nils-herrmann/clean_scirepeval huggingface dataset:
Adverse events and efficacy of TNF-alpha blockade with infliximab in patients with systemic lupus erythematosus: long-term follow-up of 13 patients.

To follow-up on all available infliximab-treated SLE patients for safety and long-term efficacy in order to extract information that is useful for planning appropriate controlled trials with infliximab in SLE.



We analysed charts of six patients treated in an open-label safety trial and seven additional patients treated with infliximab on a compassionate care basis for uncontrolled SLE organ inflammation.



Out of nine patients with lupus nephritis, six had a long-term response after four infusions of infliximab in combination with AZA, lasting for up to 5 years. All five patients with lupus arthritis responded, but this response did not last for >2 months after the last infusion. One additional patient had a long-lasting improvement in SLE interstitial lung disease. No symptoms suggestive of infliximab-induced SLE flares occurred in any patients. Short-term treatment appeared relatively safe, but one patient developed deep-vein thrombosis and several infections. Under long-term therapy, two patients had life-threatening or fatal events, namely CNS lymphoma and Legionella pneumonia. Retreatment and treatment without concomitant immunosuppression led to drug reactions.



Short-term therapy with four infusions of infliximab in combination with AZA was relatively safe, and had remarkable long-term efficacy for lupus nephritis and, potentially, also interstitial lung disease. Long-term therapy with infliximab, however, was associated with severe adverse events in two out of three SLE patients, which may have been provoked by infliximab and/or by their long-standing refractory SLE and previous therapies.
Cost-effectiveness of captopril therapy after myocardial infarction.

This study sought to assess the cost-effectiveness of captopril therapy for survivors of myocardial infarction.



The recent randomized, controlled Survival and Ventricular Enlargement (SAVE) trial showed that captopril therapy improves survival in survivors of myocardial infarction with an ejection fraction < or = 40%. The present ancillary study was designed to determine how the costs required to achieve this increase in survival compared with those of other medical interventions.



We developed a decision-analytic model to assess the cost-effectiveness of captopril therapy in 50- to 80-year old survivors of myocardial infarction with an ejection fraction < or = 40%. Data on costs, utilities (health-related quality of life weights) and 4-year survival were obtained directly from the SAVE trial, and long-term survival was estimated using a Markov model. In one set of analyses, we assumed that the survival benefit associated with captopril therapy would persist beyond 4 years (persistent-benefit analyses), whereas in another set we assumed that captopril therapy incurred costs but no survival benefit beyond 4 years (limited-benefit analyses).



In the limited-benefit analyses, the incremental cost-effectiveness of captopril therapy ranged from $3,600/quality-adjusted life-year for 80-year old patients to $60,800/quality-adjusted life-year for 50-year old patients. In the persistent-benefit analyses, incremental cost-effectiveness ratios ranged from $3,700 to $10,400/quality-adjusted life-year, depending on age. The outcome was generally not sensitive to changes in estimates of variables when they were varied individually over wide ranges. In a "worst-case" analysis, incremental cost-effectiveness ratios for captopril therapy remained favorable ($8,700 to $29,200/quality-adjusted life-year) for 60- to 80-year old patients but were higher ($217,600/quality-adjusted life-year) for 50-year old patients.



We conclude that the cost-effectiveness of captopril therapy for 50- to 80-year old survivors of myocardial infarction with a low ejection fraction compares favorably with other interventions for survivors of myocardial infarction.
Enhanced regeneration and functional recovery after spinal root avulsion by manipulation of the proteoglycan receptor PTPσ

Following root avulsion, spinal nerves are physically disconnected from the spinal cord. Severe motoneuron death and inefficient axon regeneration often result in devastating motor dysfunction. Newly formed axons need to extend through inhibitory scar tissue at the CNS-PNS transitional zone before entering into a pro-regenerative peripheral nerve trajectory. CSPGs are dominant suppressors in scar tissue and exert inhibition via neuronal receptors including PTPσ. Previously, a small peptide memetic of the PTPσ wedge region named ISP (Intracellular Sigma Peptide) was generated, and its capabilities to target PTPσ and relieve CSPG inhibition were validated. Here, we demonstrate that after ventral root avulsion and immediate re-implantation, modulation of PTPσ by systemic delivery of ISP remarkably enhanced regeneration. ISP treatment reduced motoneuron death, increased the number of axons regenerating across scar tissue, rebuilt healthy neuromuscular junctions and enhanced motor functional recovery. Our study shows that modulation of PTPσ is a potential therapeutic strategy for root avulsion.
Cognitive refocusing treatment for insomnia: a randomized controlled trial in university students.

