nils-herrmann/clean_scirepeval huggingface dataset:
Angiographic and platelet reactivity outcomes with prasugrel 60 mg pretreatment and clopidogrel 600 mg pretreatment in primary percutaneous coronary intervention

Pretreatment with 60 mg of prasugrel is more effective than 300 mg of clopidogrel in reducing thrombotic complications with primary percutaneous coronary intervention (PCI). We compared angiographic outcomes and platelet reactivity between treatment with 60 mg of prasugrel and 600 mg of clopidogrel administered before primary PCI. In this single centre non-randomized study, 65 consecutive Asian patients with ST-elevation myocardial infarction (STEMI) received 60 mg of prasugrel before primary PCI. The pre- and post-PCI corrected thrombolysis in myocardial infarction frame count (CTFC) and the 8-h post-treatment platelet vasodilator-stimulated phosphoprotein (VASP) index was compared with a matched historical Asian STEMI cohort (n = 65) receiving 600 mg of clopidogrel pretreatment. Comparing the prasugrel and clopidogrel groups, the mean age was 54.1 ± 10.2 versus 55.5 ± 11.8 years, P = 0.238, and the mean body mass index was 24.6 ± 2.0 versus 24.7 ± 2.8 kg m−2, P = 0.393. The mean pre-PCI CTFC was 82.1 ± 30.2 versus 86.1 ± 27.6, P = 0.045, and the mean post-PCI CTFC was 21.1 ± 13.9 versus 20.1 ± 9.2, P = 0.309. Pre-PCI coronary thrombi were visualised in 6.3 versus 18.1 %, P = 0.038. The median VASP index was 22.2 ± 24.5 versus 70.5 ± 17.5 %, P < 0.001, and high on-treatment platelet reactivity (VASP index > 50 %) was observed in 13.8 versus 84.3 %, P = 0.001. Rescue intracoronary glycoprotein inhibitors were administered to 29.7 versus 51.0 %, P = 0.018, respectively. Treatment with 60 mg of prasugrel before primary PCI was associated with lower platelet reactivity, a modest trend towards better pre-PCI angiographic outcomes, less pre-PCI coronary thrombi and less rescue glycoprotein inhibitor use compared with 600 mg of clopidogrel. The very high frequency of high on-clopidogrel platelet reactivity with 600 mg of clopidogrel in this Asian STEMI cohort deserves further study.
A phase II trial of huperzine A in mild to moderate Alzheimer disease.

Huperzine A is a natural cholinesterase inhibitor derived from the Chinese herb Huperzia serrata that may compare favorably in symptomatic efficacy to cholinesterase inhibitors currently in use for Alzheimer disease (AD).



We assessed the safety, tolerability, and efficacy of huperzine A in mild to moderate AD in a multicenter trial in which 210 individuals were randomized to receive placebo (n = 70) or huperzine A (200 μg BID [n = 70] or 400 μg BID [n = 70]), for at least 16 weeks, with 177 subjects completing the treatment phase. The primary analysis assessed the cognitive effects of huperzine A 200 μg BID (change in Alzheimer's Disease Assessment Scale-cognitive subscale [ADAS-Cog] at week 16 at 200 μg BID compared to placebo). Secondary analyses assessed the effect of huperzine A 400 μg BID, as well as effect on other outcomes including Mini-Mental State Examination, Alzheimer's Disease Cooperative Study-Clinical Global Impression of Change scale, Alzheimer's Disease Cooperative Study Activities of Daily Living scale, and Neuropsychiatric Inventory (NPI).



Huperzine A 200 μg BID did not influence change in ADAS-Cog at 16 weeks. In secondary analyses, huperzine A 400 μg BID showed a 2.27-point improvement in ADAS-Cog at 11 weeks vs 0.29-point decline in the placebo group (p = 0.001), and a 1.92-point improvement vs 0.34-point improvement in the placebo arm (p = 0.07) at week 16. Changes in clinical global impression of change, NPI, and activities of daily living were not significant at either dose.



The primary efficacy analysis did not show cognitive benefit with huperzine A 200 μg BID.



This study provides Class III evidence that huperzine A 200 μg BID has no demonstrable cognitive effect in patients with mild to moderate AD.
Effects of milnacipran on the multidimensional aspects of fatigue and the relationship of fatigue to pain and function: pooled analysis of 3 fibromyalgia trials.

