nils-herrmann/clean_scirepeval huggingface dataset:
Aprepitant for the prevention of chemotherapy-induced nausea and vomiting in children: a randomised, double-blind, phase 3 trial.

Oral aprepitant, a neurokinin-1 receptor antagonist, is recommended in combination with other anti-emetic agents for the prevention of nausea and vomiting associated with moderately or highly emetogenic chemotherapy in adults, but its efficacy and safety in paediatric patients are unknown. We did this phase 3 trial to examine the safety and efficacy of such treatment in children.



In this final analysis of a phase 3, randomised, multicentre, double-blind study, patients aged 6 months to 17 years with a documented malignancy who were scheduled to receive either moderately or highly emetogenic chemotherapy were randomly assigned with an interactive voice response system to an age-based and weight-based blinded regimen of aprepitant (125 mg for ages 12-17 years; 3·0 mg/kg up to 125 mg for ages 6 months to <12 years) plus ondansetron on day 1, followed by aprepitant (80 mg for ages 12-17 years; 2·0 mg/kg up to 80 mg for ages 6 months to <12 years) on days 2 and 3, or placebo plus ondansetron on day 1 followed by placebo on days 2 and 3; addition of dexamethasone was allowed. Randomisation was stratified according to patient age, planned use of chemotherapy associated with very high risk of emetogenicity, and planned use of dexamethasone as an anti-emetic. Ondansetron was dosed per the product label for paediatric use or local standard of care. The primary efficacy endpoint was the proportion of patients who achieved complete response (defined as no vomiting, no retching, and no use of rescue medication) during the 25-120 h (delayed phase) after initiation of emetogenic chemotherapy. Efficacy and safety analyses were done with all randomly assigned patients who received at least one dose of study treatment. 
Between Sept 22, 2011, and Aug 16, 2013, 307 patients were randomly assigned at 49 sites in 24 countries to either the aprepitant group (155 patients) or to the control group (152 patients). Three patients in the aprepitant group and two in the control group did not receive study medication, and thus were excluded from analyses. 77 (51%) of 152 patients in the aprepitant group and 39 (26%) of 150 in the control group achieved a complete response in the delayed phase (p<0·0001). The most common grade 3-4 adverse events were febrile neutropenia (23 [15%] of 152 in the aprepitant group vs 21 [14%] of 150 in the control group), anaemia (14 [9%] vs 26 [17%]), and decreased neutrophil count (11 [7%] vs 17 [11%]). The most common serious adverse event was febrile neutropenia (23 [15%] patients in the aprepitant group vs 22 [15%] in the control group).



Addition of aprepitant to ondansetron with or without dexamethasone is effective for the prevention of chemotherapy-induced nausea and vomiting in paediatric patients being treated with moderately or highly emetogenic chemotherapy.



Merck & Co., Inc.
A Randomized Pilot Trial Comparing Position Emission Tomography (PET)-Guided Dose Escalation Radiotherapy to Conventional Radiotherapy in Chemoradiotherapy Treatment of Locally Advanced Nasopharyngeal Carcinoma

This pilot trial is designed to determine whether PET/CT-guided radiotherapy dose escalation can improve local control while minimizing toxicity for the treatment of locally advanced nasopharyngeal carcinoma.



67 patients were randomized into the three treatment arms: conventional chemoradiotherapy (group A), CT-guided dose escalation chemoradiotherapy (group B) and PET/CT-guided dose escalation chemoradiotherapy (group C). Radiotherapy was delivered using the simultaneous modulated accelerated radiation therapy (SMART) technique in the dose-escalation treatment arms. Patients received concurrent and adjuvant chemotherapy.



The use of PET/CT significantly changed the treatment volume delineation of the gross tumor volume. 3-year local progression-free (LPF) survival rates of three groups were 83.3%, 90.9% and 100%, respectively. The 3-year regional progression-free survival (RPFS) rates were 95.8%, 95.5% and 100%, respectively. The 3-year disease free survival (DFS) rates were 79.2%, 86.4% and 95.2%, respectively. The 3-year overall survival (OS) rates were 83.3%, 90.9% and 95.2%, respectively. The 3-year disease-free survival (DFS) rates were 79.2%, 86.4% and 95.2%, respectively. No patient had grade 4 late toxicity.



