nils-herrmann/clean_scirepeval huggingface dataset:
Off-treatment virologic relapse and outcomes of re-treatment in chronic hepatitis B patients who achieved complete viral suppression with oral nucleos(t)ide analogs

The durability of off-treatment virologic responses has not been fully elucidated in chronic hepatitis B (CHB) patients who have previously achieved complete virologic suppression with nucleos(t)ide analog (NA) therapy. This study aimed to assess off-treatment virologic relapse rates and to characterize the outcomes of subsequent re-treatment in CHB patients who have discontinued oral NA following complete virologic suppression.



Ninety-five CHB patients who showed complete virologic suppression were withdrawn from NAs: entecavir, lamivudine, and clevudine in 67, 15, and 13 patients, respectively. Consolidation therapy was given for 6 and 12 months for HBeAg-positive and -negative CHB, respectively, before cessation. Virologic relapse was managed with the same NA that had induced complete virologic response before discontinuation.



The cumulative rates of virologic relapse at 12 and 24 months were 73.8% and 87.1%, respectively. The relapse rates were independent of HBeAg positivity, HBeAg seroconversion, and type of oral NA. In a multivariate analysis, duration of oral NA therapy was the only significant predicting factor associated with off-treatment virologic relapse. Although the majority of patients regained complete virologic suppression, some patients did not respond to re-treatment with the initial NA and developed genotypic resistance.



NA consolidation therapy for 6 and 12 months is associated with high off-treatment virologic relapse in HBeAg-positive and -negative CHB patients, respectively. Drugs with high genetic barriers to resistance should be considered as a rescue therapy for off-treatment relapse in CHB.
Changes in serum lipoprotein(a) in hyperlipidemic subjects undergoing long-term treatment with lipid-lowering drugs

Though the exact physiology and pathology of lipoprotein (a) [Lp(a)] remains unknown, it has been demonstrated that increased serum Lp(a) levels are correlated with an increased risk of atherosclerotic vascular disease. The effects of lipid-lowering drugs on Lp(a) levels is unclear because of inconsistencies between study designs. This study analyzes the effects of the commonly used lipid-lowering drugs pravastatin (PRAV), lovastatin (LOV), and cholestyramine (CHOL) on serum Lp(a) and other serum lipid levels in a parallel study design. Hyperlipidemic men (n=32) were enrolled from three centers and treated for 48 weeks in a multicenter clinical trial using PRAV, LOV, CHOL, or a placebo (for the first 16 weeks only). Baseline serum low-density lipoproteins (LDL-C), high-density lipoproteins (HDL-C), and triglycerides were 199±38, 40±9, and 160±70 mg/dl, respectively. At the end of 48 weeks, serum plasma LDL-C declined in patients randomized to PRAV, LOV, and CHOL, respectively, by 31%, 29%, and 23% (all p<0.001); HDL increased by 4%, 11%, and 11% (all p<0.001); and TG changed by −16%, −28%, and + 43% (all p<0.001). Subjects in PRAV and LOV changed Lp(a) by 9% and 3%, respectively. Although there was an initial Lp(a) decline in the first 8 weeks of CHOL therapy (p<0.05, ANOVA), this returned to baseline after 48 weeks. In this parallel study design PRAV, LOV, and CHOL are effective LDL-lowering medications with minimal effects on plasma Lp(a).
Effects of doxazosin and propranolol on A2A adenosine receptors in essential hypertension.

A2A adenosine receptors inhibit neutrophil adhesion and superoxide anion generation. The aim of the present study was to evaluate the effect of antihypertensive treatment with doxazosin or propranolol on the binding and functional parameters of A2A adenosine receptors of lymphocytes and neutrophils in essential hypertensive patients. Two groups of previously untreated, essential hypertensive patients were studied. The mean affinity (K(d)) and density (B(max)) of adenosine receptors, by the A2A selective radioligand [3H]-ZM-241385 binding assays, and EC50, by cAMP assays, were obtained first on no medication and a second time after treatment for up to 13 weeks with doxazosin (13 patients) or propranolol (8 patients). A third group of 15 healthy normotensive volunteers matched by age, sex, and body mass index was used as a control. Binding and functional parameters of the A2A adenosine receptors were significantly higher in the 2 hypertensive groups than in controls (P always <0.0001), both in lymphocyte and neutrophil membranes. After treatment with propranolol, the binding parameters did not change significantly, whereas after treatment with doxazosin, K(d), B(max), and EC50 values returned to control levels. In never-treated essential hypertensive patients, lower affinity, higher density, and impaired function of A2A adenosine receptors are present. The binding and functional parameters of A2A adenosine receptors appear to be normalized after treatment with doxazosin but not with propranolol.
Effect of an integrated community-based package for maternal and newborn care on feeding patterns during the first 12 weeks of life: a cluster-randomized trial in a South African township.

