nils-herrmann/clean_scirepeval huggingface dataset:
The immunogenicity, safety, and efficacy of etanercept liquid administered once weekly in patients with rheumatoid arthritis.

To evaluate the immunogenicity, safety, and efficacy of 50 mg/mL liquid etanercept.



In a multicenter, open-label study, adults with active rheumatoid arthritis (RA) received 50 mg/mL liquid etanercept subcutaneously once weekly for 24 weeks. Immunogenicity was assessed at baseline and weeks 24 and 28, safety at all study visits, and efficacy at baseline and weeks 12 and 24.



Of 222 treated patients, 88% completed the study; 81% were women; 84% were white; mean age was 53 years; mean RA duration was 10 years. Antibodies to etanercept, all non-neutralizing, were detected in 12 of 214 patients; 7 of the 12 were borderline positive (antibody titers <1:50). The presence of non-neutralizing anti-etanercept antibodies did not appear to affect clinical safety or efficacy. Few patients reported serious adverse events (6.3%), serious infections (2.3%), or withdrew because of adverse events (4.5%). Most adverse events were mild or moderate. The most common event, injection site reaction, occurred in 29.3% patients. At week 24, 63% of patients achieved an ACR20 response, 36% an ACR50 response, and 14% an ACR70 response. Similar responses were apparent by week 12. Week 24 mean improvement in the Health Assessment Questionnaire disability index scores was 0.6 points; improvement in the Short Form-36 Physical Component Score was 10.0 points.



The 50 mg/mL liquid etanercept formulation administered once weekly was well tolerated. The incidence of anti-etanercept antibodies, the nature and frequency of adverse events, and improvements in signs and symptoms of RA and patient physical function were similar to those in previous etanercept studies.
Antidepressant Ef fi cacy of Ketamine in Treatment-Resistant Major Depression : A Two-Site Randomized Controlled Trial

Sanjay J. Mathew,  Ketamine, a glutamate Nmethyl-D-aspartate (NMDA) receptor antagonist, has shown rapid antidepressant effects, but small study groups and inadequate control conditions in prior studies have precluded a definitive conclusion. The authors evaluated the rapid antidepressant efficacy of ketamine in a large group of patients with treatment-resistant major depression.
User interaction in smart ambient environment targeted for senior citizen

Many countries are facing a problem when the age-structure of the society is changing. The numbers of senior citizen are rising rapidly, and caretaking personnel numbers cannot match the problems and needs of these citizens. Using smart, ubiquitous technologies can offer ways in coping with the need of more nursing staff and the rising costs of taking care of senior citizens for the society. Helping senior citizens with a novel, easy to use interface that guides and helps, could improve their quality of living and make them participate more in daily activities. This paper presents a projection-based display system for elderly people with memory impairments and the proposed user interface for the system. The user’s process recognition based on a sensor network is also described. Elderly people wearing the system can interact the projected user interface by tapping physical surfaces (such as walls, tables, or doors) using them as a natural, haptic feedback input surface.
Key findings and clinical implications from The Epidemiology and Natural History of Asthma: Outcomes and Treatment Regimens (TENOR) study.

Patients with severe or difficult-to-treat asthma are an understudied population but account for considerable asthma morbidity, mortality, and costs. The Epidemiology and Natural History of Asthma: Outcomes and Treatment Regimens (TENOR) study was a large, 3-year, multicenter, observational cohort study of 4756 patients (n=3489 adults ≥ 18 years of age, n=497 adolescents 13-17 years of age, and n=770 children 6-12 years of age) with severe or difficult-to-treat asthma. TENOR's primary objective was to characterize the natural history of disease in this cohort. Data assessed semiannually and annually included demographics, medical history, comorbidities, asthma control, asthma-related health care use, medication use, lung function, IgE levels, self-reported asthma triggers, and asthma-related quality of life. We highlight the key findings and clinical implications from more than 25 peer-reviewed TENOR publications. Regardless of age, patients with severe or difficult-to-treat asthma demonstrated high rates of health care use and substantial asthma burden despite receiving multiple long-term controller medications. Recent exacerbation history was the strongest predictor of future asthma exacerbations. Uncontrolled asthma, as defined by the 2007 National Heart, Lung, and Blood Institute guidelines' impairment domain, was highly prevalent and predictive of future asthma exacerbations; this assessment can be used to identify high-risk patients. IgE and allergen sensitization played a role in the majority of severe or difficult-to-treat asthmatic patients.
Intensification of the stem cell transplant induction regimen results in increased treatment-related mortality without improved outcome in multiple myeloma

