nils-herrmann/clean_scirepeval huggingface dataset:
Double-blind, placebo-controlled study of zinc sulfate in the treatment of attention deficit hyperactivity disorder

The most commonly used medications for attention deficit hyperactivity disorder (ADHD) are the psychostimulants. There is, however, considerable awareness in alternative, nonstimulant therapies, because some patients respond poorly to stimulants or are unable to tolerate them. Some studies suggest that deficiency of zinc play a substantial role in the aetiopathogenesis of ADHD. Therefore, to assess the efficacy of zinc sulfate we conducted treatment trial.



Patients with a primary DSM-IV diagnosis of ADHD (N=400; 72 girls, 328 boys, mean age=9.61+/-1.7) were randomly assigned in a 1:1 ratio to 12 weeks of double-blind treatment with zinc sulfate (n=202) (150 mg/day) or placebo (n=198). Efficacy was assessed with the Attention Deficit Hyperactivity Disorder Scale (ADHDS), Conners Teacher Questionnaire, and DuPaul Parent Ratings of ADHD. Primary efficacy variables were differences from baseline to endpoint (last observation carried forward) in mean ADHDS and Conners Teacher Questionnaire scores between the zinc sulfate and the placebo groups. Safety evaluations included monitoring of adverse events, vital signs and clinical laboratory values.



Zinc sulfate was statistically superior to placebo in reducing both hyperactive, impulsive and impaired socialization symptoms, but not in reducing attention deficiency symptoms, as assessed by ADHDS. However, full therapeutic response rates of the zinc and placebo groups remained 28.7% and 20%, respectively. It was determined that the hyperactivity, impulsivity and socialization scores displayed significant decrease in patients of older age and high BMI score with low zinc and free fatty acids (FFA) levels. Zinc sulfate was well tolerated and associated with a low rate of side effect.



Zinc monotherapy was significantly superior to placebo in reducing symptoms of hyperactivity, impulsivity and impaired socialization in patients with ADHD. Although by themselves, these findings may not be sufficient, it may well be considered that zinc treatment appears to be an efficacious treatment for ADHD patients having older age and high BMI score with low zinc and FFA levels.
Assessment of right ventricular function by transthoracic echocardiography following aortic valve replacement.

Tricuspid annular plane systolic excursion (TAPSE) is a widely used clinical measure of right ventricular (RV) systolic performance. However, postsurgical changes in the pattern of RV contraction may limit the utility of TAPSE for assessing global RV function. We retrospectively examined pre- and postoperative TAPSE and RV fractional area change (FAC) in patients undergoing 3 different types of aortic valve replacement (AVR).



Fifty-two patients enrolled in the Placement of AoRTic TraNscathetER Valve Trial at our institution were randomized to receive open AVR or transcatheter AVR (TAVR) by either the transapical or transfemoral access routes. Thirty-seven of these patients had analyzable transthoracic echocardiography (TTE) before and after AVR. Using M-mode echocardiography, TAPSE was measured in the apical four-chamber view. Using two-dimensional echocardiography, RV FAC was measured in the apical four-chamber view.



The mean change in TAPSE was -0.7 ± 0.6 cm for open AVR (P = 0.002), -0.2 ± 0.4 cm for transapical TAVR (P = 0.26), and 0.1 ± 0.5 cm for transfemoral TAVR (P = 0.64). The mean change in RV FAC was -1 ± 5% for open AVR (P = 0.91), 2 ± 4% for transapical TAVR (P = 0.37), and 7 ± 10% for transfemoral TAVR (P = 0.07).



The normal pattern of RV contraction was unchanged by transapical and transfemoral TAVR, while open AVR led to a significant decrease in TAPSE with preserved RV FAC. Thus, RV FAC is a preferable method for assessing RV function in the postoperative patient.
Evaluation of Effectiveness and Cost‐Effectiveness of a Clinical Decision Support System in Managing Hypertension in Resource Constrained Primary Health Care Settings: Results From a Cluster Randomized Trial

Randomized control trials from the developed world report that clinical decision support systems (DSS) could provide an effective means to improve the management of hypertension (HTN). However, evidence from developing countries in this regard is rather limited, and there is a need to assess the impact of a clinical DSS on managing HTN in primary health care center (PHC) settings.