Fatigue is a core symptom in fibromyalgia that can negatively affect a patient's quality of life.



The objective of this study was to analyze fatigue-related data from 3 randomized, placebo-controlled trials of milnacipran (n = 3109) in fibromyalgia patients.



Fatigue was assessed with the Multidimensional Fatigue Inventory (MFI). Treatment effects were evaluated by changes in MFI total scores and identifying patients with improvement of 30% or greater from baseline. Path analyses were conducted to evaluate direct and indirect effects of treatment on fatigue.



Patients had high levels of baseline fatigue; mean MFI total score was 68.1 (of 100). After 3 months of stable-dose treatment, patients receiving milnacipran 100 and/or 200 mg/d had significant improvement in MFI total and subscale scores (P < 0.05 vs placebo). The largest treatment effect was found in patients with equal to or greater than 20% to 40% fatigue improvement. Significantly more patients met the threshold of 30% or greater with milnacipran (100 mg/d, 17.6%; 200 mg/d, 15.2%) than with placebo (9.9%); odds ratios for this responder status were 1.93 and 1.63, respectively (P < 0.05 for both doses). Path analyses indicated that up to 28% of fatigue improvement may be attributed to direct milnacipran effects (ie, not indirectly through effects on pain or other symptoms).



Fibromyalgia patients in the milnacipran studies had high levels of baseline fatigue. Patients receiving milnacipran had statistically significant and clinically meaningful reductions in fatigue that were not completely attributable to indirect treatment effects through pain reduction. Evaluating and managing fatigue are an important clinical concern when treating patients with fibromyalgia.
A randomized controlled trial of cognitive-behavioral therapy for the treatment of PTSD in the context of chronic whiplash.

Whiplash-associated disorders (WAD) are common and involve both physical and psychological impairments. Research has shown that persistent posttraumatic stress symptoms are associated with poorer functional recovery and physical therapy outcomes. Trauma-focused cognitive-behavioral therapy (TF-CBT) has shown moderate effectiveness in chronic pain samples. However, to date, there have been no clinical trials within WAD. Thus, this study will report on the effectiveness of TF-CBT in individuals meeting the criteria for current chronic WAD and posttraumatic stress disorder (PTSD).



Twenty-six participants were randomly assigned to either TF-CBT or a waitlist control, and treatment effects were evaluated at posttreatment and 6-month follow-up using a structured clinical interview, self-report questionnaires, and measures of physiological arousal and sensory pain thresholds.



Clinically significant reductions in PTSD symptoms were found in the TF-CBT group compared with the waitlist at postassessment, with further gains noted at the follow-up. The treatment of PTSD was also associated with clinically significant improvements in neck disability, physical, emotional, and social functioning and physiological reactivity to trauma cues, whereas limited changes were found in sensory pain thresholds.



This study provides support for the effectiveness of TF-CBT to target PTSD symptoms within chronic WAD. The finding that treatment of PTSD resulted in improvements in neck disability and quality of life and changes in cold pain thresholds highlights the complex and interrelating mechanisms that underlie both WAD and PTSD. Clinical implications of the findings and future research directions are discussed.
Skeletal muscle strength and endurance in patients with mild COPD and the effects of weight training.

This study poses two questions: 1) is there an abnormality in isokinetic skeletal muscle strength and endurance in mild chronic obstructive pulmonary disease (COPD)? and 2) what is the effect of a randomized, controlled, 12 week hospital outpatient weight training programme in terms of skeletal muscle function and exercise tolerance? Upper and lower limb isokinetic maximum and sustained muscle function were compared in 43 COPD patients (age 49+/-11 yrs), mean forced expiratory volume in one second (FEV1) 77+/-23% pred and 52 healthy, sedentary subjects (age 51 (10) yrs), mean FEV1 109+/-16% pred. The 43 COPD patients were randomly allocated into training (n=26) and control (n=17) groups. Isokinetic and isotonic muscle function, whole body endurance, maximal exercise capacity and lung function were measured. The COPD patients had reduced isokinetic muscle function (with the exception of sustained upper limb strength) as compared with healthy sedentary subjects. Muscle function improved after weight training in the COPD patients. Whole body endurance during treadmill walking also improved with no change in maximal oxygen consumption. A deficit in skeletal muscle function can be identified in patients with mild chronic obstructive pulmonary disease which cannot be explained by factors such as hypoxaemia and malnutrition. Intervention with weight training is effective in countering this deficit which the authors conclude is probably due to muscle deconditioning.
Cerebral Blood Flow and Glucose Metabolism in Appetite-Related Brain Regions in Type 1 Diabetic Patients After Treatment With Insulin Detemir and NPH Insulin

To test the hypothesis that insulin detemir, which is associated with less weight gain than other basal insulin formulations, exerts its weight-modulating effects by acting on brain regions involved in appetite regulation, as represented by altered cerebral blood flow (CBF) or cerebral glucose metabolism (CMRglu).