Randomized trials conducted by the Intergroupe Française du Myelome (IFM) demonstrate that the use of high-dose chemotherapy (HDCT) and stem cell transplantation (SCT) improves event-free (EFS) and overall survival (OS) in younger patients with multiple myeloma (MM). Nevertheless, current HDCT regimens remain inadequate as all patients ultimately relapse following SCT. In an attempt to improve the OS of MM patients post-SCT we used an escalated HDCT regimen incorporating both intensified melphalan (160 mg/m2) and fractionated total body irradiation (12 Gy) to maximize the dose response of myeloma cells to these agents and included infusional etoposide 60 mg/kg in an attempt to eradicate clonal B cells potentially contributing to the myeloma clone. One hundred patients with MM received this intensified SCT regimen. The 100-day treatment-related mortality was 12% predominantly reflecting the development of interstitial pneumonitis (IP) in 28% of patients of whom 7/28 (25%) died. The predicted 5-year OS and EFS following the diagnosis of MM were 60% and 35%, respectively. The median OS from the time of transplant is 41 months and the median EFS is 28 months. More than two prior chemotherapy regimens, previous radiation therapy (RT) and the presence of an abnormal karyotype involving chromosomes 11 or 13 were significantly predictive of poor outcome. Interferon maintenance was not associated with improved outcome. Intensification of the HDCT regimen utilizing etoposide together with escalated melphalan and TBI increases morbidity and mortality without increasing OS beyond that reported with less toxic regimens.
Randomised placebo-controlled trial of lisinopril in normotensive patients with insulin-dependent diabetes and normoalbuminuria or microalbuminuria

We carried out a randomised, double-blind, placebo-controlled trial of the ACE inhibitor lisinopril in 530 men and women with IDDM aged 20–59 years with normoalbuminuria or microalbuminuria. Patients were recruited from 18 European centres, and were not on medication for hypertension. Resting blood pressure at entry was at least 75 and no more than 90 mm Hg diastolic, and no more than 155 mm Hg systolic. Urinary albumin excretion rate (AER) was centrally assessed by means of two overnight urine collections at baseline, 6, 12, 18, and 24 months.
Malignant fibrous histiocytoma and fibrosarcoma of bone: a re-assessment in the light of currently employed morphological, immunohistochemical and molecular approaches

Malignant fibrous histiocytoma (MFH) and fibrosarcoma (FS) of bone are rare malignant tumours and contentious entities. Sixty seven cases labelled as bone MFH (57) and bone FS (10) were retrieved from five bone tumour referral centres and reviewed to determine whether recent advances allowed for reclassification and identification of histological subgroups with distinct clinical behaviour. A panel of immunostains was applied: smooth muscle actin, desmin, h-caldesmon, cytokeratin AE1–AE3, CD31, CD34, CD68, CD163, CD45, S100 and epithelial membrane antigen. Additional fluorescence in situ hybridisation and immunohistochemistry were performed whenever appropriate. All cases were reviewed by six bone and soft tissue pathologists and a consensus was reached. Follow-up for 43 patients (median 42 months, range 6–223 months) was available. Initial histological diagnosis was reformulated in 18 cases (26.8 %). Seven cases were reclassified as leiomyosarcoma, six as osteosarcoma, three as myxofibrosarcoma and one each as embryonal rhabdomyosarcoma and interdigitating dendritic cell sarcoma. One case showed a peculiar biphasic phenotype with epithelioid nests and myofibroblastic spindle cells. Among the remaining 48 cases, which met the WHO criteria for bone FS and bone MFH, we identified five subgroups. Seven cases were reclassified as undifferentiated pleomorphic sarcoma (UPS) and 11 as UPS with incomplete myogenic differentiation due to positivity for at least one myogenic marker. Six were reclassified as spindle cell sarcoma not otherwise specified. Among the remaining 24 cases, we identified a further two recurrent morphologic patterns: eight cases demonstrated a myoepithelioma-like phenotype and 16 cases a myofibroblastic phenotype. One of the myoepithelioma-like cases harboured a EWSR1–NFATC2 fusion. It appears that bone MFH and bone FS represent at best exclusion diagnoses.
Prospective phase II single-center study of the safety of a single very high dose of liposomal amphotericin B for antifungal prophylaxis in patients with acute myeloid leukemia.