We performed a cluster randomized trial to test the effectiveness and cost-effectiveness of a clinical DSS among Indian adult hypertensive patients (between 35 and 64 years of age), wherein 16 PHC clusters from a district of Telangana state, India, were randomized to receive either a DSS or a chart-based support (CBS) system. Each intervention arm had 8 PHC clusters, with a mean of 102 hypertensive patients per cluster (n=845 in DSS and 783 in CBS groups). Mean change in systolic blood pressure (SBP) from baseline to 12 months was the primary endpoint. The mean difference in SBP change from baseline between the DSS and CBS at the 12th month of follow-up, adjusted for age, sex, height, waist, body mass index, alcohol consumption, vegetable intake, pickle intake, and baseline differences in blood pressure, was -6.59 mm Hg (95% confidence interval: -12.18 to -1.42; P=0.021). The cost-effective ratio for CBS and DSS groups was $96.01 and $36.57 per mm of SBP reduction, respectively.



Clinical DSS are effective and cost-effective in the management of HTN in resource-constrained PHC settings.


 Unique identifier: CTRI/2012/03/002476.
Equivalent single-dose pharmacokinetics of two different dosing methods of prolonged-release fulvestrant ('Faslodex') in postmenopausal women with advanced breast cancer

To compare the pharmacokinetics of two different dosing methods of fulvestrant ('Faslodex'), an estrogen receptor antagonist with no known agonist activity, for the treatment of advanced breast cancer. Postmenopausal women with advanced breast cancer were randomly assigned to receive a single 5-ml intramuscular injection of 250 mg fulvestrant, or two 2.5-ml intramuscular injections with a total of 250 mg fulvestrant. Blood samples were taken for pharmacokinetic analysis up to 28 days after injection. Plasma concentrations of fulvestrant were measurable up to 28 days after both dosing methods. The concentration-time profiles were relatively shallow, spanning an approximate threefold range from 3 h after dosing to Cmin measured on day 28. Peak plasma concentrations (Cmax) of fulvestrant occurred between 1 and 11 days after dosing, with mean Cmax values of 6.0 and 6.2 ng/ml following one 5-ml injection and two 2.5-ml injections, respectively. The plasma concentration-time profiles were very similar in terms of duration and concentration, and overall exposure to fulvestrant was similar in both dosing groups (the ratio of the AUC0–28 of the single-injection group to that of the double-injection group was 1.01; 95% confidence interval 0.68–1.51). This study found no evidence of any pharmacokinetic difference between one 5-ml injection and two 2.5-ml injections. The two methods can be used interchangeably, depending on which is more convenient in any particular clinical setting.
Efficacy and safety of the seven-day buprenorphine transdermal system in opioid-naïve patients with moderate to severe chronic low back pain: an enriched, randomized, double-blind, placebo-controlled study.

This article presents the results of a pivotal Phase 3 study that assesses a new treatment for the management of chronic low back pain: a transdermal patch containing the opioid buprenorphine. In this randomized, placebo-controlled study with an enriched enrollment design, the buprenorphine transdermal system (BTDS) was found to be efficacious and generally well tolerated.



This enriched, multicenter, randomized, double-blind study evaluated the efficacy, tolerability, and safety of BTDS in opioid-naïve patients who had moderate to severe chronic low back pain.



Patients who tolerated and responded to BTDS (10 or 20 mcg/hour) during an open-label run-in period were randomized to continue BTDS 10 or 20 mcg/hour or receive matching placebo. The primary outcome was "average pain over the last 24 hours" at the end of the 12-week double-blind phase, collected on an 11-point scale (0=no pain, 10=pain as bad as you can imagine). Sleep disturbance (Medical Outcomes Study subscale) and total number of supplemental analgesic tablets used were secondary efficacy variables.



Fifty-three percent of patients receiving open-label BTDS (541 of 1024) were randomized to receive BTDS (n=257) or placebo (n=284). Patients receiving BTDS reported statistically significantly lower pain scores at Week 12 compared with placebo (least square mean treatment difference: -0.58, P=0.010). Sensitivity analyses of the primary efficacy variable and results of the analysis of secondary efficacy variables supported the efficacy of BTDS relative to placebo. During the double-blind phase, the incidence of treatment-emergent adverse events was 55% for the BTDS treatment group and 52% for the placebo treatment group. Laboratory, vital sign, and electrocardiogram evaluations did not reveal unanticipated safety findings.



BTDS was efficacious in the treatment of opioid-naïve patients with moderate to severe chronic low back pain. Most treatment-emergent adverse events observed were consistent with those associated with the use of opioid agonists and transdermal patches.
Effect of theophylline on CD11b and L-selectin expression and density of eosinophils and neutrophils in vitro.

