nils-herrmann/clean_scirepeval huggingface dataset:
Plasma concentrations of fluticasone propionate and budesonide following inhalation from dry powder inhalers by healthy and asthmatic subjects.

All currently available inhaled corticosteroids reach the systemic circulation and have the potential to produce adverse effects with long term use. This risk is often assessed by measuring the effect of different inhaled corticosteroids on the hypothalamic-pituitary-adrenal (HPA) axis in healthy subjects. Absorption of fluticasone propionate and its effects on the HPA axis are greater in healthy subjects than in subjects with moderately severe asthma, but we have failed to show any difference in morning budesonide plasma levels or systemic effects between healthy and asthmatic subjects following inhalation of budesonide. To provide more information on the absorption of fluticasone propionate and budesonide, we have compared the plasma levels of both drugs over 8 hours in healthy and asthmatic subjects.



The area under the plasma concentration-time curves (AUC) and the maximum concentration (Cmax) of fluticasone propionate and budesonide after a single inhaled dose of each drug were compared in 12 healthy control subjects and 12 subjects with moderately severe asthma.



Peak plasma levels of budesonide occurred much earlier and were approximately 20-fold higher than those of fluticasone propionate in both healthy and asthmatic subjects. The AUC and Cmax for fluticasone propionate were lower by 307 (95% CI 62 to 522) pg/ml/h or 43% (p=0.02) and 52 (95% CI -11 to 115) pg/ml or 39% (p=0.1) in subjects with asthma compared with healthy control subjects. In contrast, the AUC and Cmax for budesonide were almost identical between the two groups (mean differences 826 (95% CI -1493 to 3143) pg/ml/h (p=0.5) and 157 (95% CI -1026 to 1339) pg/ml (p=0.8).



Following inhalation, healthy subjects have higher plasma levels of fluticasone propionate than subjects with asthma whereas budesonide plasma levels are similar in the two groups of subjects. Comparing the systemic effects of budesonide and fluticasone propionate in healthy subjects is unlikely to be relevant to subjects with asthma.
The JAK2 46/1 haplotype is a risk factor for myeloproliferative neoplasms in Chinese patients.

The presence of JAK2 V617F is associated with an inherited JAK2 46/1 haplotype, a risk factor for myeloproliferative neoplasms (MPN) in Caucasian populations. Whether the JAK2 46/1 haplotype is also a risk factor in the Chinese population is unknown. We assessed for the JAK2 46/1 haplotype and JAK2 V617F mutation in 225 MPN patients and 226 controls using a tagged SNP rs12340895. The allele frequencies of the JAK2 46/1 haplotype were distinct among different subtypes of MPN patients. The allele frequency was significantly higher in polycythemia vera (PV), essential thrombocythemia (ET), and primary myelofibrosis (PMF) than that in controls, with PV patients having the highest allele frequency (0.58, P = 6.00E-15). The distribution of rs12340895 genotypes in the JAK2 V617F mutated MPN patients was significantly different from that in controls (P = 1.67E-15). The percentage of GG genotype in controls was 2.2 %, but 31.0 % in JAK2 V617F-positive MPN patients. All the PV, ET, and PMF patients with the GG genotype also exhibited the V617F mutation. Compared to that of controls, the difference in genotype distribution in PV patients was the most significant (P = 4.83E-21), followed by ET (P = 2.07E-05) and PMF (P = 1.99E-04). Our results suggest that the JAK2 46/1 haplotype is a risk factor for MPN in the Chinese population, and patients with GG genotype in rs12340895 locus are susceptible to JAK2 V617F mutation.
Pharmaceutical care issues encountered by post-menopausal osteoporotic women prescribed bisphosphonates.

Pharmacists have been involved in providing comprehensive interventions to osteoporosis patients, but pharmaceutical care issues (PCIs) encountered during such interventions have not been well documented. Therefore, the aim of this study was to document PCIs encountered by post-menopausal osteoporotic women prescribed bisphosphonates.



A randomized controlled study was conducted from September 2005-February 2009 in the University Malaya Medical Centre, Malaysia. This main intervention study measured the effects of pharmaceutical care on medication adherence, persistence, quality of life, knowledge and patient satisfaction. However, this manuscript is part of the main intervention study and focuses only on the PCIs encountered.



post-menopausal women diagnosed with osteoporosis (T-score≤-2·5/low-trauma fracture) and prescribed weekly alendronate/risedronate.



those with metabolic bone disease and could not communicate in English. The PCIs identified were collected via personal interviews or telephone calls, and each participant was followed-up for a period of 2 years. All PCIs were discussed with and confirmed by a physician.



