nils-herrmann/clean_scirepeval huggingface dataset:
Estimates of Serotonin and Norepinephrine Transporter Inhibition in Depressed Patients Treated with Paroxetine or Venlafaxine

Paroxetine and venlafaxine are potent serotonin transporter (SERT) antagonists and weaker norepinephrine transporter (NET) antagonists. However, the relative magnitude of effect at each of these sites during treatment is unknown. Using a novel blood assay that estimates CNS transporter occupancy we estimated the relative SERT and NET occupancy of paroxetine and venlafaxine in human subjects to assess the relative magnitude of SERT and NET inhibition. Outpatient subjects (N=86) meeting criteria for major depression were enrolled in a multicenter, 8 week, randomized, double-blind, parallel group, antidepressant treatment study. Subjects were treated by forced-titration of paroxetine CR (12.5–75 mg/day) or venlafaxine XR (75–375 mg/day) over 8 weeks. Blood samples were collected weekly to estimate transporter inhibition. Both medications produced dose-dependent inhibition of the SERT and NET. Maximal SERT inhibition at week 8 for paroxetine and venlafaxine was 90% (SD 7) and 85% (SD 10), respectively. Maximal NET inhibition for paroxetine and venlafaxine at week 8 was 36% (SD 19) and 60% (SD 13), respectively. The adjusted mean change from baseline (mean 28.6) at week 8 LOCF in MADRS total score was −16.7 (SE 8.59) and −17.3 (SE 8.99) for the paroxetine and venlafaxine-treated patients, respectively. The magnitudes of the antidepressant effects were not significantly different from each other (95%CI −3.42, 4.54, p=0.784). The results clearly demonstrate that paroxetine and venlafaxine are potent SERT antagonists and less potent NET antagonists in vivo. NET antagonism has been posited to contribute to the antidepressant effects of these compounds. The clinical significance of the magnitude of NET antagonism by both medications remains unclear at present.
Multinomial logistic estimation of Markov-chain models for modeling sleep architecture in primary insomnia patients

Hypnotic drug development calls for a better understanding of sleep physiology in order to improve and differentiate novel medicines for the treatment of sleep disorders. On this basis, a proper evaluation of polysomnographic data collected in clinical trials conducted to explore clinical efficacy of novel hypnotic compounds should include the assessment of sleep architecture and its drug-induced changes. This work presents a non-linear mixed-effect Markov-chain model based on multinomial logistic functions which characterize the time course of transition probabilities between sleep stages in insomniac patients treated with placebo. Polysomnography measurements were obtained from patients during one night treatment. A population approach was used to describe the time course of sleep stages (awake stage, stage 1, stage 2, slow-wave sleep and REM sleep) using a Markov-chain model. The relationship between time and individual transition probabilities between sleep stages was modelled through piecewise linear multinomial logistic functions. The identification of the model produced a good adherence of mean post-hoc estimates to the observed transition frequencies. Parameters were generally well estimated in terms of CV, shrinkage and distribution of empirical Bayes estimates around the typical values. The posterior predictive check analysis showed good consistency between model-predicted and observed sleep parameters. In conclusion, the Markov-chain model based on multinomial logistic functions provided an accurate description of the time course of sleep stages together with an assessment of the probabilities of transition between different stages.
Subjective, behavioral, and physiological effects of acute caffeine in light, nondependent caffeine users

Caffeine produces mild psychostimulant effects that are thought to underlie its widespread use. However, the direct effects of caffeine are difficult to evaluate in regular users of caffeine because of tolerance and withdrawal. Indeed, some researchers hypothesize that the psychostimulant effects of caffeine are due largely to the reversal of withdrawal and question whether there are direct effects of caffeine consumption upon mood, alertness, or mental performance in nondependent individuals. This study investigated the physiological, subjective, and behavioral effects of 0, 50, 150, and 450 mg caffeine in 102 light, nondependent caffeine users. Using a within-subjects design, subjects participated in four experimental sessions, in which they received each of the four drug conditions in random order under double blind conditions. Participants completed subjective effects questionnaires and vital signs were measured before and at repeated time points after drug administration. Forty minutes after the capsules were ingested, subjects completed behavioral tasks that included tests of sustained attention, short-term memory, psychomotor performance, and behavioral inhibition. Caffeine significantly increased blood pressure, and produced feelings of arousal, positive mood, and high. Caffeine increased the number of hits and decreased reaction times in a vigilance task, but impaired performance on a memory task. We confirm that acute doses of caffeine, at levels typically found in a cup of coffee, produce stimulant-like subjective effects and enhance performance in light, nondependent caffeine users. These findings support the idea that the drug has psychoactive effects even in the absence of withdrawal.
Phase II study of ifosfamide, etoposide, and oxaliplatin (IFETOx) chemotherapy for relapsed or refractory non-Hodgkin's lymphoma.

