nils-herrmann/clean_scirepeval huggingface dataset:
Lopinavir/Ritonavir Monotherapy as Second-line Antiretroviral Treatment in Resource-Limited Settings: Week 104 Analysis of AIDS Clinical Trials Group (ACTG) A5230.

The AIDS Clinical Trials Group (ACTG) A5230 study evaluated lopinavir/ritonavir (LPV/r) monotherapy following virologic failure (VF) on first-line human immunodeficiency virus (HIV) regimens in Africa and Asia.



Eligible subjects had received first-line regimens for at least 6 months and had plasma HIV-1 RNA levels 1000-200 000 copies/mL. All subjects received LPV/r 400/100 mg twice daily. VF was defined as failure to suppress to <400 copies/mL by week 24, or confirmed rebound to >400 copies/mL at or after week 16 following confirmed suppression. Subjects with VF added emtricitabine 200 mg/tenofovir 300 mg (FTC/TDF) once daily. The probability of continued HIV-1 RNA <400 copies/mL on LPV/r monotherapy through week 104 was estimated with a 95% confidence interval (CI); predictors of treatment success were evaluated with Cox proportional hazards models.



One hundred twenty-three subjects were enrolled. Four subjects died and 2 discontinued prematurely; 117 of 123 (95%) completed 104 weeks. Through week 104, 49 subjects met the primary endpoint; 47 had VF, and 2 intensified treatment without VF. Of the 47 subjects with VF, 41 (33%) intensified treatment, and 39 of 41 subsequently achieved levels <400 copies/mL. The probability of continued suppression <400 copies/mL over 104 weeks on LPV/r monotherapy was 60% (95% CI, 50%-68%); 80%-85% maintained levels <400 copies/mL with FTC/TDF intensification as needed. Ultrasensitive assays on specimens with HIV-1 RNA level <400 copies/mL at weeks 24, 48, and 104 revealed that 61%, 62%, and 65% were suppressed to <40 copies/mL, respectively.



LPV/r monotherapy after first-line VF with FTC/TDF intensification when needed provides durable suppression of HIV-1 RNA over 104 weeks.
Randomised controlled trial of high concentration versus titrated oxygen therapy in severe exacerbations of asthma.

The effect on Paco2 of high concentration oxygen therapy when administered to patients with severe exacerbations of asthma is uncertain.



106 patients with severe exacerbations of asthma presenting to the Emergency Department were randomised to high concentration oxygen (8 l/min via medium concentration mask) or titrated oxygen (to achieve oxygen saturations between 93% and 95%) for 60 min. Patients with chronic obstructive pulmonary disease or disorders associated with hypercapnic respiratory failure were excluded. The transcutaneous partial pressure of carbon dioxide (Ptco2) was measured at 0, 20, 40 and 60 min. The primary outcome variable was the proportion of patients with a rise in Ptco2 ≥4 mm Hg at 60 min.



The proportion of patients with a rise in Ptco2 ≥4 mm Hg at 60 min was significantly higher in the high concentration oxygen group, 22/50 (44%) vs. 10/53 (19%), RR 2.3 (95% CI 1.2 to 4.4, p<0.006). The high concentration group had a higher proportion of patients with a rise in Ptco2 ≥8 mm Hg, 11/50 (22%) vs. 3/53 (6%), RR 3.9 (95% CI 1.2 to 13.1, p=0.016). All 10 patients with a final Ptco2 ≥45 mm Hg received high concentration oxygen therapy, and in five there was an increase in Ptco2 ≥10 mm Hg.



High concentration oxygen therapy causes a clinically significant increase in Ptco2 in patients presenting with severe exacerbations of asthma. A titrated oxygen regime is recommended in the treatment of severe asthma, in which oxygen is administered only to patients with hypoxaemia, in a dose that relieves hypoxaemia without causing hyperoxaemia. Clinical trial number ACTRN12607000131459.
Optimizing outcomes in ST-segment elevation myocardial infarction.

