Platelet counts in ECMO-treated patients, but not in those treated with iLA, dropped significantly during extracorporeal support. A more intense systemic anticoagulation with a mean activated partial thromboplastin time (aPTT) > 53 s led to a higher need for transfusions compared with the group with a mean aPTT < 53 s, whereas the average durability of membrane oxygenators was not affected. Need for red blood cell (RBC) transfusion was highest in patients with extrapulmonary sepsis (257 mL/day), and was significantly lower in primary pulmonary adult respiratory distress syndrome (ARDS) (102 mL/day). Overall, 110 (0-274) mL RBC was transfused in the ECMO group versus 146 (41-227) mL in the iLA group per day on support. The impact of modern iLA and ECMO systems on coagulation allows comparatively safe long-term treatment of adult patients with acute respiratory failure. A moderate systemic anticoagulation seems to be sufficient. Importantly, platelets are more affected by vv-ECMO compared with pumpless iLA.
Anti-VEGF antibody bevacizumab (Avastin) with 5FU/LV as third line treatment for colorectal cancer

To evaluate the activity and safety of bevacizumab when given with standard 5FU/leukovorin (LV) regimens in patients with metastatic colorectal cancer who have failed irinotecan and oxaliplatin-based treatments. Bevacizumab was given at 5 mg/kg as an IV infusion every 2 weeks. Patients received 5FU according to Roswell Park or the de Gramont regimen. Nineteen patients enrolled, median age 60, median PS: 1. Most common toxicity attributable to bevacizumab was mild hypertension, epistaxis and mild proteinuria; 1 patient had a CNS haemorrhage. The median number of cycles was 1 (8 weeks). Clinical benefit as disease stabilisation lasting 2–6 months was noted in 9 patients, whereas 10 progressed (median f/u: 5 months). TTP was 16 weeks, and the overall survival has not been reached (24+ weeks). Bevacizumab may result in growth arrest and clinical benefit in a substantial proportion of patients with colorectal cancer and no alternative treatment.
Computed tomographic colonography versus colonoscopy for investigation of patients with symptoms suggestive of colorectal cancer (SIGGAR): a multicentre randomised trial

Colonoscopy is the gold-standard test for investigation of symptoms suggestive of colorectal cancer; computed tomographic colonography (CTC) is an alternative, less invasive test. However, additional investigation after CTC is needed to confirm suspected colonic lesions, and this is an important factor in establishing the feasibility of CTC as an alternative to colonoscopy. We aimed to compare rates of additional colonic investigation after CTC or colonoscopy for detection of colorectal cancer or large (≥10 mm) polyps in symptomatic patients in clinical practice.



This pragmatic multicentre randomised trial recruited patients with symptoms suggestive of colorectal cancer from 21 UK hospitals. Eligible patients were aged 55 years or older and regarded by their referring clinician as suitable for colonoscopy. Patients were randomly assigned (2:1) to colonoscopy or CTC by computer-generated random numbers, in blocks of six, stratified by trial centre and sex. We analysed the primary outcome-the rate of additional colonic investigation-by intention to treat. The trial is an International Standard Randomised Controlled Trial, number 95152621.



1610 patients were randomly assigned to receive either colonoscopy (n=1072) or CTC (n=538). 30 patients withdrew consent, leaving for analysis 1047 assigned to colonoscopy and 533 assigned to CTC. 160 (30.0%) patients in the CTC group had additional colonic investigation compared with 86 (8.2%) in the colonoscopy group (relative risk 3.65, 95% CI 2.87-4.65; p<0.0001). Almost half the referrals after CTC were for small (<10 mm) polyps or clinical uncertainty, with low predictive value for large polyps or cancer. Detection rates of colorectal cancer or large polyps in the trial cohort were 11% for both procedures. CTC missed 1 of 29 colorectal cancers and colonoscopy missed none (of 55). Serious adverse events were rare.



Guidelines are needed to reduce the referral rate after CTC. For most patients, however, CTC provides a similarly sensitive, less invasive alternative to colonoscopy.
Controlled-release methylphenidate improves attention during on-road driving by adolescents with attention-deficit/hyperactivity disorder.