As part of an effort to develop a more effective and safe treatment for relapsed or refractory non-Hodgkin's lymphoma (NHL), we conducted a phase II study of the oxaliplatin, etoposide, and ifosfamide (IFETOx) regimen. Patients with relapsed or refractory NHL and a performance status of 0-2 were eligible. The IFETOx consisted of etoposide at 100 mg/m(2) on days 1-3, oxaliplatin at 130 mg/m(2) on day 2, and ifosfamide 5,000 mg/m(2) on day 2, every 21 days. The primary endpoint was the overall response rate (ORR) for IFETOx regimen. A total of 23 eligible patients were enrolled. The median age was 58 years (range 19-76 years), and the male-to-female ratio was 15:8. The disease status was as follows: 15 patients had relapsed and 8 patients were refractory to treatment. The ORR for IFETOx chemotherapy was 65.2 %. In the 15 patients who responded to the protocol treatment, five underwent hematopoietic stem cell transplantation. The 2-year probability of progression-free survival and overall survival rates were 51.4 and 56.1 %, respectively. Grade 3/4 neutropenia was observed in 73.9 % of the patients. No significant renal impairment was observed. In conclusion, IFETOx chemotherapy shows a tolerable toxicity profile and efficacy as a salvage treatment regimen for relapsed or refractory NHL.
A phase 2 autologous cellular therapy trial in patients with acute, complete spinal cord injury: pragmatics, recruitment, and demographics

Post hoc analysis from a randomized controlled cellular therapy trial in acute, complete spinal cord injury (Description and quantitative review of study logistics, referral patterns, current practice patterns and subject demographics.Subjects were recruited to one of six international study centers.Data are presented from 1816 patients pre-screened, 75 participants screened and 50 randomized.Of the 1816 patients pre-screened, 53.7% did not meet initial study criteria, primarily due to an injury outside the time window (14 days) or failure to meet neurological criteria (complete SCI between C5 motor/C4 sensory and T11). MRIs were obtained on 339 patients; 51.0% were ineligible based on imaging criteria. Of the 75 participants enrolled, 25 failed screening (SF), leaving 50 randomized. The primary reason for SF was based on the neurological exam (51.9%), followed by failure to meet MRI criteria (22.2%). Of the 50 randomized subjects, there were no significant differences in demographics in the active versus control arms. In those participants for whom data was available, 93.8% (45 of 48) of randomized participants received steroids before study entry, whereas 94.0% (47 of 50) had spine surgery before study enrollment.The ‘funnel effect’ (large numbers of potentially eligible participants with a small number enrolled) impacts all trials, but was particularly challenging in this trial due to eligibility criteria and logistics. Data collected may provide information on current practice patterns and the issues encountered and addressed may facilitate design of future trials.
High-precision prostate cancer irradiation by clinical application of an offline patient setup verification procedure, using portal imaging.

To investigate in three institutions, The Netherlands Cancer Institute (Antoni van Leeuwenhoek Huis [AvL]), Dr. Daniel den Hoed Cancer Center (DDHC), and Dr, Bernard Verbeeten Institute (BVI), how much the patient setup accuracy for irradiation of prostate cancer can be improved by an offline setup verification and correction procedure, using portal imaging.