Some preclinical and pharmacokinetic studies suggested the variable safety and the potential efficacy of an antifungal prophylaxis with a single high dose of liposomal amphotericin B (L-AmB) in high-risk patients. An open-label, prospective study was conducted with 48 adults receiving induction chemotherapy for acute myeloid leukemia (AML). Patients received a single infusion of 15 mg/kg of body weight L-AmB and, eventually, a second dose after 15 days of persistent neutropenia. The primary objective was tolerability and safety. Efficacy was also evaluated as a secondary endpoint. A pharmacokinetic study was performed with 34 patients in order to evaluate any association of plasma L-AmB levels with toxicity and efficacy. Overall, only 6 patients (12.5%) reported Common Toxicity Criteria (CTC) grade 3 hypokalemia, which was corrected with potassium supplementation in all cases, and no patient developed clinically relevant nephrotoxicity. Mild infusion-related adverse events occurred after 6 of 53 (11.3%) total infusions, with permanent drug discontinuation in only one case. Proven invasive fungal disease (IFD) was diagnosed in 4 (8.3%) patients. The mean AmB plasma levels at 6 h, 24 h, and 7 days after L-AmB administration were 160, 49.5, and 1 mg/liter, respectively. The plasma AmB levels were higher than the mean values of the overall population in 3 patients who developed CTC grade 3 hypokalemia and did not significantly differ from the mean values of the overall population in 3 patients who developed IFD. Our experience demonstrates the feasibility and safety of a single 15-mg/kg L-AmB dose as antifungal prophylaxis in AML patients undergoing induction chemotherapy.
Modifiable antenatal risk factors for stillbirth amongst pregnant women in the Omusati region, Namibia

Reduction of stillbirth rates is important because of the social and economic implications. Access to quality antenatal care is important in preventing the risk factors associated with stillbirth.



To determine the prevalence of modifiable antenatal risk factors associated with stillbirth so as to determine possible gaps in their prevention.



The study was conducted at four district hospitals in the Omusati Region of Namibia.



A descriptive study using recorded antenatal data was used. Data were collected from the records of 82 women at the time that they had a stillbirth, during the period October 2013 to December 2014. Data were collected for modifiable risk factors related to maternal characteristics, antenatal care received, medical conditions and obstetric complications.



The average prevalence of each category of risk factors was as follows: quality of antenatal care (19.8%), maternal characteristics (11.4%), medical conditions (8.9%) and obstetric complications (6.5%). The most prevalent individual risk factors included: no folate supplementation (30.5%), HIV infection (25.6%), late booking (16.7%), intrauterine foetal growth retardation (13.4%) and alcohol use (12.5%).



Amongst the 14 modifiable risk factor included in the present study, 11 (78.6%) were prevalent amongst women who had a stillbirth. Risk factors associated with quality of antenatal care were the most prevalent. Whilst further investigation is needed to determine the causes behind this prevalence, health education on the availability and benefits of antenatal care, pregnancy timing and spacing may contribute to reducing the prevalence of these risk factors.
Initial therapy with the fixed-dose combination of sitagliptin and metformin results in greater improvement in glycaemic control compared with pioglitazone monotherapy in patients with type 2 diabetes.

To evaluate the efficacy and safety of initial therapy with a fixed-dose combination (FDC) of sitagliptin and metformin compared with pioglitazone in drug-naÏve patients with type 2 diabetes.



After a 2-week single-blind placebo run-in period, patients with type 2 diabetes, HbA1c of 7.5-12% and not on antihyperglycaemic agent therapy were randomized in a double-blind manner to initial treatment with a FDC of sitagliptin/metformin 50/500 mg twice daily (N = 261) or pioglitazone 30 mg per day (N = 256). Sitagliptin/metformin and pioglitazone were up-titrated over 4 weeks to doses of 50/1000 mg twice daily and 45 mg per day, respectively. Both treatments were then continued for an additional 28 weeks.