This investigation assessed the efficacy of a technique specifically designed to change the style and content of presleep thoughts in order to reduce nighttime cognitive arousal and decrease insomnia severity. This investigation, termed "cognitive refocusing treatment for insomnia" (CRT-I), previously improved sleep in a small sample of veterans with primary insomnia. In this investigation, university students with poor sleep were randomly assigned to attend either one session of CRT-I and sleep hygiene education (SH: n=27) or one session of only SH (n=24). Insomnia severity (assessed by the Insomnia Severity Index) and nighttime arousal (assessed by the Pre-Sleep Arousal Scale) were measured at baseline and 1month posttreatment. A significant Group×Time interaction for insomnia severity suggested more improved sleep over time for those receiving CRT-I+SH. A trend for a Group×Time interaction showed decreased cognitive arousal over time among those receiving CRT-I. These findings provide preliminary support for the efficacy of CRT-I for insomnia treatment among college students. Continued study of CRT-I in a community-based sample appears warranted.
The renal effects of dopamine and dobutamine in stable chronic heart failure.

Although an extensive literature exists on factors controlling sodium excretion in animal experimental models of heart failure, the relevance of these to the human condition remains largely unexplored. Increased renal sympathetic stimulation is considered responsible for heightened urinary sodium retention. Stimulation of dopamine receptors is believed to cause a diuresis. Accordingly, we sought to explore the influence of dobutamine (a beta-1 receptor agonist) and dopamine in high and low doses on a frusemide-induced diuresis in patients with chronic stable heart failure. Preliminary results indicate that low doses of dobutamine and dopamine do not increase a moderate, frusemide-induced diuresis. With higher doses dobutamine, but not dopamine, increased urine volume and sodium excretion. These results suggest that direct stimulation of beta-1 receptors increases urinary sodium excretion, either by a direct effect on the kidney or by altering systemic and renal haemodynamics.
Improved outcome for children with acute lymphoblastic leukemia: results of Dana-Farber Consortium Protocol 91-01.

The Dana-Farber Cancer Institute (DFCI) acute lymphoblastic leukemia (ALL) Consortium Protocol 91-01 was designed to improve the outcome of children with newly diagnosed ALL while minimizing toxicity. Compared with prior protocols, post-remission therapy was intensified by substituting dexamethasone for prednisone and prolonging the asparaginase intensification from 20 to 30 weeks. Between 1991 and 1995, 377 patients (age, 0-18 years) were enrolled; 137 patients were considered standard risk (SR), and 240 patients were high risk (HR). Following a 5.0-year median follow-up, the estimated 5-year event-free survival (EFS) +/- SE for all patients was 83% +/- 2%, which is superior to prior DFCI ALL Consortium protocols conducted between 1981 and 1991 (P =.03). There was no significant difference in 5-year EFS based upon risk group (87% +/- 3% for SR and 81% +/- 3% for HR, P =.24). Age at diagnosis was a statistically significant prognostic factor (P =.03), with inferior outcomes observed in infants and children 9 years or older. Patients who tolerated 25 or fewer weeks of asparaginase had a significantly worse outcome than those who received at least 26 weeks of asparaginase (P <.01, both univariate and multivariate). Older children (at least 9 years of age) were significantly more likely to have tolerated 25 or fewer weeks of asparaginase (P <.01). Treatment on Protocol 91-01 significantly improved the outcome of children with ALL, perhaps due to the prolonged asparaginase intensification and/or the use of dexamethasone. The inferior outcome of older children may be due, in part, to increased intolerance of intensive therapy.
Multiethnic genome-wide association study of cerebral white matter hyperintensities on MRI.

The burden of cerebral white matter hyperintensities (WMH) is associated with an increased risk of stroke, dementia, and death. WMH are highly heritable, but their genetic underpinnings are incompletely characterized. To identify novel genetic variants influencing WMH burden, we conducted a meta-analysis of multiethnic genome-wide association studies.



