nils-herrmann/clean_scirepeval huggingface dataset:
Improved Early-Phase Insulin Response after Candesartan Treatment in Hypertensive Patients with Impaired Glucose Tolerance

As the effect of renin-angiotensin system (RAS) blockade on beta-cells in clinical situations remains unclear, new evidence has been presented that angiotensin-converting enzyme (ACE) inhibitors and angiotensin vertical line vertical line receptor blockers (ARBs) may delay or prevent the development of insulin resistance and diabetes through novel mechanisms. This study aimed to determine the effects of ARBs on insulin excretion by beta-cells. Hypertensive patients with impaired glucose tolerance were randomly divided into two groups: group A (n = 6), which received 8 mg/day of oral candesartan for three months, and controls (n = 6). Before and after administration, a 75 g oral glucose tolerance test was conducted to compare various parameters. No significant differences in age, body mass index (BMI), systolic blood pressure (SBP), diastolic blood pressure (DBP), fasting glucose, or fasting immunoreactive insulin (IRI) were identified between the groups before administration. After three months, there were no significant changes in BMI, SBP, and DBP for the controls and in BMI and DBP for group A. However, SBP was significantly decreased from 144 +/- 2.6 mmHg to 125 +/- 4.6 mmHg in group A. Insulinogenic index tended to be slightly decreased for controls, but was significantly increased from 0.32 +/- 0.0 to 0.47 +/- 0.1 for group A. No significant changes in HOMA-R were identified in either group. To the best of our knowledge, no previous studies have documented a RAS inhibitor improving early-phase insulin response; thus, the present study may be the first of its kind.
Impaired early- but not late-phase insulin secretion in subjects with impaired fasting glucose

Subjects with impaired fasting glucose (IFG) are at increased risk for type 2 diabetes. We recently demonstrated that IFG subjects have increased hepatic insulin resistance with normal insulin sensitivity in skeletal muscle. In this study, we quantitated the insulin secretion rate from deconvolution analysis of the plasma C-peptide concentration during an oral glucose tolerance test (OGTT) and compared the results in IFG subjects with those in subjects with impaired glucose tolerance (IGT) and normal glucose tolerance (NGT). One hundred and one NGT subjects, 64 subjects with isolated IGT, 24 subjects with isolated IFG, and 48 subjects with combined (IFG + IGT) glucose intolerance (CGI) received an OGTT. Plasma glucose, insulin, and C-peptide concentrations were measured before and every 15 min after glucose ingestion. Insulin secretion rate (ISR) was determined by deconvolution of plasma C-peptide concentration. Inverse of the Matsuda index of whole body insulin sensitivity was used as a measure of insulin resistance; 56 subjects also received a euglycemic hyperinsulinemic clamp. The insulin secretion/insulin resistance (disposition) index was calculated as the ratio between incremental area under the ISR curve (∆ISR[AUC]) to incremental area under the glucose curve (∆G[AUC]) factored by the severity of insulin resistance (measured by Matsuda index during OGTT or glucose disposal during insulin clamp). Compared to NGT, the insulin secretion/insulin resistance index during first 30 min of OGTT was reduced by 47, 49, and 74% in IFG, IGT, and CGI, respectively (all < 0.0001). The insulin secretion/insulin resistance index during the second hour (60–120 min) of the OGTT in subjects with IFG was similar to that in NGT (0.79 ± 0.6 vs. 0.72 ± 0.5, respectively, P = NS), but was profoundly reduced in subjects with IGT and CGI (0.31 ± 0.2 and 0.19 ± 0.11, respectively; P < 0.0001 vs. both NGT and IFG). Early-phase insulin secretion is impaired in both IFG and IGT, while the late-phase insulin secretion is impaired only in subjects with IGT.
Duodenal stenting for malignant gastric outlet obstruction: prospective study.

To evaluate the results of duodenal stenting for palliation of gastroduodenal malignant obstruction by using a gastric outlet obstruction score (GOOS).



A prospective, non-randomized study was performed at a tertiary center between August 2005 and April 2010. Patients were eligible if they had malignant gastric outlet obstruction (GOO) and were not candidates for surgical treatment. Medical history and patient demographics were collected at baseline. Scheduled interviews were made on the day of the procedure and 15, 30, 90 and 180 d later or unscheduled as necessary.