The verification procedure consisted of two stages. During the first stage, setup deviations were measured during a number (Nmax) of consecutive initial treatment sessions. The length of the average three dimensional (3D) setup deviation vector was compared with an action level for corrections, which shrunk with the number of setup measurements. After a correction was applied, Nmax measurements had to be performed again. Each institution chose different values for the initial action level (6, 9, and 10 mm) and Nmax (2 and 4). The choice of these parameters was based on a simulation of the procedure, using as input preestimated values of random and systematic deviations in each institution. During the second stage of the procedure, with weekly setup measurements, the AvL used a different criterion ("outlier detection") for corrective actions than the DDHC and the BVI ("sliding average"). After each correction the first stage of the procedure was restarted. The procedure was tested for 151 patients (62 in AvL, 47 in DDHC, and 42 in BVI) treated for prostate carcinoma. Treatment techniques and portal image acquisition and analysis were different in each institution.



The actual distributions of random and systematic deviations without corrections were estimated by eliminating the effect of the corrections. The percentage of mean (systematic) 3D deviations larger than 5 mm was 26% for the AvL and the DDHC, and 36% for the BVI. The setup accuracy after application of the procedure was considerably improved (percentage of mean 3D deviations larger than 5 mm was 1.6% in the AvL and 0% in the DDHC and BVI), in agreement with the results of the simulation. The number of corrections (about 0.7 on the average per patient) was not larger than predicted.



The verification procedure appeared to be feasible in the three institutions and enabled a significant reduction of mean 3D setup deviations. The computer simulation of the procedure proved to be a useful tool, because it enabled an accurate prediction of the setup accuracy and the required number of corrections.
Effect of coronary dominance on 2-year outcomes after percutaneous coronary intervention in patients with acute coronary syndrome.

This retrospective, single-center, observational analysis from prospectively collected database evaluated whether left dominance affected the long-term outcomes of acute coronary syndrome patients undergoing percutaneous coronary intervention, and whether the effect was independent of SYNTAX score.



Left dominance is believed to be associated with worse prognoses. The anatomical SYNTAX score is a scoring system based on the complexity and severity of coronary lesions and is thought to be a prognostic tool to predict short- and long-term outcomes. There are few studies about whether the effect of left dominance is independent of SYNTAX score.



Between January 2013 and December 2013, 6255 consecutive acute coronary syndrome patients who were admitted to Fuwai hospital and underwent percutaneous coronary intervention (PCI) were enrolled in this study. Based on coronary dominance and the calculation methods of the SYNTAX score, patients were divided into a left-dominant group (LD group; 390 patients) and a right-dominant or co-dominant group (RD + Co group, 5865 patients).



The 2-year mortality rate was significantly higher in the LD group than in the RD + Co group (2.58% vs. 1.23%, P = 0.024). In multivariate Cox analysis, the independent predictors of mortality were coronary dominance, IABP support, age, baseline SYNTAX score, and ejection fraction.



LD was an independent predictor of long-term mortality in ACS patients undergoing PCI. The effect of LD still existed after adjustment for several important variables and was independent of SYNTAX score.
Lumbar multifidus muscle thickness does not predict patients with low back pain who improve with trunk stabilization exercises.

To understand lumbar multifidus (LM) muscle activation as a clinical feature to predict patients with low back pain (LBP) who are likely to benefit from stabilization (STB) exercises.



Prospective, cohort study.



Outpatient physical therapy clinics.



Persons with LBP were recruited for this study. Subjects (N=25) were classified as either eligible to receive STB exercises or ineligible on the basis of current clinical prediction rules.



Six weeks of STB treatment.



Before and after treatment, subjects underwent rehabilitative ultrasound imaging to quantify LM-muscle activation and completed disability and pain questionnaires. Analyses were performed to examine the (1) relation between LM-muscle activation and current clinical features used to predict patients with LBP likely to benefit from STB exercises, (2) LM-muscle activation between the STB-eligible and STB-ineligible groups before and after STB treatment, and (3) relation between LM-muscle activation before STB treatment and (a) disability and (b) pain outcomes after treatment for both groups.



No relation was found between LM-muscle activation and the number of clinical features. Before STB treatment, LM-muscle activation between the STB-eligible and STB-ineligible groups did not differ. After STB treatment, LM-muscle activation differed between the groups; however, this interaction was because the LM-muscle activation for the STB-eligible group decreased after treatment while that for the STB-ineligible group increased after treatment. Finally, only the STB-eligible group had a significant reduction in disability following treatment; however, no relation was found between LM-muscle activation before treatment and (a) disability or (b) pain outcomes after treatment in the STB-eligible group.