Twenty-eight male type 1 diabetic patients (age 36.9 ± 9.7 years, BMI 24.9 ± 2.7 kg/m(2), A1C 7.5 ± 0.6%) successfully completed a randomized crossover study, consisting of two periods of 12-week treatment with either insulin detemir or NPH insulin, both in combination with prandial insulin aspart. After each treatment period, patients underwent positron emission tomography scans to measure regional CBF and CMRglu.



After 12 weeks, A1C, daily insulin doses, fasting insulin, and blood glucose levels were similar between treatments. Insulin detemir resulted in body weight loss, whereas NPH insulin induced weight gain (between-treatment difference 1.3 kg; P = 0.02). After treatment with insulin detemir relative to NPH insulin, CBF was higher in brain regions involved in appetite regulation, whereas no significant difference in CMRglu was observed.



Treatment with insulin detemir versus NPH insulin resulted in weight loss, paralleled by increased CBF in appetite-related brain regions in the resting state, in men with well-controlled type 1 diabetes. These findings lend support to the hypothesis that a differential effect on the brain may contribute to the consistently observed weight-sparing effect of insulin detemir.
Prolonged intrathecal chemotherapy replacing cranial irradiation in high-risk acute lymphatic leukaemia: Long-term follow up with cerebral computed tomography scans and endocrinological studies

Cranial irradiation in children with acute lymphatic leukaemia (ALL) decreases the risk of CNS relapse but is associated with serious long-term side-effects. We present the long-term outcome of 21 children with high-risk ALL who received prolonged intrathecal chemotherapy instead of the recommended cranial irradiation. Intrathecal triple therapy (methotrexate, hydrocortisone, and cytarabine) was administered every 2nd month throughout the maintenance phase. The average number of courses of intrathecal methotrexate was 8.7 and of triple 9.0. The 5-year event-free survival was 79%. No CNS relapses occurred. CT scan was performed at diagnosis, at cessation of therapy, and 3 years thereafter. No density abnormalities, pathological contrast enhancement, ventricular dilatation, or calcifications were found. One child showed cortical atrophy both at diagnosis and at cessation of therapy. There was a slight decrease in height SDS with time but no change in weight SDS. Delayed bone age was found in 5 children. No abnormalities of growth hormone, thyroid, adrenal, or gonadal function were observed. The study indicates that extended intrathecal chemotherapy in children with high-risk ALL may provide an effective protection from CNS relapses and is associated with a low risk of long-term side-effects.
Development of a clinical prediction score for congestive heart failure diagnosis in the emergency care setting: The Brest score.

To derive and validate a clinical prediction rule of acute congestive heart failure obtainable in the emergency care setting.



Derivation of the score was performed on a retrospective 927 patients cohort admitted to our Emergency Department for dyspnea. The prediction model was externally validated on an independent 206-patient prospective cohort.



During the derivation phase, variables associated with acute congestive heart failure were included in a multivariate regression model. Logistic regression coefficients were used to assign scoring points to each variable. During the validation phase, every diagnosis was confirmed by an independent adjudication committee.



The score comprised 11 variables: age ≥65 years (1 point), seizure dyspnea (2 points), night outbreak (1 point), orthopnea (1 point), history of pulmonary edema (2 points), chronic pulmonary disease (-2 points), myocardial infarction (1 point), crackles (2 points), leg edema (1 point), ST-segment abnormality (1 point), atrial fibrillation/flutter (1 point) on electrocardiography. In the validation step, 30 patients (14.6%) had a low clinical probability of acute congestive heart failure (score ≤3), of which only 2 (6.7%) had a proven acute cardiogenic pulmonary edema. The prevalence of acute congestive heart failure was 58.5% in the 94 patients with an intermediate probability (score of 4-8) and 91.5% in the 82 patients (39.8%) with a high probability (score ≥9).



