nils-herrmann/clean_scirepeval huggingface dataset:
Lanreotide 60 mg, a Longer-Acting Somatostatin Analog: Tumor Shrinkage and Hormonal Normalization in Acromegaly

Somatostatin analogues are nowadays the milestone in the medical treatment of acromegaly. We evaluated the effects of a new 60 mg longer-acting formulation of lanreotide (LAN60) on GH/IGF-I levels and tumor size.  Twenty-one acromegalics entered a prospective monocentric open study. Eight were consecutive “de novo” patients (group I). Thirteen patients sensitive to SA (GH levels < 2.5 μg/l and/or IGF-I normalization on chronic LAN 30 mg (LAN30) treatment) were switched to LAN60 (group II). Protocol: LAN60 was administered IM for 6 cycles at 28 day intervals. In group I when GH/IGF-I remained pathological, the intervals were shortened to 21 days for the last three cycles. Controls: GH/IGF-I at the end of the 1st, 3rd and 6th cycle; MRI at the end of the study in all patients in group I bearing an adenoma.  Group I. GH (p = 0.00638, below 2.5 μg/l in two patients) and IGF-I (p = 0.0289, normalized in 5) significantly decreased. In one of two patients shortening the LAN60 schedule was more effective in suppressing GH/IGF-I. Group II. No change in GH and IGF-I levels was observed with the administration of LAN60, instead of LAN30. On LAN60 GH remained below 2.5 μg/l in 8/10 patients and IGF-I normal in 11/11 patients that had attained those values on LAN30. Tumor markedly shrank (23% to 64% vs basal), from 1400 (664–1680) mm3 to 520 (500–960) mm3 (median, interquartile, p = 0.0218) in all the 5 evaluable patients.  LAN60 is a very effective and longer-lasting formulation for the treatment of acromegaly. A closer administration schedule might achieve greater efficacy. Its effectiveness in shrinking tumor opens new perspectives in the therapy of acromegaly.
Difficult aneurysms for endovascular treatment: overwide or undertall?

Aneurysm geometry has been shown to predict the need for adjunctive techniques in the endovascular treatment of intracranial aneurysms. We conducted a systematic retrospective study examining which thresholds of dome-to-neck ratio, maximum neck width, and aspect ratio of intracranial aneurysms best predict the need for adjunctive techniques in endovascular management.



One hundred seventy-five consecutive patients who were selected for attempted embolization of 185 intracranial aneurysms were included in this study. Aneurysm dome-to-neck ratio (maximum dome width/maximum neck width), maximum neck width, and aspect ratio (dome height/maximum neck width) were measured on 2D digital subtraction angiography. Statistical analysis was conducted to determine which thresholds of dome-to-neck ratio, maximum neck width, and aspect ratio were most predictive of the need for adjunctive devices in endovascular management of these aneurysms.



We demonstrated that 75% of aneurysms with dome-to-neck ratios >1.6 (P < .0001), 75% of aneurysms with aspect ratios >1.6 (P < .0001), and 70% of aneurysms with neck diameters <4.0 mm (P < .0001) did not need adjunctive techniques in their management. Adjunctive techniques were essential to treatment of 80% of aneurysms with dome-to-neck ratios <1.2 (P = .02) and 89% of aneurysms with aspect ratios <1.2 (P < .0001). Multivariate logistic regression analysis demonstrated that aspect ratio was the best predictor of the need for an adjunctive device (P = .0004).



Aneurysms with aspect and dome-to-neck ratios >1.6 usually did not require adjunctive techniques. Aneurysms with aspect and dome-to-neck ratios <1.2 almost always required adjunctive techniques. In this single-center series, aspect ratio was the independent predictor of the need for adjunctive techniques in the endovascular management of intracranial aneurysms.
Nebivolol treatment reduces serum levels of asymmetric dimethylarginine and improves endothelial dysfunction in essential hypertensive patients.

This study was conducted to evaluate (i) the effect of nebivolol, a selective beta1-adrenergic receptor antagonist, on plasma concentration of asymmetric dimethylarginine (ADMA) and on flow-mediated dilation (FMD) in essential hypertensive patients; (ii) the effect of serum derived from the treated hypertensive patients on ADMA and on dimethylarginine dimethylaminohydrolase 2 (DDAH2), the enzyme that selectively degrades ADMA, in human umbilical vein endothelial cells (HUVECs).



