nils-herrmann/clean_scirepeval huggingface dataset:
Beta-cell function assessment from modelling of oral tests: an effective approach.

The quantitative study of beta-cell function has relied on mathematical models for almost 40 years. During the last decades, the initial elaborate models have been simplified with the aim of obtaining mathematical methods suitable for the assessment of beta-cell function in an individual from an intravenous test. In more recent times, modelling methods have been proposed for analysing oral glucose tolerance tests or meal tests. In this review, we describe these methods with particular emphasis on an approach we have developed. We discuss the relevance of potentiation of insulin secretion in an oral glucose test, which our model has reintroduced after the historical models. We provide evidence on the validity of the method and illustrate significant applications. We emphasize the importance of quantifying beta-cell function through multiple indices and highlight how our approach has provided new insight on the relationships between beta-cell function and insulin sensitivity and on the role of beta-cell function in glucose intolerance and diabetes.
Understanding physicians’ behavior toward alerts about nephrotoxic medications in outpatients: a cross-sectional analysis

Although most outpatients are relatively healthy, many have chronic renal insufficiency, and high override rates for suggestions on renal dosing have been observed. To better understand the override of renal dosing alerts in an outpatient setting, we conducted a study to evaluate which patients were more frequently prescribed contraindicated medications, to assess providers' responses to suggestions, and to examine the drugs involved and the reasons for overrides.



We obtained data on renal alert overrides and the coded reasons for overrides cited by providers at the time of prescription from outpatient clinics and ambulatory hospital-based practices at a large academic health care center over a period of 3 years, from January 2009 to December 2011. For detailed chart review, a group of 6 trained clinicians developed the appropriateness criteria with excellent inter-rater reliability (κ=0.93). We stratified providers by override frequency and then drew samples from the high- and low-frequency groups. We measured the rate of total overrides, rate of appropriate overrides, medications overridden, and the reason(s) for override.



A total of 4120 renal alerts were triggered by 584 prescribers in the study period, among which 78.2% (3,221) were overridden. Almost half of the alerts were triggered by 40 providers and one-third was triggered by high-frequency overriders. The appropriateness rates were fairly similar, at 28.4% and 31.6% for high- and low-frequency overriders, respectively. Metformin, glyburide, hydrochlorothiazide, and nitrofurantoin were the most common drugs overridden. Physicians' appropriateness rates were higher than the rates for nurse practitioners (32.9% vs. 22.1%). Physicians with low frequency override rates had higher levels of appropriateness for metformin than the high frequency overriders (P=0.005).



A small number of providers accounted for a large fraction of overrides, as was the case with a small number of drugs. These data suggest that a focused intervention targeting primarily these providers and medications has the potential to improve medication safety.
The effects of concentrated barley beta-glucan on blood lipids in a population of hypercholesterolaemic men and women.

Barley, like oats, is a rich source of the soluble fibre beta-glucan, which has been shown to significantly lower LDL-cholesterol (LDL-C). However, barley foods have been less widely studied. Therefore, we evaluated the LDL-C-lowering effect of a concentrated barley beta-glucan (BBG) extract as a vehicle to deliver this potential health benefit of barley. In a 10-week blinded controlled study, subjects were randomized to one of four treatment groups or control. Treatment groups included either high molecular weight (HMW) or low molecular weight (LMW) BBG at both 3 and 5 g doses. Treatment was delivered twice per day with meals in the form of two functional food products: a ready-to-eat cereal and a reduced-calorie fruit juice beverage. Levels of total cholesterol, LDL-C, HDL-cholesterol (HDL-C), and TAG were determined at baseline and after 6 weeks of treatment. The study group comprised 155 subjects. All treatments were well tolerated and after 6 weeks of treatment the mean LDL-C levels fell by 15 % in the 5 g HMW group, 13 % in the 5 g LMW group and 9 % in both the 3 g/d groups, versus baseline. Similar results were observed for total cholesterol. HDL-C levels were unchanged by treatment. Concentrated BBG significantly improves LDL-C and total cholesterol among moderately dyslipidaemic subjects. Food products containing concentrated BBG should be considered an effective option for improving blood lipids.
Robust antiviral activity of R1626, a novel nucleoside analog: a randomized, placebo-controlled study in patients with chronic hepatitis C.

