nils-herrmann/clean_scirepeval huggingface dataset:
Tenofovir discontinuation could predispose to urolithiasis in atazanavir-treated patients.

Urolithiasis has been recognized as a potential complication of antiretroviral therapy. Protease inhibitors are the drugs most commonly involved: indinavir can cause renal colic in about 8% of patients and lopinavir/ritonavir has been associated with seven cases of nephrolithiasis. The occurrence of renal colic during treatment with atazanavir is a rare, but reported event. Here we describe the case of a 43 years-old male patient enrolled in a pilot study evaluating the efficacy, safety and tolerability of treatment simplification to a dual therapy with atazanavir/ritonavir plus lamivudine in HIV-positive patients with optimal virological response (AtLaS study). The study was conducted in accordance with the Declaration of Helsinki and national and institutional standards and was approved by local ethic committee; signed informed consent was collected from all participants. At baseline, the patient, treated with atazanavir/ ritonavir þ tenofovir þ lamivudine for 4 years, with a CD4 count of 718 cells/mL and an HIV-RNA < 50 copies/mL, without hepatitis B or C co-infection, discontinued tenofovir according to the study design. Eight weeks thereafter he was hospitalized for severe right flank pain and fever. Serum blood exams revealed increased creatinine (1.6 mg/dL) with normal calcium, phosphate and uric acid levels. Urinanalysis showed a pH of 6.5, with no calcium, phosphate and uric acid abnormalities. The same day a spontaneous urinary stone emission occurred. A renal TC scan performed 3 days later revealed a right pyelic dilatation without any other stone. Two stones, weighting 5.9 and 13.6 mg respectively, were analyzed. They were dissolved in 250 mL of 20% H2SO4 and the supernatants were injected in an HPLC-UV apparatus for atazanavir measurement, as previously described. Drug concentrations in the two stones were 3.72 and 3.33 mg/mL. The estimated total amount of atazanavir was 0.93 and 1.08 mg respectively, which corresponded to a percent compositionof atazanavir ranging from7.9% to15.8% . Four and 12 weeks after tenofovir discontinuation, atazanavir plasma levels increased from 3.84 to 3.89 and 6.27 mg/mL, respectively (all samples collected 9 h after drug intake).
Different intraoperative kinematics with comparable clinical outcomes of ultracongruent and posterior stabilized mobile-bearing total knee arthroplasty

There remains no consensus as to whether mobile total knee arthroplasty (TKA) should use a posterior cruciate ligament-sacrificing ultracongruent (UC) or a posterior cruciate ligament-substituting posterior stabilized (PS) prosthesis. The purpose of this study was to assess intraoperative kinematics and clinical outcomes of UC and PS rotating platform mobile-bearing TKA. In this randomized controlled study, mobile UC TKA prostheses (n = 45) were compared with mobile PS TKA prostheses (n = 45) with regard to intraoperative kinematics and clinical outcomes. The passive kinematic study using intraoperative navigation system included anterior/posterior translation, varus/valgus alignment and rotation of femur during flexion. The patients were clinically and radiographically evaluated over a 3-year follow-up. Paradoxical anterior translation of the femur was 10.8 ± 5.2 mm in the UC knee from 0° to 82° of knee flexion and 8.7 ± 3.0 mm in the PS knee from 0° to 70° of knee flexion (p = 0.027). Paradoxical internal rotation of the femur was 5.8° in the UC knees and 9.9° in the PS knees (p = 0.003). But, there was no significant difference between the groups in regard to the coronal alignment. There was no significant difference in the range of motion, KS knee scores, KS function scores, and WOMAC index scores. Despite different intraoperative kinematics between mobile UC and mobile PS TKA, neither design reproduced physiologic knee kinematics and there was no difference in clinical outcomes between the two groups. The clinical relevance of the study is that despite different intraoperative kinematics, UC design can be a considerable alternative to PS design in mobile-bearing TKA in respect of clinical outcomes. II.
Comparison of the efficacy and safety of arformoterol 15 microg twice daily and arformoterol 30 microg once daily in COPD: a single-dose, multicenter, randomized, modified-blind, two-way crossover study.

The aim of this study was to compare the efficacy and safety of nebulized arformoterol 15 microg/2 mL twice daily (ARF15 BID) and 30 microg/4 mL once daily (ARF30 QD) in subjects with moderate to severe chronic obstructive pulmonary disease (COPD).