Fifteen patients (6 male, 9 female; median age 61 years) with GOO who had undergone duodenal stenting were evaluated. Ten patients had metastasis at baseline (66.6%) and 14 were unable to accept oral intake (93.33%), including 7 patients who were using a feeding tube. Laboratory data showed biliary obstruction in eight cases (53.33%); all were submitted to biliary drainage. Two patients developed obstructive symptoms due to tumor ingrowth after 30 d and another due to tumor overgrowth after 180 d. Two cases of stent migration occurred. A good response to treatment was observed, with a mean time of approximately 1 d (19 h) until toleration of a liquid diet and slightly more than 2 d for both soft solids (51 h) and a solid food/normal diet (55 h). The mean time to first failure to maintain liquid intake (GOOS ≥ 1) was 93 d. During follow-up, the mean time to first failure to maintain the previously achieved GOOS of 2-3 (solid/semi-solid food), considered technical failure, was 71 d. On the basis of oral intake a GOOS is defined: 0 for no oral intake; 1 for liquids only; 2 for soft solids only; 3 for low-residue or full diet.



Enteral stenting to alleviate gastroduodenal malignant obstruction improves quality of life in patients with limited life expectancy, which can be evaluated by using a GOO scoring system.
Correlations of alcohol consumption with related covariates and heritability estimates in older adult males over a 14- to 18-year period: the NHLBI Twin Study.

Consistent maximum-likelihood heritability estimates of consumption of alcoholic beverages were observed at three separate times during a 14- to 18-year period in adult twin males initially aged 42-56 years in 1969-1973. Log transformation of the average number of drinks/week of the returnees to all three examinations was examined relative to potential covariates representing both antecedents of drinking alcohol and consequences of alcohol consumption. Significant relationships were noted for 38 of the covariates at one or more of the separate examinations, including positive correlations with smoking, coffee consumption, high-density lipoprotein cholesterol, mean corpuscular volume, systolic blood pressure, uric acid and behavioral measures, and negative correlations with blood urea nitrogen, red blood cell count, tea consumption, and tricep skinfolds. Analysis of the average alcohol consumption adjusted for nine independent covariates selected from multiple stepwise regression resulted in a modest decline in maximum-likelihood heritability estimates compared with unadjusted data, but little difference from heritability estimates obtained when abstainers from alcohol (no alcoholic beverages consumed at all three examinations) were excluded. The most striking effect of omitting abstainers from alcohol was the decline in the intraclass correlations in dizygotic twins. Bivariate analyses of alcohol and individual covariates revealed the phenotypic correlation between alcohol consumption and a measure of hostility was primarily environmental, that for high-density lipoprotein, smoking and coffee drinking with alcohol was primarily genetic, and the phenotypic correlation between alcohol consumption and mean corpuscular volume had both significant genetic and environmental correlations.(ABSTRACT TRUNCATED AT 250 WORDS)
Relapse prevention in pediatric patients with ADHD treated with atomoxetine: a randomized, double-blind, placebo-controlled study.

Attention-deficit/hyperactivity disorder (ADHD) is typically treated over extended periods; however, few placebo-controlled, long-term studies of efficacy have been reported.



In a global multicenter study, children and adolescents who responded to an initial 12-week, open-label period of treatment with atomoxetine, a nonstimulant treatment for ADHD, were randomized to continued atomoxetine treatment or placebo for 9 months under double-blind conditions.



A total of 416 patients completed acute atomoxetine treatment and were randomized. At end point, atomoxetine was superior to placebo in preventing relapse defined as a return to 90% of baseline symptom severity (proportion relapsing: atomoxetine 65 of 292 [22.3%], placebo 47 of 124 [37.9%], p =.002). The proportion of patients with a 50% worsening in symptoms post-randomization was also lower on atomoxetine (atomoxetine 83 of 292 [28.4%], placebo 59 of 124 [47.6%], p <.001). Compared with patients in the placebo group, atomoxetine-treated patients had superior psychosocial functioning at end point. Discontinuations for adverse events were low in both groups, and tolerability was similar to that observed in acute treatment trials.