From a mean baseline HbA1c of 8.9% in both groups, least squares (LS) mean changes in HbA1c at week 32 were -1.9 and -1.4% for sitagliptin/metformin and pioglitazone, respectively (between-group difference = -0.5%; p < 0.001). A greater proportion of patients had an HbA1c of <7% at week 32 with sitagliptin/metformin vs. pioglitazone (57% vs. 43%, p < 0.001). Compared with pioglitazone, sitagliptin/metformin treatment resulted in greater LS mean reductions in fasting plasma glucose (FPG) [-56.0 mg/dl (-3.11 mmol/l) vs. -44.0 mg/dl (-2.45 mmol/l), p < 0.001] and in 2-h post-meal glucose [-102.2 mg/dl (-5.68 mmol/l) vs. -82.0 mg/dl (-4.56 mmol/l), p < 0.001] at week 32. A substantially greater reduction in FPG [-40.5 mg/dl (-2.25 mmol/l) vs. -13.0 mg/dl (-0.72 mmol/l), p < 0.001] was observed at week 1 with sitagliptin/metformin vs. pioglitazone. A greater reduction in the fasting proinsulin/insulin ratio and a greater increase in homeostasis model assessment of β-cell function (HOMA-β) were observed with sitagliptin/metformin than with pioglitazone, while greater decreases in fasting insulin and HOMA of insulin resistance (HOMA-IR), and a greater increase in quantitative insulin sensitivity check index (QUICKI) were observed with pioglitazone than with sitagliptin/metformin. Both sitagliptin/metformin and pioglitazone were generally well tolerated. Sitagliptin/metformin led to weight loss (-1.4 kg), while pioglitazone led to weight gain (3.0 kg) (p < 0.001 for the between-group difference). Higher incidences of diarrhoea (15.3% vs. 4.3%, p < 0.001), nausea (4.6% vs. 1.2%, p = 0.02) and vomiting (1.9% vs. 0.0%, p = 0.026), and a lower incidence of oedema (1.1% vs. 7.0%, p < 0.001), were observed with sitagliptin/metformin vs. pioglitazone. The between-group difference in the incidence of hypoglycaemia did not reach statistical significance (8.4 and 4.3% with sitagliptin/metformin and pioglitazone, respectively; p = 0.055).



Compared with pioglitazone, initial therapy with a FDC of sitagliptin and metformin led to significantly greater improvement in glycaemic control as well as a higher incidence of prespecified gastrointestinal adverse events, a lower incidence of oedema and weight loss vs. weight gain.
Short- and Long-Term Effects of Real-Time Continuous Glucose Monitoring in Patients With Type 2 Diabetes

To determine whether short-time, real-time continuous glucose monitoring (RT-CGM) has long-term salutary glycemic effects in patients with type 2 diabetes who are not on prandial insulin.



This was a randomized controlled trial of 100 adults with type 2 diabetes who were not on prandial insulin. This study compared the effects of 12 weeks of intermittent RT-CGM with self-monitoring of blood glucose (SMBG) on glycemic control over a 40-week follow-up period. Subjects received diabetes care from their regular provider without therapeutic intervention from the study team.



There was a significant difference in A1C at the end of the 3-month active intervention that was sustained during the follow-up period. The mean, unadjusted A1C decreased by 1.0, 1.2, 0.8, and 0.8% in the RT-CGM group vs. 0.5, 0.5, 0.5, and 0.2% in the SMBG group at 12, 24, 38, and 52 weeks, respectively (P = 0.04). There was a significantly greater decline in A1C over the course of the study for the RT-CGM group than for the SMBG group, after adjusting for covariates (P < 0.0001). The subjects who used RT-CGM per protocol (≥48 days) improved the most (P < 0.0001). The improvement in the RT-CGM group occurred without a greater intensification of medication compared with those in the SMBG group.



