nils-herrmann/clean_scirepeval huggingface dataset:
A double-blind, placebo-controlled study of selegiline transdermal system in depressed adolescents.

A randomized, double-blind, placebo-controlled flexible-dose, parallel group trial was conducted at 26 clinical investigational sites in the United States to examine the safety and efficacy of the selegiline transdermal system (STS) (EMSAM®) in adolescents (ages 12-17 years) meeting American Psychiatric Association, Diagnostic and Statistical Manual of Mental Disorders, 4th ed. (DSM-IV) criteria for moderate to severe major depressive disorder (MDD) without psychotic features.



Adolescents (n=308) with moderate to severe MDD were randomized to either STS (n=152) or placebo (n=156). Two hundred and fifteen (69.8%) subjects completed the study and 17 (5.5%) reported discontinuation because of adverse events (AEs). The primary efficacy outcome measure was the mean change from baseline to end of study (week 12 last observation carried forward [LOCF]) in the Children's Depression Rating Scale-Revised (CDRS-R) total score. Secondary outcome measures included end-point Clinical Global Impressions - Severity (CGI-S) and Clinical Global Impressions - Improvement (CGI-I).



Patients on STS or placebo had a significant decline from baseline (p<0.001) on their CDRS-R total score with mean reductions±SD as follows: STS 21.4±16.6; placebo 21.5±16.5. Both groups had similar response rates (58.6% vs. 59.3%) defined as CGI-I of 1 or 2 at study end. However, these between-group efficacy findings were without statistical significance. The overall incidence of reported AEs was 62.5% for STS-treated patients and 57.7% for placebo-treated patients. Most commonly reported AEs in STS or placebo groups were application site reactions (STS=24.3%; placebo=21.8%), headache (STS=17.1%; placebo=16.7%), and nausea (STS=7.2%; placebo=7.7%). Treatment groups did not differ on any laboratory parameters, vital signs, or electrocardiogram (ECG) findings. No suspected hypertensive crises were reported in the trial.



These data demonstrated that the STS was safe and well tolerated in this adolescent sample. However, both STS-treated and placebo-treated subjects demonstrated a decline from baseline in depressive symptoms (CDRS-R total score) over the length of the study, without statistical superiority by either group.
Temozolomide chemotherapy alone versus radiotherapy alone for malignant astrocytoma in the elderly: the NOA-08 randomised, phase 3 trial.

Radiotherapy is the standard care in elderly patients with malignant astrocytoma and the role of primary chemotherapy is poorly defined. We did a randomised trial to compare the efficacy and safety of dose-dense temozolomide alone versus radiotherapy alone in elderly patients with anaplastic astrocytoma or glioblastoma.



Between May 15, 2005, and Nov 2, 2009, we enrolled patients with confirmed anaplastic astrocytoma or glioblastoma, age older than 65 years, and a Karnofsky performance score of 60 or higher. Patients were randomly assigned 100 mg/m(2) temozolomide, given on days 1-7 of 1 week on, 1 week off cycles, or radiotherapy of 60·0 Gy, administered over 6-7 weeks in 30 fractions of 1·8-2·0 Gy. The primary endpoint was overall survival. We assessed non-inferiority with a 25% margin, analysed for all patients who received at least one dose of assigned treatment. 
Of 584 patients screened, we enrolled 412. 373 patients (195 randomly allocated to the temozolomide group and 178 to the radiotherapy group) received at least one dose of treatment and were included in efficacy analyses. Median overall survival was 8·6 months (95% CI 7·3-10·2) in the temozolomide group versus 9·6 months (8·2-10·8) in the radiotherapy group (hazard ratio [HR] 1·09, 95% CI 0·84-1·42, p(non-inferiority)=0·033). Median event-free survival (EFS) did not differ significantly between the temozolomide and radiotherapy groups (3·3 months [95% CI 3·2-4·1] vs 4·7 [4·2-5·2]; HR 1·15, 95% CI 0·92-1·43, p(non-inferiority)=0·043). Tumour MGMT promoter methylation was seen in 73 (35%) of 209 patients tested. MGMT promoter methylation was associated with longer overall survival than was unmethylated status (11·9 months [95% CI 9·0 to not reached] vs 8·2 months [7·0-10·0]; HR 0·62, 95% CI 0·42-0·91, p=0·014). EFS was longer in patients with MGMT promoter methylation who received temozolomide than in those who underwent radiotherapy (8·4 months [95e% CI 5·5-11·7] vs 4·6 [4·2-5·0]), whereas the opposite was true for patients with no methylation of the MGMT promoter (3·3 months [3·0-3·5] vs 4·6 months [3·7-6·3]). The most frequent grade 3-4 intervention-related adverse events were neutropenia (16 patients in the temozolomide group vs two in the radiotherapy group), lymphocytopenia (46 vs one), thrombocytopenia (14 vs four), raised liver-enzyme concentrations (30 vs 16), infections (35 vs 23), and thromboembolic events (24 vs eight).