Of the 198 participants recruited, 64 (32·3%) experienced adverse effects because of bisphosphonates whereas one participant (0·5%) refused to start bisphosphonates because of fear of adverse effects. Most adverse effects [50 (74·6%)] were reported during the first 3 months of therapy with gastrointestinal problems being the main issue [23 (11·6%)]. Of the nine participants (4·5%) who discontinued bisphosphonates, only three agreed to take another medication. From the 97 PCIs identified, 77 issues could be classified as drug-related problems [according to the Pharmaceutical Care Network Europe Classification v6·2]. There were 87 causes, 178 interventions and 77 outcomes. The main problem and cause of the PCIs encountered were adverse drug events (83·1% and 74·7% respectively), whereas the main intervention provided was patient counselling (41·0%). All problems were solved (98·5%) except for one because of the lack of cooperation of a patient. After 2 years, 36 participants (20%) were no longer persistent with therapy, 19 (10·6%) did not have clinic follow-up and 53 (26·8%) did not have a bone mineral density scan.



The main PCIs identified were related to the use of bisphosphonates and its adverse effects. The study showed that the presence of a clinical pharmacist has enabled patients to voice their medication-related issues and to allow appropriate recommendations and actions to be taken to resolve these issues.
Efficacy of a simple dosage scheme to convert from shorter-acting erythropoiesis-stimulating agent to continuous erythropoietin receptor activator in kidney transplantation patients.

Anemia after kidney transplantation (KT) has a negative impact on graft and patient survival. Anemia management includes iron supplements and erythropoiesis-stimulating agents (ESAs). Most ESAs require short frequency of administration and conversion to ESAs with longer half-life are complex.



This study was performed to assess the efficacy of continuous erythropoietin receptor activator (CERA) in hemoglobin (Hb) maintenance after conversion from shorter-acting ESAs with a simple conversion scheme in kidney transplant recipients.



 77 anemic KT patients with stable renal function. Baseline and monthly measurements of Hb, iron, and creatinine were performed. The conversion scheme from darbepoetin alfa or epoetin was as follows: <30 μg or 5000 IU/week was switched to 75 μg/mo; between 30-50 or 5000-8000 was switched to 100 μg/mo; >50 μg or 8000 IU was changed to 150 μg/month of CERA. Dose adjustments were performed to maintain Hb levels between 10 g/dL and 12 g/dL.



The mean age was 57 ± 19 years. The mean time of conversion after KT was 61 ± 49 months. Before conversion, 62.9% of patients were administered epoetin and 37.1% with darbepoetin alfa. Baseline Hb is noted at 10.6 ± 1.3 g/dL. Thirteen percent of patients started receiving CERA at doses of 50 μg/mo, 66% at 75 μg/mo, 13% at 100 μg/mo, and 8% at 150 μg/mo. During the first month, 21% required dose adjustment (6% were increased, 15% were decreased). The final Hb was 11.2 ± 0.8 g/dL. Iron and creatinine levels remained stable during the follow-up examination.



We propose a simple scheme of conversion from short-acting ESAs to a once-monthly dose of CERA that provides sustained Hb levels within the recommended target with small dose adjustments and low CERA doses.
Assessment of intravenous adipose-derived allogeneic mesenchymal stem cells for the treatment of feline chronic kidney disease: a randomized, placebo-controlled clinical trial in eight cats.

Feline chronic kidney disease (CKD) is characterized by chronic tubulointerstitial nephritis, and inflammation contributes to the progression of renal fibrosis. Mesenchymal stem cells (MSCs) have demonstrated anti-inflammatory and antifibrotic effects in rodent CKD models. However, few randomized trials evaluating the effectiveness of MSC therapy for diseases in companion animals have been reported. The purpose of this study was to evaluate the effectiveness of allogeneic MSCs for the treatment of feline CKD using a randomized, placebo-controlled trial.



