nils-herrmann/clean_scirepeval huggingface dataset:
A randomised, double-blind comparison of the angiotensin II receptor antagonist, irbesartan, with the full dose range of enalapril for the treatment of mild-to-moderate hypertension

To compare the anti-hypertensive efficacy, safety, and tolerability of irbesartan with those of the full dose range of enalapril in patients with mild-to-moderate hypertension.  A total of 200 patients were randomised to irbesartan 75 mg or enalapril 10 mg (once daily). Doses were doubled at Weeks 4 and/or 8 if seated diastolic blood pressure (DBP) was ⩾90 mm Hg. Trough blood pressure was measured after completion of a 4- to 5-week placebo lead-in period and again after 2, 4, 8, and 12 weeks of treatment.  Efficacy was evaluated by determining the change from baseline in trough seated blood pressure and the proportion of patients normalised (seated DBP <90 mm hg) at week 12. safety and tolerability were assessed by adverse events reported by physicians, by patients in response to a specific-symptoms questionnaire, by open-ended questioning of patients by physicians, and by clinical laboratory evaluations.  Both treatments significantly lowered blood pressure with no significant difference in efficacy between treatment groups. At Week 12, the percentage of patients titrated to either enalapril 40 mg or irbesartan 300 mg was 24% and 28%, respectively. The frequency of overall adverse events was similar in both groups. The incidence of cough in the enalapril and irbesartan groups was 17% and 10%, respectively. In contrast to other AII receptor antagonists, there was no change in uric acid concentrations with irbesartan.  Irbesartan was as effective as the full dose range of enalapril. Irbesartan also demonstrated an excellent tolerability profile.
A 13-week, multicenter, randomized, double-blind study of lumiracoxib in hip osteoarthritis

The aim of this 13-week, multicenter, randomized, double-blind, double-dummy, placebo- and positive-internal (celecoxib)-controlled, parallel-group study was to demonstrate the efficacy, safety, and tolerability of lumiracoxib in primary hip osteoarthritis (OA) patients. Eligible patients (n = 1,262; ACR criteria) were randomized (1:1:1) to receive lumiracoxib 100 mg once daily (o.d.) (n = 427), celecoxib 200 mg o.d. (n = 419), or matching placebo o.d. (n = 416) administered orally. The primary objective was to compare lumiracoxib 100 mg o.d. and placebo with respect to three co-primary efficacy variables: the pain subscale of the Western Ontario and McMaster Universities Osteoarthritis Index Likert version 3.1 (WOMAC™ LK 3.1) questionnaire, the function subscale of the WOMAC™ LK 3.1 questionnaire, and patient’s global assessment of disease activity (100-mm visual analog scale (VAS)) after 13 weeks of treatment. Of the 1,262 randomized patients, 951 completed the study. All randomized patients were included in the intention-to-treat and safety populations. Lumiracoxib was superior to the placebo (p < 0.001) after 13 weeks for all three co-primary endpoints. By week 13, the patient’s global assessment of disease activity (100-mm VAS) improved by 23.3 mm (±SD, 27.83 mm) with lumiracoxib and 13.3 mm (±26.71 mm) with placebo. The WOMAC™ function score decreased by 10.4 (±13.56) with lumiracoxib and 6.8 (±12.55) with placebo. The WOMAC™ pain scores decreased by 3.4 (±4.16) with lumiracoxib and 2.2 (±3.94) with placebo at week 13. Similar results were observed for secondary endpoints: OA pain intensity and WOMAC™ total score. Lumiracoxib was similar to celecoxib for all three co-primary endpoints. All treatments were well tolerated. In conclusion, lumiracoxib is effective in reducing pain and improving function in hip OA patients.
Validity of predischarge measures for predicting time to harm in older adults.

Concern is often expressed about the ability of persons with cognitive impairment to manage safely after discharge home from hospital. Measures validated for predicting safety are required.



The purpose of this study was to determine whether two predischarge functional measures were valid for predicting time to incident of harm after discharge.



Participants (n = 47) were recruited from an inpatient rehabilitation unit. The Assessment of Motor and Process Skills (AMPS) and Cognitive Performance Test (CPT) were administered in hospital. Incident-of-harm outcome was measured by caregiver telephone questionnaire monthly for 6 months.



Compared with all independent variables, AMPS Process scale was the best single predictor of time to incident of harm (p = .01). CPT had a high specificity (91%) for identifying persons who did not have harm.