Attention-deficit/hyperactivity disorder (ADHD) is associated with a 3- to 4-fold increase in both driving-related accidents and associated injuries. Methylphenidate (MPH) is the most commonly prescribed psychostimulant medication for ADHD. It has been demonstrated to improve performance on a driving simulator. This study investigated whether a once-daily, long-acting, osmotic, controlled-release MPH formulation improves the driving performance of ADHD adolescents while driving their own car on an actual road segment.



Twelve ADHD-diagnosed male adolescent drivers (mean age, 17.8 years) prescribed a standard dose of 1.0 mg/kg (if they were not already taking methylphenidate) of controlled-release MPH participated in this repeated-measures crossover study. On 2 separate occasions (off/on medication randomized), participants drove a standard 16-mile road course incorporating rural, highway, and urban streets. A rater, blind to medication conditions, sat in the back seat and rated impulsive (eg, "cutting off" another driver) and inattentive (eg, drove past designated turn) driving errors.



Impulsive driving errors were observed to occur rarely under both medication and no medication conditions. Inattentive driving errors were more common and were significantly reduced while the subject was on medication (4.6 versus 7.8; P <.01). The improvement in driving performance (change in number of errors recorded) from first to second testing was positively correlated with medication dosage (r = 0.60; P <.01).



Once-daily controlled-release MPH improves real-life driving performance of adolescent males diagnosed with ADHD. In particular, it significantly reduces driving errors arising from inattention.
A Phase I and pharmocokinetic study of exatecan mesylate administered as a protracted 21-day infusion in patients with advanced solid malignancies.

The purpose of this study was to assess the feasibility of administering exatecan, a water-soluble, potent camptothecin analogue, as a protracted 21-day continuous i.v. infusion (CIVI). The study also sought to determine the maximum tolerated dose (MTD) of exatecan on a 21-day CIVI schedule, characterize its pharmacokinetic behavior, and seek preliminary evidence of anticancer activity.



Exatecan dose-schedule development was performed in two stages using the modified Continual Reassessment Method and single patient cohorts. First, patients with advanced solid malignancies were treated with exatecan (0.15 mg/m(2)/day) as a CIVI for 5 days, and the duration of the CIVI was incrementally increased from 5 to 21 days. In the second stage of the study, the dose was incrementally increased to derive a tolerable dose of exatecan administered as 21-day CIVI. The MTD was defined for both minimally pretreated (MP) and heavily pretreated (HP) patients as the highest dose level at which the incidence of dose-limiting toxicity does not exceed 20%.



Thirty-one patients were treated with 100 courses of exatecan at 6 dose-schedule levels. The incidence of the principal dose-limiting toxicities, neutropenia and thrombocytopenia, was unacceptably high at exatecan doses exceeding 0.15 mg/m(2)/day as a 21-day CIVI, which was determined to be the MTD for both MP and HP patients. The pharmacokinetics of exatecan were dose-proportional, and mean [coefficient of variation (percentage) steady-state concentration (plasma concentration at steady-state)] values ranged from 6.88 (80.6) to 19.41 (74.2) ng/ml at exatecan dose levels ranging from 0.15 to 0.30 mg/m(2)/day, which are similar to IC(50) values against human tumor cell lines treated for shorter periods. Mean pharamacokinetic parameters for total exatecan derived from a compartmental model included clearance and volume of distribution values of 1.39 (86.9) liters/h/m(2) and 39.66 (197.4) liters, respectively. Two HP patients with non-small cell lung and unknown primary carcinomas had partial responses, and objective evidence of anticancer activity and clinical benefit were noted in several other individuals.



The administration of exatecan as a 21-day CIVI at doses as high as 0.15 mg/m(2)/day is safe and feasible for both MP and HP patients. The characteristics of the myelosuppressive effects of exatecan on this schedule, the paucity of severe nonhematological toxicities, and documented anticancer activity in several drug-refractory malignancies warrant further evaluation of the merits of administering exatecan by either a CIVI or alternate drug delivery systems to achieve protracted systemic exposure.
Mitoxantrone in the treatment of relapsed and refractory acute leukemia