To analyse the effect of community-based counselling on feeding patterns during the first 12 weeks after birth, and to study whether the effect differs by maternal HIV status, educational level or household wealth.



Cluster-randomized trial with fifteen clusters in each arm to evaluate an integrated package providing two pregnancy and five postnatal home visits delivered by community health workers. Infant feeding data were collected using 24 h recall of nineteen food and fluid items.



A township near Durban, South Africa.



Pregnant women (1894 intervention and 2243 control) aged 17 years or more.



Twelve weeks after birth, 1629 (intervention) and 1865 (control) mother-infant pairs were available for analysis. Socio-economic conditions differed slightly across intervention groups, which were considered in the analyses. There was no effect on early initiation of breast-feeding. At 12 weeks of age the intervention doubled exclusive breast-feeding (OR=2·29; 95 % CI 1·80, 2·92), increased exclusive formula-feeding (OR=1·70; 95 % CI 1·28, 2·27), increased predominant breast-feeding (OR=1·71; 95 % CI 1·34, 2·19), decreased mixed formula-feeding (OR=0·68; 95 % CI 0·55, 0·83) and decreased mixed breast-feeding (OR=0·54; 95 % CI 0·44, 0·67). The effect on exclusive breast-feeding at 12 weeks was stronger among HIV-negative mothers than HIV-positive mothers (P=0·01), while the effect on mixed formula-feeding was significant only among HIV-positive mothers (P=0·03). The effect on exclusive feeding was not different by household wealth or maternal education levels.



A perinatal intervention package delivered by community health workers was effective in increasing exclusive breast-feeding, exclusive formula-feeding and decreasing mixed feeding.
Physical inactivity and arterial stiffness in COPD

Arterial stiffness is an important predictor of cardiovascular risk besides classic cardiovascular risk factors. Previous studies showed that arterial stiffness is increased in patients with COPD compared to healthy controls and exercise training may reduce arterial stiffness. Since physical inactivity is frequently observed in patients with COPD and exercise training may improve arterial stiffness, we hypothesized that low daily physical activity may be associated with increased arterial stiffness.



In 123 patients with COPD (72% men; mean [standard deviation] age: 62 [7.5] years; median [quartile] forced expiratory volume in 1 second 35 [27/65] %predicted), arterial stiffness was assessed by augmentation index (AI). Daily physical activity level (PAL) was measured by an activity monitor (SenseWear Pro™) >1 week. The association between AI and PAL was investigated by univariate and multivariate regression analysis, taking into account disease-specific characteristics and comorbidities.



Patients suffered from moderate (35%), severe (32%), and very severe (33%) COPD, and 22% were active smokers. Median (quartile) PAL was 1.4 (1.3/1.5) and mean (standard deviation) AI 26% (9.2%). PAL showed a negative association with AI (B=-9.32, P=0.017) independent of age, sex, blood pressure, and airflow limitation.



In COPD patients, a higher PAL seems to favorably influence arterial stiffness and therefore may reduce cardiovascular risk.
The cost-effectiveness of aripiprazole as adjunctive therapy in major depressive disorder: Thai economic model.

Aripiprazole is the first atypical antipsychotic approved for adjunctive treatment to antidepressant therapy in patients with major depressive disorder (MDD). The current study aims to present an economic model and cost-effectiveness estimates for aripiprazole compared with placebo as adjunctive therapy to antidepressant treatment in patients with MDD who showed an incomplete response to a prospective 8-week trial of antidepressant therapy.



An economic model of MDD treatment was developed to estimate the clinical and economic outcomes in Thai patients. Efficacy data were derived from a pooled analysis of two studies. A cost-effectiveness analysis was constructed in simulate the impact of treatment outcomes and costs over a 6-week time horizon. The primary outcome of the model was remission of symptoms. Quality-adjusted life-year (QALYs) was the secondary outcome. The event probabilities were used to derive the transitional probability used in the model and to calculate the weighted cost of each treatment outcome. Only direct costs were considered. One-way sensitivity analysis was performed to test the sensitivity of the model outputs.



Treatment with aripiprazole came at the total costs per remission of 30,970 Baht while treatment with placebo came at the total costs per remission of 28,409 Baht. Placebo had lower total costs per QALY than aripiprazole (35,511 Baht vs. 38,713 Baht). The incremental cost-effectiveness ratio (ICER) of augmentation with aripiprazole compared with placebo was 2,561 Baht per remission gained and 3,201 Baht per QALY gained. Aripiprazole dominated placebo if the value of transitional probability of remission changed to a value of greater than 0.348 from the base-case value of 0.257. Aripiprazole was more cost-effective than placebo as adjunctive therapy if the unit cost of aripiprazole is more than 48.9% discount.