Temozolomide alone is non-inferior to radiotherapy alone in the treatment of elderly patients with malignant astrocytoma. MGMT promoter methylation seems to be a useful biomarker for outcomes by treatment and could aid decision-making.
Short-term and long-term outcome of endoluminal gastroplication for the treatment of GERD: the first multicenter trial in Japan

Endoluminal gastroplication (ELGP) was the first endoscopic therapy for gastroesophageal reflux disease (GERD). Data on the long-term outcomes, including the plication status and data from Asian populations, are limited. The aim of this study was to evaluate the short-term and long-term effectiveness and safety of ELGP for GERD in the Japanese population.  Forty-eight patients with GERD were enrolled. The procedure involved placing circumferential plications 1–2 cm below the GE junction using the EndoCinch system. Outcome measurements were improvement of heartburn, medication use, endoscopic Los Angeles grade, durability of plications, 24-h esophageal acid exposure, esophageal manometry, and frequency of adverse events. During the 24-month follow-up, the rate of complete resolution of heartburn ranged from 54 to 66%, the rate of discontinuation or reduction of PPI/H2RA use ranged from 65 to 76%, and the rate of endoscopic classification to grade O ranged from 66 to 81%. The status with more than one plication remaining was associated with higher rates of improvement of heartburn, PPI/H2RA use, and endoscopic findings as compared with those associated with the loss of all plications. A modest decrease of the esophageal acid exposure level, but no change of the manometric parameters, was observed after ELGP. No serious adverse events were observed. In this 24-month follow-up study conducted in Japanese subjects, ELGP was found to be effective in about 60% of patients with GERD, and the procedure was safe.
Adiponectin as a Protective Factor Against the Progression Toward Type 2 Diabetes Mellitus in Postmenopausal Women

Serum adiponectin levels have been suggested to be predictors of type 2 diabetes mellitus in diverse populations. However, the relationship between circulating adiponectin levels and the risk of development of type 2 diabetes in postmenopausal women has not been investigated.A total of 382 healthy postmenopausal women who participated in a prospective cohort study were followed for 5.8 years. Type 2 diabetes mellitus was defined according to the criteria set out by the American Diabetes Association. Adiponectin, osteoprotegerin (OPG), and high-sensitivity C-reactive protein (hs-CRP) levels were measured using ELISA.Of 195 women who did not have diabetes at baseline and who were reexamined in the second phase of the study for diabetic status, 35 subjects (17.9%) developed type 2 diabetes mellitus during the 5.8 years follow-up period. The women with type 2 diabetes had lower adiponectin levels than the healthy postmenopausal women. Multiple regression analysis showed that, after adjustments were made for age, cardiovascular risk factors, OPG, and hs-CRP levels, higher baseline adiponectin levels were associated with a lower relative risk (RR) of having type 2 (RR = 0.07, confidence interval [CI]: 0.01-0.66, P = 0.021).Higher baseline adiponectin levels functioned as a predictor of a lower risk of developing type 2 diabetes mellitus among postmenopausal women during a 5.8 years follow-up study. Therefore, it is suggested that elevated adiponectin levels may offer protection against the development of type 2 diabetes mellitus after the menopause.
Regenerative responses in slow- and fast-twitch muscles following moderate contusion spinal cord injury and locomotor training

