nils-herrmann/clean_scirepeval huggingface dataset:
Once versus twice daily injection of enoxaparin for thromboprophylaxis in bariatric surgery: effects on antifactor Xa activity and procoagulant microparticles. A randomized controlled study.

The optimal scheme of thromboprophylaxis in bariatric surgery remains uncertain, because clinical practice is different between countries and randomized trials are lacking.



The primary objective of this randomized multicenter study was to determine the optimal regimen of enoxaparin providing an antifactor Xa peak activity between .3 and .5 IU/mL at equilibrium and to evaluate the course of procoagulant microparticles (MPs).



University hospital.



A total of 164 patients scheduled for gastric bypass were allocated to 3 groups (A, B, and C) of enoxaparin treatment (4000, 6000, or 2×4000 IU, respectively). Antifactor Xa activity was measured before and 4 hours after each injection from D0 to D2. Doppler screening of the lower limbs was performed at D1, D9, and D30. Bleeding (BE) and thrombotic events (TE) were recorded during the first postoperative month. Total MPs were measured at D0, D9, and D30. MPs of leucocyte, platelet, and granulocyte origin were assessed in one third of the patients from each group. The 3 groups were compared by ANOVA.



A total of 135 patients were analyzed. The equilibrium of antifactor Xa peak levels was obtained 52 hours after the presurgery injection and 12.8%, 56.4%, and 27.3% of the patients reached the target in groups A, B, and C, respectively (P<.001). No TE was detected. BE occurred in 1, 2, and 6 patients in groups A, B, and C, respectively). Total MPs remained unchanged over time. While no significant variation was observed in the other groups, platelet GP1 b(+)-MPs increased (P = .01) at D9 in group C, suggesting an incomplete control of anticoagulation leading to cell activation and procoagulant MP release that was confirmed by the higher MP levels measured at D30 (P = .04). CD66(+)-MPs were also highly elevated at J9 and D30 in group C indicating a granulocyte contribution.



This study shows that a single dose of enoxaparin 6000 IU/d allowed most of the patients to reach the target range of antifactor Xa activity without increasing the bleeding risk, with the most likely efficient reduction of procoagulant MPs.
Peripheral Microvascular Vasodilatory Response to Estradiol and Genistein in Women with Insulin Resistance.

E2 enhances vasodilation in healthy women, but vascular effects of the phytoestrogen GEN are still under investigation. IR compromises microvascular function. We therefore examined the interaction of E2 , GEN, and IR on microvascular vasodilatory responsiveness.



We hypothesized that E2 and GEN increase microvascular vasodilation in healthy women (control, n = 8, 23 ± 2 year, BMI: 25.9 ± 2.9 kg/m2) but not in women with IR (n = 7, 20 ± 1 year, BMI: 27.3 ± 3.0 kg/m2). We used the cutaneous circulation as a model of microvascular vasodilatory function. We determined CVC with laser Doppler flowmetry and beat-to-beat blood pressure during local cutaneous heating (42 °C) with E2 or GEN microdialysis perfusions. Because heat-induced vasodilation is primarily an NO-mediated response, we examined microvascular vasodilation with and without L-NMMA.



In C, E2 enhanced CVC (94.4 ± 2.6% vs. saline 81.6 ± 4.2% CVCmax , p < 0.05), which was reversed with L-NMMA (80.9 ± 7.8% CVCmax , p < 0.05), but GEN did not affect vasodilation. Neither E2 nor GEN altered CVC in IR, although L-NMMA attenuated CVC during GEN.



Our study does not support improved microvascular responsiveness during GEN exposure in healthy young women, and demonstrates that neither E2 nor GEN improves microvascular vasodilatory responsiveness in women with IR.
Faster‐acting insulin aspart: earlier onset of appearance and greater early pharmacokinetic and pharmacodynamic effects than insulin aspart

To evaluate the pharmacokinetics and pharmacodynamics of faster-acting insulin aspart and insulin aspart in a randomized, single-centre, double-blind study.



Fifty-two patients with type 1 diabetes (mean age 40.3 years) received faster-acting insulin aspart, insulin aspart, or another faster aspart formulation (not selected for further development), each as a single 0.2 U/kg subcutaneous dose, under glucose-clamp conditions, in a three-way crossover design (3-12 days washout between dosing).