We included 21 079 middle-aged to elderly individuals from 29 population-based cohorts, who were free of dementia and stroke and were of European (n=17 936), African (n=1943), Hispanic (n=795), and Asian (n=405) descent. WMH burden was quantified on MRI either by a validated automated segmentation method or a validated visual grading scale. Genotype data in each study were imputed to the 1000 Genomes reference. Within each ethnic group, we investigated the relationship between each single-nucleotide polymorphism and WMH burden using a linear regression model adjusted for age, sex, intracranial volume, and principal components of ancestry. A meta-analysis was conducted for each ethnicity separately and for the combined sample. In the European descent samples, we confirmed a previously known locus on chr17q25 (P=2.7×10(-19)) and identified novel loci on chr10q24 (P=1.6×10(-9)) and chr2p21 (P=4.4×10(-8)). In the multiethnic meta-analysis, we identified 2 additional loci, on chr1q22 (P=2.0×10(-8)) and chr2p16 (P=1.5×10(-8)). The novel loci contained genes that have been implicated in Alzheimer disease (chr2p21 and chr10q24), intracerebral hemorrhage (chr1q22), neuroinflammatory diseases (chr2p21), and glioma (chr10q24 and chr2p16).



We identified 4 novel genetic loci that implicate inflammatory and glial proliferative pathways in the development of WMH in addition to previously proposed ischemic mechanisms.
Extent, patterns, and burden of uncontrolled disease in severe or difficult-to-treat asthma.

Characterization of uncontrolled asthma burden in a natural treatment setting can influence treatment recommendations and clinical practice. The objective was to characterize and compare the economic burden of severe or difficult-to-treat asthma in uncontrolled and controlled patients.



Baseline patient data (age > or = 13 years; n = 3916) were obtained from The Epidemiology and Natural History of Asthma: Outcomes and Treatment Regimens study. Disease control was assessed using two approaches: (i) applying criteria for control based on the Gaining Optimal Asthma Control study, and (ii) using the Asthma Therapy Assessment Questionnaire (ATAQ) to identify the number of asthma control problems. Assessments were performed at baseline, and at months 12 and 24. Monetary values were assigned to productivity loss and medical resource use. Direct and indirect costs were aggregated over 24 months and compared using Student's t-test for continuous measures and chi-squared for categorical variables.



Throughout the study, most patients had uncontrolled asthma (83% uncontrolled; 16% inconsistent control; 1.3% controlled). Controlled patients experienced fewer work or school absences and less healthcare resource use than uncontrolled patients at all study time points. Using the multilevel ATAQ control score, asthma costs increased directly with the number of asthma control problems. Costs for uncontrolled patients were more than double those of controlled patients throughout the study (14,212 vs 6,452 US Dollars; adjusted to 2002 Dollars; P < 0.0001).



This study demonstrated that few severe or difficult-to-treat asthma patients achieved control over a 2-year period and the economic consequence of uncontrolled disease is substantial.
Safety and tolerability of velafermin (CG53135-05) in patients receiving high-dose chemotherapy and autologous peripheral blood stem cell transplant

The objective of this study was to evaluate the safety and tolerability of velafermin in patients at risk of developing severe oral mucositis (OM) from chemotherapy. This study was a single-center, open-label, single-dose escalation, phase I trial in patients undergoing high-dose chemotherapy (HDCT) and autologous peripheral blood stem cell transplant (PBSCT). Velafermin was administered 24 h after stem cell infusion as a single intravenous dose infused over 15 min. Clinical safety variables were assessed and OM status scored daily for 30 days using the World Health Organization (WHO) grading scale. Thirty patients were treated with velafermin at doses of 0.03 (n = 10), 0.1 (n = 10), 0.2 (n = 8), or 0.33 mg/kg (n = 2). Patients were diagnosed with multiple myeloma (n = 16), non-Hodgkin’s lymphoma (n = 12), acute myelogenous leukemia (n = 1), or desmoplasmic round cell tumor (n = 1). Velafermin was well tolerated at doses up to 0.2 mg/kg. There were no drug-related serious adverse events. No patient discontinued because of adverse events; however, two patients administered 0.33 mg/kg developed adverse reactions immediately after infusion of the study drug. No other patients were treated at this dose level. The most frequent (>35% of patients) treatment-emergent adverse events were diarrhea, fatigue, pyrexia, vomiting, and nausea. Most adverse events were mild or moderate and resolved the same day without sequelae. Eight (27%) patients developed WHO grade 3 or 4 OM during the study; seven of these patients received high-dose melphalan as a conditioning regimen. Velafermin was well tolerated by autologous PBSCT patients at doses up to 0.2 mg/kg.
Hypofractionated concomitant intensity-modulated radiotherapy boost for high-risk prostate cancer: late toxicity.