The nucleoside analog R1479 is a potent and highly selective inhibitor of nonstructural protein 5B-directed hepatitis C virus (HCV) replication in vitro. R1626, a tri-isobutyl ester prodrug of R1479, was developed to increase bioavailability and improve antiviral activity. A multicenter, observer-blinded, randomized, placebo-controlled, multiple ascending dose, phase 1b study was designed to evaluate the safety, pharmacokinetics, and antiviral activity and to potentially identify the maximum tolerated dose of R1626 in patients with chronic hepatitis C. Forty-seven treatment-naïve patients infected with HCV genotype 1 were treated with R1626 orally at doses of 500 mg, 1500 mg, 3000 mg, or 4500 mg or placebo twice daily for 14 days with 14 days of follow-up. Safety, tolerability, pharmacokinetics, and antiviral activity were assessed. Doses up to and including 3000 mg twice daily were well tolerated after 14 days of treatment. There was an increase in frequency of adverse events at the highest dose (4500 mg). Reversible mild to moderate hematological changes were observed with increasing doses. R1626 was efficiently converted to R1479, with dose-proportional pharmacokinetics observed over the entire dose range. The pharmacokinetics of R1479 were linear over the dose range evaluated. Dose-dependent and time-dependent reductions in HCV RNA were observed. Mean decreases (median; range) in viral load after 14 days of treatment with doses of 500, 1500, 3000, and 4500 mg were 0.32 (0.22; 0.01-0.71), 1.2 (0.8; 0.49-2.46), 2.6 (2.7; 1.27-3.93) and 3.7 (4.1; 2.15-4.39) log(10), respectively. No resistance to R1479 was observed after 14 days of treatment with R1626.



These data support further studies of R1626 in combination with peginterferon alfa-2a and ribavirin for the treatment of patients with chronic HCV infection.
Pharmacodynamic effects during the transition between cangrelor and ticagrelor.

This study sought to determine pharmacodynamic effects during transition from intravenous cangrelor to oral ticagrelor and from oral ticagrelor to intravenous cangrelor.



Cangrelor is an intravenous antagonist of P2Y12 and its use will require transition to and from oral agents.



Patients (n = 12) with stable coronary artery disease who were taking aspirin 81 mg daily were recruited. On study day 1, they received a bolus plus 2-h infusion of cangrelor plus a 180-mg dose of ticagrelor at either 0.5 h (n = 6) or 1.25 h (n = 6). Pharmacodynamic effects (light transmission platelet aggregation in response to 20 and 5 μmol/l adenosine diphosphate, VerifyNow, P2Y12 assay (Accumetrics, San Diego, California), vasodilator-stimulated phosphoprotein index, and flow cytometry) were assessed during and after the cangrelor infusion. Patients took 90 mg of ticagrelor twice daily for either 6 (n = 6) or 7 (n = 6) doses. On study day 5, pharmacodynamic effects were assessed before and during a bolus plus 2-h infusion of cangrelor.



During cangrelor infusion, extensive inhibition of platelet function reflected by limited residual platelet reactivity was apparent. After cangrelor was stopped, the antiplatelet effects of ticagrelor were preserved despite a modest increase in platelet reactivity.