PET/CT-guided dose escalation radiotherapy is well-tolerated and appears to be superior to conventional chemoradiotherapy for locally advanced NPC.
The dose-dependent effects of phenylephrine for elective cesarean delivery under spinal anesthesia.

Hypotension is the most common serious side effect of spinal anesthesia for cesarean delivery. There has been a move recently toward the use of phenylephrine as a vasopressor infusion to improve maternal cardiovascular stability and fetal outcome. Although it seems safe in the elective setting, there have been concerns about its propensity for causing an increase in afterload and a baroreceptor-mediated bradycardia in the mother, with a consequent reduction in maternal cardiac output (CO). Using a noninvasive measure of CO, our aim was to investigate whether there were any dose-dependent effects of phenylephrine on maternal cardiovascular stability and, if so, any impact on fetal outcome.



In this randomized, double-blind study, 75 women scheduled for elective cesarean delivery were allocated to receive a phenylephrine infusion at 25 μg/min, 50 μg/min, or 100 μg/min. This infusion was titrated to maintain maternal baseline systolic blood pressure (SBP), from induction of spinal anesthesia until delivery. The maternal cardiovascular variables recorded included heart rate (HR) and SBP. A suprasternal Doppler monitor measured CO and stroke volume, as well as measures of venous return (corrected flow time) and contractility, at baseline, and then every 5 minutes for 20 minutes after initiation of spinal anesthesia. Apgar scores and umbilical cord blood gases were recorded.



SBP control was satisfactory in all groups; however, the group receiving phenylephrine 100 μg/min required significantly higher doses to achieve arterial blood pressure control compared with the lower infusion rates. There were no significant differences in the number of times SBP decreased below 80% of baseline, or the numbers of boluses of ephedrine or phenylephrine required to maintain SBP above 80% of baseline. There were significant time and dose-dependent reductions in HR and CO with phenylephrine, such that HR and CO were seen to decrease with time in each group, and also with increasing concentrations of phenylephrine. Stroke volume remained stable throughout. Apgar scores and umbilical cord blood gases were similar among groups.



By infusing a higher concentration (100 μg/min), we subject the mother and fetus to a much higher dose of phenylephrine, with significant effects on maternal HR and CO (up to a 20% reduction). Future investigation is required to determine whether this reduction in maternal CO has detrimental effects when providing anesthesia for an emergency cesarean delivery for a compromised fetus.
Criterion validation of the rate of recovery, single alphanumeric measure, in patients with low back pain.

The aim of this study was to determine the criterion validity of patient rate of recovery with the Oswestry Disability Index (ODI) and the Numeric Pain Rating Scale (NPRS).



Associations between rate of recovery and ODI and pain were examined using a receiver operating characteristic (ROC) curve. Participants were dichotomized to ODI 50% change versus a <50% change. Pearson correlation coefficients were performed to determine the relationship between the continuous variables of rate of recovery and final ODI score at discharge. Spearman correlation coefficients were performed to determine the relationship between the continuous variable rate of recovery and ordinal variable final pain score at discharge.



ROC curve statistics suggest that a cut-point of greater than 82.5% on the self-report rate of recovery (sensitivity = 0.72, specificity = 0.71 and positive likelihood ratio = 2.44) corresponded to a 50% change on the ODI. The correlation between ODI final score and self-report rate of recovery was a moderate, -0.45 (p < 0.01). Cut-points on the self-reported rate of recovery ranged from 72.5% to 82.5% depending upon the definition of change in pain (≥2, ≥3 and ≥4 points) score or final pain score (<5/10, <4/10 and <3/10). The correlation between NPRS final score and self-report rate of recovery was -0.72 (p < 0.01). The correlation between NPRS change score and self-report rate of recovery was 0.42 (p < 0.01).