MSCs were isolated from the cryopreserved adipose tissues of specific pathogen-free research cats and culture expanded. CKD cats were enrolled in a randomized, placebo-controlled, blinded one-way crossover clinical study. Four CKD cats were randomized to receive 2 × 10(6) MSCs/kg intravenously at 2, 4 and 6 weeks. Four CKD cats were randomized to receive placebo, with two cats crossing over to the MSC treatment group and one cat failing to complete the trial. Complete blood counts, chemistry and urinalysis were performed at weeks 0, 2, 4, 6 and 8. Glomerular filtration rate (GFR) via nuclear scintigraphy and urine protein:creatinine ratio (UPC) were determined at weeks 0 and 8.



Six cats received three doses of allogeneic MSC culture expanded from cryopreserved adipose without adverse effects. No significant change in serum creatinine, blood urea nitrogen, potassium, phosphorus, GFR by nuclear scintigraphy, UPC or packed cell volume was seen in cats treated with MSCs. Individual changes in GFR were 12%, 8%, 8%, 2%, -13% and -67% in treated cats compared with 16%, 36% and 0% in placebo-treated cats.



While administration of MSC culture expanded from cryopreserved adipose was not associated with adverse effects, significant improvement in renal function was not observed immediately after administration. Long-term follow-up is necessary to determine whether MSC administration affects disease progression in cats with CKD.
A profile of volatile organic compounds in breath discriminates COPD patients from controls.

Chronic obstructive pulmonary disease (COPD) is an inflammatory condition characterized by oxidative stress and the formation of volatile organic compounds (VOCs) secreted via the lungs. We recently developed a methodological approach able to identify profiles of VOCs in breath unique for patient groups. Here we applied this recently developed methodology regarding diagnosis of COPD patients.



Fifty COPD patients and 29 controls provided their breath and VOCs were analyzed by gas chromatography-mass spectrometry to identify relevant VOCs. An additional 16 COPD patients and 16 controls were sampled in order to validate the model, and 15 steroid naïve COPD patients were sampled to determine whether steroid use affects performance.



1179 different VOCs were detected, of which 13 were sufficient to correctly classify all 79 subjects. Six of these 13 VOCs classified 92% of the subjects correctly (sensitivity: 98%, specificity: 88%) and correctly classified 29 of 32 subjects (sensitivity: 100%, specificity: 81%) from the independent validation population. Fourteen out of 15 steroid naïve COPD patients were correctly classified thus excluding treatment influences.



This is the first study distinguishing COPD subjects from controls solely based on the presence of VOCs in breath. Analysis of VOCs might be highly relevant for diagnosis of COPD.
Botulinum toxin A for treatment of upper limb spasticity following stroke: a multi-centre randomized placebo-controlled study of the effects on quality of life and other person-centred outcomes.

Botulinum toxin is known to relieve upper limb spasticity, which is a disabling complication of stroke. We examined its effect on quality of life and other person-centred perspectives.



A multi-centre, randomized, double-blind, placebo-controlled study.



Ninety-six patients were randomized (mean age 59.5 years) at least 6 months post-stroke. Mean time since stroke was 5.9 years.



Patients received either botulinum toxin type A or placebo into the affected distal upper limb muscles on 2 occasions, 12 weeks apart. Assessment was undertaken at baseline, 8, 12, 20 and 24 weeks. The primary outcome measure was the Assessment of Quality of Life scale (AQoL). Secondary outcome assessments included Goal Attainment Scaling (GAS), pain, mood, global benefit, Modified Ashworth Scale (MAS), disability and carer burden.



The groups did not differ significantly with respect to quality of life, pain, mood, disability or carer burden. However, patients treated with botulinum toxin type A had significantly greater reduction in spasticity (MAS) (p < 0.001), which translated into higher GAS scores (p < 0.01) and greater global benefit (p < 0.01).



Although no change in quality of life was demonstrated using the AQoL, botulinum toxin type A was found to be safe and efficacious in reducing upper limb spasticity and improving the ability to achieve personal goals.
Prevention, incidence, and outcomes of contrast-induced acute kidney injury.

Little is known about whether health care providers (physicians) implement preventive care for contrast-induced acute kidney injury (CIAKI). The objectives of our prospective cohort study were (1) to assess provider use of preventive strategies for CIAKI, (2) to determine the incidence of CIAKI, and (3) to examine the association of CIAKI with adverse outcomes at 30 days, including death, need for dialysis, and hospital admission.