To report the acute and late toxicities of patients with high-risk localized prostate cancer treated using a concomitant hypofractionated, intensity-modulated radiotherapy boost combined with long-term androgen deprivation therapy.



A prospective Phase I-II study of patients with any of the following: clinical Stage T3 disease, prostate-specific antigen level ≥ 20 ng/mL, or Gleason score 8-10. A dose of 45 Gy (1.8 Gy/fraction) was delivered to the pelvic lymph nodes with a concomitant 22.5 Gy prostate intensity-modulated radiotherapy boost, to a total of 67.5 Gy (2.7 Gy/fraction) in 25 fractions within 5 weeks. Image guidance was performed using three gold seed fiducials. The National Cancer Institute Common Terminology Criteria for Adverse Events, version 3.0, and Radiation Therapy Oncology Group late morbidity scores were used to assess the acute and late toxicities, respectively. Biochemical failure was determined using the Phoenix definition.



A total of 97 patients were treated and followed up for a median of 39 months, with 88% having a minimum of 24 months of follow-up. The maximal toxicity scores were recorded. The grade of acute gastrointestinal toxicity was Grade 0 in 4%, 1 in 59%, and 2 in 37%. The grade of acute urinary toxicity was Grade 0 in 8%, 1 in 50%, 2 in 39%, and 3 in 4%. The grade of late gastrointestinal toxicity was Grade 0 in 54%, 1 in 40%, and 2 in 7%. No Grade 3 or greater late gastrointestinal toxicities developed. The grade of late urinary toxicity was Grade 0 in 82%, 1 in 9%, 2 in 5%, 3 in 3%, and 4 in 1% (1 patient). All severe toxicities (Grade 3 or greater) had resolved at the last follow-up visit. The 4-year biochemical disease-free survival rate was 90.5%.



A hypofractionated intensity-modulated radiotherapy boost delivering 67.5 Gy in 25 fractions within 5 weeks combined with pelvic nodal radiotherapy and long-term androgen deprivation therapy was well tolerated, with low rates of severe toxicity. The biochemical control rate at early follow-up has been promising. Additional follow-up is needed to determine the long-term biochemical control and prostate biopsy results.
Understanding falls in osteoporosis: the viscoelastic modeling perspective.

Unsteadiness and increased postural sway predispose individuals with osteoporosis to falling. We examined this relationship from a biomechanical perspective using a viscoelastic model. Specifically, we investigated the center-of-pressure (COP) in quiet stance in 37 postmenopausal women (aged 42-79 years), diagnosed with osteopenia or osteoporosis and who engaged in a range of activity levels. Subjects stood on a force platform for two 20s intervals: one with eyes open (EO) and the other with eyes closed (EC). The COP signals were used to compute traditional measures of sway: standard deviation, range, and mean velocity. Based on the difference between the COP and its smoothed representation, we used the "COP minus center-of-mass" signal to compute selected properties of postural mechanics (stiffness and viscosity) and dynamics (frequency and damping) of stance. Sway variability and incidence of falls were not correlated even though our subjects displayed higher sway than age-matched subjects from other studies. Bone density was correlated with frequency in the mediolateral (ML) plane with EO (r=0.50, p<0.002). Irrespective of age, the decrease in postural frequency and increase in postural viscosity in the ML plane were determinants of imbalance and accounted for 18% and 8% of the variance, respectively. With EC, an additional 10% of the variance was contributed by the ML range. The increased ML viscosity was the sole predictor of falls accounting for 20% of the variance of the tendency to fall. Thus, ML frequency plays a fundamental role in preserving balance in that a low value is an important predictor of falls. Finally, although being physical activity may reduce sway, physical activity fails to improve poor postural strategies. To conclude, increases in viscosity and range elucidate further the unique strategy of ML body sway in individuals with osteopenia or osteoporosis and provide insight into how posture may be maintained by those who fear falling.
Metoprolol vs ivabradine in patients with mitral stenosis in sinus rhythm.