Patients reporting greater than or equal to 82.5% on rate of recovery are likely to have met a 50% change on the ODI. The moderate correlation between rate of recovery and ODI suggests that rate of recovery may capture a dimension of recovery in addition to the self-reported function in patients with low back pain. Both outcomes measures can be used to capture a more comprehensive evaluation of recovery from low back pain.
A randomised study of adjuvant chemotherapy after mantle radiotherapy in supradiaphragmatic Hodgkin's disease PS IA-IIB: a report from the Manchester lymphoma group.

One hundred and fourteen untreated patients with pathological stage (PS) IA-IIB supradiaphragmatic Hodgkin's Disease were randomised to mantle radiotherapy alone (55) or mantle radiotherapy followed by 6 courses of adjuvant chemotherapy with mustine, vinblastine, prednisolone and procarbazine- MVPP (59). Patients excluded were those outside the age range 16-65 years and those with massive mediastinal disease precluding laparotomy. Bulk disease was defined as a mass of lymph nodes measuring five centimetres or more in any axis. Mediastinal bulk was present if the ratio of the maximum width of mediastinal disease to the maximal chest diameter was more than one third. All patients achieved a complete remission. Median duration of follow-up was 62 months (range 16-97). The relapse free survival (RFS) was 81%; 69% for radiotherapy alone and 93% for adjuvant chemotherapy (P = 0.002). RFS was also shown to be adversely affected by B symptoms (P = 0.0003), bulk disease (P = 0.018), abnormal CXR (P = 0.037), and increasing stage (P = 0.039). Age, sex, histology, and number of sites involved had no significant effect upon RFS. A Cox multivariate analysis showed that only three variables had a significant adverse effect on RFS - radiotherapy alone, the presence of bulk disease, and B symptoms. The overall 5 year survival was 93% with no statistically significant difference between the two treatment groups (P = 0.54). Survival was adversely affected by three variables - B symptoms (P = 0.02), the presence of bulk disease (P = 0.002), and pathological stage (P = 0.05). High risk groups for relapse are those with bulk and B symptoms. This analysis has shown that RFS was significantly improved by adjuvant chemotherapy, but that overall survival was not.
Plasma nutrient biomarkers are associated with waist-to-height ratio in youth with type 1 diabetes.

Plasma fatty acids (FAs) and micronutrients have been associated with central obesity in adults; however, previous studies of these associations in adults have yielded mixed results. In addition, no comparable research has been conducted among youth with type 1 diabetes (T1D).



We investigated the cross-sectional and longitudinal associations between plasma nutrient biomarkers and waist-to-height ratio (WHtR) in youth with T1D.



These analyses included 1324 youth aged 3-20 y at T1D diagnosis with a baseline visit in the SEARCH (Search for Diabetes in Youth) Study and a subset of 1178 of these youth with a follow-up visit an average of 23 mo (range: 16-40 mo) after their baseline visit. Plasma phospholipid FAs and vitamins were measured, and estimated desaturase activities were calculated at baseline. Anthropometric measurements and diabetes-related assessments were collected at each visit. Multiple linear regression was used to examine the association between plasma nutrient biomarkers and WHtR.



In cross-sectional analysis, plasma palmitic acid (P = 0.004), dihomo-γ-linolenic acid (DGLA; P = 0.017) and Δ6 desaturase (D6D; P = 0.006) were positively correlated with WHtR after adjustment of confounders. Oleic acid (OA; P = 0.002), linoleic acid (LA; P = 0.015), Δ9 desaturase 18 (D9D-18; P = 0.027), and vitamin D (P < 0.0001) were negatively correlated with WHtR after adjustment. Weight status was an effect modifier (P < 0.05). In normal-weight youth, vitamin D (P = 0.003) was negatively associated with WHtR. In obese youth, stearic acid (P = 0.037), DGLA (P < 0.0001), and D6D (P < 0.0001) were positively associated and OA (P = 0.0008), D9D-18 (P = 0.0006), and vitamin D (P < 0.0001) were negatively associated with WHtR. In longitudinal analysis, baseline linoleic acid (P = 0.018), n-6:n-3 (ω-3:ω-6) FA ratio (P = 0.029), vitamin D (P = 0.003), and vitamin E (P < 0.0001) were negatively correlated with WHtR at follow-up only in obese participants.