In this single-dose, multicenter, randomized, modified-blind, 2-way crossover study, subjects aged > or =45 years with moderate to severe COPD, a forced expiratory volume in 1 second (FEV(1)) > or =0.7 L, and < or =65% predicted FEV1, and a FEV(1):forced vital capacity ratio < or =70% were randomly assigned to receive single-day treatment with ARF15 BID or ARF30 QD in random order, separated by a 5 +/- 2-day washout period. The primary efficacy end point was time-normalized AUC of FEV(1) from baseline (hour 0) to 24 hours (FEV(1)AUC(0-24)). Secondary efficacy end points were time-normalized AUC of FEV(1) from baseline to 12 hours (FEV(1)AUC(0-12)) and from 12 to 24 hours (FEV(1)AUC(12-24)), and FEV(1) at 24 hours after administration of the morning dose (trough FEV(1)). Equivalence of the 2 therapies was assessed by comparing the 90% CI value for the difference of the least squares mean (LSM) to a study-specific predefined equivalence range for change in FEV(1)AUC(0-24) of -0.07 to 0.07 L.



A total of 33 subjects were enrolled (20 men, 13 women; mean [SD] age, 64.5 [8.8] years; 15 subjects received ARF15 BID first; 18 received ARF30 QD first). ARF15 BID and ARF30 QD were associated with similar improvements from baseline in (FEV(1)AUC(0-24), LSM 0.15 and 0.16 L, respectively; Delta, 0.01 L; 90% CI, -0.02 to 0.04) and trough FEV(1) (LSM, 0.15 and 0.12 L, respectively; Delta, -0.03 L; 90% CI, -0.09 to 0.03). FEV(1)AUC(0-12) was improved more with ARF30 QD than ARF15 BID (Delta, 0.06 L; 90% CI, 0.04 to 0.09), and FEV(1)AUC(12-24) was improved more with ARF15 BID than ARF30 Qd (Delta, -0.04 L; 90% CI, -0.08 to 0.01). The 90% CI for FEV(1)AUC(0-24) for the treatment difference between ARF15 BID and ARF30 QD was within the prespecified range of -0.07 to 0.07 L, indicating that both treatments resulted in equivalent FEV(1)AUC(0-24) values.



In these subjects with moderate to severe COPD, single-day administrations of ARF15 BID or ARF30 QD were associated with FEV(1) responses over a period of 24 hours that were considered equivalent per the protocol definition employed in the present study. FEV1 improvement over 12 hours was greater for ARF30 QD after the morning dose and for ARF15 BID after the evening dose.
Exploring User Experience of a Telehealth System for the Danish TeleCare North Trial

The aim was to explore user experiences of using a telehealth system (Telekit) designed for the Danish TeleCare North trial. Telekit is designed for patients diagnosed with chronic obstructive pulmonary disease (COPD) in order to manage the disease and support patient empowerment. This article sums up COPD-participants' user experiences in terms of increased sense of freedom, of security, of control, and greater awareness of COPD symptoms. A consecutive sample of sixty participants (27 women, 33 men) were recruited from the TeleCare North trial. At home the participants completed a non-standardised questionnaire while a researcher was present. The questionnaire identified their health status, their use of specific technologies, and their user experiences with the telehealth system. Results from the questionnaire indicate that the majority of participants (88%) considered the Telekit system as easy to use. 43 (72%) participants felt increased sense of security, and 37 (62%) participants felt increased sense of control by using the system. 30 (50%) participants felt greater awareness of their COPD symptoms, but only 16 (27%) participants felt increased freedom. The study has provided a general picture of COPD participants' user experiences which is important to emphasise as it has a bearing on whether a given implementation will be successful or not.
Phase II trial of temsirolimus in patients with relapsed or refractory multiple myeloma.

In a phase II trial, 16 patients with relapsed refractory multiple myeloma received temsirolimus 25mg I.V. weekly until progression. One partial response and 5 minor responses were observed for a total response rate of 38%. The median time to progression was 138 days. Grade 3-4 toxicity included fatigue (n=3), neutropenia (n=2), thrombocytopenia (n=2), interstitial pneumonitis (n=1), stomatitis (n=1) and diarrhea (n=1). Clinical activity was associated with a higher area under the curve (AUC) and maximal reduction in phosphorylated p70(S6)K and 4EBP1 in peripheral blood mononuclear cells. At the dose and schedule used, temsirolimus had low single agent activity. Investigation of alternate dosing schedules and use in combinations is indicated.
The Young Netherlands Twin Register (YNTR): longitudinal twin and family studies in over 70,000 children.

