nils-herrmann/clean_scirepeval huggingface dataset:
Fibrin-Sealant-Delivered Cisplatin Chemotherapy Versus Cisplatin Hyperthermic Intraperitoneal Perfusion Chemotherapy for Locally Advanced Gastric Cancer Without Peritoneal Metastases: A Randomized Phase-II Clinical Trial with a 40-Month Follow-up

A new intraoperative cisplatin administration method for patients with locally advanced gastric cancer (AGC) and without peritoneal metastasis, fibrin-sealant-delivered cisplatin chemotherapy, was reported, and its safety, pharmacokinetics, and efficacy were compared with cisplatin hyperthermic intraperitoneal perfusion chemotherapy. Forty-two AGC patients were randomly divided into 2 groups: fibrin-sealant-delivered cisplatin chemotherapy (FS) (n = 21) and cisplatin hyperthermic intraperitoneal perfusion chemotherapy (CHIC) (n = 21). Both groups received 120 mg cisplatin after complete cytoreductive surgery. At different time points, cisplatin concentrations in patients’ sera and urine samples were measured to determine time-dependent maximal concentration (Cmax) and the area under the curve (AUC). The primary and secondary end-points were overall survival (OS) and safety profiling, respectively. Occurrence of grade-3 to grade-4 liver or kidney dysfunction was less frequent in the FS group than in the CHIC group (28.6 % vs 47.6 %). Cisplatin Cmax and AUC for the serum and urine of the FS patients were significantly lower than that of the CHIC patients. Elimination half-life of cisplatin in the FS group was significantly longer than in the CHIC group (24.1 h vs 14.2 h). After a median follow-up of 40 months, 1-, 2-, and 3-years OS were 90.5 %, 71.4 %, and 61.9 % in the FS group, and 61.9 %, 47.6 %, and 42.8 % in the CHIC group, respectively. The median OS was 35.9 months in the FS group and 29.1 months in the CHIC group. Fibrin-sealant-delivered cisplatin chemotherapy was as effective and had a favorable pharmacokinetic profile with similar survival outcomes as cisplatin hyperthermic intraperitoneal perfusion chemotherapy following complete cytoreductive surgery of locally advanced GC without peritoneal metastases.
Impact of drug policy on regional trends in ezetimibe use.

Ezetimibe use has steadily increased in Canada during the past decade even in the absence of evidence demonstrating a beneficial effect on clinical outcomes. Among the 4 most populated provinces in Canada, there is a gradient in the restrictiveness of ezetimibe in public-funded formularies (most to least strict: British Columbia, Alberta, Quebec, and Ontario). The effect of formulary policy on the use of ezetimibe over time is unknown.



We conducted a population-level cohort study using Intercontinental Marketing Services Health Canada's data from June 2003 to December 2012 to examine ezetimibe use in these 4 provinces to better understand the association between use and formulary restrictiveness. We found regional variations in the patterns of ezetimibe use. From June 2003 to December 2012, British Columbia (most restrictive) had the lowest monthly increasing rate from $261 to $21 926 ($190/100 000 population/mo), whereas Ontario (least restrictive) had the most rapid monthly increase from $223 to $74 030 ($ 647/100 000 population/mo), and Quebec from $130 to $59 690 ($522/100 000 population/mo) and Alberta from $356 to $ 37 604 ($327/100 000 population/mo) were intermediate (P<0.001).



Ezetimibe use remains common, increasing during the past decade. Use steadily increased in provinces with the most lenient formularies. In contrast, use was lower, plateauing since 2008 in British Columbia and Alberta, which have more restrictive formularies. The gradient in ezetimibe use was related to variability in restrictiveness of the provincial formularies, illustrating the potential of a policy response gradient that may be used to more effectively manage medication use.
Relation between headaches from oral contraceptives and development of endometrial arterioles.