The aim of this study was to use the rat moderate spinal cord contusion model to investigate the effects of incomplete spinal cord injury (SCI) on the muscle regeneration process, comparing regeneration of slow-twitch plantarflexor soleus muscle and fast-twitch dorsiflexor tibialis anterior (TA) muscle. Additionally, we wanted to examine the effect of a week of locomotor training following incomplete SCI on the muscle regeneration process in these muscles and also determine if a week of similar locomotor training is sufficient to initiate muscle regeneration in control, non-injured rats. Thirty-two, adult, female, Sprague–Dawley rats were chosen for the study. Moderate, midthoracic contusion SCIs were produced using a NYU (New York University) impactor in all rats except controls. Animals were randomly assigned to treadmill training or untrained groups. Rats in the treadmill training group were manually treadmill trained starting at 1 week after SCI, for 10 bouts (2 sessions of 20 min of actual stepping) over 5 days and control rats in the training group received similar training. Our results indicate that a muscle regenerative response was initiated only in the slow-twitch soleus muscle in the initial 2 weeks following SCI, the addition of 1 week of locomotor treadmill training led to a significant increase in soleus regenerative process. No significant regenerative process was observed in the fast-twitch TA. Increased muscle regeneration in soleus is suggested by our findings of increased expression of (1) insulin-like growth factor-1, involved in the activation of satellite cells; (2) Pax7, a marker of satellite cell activation; (3) myogenin, a muscle regulatory protein; and (4) embryonic myosin, an indicator of new muscle fiber formation. Locomotor training in control, non-injured animals did not induce similar changes towards the regenerative process.
A phase I/II trial of gefitinib given concurrently with radiotherapy in patients with nonmetastatic prostate cancer.

e16079  We estimated the safety and tolerability of 250 mg gefitinib q.d. given concurrently with three- dimensional conformal radiotherapy (3D-CRT) in patients with non-metastatic prostate cancer (PC).



42 patients with T2/T3N0M0 PC were treated in a single centre, non-randomized study (study code ZD1839/IL0118). PSA<20 and good performance status (WHO 0-1) were required. Adjuvant or neo-adjuvant hormonal treatments were not allowed. 250 mg gefitinib q.d. was started one week before and lasted for the duration of radiation therapy. 50.4 Gy (1.8 Gy/day) of 3D-CRT was administered to the tumor, prostate and seminal vesicles, followed by a 22 Gy booster (2 Gy/day) for a 72.4 Gy total dose. EGFR expression, presence of EGFRvIII and activated pEGFR were studied. Levels of serum TNF, IL-1 α and IL-6 were also evaluated.



Maximum tolerated dose was not reached in phase I (12 patients) and 30 additional patients were treated in phase II. Thirty (71.4%) patients completed trial medication and 12 (28.6%) prematurely discontinued because of adverse events. Dose-limiting toxicities were recorded in 16 (38.1%) patients, the most common of which was grade 3-4 transaminase increase (6 patients). After median follow-up of 38 months nobody had died of PC. The estimated PSA-free survival rate at 4 years (Kaplan-Meier) was 97%, hormone-free survival 91% and overall survival 87%. These figures compared favourably with matched, non-randomized patients treated with radiation only. Data on biochemical analyses will be presented.



The combination of gefitinib and radiation is reasonably well tolerated and has promising activity in non-metastatic PC. A randomized study is being discussed for evaluating the efficacy of the approach.
The Role of the Pharmacist in the Treatment of Patients with Infantile Hemangioma Using Propranolol

Infantile hemangiomas (IH) are the most common benign vascular tumors of childhood, with an incidence of 5-10% during the first year of age. Propranolol is considered the first-line treatment for this condition. Potentially there is a high probability of negative results to therapy, because in many countries there are no treatment protocols or propranolol formulations appropriate for the pediatric population. The objective of the present study was to evaluate the impact of pharmacist interventions such as detecting, analyzing, and solving problems presented during treatment with propranolol in patients with IH.



An open observational prospective study was performed over 25 months in a group of pediatric patients diagnosed with infantile hemangioma treated with propranolol. Pharmacist participation consisted of development of an extemporaneous formulation and counseling the child's parents. At each visit to the pharmacy service, family members were interviewed, detecting and classifying problems related to treatment.



Sixty-three children with IH were treated during the period under review. Patient ages ranged from 3 to 11 months old; 64% were female and 36% were male. Forty-nine problems in 30 patients were detected, principally inadequate dose (18.4%), non-adherence to treatment (16.3%), side effects (14.3%), and wrong administration (14.3%). Of the problems detected, 81.6% were resolved. Interventions by the pharmacist in 27 patients were intensive counseling on adherence to therapy (20%), detection of adverse effects (11.4%), and adjustment of the dose (22.9%). In 95.2% of patients a good response to treatment was obtained compared with 77.2% reported in European studies without pharmacist intervention.