In patients who responded favorably to 12 weeks of initial treatment, atomoxetine was superior to placebo in maintaining response for the ensuing 9 months. This result supports the value of maintenance treatment with atomoxetine in patients with ADHD who respond to initial treatment.
Surgical Management of Carotid Body Tumors

Carotid body tumors (CBT) should be considered when evaluating every lateral neck mass. A retrospective study was conducted of 52 patients with 57 CBT. The surgical approach and complications were reviewed. All patients were operated on without preoperative embolization. Multifocal paraganglioma (PG) were detected in six cases. A succinate dehydrogenase subunit D (SDHD) mutation was discovered in four patients. Vascular peroperative complication occurred in one case. Vascular reconstruction was decided peroperatively in five cases (8.8%). Vascular reconstruction was 0% for Shamblin 1 or 2 tumors, but 28.5% for Shamblin 3. A postoperative nerve paresis was reported in 24 patients (42.1%) and vagal nerve paralysis persisted in four cases (7.01%). The rate of serious complications, e.g., permanent nerve palsy, preoperative and postoperative complications, was 14.03%; it was 2.3% for Shamblin 1 or 2 tumors and 35.7% for Shamblin 3. One patient had malignant PG with node metastasis and was not referred for radiotherapy. No recurrence or metastasis was reported after 6-year follow-up. Early surgical treatment is recommended in almost all patients after preoperative evaluation and detection of multifocal tumors. Surgical excision of small tumors was safe and without complication, but resection of Shamblin 3 tumors can be challenging. Routine preoperative embolization of carotid body paragangliomas is not required.
Safety, efficacy, and pharmacokinetics of adefovir dipivoxil in children and adolescents (age 2 to <18 years) with chronic hepatitis B.

This study investigated the efficacy, safety, and pharmacokinetics of adefovir dipivoxil (ADV) in children and adolescents with chronic hepatitis B (CHB). A total of 173 treatment-naive and treatment-experienced children with hepatitis B e antigen (HBeAg)+ CHB were randomized to ADV or placebo. Randomization was stratified by age (2 to <7 years; >7 to <12 years; >12 to <18 years) and prior treatment. Significantly more ADV-treated subjects aged 12 to <18 years achieved the primary efficacy endpoint (serum hepatitis B virus [HBV] DNA <1,000 copies/mL and normal alanine aminotransferase) compared to placebo-treated subjects (23% versus 0%; P = 0.007). In the younger groups, differences between ADV and placebo at the end of blinded treatment were not statistically significant. More ADV-treated subjects had HBeAg seroconversion: 18 of 113 (15.9%) versus three of 57 (5.3%) (but P = 0.051), and more met the combined endpoint of HBeAg seroconversion, HBV DNA <1,000 copies/mL and normal alanine aminotransferase (12/113 versus 0/57; P = 0.009). No subject developed an ADV-associated mutation that has been linked to HBV DNA rebound (that is, mutations rtN236T or rtA181V). ADV plasma concentrations were comparable across groups and within the target range. ADV treatment was well tolerated; no new safety issues were identified. Treatment-related adverse events were reported for 12% of ADV-treated and 10% of placebo-treated subjects. After 48 weeks of ADV treatment, antiviral efficacy in subjects ages 12 to <18 years with HBeAg+ CHB was similar to that observed in a study in adult treatment-naive subjects with HBeAg+ CHB. ADV was not different from placebo in subjects aged 2 to 11 years despite adequate plasma ADV exposure in all three age groups.



ADV showed significant antiviral efficacy in subjects aged 12 to 17 years with HBeAg+ CHB, but was not different from placebo in subjects aged 2 to 11 years.
Continental differences in clinical characteristics, management, and outcomes in patients hospitalized with worsening heart failure results from the EVEREST (Efficacy of Vasopressin Antagonism in Heart Failure: Outcome Study with Tolvaptan) program.

Our aim was to examine continental and regional differences in baseline characteristics and post-discharge clinical outcomes in the EVEREST (Efficacy of Vasopressin Antagonism in Heart Failure: Outcome Study with Tolvaptan) trial.



Continental and regional differences in clinical trials of acute heart failure syndromes (AHFS) have not been well studied.



We analyzed data from the EVEREST trial, which randomized 4,133 patients hospitalized for worsening (HF) and left ventricular ejection fraction < or =40% to oral tolvaptan, a vasopressin antagonist, or placebo and followed for a median of 9.9 months. Baseline characteristics, mortality, and outcomes were analyzed across North America (n = 1,251), South America (n = 688), Western Europe (564 patients), and Eastern Europe (n = 1,619).