Faster-acting insulin aspart had a faster onset of exposure compared with insulin aspart, shown by a 57% earlier onset of appearance [4.9 vs 11.2 min; ratio 0.43, 95% confidence interval (CI) 0.36; 0.51], a 35% earlier time to reach 50% maximum concentration (20.7 vs 31.6 min; ratio 0.65, 95% CI 0.59; 0.72) and a greater early exposure within 90 min after dosing. The greatest difference occurred during the first 15 min, when area under the serum insulin aspart curve was 4.5-fold greater with faster-acting insulin aspart than with insulin aspart. Both treatments had a similar time to maximum concentration, total exposure and maximum concentration. Faster-acting insulin aspart had a significantly greater glucose-lowering effect within 90 min after dosing [largest difference: area under the curve for the glucose infusion rate (AUC(GIR), 0-30 min) ratio 1.48, 95% CI 1.13; 2.02] and 17% earlier time to reach 50% maximum glucose infusion rate (38.3 vs 46.1 min; ratio 0.83, 95% CI 0.73; 0.94). The primary endpoint (AUC(GIR, 0-2 h)) was 10% greater for faster-acting insulin aspart, but did not reach statistical significance (ratio 1.10, 95% CI 1.00; 1.22). Both treatments had similar total and maximum glucose-lowering effects, indicating similar overall potency.



Faster-acting insulin aspart was found to have earlier onset and higher early exposure than insulin aspart, and a greater early glucose-lowering effect, with similar potency.
Can a nonequivalent choice of dosing regimen bias the results of flexible dose double blind trials? The CATIE schizophrenia trial

One of the major challenges in the design of double-blind flexible-dosing clinical trials comparing active drugs is the selection of dosing regimens that are equivalent across drugs. This study uses data from the CATIE schizophrenia trial to evaluate the hypothesis that drugs that were dosed somewhat higher in the trial than in typical practice would show greater efficacy and more side effects, especially at high capsule levels, than drugs that were dosed at lower relative strengths.



CATIE was a large (N=1460) randomized trial comparing 5 antipsychotics in patients with chronic schizophrenia. The blind was maintained in CATIE by prescribing identical-looking capsules of each medication. Dosing was flexible, such that PIs could prescribe from one to four capsules per day, and could modify the dose based on a patient's symptoms and side effects. Capsule strengths for olanzapine (7.5 mg) and quetiapine (200 mg) were relatively higher than for risperidone (1.5 mg), perphenazine (8 mg) or ziprasidone (40 mg). Proportional hazards models of time to all cause discontinuation and mixed regression models for continuous measures of symptoms, quality of life and side effects were used to test for interactions between randomly assigned drug and number of capsules prescribed per visit. We hypothesized that if a dosing bias was present, the flex-dosing design would result in a significant interaction such that drugs with higher relative dosing per capsule would be more effective and have more side effects than drugs with lower relative dosing and that this effect would be greatest at the largest prescribed dosing regimen (4 capsules).



There were no significant interactions between drug assignment and number of capsules in the proportional hazards analyses of time to all cause discontinuation (p=.77, excluding ziprasidone and .74 in the ziprasidone cohort) or in the mixed model analysis of PANSS symptoms (p=.49), quality of life (p=.45); or measures of tardive dyskinesia (AIMS, p=.47). However a significant interaction was observed on the Barnes akathisia scale (p=.0005), on the Simpson Angus EPS scale (p=.10) and on the analysis of weight (p=0.014). Paired comparisons did not show the hypothesized pattern of relationships for akathisia or EPS, but such a pattern was suggested for olanzapine in the analysis of weight although it emerged at 2, 3 and 4 capsules indicating a general drug effect rather than a relative dosing difference.



Dosing biases do not seem to have affected the results of the CATIE trial.
Bortezomib in combination with conventional chemotherapeutic agents for multiple myeloma compared with bortezomib alone.

Recent studies have demonstrated synergy between bortezomib and a number of conventional cytotoxic agents. This study examined whether or not the speed of the response, progression and safety from a combination treatment of bortezomib with common chemotherapeutic drugs is superior to bortezomib monotherapy.