This score of acute congestive heart failure based on easily available and objective variables is entirely standardized. Applying the score to dyspneic adult emergency patients may enable a more rapid and efficient diagnostic process.
Detection of diabetic foot hyperthermia by infrared imaging

In diabetic foot, the occurrence of an ulcer is often associated with hyperthermia. Hyperthermia is defined as a temperature greater than 2.2oC in a given region of one of the foot compared to the temperature of the same region of the contralateral foot. Unfortunately, hyperthermia is not yet assessed in current diabetic foot therapy. In this paper, we propose an easy way to detect a possible hyperthermia by using an infrared camera. A specific acquisition protocol of the thermal images is proposed. A dedicated image analysis is developed: it is composed of a contour detection of the 2 feet using the Chan and Vese active contour method associated to the ICP rigid registration technique. Among 85 type II diabetes persons recruited in the Dos de Mayo hospital in Lima, Peru, 9 individuals show significant hyperthermia. It is expected that the new possibility of detecting hyperthermia in hospitals or in diabetic health centers which is now available, thanks to the proposed method, will help in reducing foot ulcer occurrence for diabetic persons.
Autophagy plays an essential role in HIV-1 infection

HIV-1 can infect and replicate in both CD4 T cells and macrophages, and direct cell-to-cell spread is an important route of HIV-1 propagation. It requires interaction between HIV-1 envelope glycoproteins (Env, composed of gp120 and gp41), expressed at the surface of infected cells, and HIV-1 receptors, CD4 and a coreceptor, on the target cells. The gp120 interacts first with CD4, which triggers conformational changes leading to increased exposure of gp120 regions (including the V3 loop) able to bind to the coreceptor, mainly CCR5 or CXCR4. This interaction induces a structural rearrangement in gp41, insertion of its N terminus fusion peptide into the target membrane, and fusion. R5 and X4 HIV-1 strains use CCR5 and CXCR4, respectively, for entry. We have previously demonstrated that, independently of HIV-1 replication, X4 HIV-infected cells trigger autophagy in the uninfected CD4 T lymphocytes. Env-mediated autophagy is dependent on the gp41 fusogenic activity but is independent of a direct CD4and CXCR4-mediated signaling pathway. Furthermore, this autophagy process is required to trigger CD4 T cell apoptosis since blockade of autophagy at different steps, by either drugs or short interfering RNAs specific for autophagy genes, totally inhibits Env-mediated apoptosis. Our last results show that autophagy and cell death are also induced in the uninfected CD4 T cells by HIV-1 R5 Env, while autophagy is inhibited in productively X4 or R5-infected CD4 T cells. In contrast, uninfected macrophages, a preserved cell population during HIV-1 infection, do not undergo X4 or R5 Env-mediated autophagy. Autophagosomes, however, are present in macrophages exposed to infectious HIV-1 particles, independently of coreceptor use. Interestingly, two populations of autophagic macrophages can be observed during their coculture with HIV-1-infected cells: one highly autophagic and the other weakly autophagic. Surprisingly, viruses could be detected in the weakly autophagic cells but not in the highly autophagic cells. In addition, we show that the triggering of autophagy in macrophages is necessary for viral replication but addition of Bafilomycin A1, which blocks the final stages of autophagy, strongly increases productive infection. Taken together, our data suggest that autophagy plays a complex, but essential, role in HIV pathology by regulating both viral replication and the fate of the target cells.
Prevention of Nocturnal Hypoglycemia Using Predictive Alarm Algorithms and Insulin Pump Suspension

The aim of this study was to develop a partial closed-loop system to safely prevent nocturnal hypoglycemia by suspending insulin delivery when hypoglycemia is predicted in type 1 diabetes.



Forty subjects with type 1 diabetes (age range 12-39 years) were studied overnight in the hospital. For the first 14 subjects, hypoglycemia (<60 mg/dl) was induced by gradually increasing the basal insulin infusion rate (without the use of pump shutoff algorithms). During the subsequent 26 patient studies, pump shutoff occurred when either three of five (n = 10) or two of five (n = 16) algorithms predicted hypoglycemia based on the glucose levels measured with the FreeStyle Navigator (Abbott Diabetes Care).