LM-muscle activation does not appear to be a clinical feature that predicts patients with LBP likely to benefit from STB exercises.
Levodopa and orphenadrine hydrochloride in parkinsonism

In Parkinsonian patients on maximum tolerated doses of levodopa, a double-blind, cross-over trial showed that greater benefit was conferred by additional orphenadrine hydrochloride than by placebo. Further observations suggest that the benefit conferred by supplemental orphenadrine is lost if the drug is withdrawn either suddenly or gradually. The greatest improvements were seen in balance, posture, handwriting, performance of domestic tasks, dressing and feeding.
Detection of generalized tonic-clonic seizures by a wireless wrist accelerometer: a prospective, multicenter study.

Our objective was to assess the clinical reliability of a wrist-worn, wireless accelerometer sensor for detecting generalized tonic-clonic seizures (GTCS). Seventy-three consecutive patients (age 6-68 years; median 37 years) at risk of having GTCS and who were admitted to the long-term video-electroencephalography (EEG) monitoring unit (LTM) were recruited in three centers. The reference standard was considered the seizure time points identified by experienced clinical neurophysiologists, based on the video-EEG recordings and blinded to the accelerometer sensor data. Seizure time points detected real-time by the sensor were compared with the reference standard. Patients were monitored for 17-171 h (mean 66.8; total 4,878). Thirty-nine GTCS were recorded in 20 patients. The device detected 35 seizures (89.7%). In 16 patients all seizures were detected. In three patients more than two thirds of the seizures were detected. The mean of the sensitivity calculated for each patient was 91%. The mean detection latency measured from the start of the focal seizure preceding the secondarily GTCS was 55 s (95% confidence interval [CI] 38-73 s). The rate of false alarms was 0.2/day. Our results suggest that the wireless wrist accelerometer sensor detects GTCS with high sensitivity and specificity. Patients with GTCS have an increased risk for injuries related to seizures and for sudden unexpected death in epilepsy (SUDEP), and many nocturnal seizures remain undetected in unattended patients. A portable automatic seizure detection device will be an important tool for helping these patients.
Inguinal hernia after radical prostatectomy for prostate cancer: results from a randomized setting and a nonrandomized setting.

Observational data indicate that retropubic radical prostatectomy (RRP) for prostate cancer (PCa) may induce inguinal hernia (IH) formation. Little is known about the influence of robot-assisted radical prostatectomy (RALP) on IH risk.



To compare the incidence of IH after RRP and RALP to that of nonoperated patients with PCa and to a population control.



We studied two groups. All 376 men included in the Scandinavian Prostate Cancer Group Study Number 4 constitute study group 1. Patients were randomly assigned RRP or watchful waiting (WW). The 1411 consecutive patients who underwent RRP or RALP at Karolinska University Hospital constitute study group 2. Men without PCa, matched for age and residence to each study group, constitute controls.



Postoperative IH incidence was detected through a validated questionnaire. The participation rates were 82.7% and 88.4% for study groups 1 and 2, respectively.



The Kaplan-Meier cumulative occurrence of IH development after 48 mo in study group 1 was 9.3%, 2.4%, and 0.9% for the RRP, the WW, and the control groups, respectively. There were statistically significant differences between the RRP group and the WW and control groups, but not between the last two. In study group 2 the cumulative risk of IH development at 48 mo was 12.2%, 5.8%, and 2.6% for the RRP, the RALP, and the control group, respectively. There were statistically significant differences between the RRP group and the RALP and control groups, but not between the last two.



RRP for PCa leads to an increased risk of IH development. RALP may lower the risk as compared to open surgery.
Independent and combined effects of calcium-vitamin D3 and exercise on bone structure and strength in older men: an 18-month factorial design randomized controlled trial.

Exercise and calcium-vitamin D are independently recognized as important strategies to prevent osteoporosis, but their combined effects on bone strength and its determinants remain uncertain.



To assess whether calcium-vitamin D(3) fortified milk could enhance the effects of exercise on bone strength, structure, and mineral density in middle-aged and older men.