Ticagrelor given before or during infusion of cangrelor did not attenuate the pharmacodynamic effects of cangrelor. The pharmacodynamic effects of ticagrelor were preserved when ticagrelor was given during infusion of cangrelor. Consistent with the reversible binding of ticagrelor, this oral P2Y12 antagonist can be administered before, during, or after treatment with cangrelor.
Vasopressin V 2-Receptor Blockade With Tolvaptan in Patients With Chronic Heart Failure Results From a Double-Blind , Randomized Trial

In this study, we evaluated the effects of tolvaptan (OPC-41061), a novel, oral, nonpeptide vasopressin V2-receptor antagonist in patients with chronic heart failure (CHF). This was a double-blind study investigating the effects of three doses of tolvaptan and placebo in patients with CHF. After a run-in period, 254 patients were randomly assigned to placebo (n 63) or tolvaptan [30 mg (n 64), 45 mg (n 64), or 60 mg (n 63)] once daily for 25 days. Patients were not fluid-restricted and were maintained on stable doses of furosemide. At day 1, when compared with baseline, a decrease in body weight of 0.79 0.99, 0.96 0.93, and 0.84 0.02 kg was observed in the 30-, 45-, and 60-mg tolvaptan groups, respectively, and a body weight increase of 0.32 0.46 kg in the placebo group (P 0.001 for all treatment groups versus placebo). Although the initial decrease in body weight was maintained during the study, no further reduction was observed beyond the first day. An increase in urine volume was observed with tolvaptan when compared with placebo (3.9 0.6, 4.2 0.9, 4.6 0.4, and 2.3 0.2 L/24 hours at day 1 for 30-, 45-, and 60-mg tolvaptan groups, and placebo, respectively; P 0.001). A decrease in edema and a normalization of serum sodium in patients with hyponatremia were observed in the tolvaptan group but not in the placebo group. No significant changes in heart rate, blood pressure, serum potassium, or renal function were observed. In patients with CHF, tolvaptan was well tolerated; it reduced body weight and edema and normalized serum sodium in the hyponatremic patients. (Circulation. 2003;107:2690-2696.
The effect of a pre- and postoperative orthogeriatric service on cognitive function in patients with hip fracture: randomized controlled trial (Oslo Orthogeriatric Trial)

Delirium is a common complication in patients with hip fractures and is associated with an increased risk of subsequent dementia. The aim of this trial was to evaluate the effect of a pre- and postoperative orthogeriatric service on the prevention of delirium and longer-term cognitive decline.



This was a single-center, prospective, randomized controlled trial in which patients with hip fracture were randomized to treatment in an acute geriatric ward or standard orthopedic ward. Inclusion and randomization took place in the Emergency Department at Oslo University hospital. The key intervention in the acute geriatric ward was Comprehensive Geriatric Assessment including daily interdisciplinary meetings. Primary outcome was cognitive function four months after surgery measured using a composite outcome incorporating the Clinical Dementia Rating Scale (CDR) and the 10 words learning and recalls tasks from the Consortium to Establish a Registry for Alzheimer's Disease battery (CERAD). Secondary outcomes were pre- and postoperative delirium, delirium severity and duration, mortality and mobility (measured by the Short Physical Performance Battery (SPPB)). Patients were assessed four and twelve months after surgery by evaluators blind to allocation.



A total of 329 patients were included. There was no significant difference in cognitive function four months after surgery between patients treated in the acute geriatric and the orthopedic wards (mean 54.7 versus 52.9, 95% confidence interval for the difference -5.9 to 9.5; P = 0.65). There was also no significant difference in delirium rates (49% versus 53%, P = 0.51) or four month mortality (17% versus 15%, P = 0.50) between the intervention and the control group. In a pre-planned sub-group analysis, participants living in their own home at baseline who were randomized to orthogeriatric care had better mobility four months after surgery compared with patients randomized to the orthopedic ward, measured with SPPB (median 6 versus 4, 95% confidence interval for the median difference 0 to 2; P = 0.04).



