nils-herrmann/clean_scirepeval huggingface dataset:
Controlled release recombinant human interferon-α2b for treating patients with chronic hepatitis C genotype 1: a phase 2a clinical trial.

Better convenience and tolerability and sustained therapeutic concentrations might improve interferon (IFN) treatment for chronic hepatitis C virus (HCV) infection. In an open-label, randomized study, controlled release free (chemically unmodified) recombinant human IFN-α(2b) in poly(ether-ester) microspheres (CR-rhIFN-α(2b)), was injected at doses of 160, 320, 480 or 640 μg every 2 weeks for 12 weeks with concomitant weight-based oral ribavirin in 32 treatment-naïve patients with chronic HCV genotype 1. Treatment was well tolerated, with 31 patients (97%) successfully completing the study. Full doses of CR-rhIFN-α(2b) were administered on 96% of scheduled occasions. Flu-like symptoms were generally mild and brief. Injection site reactions developed in 13 patients (41%), and neutropenia occurred in six of eight patients receiving 640 μg. In the 320, 480 and 640 μg groups, 62-75% of patients achieved a ≥2 log(10) HCV RNA reduction by 4 weeks and 88-100% by 12 weeks. For those groups, the pooled median time to ≥2 log(10) reduction was 11 days (95% confidence interval, 7-35 days). In those groups, viral reduction below the limit of detection was accomplished in 25% of patients by 4 weeks and in 62% by 12 weeks. The 160-μg dose was less potent. After CR-rhIFN-α(2b) injection, stable plateau levels of serum IFN-α(2b) were generally reached within 72 h. Treatment-emergent neutralizing antibodies to IFN-α(2b) were observed in one patient. No antibodies to host plant proteins were detected. CR-rhIFN-α(2b) with ribavirin cotherapy was well tolerated and displayed potent early antiviral activity in patients with chronic HCV genotype 1.
Oral isosorbide dinitrate in the treatment of angina pectoris. Dose-response relationship and duration of action during acute therapy.

The duration of effects of single oral doses of 15, 30 and 60 mg of isosorbide dinitrate (ISDN) were studied in 12 patients with stable, exercise-induced angina pectoris. The effects of a 120-mg dose were also studied in seven of these 12 patients. The average peak values for plasma ISDN concentration were 6.8, 14.3, 17.5 and 26.0 ng/ml after 15, 30, 60 and 120 mg of ISDN, respectively, and there was a 5-, 12-, 6-, and 5fold interindividual variation in peak plasma concentration at these doses. At rest, both the systolic and diastolic blood pressures decreased after each dose of ISDN in both the supine (p < 0.05) and standing (p < 0.01) positions. The reduction in systolic blood pressure was more marked in the standing position. This effect occurred at 1 hour and persisted for 6 hours after 15 mg of ISDN and for 8 hours after other doses of ISDN. Exercise duration to the onset of angina and to the development of moderate angina increased by a similar degree after each dose of ISDN compared with placebo values (p < 0.001). This was apparent by 1 hour and the effects persisted for 8 hours. The maximum increase in walking time to angina occurred after 15 mg in six patients, after 30 mg in two patients, and after 60 mg in three patients. One patient did not improve after any of the doses. The heart rate (p < 0.01) and rate-pressure product (p < 0.05) at the onset of angina after any dose of ISDN increased compared with placebo values. However, ST-segment depression at the onset of angina was similar after ISDN and placebo. At the onset of moderate angina, the values for rate-pressure product after ISDN were similar to those after placebo, but ST-segment depression was less after ISDN (p < 0.05). These data show that administration of single doses of ISDN from 15-120 mg increased exercise tolerance to angina for 8 hours, but for the whole group, higher doses did not have a quantitative greater effect on exercise tolerance than the lower doses.
Effects of two commercially available feline diets on glucose and insulin concentrations, insulin sensitivity and energetic efficiency of weight gain.