In T1D youth, plasma FAs and vitamins are associated with WHtR and are modified by weight status. These associations are particularly marked in obese youth.
A Phase 1 study to evaluate the safety and immunogenicity of a recombinant HIV type 1 subtype C-modified vaccinia Ankara virus vaccine candidate in Indian volunteers.

A recombinant modified vaccinia Ankara virus vaccine candidate (TBC-M4) expressing HIV-1 subtype C env, gag, tat-rev, and nef-RT genes was tested in a randomized, double-blind, dose escalation Phase I trial in 32 HIV-uninfected healthy volunteers who received three intramuscular injections of TBC-M4 at 0, 1, and 6 months of 5 x 10(7) plaque-forming units (pfu) (low dosage, LD) (n = 12) or 2.5 x 10(8) pfu (high dosage, HD) (n = 12) or placebo (n = 8). Local and systemic reactogenicity was experienced by approximately 67% and 83% of vaccine recipients, respectively. The reactogenicity events were mostly mild in severity. Severe but transient systemic reactogenicity was seen in one volunteer of the HD group. No vaccine-related serious adverse events or events suggesting perimyocarditis were seen. A higher frequency of local reactogenicity events was observed in the HD group. Cumulative HIV-specific IFN-gamma ELISPOT responses were detected in frozen PBMCs from 9/11 (82%), 12/12 (100%), and 1/8 (13%) volunteers after the third injection of the LD, HD, and placebo groups, respectively. Most of the responses were to gag and env proteins (maximum of 430 SFU/10(6) PBMCs) persisting across multiple time points. HIV-specific ELISA antibody responses were detected in 10/11, 12/12, and 0/8 volunteers post-third vaccination, in the LD, HD, and placebo groups, respectively. No neutralizing activity against HIV-1 subtype C isolates was detected. TBC-M4 appears to be generally safe and well-tolerated. The immune response detected was dose dependent, modest in magnitude, and directed mostly to env and gag proteins, suggesting further evaluation of this vaccine in a prime-boost regimen.
Reboxetine versus methylphenidate in treatment of children and adolescents with attention deficit-hyperactivity disorder

Attention deficit-hyperactivity disorder (ADHD) is a common psychiatric diagnosis among children and adolescents. This study has been conducted to evaluate the efficacy and tolerability of reboxetine in comparison with methylphenidate in treatment of children and adolescents with ADHD. Thirty three children, 7–16 years of age, diagnosed with ADHD, participated in a 6-week, double-blind clinical trial with reboxetine (4–6 mg/d) and methylphenidate (20–50 mg/d) in two divided doses. The principal measure of the outcome was the Teacher and Parent ADHD Rating Scale. Patients were assessed by a child psychiatrist at baseline, 14, 28, and 42 days after the start of medication. No significant differences were observed between the two protocols on the Parent (P = 0.26) and Teacher (P = 0.97) ADHD Rating Scale scores and in treatment dropouts. A significant improvement in ADHD symptoms was observed over the 6 weeks of treatment for Parent ADHD Rating Scale (P < 0.001) and Teacher ADHD Rating Scale score in both groups (P < 0.001). The most common adverse effects reported with reboxetine were drowsiness and anorexia with mild to moderate severity. The study revealed that reboxetine may be beneficial in treatment of ADHD. Further studies are required to clarify the potential therapeutic effects on comorbid depression and anxiety and adverse effect profile.
A medication self-management program to improve adherence to HIV therapy regimens.

This study examined whether a self-management intervention based on feedback of adherence performance and principles of social cognitive theory improves adherence to antiretroviral dosing schedules. Forty-three individuals with HIV/AIDS who were starting or switching to a new protease inhibitor regimen were randomly assigned to be in a medication self-management program or usual care control group. The self-management program included skills development exercises, three monthly visits for medication consultations, and monthly feedback of adherence performance using electronic monitors on medication bottles. Participants also completed a 40-item questionnaire that measured self-efficacy to take medications, on schedule, in a variety of situations. Logistic regression analysis indicated that individuals in the self-management group were significantly more likely to take 80% or more of their doses each week than individuals in the control group (n=29, OR=7.8, 95% CI=2.2-28.1). Self-management training with feedback of adherence performance is a potentially useful model for improving adherence to complex regimens in HIV/AIDS care.
Effects of a brief office-based intervention to facilitate diabetes dietary self-management.