The nonspecific phosphodiesterase inhibitor theophylline, widely used in asthma therapy, may cause a decrease in inflammatory responses of airways. In asthma, eosinophils migrate to the airway wall and become activated. Activated eosinophils are characterized by low cell density, as well as increased expression of CD11b and reduced expression of L-selectin, two adhesion molecules involved in transendothelial migration. To study the anti-inflammatory effect of theophylline on granulocyte adhesion molecules in vitro, the platelet-activating factor (PAF)-induced density shift was determined by density centrifugation and the modulation of CD11b and L-selectin expression by flow cytometry on eosinophils and neutrophils in human whole blood. A relatively high concentration of theophylline (10(-3) M) inhibited the increase in the percentage of hypodense eosinophils and neutrophils in whole-blood samples after PAF stimulation in vitro. A more pharmacological concentration (10(-4) M) inhibited the CD11b upregulation and L-selectin shedding induced by PAF (10(-7) M) on both eosinophils and neutrophils. The effect of isoproterenol on the inhibitory effect of theophylline was mainly additive, but a small synergistic effect could not be excluded. In conclusion theophylline can attenuate eosinophil and neutrophil activation in vitro at the level of adhesion molecule expression and changes in cell density. This may have implications for transendothelial migration of these cells in asthma.
28-Day safety and tolerability of umeclidinium in combination with vilanterol in COPD: a randomized placebo-controlled trial.

Umeclidinium (UMEC; GSK573719) is a new long-acting muscarinic antagonist (LAMA) currently in development in combination with vilanterol (VI), an inhaled, long-acting beta₂ agonist for the treatment of chronic obstructive pulmonary disease (COPD). The primary aim of this study was to evaluate the safety and tolerability of repeat dosing of UMEC and VI in combination once daily for 28 days in patients with COPD.



This was a multicenter, double-blind, placebo-controlled, parallel group study. Patients aged ≥40 years with post-bronchodilator FEV₁ ≤80% of predicted normal values and FEV₁/FVC ratio ≤0.70, and a smoking history of ≥10 pack-years, were randomized 4:1 to once-daily UMEC/VI (500/25 mcg; n = 42) or placebo (n = 9).



UMEC/VI was non-inferior to placebo in weighted mean pulse rate over 0-6 h at Day 28 (primary endpoint: difference of -0.5 bpm, 95% CI: -5.5 to 4.5). There was no evidence of a difference between UMEC/VI compared with placebo in blood pressure, minimum and maximum pulse rate, or QTcF assessments. Adverse events (AEs) were reported by 11 (26%) patients in the UMEC/VI group and one (11%) patient in the placebo group. No serious AEs were reported. Both UMEC and VI showed rapid absorption (median t(max) ∼6 min for both drugs) with no evidence of accumulation for AUC or C(max) on Day 28 compared with Day 1 for UMEC or VI. There was no correlation between individual steady-state C(max) and pulse rate on Day 28. Change from baseline in trough FEV₁ on Day 29 showed numerically greater improvements with UMEC/VI compared with placebo.



Once-daily dosing with UMEC in combination with VI in patients with moderate-to-very-severe COPD was well tolerated over 28 days.
"Low-field" intraoperative MRI: a new scenario, a new adaptation.

To describe the adaptation of Cruces University Hospital to the use of intraoperative magnetic resonance imaging (ioMRI), and how the acquisition and use of this technology would impact the day-to-day running of the neurosurgical suite.



With the approval of the ethics committee, an observational, prospective study was performed from June 2012 to April 2014, which included 109 neurosurgical procedures with the assistance of ioMRI. These were performed using the Polestar N-30 system (PSN30; Medtronic Navigation, Louisville, CO), which was integrated into the operating room.



A total of 159 procedures were included: 109 cranial surgeries assisted with ioMRI and 50 control cases (no ioMRI use). There were no statistical significant differences when anaesthetic time (p=0.587) and surgical time (p=0.792) were compared; however, an important difference was shown in duration of patient positioning (p<0.0009) and total duration of the procedure (p<0.0009) between both groups.