A low-carbohydrate, high-protein (LCHP) diet is often recommended for the prevention and management of diabetes in cats; however, the effect of macronutrient composition on insulin sensitivity and energetic efficiency for weight gain is not known. The present study compared the effect in adult cats (n 32) of feeding a LCHP (23 and 47 % metabolisable energy (ME)) and a high-carbohydrate, low-protein (HCLP) diet (51 and 21 % ME) on fasting and postprandial glucose and insulin concentrations, and on insulin sensitivity. Tests were done in the 4th week of maintenance feeding and after 8 weeks of ad libitum feeding, when weight gain and energetic efficiency of each diet were also measured. When fed at maintenance energy, the HCLP diet resulted in higher postprandial glucose and insulin concentrations. When fed ad libitum, the LCHP diet resulted in greater weight gain (P < 0.01), and was associated with higher energetic efficiency. Overweight cats eating the LCHP diet had similar postprandial glucose concentrations to lean cats eating the HCLP diet. Insulin sensitivity was not different between the diets when cats were lean or overweight, but glucose effectiveness was higher after weight gain in cats fed the HCLP diet. According to the present results, LCHP diets fed at maintenance requirements might benefit cats with multiple risk factors for developing diabetes. However, ad libitum feeding of LCHP diets is not recommended as they have higher energetic efficiency and result in greater weight gain.
Influence of MRP2 on MPA pharmacokinetics in renal transplant recipients-results of the Pharmacogenomic Substudy within the Symphony Study.

The aim of this study was to determine the relationship between single-nucleotide polymorphisms (SNPs) in MRP2 genes and mycophenolic acid (MPA) pharmacokinetics in renal transplant recipients of the Symphony Pharmacogenomic substudy.



Sixty-six renal transplant recipients of eight Spanish centres were randomized into four branches of immunosuppressive regimen: low dose of cyclosporine, standard dose of cyclosporine, tacrolimus and sirolimus, all in addition to mycophenolate mofetil and steroids. Fifty-five patients were genotyped for SNPs in MRP2, C24T and C3972T. Pharmacokinetic sampling was done before MPA administration and up to 12 h post-dose at Day 7, 1 month and 3 months post-transplant. Relationships of area under the curve (AUC) of MPA and MPAG plasma sampling with the presence of MRP2 SNPs and with the immunosuppressive regimens were studied.



At steady-state conditions, MPA-reduced exposure was observed in C24T variant allele in MRP2 (CC: 68.73 ± 6.78; *T: 48.12 ± 4.90, P = 0.023); no significant differences linked to C3972T SNP were observed. Taking into account groups of treatment, lower MPA AUC in variant allele of C24T was only found under macrolides treatment with statistically significant differences at Month 3 (Tac and SRL, CC: 86.52 ± 10.98 versus *T: 41.99 ± 4.82, P = 0.001; CsA, CC: 52.31 ± 5.30 versus *T: 54.24 ± 8.30, P = 0.772); for C3972T, the same tendency was found but differences at steady state did not reach statistical significance.



Renal transplant recipients T carriers of C24T MRP2 with macrolides treatment were associated with reduced MPA AUC in steady-state conditions. Patients treated with cyclosporine lost the effect of this polymorphism.
Diagnostic Performance of Resting and Hyperemic Invasive Physiological Indices to Define Myocardial Ischemia: Validation With 13N-Ammonia Positron Emission Tomography.

The authors sought to compare the diagnostic performance of fractional flow reserve (FFR), instantaneous wave-free ratio (iFR), and resting distal coronary artery pressure/aortic pressure (Pd/Pa) using 13N-ammonia positron emission tomography (PET).



The diagnostic performance of invasive physiological indices was reported to be different according to the reference to define the presence of myocardial ischemia.



A total of 115 consecutive patients with left anterior descending artery stenosis who underwent both 13N-ammonia PET and invasive physiological measurement were included. Optimal cutoff values and diagnostic performance of FFR, iFR, and resting Pd/Pa were assessed using PET-derived coronary flow reserve (CFR) and relative flow reserve (RFR) as references. To compare discrimination and reclassification ability, each index was compared with integrated discrimination improvement (IDI) and category-free net reclassification index (NRI).



All invasive physiological indices correlated with CFR and RFR (all p values <0.001). The overall diagnostic accuracies of FFR, iFR, and resting Pd/Pa were not different for CFR <2.0 (FFR 69.6%, iFR 73.9%, and resting Pd/Pa 70.4%) and RFR <0.75 (FFR 73.9%, iFR 71.3%, and resting Pd/Pa 74.8%). Discrimination and reclassification abilities of invasive physiological indices were comparable for CFR. For RFR, FFR showed better discrimination and reclassification ability than resting indices (IDI = 0.170 and category-free NRI = 0.971 for iFR; IDI = 0.183 and category-free NRI = 1.058 for resting Pd/Pa; all p values <0.001).