The incidence of headaches during the first year on oral cotraceptives corrleates closely with the incidence of well-developed arterioles in endometrial biopsy specimens. This relationship appears to depend on the ratio between progestogenic and oestrogenic components of the pill as well as the particular steroids. Therefore endometrial biopsies are useful for assessing the vascular response to an oral contraceptive and also provide a short cut to clinical evaluation of new formulations.
Continuous variable control approach for home care crew scheduling

The home care crew scheduling problem (HCCSP) is defined as a dynamic routing and scheduling problem with caretakers' fixed appointments, and therefore has many similarities with the vehicle routing problem with time windows. Considering frequent demand changes regarding resource priorities, appointment alterations, and time windows in HCCSP, the control theoretic approach with discrete event distributed simulation provide substantial benefits by offering real-time response to demand changes. We develop dynamic models for HCCSP with dynamic patient appointments, and explain dynamics that span from controlling crew work times to home-visit scheduling. Also, the real-time feedback control algorithm is proposed to solve HCCSP, where it is performed based on the time-scaled approach that possibly eliminates the need for directly synchronizing events and thereby eliminates the complexity associated with discrete event distributed simulation approaches.
First-line treatment with bortezomib rapidly stimulates both osteoblast activity and bone matrix deposition in patients with multiple myeloma, and stimulates osteoblast proliferation and differentiation in vitro

The aim of the study was to investigate the effect of bortezomib on osteoblast proliferation and differentiation, as well as on bone matrix deposition for the first time in bisphosphonate-naïve, previously untreated patients with myeloma.



Twenty newly diagnosed patients received four cycles of bortezomib treatment, initially as monotherapy and then combined with a glucocorticoid from cycle two to four. Bone remodeling markers were monitored closely during treatment. Furthermore, the effects of bortezomib and a glucocorticoid on immature and mature osteoblasts were also studied in vitro.



Treatment with bortezomib caused a significant increase in bone-specific alkaline phosphatase and pro-collagen type I N-terminal propeptide, a novel bone formation marker. The addition of a glucocorticoid resulted in a transient decrease in collagen deposition. In vitro bortezomib induced osteoblast proliferation and differentiation. Differentiation but not proliferation was inhibited by glucocorticoid treatment.



Bortezomib used as first-line treatment significantly increased collagen deposition in patients with multiple myeloma and osteolytic lesions, but the addition of a glucocorticoid to the treatment transiently inhibited the positive effect of bortezomib, suggesting that bortezomib may result in better healing of osteolytic lesions when used without glucocorticoids in patients that have obtained remission with a previous therapy. The potential bone-healing properties of single-agent bortezomib are currently being explored in a clinical study in patients who have undergone high-dose therapy and autologous stem cell transplantation.
Leksell gamma knife radiosurgery for cerebral arteriovenous malformations in pediatric patients

The Verona neurosurgical group provides us with a very important contribution regarding the results of GK surgery in pediatric arteriovenous malformations (AVM). Based on one of the largest studies on AVM radiosurgery in pediatric patients, they report a high rate of success and a very limited number of side effects. More importantly, the factors influencing the outcome have been analyzed. The volume of the nidus turns out to be, as previously reported, a major determinant. Most of the time, multimodality treatment is useful in difficult cases. We agree with the authors that new bleeding is more frequent in children. Thus, in small AVMs in functional areas, short-term complete obliteration with angiographic control must be the goal. We agree with the authors that when the goal can be reached with radiosurgery alone, previous attempts at endovascular reduction are not beneficial. We must congratulate the authors on this remarkably clear and well-presented work. This commentary refers to the article http:// dx.doi.org/10.1007/s00381-004-1049-5
Use and misuse of serum troponin assays in pediatric practice.