Fifty-seven patients with relapsed, refractory multiple myeloma (MM) who had received at least two cycles of treatment including bortezomib were enrolled in this study. The median age was 56 (35-79) years and 49.1% were male. Thirty-two patients were treated with bortezomib alone and 25 were treated with chemotherapeutic agents that were given in combination with bortezomib. The monoclonal immunoglobulin (mIg) or free light chain (FLC) concentrations were determined in the sera before and after two cycles of bortezomib treatment. The adverse events were assessed and graded according to the NCI Common Toxicity Criteria (version 2.0).



Thirty-one of the 57 patients (54.4%) attained an early objective response (EOR) after the second bortezomib treatment, defined as a >/=50% decrease in the serum mIg or FLC concentration. Improvements in the response were observed when common chemotherapeutic agents were added to bortezomib monotherapy. In patients who received bortezomib combined with chemotherapeutic agents, 19 out of 25 patients (76%) showed an EOR, whereas 12 out of 32 patients (37.5%) given bortezomib monotherapy achieved an EOR after the second cycle of bortezomib treatment (P = 0.004); the median decrease from the baseline in the paraprotein level was 74.6 +/- 5.9 and 39.7 +/- 4.2%, respectively (P = 0.003). A statistically significant elevation of serum lactic dehydrogenase (P = 0.007) and alkaline phosphatase (P = 0.027) from baseline within two cycles of bortezomib treatment was observed in responding patients. With the combination treatment, peripheral neuropathy of >/=Grade II occurred in 12 out of 25 patients (48%) compared with 12 of 32 (37.5%) in those given bortezomib alone (P = 0.589). The median time to progression of disease was similar in the two groups (359 +/- 43.5 versus 365 +/- 103.5, P = 0.688). The multivariate Cox regression model showed that a high serum albumin and low beta2-microglobulin are favorable factors for the progression-free survival following bortezomib treatment.



Bortezomib in combination with common chemotherapeutic agents is more active in the treatment of relapsed, refractory MM than with bortezomib alone. However, more effective post-bortezomib treatment is needed to reduce the rate of disease progression particularly in patients with high tumor burden.
Opioid use among low back pain patients in primary care: Is opioid prescription associated with disability at 6-month follow-up?

Opioid prescribing for chronic noncancer pain is increasing, but there is limited knowledge about longer-term outcomes of people receiving opioids for conditions such as back pain. This study aimed to explore the relationship between prescribed opioids and disability among patients consulting in primary care with back pain. A total of 715 participants from a prospective cohort study, who gave consent for review of medical and prescribing records and completed baseline and 6month follow-up questionnaires, were included. Opioid prescription data were obtained from electronic prescribing records, and morphine equivalent doses were calculated. The primary outcome was disability (Roland-Morris Disability Questionnaire [RMDQ]) at 6months. Multivariable linear regression was used to examine the association between opioid prescription at baseline and RMDQ score at 6months. Analyses were adjusted for potential confounders using propensity scores reflecting the probability of opioid prescription given baseline characteristics. In the baseline period, 234 participants (32.7%) were prescribed opioids. In the final multivariable analysis, opioid prescription at baseline was significantly associated with higher disability at 6-month follow-up (P<.022), but the magnitude of this effect was small, with a mean RMDQ score of 1.18 (95% confidence interval: 0.17 to 2.19) points higher among those prescribed opioids compared to those who were not. Our findings indicate that even after adjusting for a substantial number of potential confounders, opioids were associated with slightly worse functioning in back pain patients at 6-month follow-up. Further research may help us to understand the mechanisms underlying these findings and inform clinical decisions regarding the usefulness of opioids for back pain.
The Study on the Efficacy of Fibrin Glue in Preventing Post-traumatic Focal Pancreatitis (PTFP) After Radical Gastrectomy