Forty healthy subjects and 40 matched essential hypertensive patients treated with atenolol and nebivolol according to a double-blind, randomized design participated in the study. Evaluation of brachial artery (BA) reactivity was performed by a longitudinal B-mode scan of the right BA. ADMA and L-arginine were measured by high-performance liquid chromatography. DDAH2 expression and endothelial nitric oxide synthase activity (eNOS) were also evaluated in HUVECs.



ADMA levels were significantly decreased and FMD increased only in patients receiving nebivolol (P < 0.01). Furthermore, in nebivolol group, we found a significant correlation between changes in ADMA levels and changes in FMD (P < 0.01). Sera derived from patients treated with nebivolol but not with atenolol decreased ADMA and increased DDAH2 expression and eNOS activity (P < 0.001) in HUVECs.



The results of this study demonstrate that the improvement of endothelial dysfunction induced by nebivolol in hypertensive patients may be related to its effect on circulating ADMA levels. Although the mechanism by which nebivolol reduces circulating ADMA in hypertensive patients remains unclear, our ex vivo results suggest that the upregulation of DDAH2 expression may have a role.
Pharmacokinetic and Pharmacodynamic Analyses of Ceftaroline in Adults with Cystic Fibrosis.

To evaluate the pharmacokinetics and pharmacodynamics of ceftaroline in adults with cystic fibrosis (CF).



Open-label, single-center, prospective study.



University-affiliated teaching institution.



Eight patients with a diagnosis of CF and a history of methicillin-resistant Staphylococcus aureus who were treated with ceftaroline between November 2013 and September 2014.



All patients received at least three doses of intravenous ceftaroline 600 mg every 12 hours, administered as a 60-minute infusion, to achieve steady-state concentrations before blood sample collection. After an interim analysis of the first four patients' pharmacokinetic data, the remaining four patients received a change in dosage of ceftaroline to 600 mg every 8 hours.



Patients' blood samples were collected at two time points, 2 and 6 hours after infusion initiation, after administration of at least three doses of ceftaroline. Serum ceftaroline concentrations were determined by using a validated mass spectrometry, with a lower limit of detection of 20 ng/ml. These ceftaroline concentrations were used to estimate patient-specific pharmacokinetic parameters, and 10,000-patient Monte Carlo simulations were performed to determine the pharmacodynamic probability of target attainment (PTA) for ceftaroline in adults with CF. A PTA of 90% or higher for the desired pharmacodynamic target was considered adequate. The PTA for 60% or higher of the dosing interval during which free (unbound) drug concentrations exceed the minimum inhibitory concentration (%fT > MIC) was simulated for various MICs. Compared with values previously reported in other populations, the volume of distribution was increased in the study patients, and the estimated half-life was shorter. Monte Carlo simulations revealed that a dose of ceftaroline 600 mg every 8 hours, infused over 60 minutes, maintained a higher than 90% PTA for %fT > MIC of 60% or higher for an MIC at the susceptibility breakpoint of 1 mg/L.



The pharmacokinetics of ceftaroline is altered in adults with CF, which suggests the need for modified dosing in this patient population to achieve adequate %fT > MIC. A dosage of intravenous ceftaroline 600 mg every 8 hours administered as a 60-minute infusion should be considered to achieve 60% fT > MIC.
Treating heart failure with enhanced external counterpulsation (EECP): design of the Prospective Evaluation of EECP in Heart Failure (PEECH) trial.

Enhanced external counterpulsation (EECP) treatment can improve exercise tolerance in patients with ischemic heart disease; however, the possible benefits of EECP in patients with stable heart failure (HF) and left ventricular dysfunction (LVD) are unclear. An open pilot study showed significant increases in exercise tolerance in HF patients undergoing EECP. Thus a larger, controlled study of EECP in patients with stable HF (New York Heart Association [NYHA] classes II and III) and LVD was undertaken.



The PEECH trial is a controlled, randomized, single-blind, parallel-group, multicenter study of 187 patients with symptomatic but stable HF (NYHA classes II and III) and an LV ejection fraction < or =35% was designed to assess the efficiency of EECP in patients with stable HF. Medical therapy is optimized in all patients based on the recommendations of the Heart Failure Society of America ("Usual Care"), and then randomized between 2 treatment groups; UC or EECP (35 hours over 7 weeks).