The Netherlands Twin Register (NTR) began in 1987 with data collection in twins and their families, including families with newborn twins and triplets. Twenty-five years later, the NTR has collected at least one survey for 70,784 children, born after 1985. For the majority of twins, longitudinal data collection has been done by age-specific surveys. Shortly after giving birth, mothers receive a first survey with items on pregnancy and birth. At age 2, a survey on growth and achievement of milestones is sent. At ages 3, 7, 9/10, and 12 parents and teachers receive a series of surveys that are targeted at the development of emotional and behavior problems. From age 14 years onward, adolescent twins and their siblings report on their behavior problems, health, and lifestyle. When the twins are 18 years and older, parents are also invited to take part in survey studies. In sub-groups of different ages, in-depth phenotyping was done for IQ, electroencephalography , MRI, growth, hormones, neuropsychological assessments, and cardiovascular measures. DNA and biological samples have also been collected and large numbers of twin pairs and parents have been genotyped for zygosity by either micro-satellites or sets of short nucleotide polymorphisms and repeat polymorphisms in candidate genes. Subject recruitment and data collection is still ongoing and the longitudinal database is growing. Data collection by record linkage in the Netherlands is beginning and we expect these combined longitudinal data to provide increased insights into the genetic etiology of development of mental and physical health in children and adolescents.
Evaluating the efficacy, safety and evolution of renal function with early initiation of everolimus-facilitated tacrolimus reduction in de novo liver transplant recipients: Study protocol for a randomized controlled trial

Introduction of calcineurin inhibitors had led to improved survival rates in liver transplant recipients. However, long-term use of calcineurin inhibitors is associated with a higher risk of chronic renal failure, neurotoxicity, de novo malignancies, recurrence of hepatitis C viral (HCV) infection and hepatocellular carcinoma. Several studies have shown that everolimus has the potential to provide protection against viral replication, malignancy, and progression of fibrosis, as well as preventing nephrotoxicity by facilitating calcineurin inhibitor reduction without compromising efficacy. The Hephaistos study evaluates the beneficial effects of early initiation of everolimus in de novo liver transplant recipients.



Hephaistos is an ongoing 12-month, multi-center, open-label, controlled study aiming to enroll 330 de novo liver transplant recipients from 15 centers across Germany. Patients are randomized in a 1:1 ratio (7-21 days post-transplantation) to receive everolimus (trough levels 3-8 ng/mL) with reduced tacrolimus (trough levels <5 ng/mL), or standard tacrolimus (trough levels 6-10 ng/mL) after entering a run-in period (3-5 days post-transplantation). In the run-in period, patients are treated with induction therapy, mycophenolate mofetil, tacrolimus, and corticosteroids according to local practice. Randomization is stratified by HCV status and model of end-stage liver disease scores at transplantation. The primary objective of the study is to exhibit superior renal function (estimated glomerular filtration rate assessed by the Modification of Diet in Renal Disease (MDRD)-4 formula) with everolimus plus reduced tacrolimus compared to standard tacrolimus at Month 12. Other objectives are: to assess the incidence of treated biopsy-proven acute rejection, graft loss, or death; the incidences of components of the composite efficacy endpoint; renal function via estimated glomerular filtration rate using various formulae (MDRD-4, Nankivell, Cockcroft-Gault, chronic kidney disease epidemiology collaboration and Hoek formulae); the incidence of proteinuria; the incidence of adverse events and serious adverse events; the incidence and severity of cytomegalovirus and HCV infections and HCV-related fibrosis.



This study aims to demonstrate superior renal function, comparable efficacy, and safety in de novo liver transplant recipients receiving everolimus with reduced tacrolimus compared with standard tacrolimus. This study also evaluates the antiviral benefit by early initiation of everolimus.
Incidence and impact of totally occluded culprit coronary arteries in patients presenting with non-ST-segment elevation myocardial infarction.