Severe mitral stenosis is usually symptomatic and is treated by BMV or surgery, whereas mild to moderate mitral stenosis is usually asymptomatic or mildly symptomatic and managed medically. Patients in the later group may become symptomatic during episodes of exercise and increased heart rate. Beta-blockers are frequently used in patients with mitral stenosis to control the heart rate and alleviate exercise-related symptoms. The objective of our study was to investigate the comparative efficacy of ivabradine versus metoprolol in patients with mitral stenosis in sinus rhythm.



We studied 97 patients of mitral stenosis in sinus rhythm presented with exertional symptoms. The effectiveness of Metoprolol was compared with ivabradine in alleviating these exertional symptoms in a randomized, open label non crossover study. We also assessed various stress ECG parameters, 24 hour Holter parameters and 2D Echo parameters to objectively compare the effects of ivabradine and metoprolol in these patients.



Ivabradine and metoprolol both were effective in controlling exertional symptoms. Significant improvement in objective parameters like TMT (work capacity, baseline heart rate and maximal heart rate) and 2D echocardiography (right ventricular systolic pressure) are seen with both drugs. Ivabradine controls the exertional symptoms significantly more than metoprolol. On head to head comparison there was a significant benefit of working capacity and heart rate at maximal exercise in favour of ivabradine.



Ivabradine should be strongly considered in medical management of mitral stenosis patients where beta blockers are contraindicated such as reactive airway disease. The cost of ivabradine is higher than metoprolol which might possess constraints as most of the rheumatic heat disease patients belong to low socio economic status.
Medical exercise therapy, and not arthroscopic surgery, resulted in decreased depression and anxiety in patients with degenerative meniscus injury.

The purpose of this pilot study was to compare the effectiveness of conservative therapy involving medical exercise therapy (MET) versus arthroscopic surgery in patients with knee pain, with MRI-verified degenerative meniscus. The patients were randomly assigned either to MET (n = 9) or to arthroscopic surgery (n = 8). Patients receiving MET had 3 treatments a week for 3 months, a total of 36 treatments. The arthroscopy consisted of meniscectomy with no structured conservative therapy after surgery. Assessment of pain, function, anxiety and depression were performed at inclusion and after 3 months. At the end of treatment, which was 3 months after inclusion, there were no statistical differences between the two groups regarding pain and function. However, anxiety and depression were significantly reduced in the MET group compared with the patients receiving arthroscopic surgery. Bearing in mind the low number of included patients in this pilot study, arthroscopy was found to be no better than MET regarding knee pain and overall daily function. The results from this pilot study are similar to other clinical studies, thereby demonstrating that conservative therapy is just as effective as surgery.
Efficacy and tolerability of high-dose dronabinol maintenance in HIV-positive marijuana smokers: a controlled laboratory study

Dronabinol (Δ9tetrahydrocannabinol) is approved for HIV-related anorexia, yet, little is known about its effects in HIV-positive marijuana smokers. HIV-negative marijuana smokers require higher than recommended dronabinol doses to experience expected effects. Employing a within-subjects, double-blind, placebo-controlled design, we assessed the effects of repeated high-dose dronabinol in HIV-positive marijuana smokers taking antiretroviral medication. Participants (N = 7), who smoked marijuana 4.2 ± 2.3 days/week, resided in a residential laboratory for two 16-day stays, receiving dronabinol (10 mg QID) in one stay and placebo in the other. Efficacy was assessed with objectively verified food intake and body weight. Tolerability was measured with sleep, subjective, and cognitive assessments. For analyses, each inpatient stay was divided into two phases, days 1–8 and 9–16; we compared dronabinol’s effects with placebo in each 8-day phase to investigate tolerance. Despite sustained increases in self-reported food cravings, dronabinol only increased caloric intake in the initial 8 days of dosing. Similarly, sleep quality was improved only in the first 8 days of dosing. Dronabinol’s mood-enhancing effects were sustained across the 16-day inpatient stay. Dronabinol was well tolerated, causing few negative subjective or cognitive effects. In HIV-positive marijuana smokers, high dronabinol doses safely and effectively increased caloric intake. However, repeated high-dose dronabinol appeared to result in selective tolerance to these effects. These findings indicate that HIV-positive individuals who smoke marijuana may require higher dronabinol doses than are recommended by the FDA. Future research to establish optimal dosing regimens, and reduce the development of tolerance, is required.