During the past two decades, major advances in the treatment of acute ST-segment elevation myocardial infarction (STEMI), including coronary care units and thrombolysis, have lowered the mortality after hospital presentation to approximately 5%. However, in recent years, there has been little further improvement in survival (1). Neither newer fibrinolytic agents nor attempts to combine a reduced-dose fibrinolytic agent with a glycoprotein (GP) IIb/IIIa inhibitor, which increase 60to 90-min infarct-artery–related patency, have resulted in improved survival (2–4). Reasons for this apparent paradox may include poor myocardial perfusion through the microvasculature despite optimal epicardial coronary artery flow, continued myocardial cell death in ischemic border zones, or an inability to impact the high mortality associated with cardiogenic shock.
A simple agent based model for detecting abnormal event patterns in distributed wireless sensor networks

Wireless Sensor networks (WSN) is a promising technology for current as well as future. There is vast use of WSN in different fields like military surveillance and target tracking, traffic management, weather forecasting, habitat monitoring, designing smart home, structural and seismic monitoring, etc. For success application of ubiquitous WSN it is important to maintain the basic security, both from external and internal attacks else entire network may collapse. Maintaining security in WSN network is not a simple job just like securing wireless networks because sensor nodes are deployed in randomize manner. Hence major challenges in WSNs are security. In this paper we have discussed different attacks in WSN and how these attacks were efficiently detected by using our agent based model. Our model identifies the abnormal event pattern sensor nodes in a largely deployed distributed sensor network under a common anomaly detection framework which will design by agent based learning and distributed data mining technique.
Effect of baseline or changes in adrenergic activity on clinical outcomes in the beta-blocker evaluation of survival trial.

Adrenergic activation is thought to be an important determinant of outcome in subjects with chronic heart failure (CHF), but baseline or serial changes in adrenergic activity have not been previously investigated in a large patient sample treated with a powerful antiadrenergic agent.



Systemic venous norepinephrine was measured at baseline, 3 months, and 12 months in the beta-Blocker Evaluation of Survival Trial (BEST), which compared placebo treatment with the beta-blocker/sympatholytic agent bucindolol. Baseline norepinephrine level was associated with a progressive increase in rates of death or death plus CHF hospitalization that was independent of treatment group. On multivariate analysis, baseline norepinephrine was also a highly significant (P<0.001) independent predictor of death. In contrast, the relation of the change in norepinephrine at 3 months to subsequent clinical outcomes was complex and treatment group-dependent. In the placebo-treated group but not in the bucindolol-treated group, marked norepinephrine increase at 3 months was associated with increased subsequent risks of death or death plus CHF hospitalization. In the bucindolol-treated group but not in the placebo-treated group, the 1st quartile of marked norepinephrine reduction was associated with an increased mortality risk. A likelihood-based method indicated that 18% of the bucindolol group but only 1% of the placebo group were at an increased risk for death related to marked reduction in norepinephrine at 3 months.



In BEST, a subset of patients treated with bucindolol had an increased risk of death as the result of sympatholysis, which compromised the efficacy of this third-generation beta-blocker.
Phase I study of capecitabine in combination with cisplatin and irinotecan in patients with advanced solid malignancies

This phase I trial assessed the safety and the maximum tolerated dose of capecitabine given for 10 days prior to a combination of cisplatin and irinotecan in patients with advanced solid malignancies. It also evaluated the changes in cisplatin DNA adducts induced by capecitabine.  Patients with refractory solid tumors who had not failed 5-fluorouracil (5-FU) analogs or topoisomerase I inhibitors were eligible. All cohorts of patients first received a 28-day cycle of cisplatin and irinotecan. Both drugs were given at a dose of 50 mg/m2 intravenously on day 1, followed by irinotecan on days 8 and 15 at the same dose. The first cycle served as an internal control. Starting from the second cycle, patients received increasing doses per cohort of capecitabine from day 1 to 10 of each cycle, followed by cisplatin on day 11 and irinotecan on days 11, 18 and 25, both at same doses as the first cycle. Cycles were repeated every 38 days. The starting dose of capecitabine was 500 mg/m2/day which was escalated by 250 mg/m2/day in the subsequent cohort of patients to reach the maximum tolerated dose (MTD). Later, additional patients were treated at the MTD of capecitabine to further evaluate the safety, pharmacodynamics, and tumor response. Patients blood was tested for cisplatin-DNA adducts to determine the impact of capecitabine on cisplatin-based therapy.  Fifteen patients received at least 2 cycles of treatment. At 1,250 mg/m2, two DLT of prolonged neutropenia of grade ≥3 were observed. The MTD for capecitabine was thus determined to be 1000 mg/m2/day. Fatigue and diarrhea of grade 1 or 2 were the most frequent toxicities at this dose level. No significant hematologic toxicity was observed at the MTD. Two complete and three partial remissions were observed. Four of the responders had received a platinum agent and/or 5-FU in the past.  A sequential treatment with capecitabine followed by cisplatin and irinotecan is well tolerated and demonstrates clinical activity in patients with advanced solid malignancies. The influence of capecitabine, if any, on the efficacy of the cisplatin-irinotecan combination is not related to a variation in cisplatin-DNA adducts.
Risk of Cardiovascular Hospitalizations from Exposure to Coarse Particulate Matter (PM10) Below the European Union Safety Threshold.