The accuracy of the 12-lead electrocardiogram in detecting coronary artery occlusion is limited. We sought to determine the incidence, distribution, and outcomes of patients who have total occlusion of the culprit artery but present with non-ST-segment elevation myocardial infarction (NSTEMI). The randomized Acute Catheterization and Urgent Intervention Triage Strategy trial enrolled 13,819 patients presenting with non-ST-segment elevation acute coronary syndromes who underwent an early invasive strategy. The present study includes 1,319 patients with baseline biomarker elevation (NSTEMI) and no history of coronary artery bypass graft who underwent percutaneous coronary intervention of a single culprit vessel. We compared the baseline characteristics and outcomes according to whether the culprit vessel was occluded (baseline Thrombolysis In Myocardial Infarction [TIMI] 0 to 1) or patent (TIMI 2 to 3 flow) by angiographic core laboratory assessment. TIMI 0 to 1 flow in the culprit artery was present in 262 of 1,319 (19.9%) patients. The incidence of coronary occlusion was 28.4%, 19.3%, and 12.6% in patients with NSTEMI because of right coronary, left circumflex, and left anterior descending artery disease, respectively. Patients with an occluded culprit artery were more commonly men and had ST-segment deviation ≥1 mm. One-year outcomes, including death (3.5% vs 3.0%, p = 0.68) and myocardial infarction (8.4% vs 9.6%, p = 0.47), did not differ significantly between patients with versus without occluded culprit arteries, respectively. In conclusion, the present study demonstrates that the culprit artery is totally occluded in approximately 1 in 5 patients presenting with NSTEMI and single-vessel disease; however, the presence of total occlusion in NSTEMI was not associated with an incremental hazard of death or reinfarction at 1 year.
Coronary stenting with the sirolimus-eluting stent in patients with restenosis after intracoronary brachytherapy: results from the prospective multicentre German Cypher Stent Registry

Treatment of restenosis following intracoronary brachytherapy (ICB) is still a challenging problem. Implantation of sirolimus-eluting stents (SES) in this setting may be an option to be evaluated. We analysed the prospective multicentre SES registry, the German Cypher Stent Registry. 7,445 patients treated with an SES during percutaneous coronary intervention (PCI) were registered. Out of these patients, 61 (0.8%) were treated for restenosis after ICB: 56 patients with completed follow-up could be evaluated. Median age was 65 years, with 80% male patients. 48% of patients had a prior myocardial infarction and 25% had already coronary bypass surgery (CABG). Type B2 lesion was present in 40% and type C lesion in 22.4%. Event rates from SES implantation until 6.6 months follow-up were death 0%, myocardial infarction 3.6%, stroke 2.1%. Target vessel revascularization rate (TVR) was 16.4%, and major adverse cardiovascular or cerebral events (MACCE) or TVR occurred in 17.9% of patients. This TVR rate was higher compared with that of other patients treated with an SES: 8.4% (P = 0.04). During 65 months follow-up MACCE or TVR occurred in 44.6% of patients. The treatment of lesions after ICB occurred in 0.8% out of all patients treated with an SES. Clinical event rates during early follow-up were low. However, the TVR rate was 16.4%, which was significantly higher when compared with other SES-treated patients (8.4%, P = 0.04). The treatment of restenosis after ICB with SES seems to be safe and reasonably effective; however, there might be a late catch-up phenomenon.
N-terminal pro-brain natriuretic peptide and risk of coronary artery lesions and resistance to intravenous immunoglobulin in Kawasaki disease.

To determine whether the serum N-terminal pro-brain natriuretic peptide (NT-proBNP) can be a useful marker not only to identify the patients with Kawasaki disease (KD) who are at a higher risk of developing coronary artery lesions (CAL), and predict resistance to intravenous immunoglobulin (IVIG).



We enrolled 80 patients with the acute phase of KD at a single center. The demographic, clinical, and laboratory data were prospectively collected.



Nineteen of the 80 patients developed CAL, despite IVIG administration. They had a significantly higher serum NT-proBNP level in comparison with the patients without CAL. The NT-proBNP cut-off value of 1300 pg/mL yielded a sensitivity of 95% and a specificity of 85% for predicting CAL. However, 17 of the 80 patients were IVIG non-responders. They also had a significantly higher serum NT-proBNP level in comparison with the IVIG responders. The NT-proBNP cut-off value of 800 pg/mL yielded a sensitivity of 71% and a specificity of 62% for predicting IVIG non-responders.



The serum NT-proBNP level is increased in children with KD with CAL and IVIG resistance. It may be useful to predict CAL and IVIG resistance in KD.
Phobic anxiety in 11 nations. Part I: Dimensional constancy of the five-factor model.