This study was intended to evaluate the efficacy of fibrin glue (FG) in preventing post-traumatic focal pancreatitis (PTFP) after radical gastrectomy by examining the drainage fluids over 7 days post-op. Ninety-five patients who underwent D2 radical gastrectomy for gastric cancer were randomly assigned to a fibrin glue group (n = 48) receiving fibrin glue on the raw surface of the pancreas during surgery and a control group (n = 47), which did not receive fibrin glue. We found no significant difference in operation time and intraoperative blood loss between groups (p > 0.05); no deaths occurred during surgery. The volume of ascitic fluid containing blood cells in the fibrin glue group was significantly lower than that in the control group (p < 0.001) at all times observed. Amylase levels in the drained fluids were highest at 24 h postoperatively in both groups, suggesting pancreatitis, but gradually decreased to normal levels within 7 days. The amylase in the drains in the control group was significantly higher than that in the FG group (p < 0.001) at all times observed, but it returned to normal 72 h postoperatively in the FG group. One death by hemorrhagic shock associated with PTFP was recorded in the control group. Fibrin glue is safe and effective in preventing PTFP following gastric surgery and shortens the clinical course of the disease.
Effects of long-term pravastatin treatment on spermatogenesis and on adrenal and testicular steroidogenesis in male hypercholesterolemic patients.

To evaluate the influence of an hydrophilic statin, pravastatin, on adrenal and testicular steroidogenesis and spermatogenesis, eight male hypercholesterolemic patients were studied. All patients observed a hypocholesterolemic diet and received placebo for 4 weeks followed by pravastatin (20 mg/die) for 6 months. Before, during (4th-5th week) and at the end (23th-24th week) of active treatment, CRH (1 microgram i.v.), ACTH (Synacthen 250 micrograms i.v.) and human CG (HCG 3000 IU i.m.) tests were performed in addition to semen analysis. Pravastatin significantly reduced total cholesterol (20.3%), calculated LDL-cholesterol (24.6%) and apolipoprotein B (10.5%, increased apolipoprotein A1 (16.1%) and did not influence plasma HDL-cholesterol and triglycerides. Basal plasma cortisol, aldosterone, androstenedione, testosterone and oestradiol did not change under active treatment. Pravastatin administration affected neither adrenal hormone responses to CRH and ACTH or testicular response to HCG nor spermatogenesis in respect of motility, morphology and sperm count. In conclusion, long-term pravastatin treatment, at doses effective in improving lipid profile, did not influence testicular reproductive and endocrine function and did not interfere with basal and stimulated adrenal activity of male hypercholesterolemic patients.
Multidetector computed tomography of the head in acute stroke: predictive value of different patterns of the dense artery sign revealed by maximum intensity projection reformations for location and extent of the infarcted area

Maximum intensity projections reconstructions from 2.5 mm unenhanced multidetector computed tomography axial slices were obtained from 49 patients within the first 6 h of anterior-circulation cerebral strokes to identify different patterns of the dense artery sign and their prognostic implications for location and extent of the infarcted areas. The dense artery sign was found in 67.3% of cases. Increased density of the whole M1 segment with extension to M2 of the middle cerebral artery was associated with a wider extension of cerebral infarcts in comparison to M1 segment alone or distal M1 and M2. A dense sylvian branch of the middle cerebral artery pattern was associated with a more restricted extension of infarct territory. We found 62.5% of patients without a demonstrable dense artery to have a limited peripheral cortical or capsulonuclear lesion. In patients with a 7–10 points on the Alberta Stroke Early Programme Computed Tomography Score and a dense proximal MCA in the first hours of ictus the mean decrease in the score between baseline and follow-up was 5.09±1.92 points. In conclusion, maximum intensity projections from thin-slice images can be quickly obtained from standard computed tomography datasets using a multidetector scanner and are useful in identifying and correctly localizing the dense artery sign, with prognostic implications for the entity of cerebral damage.
Circulating intercellular cell adhesion molecule-1, endothelin-1 and von Willebrand factor-markers of endothelial dysfunction in uncomplicated essential hypertension: the effect of treatment with ACE inhibitors