We prospectively identified patients with estimated glomerular filtration rates less than 60 mL/min/1.73 m(2) undergoing procedures with intravascular radiocontrast agents and recorded the use of intravenous fluids and N-acetylcysteine and the discontinuation of nonsteroidal anti-inflammatory medications. We measured postprocedure serum creatinine levels to quantify the incidence of CIAKI and tracked 30-day mortality and need for dialysis or hospitalization to evaluate the association of CIAKI with these outcomes.



Preprocedure and postprocedure intravenous fluids were administered to 264 of 660 study patients (40.0%), more commonly with coronary angiography than with computed tomography (91.2% vs 16.6%, P < .001). N-acetylcysteine was administered to 39.2% of patients, while only 6.8% of patients using nonsteroidal anti-inflammatory drugs were instructed to discontinue the medication. In a propensity analysis, the use of intravenous fluids was associated with a reduced rate of CIAKI. The incidence of CIAKI was lowest following computed tomography (range, 0.0%-10.9%) and was highest following noncoronary angiography (range, 1.9%-34.0%). Eleven patients (1.7%) died, 1 patient (0.2%) required dialysis, and 83 patients (12.6%) were hospitalized; however, CIAKI was not independently associated with hospital admission or death.



Strategies to prevent CIAKI are implemented nonuniformly. Although biochemical evidence of CIAKI is relatively common, clinically significant CIAKI is rare. These findings should help health care providers focus the use of preventive care on the highest-risk patients and have important implications for future clinical trials.
Evolution of MS lesions to black holes under DNA vaccine treatment

Persistent black holes (PBH) are associated with axonal loss and disability progression in multiple sclerosis (MS). The objective of this work was to determine if BHT-3009, a DNA plasmid-encoding myelin basic protein (MBP), reduces the risk of new lesions becoming PBH, compared to placebo, and to test if pre-treatment serum anti-MBP antibody levels impact on the effect of BHT-3009 treatment. In this retrospective, blinded MRI study, we reviewed MRI scans of 155 MS patients from a double-blind, randomized, phase II trial with three treatment arms (placebo, 0.5 and 1.5 mg BHT-3009). New lesions at weeks 8 and 16 were tracked at week 48 and those appearing as T1-hypointense were classified as PBH. A subset of 46 patients with available pre-treatment serum anti-MBP IgM levels were analyzed separately. Overall, there was no impact of treatment on the risk for PBH. However, there was a significant interaction between anti-MBP antibodies and treatment effect: patients receiving 0.5 mg BHT-3009 showed a reduced risk of PBH with higher antibody levels compared to placebo (p < 0.01). Although we found no overall reduction of the risk for PBH in treated patients, there may be an effect of low-dose BHT-3009, depending on the patients’ pre-treatment immune responses.
Peri-operative prophylaxis with phenytoin: Dosage and therapeutic plasma levels

Early postoperative epilepsy is a frequent complication of supratentorial intracranial surgery. The lack of consensus on prophylaxis of early postoperative seizures with phenytoin (PHT) may be due to the different dosages used in several studies, owing to inadequate therapeutic plasma level. The aim of this study was to evaluate which dosage of PHT can maintain the therapeutic range in the early postoperative period. Twenty patients operated on for supratentorial neoplasms were randomly allocated to receive, during the last hour of the surgical procedure, loading doses of either 10 mg/kg (group A, n = 10) or 15 mg/kg (group B, n = 10) of PHT. PHT infusion rate never exceeded 30 mg/min. Six hours after the loading dose, PHT maintenance treatment (250 mg, i.V., every 8 hours) was started in all patients. PHT plasma levels were evaluated from the end of the intra-operative loading infusion up to 24 h. During the first six hours after the loading dose, phenytoin plasma levels fell below the therapeutic range (10–20 mg/1) in 7 out of the 10 patients receiving 10 mg/kg, while in the patients treated with 15 mg/kg, PHT plasma levels were always in the therapeutic range (P ⩽ 0.0001). PHT maintenance dose was sufficient to keep plasma levels within the therapeutic range in 8 patients in group A, and in all the patients in group B. It is concluded that a loading dose of 15 mg/kg, followed by postoperative treatment, is necessary to guarantee therapeutic plasma levels of phenytoin in the immediate postoperative period, when seizure risk is very high.
Effect of multivitamin and vitamin A supplements on weight gain during pregnancy among HIV-1-infected women.