Pre- and postoperative orthogeriatric care given in an acute geriatric ward was not effective in reducing delirium or long-term cognitive impairment in patients with hip fracture. The intervention had, however, a positive effect on mobility in patients not admitted from nursing homes.
Six-Minute Walk Test as a Predictor for Outcome in Children with Dilated Cardiomyopathy and Chronic Stable Heart Failure

Cardiopulmonary exercise testing is an important tool to predict prognosis in children and adults with heart failure. A much less sophisticated exercise test is the 6 min walk test, which has been shown an independent predictor for morbidity and mortality in adults with heart failure. Therefore, we hypothesized that the 6 min walk test could be predictive for outcome in children with dilated cardiomyopathy. We prospectively included 49 children with dilated cardiomyopathy ≥6 years who performed a 6 min walk test. Median age was 11.9 years (interquartile range [IQR] 7.4–15.1), median time after diagnosis was 3.6 years (IQR 0.6–7.4). The 6 min walk distance was transformed to a percentage of predicted, using age- and gender-specific norm values (6MWD%). For all patients, mean 6MWD% was 70 ± 21%. Median follow-up was 33 months (IQR 14–50). Ten patients reached the combined endpoint of death or heart transplantation. Using univariable Cox regression, a higher 6MWD% resulted in a lower risk of death or transplantation (hazard ratio 0.95 per percentage increase, p = 0.006). A receiver operating characteristic curve was generated to define the optimal threshold to identify patients at highest risk for an endpoint. Patients with a 6MWD% < 63% had a 2 year transplant-free survival of 73%, in contrast to a transplant-free survival of 92% in patients with a 6MWD% ≥ 63% (p = 0.003). In children with dilated cardiomyopathy, the 6 min walk test is a simple and feasible tool to identify children with a higher risk of death or heart transplantation.
Limitations of computed tomography coronary angiography.

t seems so simple and elegant. Fifty years after the ntroduction of coronary angiography, advances in technolgy allow imaging of the coronary arteries noninvasively sing multidetector computed tomography (CT) scanners 1). Within a few short years, these imaging systems have egun appearing everywhere, first in hospitals and clinics, hen in individual doctors’ offices, offering the promise of afe and painless detection of coronary obstructions (2). eekend courses allow the members of our profession to learn” this new technology and apply it routinely to patient are (3). The manufacturers of the equipment, all large ultinational providers of radiological imaging devices, are uite pleased to show practitioners how they can rapidly ecoup their million-dollar investments (4,5). What could ossibly be wrong with this picture? Medical progress to the etterment of patients (and practitioners).
Impact of computer-generated personalized goals on HbA(1c).

The public is increasingly aware of the importance of HbA(1c) testing, yet the vast majority of patients with diabetes do not know their HbA(1c) status or goal. We set forth to evaluate the impact of a system that provides uniquely formatted and personalized reports of diabetes status and goals on changes in HbA(1c) levels.



A total of 150 patients with diabetes were randomized to receive either standard care or intervention inclusive of a computer-generated 11" x 17" color poster depicting an individual's HbA(1c) status and goals along with personalized steps to aid in goal achievement. All patients enrolled received diabetes education during the 3 months before enrollment. HbA(1c) was performed at baseline and 6 months.



At baseline, there were no significant differences between patient groups in terms of age, sex, education level, race, and HbA(1c) or lipid levels. Among patients with baseline HbA(1c) > or =7.0%, there was an 8.6% (0.77% absolute) reduction in HbA(1c) among control subjects compared with a 17.0% (1.69% absolute) decline in the intervention group (P = 0.032). There were no differences between the control and intervention groups with respect to the frequency of patients experiencing any decline in HbA(1c) (63 vs. 69%, P = 0.87); among these patients experiencing a decline, the most substantial reductions were seen with the control group, which had a 13.3% (1.15% absolute) decline compared with the intervention patients, who reduced their HbA(1c) by 24.2% (2.26% absolute reduction; P = 0.0048). At study close, 77% of the patients had their poster displayed on their refrigerator.



This unique and personalized computer-generated intervention resulted in HbA(1c) lowering comparable to that of hypoglycemic agents.
A randomized trial on the efficacy of group psychoeducation in the prophylaxis of recurrences in bipolar patients whose disease is in remission.

Studies on individual psychotherapy indicate that some interventions may reduce the number of recurrences in bipolar patients. However, there has been a lack of structured, well-designed, blinded, controlled studies demonstrating the efficacy of group psychoeducation to prevent recurrences in patients with bipolar I and II disorder.