The introduction of ioMRI is necessary for most neurosurgical suites; however, a few things need to be taken into consideration when adapting to it. Increase procedure time, the use of specific MRI-safe devices, as well as a checklist for each patient to minimise risks, should be taken into consideration.
Contribution of long axis motion of left ventricular outflow to calculation of left ventricular stroke volume

Stroke volume can be calculated by using noninvasive Doppler techniques. The products of pulsed Doppler stroke distance of left ventricular outflow and left ventricular outflow area can often be used to calculate stroke volume. However, left ventricular outflow also moves longitudinally toward the apex of the ventricle during systole, so that zero velocity flow cannot be detected by the usual pulsed Doppler studies. We evaluated the contribution of these zero velocity flow to the noninvasive estimation of left ventricular stroke volume in 20 patients with left ventricular disease and in 20 age matched healthy controls. Left ventricular stroke distance was calculated by summing the Doppler stroke distance and the outflow long axis motion. The percentage of zero velocity flow for total stroke volume was calculated in each group. Cardiac output was also measured by thermo-dilution technique. The percentage of zero velocity flow for total noninvasive stroke volume in patients with left ventricular disease was 2.5±1.1 ml (4.0±1.5%), significantly lower than in normal subjects, 3.6±1.0 ml (5.5±1.5%) (p<0.05). These long axis motions are significantly reduced, especially in left ventricular disease. Amplitudes of the left ventricular outflow long axis motion were correlated with Doppler stroke distance in all (r=0.54, p<0.01). In patients with myocardial infarction, stroke volume by thermo-dilution methods and calculated stroke volume showed good correlation both only by Doppler stroke distance (y=1.044x+0.547, r=0.968) and by Doppler and long axis motion (y=0.989x+0.521, r=0.974). Compared with stroke volume measured by thermodilution method, stroke volume calculated only by Doppler stroke distance was underestimated. We thus demonstrated the influence of zero velocity flow on left ventricular outflow both in patients with left ventricular disease and in normal subjects.
High frequency of antiphospholipid antibodies in relapse of multiple sclerosis: a possible indicator of inflammatory–thrombotic processes

The exact prevalence and pathogenic role of antiphospholipid antibodies (aPL) in multiple sclerosis (MS) remain unclear. This observational laboratory-blinded study evaluated the rate of aPL positivity in healthy controls and MS patients in different disease phases to recognize their frequency and possible pathogenic meaning. Reactivity for anti-cardiolipin, anti-β2 glycoprotein I, anti-prothrombin, anti-annexin V (IgG and IgM) was studied by enzyme immunoassays in 60 healthy controls and 100 consecutive MS patients [58 relapsing–remitting (RR) patients in remission, 26 RR patients in relapse, and 16 secondary progressive patients]. The overall rate of positivity for at least one aPL was significantly higher in MS patients compared to controls (32 % vs. 7 %, respectively, p < 0.0001), and in relapsing phase compared to those remitting or secondary progressive (53.8, 20.7 and 37.5 %, respectively, p = 0.002). In the single aPL analysis, the rate of positivity was significantly higher in MS patients compared to controls for anti-prothrombin IgM (7 % vs. 0, p = 0.05), and in relapsing phase compared to remitting and secondary progressive phases for anti-β2 glycoprotein I IgM (26.9, 1.7, 6.3 %, respectively, p < 0.0001), anti-prothrombin IgM (15.4, 3.4, 6.3 %, respectively, p = 0.05) and IgG (19.2, 5.2, 0 %, respectively, p = 0.05). We showed a significant aPL increase in MS patients compared to healthy controls, particularly during disease relapse which was also associated with significantly higher values of anti-β2 glycoprotein I and anti-prothrombin. These data suggest that antiphospholipid antibody occurrence in multiple sclerosis could be related to modification of structure and function of proteins involved in the inflammatory–thrombotic processes during disease re-activation.
The efficacy of intermittent cervical traction in patents with chronic neck pain