Subjects with type 2 diabetes not on prandial insulin who used RT-CGM intermittently for 12 weeks significantly improved glycemic control at 12 weeks and sustained the improvement without RT-CGM during the 40-week follow-up period, compared with those who used only SMBG.
Interactions between 6-mercaptopurine therapy and thiopurinemethyl-transferase (TPMT) activity

Thiopurine-methyl-transferase (TPMT) is a key enzyme in the catabolism of 6-mercaptopurine into inactive 6methylmercaptopurine. Its activity is regulated by a genetic polymorphism. In a North American Caucasian population and in English children treated for acute lymphoblastic leukaemia 89 % have high activity, 11% have intermediate activity, and less than i % have undetectable activity . The last are at high risk of 6-mercaptopurine toxicity. Other factors might be involved in the regulation of enzyme activity. It has previously been reported that men can tolerate a higher dose of 6-mercaptopurine than women . This observation was recently supported by a Norwegian study showing higher enzyme activity in men [3], contrasting with the results of two other studies [1, 4]. In addition, the results of the former study suggested a geographical relation, in that the population living in the Northern part of the country had a greater enzyme activity than the Southern population. They also showed an interaction between enzyme activity and the use of diuretics or non-steroidal anti-inflammatory drugs. Furthermore, it has previously been suggested that the activity of TPMT may be induced by 6-mercaptopurine [4]; however, no serial measurements were performed while on treatment, so that the effect of long-term 6-mercaptopurine on TPMT activity over time is not fully understood. To address this problem directly, we have prospectively studied TPMT activity in 23 children treated in our institution for acute lymphoblastic leukaemia. The maintenance treatment consisted of daily oral 6-mercaptopurine (50 mg. m -2. day -1) adjusted to maintain granulocytes between 2 and 3 x 109/1, weekly oral methotrexate (25 rag-m -2-week -1) and for half of the patients monthly
Administration of enoxaparin 24 h after total knee arthroplasty: safer for bleeding and equally effective for deep venous thrombosis prevention

The purpose of this study was to determine the safety and effectiveness, as assessed by risk of bleeding and incidence of deep venous thrombosis (DVT), of administering delayed low-molecular-weight heparin (LMWH) after total knee arthroplasty. A prospective study of 210 consecutive patients undergoing primary unilateral total knee arthroplasty was undertaken. The patients were randomized into two groups: one of which was managed according to a standard LMWH program (LMWH-s group) and the other with delayed LMWH (LMWH-p). LMWH was initiated 12 h after wound closure in the LMWH-s group, and 24 h after wound closure in the LMWH-p group. The total blood loss in the first three postoperative days was calculated and all complications were recorded. The mean total blood loss was 435 and 387 mL in the LMWH-s group and LMWH-p group, respectively (p < 0.01). No significant difference in the incidence of symptomatic DVT was observed. The mean length of hospital stay was 7.29 days in the LMWH-s group and 6.56 days in the LMWH-p group (p < 0.05). After total knee arthroplasty, LMWH-p is safer for bleeding than LMWH-s and equally effective concerning prevention of DVT.
Long-acting injectable risperidone and metabolic ratio: a possible index of clinical outcome in treatment-resistant schizophrenic patients

It is still common to encounter a partial or no response to antipsychotic treatment in clinical practice, but only individual case reports are currently available concerning the efficacy of long-acting risperidone (RLAI) in treatment-resistant schizophrenia. The relationship between RSP and 9-OH-RSP plasma levels, and clinical response or tolerability has not yet been thoroughly assessed. This open-label, non-randomised study involved 30 outpatients with treatment-resistant schizophrenia, who were prescribed RLAI for 6 months, and clinically evaluated using the Brief Psychiatric Rating Scale (BPRS), the Positive and Negative Symptoms Scale (PANSS), the Clinical Global Impression-Improvement Scale (CGI-I), and the Simpson and Angus Scale for Extrapyramidal Side Effects (EPSE). Plasma RSP and 9-OH-RSP levels were determined at steady-state, and the metabolic ratio (MR) was calculated as plasma 9-OH-RSP/RSP levels. At the end of the study, 60% of the patients responded to RLAI (a ≥20% reduction in the PANSS score). Linear regression analysis showed a significant positive relationship between the RSP dose and active moiety (RSP + 9-OH-RSP) (r = 0.4; p = 0.02). There was a significant positive relationship between active moiety and EPSE scores (r = 0.6; p = 0.00). The BPRS responders had a significantly higher mean MR than the non-responders (3.41 ± 1.87 SD vs 1.60 ± 0.98 SD) (p = 0.00). Therapeutic drug monitoring seems to be useful in optimising the dose of RLAI, especially in the case of tolerability problems. MR might be a better index of clinical response to RLAI than the value of the active moiety, although this needs to be confirmed by further data.