The Fear Survey Schedule-III (FSS-III) was administered to a total of 5491 students in Australia, East Germany, Great Britain, Greece, Guatemala, Hungary, Italy, Japan, Spain, Sweden, and Venezuela, and submitted to the multiple group method of confirmatory analysis (MGM) in order to determine the cross-national dimensional constancy of the five-factor model of self-assessed fears originally established in Dutch, British, and Canadian samples. The model comprises fears of bodily injury-illness-death, agoraphobic fears, social fears, fears of sexual and aggressive scenes, and harmless animals fears. Close correspondence between the factors was demonstrated across national samples. In each country, the corresponding scales were internally consistent, were intercorrelated at magnitudes comparable to those yielded in the original samples, and yielded (in 93% of the total number of 55 comparisons) sex differences in line with the usual finding (higher scores for females). In each country, the relatively largest sex differences were obtained on harmless animals fears. The organization of self-assessed fears is sufficiently similar across nations to warrant the use of the same weight matrix (scoring key) for the FSS-III in the different countries and to make cross-national comparisons feasible. This opens the way to further studies that attempt to predict (on an a priori basis) cross-national variations in fear levels with dimensions of national cultures.
Comparative study between the effects of replacement therapy with liquid and tablet formulations of levothyroxine on mood states, self-perceived psychological well-being and thyroid hormone profile in recently thyroidectomized patients

Following thyroid surgery, levothyroxine therapy is used to replace deficient thyroid hormones and prevent postoperative thyroid hypofunction. We compared the effects of replacement therapy with either liquid or tablet formulation of levothyroxine on mood states, self-perceived mental well-being and thyroid hormone profile in recently thyroidectomized patients. Profile of mood states, General Heath Questionnaire 12-items and thyroid hormone profile were assessed in recently (5–7 days) thyroidectomized patients at baseline and 2 months after randomization to replacement therapy with either liquid (n = 77) or tablet (n = 78) formulation of levothyroxine. After 2 months under levothyroxine replacement treatment, significant improvements of Positive Affect Scale (p < 0.001) and Negative Affect Scale (p < 0.001) of Profile of mood states, as well as of General Heath Questionnaire 12-items (p < 0.001) were observed in the study population. However, there were greater variations observed in patients assigned to liquid levothyroxine formulation in comparison to those who were assigned to levothyroxine in the form of tablet (time × treatment interaction: Positive Affect Scale of Profile of mood states, p = 0.030; Negative Affect Scale of Profile of mood states, p < 0.0001; General Heath Questionnaire 12-items, p = 0.003). As expected, circulating TSH levels significantly decreased (p <0.001) while FT3 and FT4 levels significantly increased (p < 0.0001 for both) under levothyroxine replacement therapy. These changes were significantly greater in patients treated with liquid levothyroxine formulation (time × treatment interaction: TSH, p = 0.011; FT3, p = 0.016; FT4, p = 0.028). Our data indicate a greater efficacy of liquid formulation of levothyroxine in ameliorating mood states and self-perception of mental well-being and thyroid hormone profile after 2 months of replacement therapy in recently thyroidectomized patients.
The Hawthorne Effect: a randomised, controlled trial

The 'Hawthorne Effect' may be an important factor affecting the generalisability of clinical research to routine practice, but has been little studied. Hawthorne Effects have been reported in previous clinical trials in dementia but to our knowledge, no attempt has been made to quantify them. Our aim was to compare minimal follow-up to intensive follow-up in participants in a placebo controlled trial of Ginkgo biloba for treating mild-moderate dementia.



Participants in a dementia trial were randomised to intensive follow-up (with comprehensive assessment visits at baseline and two, four and six months post randomisation) or minimal follow-up (with an abbreviated assessment at baseline and a full assessment at six months). Our primary outcomes were cognitive functioning (ADAS-Cog) and participant and carer-rated quality of life (QOL-AD).



We recruited 176 participants, mainly through general practices. The main analysis was based on Intention to treat (ITT), with available data. In the ANCOVA model with baseline score as a co-variate, follow-up group had a significant effect on outcome at six months on the ADAS-Cog score (n = 140; mean difference = -2.018; 95%CI -3.914, -0.121; p = 0.037 favouring the intensive follow-up group), and on participant-rated quality of life score (n = 142; mean difference = -1.382; 95%CI -2.642, -0.122; p = 0.032 favouring minimal follow-up group). There was no significant difference on carer quality of life.



We found that more intensive follow-up of individuals in a placebo-controlled clinical trial of Ginkgo biloba for treating mild-moderate dementia resulted in a better outcome than minimal follow-up, as measured by their cognitive functioning.