Both AMPS and CPT demonstrated predictive validity for harm outcome over less predictive variables, such as comorbidities and activities-of-daily-living burden of care.
Melatonin pharmacokinetics following two different oral surge-sustained release doses in older adults.

Melatonin is increasingly used for the treatment of sleep disorders. Surge-sustained formulations consisting of combined immediate release and controlled release dosing may mimic the endogenous melatonin physiologic profile. However, relatively little is known about the pharmacokinetic properties of low-dose (<0.5mg) and high-dose (>2mg) melatonin in a combined immediate release/controlled release dose, especially in older adults who may also exhibit altered melatonin disposition. To assess this, we conducted a randomized, double-blind, placebo-controlled study of low-dose (0.4mg) and high-dose (4.0mg) melatonin (25% immediate release+75% controlled release) in 27 older adults with insomnia complaints and low endogenous melatonin levels to determine whether melatonin pharmacokinetic properties differ between these two doses. The time to maximum level (1.3hrs versus 1.5hrs), elimination half-life (1.8hrs versus 2.1hrs), and apparent total clearance (379L/hr versus 478L/hr) did not differ significantly between the low- and high-dose arms, respectively. The maximum concentration was 405 ±93pg/mL for the low-dose arm and 3999±700pg/mL for the high-dose arm, both of which are substantially higher than physiologic melatonin levels for this age group. In addition, subjects in the high-dose arm maintained melatonin levels >50pg/mL for an average of 10hrs, which could result in elevated melatonin levels beyond the typical sleep period. Renal and liver function parameters remained stable after 6wks of treatment. The linear pharmacokinetic behavior of melatonin observed in the elderly can form the basis for future studies exploring a wider range of dosing scenarios to establish exposure-response relationships for melatonin-mediated sleep outcomes.
Memantine prevents hypoglycemia-induced decrements of the cerebral energy status in healthy subjects.

The risk to develop dementia is significantly increased in diabetes mellitus. Memantine, an N-methyl-D-aspartate receptor antagonist, which is clinically applied in dementia, has been shown to exert neuroprotective effects under hypoglycemic conditions in rats.



We hypothesized that memantine may prevent hypoglycemia-induced decrements in the cerebral high-energy phosphate, i.e. ATP, metabolism to exert its neuroprotective action under these conditions.



In a randomized, double-blind crossover design, we applied memantine vs. placebo in 16 healthy male subjects and examined the cerebral high-energy phosphate metabolism by (31)phosphor magnetic resonance spectroscopy, hormonal counterregulation, and neurocognitive performance during hypoglycemic glucose clamp conditions.



We found increments in hormonal counterregulation and reduced neurocognitive performance during hypoglycemia (P < 0.05). Cerebral ATP levels increased upon hypoglycemia in the memantine condition as compared with placebo (P = 0.006) and remained higher after renormalizing blood glucose concentrations (P = 0.018), which was confirmed by ATP to inorganic phosphate ratio (P = 0.046). Phosphocreatine levels and phosphocreatine to inorganic phosphate ratio remained stable throughout the experiments and did not differ between conditions (P > 0.1 for both).



Our data demonstrate that memantine preserves the cerebral energy status during experimentally induced hypoglycemia in healthy subjects. An improved neuronal energy status may thus be involved in the neuroprotective effect under these conditions and may qualify memantine as potential future option to combat cognitive impairments and dementia in diabetes.
Diagnostic accuracy of currently available anti-double-stranded DNA antibody assays. An Italian multicentre study.

An Italian multicentre study was promoted in order to assess the accuracy of four anti-double-stranded DNA (dsDNA) antibody assays for SLE diagnosis and monitoring.



Two hundred and twenty-three patients with established SLE according to ACR classification criteria were enrolled from 9 centres. They included 59 patients at first evaluation (disease duration <12 months) and 164 with longer disease duration (median disease duration 120 months). The sera from 55 healthy subjects and 161 patients with rheumatic, infectious or neoplastic diseases were tested as controls. SLE activity was measured by ECLAM score. Anti-dsDNA antibodies were detected in serum by means of FarrzymeTM assay, fluoroenzymeimmunoassay (EliATM), Crithidia luciliae indirect immunofluorescence (CLIFT) or Farr radioimmunoassay (Farr). Cut-off values of quantitative assays were chosen by ROC curves analysis. Statistics were conducted by SPSS software package.