Cardiac troponin (cTn) is instrumental in screening and diagnosing myocardial ischemia in adults. However, the role of cTn screening in the pediatric population is less clear. The purpose of this study was to evaluate the current clinical practice, diagnostic and prognostic value, and resource utilization associated with cTn assays in the pediatric population. A multicenter, retrospective review of all cTn assays performed on patients aged ≤18 years from January 2003 to December 2010 in the Intermountain Healthcare system was conducted. Data collected included patient demographics, location, presenting symptoms, provisional and discharge diagnoses, additional tests, clinical outcomes (hospitalization days, ventilation, and death), and patient charges. During the study period, cTn assays were performed on 3,497 pediatric patients. The most common presenting diagnoses were chest pain (40%), trauma (11%), and poisoning or drug overdose (9%). Irrespective of diagnosis, elevated cTn was associated with an increased rate of hospitalization, ventilation, and death. Overall, 12% of patients had elevated cTn. Of the patients with chest pain, 4% had elevated cTn, 53% of whom were diagnosed with myopericarditis. In the myopericarditis group, 66% presented with fever, and 98% had abnormal electrocardiographic findings. For patients presenting with chest pain, approximately $162,000 was spent per positive result. In conclusion, cTn screening has strong prognostic value in pediatric patients, even in noncardiac diagnoses such as trauma or drug overdose. However, cTn screening in pediatric patients with chest pain provides minimal benefits and is associated with increased resource utilization, unless patients have constitutional symptoms, such as fever and/or electrocardiographic abnormalities.
Gender-related differences of diabetic patients undergoing percutaneous coronary intervention with drug-eluting stents: a real-life multicenter experience.

Gender-based differences in diabetic patients are understudied in the field of percutaneous coronary intervention (PCI) with drug-eluting stents.



Data were obtained from a multicenter registry of 2420 consecutive patients with diabetes mellitus (DM) who underwent PCI with paclitaxel- or sirolimus-eluting stents between 2003 and 2009. Among them, 679 (28.1%) women were compared to 1741 (71.9%) men in terms of clinical aspects and major adverse cardiac events (MACE), including all-cause death, myocardial infarction (MI) and target lesion revascularization (TLR). Target vessel revascularization (TVR) and any revascularization were also reported.



Women were less numerous, older, used more insulin and showed more tortuous coronary arteries, while men were more frequently smokers and received larger stents. At the median follow-up of 24.3 months (interquartile range 12.3-39.7), MACE, TVR and any revascularization did not significantly differ between females and males (19.9% vs 18.7%, 12.2% vs 13.4%, 14.1% vs 15.1%, respectively). At multivariable analysis of the overall cohort, female gender was not a predictor of MACE (hazard ratio [HR] 1.02, 95% confidence interval [CI] 0.92-2.36, p=0.11), death (HR 1.04, 95% CI 0.84-1.24, p=0.86), MI (HR 1.48, 95% CI 0.92-2.36, p=0.11), and TLR (HR 1.14, 95% CI 0.85-1.52, ).



In this registry of diabetic patients treated by drug-eluting stents, women were less represented, older and needed more insulin compared to men who, on the other hand, received larger stents. Gender-related outcomes were similar and female sex did not predict MACE.
Telaprevir with peginterferon and ribavirin for treatment-naive patients chronically infected with HCV of genotype 1 in Japan.

To evaluate the efficacy and safety of telaprevir in combination with peginterferon-α2b (PEG-IFN) and ribavirin (RBV) in patients with chronic hepatitis C.



In a multi-center randomized clinical trial in Japan, on patients infected with HCV of genotype 1, 126 patients were assigned to telaprevir for 12 weeks along with PEG-IFN and RBV for 24 weeks (Group A), while 63 to PEG-IFN and RBV for 48 weeks (Group B).



HCV RNA disappeared more swiftly in patients in Group A than B, and the frequency of patients without detectable HCV RNA at week 4 (rapid virological response (RVR)) was higher in Group A than B (84.0% vs. 4.8%, p <0.0001). Grade 3 and 4 skin disorders, including Stevens-Johnson syndrome and drug rashes with eosinophilia and systemic symptoms, as well as Grade 3 anemia (<8.0 g/dl), occurred more frequently in Group A than B (skin disorders, 11.9% vs. 4.8%; anemia, 11.1% vs. 0.0%). The total RBV dose was smaller in Group A than B (47.0% vs. 77.7% of the target, p <0.0001). Despite these drawbacks, sustained virological response (SVR) was achieved more frequently in Group A than B (73.0% vs. 49.2%, p=0.0020).



Although the triple therapy with telaprevir-based regimen for 24 weeks resulted in more adverse events and less total RBV dose than PEG-IFN and RBV for 48 weeks, it was able to achieve higher SVR within shorter duration by carefully monitoring adverse events and modifying the RBV dose as required.
Mental health of postgraduate orthodontic students in India: a multi-institution survey.