Previous studies about the usefulness of traction therapy have concluded with conflicting results. The aim of this study was to examine its efficacy in chronic neck pain. Forty-two patients with at least 6 weeks of nonspecific neck pain were selected for the study. Data about demographic characteristics including age, sex, body mass index, duration of cervical pain, working status, smoking status, and regular exercise were recorded. Each patient was randomly assigned to Group 1—receiving only standard physical therapy including hot pack, ultrasound therapy and exercise program and Group 2—treated with traction therapy in addition to standard physical therapy. The patients were reevaluated at the end of the therapy. The main outcome measures of the treatment were pain intensity by visual analog scale (VAS), disability by neck disability index (NDI), and quality of life assessed by Nottingham Health Profile (NHP). Twenty-four female and 18 male patients with mean age of 48.2 ± 11.5 years and a mean disease duration of 4.3 ± 2.9 years were included to the study. There were no differences between the groups in terms of age, sex, pain intensity, and scores of NHP and NDI at entry. There were 21 patients in both groups. Both groups improved significantly in pain intensity and the scores of NDI and physical subscles of NHP at the end of the therapies (p < 0.05). There was an association between NDI and VAS pain scores in both groups (p < 0.05). No correlation was observed between clinical variables and age and duration of disease. In conclusion, no specific effect of traction over standard physiotherapeutic interventions was observed in adults with chronic neck pain. We suggest the clinicians to consider this condition and to focus on exercise therapy in the management of patients suffering from this condition.
Impact of Exposure to Intimate Partner Violence on CD4+ and CD8+ T Cell Decay in HIV Infected Women: Longitudinal Study

Intimate partner violence (IPV) is a risk factor for HIV acquisition in many settings, but little is known about its impact on cellular immunity especially in HIV infected women, and if any impact differs according to the form of IPV. We tested hypotheses that exposure to IPV, non-partner rape, hunger, pregnancy, depression and substance abuse predicted change in CD4+ and CD8+ T-cell count in a dataset of 103 HIV infected young women aged 15-26 enrolled in a cluster randomised controlled trial. Multiple regression models were fitted to measure rate of change in CD4 and CD8 and including terms for age, person years of CD4+/CD8+ T-cell observation, HIV positivity at baseline, and stratum. Exposure variables included drug use, emotional, physical or sexual IPV exposure, non-partner rape, pregnancy and food insecurity. Mean CD4+ T cell count at baseline (or first HIV+ test) was 567.6 (range 1121-114). Participants were followed for an average of 1.3 years. The magnitude of change in CD4 T-cells was significantly associated with having ever experienced emotional abuse from a current partner at baseline or first HIV+ test (Coeff -132.9 95% CI -196.4, -69.4 p<0.0001) and drug use (Coeff -129.9 95% CI -238.7, -21.2 p=0.02). It was not associated with other measures. The change in CD8 T-cells was associated with having ever experienced emotional abuse at baseline or prior to the first HIV+ test (Coeff -178.4 95%CI -330.2, -26.5 p=0.02). In young ART-naive HIV positive women gender-based violence exposure in the form of emotional abuse is associated with a faster rate of decline in markers of cellular immunity. This highlights the importance of attending to emotional abuse when studying the physiological impact of IPV experience and the mechanisms of its impact on women's health.
Alternating v repeated postremission treatment in adult acute myelogenous leukemia: a randomized phase III study (AML6) of the EORTC Leukemia Cooperative Group.

The value of a postremission treatment in acute myelogenous leukemia (AML), with alternating combinations of non-cross-resistant drugs, has been prospectively assessed. Of 515 evaluable patients, 347 (67.4%) entered into complete remission (CR), following induction treatment with daunorubicin (DNR), vincristine (VCR), and cytosine arabinoside (ara-C). After one consolidation course, 248 patients were randomized for six courses of intensive maintenance: either repeated treatment with DNR-VCR-ara-C, or alternating treatment where amsacrine (AMSA) was combined with high dose ara-C on cycle 1,3, and 5 and with 5-azacytidine on cycle 2, 4, and 6. Ninety-nine patients were not randomized: 57 were introduced in a bone marrow transplantation (BMT) program, and 42 went off study, mainly for treatment toxicity or refusal. The main prognostic factors for achievement of CR were performance status, cytogenetics, and age, and for the disease-free survival (DFS): age and number of courses to CR. The rate of second remission was fairly high (64%) for patients relapsing off therapy. The DFS appeared identical (median, 53 weeks), in the two randomized arms, the alternating treatment not showing superiority to the repeated one, in spite of an increased toxicity. The median overall survival for patients achieving a CR was 90 weeks. The reason for the failure of alternating maintenance treatment to improve the DFS is probably related to an insufficient dose intensity: five patients who relapsed during maintenance arm B achieved a second CR with a more intensive combination of high-dose ara-C and AMSA. In addition, 60 patients underwent a BMT (43 allogeneic and 17 autologous). The DFS of patients treated with allogeneic BMT tended to be superior to the one obtained with the chemotherapy program. However the overall survival, as well as the event-free survival, seemed equivalent, including patients who relapsed before the planned BMT. Comparisons between allogeneic BMT, autologous BMT, and intensive consolidation during first CR deserve further prospective studies in AML.