The aim of the study was to examine whether the circulating cell adhesion molecules, von Willebrand factor (vWf) and endothelin-1, are elevated in patients with essential hypertension with no other risk factors for atherosclerosis and thus may serve as a markers of endothelial dysfunction in uncomplicated hypertension. Furthermore, the effect of treatment with the ACE inhibitor, quinapril, on levels of endothelial dysfunction markers were studied. The levels of adhesion molecules (intercellular cell adhesion molecule-1 [ICAM-1], E-selectin, P-selectin), von Wilebrand factor (vWf) and endothelin-1 were measured in patients with hypertension without any other risk factors of atherosclerosis before and after treatment with quinapril (n = 22) and in normotensive controls (n = 22). Compared with normotensive subjects, the hypertensive patients had significantly higher levels of ICAM-1 (238 vs 208 ng/ml, P = 0.02), vWf (119 vs 105 IU/dl, P < 0.05) and endothelin-1 (5.76 vs 5.14 fmol/ml, P < 0.05). Three-month treatment of hypertensive patients with quinapril led to a significant decrease in the levels of endothelin-1 (5.76 vs 5.28 fmol/ml, P < 0.01). We did not observe significant changes in the levels of adhesion molecules and vWf after ACE inhibitor treatment, although a trend toward a decrease was apparent with all these parameters. Patients with uncomplicated hypertension with no other risk factors of atherosclerosis had significantly elevated levels of ICAM-1, vWf, and endothelin-1. Our data suggest that these factors may serve as markers of endothelial damage even in uncomplicated hypertension. In hypertensive patients, treatment with the ACE inhibitor quinapril resulted in a significant decrease in endothelin-1 levels. These findings indicate a beneficial effect of ACE inhibitors on endothelial dysfunction in hypertensive patients.
Hyperactivity of the default-mode network in first-episode, drug-naive schizophrenia at rest revealed by family-based case–control and traditional case–control designs

Abnormal regional activity and functional connectivity of the default-mode network (DMN) have been reported in schizophrenia. However, previous studies may have been biased by unmatched case-control design. To limit such bias, the present study used both the family-based case-control design and the traditional case-control design to investigate abnormal regional activity of the DMN in patients with schizophrenia at rest.Twenty-eight first-episode, drug-naive patients with schizophrenia, 28 age-, sex-matched unaffected siblings of the patients (family-based controls, FBC), and 40 healthy controls (HC) underwent resting-state functional magnetic resonance imaging (fMRI) scans. The group-independent component analysis and fractional amplitude of low-frequency fluctuation (fALFF) methods were used to analyze the data.Patients with schizophrenia show increased fALFF in an overlapped region of the right superior medial prefrontal cortex (MPFC) relative to the FBC and the HC. Compared with the HC, the patients and the FBC exhibit increased fALFF in an overlapped region of the left posterior cingulate cortex/precuneus (PCC/PCu). Furthermore, the z values of the 2 overlapped regions can separate the patients from the FBC/HC, and separate the patients/FBC from the HC with relatively high sensitivity and specificity.Both the family-based case-control and traditional case-control designs reveal hyperactivity of the DMN in first-episode, drug-naive patients with paranoid schizophrenia, which highlights the importance of the DMN in the neurobiology of schizophrenia. Family-based case-control design can limit the confounding effects of environmental factors in schizophrenia. Combination of the family-based case-control and traditional case-control designs may be a viable option for the neuroimaging studies.
Stress Biomarkers as Outcomes for HIV+ Prevention: Participation, Feasibility and Findings Among HIV+ Latina and African American Mothers

Mothers living with HIV (MLH) are at high risk for acute and chronic stress, given challenges related to their HIV status, ethnicity, economic and urban living conditions. Biomarkers combined into a composite index show promise in quantifying psychosocial stress in healthy people, but have not yet been examined among MLH. According, we examined potential biomarker correlates of stress [cortisol and catecholamines from home-collected urine and basic health indicators (blood pressure, height and weight, waist-to-hip ratio) measured during an interview] among 100 poor African American and Latina mothers MLH and demographic-matched control mothers without HIV (n = 50). Participants had been enrolled in a randomized controlled trial about 18 months earlier and had either received (MLH-I) or were awaiting (MLH-W) the psychosocial intervention. Participation was high, biomarkers were correctly collected for 93% of cases, and a complete composite biomarker index (CBI) calculated for 133 mothers (mean age = 42). As predicted, MLH had a significantly higher CBI than controls, but there was no CBI difference across ethnicity or intervention group. CBI predicted CD4 counts independently after controlling for age, years since diagnosis, prior CD4 counts, medication adherence, and depression symptoms. The study demonstrates acceptability, feasibility and potential utility of community-based biomarker collections in evaluating individual differences in psychosocial stress.