One hundred twenty bipolar I and II outpatients in remission ( Rating Scale-17 score <8) for at least 6 months prior to inclusion in the study, who were receiving standard pharmacologic treatment, were included in a controlled trial. Subjects were matched for age and sex and randomized to receive, in addition to standard psychiatric care, 21 sessions of group psychoeducation or 21 sessions of nonstructured group meetings. Subjects were assessed monthly during the 21-week treatment period and throughout the 2-year follow-up.



Group psychoeducation significantly reduced the number of relapsed patients and the number of recurrences per patient, and increased the time to depressive, manic, hypomanic, and mixed recurrences. The number and length of hospitalizations per patient were also lower in patients who received psychoeducation.



Group psychoeducation is an efficacious intervention to prevent recurrence in pharmacologically treated patients with bipolar I and II disorder.
Are we targeting the right metric for heart failure? Comparison of hospital 30-day readmission rates and total episode of care inpatient days.

Hospitals are challenged to reduce length of stay (LOS), yet simultaneously reduce readmissions for patients with heart failure (HF). This study investigates whether 30-day rehospitalization or an alternative measure of total inpatient days over an episode of care (EOC) is the best indicator of resource use, HF quality, and outcomes.



Using data from the American Heart Association's Get With The Guidelines-Heart Failure Registry linked to Medicare claims, we ranked and compared hospitals by LOS, 30-day readmission rate, and overall EOC metric, defined as all hospital days for an HF admission and any subsequent admissions within 30 days. We divided hospitals into quartiles by 30-day EOC and 30-day readmission rates. We compared performance by EOC and readmission rate quartiles with respect to quality of care indicators and 30-day postdischarge mortality.



The population had a mean age of 80 ± 7.95 years, 45% were male, and 82% were white. Hospital-level unadjusted median index LOS and overall EOC were 4.9 (4.2-5.6) and 6.2 (5.3-7.4) days, respectively. Median 30-day readmission rate was 23.2%. Hospital HF readmission rate was not associated with initial hospital LOS, only slightly associated with total EOC rank (r = 0.26, P = .001), and inversely related to HF performance measures. After adjustment, there was no association between 30-day readmission and decreased 30-day mortality. In contrast, better performance on the EOC metric was associated with decreased odds of 30-day mortality.



Although hospital 30-day readmission rate was poorly correlated with LOS, quality measures, and 30-day mortality, better performance on the EOC metric was associated with better 30-day survival. Total inpatient days during a 30-day EOC may more accurately reflect overall resource use and better serve as a target for quality improvement efforts.
Variables associated with feeding tube placement in head and neck cancer.

To identify clinical factors associated with enteral feeding tube placement in a head and neck cancer population.



A self-administered survey was given to patients being treated for head and neck cancer while they were waiting to be seen in 1 of 4 otolaryngology clinics. The post hoc analysis presented here combines survey and chart review data to determine clinical and demographic variables associated with feeding tube placement.



Four otolaryngology clinics.



Otolaryngology clinic patients being treated for head and neck cancer.



Enteral feeding tube placement.



Of the 724 patients eligible for this study, 14% (n = 98) required enteral feeding tube placement. Multivariate analysis found the following variables to be independently associated with feeding tube placement: oropharynx/hypopharynx tumor site (odds ratio [OR], 2.4; P = .01), tumor stage III/IV (OR, 2.1; P = .03), flap reconstruction (OR, 2.2; P = .004), current tracheotomy (OR, 8.0; P<.001), chemotherapy (OR, 2.6; P<.001), and increased age (OR, 1.3; P = .02). In addition, there was a curvilinear relationship between time since treatment and feeding tube placement, with about 30% having a feeding tube at 1 month posttreatment, tapering down during the first 3 years to about 8% and leveling off thereafter.



Identification of factors associated with an increased risk of feeding tube placement may allow physicians to better counsel patients regarding the possibility of feeding tube placement during treatment. Since feeding tube placement has been linked to decreased quality of life in head and neck cancer, such counseling is an integral part of the clinical management of these patients.