Efficacy measures include standard exercise tolerance tests on a treadmill (modified Naughton protocol), with measurements of peak oxygen uptake and exercise duration time; quality of life questionnaires; NYHA classification; and neurohormonal markers of HF.
Environmental advantage: marketing the messages.

Verhoeven@lond.azr.nl BAC K GROU ND : In smoking COPD patients the bronchoalveolar lavage (BAL) fluid contains high numbers of inflammatory cells. These cells might produce arachidonic acid (AA) metabolites, which contribute to inflammation and an increased bronchomotor tone.  To investigate levels of AA metabolites in BAL fluid, before and after inhaled glucocorticoid therapy: fluticasone propionate (FP) 1 mg per day, or placebo.  A double-blind placebo controlled trial lasting six months. COPD patients were selected by clinical criteria and the presence of bronchial hyperresponsiveness (BHR). Lung function was recorded and in BAL fluid we counted cell numbers and measured LTB4 , LTC4/D4/E4 , PGE2 , 6kPGF1 a , PGF2 a and TxB2 . A control group consisted of asymptomatic smokers (n=6).  Paired data were obtained from 9 FP treated and 11 placebo patients. BAL cells were almost exclusively alveolar macrophages. In patients and controls both cellularity and levels of AA metabolites were equal. Cell numbers did not change after treatment. Statistically significant decreases after FP therapy were noticed for PGE2 (30%), 6kPGF1 a (41%) and PGF2 a (54%).  In COPD, the capability of inflammatory cells to produce certain AA metabolites was decreased after inhaled FP treatment. This result is discussed in its relation to clinical effects, the influence of smoking, and the results of an earlier, similar study in asthma patients.
Suitability of forced expiratory volume in 1 second/forced vital capacity vs percentage of predicted forced expiratory volume in 1 second for the classification of asthma severity in adolescents.

To determine whether lung function alters asthma severity based on symptom history in asthmatic adolescents.



Data on asthma symptoms and lung function were collected from adolescents randomly selected from the general population.



Five schools from the central Wellington, New Zealand, area during 2003 to 2005.



Two hundred twenty-four secondary school students aged 13 to 17 years (asthmatic, 118; nonasthmatic, 106).



Asthma questionnaire and lung function testing.



Distribution of asthmatic adolescents in each severity class based on symptoms, lung function, or a combination of both.



Median values for all spirometric parameters for asthmatic adolescents, apart from forced expiratory volume in the first second of expiration (FEV(1))/forced vital capacity (FVC), were in the normal range. Distribution of severity (based on symptoms and beta(2)-agonist use with adjustment for regular inhaled corticosteroid use) was 48.3%, mild; 28.8%, moderate; and 22.9%, severe asthma. For severity based on percentages of predicted FEV(1) and predicted forced expiratory flow, midexpiratory phase (FEF(25%-75%)) and FEV(1)/FVC, the percentages were 89.8%, 86.4%, and 63.5%, mild; 9.3%, 10.2%, and 18.6%, moderate; and 0.9%, 3.4%, and 17.8%, severe asthma, respectively. When percentages of predicted FEV(1) or predicted FEF(25%-75%) or FEV(1)/FVC were added to symptom severity, 6.8%, 5.1%, and 16.9% of asthmatic adolescents were reclassified into another severity group, respectively.



The majority of asthmatic adolescents have normal lung function despite experiencing significant asthma symptoms. Adding FEV(1)/FVC to symptom history changes the distribution of severity; however, both percentages of predicted FEV(1) and FEF(25%-75%) have little added effect in assessing asthma severity in adolescents.
Sofosbuvir and Velpatasvir for HCV Genotype 1, 2, 4, 5, and 6 Infection.

A simple treatment regimen that is effective in a broad range of patients who are chronically infected with the hepatitis C virus (HCV) remains an unmet medical need.