The pattern of weight gain during pregnancy among HIV-infected women is largely unknown. Multivitamin supplementation was shown to be effective in preventing adverse pregnancy outcomes among HIV-positive women. These protective effects could be mediated in part by an improvement in the pattern of gestational weight gain.



We examined the effects of multivitamin and vitamin A supplements on weight gain during the second and third trimesters of pregnancy among HIV-infected women.



We enrolled 1075 pregnant, HIV-1-positive women from Dar es Salaam, Tanzania, in a randomized, placebo-controlled trial. Using a 2-by-2 factorial design, we assigned each woman to 1 of 4 regimens: multivitamins (thiamine, riboflavin, niacin, folic acid, and vitamins B-6, B-12, C, and E), vitamin A, multivitamins including vitamin A, or placebo. The women took these oral supplements daily and were weighed monthly until the end of pregnancy.



The mean rate of weight gain was 306 g/wk during the second trimester and 247 g/wk during the third trimester. During the third trimester, average weight gain was significantly greater (by 304 g; 95% CI: 17, 590; P = 0.04) and the risk of low rate of weight gain (<or= 100 g/wk) was significantly lower (relative risk: 0.73; 95% CI: 0.58, 0.93) in women who received multivitamins than in women who did not. Multivitamins including vitamin A were protective against low weight gain during the second trimester compared with multivitamins alone.



Multivitamin supplementation during pregnancy improves the pattern of weight gain among HIV-infected women.
Erratum to: Alendronate sodium/vitamin D3 combination tablet versus calcitriol for osteoporosis in Chinese postmenopausal women: a 6-month, randomized, open-label, active-comparator-controlled study with a 6-month extension

This study compares efficacy of ALN/D5600 versus that of calcitriol in osteoporotic Chinese postmenopausal women. ALN/D5600 produced greater bone mineral density (BMD) increases, greater bone turnover marker decreases, and less vitamin D insufficiency. This study provided detailed clinical information regarding ALN/D5600 treatment versus calcitriol 0.25 μg/day. The study did not evaluate fracture risk. The aim of this study is to investigate efficacy of alendronate 70 mg/vitamin D3 5600 IU combination tablets (ALN/D5600) versus calcitriol in osteoporotic Chinese postmenopausal women. This study is a 6-month, randomized, open-label, active-comparator study with 6-month extension (clinicaltrials.gov number NCT01350934) in postmenopausal women aged >55 years with osteoporosis (low bone mineral density (BMD) with/without prior fragility fracture). Patients were randomized to ALN/D5600 once weekly or calcitriol 0.25 μg daily. The primary efficacy end point of the base study was percent change from baseline in lumbar spine BMD (month 6). Hypercalcemia and hypercalciuria were safety events of special interest. A total of 219 patients (ALN/D5600 n = 111, calcitriol n = 108) were randomized. Baseline characteristics were similar, 30.3 % baseline 25-hydroxyvitamin D (25(OH)D) ≤15 ng/mL. At months 6 and 12, changes in lumbar spine BMD from baseline were 3.5 versus 1.6 % and 5.2 versus 2.3 % for ALN/D5600 versus calcitriol (between-group differences p < 0.001), respectively. Between-group differences for ALN/D5600 versus calcitriol were significant (p < 0.001) at months 6 and 12 for change from baseline in procollagen type 1 N-terminal propeptide (−59.1 versus −16.8 %, −68.1 versus −17.0 %) and serum C-telopeptides (−79.2 versus −27.2 %, −76.2 versus −24.2 %). Drug-related adverse events (AEs) and discontinuations due to drug-related AEs occurred in 15 (14.0 %) versus 8 (7.4 %) patients and 3 (2.8 %) versus 0 patients in the ALN/D5600 and calcitriol group, respectively. Hypercalciuria 12-month incidence (24-h urine Ca >300 mg) was 8.4 (ALN/D5600) versus 13.9 % (calcitriol) (p > 0.05). One patient (calcitriol) had hypercalcemia. ALN/D5600 produced greater increases in lumbar spine BMD and greater decreases in bone turnover markers versus calcitriol in osteoporotic Chinese women. It is not known whether the greater increase in BMD results in fewer fractures. ALN/D5600 was generally well tolerated in Chinese patients.