There is a pressing need for brief practical interventions that address diabetes management. Using a randomized design, we evaluated a medical office-based intervention focused on behavioral issues relevant to dietary self-management.



There were 206 adult diabetes patients randomized to usual care or brief intervention, which consisted of touchscreen computer-assisted assessment to provide immediate feedback on key barriers to dietary self-management, and goal setting and problem-solving counseling for patients. Follow-up components to the single session intervention included phone calls and interactive video or videotape instruction as needed.



Multivariate analyses of covariance revealed that the brief intervention produced greater improvements than usual care on a number of measures of dietary behavior (e.g., fewer calories from saturated fat, fewer high-fat eating habits and behaviors) at the 3-month follow-up. There were also significant differences favoring intervention on changes in serum cholesterol levels and patient satisfaction but not on glycosylated hemoglobin. The intervention effects were relatively robust across a variety of patient characteristics, the two participating physicians, and intervention staff members.



If the long-term results are equally positive and generalize to other setting, this intervention could provide a prototype for a feasible cost-effective way to integrate patient views and behavioral management into office-based care for diabetes.
Smoking during pregnancy and offspring externalizing problems: an exploration of genetic and environmental confounds.

Previous studies have documented that smoking during pregnancy (SDP) is associated with offspring externalizing problems, even when measured covariates were used to control for possible confounds. However, the association may be because of nonmeasured environmental and genetic factors that increase risk for offspring externalizing problems. The current project used the National Longitudinal Survey of Youth and their children, ages 4-10 years, to explore the relations between SDP and offspring conduct problems (CPs), oppositional defiant problems (ODPs), and attention-deficit/hyperactivity problems (ADHPs) using methodological and statistical controls for confounds. When offspring were compared to their own siblings who differed in their exposure to prenatal nicotine, there was no effect of SDP on offspring CP and ODP. This suggests that SDP does not have a causal effect on offspring CP and ODP. There was a small association between SDP and ADHP, consistent with a causal effect of SDP, but the magnitude of the association was greatly reduced by methodological and statistical controls. Genetically informed analyses suggest that unmeasured environmental variables influencing both SDP and offspring externalizing behaviors account for the previously observed associations. That is, the current analyses imply that important unidentified environmental factors account for the association between SDP and offspring externalizing problems, not teratogenic effects of SDP.
Functional and psychosocial effects of either a traditional dancing or a formal exercising training program in patients with chronic heart failure: a comparative randomized controlled study.

To compare the effects of traditional dancing with formal exercise training in terms of functional and cardiovascular benefits and motivation in patients with chronic heart failure.



Randomized controlled trial.



Sports Medicine Laboratory.



Fifty-one Greek male patients aged 67.1±5.5 years with chronic heart failure of New York Heart Association (NYHA) class II-III, participated in an eight-month study.



They were randomly assigned to either training with Greek traditional dances (group A, n=18), formal exercise training (group B, n=16) or a sedentary control group (group C, n=17).



At entry and the end of the study all patients underwent cardiopulmonary exercise testing, functional ability assessment and quality of life evaluations. The Intrinsic Motivation Inventory was also used to assess participants' subjective experience.



After training group A showed increased peak oxygen consumption by 33.8% (19.5 vs. 26.1 ml/kg/min, p<0.05) and B by 32.3% (19.5 vs. 25.8 ml/kg/min, p<0.05), maximal treadmill tolerance by 48.5% (p<0.05) and by 46.4% (p<0.05), and a decreased Slope of expired minute ventilation for carbon dioxide output (VE/VCO2) slope by 18% (p<0.05) and 19.5% (p<0.05), respectively. Trained patients revealed significant improvement in the quality of life indices. Intrinsic Motivation Inventory was increased only in group A by 26.2% (3.08 vs. 3.87, p<0.05).



Exercise training in chronic heart failure patients with Greek traditional dances led to functional and cardiovascular benefits similar to formal exercise training and to a higher level of motivation.