We conducted a phase 3, double-blind, placebo-controlled study involving untreated and previously treated patients with chronic HCV genotype 1, 2, 4, 5, or 6 infection, including those with compensated cirrhosis. Patients with HCV genotype 1, 2, 4, or 6 were randomly assigned in a 5:1 ratio to receive the nucleotide polymerase inhibitor sofosbuvir and the NS5A inhibitor velpatasvir in a once-daily, fixed-dose combination tablet or matching placebo for 12 weeks. Because of the low prevalence of genotype 5 in the study regions, patients with genotype 5 did not undergo randomization but were assigned to the sofosbuvir-velpatasvir group. The primary end point was a sustained virologic response at 12 weeks after the end of therapy.



Of the 624 patients who received treatment with sofosbuvir-velpatasvir, 34% had HCV genotype 1a, 19% genotype 1b, 17% genotype 2, 19% genotype 4, 6% genotype 5, and 7% genotype 6. A total of 8% of patients were black, 19% had cirrhosis, and 32% had been previously treated for HCV. The rate of sustained virologic response among patients receiving sofosbuvir-velpatasvir was 99% (95% confidence interval, 98 to >99). Two patients receiving sofosbuvir-velpatasvir, both with HCV genotype 1, had a virologic relapse. None of the 116 patients receiving placebo had a sustained virologic response. Serious adverse events were reported in 15 patients (2%) in the sofosbuvir-velpatasvir group and none in the placebo group.



Once-daily sofosbuvir-velpatasvir for 12 weeks provided high rates of sustained virologic response among both previously treated and untreated patients infected with HCV genotype 1, 2, 4, 5, or 6, including those with compensated cirrhosis.
Value of serum cartilage oligomeric matrix protein as a prognostic marker of large-joint damage in rheumatoid arthritis--data from the RAPIT study.

To investigate the utility of serum COMP level measurements as a predictor of future damage of the weight-bearing (large) joints in RA patients participating in intensive exercise.



Data of the 281 completers of a 2-yr randomized controlled trial (Rheumatoid Arthritis Patients In Training; RAPIT) comparing the effects of usual care physical therapy with high-intensity weight-bearing exercises were analysed. The primary outcome variable was defined as the change in radiological joint damage (Larsen score) of the large joints. Potential predictors of outcome were defined: baseline and change in serum level of COMP after 3 months, baseline radiological damage of the large and small joints, number of months on glucocorticoids, change in disease activity and in physical capacity (aerobic fitness and muscle strength) after 2 yrs, and participation in the exercise group.



In cross-sectional evaluation of baseline data, we found strong association between the high serum COMP level and current damage of the large joints. Serum COMP level at baseline, however, was not associated with an increased rate of radiological joint damage after 2 yrs of follow-up. Furthermore, neither interaction between baseline COMP level and participation in exercises, nor change in COMP level after 3 months of exercising were associated with future damage of the large joints.



Neither baseline serum COMP level nor its individual change after 3 months from start of intensive exercise predict longitudinal progression of damage of the large joints in this population.
Evaluation of short-term outcomes of laparoscopic-assisted surgery for colorectal cancer in elderly patients aged over 75 years old: a multi-institutional study (YSURG1401)

The short-term outcomes of laparoscopic-assisted surgery for colorectal cancer (LAC) have not been fully evaluated in elderly patients. The aim of this study was to compare the short term surgical outcomes of LAC between the patients older than 75 years and those with non-elderly patients.



This retrospective multi-institutional study selected patients who underwent LAC between April 2013 and March 2014 at Yokohama City University Hospital and its related general hospitals. The patients were categorized into two groups: elderly patients (>75 years of age: group A) and non-elderly patients (<75 years of age: group B). Surgical outcomes and post operative complications were compared between the two groups.



A total of 237 patients were evaluated in the present study. Eighty-four patients were classified into group A, and 153 into group B. Preoperative clinicopathological outcomes demonstrated no significant differences except for the ASA score. When comparing the surgical outcomes between group A and group B, the rate of conversion to open procedure (3.6% vs 5.2%, P = 0.750), median operation time (232 min vs 232 min, P = 0.320), median blood loss (20 ml vs 12 ml, P = 0.350). The differences were not significantly different in the surgical outcomes. The incidences of > grade 2 post operative surgical complications were similar between two groups ((19.0% vs 15.7%, p = 0.587). No mortality was observed in this study. The length of postoperative hospital stay was also similar (10 days vs 10 days, p = 0.350).