It seems that pharmacist participation increases adherence to treatment and reduces the likelihood of adverse effects, allowing for safe and effective therapy in patients with IH.
Neurodevelopmental outcome among multiples and singletons: a regional neonatal intensive care unit's experience in Turkey.

The aim of this study was to compare the neurodevelopmental outcome at 12-18 months' corrected age between multiples and singleton preterm infants.



We designed a prospective study of preterm infants (≤32 weeks gestation) born and hospitalized in the neonatal intensive care unit between November 2008 and November 2009, whose assessments were performed at 12-18 months' corrected age. Neurodevelopmental impairment was defined as the presence of any one of the following: moderate or severe cerebral palsy, severe bilateral hearing loss or bilateral blindness, mental developmental index score, or psychomotor developmental index score less than 70. Results were compared for both multiples and singleton infants.



One hundred and fifty-nine multiples and 211 singleton infants were assessed at 12-18 months' corrected age. The neurodevelopmental outcome including all parameters at 12-18 months' corrected age in multiples was not significantly different from singleton preterm infants.



Multiple gestation in preterm infants is not associated with an increased risk of neurodevelopmental impairment at 12-18 months' corrected age compared with singleton preterm infants. For further information, long term and high participation in neurodevelopmental follow-up and evaluation at pre-school age will be needed.
Olive oil consumption, plasma oleic acid, and stroke incidence: the Three-City Study.

To determine whether high olive oil consumption, and high plasma oleic acid as an indirect biological marker of olive oil intake, are associated with lower incidence of stroke in older subjects.



Among participants from the Three-City Study with no history of stroke at baseline, we examined the association between olive oil consumption (main sample, n = 7,625) or plasma oleic acid (secondary sample, n = 1,245) and incidence of stroke (median follow-up 5.25 years), ascertained according to a diagnosis validated by an expert committee.



In the main sample, 148 incident strokes occurred. After adjustment for sociodemographic and dietary variables, physical activity, body mass index, and risk factors for stroke, a lower incidence for stroke with higher olive oil use was observed (p for trend = 0.02). Compared to those who never used olive oil, those with intensive use had a 41%(95% confidence interval 6%-63%, p = 0.03) lower risk of stroke. In the secondary sample, 27 incident strokes occurred. After full adjustment, higher plasma oleic acid was associated with lower stroke incidence (p for trend = 0.03). Compared to those in the first tertile, participants in the third tertile of plasma oleic acid had a 73% (95% confidence interval 10%-92%, p = 0.03) reduction of stroke risk.



These results suggest a protective role for high olive oil consumption on the risk of stroke in older subjects.
Prostate-specific antigen testing rates and referral patterns from general practice data in England.

There is currently no national screening programme for prostate cancer in England, but eligible men can request a prostate-specific antigen (PSA) test from their general practitioner (GP). There are no routinely available data to monitor the extent of PSA testing and referral.



The aim of this study was to investigate the rate of PSA testing in general practice and subsequent patterns of referral.



Data obtained from the Clinical Practice Research Datalink (CPRD) for men aged 45-84 years who had a PSA test during 2010-2011, registered in practices in England with linked Hospital Episode Statistics (HES) data.



Patient data were linked to previous tests and consultations. Rates of PSA testing and proportions of men retested and referred to secondary care were calculated.



Overall, 8.74 (95% CI 8.67-8.82) of men per 100 person-years were tested at least once in 2010, and 9.45 (95% CI 9.37-9.53) in 2011. Rates increased with age and decreased with increasing level of deprivation. Of the 53,069 men tested in 2010, 11,289 (21.3%) had a previous PSA test within the past 12 months. Of men with raised PSA according to age specific guidelines, 22.4% (2113/9425) were referred to secondary care within 14 days, with 36% of the remainder retested within 6 months.