There were major differences between the 4 groups in the severity, etiology, and management of HF. Unadjusted 1-year mortality and cardiovascular mortality/HF hospitalization were 30.4% and 52.5% in North America, 27.2% and 41.6% in South America, 27.1% and 47.3% in Western Europe, and 20.5% and 35.3% in Eastern Europe. After adjustment, South American patients had the highest overall mortality (hazard ratio: 1.42, 95% confidence interval: 1.15 to 1.76), while Eastern European patients had the lowest cardiovascular death and HF hospitalization rate (hazard ratio: 0.84, 95% confidence interval: 0.73 to 0.97), compared with patients in North America.



Major continental and regional differences in HF severity, etiology, and management exist among AHFS patients, resulting in varied post-discharge outcomes, despite pre-defined selection criteria. These differences should be taken into account when planning global trials in AHFS.
Establishing moderators and biosignatures of antidepressant response in clinical care (EMBARC): Rationale and design.

Remission rates for Major Depressive Disorder (MDD) are low and unpredictable for any given antidepressant. No biological or clinical marker has demonstrated sufficient ability to match individuals to efficacious treatment. Biosignatures developed from the systematic exploration of multiple biological markers, which optimize treatment selection for individuals (moderators) and provide early indication of ultimate treatment response (mediators) are needed. The rationale and design of a multi-site, placebo-controlled randomized clinical trial of sertraline examining moderators and mediators of treatment response is described. The target sample is 300 participants with early onset (≤30 years) recurrent MDD. Non-responders to an 8-week trial are switched double blind to either bupropion (for sertraline non-responders) or sertraline (for placebo non-responders) for an additional 8 weeks. Clinical moderators include anxious depression, early trauma, gender, melancholic and atypical depression, anger attacks, Axis II disorder, hypersomnia/fatigue, and chronicity of depression. Biological moderator and mediators include cerebral cortical thickness, task-based fMRI (reward and emotion conflict), resting connectivity, diffusion tensor imaging (DTI), arterial spin labeling (ASL), electroencephalograpy (EEG), cortical evoked potentials, and behavioral/cognitive tasks evaluated at baseline and week 1, except DTI, assessed only at baseline. The study is designed to standardize assessment of biomarkers across multiple sites as well as institute replicable quality control methods, and to use advanced data analytic methods to integrate these markers. A Differential Depression Treatment Response Index (DTRI) will be developed. The data, including biological samples (DNA, RNA, and plasma collected before and during treatment), will become available in a public scientific repository.
Development of a multi-dimensional scale for PDD and ADHD.

A novel assessment scale, the multi-dimensional scale for pervasive developmental disorder (PDD) and attention-deficit/hyperactivity disorder (ADHD) (MSPA), is reported. Existing assessment scales are intended to establish each diagnosis. However, the diagnosis by itself does not always capture individual characteristics or indicate the level of support required, since inter-individual differences are substantial and co-morbidity is common. The MSPA consists of 14 domains and each domain is rated by a nine-point quantitative scale. The clinical and behavioral features are projected onto a radar-chart, which facilitates understanding of the disorders both by the patients themselves and by those in their surroundings. We assessed 179 patients and analyzed features by six diagnostic subgroups, which showed relationships between features and diagnoses. The inter-rater reliability was satisfactory.
Perampanel in the treatment of partial seizures: Time to onset and duration of most common adverse events from pooled Phase III and extension studies

Perampanel (PER) is a novel noncompetitive AMPA-receptor antagonist approved in over 40 countries for treatment of partial seizures. The safety and tolerability of PER have been well-documented in three double-blind, randomized, placebo (PBO)-controlled Phase III studies and an open-label extension (OLE). This post hoc analysis evaluated the occurrence and characteristics of the most common treatment-emergent adverse events (TEAEs) associated with PER. Results from the Phase III studies were pooled; post hoc analyses on the double-blind phase and up to 1 year of the OLE were performed on the four most common TEAEs for which incidence was higher for PER than PBO. The four most common TEAEs were dizziness, somnolence, fatigue, and irritability. For most subjects in the Phase III double-blind studies, these TEAEs were observed during 6-week titration and were mild or moderate in severity. For severe AEs, no dose-response relationship was observed. Patients in the PBO group during Phase III (who therefore received their first PER treatment during OLE) experienced these TEAEs with incidence and timing similar to that of PER-treated patients in Phase III. The first onset of these TEAEs occurred during the early weeks of PER conversion in the OLE. After 6months and up to 1 year of PER treatment, low to no incidence of the first onset of the four TEAEs was observed. Post hoc analyses of data from pooled Phase III studies provide greater insight into occurrence/duration of TEAEs. Phase III double-blind and OLE data showed that dizziness, somnolence, fatigue, and irritability were the most common TEAEs reported by patients taking PER. Additionally, these results suggest consistency between studies in patient responses to onset of these TEAEs. Although concomitant antiepileptic drugs (AEDs) might be predicted to affect development of TEAEs in patients taking PER, an effect was not observed in this analysis. The low incidence of TEAEs in these studies provides additional support for long-term PER treatment.
Phase II study of gemcitabine and cisplatin as first-line chemotherapy in inoperable biliary tract carcinoma.