Twenty-four patients with acute leukemia or blast crisis (BC) of chronic myelocytic leukemia (CML) in relapse or refractory to standard chemotherapy, were eligible for treatment with mitoxantrone. Mitoxantrone (Novantrone®; dihydroxyanthracenedione) was administered in a dose of 8–13 mg/m2 on five consecutive days. Five of 20 evaluable patients were induced into complete remission, one patient achieved a partial remission. Side-effects included moderate to severe bone marrow suppression, moderate mucositis and hair loss. No cardiotoxicity was observed. We believe that mitoxantrone is an active agent in the treatment of acute leukemia and suggest further studies in combination chemotherapy.
Gender-specific prevalence and associated risk factors of high normal blood pressure and hypertension among multi-ethnic Chinese adolescents aged 8-18 years old.

To date, accurate reports about the prevalence of high normal blood pressure (BP) and hypertension among Chinese adolescents have been rare. We examine the sex-specific and age-specific prevalence of high normal BP and hypertension, and the associated risk factors among multi-ethnic Chinese adolescents from a large and representative sample.



29,997 adolescents aged 8-18 years old received blood pressure measurement on one clinical visit.



The overall prevalence was 4.15% for hypertension (4.73% for boys and 3.62% for girls) and 29.85% for high normal BP (33.40% for boys and 26.65% for girls). The odds ratios (ORs) increased with age, but the absolute changes of ORs were significantly different between boys and girls. Compared with that of the Han counterparts, the risk of high normal BP was 1.960-fold, 1.283-fold and 1.618-fold for Yi boys, Mongolian boys and Yi girls, respectively, whereas the OR was 0.440 for Tibetan boys, 0.492 for Tibetan girls and 0.794 for Korean girls. Compared with those of normal weight, overweight and obese adolescents had significantly increased risk of high normal BP (OR = 3.377 for obese boys and OR = 2.009 for overweight boys; OR = 2.865 for obese girls and OR = 1.738 for overweight girls). Rural adolescents had a higher risk of hypertension than those living in urban areas.



The prevalence of high normal BP and hypertension was high in Chinese adolescents. Age, ethnicity, obesity, overweight, abnormal waist circumference, family history of cardiovascular diseases and dwelling at rural districts were significantly associated with pediatric high normal BP or hypertension.
Evaluation of novel formula of PSA, age, prostate volume, and race in predicting positive prostate biopsy findings.

To develop a formula that incorporates age, prostate volume, race, and prostate-specific antigen (PSA) level into a single score for prostate cancer detection.



We developed a PSA-age volume (AV) score by multiplying the patient age by the prostate volume and dividing it by the PSA level. The PSA-AV was developed using 1000 prostate biopsy specimens and was validated on 318 internal and 4406 external biopsy specimens.



We analyzed 1000 biopsy specimens (mean age 63 ± 8 years, 63% white and 35% black, mean PSA 6.8 ± 4 ng/mL, mean prostate volume 41 ± 18 cm(3), mean PSA-AV 485 ± 304). Of the 1000 biopsy specimens, 556 (55.6%) had positive findings. A lower PSA-AV score correlated with a greater cancer risk (R(2) = 0.91). A PSA-AV score of 700 had a sensitivity and specificity of 87% and 35%, respectively. These values matched or exceeded the sensitivity and specificity for age-adjusted PSA level and a PSA cutoff of 4 ng/mL. Compared with using the age-adjusted PSA level, using a score of 700 increased the number of biopsies by 64 and detected 62 more cancers. Using a PSA-AV cutoff of 700, rather than a PSA cutoff of 4 ng/mL, led to 16 fewer biopsies with 7 additional cancers detected. Our data were internally and externally validated.



According to our data, a PSA-AV score has shown to be a useful formula for predicting positive biopsy findings. A PSA-AV score of 700 is useful in ruling out cancer in younger patients and patients with small prostates, and in ruling in cancer in older patients and patients with a large prostate.
Myocardial uptake and biochemical and hemodynamic effects of ACE inhibitors in humans.