The association between exposure to air pollution and acute cardiovascular (CV) events is well documented; however, limited data are available evaluating the public health safety of various "doses" of particular matter (PM) below currently accepted safety thresholds. We explored the cross-sectional association between PM with aerodynamic diameter <10 μm (PM10) and daily CV hospitalizations in Brescia, Italy, using Poisson regression models adjusted for age, gender, and meteorologic indices. Average daily exposure to PM10 obtained from arithmetic means of air pollution data were captured by 4 selected monitoring stations. PM10 data were expressed as daily means (lag 0-day) or 3-day moving averages (lag 3-day) and categorized according to the European Union daily limit value of 50 μg/m(3). From September 2004 to September 2007, data from 6,000 acute CV admissions to a tertiary referral center were collected. An increase of 1 μg/m(3) PM10 at lag 0-day was independently associated with higher rates of acute hospitalizations for composite CV-related events (relative risk [RR] 1.004, 95% confidence interval [CI] 1.002 to 1.006), acute heart failure (RR 1.004, 95% CI 1.001 to 1.008), acute coronary syndromes (RR 1.002, 95% CI 0.999 to 1.005), malignant ventricular arrhythmias (RR 1.004, 95% CI 0.999 to 1.010), and atrial fibrillation (RR 1.008, 95% CI 1.003 to 1.012). Similar results were obtained using PM10 lag 3-day data. The excess PM10 CV hospitalization risk (by lag 0-day and lag 3-day) did not vary significantly above and below the 50 μg/m(3) safety threshold or by age and gender. In conclusion, increased levels of PM10, even below the current limits set by the European Union, were associated with excess risk for admissions for acute CV events.
Vitreomacular traction as a consequence of posterior hyaloidal contraction after transpupillary thermotherapy.

To describe the pathogenesis, clinical characteristics, management, and outcomes of patients in whom vitreomacular traction evolved pursuant to treatment of choroidal melanoma with transpupillary thermotherapy.



Retrospective, uncontrolled, observational, interventional case series.



Vitreomacular traction with macular distortion, macular edema, and vision loss developed in 6 eyes of 6 patients after successful transpupillary thermotherapy for choroidal melanoma. Clinical examination, fluorescein angiography, fundus photography, and spectral-domain optical coherence tomography were performed. Symptomatic patients underwent pars plana vitrectomy (PPV). Primary outcome measures include visual acuity and resolution of macular distortion by clinical examination, spectral-domain optical coherence tomography, or both.



In all 6 patients, the malignant lesions were treated successfully. The posterior hyaloid was attached in all eyes before transpupillary thermotherapy. All eyes demonstrated focal hyaloidal contraction and vitreomacular traction between the transpupillary thermotherapy scar and the macula. Mean time from transpupillary thermotherapy to PPV for treatment of vitreomacular traction was 23 ± 18 months. Mean length of follow-up was 11 months. Mean logarithm of the minimal angle of resolution visual acuity before transpupillary thermotherapy was 0.23 ± 0.38. Mean visual acuity after transpupillary thermotherapy was 0.53 ± 0.42. Mean visual acuity before membrane peel was 0.65 ± 0.34. Mean visual acuity after membrane peel was 0.44 ± 0.21. All patients undergoing PPV showed visual improvement.