The standardized protocol induced hypoglycemia on 13 (93%) of the 14 nights. With use of a voting scheme that required three algorithms to trigger insulin pump suspension, nocturnal hypoglycemia was prevented during 6 (60%) of 10 nights. When the voting scheme was changed to require only two algorithms to predict hypoglycemia to trigger pump suspension, hypoglycemia was prevented during 12 (75%) of 16 nights. In the latter study, there were 25 predictions of hypoglycemia because some subjects had multiple hypoglycemic events during a night, and hypoglycemia was prevented for 84% of these events.



Using algorithms to shut off the insulin pump when hypoglycemia is predicted, it is possible to prevent hypoglycemia on 75% of nights (84% of events) when it would otherwise be predicted to occur.
Decision trees for indication of total hip replacement on patients with osteoarthritis.

To develop a decision tree based on health-related quality of life outcomes rather than expert consensus for determining the appropriateness of total hip replacement (THR) among patients with hip OA.



This is a prospective observational study of two independent cohorts. The derivation cohort included 590 patients recruited from seven hospitals between March 1999 and March 2000. The validation cohort included 339 patients recruited from six hospitals between September 2003 and September 2004. Socio-demographic and clinical data were collected for the participants, all of whom completed the WOMAC before hip replacement and 6 months later. Univariate and Regression Trees, by classification and regression trees (CART), analyses were performed in the derivation cohort. The decision trees derived in the derivation cohort were validated in the validation cohort.



Main variables that predicted change in the WOMAC pain and functional limitation domains were pre-intervention pain or functional limitation and the application of non-surgical treatments. CART analysis showed that when pre-intervention pain was classified as minor, or WOMAC pain or functional limitation scores were < or = 40, there was an odds ratio of 0.076 (95% CI 0.031, 0.185) of having an expected gain after THR in the WOMAC pain domain of > 30 or > 25 in the WOMAC functional limitation domain.



A simple decision tree based on WOMAC outcomes can help to determine the appropriate application of THR. It could also be used to evaluate clinical practice or for quality control.
Glycemic control with insulin glargine plus insulin glulisine versus premixed insulin analogues in real-world practices: a cost-effectiveness study with a randomized pragmatic trial design.

Cost can be an important consideration, along with safety and efficacy, in deciding the most appropriate treatment for patients with type 2 diabetes. Both basal-bolus and premixed insulin analogue regimens are widely used in clinical practice; however, limited information is available regarding cost-effectiveness.



The goal of this study was to compare glycemic control, cost-effectiveness, and quality of life effects of insulin glargine plus insulin glulisine (glargine/glulisine) versus premixed insulin analogues in real-world clinical practice.



Adults with type 2 diabetes (glycosylated hemoglobin [HbA(1c)] ≥7.0%) at 3 US endocrinology centers were randomly assigned to receive either glargine/glulisine or premixed insulin analogues and continued treatment following the centers' usual practice. HbA(1c), weight, insulin dose, concomitant oral antidiabetic drug (OAD) usage, and hypoglycemia were evaluated at baseline and 3, 6, and 9 months. Medication costs, including costs for all insulin or OAD regimens, were estimated using published wholesale acquisition costs.



A total of 197 patients were randomized to receive glargine/glulisine therapy (n = 106) or premixed analogue therapy (n = 91). Overall, the mean age was 56 years, the mean duration of diabetes was 13 years, with a mean HbA(1c) of 9.25% and mean BMI of 35.8 kg/m(2) at baseline. Patients randomized to receive glargine/glulisine had a greater mean HbA(1c) reduction from baseline (-2.3%) than patients receiving a premixed analogue regimen (-1.7%). Adjusted mean follow-up HbA(1c) was 6.9% versus 7.5%, respectively (difference, -0.59%; P < 0.01). The glargine/glulisine group also used a lower mean number of OADs (0.86 vs 1.14; difference, -0.28; P = 0.04) but had a higher weight (240 vs 235 lb; difference, 4.55 lb; P = 0.03) than the premixed analogue group at follow-up. There were no significant differences in daily insulin dose and rates of hypoglycemia. Overall medication costs per 1.0% reduction in HbA(1c) were $841 with glargine/glulisine and $1308 with premixed analogues.



Overall, treatment with glargine/glulisine provided greater improvement in glycemic control and may represent a more cost-effective treatment option than premixed regimens for patients with type 2 diabetes in real-world clinical practice. However, due to the pragmatic trial design, the study concluded before follow-up assessments were available for all randomized patients.