The prognosis for patients with unresectable biliary tract cancer is poor and existing chemotherapy is relatively ineffective. Therefore, a need exists for new, effective chemotherapeutic regimens. The aim of this study was to determine the efficacy and safety profile of gemcitabine plus cisplatin in patients with unresectable biliary tract cancer (cholangiocarcinoma) and gall bladder cancer.



From December 2000 to July 2002, 43 patients received gemcitabine 1250 mg/m(2) in a 30-min i.v. infusion on d1, 8 and cisplatin 75 mg/m(2) in a 2-h i.v. infusion on d1 (with appropriate hydration), every 3 weeks.  Normal hematologic parameters and creatinine levels; serum bilirubin < 5 mg/dl.



Forty-three patients enrolled; 40 were assessable (three patients were not assessable due to incomplete treatment; they chose to discontinue chemotherapy after the first cycle). There were 23 males and 17 females, median age 50 years (range 31-69), median Karnofsky PS 80%. Tumor types: cholangiocarcinoma (39), gall bladder cancer (1). Median number of chemotherapy courses was four (range 1-8). Overall response rate was 27.5% (PR in 11 pts), with 32.5% SD and/or minor response. Median survival time was 36 weeks. Grade 3 hematologic toxicity: anemia (4.33%), leukopenia (1.73%). Non-hematologic toxicity (i.e. rash, nausea, vomiting, neuropathy and myalgia) ranged from mild to moderate.



Gemcitabine plus cisplatin is active in biliary tract carcinoma. These data warrant further investigation of single-agent gemcitabine versus gemcitabine plus cisplatin or its derivative, i.e. oxaliplatin.
Manipulation of host resistance in cancer therapy

The notion that malignant cells may be subject to control by the immunological network of the host has developed basically from studies of the immune rejection of rodent tumours, particulary those induced with chemical carcinogens or oncogenic viruses [15, 25, 98]. In one series of studies reported some 25 to 30 years ago, it was established that sarcomas induced by polycyclic hydrocarbon carcinogens in rodents of inbred (syngeneic) strains grew progressively following transplantation into compatible recipients [3, 36, 80]. However, pre-immunization of normal animals with tumour cells treated so as to restrict their progressive growth led to the development of a specific tumour immunity, so that a subsequent challenge with cells of the immunizing tumour was rejected. The repertoire of tumours in which there is conclusive evidence for the expression of antigens which can be manipulated to produce tumour rejection responses was rapidly expanded following these early studies. It now includes tumours of many types including carcinomas and sarcomas induced with a broad spectrum of chemical carcinogens , many of these belonging to the classes (polycyclic hydrocarbons, nitrosamines, amino azo dyes, and aromatic amines) which are known, or suspected to be, human carcinogens. Rodent tumours induced with DNAand RNA-containing oncogenic viruses have also been shown to express antigens able to induce turnout rejection [41, 50]. Recently tumours induced with UV-radiation also were shown to express antigens which elicit tumour rejection [57]. Faced with this wealth of evidence from rodent tumour studies that the adaptive immune system of the host can respond to tumours, it is not surprising that consideration has been given over the past 10 years or more to the possibility that specific immunotherapy may be introduced for cancer treatment. This approach initially received encouragement from early studies reporting that administration of vaccines containing radiation attenuated leukaemia cells with BCG as an immunostimulant produced a therapeutic response in acute lymphoblastic leukaemia [60]. Also in vitro cytotoxicity tests with blood lymphocytes from cancer patients