There is little information on the processes affecting selective tissue ACE inhibition and the implications in human subjects. We compared intravenously administered ACE inhibitors, perindoprilat and enalaprilat, for myocardial drug uptake and effects on angiotensin and bradykinin peptides versus hemodynamic effects in 25 patients with stable angina and well-preserved left ventricular systolic function. Myocardial uptake was rapid and more efficient for perindoprilat than for enalaprilat (peak content at 26+/-3 and 30+/-4 seconds, 0.58+/-0.12% and 0.27+/-0.07% of the administered dose for perindoprilat and enalaprilat, respectively, P=0.04 for difference). Both drugs caused a decrease in angiotensin (Ang) II level, an increase in Ang I level, and reduction in Ang II/Ang I ratio in arterial and coronary sinus blood. Bradykinin (BK)-(1-9) and BK-(1-8) levels increased in arterial blood and BK-(1-8) levels increased in coronary sinus blood after drug administration. Perindoprilat and enalaprilat caused a small decrease in mean arterial pressure (-3+/-1%, P<0.05; and -4+/-1%, P<0.01, respectively) and LV+dP/dt (-5.8+/-1.7%, P<0.01 and -4.2+/-2.8%, P<0.05, respectively), whereas systemic vascular resistance index was unchanged. Despite relatively cardioselective uptake of perindoprilat, both drugs had similar effects on the cardiac metabolism of angiotensin and bradykinin and on cardiac function. Under resting conditions, both drugs exerted small negative inotropic effects.
Validation of a screening tool to identify older children living with HIV in primary care facilities in high HIV prevalence settings

We previously proposed a simple tool consisting of five items to screen for risk of HIV infection in adolescents (10-19 years) in Zimbabwe. The objective of this study is to validate the performance of this screening tool in children aged 6-15 years attending primary healthcare facilities in Zimbabwe.



Children who had not been previously tested for HIV underwent testing with caregiver consent. The screening tool was modified to include four of the original five items to be appropriate for the younger age range, and was administered. A receiver operator characteristic analysis was conducted to determine a suitable cut-off score. The sensitivity, specificity and predictive value of the modified tool were assessed against the HIV test result.



A total of 9568 children, median age 9 (interquartile, IQR: 7-11) years and 4971 (52%) men, underwent HIV testing. HIV prevalence was 4.7% (95% confidence interval, CI:4.2-5.1%) and increased from 1.4% among those scoring zero on the tool to 63.6% among those scoring four (P < 0.001). Using a score of not less than one as the cut-off for HIV testing, the tool had a sensitivity of 80.4% (95% CI:76.5-84.0%), specificity of 66.3% (95% CI:65.3-67.2%), positive predictive value of 10.4% and a negative predictive value of 98.6%. The number needed to screen to identify one child living with HIV would drop from 22 to 10 if this screening tool was used.



The screening tool is a simple and sensitive method to identify children living with HIV in this setting. It can be used by lay healthcare workers and help prioritize limited resources.
Use of the osmolal gap to guide the start and duration of dialysis in methanol poisoning.

Rapid diagnosis and treatment of methanol poisoning is mandatory. Dependence on serum methanol analysis in this situation may delay diagnosis and treatment. The anion and osmolal gaps have been recommended for use as diagnostic tools, but the use of these gaps to evaluate the length of hemodialysis treatment has only been emphasized in a few reports. We evaluated the usefulness of the osmolal gap in estimating the need for dialysis and the duration of this treatment in 17 methanol-poisoned subjects.



Patients were part of a recent outbreak of methanol poisoning, in which the diagnosis upon admission was mainly based on use of the anion and osmolal gaps. The duration of dialysis generally followed the standard recommendation of 8h. During dialysis, blood samples were frequently collected and analyzed to determine acid-base status and serum methanol and to calculate the osmolal gap. In nine patients, the duration of dialysis was compared with the duration necessary to normalize serum methanol and the osmolal gap.



There was a good correlation between serum methanol and the osmolal gap during hemodialysis (y=1.09x+3.82; R(2)=0.92). The osmolal gap therefore gives a good estimate of the serum methanol level during hemodialysis, and could have saved a total of 23 h of dialysis treatment (34%) in nine patients had it been applied.



In the absence of serum methanol analyses, the osmolal gap is useful to assess the indication for and duration of hemodialysis in methanol-poisoned patients. In mass poisoning situations, use of the osmolal gap makes it possible to reduce the duration of dialysis in a safe manner.