Rates of PSA testing have increased compared with earlier studies; the data suggest that many GPs are retesting men with raised PSA rather than referring immediately. More routine data on PSA testing, including reasons for testing, and subsequent management and outcomes, are required.
Effects of mycophenolic acid on human immunodeficiency virus infection in vitro and in vivo

Mycophenolic acid, a selective inhibitor of the de novo synthesis of guanosine nucleotides in T and B lymphocytes, has been proposed to inhibit human immunodeficiency virus (HIV) replication in vitro by depleting the substrate (guanosine nucleotides) for reverse transcriptase. Here we show that mycophenolic acid induced apoptosis and cell death in a large proportion of activated CD4+ T cells, thus indicating that it may inhibit HIV infection in vitro by both virological mechanisms and immunological mechanisms (depletion of the pool of activated CD4+ T lymphocytes). Administration of mycophenolate mophetil, the ester derivate of mycophenolic acid, to HIV-infected subjects treated with anti-retroviral therapy and with undetectable viremia resulted in the reduction of the number of dividing CD4+ and CD8+ T cells and in the inhibition of virus isolation from purified CD4+ T-cell populations. Based on these results, the potential use of mycophenolate mophetil in the treatment of HIV infection deserves further investigation in controlled clinical trials.
Associations of cytokine concentrations with key osteopathic lesions and clinical outcomes in patients with nonspecific chronic low back pain: results from the OSTEOPATHIC Trial.

Little is known about the role that cytokines play in osteopathic manual treatment (OMT) of patients with chronic low back pain (LBP).



To measure the baseline concentrations of interleukin (IL)-1β, IL-6, IL-8, IL-10, and tumor necrosis factor (TNF)-α in patients with chronic LBP; the correlations of these cytokine concentrations with clinical measures, including the number of key osteopathic lesions; the changes in cytokine concentrations with OMT; and the association of such changes with clinical outcomes.



Substudy nested within a randomized controlled trial of OMT for nonspecific chronic LBP.



University-based study in Dallas-Fort Worth, Texas.



Seventy adult research patients with nonspecific chronic LBP.



A 10-cm visual analog scale, the Roland-Morris Disability Questionnaire, and the Medical Outcomes Study Short Form-36 Health Survey were used to measure LBP severity, back-specific functioning, and general health, respectively.



At baseline, IL-1β (ρ = 0.33; P = .005) and IL-6 (ρ = 0.32; P = .006) were each correlated with the number of key osteopathic lesions; however, only IL-6 was correlated with LBP severity (ρ = 0.28; P = .02). There was a significantly greater reduction of TNF-α concentration after 12 weeks in patients who received OMT compared with patients who received sham OMT (Mann-Whitney U = 251.5; P = .03). Significant associations were found between OMT and a reduced TNF-α concentration response at week 12 among patients who achieved moderate (response ratio, 2.13; 95% confidence interval [CI], 1.11-4.06; P = .006) and substantial (response ratio, 2.13; 95% CI, 1.07-4.25; P = .01) LBP improvements, and improvement in back-specific functioning (response ratio, 1.68; 95% CI, 1.04-2.71; P = .03).



This study found associations between IL-1β and IL-6 concentrations and the number of key osteopathic lesions and between IL-6 and LBP severity at baseline. However, only TNF-α concentration changed significantly after 12 weeks in response to OMT. These discordant findings indicate that additional research is needed to elucidate the underlying mechanisms of action of OMT in patients with nonspecific chronic LBP.
Probucol reduces lysophosphatidylcholines in low-density lipoprotein

Lysophosphatidylcholine (LPC) in low-density lipoprotein (LDL) comes into notice as an important atherogenic substance.  Since the effect of probucol, an antioxidative lipid-lowering drug, on LPC molecular species has not been elucidated, two LPC molecular species, stearoyl LPC (SLPC) and palmitoyl LPC (PLPC), were measured in LDL using high-pressure liquid chromatography. LDL was obtained from 11 hyperlipidemic patients, including 9 diabetic patients, in comparison with 11 age- and gender-matched controls.  Hyperlipidemic patients showed nearly twofold higher levels of SLPC and PLPC per gram of LDL protein than those of controls. All hyperlipidemic patients were treated with oral administration of 500 mg/day of probucol for 3 months. Both LPCs in LDL were significantly reduced to control levels and were increased again up to the pretreatment levels 4 weeks after cessation of the treatment. Therefore, probucol has a potent effect in reducing LPC and may contribute to decreasing the atherogenicity of LDL.