The present study suggested that LAC is safe and feasible, regardless of the age of the patient, especially for elderly patients who may be candidates for colon cancer surgery.
Measurement of serum total and free prostate-specific antigen in women with colorectal carcinoma

We investigated the diagnostic value and the relationship with clinicopathological features of total and free prostate-specific antigen by measuring the concentrations of these markers in the sera of 75 women with colorectal carcinoma and in 30 healthy women. Measurements were performed by immunoradiometric assay which utilizes monoclonal and polyclonal anti-prostate-specific antigen antibodies; the lowest detection level for both markers was 0.01 ng ml−1. Free prostate-specific antigen levels were significantly higher in women with colorectal carcinoma than healthy women (P=0.006). The percentage of free prostate-specific antigen predominant (free prostate-specific antigen/total prostate-specific antigen >50%) subjects was 20% in colorectal carcinoma patients and 3.3% in healthy women (P=0.035). Cut-off values were 0.34 ng ml−1 for total prostate-specific antigen and 0.01 ng ml−1 for free prostate-specific antigen. In women with colorectal carcinoma, total prostate-specific antigen positivity was 20% and free prostate-specific antigen positivity was 34.6%. When compared to negatives, total prostate-specific antigen positive patients had a lower percentage of well-differentiated (P=0.056) and early stage (stages I and II) tumours (P=0.070). However, patients with predominant free prostate-specific antigen, had a higher percentage of well-differentiated (P=0.014) and early stage tumours (P=0.090) than patients with predominant bound prostate-specific antigen. In conclusion, although the sensitivity of free prostate-specific antigen predominancy is low (20%), in distinguishing women with colorectal carcinoma than healthy women, its specificity is high (96.7%). Free prostate-specific antigen predominancy tends to be present in less aggressive tumours. These findings may indicate clinical significance of preoperative measurement of serum total and free prostate-specific antigen in women with colorectal carcinoma.
Issues of “life” and “death” for patients receiving palliative care—comments when confronted with a research tool

To be able to study the desire for hastened death (DhD) in patients receiving palliative care, research tools reflecting the thoughts of patients are needed. In order to better understand what issues of “life” and “death” mean to patients receiving palliative care in Germany, we analysed their spontaneous comments during a validation study of the German version of the Schedule of Attitudes Towards Hastened Death. Field notes and transcripts of 39 interviews were analysed by thematic analysis. Field notes from 32 patients were related to differentiating either an acute or a non-acute DhD. Furthermore, the patients’ comments were categorized and the distribution of codes analysed, leading to three types of comments: (a) longing for life excluding a hastened death, (b) wanting to live on, but perceiving death as an option, and (c) longing for death, but struggling for life. The existing construct of an increased DhD may benefit from a further differentiation between “non-acute” and “acute.” In addition, it could be helpful to conceptualize “will to live” and “desire for death” not as polarities from one dimension (two sides of the same coin), but to think them as two independent dimensions.
The efficacy of gabapentin in migraine prophylaxis: an observational open label study.

Migraine is often a chronic and disabling disorder. The objective of our study was to assess the efficacy and safety of gabapentin in the prophylaxis of migraine in patients refractory to other prophylactic treatments. The study included 67 migraine patients, 55 women and 12 men; 52 patients completed this prospective, open-label study. Patients were given 900-1800 mg of gabapentin in 3 doses; the mean duration of treatment was 7.2 months. Reduction in the number of days with headache, pain intensity and number of acute medications was assessed through patient diary. The mean number of migraine days/4 weeks was reduced from 15.8 to 8.6, yielding a reduction of 7.2 migraine days/4 weeks (P=0.001). Pain intensity was reduced by 25% in 14 (26.9%), by 50% in 29 (55.7%) and by 75% in three (5.7%) patients, whereas no improvement was reported by six (11.5%) patients at the end of follow up. A significant reduction was recorded in acute medication use (P=0.001). Adverse events were reported by 32/67 (47.8%) patients, in 15 (22.4%) of them causing discontinuation of the drug. The most frequently reported adverse events were drowsiness, dizziness and slowness. Prophylactic treatment with gabapentin was found to be associated with a significant reduction in the number of days with headache, use of acute medications and pain intensity.