The diagnostic performance of invasive physiological indices showed no differences in the prediction of myocardial ischemia defined by CFR. Using RFR as a reference, FFR showed a better discrimination and reclassification ability than resting indices.
[Influence of hospital type on treatment and prognosis in patients with non-ST elevation acute coronary syndrome].

Clinical practice guidelines on non-ST-segment elevation acute coronary syndrome (NSTEACS) do not take either hospital infrastructure or the availability of a catheterization laboratory into account. The aim of this study was to determine the influence of hospital type, either with or without a catheterization laboratory, on treatment and medium-term prognosis in patients with NSTEACS.



The GYSCA multicenter study (covering 15 hospitals) investigated the implementation of clinical practice guidelines in patients with NSTEACS at six hospitals with catheterization laboratories (i.e. tertiary-care hospitals; THs) and nine without (i.e. secondary-care hospitals; SHs). Patients were assessed clinically at hospital discharge and after 3 and 12 months.



In total, 1133 consecutive patients were recruited: 599 (52.9%) in THs and 534 (47.1%) in SHs. The use of specific class-I interventions (i.e. aspirin, clopidogrel, beta-blockers, angiotensin-converting enzyme inhibitors and statins) was more common in THs (P< .01) and more patients in THs underwent revascularization while in hospital (43% vs. 30%; P< .01). The number of SH patients who were readmitted for NSTEACS at 1 year was 5-fold greater than the number of TH patients (12.8% vs. 2.3%; P< .01), and hospital type was a predictor of an adverse event.



Patients admitted for NSTEACS to a hospital without a catheterization laboratory were managed less invasively and their drug treatment was less likely to have been modified to match guideline recommendations. In addition to other well-known prognostic factors, hospital type can also have an influence on patient outcomes.
Hypocellularity and insufficient expression of angiogenic factors in implanted autologous bone marrow in patients with chronic critical limb ischemia

The aim of this study was to identify the clinical parameters of absolutely poor-prognosis patients with chronic critical limb ischemia (AP-CLI). Sixteen no-option CLI patients with arteriosclerosis obliterans: ASO (nine) and non-ASO patients (seven) treated with bone marrow-mononuclear cell implantation (BMI) were analyzed. There were three AP-CLI patients (all ASO). The mRNA expression of several angiogenic factors in the implanted cells was analyzed in comparison with normal donor bone marrow. To observe the response of bone marrow components to hypoxia, normal bone marrow cells were cultured for 24 h in 2.5% O2, and mRNA expression of angiogenic factors were measured. AP-CLI patients exhibited extraordinary low bone marrow cellularity as well as the percentage of CD34-positive cells. Among angiogenic factors, only VEGF expression was maintained in response to HIF-1, while other factors such as HGF, Ang-1, PLGF, and SDF-1 decreased in the implanted bone marrow cells of the patients with CLI compared to normal bone marrow cells. HIF-1 and all of the five angiogenic factors increased in vitro in response to hypoxia. Thus it is highly likely that angiogenic factors except VEGF do not respond to chronic ischemia in bone marrow in vivo. An organ-protection system against tissue ischemia may be applied for acute hypoxia, but it may be insufficient for chronic ischemia.
Use of warfarin for venous thromboembolism prophylaxis following knee and hip arthroplasty: results of the Michigan Anticoagulation Quality Improvement Initiative (MAQI2)