Hyaloidal contraction can occur after transpupillary thermotherapy and is a reversible cause of vision loss. The mechanism of vision loss resulting from hyaloidal contraction is flat vitreomacular traction. PPV and membrane peeling are effective in improving macular anatomic features and visual function.
Use of DNA microarray chips for the rapid detection of Mycobacterium tuberculosis resistance to rifampicin and isoniazid

The objective of the present study was to evaluate the potential development of DNA microarray chips to detect rifampicin (RFP) and isoniazid (INH) resistance in Mycobacterium tuberculosis (MTB), using samples from clinical tuberculosis (TB) patients in Soochow City, China. The sputum samples of 42 patients with TB in the Affiliated Hospital of Infectious Diseases of Soochow University (Soochow, China) were collected. The conventional Lowenstein-Jensen culture medium (Gold Standard) was used to assess drug sensitivity using the absolute concentration method. GeeDom MTB drug detection kits were also used to create a DNA microarray chip and examine the RFP-resistance associated gene mutation points rpoB-RRDR 511, 513, 516, 526, 531 and 533, and the INH-resistance associated gene mutation points katG315 and inhA-15 of the sputum samples. Compared with the results from the absolute concentration method, the susceptibility and specificity of RFP sensitivity detected by the DNA microarray chip were 92.8 and 93.8%, respectively. The susceptibility and specificity of INH sensitivity detected were 66.7 and 81%, respectively. The rpoB-RRDR 526, 531 mutations were the primary causes of MTB RFP resistance and the katG315 mutation was the primary cause of INH resistance. The detection of rpoB and katG gene mutation points by a DNA microarray chip may be used as a rapid, accurate and bulk clinical detection method for RFP and INH resistance in MTB. This is very valuable for the control of TB epidemics.
Effect of two intensive statin regimens on progression of coronary disease.

Statins reduce adverse cardiovascular outcomes and slow the progression of coronary atherosclerosis in proportion to their ability to reduce low-density lipoprotein (LDL) cholesterol. However, few studies have either assessed the ability of intensive statin treatments to achieve disease regression or compared alternative approaches to maximal statin administration.



We performed serial intravascular ultrasonography in 1039 patients with coronary disease, at baseline and after 104 weeks of treatment with either atorvastatin, 80 mg daily, or rosuvastatin, 40 mg daily, to compare the effect of these two intensive statin regimens on the progression of coronary atherosclerosis, as well as to assess their safety and side-effect profiles.



After 104 weeks of therapy, the rosuvastatin group had lower levels of LDL cholesterol than the atorvastatin group (62.6 vs. 70.2 mg per deciliter [1.62 vs. 1.82 mmol per liter], P<0.001), and higher levels of high-density lipoprotein (HDL) cholesterol (50.4 vs. 48.6 mg per deciliter [1.30 vs. 1.26 mmol per liter], P=0.01). The primary efficacy end point, percent atheroma volume (PAV), decreased by 0.99% (95% confidence interval [CI], -1.19 to -0.63) with atorvastatin and by 1.22% (95% CI, -1.52 to -0.90) with rosuvastatin (P=0.17). The effect on the secondary efficacy end point, normalized total atheroma volume (TAV), was more favorable with rosuvastatin than with atorvastatin: -6.39 mm(3) (95% CI, -7.52 to -5.12), as compared with -4.42 mm(3) (95% CI, -5.98 to -3.26) (P=0.01). Both agents induced regression in the majority of patients: 63.2% with atorvastatin and 68.5% with rosuvastatin for PAV (P=0.07) and 64.7% and 71.3%, respectively, for TAV (P=0.02). Both agents had acceptable side-effect profiles, with a low incidence of laboratory abnormalities and cardiovascular events.



Maximal doses of rosuvastatin and atorvastatin resulted in significant regression of coronary atherosclerosis. Despite the lower level of LDL cholesterol and the higher level of HDL cholesterol achieved with rosuvastatin, a similar degree of regression of PAV was observed in the two treatment groups.
Treatment of Postmenopausal Women with Osteoporosis or Low Bone Density with Raloxifene