Sensitivity for SLE diagnosis ranged between 66% with Farrzyme to 95% with Farr, with about 90% specificity for all the methods tested. Farrzyme assay was more specific than the others towards patients with non-SLE connective tissue disease. The four methods were moderately concordant and correlated among them, all showing a positive association with active disease, renal or haematologic involvement, and a negative association with central nervous system disease. Whatever the assay used, anti-dsDNA antibody levels correlated with disease activity with r correlation coefficients ranging from 0.336 to 0.425 (p<0.0001).



The diagnostic accuracy for SLE of evaluated anti-dsDNA antibody assays is comparable and potentially improvabile especially in terms of specificity. The clinical adherence of the assays confirms the value of anti-dsDNA antibody for SLE monitoring.
Instrumented lumbar arthrodesis in elderly patients: prospective study using cannulated cemented pedicle screw instrumentation

Lumbar fusion in elderly patients is increasingly common. This study prospectively investigated the clinical and radiological outcome of osteoporotic patients >70 years with degenerative lumbar instability treated with fusion using a new cannulated, cemented, pedicle screw instrumentation augmented with PMMA. The surgical protocols, patient records, densitometry, imaging studies, and pre- and postoperative patient-reported outcome questionnaires of 23 patients (mean age, 77 years) with a follow-up of 20–49 months were reviewed. All patients underwent postoperative 3D CT scan control to assess cement leakage and instrumentation position. Serial radiological controls were analyzed for secondary complications, i.e., adjacent fractures, hardware mobilization and radiological evidence of fusion. Pain and function improved at 6 months and were maintained at the final follow-up. No clinical complications secondary to PMMA leakage developed. No clinical or radiological cases of non-union were observed with a mean of 1.8 levels fused. No fractures occurred in adjacent segments. There were four cases of adjacent disc disease. Three deep infections required surgical revision without removal of material and one superficial infection, all with complete remission. This new instrumentation for degenerative lumbar disease in elderly patients is safe and effective.
Effects of enalapril in systolic heart failure patients with and without chronic kidney disease: insights from the SOLVD Treatment trial.

Angiotensin-converting enzyme inhibitors improve outcomes in systolic heart failure (SHF). However, doubts linger about their effect in SHF patients with chronic kidney disease (CKD).



In the Studies of Left Ventricular Dysfunction (SOLVD) Treatment trial, 2569 ambulatory chronic HF patients with left ventricular ejection fraction ≤ 35% and serum creatinine level ≤ 2.5mg/dl were randomized to receive either placebo (n=1284) or enalapril (n=1285). Of the 2502 patients with baseline serum creatinine data, 1036 had CKD (estimated glomerular filtration rate <60 ml/min/1.73 m(2)).



Overall, during 35 months of median follow-up, all-cause mortality occurred in 40% (502/1252) and 35% (440/1250) of placebo and enalapril patients, respectively (hazard ratio {HR}, 0.84; 95% confidence interval {CI}, 0.74-0.95; p=0.007). All-cause mortality occurred in 45% and 42% of patients with CKD (HR, 0.88; 95% CI, 0.73-1.06; p=0.164), and 36% and 31% of non-CKD patients (HR, 0.82; 95% CI, 0.69-0.98; p=0.028) in the placebo and enalapril groups, respectively (p for interaction=0.615). Enalapril reduced cardiovascular hospitalization in those with CKD (HR, 0.77; 95% CI, 0.66-0.90; p<0.001) and without CKD (HR, 0.80; 95% CI, 0.70-0.91; p<0.001). Among patients in the enalapril group, serum creatinine elevation was significantly higher in those without CKD (0.09 versus 0.04 mg/dl in CKD; p=0.003) during first year of follow-up, but there was no differences in changes in systolic blood pressure (mean drop, 7 mm Hg, both) and serum potassium (mean increase, 0. /L, both).