The aim of this study was to evaluate the mental health of postgraduate orthodontic students in India by assessing the extent of three common negative affective states: depression, anxiety, and stress. Three hundred and thirty postgraduate students from thirty-two dental colleges across India anonymously completed the short version of the Depression Anxiety Stress Scale (DASS21). The statistical analysis included summary statistics, nonparametric tests for intergroup comparisons, and logistic regressions to evaluate the influence of age, gender, year of study, and marital status on these mental states. In comparison to the general population, the students experienced mildly elevated levels of depression and anxiety (11±5.1 and 8.2±4.1, respectively) and a moderately elevated level of psychological stress (22±5.2). A moderate or higher level of coexisting symptoms of all three affective states was seen in 15.8 percent of the students. Female students reported a higher level of depression than males and were two and half times more likely to experience depression to a moderate or higher level. First-year students exhibited lower levels in all three states than those in the second and third years and had lower odds than third-year students of developing a moderate or higher level of any of the three affective states. Marriage had a significant buffering potential against all these states. The results clearly indicate a suboptimal level of mental health in these postgraduate students of the specialty and the need to improve their mental resilience and the academic climate.
The Impact of Perceived Treatment Assignment on Smoking Cessation Outcomes Among African-American Smokers

The double-blind placebo-controlled design is commonly considered the gold standard in research methodology; however, subject expectation bias could subvert blinding. The primary aim of this study was to examine the impact of expectation bias. Specifically, we examined perceived treatment assignment on smoking cessation outcome rates among participants enrolled in a clinical trial of bupropion (150 mg SR, BID). Analyses were conducted on data collected during “Kick It at Swope,” a double-blind, placebo-controlled, randomized trial of 600 African-American smokers. Chi-square and multiple logistic regression analyses were used to examine the impact of perception of assignment on treatment effect and cotinine-verified smoking abstinence rates. Participants were predominantly middle-aged (mean 44.7, SD 11.2), African-American women (68.6%), who smoked 19 CPD (SD = 8.1). Most had completed at least a high school education or GED (51.6%), and 55% had a monthly family income <$1,800. At week 6 (end of treatment) and week 26 (end of study), participants were asked to report their perceived treatment group assignment. Self-reported abstinence (weeks 6 and 26) was confirmed using CO and cotinine biochemical verification. After adjusting for actual treatment assignment, age and baseline cotinine, participants who perceived being assigned to bupropion vs. placebo were more likely to be abstinent at weeks 6 (OR = 2.07, 95% CI: 1.29 to 3.33, p = 0.002) and 26 (OR = 1.85, 95% CI: 1.05 to 3.24, p = 0.032). Results support previous research that expectation bias associated with judgment of treatment assignment is a strong predictor of outcome and confirms this relationship in a smoking cessation trial using bupropion SR among African-American smokers.
Evaluation of atomoxetine for first-line treatment of newly diagnosed, treatment-naïve children and adolescents with attention deficit/hyperactivity disorder.

To test the hypothesis that first-line treatment with atomoxetine provides superior efficacy than placebo for up to 12 weeks in improving the symptoms of Attention Deficit/Hyperactivity Disorder (ADHD).



This double-blind, randomized, placebo-controlled, parallel clinical trial included 151 treatment-naïve children (n = 113) and adolescents (n = 38) with newly diagnosed (< or =3 months) ADHD. Atomoxetine dose was uptitrated from 0.5 to 1.2 mg/kg/day after two weeks. Outcome assessments included the ADHD Rating Scale-IV-Parent-reported Investigator-rated (ADHDRS-IV-Parent:Inv), the Clinical Global Impression of Severity of ADHD (CGI-ADHD-S), and the incidence of adverse events. Mixed-model repeated measures analysis was used to compare scale score changes between groups.