Total knee arthroplasty (TKA) and total hip arthroplasty (THA) are associated with high rates of venous thromboembolism (VTE). Anticoagulants, such as warfarin, are commonly used to prevent VTE in such patients. The practice and effectiveness of warfarin in real world populations is not well documented. 595 TKA and THA patients treated with warfarin were followed by two anticoagulation clinics in the Michigan Anticoagulation Quality Improvement Initiative. Length of prescribed anticoagulation, percent time in therapeutic range (%TTR) and time to first therapeutic INR were calculated for each surgical group. For THA, all 300 patients received at least ten days with a 28-day median length of anticoagulation therapy. For TKA, all 295 patients received at least 10 days with a 28-day median length of anticoagulation therapy. For THA patients, time to first therapeutic INR was on average 12.0 ± 8.0 days with a mean %TTR of 36.6 ± 26.8 % for goal INR 2.0–3.0. For THA patients, 39 (13 %) never reached target INR. For TKA patients, time to first therapeutic INR was on average 12.8 ± 10.3 days with a mean %TTR of 36.0 ± 28.3 % for goal INR 2.0–3.0. For TKA patients, 44 (14.9 %) never reached target INR. Many orthopaedic surgeons who use warfarin for post-arthroplasty VTE prophylaxis do so in accordance with national guidelines. The time to first therapeutic INR is strikingly long and %TTR markedly low for these patients, raising questions about the efficacy of warfarin therapy in the first 1–2 post-operative weeks. Further studies to investigate the best target INR for warfarin prophylaxis, as well as the composite rates of VTE and clinically relevant bleeding from treatment with warfarin, LMWH and newer anticoagulants are needed.
Beyond Identity: Addressing Problems that Persist in an Electronic Mail System with Reliable Sender Identification

Many abuses of the Internet’s electronic mail system rely on its intrinsic lack of reliable sender identification, and many parties have proposed schemes to retro-fit sender identification into the system to combat such abuse. This paper considers what the spam problem and its countermeasures would be like under a theoretically ideal sender identification scheme, with some attention to the resource consumption the countermeasures entail—the economics of spam. Analysis suggests that no one single technique is likely to prove adequate, but a blended approach could be effective. Such an approach will create a need for integrated policy management facilities in future mail user agents.
An integrated workplace mental health intervention in a policing context: Protocol for a cluster randomised control trial

In this paper, we present the protocol for a cluster-randomised trial to evaluate the implementation and effectiveness of a workplace mental health intervention in the state-wide police department of the south-eastern Australian state of Victoria. n. The primary aims of the intervention are to improve psychosocial working conditions and mental health literacy, and secondarily to improve mental health and organisational outcomes.



The intervention was designed collaboratively with Victoria Police based on a mixed methods pilot study, and combines multi-session leadership coaching for the senior officers within stations (e.g., Sergeants, Senior Sergeants) with tailored mental health literacy training for lower and upper ranks. Intervention effectiveness will be evaluated using a two-arm cluster-randomised trial design, with 12 police stations randomly assigned to the intervention and 12 to the non-intervention/usual care control condition. Data will be collected from all police members in each station (estimated at >20 per station). Psychosocial working conditions (e.g., supervisory support, job control, job demands), mental health literacy (e.g., knowledge, confidence in assisting someone who may have a mental health problem), and mental health will be assessed using validated measures. Organisational outcomes will include organisational depression disclosure norms, organisational cynicism, and station-level sickness absence rates. The trial will be conducted following CONSORT guidelines. Identifying data will not be collected in order to protect participant privacy and to optimise participation, hence changes in primary and secondary outcomes will be assessed using a two-sample t-test comparing summary measures by arm, with weighting by cluster size.



This intervention is novel in its integration of stressor-reduction and mental health literacy-enhancing strategies. Effectiveness will be rigorously evaluated, and if positive results are observed, the intervention will be adapted across Victoria Police (total employees ~16,500) as well as possibly in other policing contexts, both nationally and internationally.
Intra-articular hyaluronic acid compared to exercise therapy in osteoarthritis of the ankle. A prospective randomized trial with long-term follow-up.

The goal of this study has been to determine whether hyaluronic acid (HA) or exercise therapy can improve functional parameters in patients with osteoarthritis (OA) of the ankle.



In a prospective clinical trial, 43 ankles (30 patients) with radiographic Kellgren Lawrence grade III OA were randomized to receive three intra-articular HA injections, with one-week interval of or exercise therapy for six weeks. Patients were evaluated by the American Orthopaedic Foot and Ankle Society (AOFAS) Ankle-Hindfoot Scale and followed-up after 12 months.



Total AOFAS Ankle-Hindfoot score of OA patients has improved in both groups, varying from 61.6+/-16.8 to 90.1+/-9.7 with HA treatment and from 72.1+/-16.6 to 87.5+/-17.5 using exercise therapy at the end of the trial (p<0.01). There were no statistically significant differences between the groups.