Enalapril reduces mortality and hospitalization in SHF patients without significant heterogeneity between those with and without CKD.
Relationships between Hepatic Iron Content and Virologic Response in Chronic Hepatitis C Patients Treated with Interferon and Ribavirin

The aims of this study were to determine the effect of pretreatment hepatic iron concentration (HIC) on response to combination therapy with interferon and ribavirin, and to examine the change in HIC associated with this treatment.Patients with hepatitis C who underwent liver biopsy before and after combination therapy were studied retrospectively. HIC was measured from paired pre- and posttreatment liver biopsy specimens, and histologic grade and stage were recorded.Sixty of 112 (54%) patients achieved sustained virologic response (SVR); response varied by genotype (genotype 1 (44%), genotype 2 or 3 (85%)). There was no difference in pretreatment median HIC between responders and nonresponders (404 μg/g and 394 μg/g, respectively; p = 0.31); patients with HIC ≥ 500 μg/g were not less likely to achieve SVR (OR = 1.1; 95% CI 0.5–2.3). In a multivariate analysis, factors associated with SVR included genotype 2 or 3 (OR = 12.2; 95% CI 3.1–47.8) and viral load <2 million copies/ml (OR = 3.6; 95% CI 1.3–10.0). HIC ≥ 500 μg/g did not decrease the likelihood of SVR (OR = 0.8; 95% CI 0.3–2.1). There was no significant change in HIC after combination therapy (median increase in HIC = 29.5 μg/g), and the change in HIC did not differ between responders and nonresponders (p = 0.73).CONCLUSIONS:Pretreatment HIC is not an independent predictor of response to therapy with interferon and ribavirin. Combination therapy does not significantly change HIC regardless of baseline histology or virologic response.
Validation of a rule for termination of resuscitation in out-of-hospital cardiac arrest.

We prospectively evaluated a clinical prediction rule to be used by emergency medical technicians (EMTs) trained in the use of an automated external defibrillator for the termination of basic life support resuscitative efforts during out-of-hospital cardiac arrest. The rule recommends termination when there is no return of spontaneous circulation, no shocks are administered, and the arrest is not witnessed by emergency medical-services personnel. Otherwise, the rule recommends transportation to the hospital, in accordance with routine practice.



The study included 24 emergency medical systems in Ontario, Canada. All patients 18 years of age or older who had an arrest of presumed cardiac cause and who were treated by EMTs trained in the use of an automated external defibrillator were included. The patients were treated according to standard guidelines. Characteristics of diagnostic tests for the prediction rule were calculated. These characteristics include sensitivity, specificity, and positive and negative predictive values.



Follow-up data were obtained for all 1240 patients. Of 776 patients with cardiac arrest for whom the rule recommended termination, 4 survived (0.5 percent). The rule had a specificity of 90.2 percent for recommending transport of survivors to the emergency department and had a positive predictive value for death of 99.5 percent when termination was recommended. Implementation of this rule would result in a decrease in the rate of transportation from 100 percent of patients to 37.4 percent. The addition of other criteria (a response interval greater than eight minutes or a cardiac arrest not witnessed by a bystander) would further improve both the specificity and positive predictive value of the rule but would result in the transportation of a larger proportion of patients.



The use of a clinical prediction rule for the termination of resuscitation may help clinicians decide whether to terminate basic life support resuscitative efforts in patients having an out-of-hospital cardiac arrest.
Nicotinic antagonist augmentation of selective serotonin reuptake inhibitor-refractory major depressive disorder: a preliminary study.

There is evidence for nicotinic hypercholinergic mechanisms in depression. Clinical relationships between tobacco use and depression suggest important effects of nicotine in major depressive disorder (MDD). It has been hypothesized that cigarette smoking may exert antidepressant effects, presumably mediated through stimulation of nicotinic acetylcholine receptor systems. We compared the nicotinic antagonist, mecamylamine hydrochloride (MEC), with placebo as an augmentation strategy for patients with MDD who were refractory to selective serotonin reuptake inhibitor (SSRI) treatment.



Twenty-one SSRI-treated subjects with MDD were randomized to MEC (up to 10 mg/d; n = 11) or placebo (PLO group; n = 10) during an 8-week trial. The primary outcome measure was the change in depressive symptoms assessed using the 17-item Hamilton Depression Rating Scale during the 8-week trial.



There was a significant reduction in 17-item Hamilton Depression Rating Scale scores in the MEC versus PLO groups, as evidenced by a significant medication x time interaction (F1,19 = 6.47, P < 0.05). Five (45.5%) of 11 subjects in the active study medication group demonstrated a 50% or more decrease in depressive symptoms from baseline as compared with 1 (10%) of 10 subjects assigned to placebo medication, but this difference was not significant (P = 0.15; Fisher exact test). The primary side effects of MEC were constipation and orthostatic hypotension.