An 18-month factorial design randomized controlled trial in which 180 men aged 50-79 years were randomized to the following: exercise + fortified milk; exercise; fortified milk; or controls. Exercise consisted of progressive resistance training with weight-bearing impact activities performed 3 d/week. Men assigned to fortified milk consumed 400 ml/d of 1% fat milk containing 1000 mg/d calcium and 800 IU/d vitamin D(3).



Changes in bone mineral density (BMD), bone structure, and strength at the lumbar spine (LS), proximal femur, mid-femur, and mid-tibia measured by dual energy x-ray absorptiometry and/or quantitative computed tomography.



There were no exercise-by-fortified milk interactions at any skeletal site. Main effect analysis showed that exercise led to a 2.1% (95% confidence interval, 0.5-3.6) net gain in femoral neck section modulus, which was associated with an approximately 1.9% gain in areal BMD and cross-sectional area. Exercise also improved LS trabecular BMD [net gain 2.2% (95% confidence interval, 0.2-4.1)], but had no effect on mid-femur or mid-tibia BMD, structure, or strength. There were no main effects of the fortified milk at any skeletal site.



A community-based multi-component exercise program successfully improved LS and femoral neck BMD and strength in healthy older men, but providing additional calcium-vitamin D(3) to these replete men did not enhance the osteogenic response.
The Spanish version of the Insomnia Severity Index: a confirmatory factor analysis.

To examine the psychometric properties of the Spanish version of the Insomnia Severity Index (ISI) and to determine its factor structure with confirmatory factor analysis (CFA).



Self-reported information was collected from a sample of 500 adults (mean age 39.13 [standard deviation 15.85]years) drawn from a population of medical students and their social networks. Together with the ISI, a measure of the subjective severity of insomnia, subjects completed the Pittsburg Sleep Quality Index, the Epworth Sleepiness Scale, and the Profile of Mood States to study concurrent validity of the ISI. CFA was used to test alternative models to ascertain the factorial structure of the ISI.



The Spanish version of the ISI showed adequate indices of internal consistency (Cronbach's α=0.82). CFA showed that a three-factor structure provided a better fit to the data than one-factor and two-factor structures. The ISI was significantly correlated with poor sleep quality, fatigue, anxiety, and depression, and discriminated between good and poor sleepers.



The ISI is a reliable and valid instrument to assess the subjective severity of insomnia in Spanish-speaking populations. Its three-factor structure (i.e., night-time sleep difficulties, sleep dissatisfaction and daytime impact of insomnia) makes it a psychometrically robust and clinically useful measure.
Post-resistance exercise hypotension, hemodynamics, and heart rate variability: influence of exercise intensity

The occurrence of post-exercise hypotension after resistance exercise is controversial, and its mechanisms are unknown. To evaluate the effect of different resistance exercise intensities on post-exercise blood pressure (BP), and hemodynamic and autonomic mechanisms, 17 normotensives underwent three experimental sessions: control (C—40 min of rest), low- (E40%—40% of 1 repetition maximum, RM), and high-intensity (E80%—80% of 1 RM) resistance exercises. Before and after interventions, BP, heart rate (HR), and cardiac output (CO) were measured. Autonomic regulation was evaluated by normalized low- (LFR–Rnu) and high-frequency (HFR–Rnu) components of the R–R variability. In comparison with pre-exercise, systolic BP decreased similarly in the E40% and E80% (−6 ± 1 and −8 ± 1 mmHg, P < 0.05). Diastolic BP decreased in the E40%, increased in the C, and did not change in the E80%. CO decreased similarly in all the sessions (−0.4 ± 0.2 l/min, P < 0.05), while systemic vascular resistance (SVR) increased in the C, did not change in the E40%, and increased in the E80%. Stroke volume decreased, while HR increased after both exercises, and these changes were greater in the E80% (−11 ± 2 vs. −17 ± 2 ml/beat, and +17 ± 2 vs. +21 ± 2 bpm, P < 0.05). LFR–Rnu increased, while ln HFR–Rnu decreased in both exercise sessions.  Low- and high-intensity resistance exercises cause systolic post-exercise hypotension; however, only low-intensity exercise decreases diastolic BP. BP fall is due to CO decrease that is not compensated by SVR increase. BP fall is accompanied by HR increase due to an increase in sympathetic modulation to the heart.