Most patients were male (79.2%), of caucasian origin (96.0%) and severely ill (72.5%). Their mean age was 10.3 years. Atomoxetine-treated patients showed greater reductions from baseline to week 12 of total ADHDRS-IV-Parent:Inv score than placebo-treated patients (least square mean difference: -7.9 [95% CI: -11.0 to -4.8], corresponding to a large effect size of 0.8). Between-group mean differences increased progressively with treatment exposure from week 6 to 12 (-2.7 [-4.9 to -0.6] for total and -1.6 [-2.9 to -0.3] for inattention scores). At the end of the study, 50% of atomoxetine-treated patients (14% with placebo) showed a reduction > or =40% in total ADHDRS-IV-Parent:Inv score, and only 29% (46% with placebo) were severely ill (by CGI-ADHD-S). Treatment-related adverse events were significantly more frequent with atomoxetine (65.0%) than with placebo (37.3%), the most frequent being decreased appetite and somnolence. Only one case of decreased appetite was rated as severe. No patient discontinued treatment because of adverse events.



A continued improvement of symptoms is expectable until 12 weeks in treatment-naïve ADHD patients treated with atomoxetine as first-line medication. Chief limitations are the small, national sample size and the absence of data beyond the 12-week time-point.
Growth-differentiation factor-15 for early risk stratification in patients with acute chest pain

Growth-differentiation factor-15 (GDF-15) has emerged as a biomarker of increased mortality and recurrent myocardial infarction (MI) in patients diagnosed with non-ST-elevation acute coronary syndrome. We explored the usefulness of GDF-15 for early risk stratification in 479 unselected patients with acute chest pain.



Sixty-nine per cent of the patients presented with GDF-15 levels above the previously defined upper reference limit (1200 ng/L). The risks of the composite endpoint of death or (recurrent) MI after 6 months were 1.3, 5.1, and 12.6% in patients with normal (<1200 ng/L), moderately elevated (1200-1800 ng/L), or markedly elevated (>1800 ng/L) levels of GDF-15 on admission, respectively (P < 0.001). By multivariable analysis that included clinical characteristics, ECG findings, peak cardiac troponin I levels within 2 h (cTnI(0-2 h)), N-terminal pro-B-type natriuretic peptide, C-reactive protein, and cystatin C, GDF-15 remained an independent predictor of the composite endpoint. The ability of the ECG combined with peak cTnI(0-2 h) to predict the composite endpoint was markedly improved by addition of GDF-15 (c-statistic, 0.74 vs. 0.83; P < 0.001).



GDF-15 improves risk stratification in unselected patients with acute chest pain and provides prognostic information beyond clinical characteristics, the ECG, and cTnI.
Nutrition intervention using an eicosapentaenoic acid (EPA)-containing supplement in patients with advanced colorectal cancer. Effects on nutritional and inflammatory status: a phase II trial

The aim of the study was to assess the impact of an eicosapentanoic acid-containing protein and energy dense oral nutritional supplement (EPA-ONS) on nutritional and inflammatory status, quality of life (QOL), plasma phospholipids (PPL) and cytokine profile, tolerance of irinotecan-containing chemotherapy and EPA-ONS in patients with advanced colorectal cancer (CRC) receiving chemotherapy. Patients with advanced CRC having one prior chemotherapy regimen received 480 ml of EPA-ONS daily for 3 weeks before commencing chemotherapy with folinic acid, 5-fluorouracil, irinotecan (FOLFIRI), and continued for 3 cycles of treatment (9 weeks). All assessments including weight, body composition, C-reactive protein (CRP), QOL, dietary intake, PPL and cytokine analyses were performed at baseline, 3 and 9 weeks. Twenty-three patients were enrolled, 20 completed 3 weeks, and 15 completed 9 weeks. The mean EPA-ONS intake was 1.7 tetrapaks (408 ml) daily. There was a significant increase in mean weight (2.5 kg) at 3 weeks (p = 0.03). Lean body mass (LBM) was maintained. Protein and energy intake significantly decreased after the commencement of chemotherapy (protein p = 0.003, energy p = 0.02). There was a significant increase in energy levels (p = 0.03), whilst all other QOL measures were maintained. PPL EPA levels increased significantly over the first 3 weeks. Mean CRP increased by 14.9 mg/L over the first 3 weeks (p = 0.004), but decreased to baseline levels by the end of the trial. There was a significant correlation between plasma IL-6 and IL-10 concentrations and survival, and between IL-12 and toxicity. Dietary counseling and the provision of EPA-ONS may result in maintenance of nutritional status and QOL, however randomized trials are required to evaluate the impact of EPA on toxicity from chemotherapy.