These preliminary findings suggest that the nicotinic acetylcholine receptor antagonist, MEC, may have utility as an augmentation strategy for patients with SSRI-refractory MDD.
Established dietary estimates of net acid production do not predict measured net acid excretion in patients with Type 2 diabetes on Paleolithic–Hunter–Gatherer-type diets

Formulas developed to estimate diet-dependent net acid excretion (NAE) generally agree with measured values for typical Western diets. Whether they can also appropriately predict NAE for ‘Paleolithic-type’ (Paleo) diets—which contain very high amounts of fruits and vegetables (F&V) and concurrent high amounts of protein is unknown. Here, we compare measured NAEs with established NAE estimates in subjects with Type 2 diabetes (T2D).Subjects/methods:Thirteen subjects with well-controlled T2D were randomized to either a Paleo or American Diabetes Association (ADA) diet for 14 days. Twenty-four hour urine collections were performed at baseline and end of the diet period, and analyzed for titratable acid, bicarbonate and ammonium to calculate measured NAE. Three formulas for estimating NAE from dietary intake were used; two (NAE_diet R or L) that include dietary mineral intake and sulfate- and organic acid (OA) production, and one that is empirically derived (NAE_diet F) only considering potassium and protein intake.Measured NAE on the Paleo diet was significantly lower than on the ADA-diet (+31±22 vs 112±52 mEq/day, P=0.002). Although all formula estimates showed similar and reasonable correlations (r=0.52–0.76) with measured NAE, each one underestimated measured values. The formula with the best correlation did not contain an estimate of dietary OA production.Paleo-diets are lower in NAE than typical Western diets. However, commonly used formulas clearly underestimate NAE, especially for diets with very high F&V (as the Paleo diet), and in subjects with T2D. This may be due to an inappropriate estimation of proton loads stemming from OAs, underlining the necessity for improved measures of OA-related proton sources.
Image Segmentation in Video Sequences: A Probabilistic Approach

"Background subtraction" is an old technique for finding moving objects in a video sequence-for example, cars driving on a freeway. The idea is that subtracting the current image from a time­ averaged background image will leave only non­ stationary objects. It is, however, a crude ap­ proximation to the task of classifying each pixel of the current image; it fails with slow-moving objects and does not distinguish shadows from moving objects. The basic idea of this paper is that we can classify each pixel using a model of how that pixel looks when it is part of different classes. We learn a mixture-of-Gaussians classi­ fication model for each pixel using an unsuper­ vised technique-an efficient, incremental ver­ sion of EM. Unlike the standard image-averaging approach, this automatically updates the mixture component for each class according to likelihood of membership; hence slow-moving objects are handled perfectly. Our approach also identifies and eliminates shadows much more effectively than other techniques such as thresholding. Ap­ plication of this method as part of the Roadwatch traffic surveillance project is expected to result in significant improvements in vehicle identification and tracking.
Pilot study of adjuvant chemotherapy with 3-week combination of S-1 and cisplatin for patients with stage II-IV (M0) gastric cancer

The feasibility of a 3-week combination of S-1 and cisplatin as an adjuvant chemotherapy for patients with curatively resected gastric cancer was investigated. Experimental design Korean patients with stage II-IV (M0) gastric adenocarcinoma who underwent a gastrectomy with D2 lymph node resection were enrolled. The S-1 was administered orally at 80 mg/m2 divided into two daily doses for 14 days, while the cisplatin was administered at 60 mg/m2 intravenously over 2 h every 21 days. The patients received a maximum of six cycles.  From January 2006 to July 2010, 74 patients were included in this study. The median patient age was 56 years (range, 22–71), and 51.4% (38/74) of the patients had a performance status of 0. The median number of chemotherapy cycles administered was 6 (range, 1–6). The median relative dose intensity was 86.4% for S-1 and 80.0% for cisplatin. With a median follow-up duration of 13.9 months, the median relapse-free survival (RFS) and overall survival (OS) have not yet been reached. Fifteen relapses (20.3%) were documented. Plus, the estimated RFS rate was 60.5% at 3 years. The treatments were generally well tolerated. The most frequently observed grade 3–4 hematological toxicity was neutropenia (35.1%), and only 1 cycle of neutropenic fever occurred. The most frequently observed grade 3–4 non-hematological toxicities were nausea (4.1%) and asthenia (4.1%), and all the other grade 3–4 non-hematological toxicities were observed in less than 3% of the patients.  Postoperative adjuvant S-1 plus cisplatin for 18 weeks was found to be feasible for patients with stage II-IV (M0) gastric adenocarcinoma following complete surgical resection.