Raloxifene, a selective estrogen receptor modulator (SERM), has been shown to improved bone mineral density (BMD) and serum lipid profiles in healthy postmenopausal women. The objective of this study was to examine the effects of raloxifene on BMD, biochemical markers of bone metabolism and serum lipids in postmenopausal women with low bone density or osteoporosis. This Phase II, multicenter, 24-month, double-masked study assessed the efficacy and safety of raloxifene in 129 postmenopausal women (mean age ± SD: 60.2 ± 6.7 years) with osteoporosis or low bone density (baseline mean lumbar spine BMD T-score: −2.8). Women were randomly assigned to one of three treatment groups: placebo, 60 mg/day raloxifene-HCl (RLX 60) or 150 mg/day raloxifene-HCl (RLX 150) and concomitantly received 1000 mg/day calcium and 300 U/day vitamin D3. At 24 months, BMD was significantly increased in the lumbar spine (+3.2%), femoral neck (+2.1%), trochanter (+2.7%) and total hip (+1.6%) in the RLX 60 group compared with the placebo group (p<0.05). The RLX 150 group had increases in BMD similar to those observed with RLX 60. A greater percentage of raloxifene-treated patients, compared with those receiving placebo, had increased BMD (p<0.05). Serum bone-specific alkaline phosphatase activity, serum osteocalcin, and urinary type I collagen:creatinine ratio were significantly decreased in the RLX-treated groups, compared with the placebo group (p<0.01). RLX 60 treatment significantly decreased serum levels of triglycerides, and total- and LDL-cholesterol levels (p<0.01). The rates of patient discontinuation and adverse events were not significantly different among groups. In this study, raloxifene increased bone density, decreased bone turnover, and improved the serum lipid profile with minimal adverse events, and may be a safe and effective treatment for postmenopausal women with osteoporosis or low bone density.
Effects of Posttraumatic Stress Disorder and Metabolic Syndrome on Cognitive Aging in Veterans.

With the influx of veterans entering older adulthood, it is increasingly important to understand risk factors for cognitive decline. Posttraumatic stress disorder (PTSD) and the metabolic syndrome (MetS) are highly prevalent in older veterans. Although both increase risk for cognitive decline and often co-occur, it is unclear how they may interact to negatively impact cognition. The aim of this cross-sectional study was to investigate associations among PTSD, MetS, and cognitive function in older veterans. We hypothesized that co-occurring PTSD and MetS would be associated with worse cognitive performance than seen in either illness alone.



Participants completed cognitive testing to assess processing speed, verbal memory, and executive function. Data from 204 male veterans aged 55-89 were analyzed with the use of hierarchical multiple regression models.



Veterans with MetS demonstrated poorer performance on tasks of executive function (response inhibition and cognitive set shifting) and immediate verbal memory regardless of PTSD status. There was an interaction between MetS and PTSD on delayed verbal memory, suggesting that the negative impact of MetS on verbal memory was only significant for veterans not classified as having PTSD.



This is the first study to examine the impact of comorbid PTSD and MetS on cognition. The results suggest that MetS is associated with poorer verbal learning and executive functioning independent of PTSD. We discuss the necessity of monitoring cerebrovascular risk factors and providing early behavioral and/or pharmaceutical interventions to lessen the risk of cognitive decline in older age.
Phase II trial of sequential high-dose chemotherapy with paclitaxel, melphalan and cyclophosphamide, thiotepa and carboplatin with peripheral blood progenitor support in women with responding metastatic breast cancer

A single high-dose cycle of chemotherapy can produce response rates in excess of 50%. However, disease-free survival (DFS) is 15–20% at 5 years. The single most important predictor of prolonged DFS is achieving a complete response (CR). Increasing the proportion of patients who achieve a complete response may improve disease-free survival. Women with metastatic breast cancer and at least a partial response (PR) to induction chemotherapy received three separate high-dose cycles of chemotherapy with peripheral blood progenitor support and G-CSF. The first intensification was paclitaxel (825 mg/m2), the second melphalan (180 mg/m2) and the third consisted of cyclophosphamide 6000 mg/m2 (1500 mg/m2/day × 4), thiotepa 500 mg/m2 (125 mg/m2/day × 4) and carboplatin 800 mg/m2 (200 mg/m2/day × 4) (CTCb). Sixty-one women were enrolled and 60 completed all three cycles. Following the paclitaxel infusion most patients developed a reversible, predominantly sensory polyneuropathy. Of the 30 patients with measurable disease, 12 converted to CR, nine converted to a PR*, and five had a further PR, giving an overall response rate of 87%. The toxic death rate was 5%. No patient progressed on study. Thirty percent are progression-free with a median follow-up of 31 months (range 1–43 months) and overall survival is 61%. Three sequential high-dose cycles of chemotherapy are feasible and resulted in a high response rate. The challenge continues to be maintenance of response and provides the opportunity to evaluate strategies for eliminating minimal residual disease.