This prospective randomized trial confirmed that, both HA injections and exercise therapy provide functional improvement. However, larger trials with longer follow-up are necessary for more definite conclusions.
Physical activity in COPD patients: patterns and bouts.

The present study aims to describe the pattern of physical activity and the frequency, duration and intensity of physical activity bouts in patients with chronic obstructive pulmonary disease (COPD), to assess how these patterns differ according to COPD severity, and to explore whether these patients meet the general guidelines for physical activity for older adults. 177 patients (94% male, mean±sd age 71±8 years and forced expiratory volume in 1 s 52±16% predicted) wore the SenseWear Pro2 Armband accelerometer for eight consecutive days. Physical activity bouts were defined as periods of ≥10 min above 1.5 metabolic equivalent tasks and classified according to their median intensity. Patients engaged in activity a median of 153 min·day(-1) and 57% of that time was spent in bouts. Median frequencies of bouts per day were four and three for all and moderate-to-vigorous intensities, respectively. With increasing COPD severity, time in physical activity, proportion of time in bouts and frequency of bouts decreased. 61% of patients fulfilled the recommended physical activity guidelines. In conclusion, COPD patients of all spirometric severity stages engage in physical activity bouts of moderate-to-vigorous intensities. Patients with severe and very severe COPD perform their daily activities in fewer and shorter bouts than those in mild and moderate stages.
Physical activity and osteoporotic hip fracture risk in men.

Physical activity has been related to reduced risk of osteoporotic hip fractures, but the evidence among men is weak.



To determine the association between baseline leisure physical activity and future risk of osteoporotic hip fracture in men.



At baseline in 1975 our prospective study cohort included 3,262 men who were 44 years or older and did not have chronic disease restricting their ability to exercise. At baseline, physical activity was assessed by a questionnaire. Hip fractures were followed for 21 years, or from the age of 50 years for subjects who were initially younger than 50 years.



The hazard ratio of osteoporotic hip fracture, adjusted for other possible predictors (height, body mass index, baseline diseases, smoking, use of alcohol, work-related physical activity, and occupational group), in men participating in vigorous physical activity compared with men not participating was 0.38 (95% confidence interval, 0.16-0.91) (P = .03).



These results provide further evidence that there is an inverse association between baseline physical activity and future hip fracture risk among men.
Influence of varying doses of granulocyte-macrophage colony-stimulating factor on pharmacokinetics and antibody-dependent cellular cytotoxicity

Recombinant granulocyte-macrophage colony-stimulating factor (GM-CSF) is used in immunotherapy for correction of neutropoenia. The optimal dose for activation of immune functions and the pharmacokinetics following repeated administrations is less analysed in depth. In this study, the pharmacokinetics and the effects on haematological functions and antibody-dependent cellular cytotoxicity (ADCC) were analysed in 50 patients with metastatic colorectal carcinoma receiving monoclonal antibody based therapy in combination with Escherichia coli-derived GM-CSF (molgramostim) administered s.c. once daily for 10 days every month over a period of 4 months. Thirty-three patients received a GM-CSF dose of 200–250 μg/m2/day. Seventeen patients received GM-CSF doses varying between 65 and 325 μg/m2/day in the different treatment cycles. Serum GM-CSF concentration was measured (ELISA) before and 3–4 h after (peak serum concentration) GM-CSF administration days 1, 5 and 10. Prior to therapy, GM-CSF was not detectable in serum. Following repeated daily administrations, the peak serum concentration of GM-CSF gradually decreased on days 5 and 10 compared to day 1 (P < 0.05). During a 10-day treatment cycle, the total number of leukocytes, neutrophils, eosinophils, monocytes and lymphocytes increased. A dose-dependent increment in total white blood cell count and neutrophils was observed. The total numbers of GM-CSF receptor (α-subunit) expressing cells (granulocytes and monocytes) increased significantly during treatment while a transient decline in expression intensity was observed at day 5, suggesting a receptor-mediated removal of GM-CSF as a mechanism for the elimination of GM-CSF from circulation. ADCC of peripheral mononuclear cells was decreased at day 10 compared to baseline. An inverse correlation between the dose and ADCC was noted. The data might indicate that high doses of GM-CSF may have a negative impact on ADCC.