Adjunctive aripiprazole is not more cost-effective than adjunctive placebo in Thai patients with MDD who showed an inadequate response to at least one prospective antidepressant therapy. Remission rates and unit cost are the key parameters involving the cost-effectiveness of aripiprazole.
Serum steroid and sex hormone-binding globulin concentrations and the risk of incident benign prostatic hyperplasia: results from the prostate cancer prevention trial.

The authors conducted a nested case-control study of serum steroid concentrations and risk of benign prostatic hyperplasia (BPH), using data from the placebo arm of the Prostate Cancer Prevention Trial (1993-2003). Incident BPH over 7 years (n = 708) was defined as receipt of treatment, a report of 2 International Prostate Symptom Score (IPSS) values greater than 14, or 2 increases of 5 or more from baseline IPSS values with at least 1 value greater than or equal to 12. Controls (n = 709) were selected from men who reported no BPH treatment or any IPSS greater than 7. Baseline serum was analyzed for testosterone, estradiol, estrone, 5alpha-androstane-3alpha, 17beta-diol-glucuronide, and sex hormone-binding globulin. Covariate-adjusted odds ratios contrasting the highest quartiles with the lowest quartiles of testosterone, estradiol, and testosterone:17beta-diol-glucuronide ratio were 0.64 (95% confidence interval (CI): 0.43, 0.95; P(trend) = 0.04), 0.72 (95% CI: 0.53, 0.98; P(trend) = 0.09), and 0.64 (95% CI: 0.46, 0.89; P(trend) = 0.004), respectively. Findings did not differ by age, body mass index, time to BPH endpoint, or type of BPH endpoint. High testosterone levels, estradiol levels, and testosterone:17beta-diol-glucuronide ratio are associated with reduced BPH risk, which may reflect decreased activity of 5-alpha-reductase. Genetic or environmental factors that affect the activity of 5-alpha-reductase may be important in the development of symptomatic BPH.
Phase II randomized trial of neoadjuvant metformin plus letrozole versus placebo plus letrozole for estrogen receptor positive postmenopausal breast cancer (METEOR)

Neoadjuvant endocrine therapy with an aromatase inhibitor has shown efficacy comparable to that of neoadjuvant chemotherapy in patients with postmenopausal breast cancer. Preclinical and clinical studies have shown that the antidiabetic drug metformin has anti-tumor activity. This prospective, multicenter, phase II randomized, placebo controlled trial was designed to evaluate the direct anti-tumor effect of metformin in non-diabetic postmenopausal women with estrogen-receptor (ER) positive breast cancer. Patients meeting the inclusion criteria and providing written informed consent will be randomized to 24 weeks of neoadjuvant treatment with letrozole (2.5 mg/day) and either metformin (2000 mg/day) or placebo. Target accrual number is 104 patients per arm. The primary endpoint will be clinical response rate, as measured by calipers. Secondary endpoints include pathologic complete response rate, breast conserving rate, change in Ki67 expression, breast density change, and toxicity profile. Molecular assays will be performed using samples obtained before treatment, at week 4, and postoperatively. This study will provide direct evidence of the anti-tumor effect of metformin in non-diabetic, postmenopausal patients with ER-positive breast cancer.
Mindfulness based cognitive therapy versus treatment as usual in adults with attention deficit hyperactivity disorder (ADHD)

Adults with attention deficit hyperactivity disorder (ADHD) often present with a lifelong pattern of core symptoms that is associated with impairments of functioning in daily life. This has a substantial personal and economic impact. In clinical practice there is a high need for additional or alternative interventions for existing treatments, usually consisting of pharmacotherapy and/or psycho-education. Although previous studies show preliminary evidence for the effectiveness of mindfulness-based interventions in reducing ADHD symptoms and improving executive functioning, these studies have methodological limitations. This study will take account of these limitations and will examine the effectiveness of Mindfulness Based Cognitive Therapy (MBCT) in further detail.



A multi-centre, parallel-group, randomised controlled trial will be conducted in N = 120 adults with ADHD. Patients will be randomised to MBCT in addition to treatment as usual (TAU) or TAU alone. Assessments will take place at baseline and at three, six and nine months after baseline. Primary outcome measure will be severity of ADHD symptoms rated by a blinded clinician. Secondary outcome measures will be self-reported ADHD symptoms, executive functioning, mindfulness skills, self-compassion, positive mental health and general functioning. In addition, a cost-effectiveness analysis will be conducted.



This trial will offer valuable information about the clinical and cost-effectiveness of MBCT in addition to TAU compared to TAU alone in adults swith ADHD.
A phase II study of weekly high-dose 5-fluorouracil and leucovorin plus biweekly alternating doxorubicin and cisplatin for advanced gastric carcinoma

On the basis of recent clinical data suggesting that high-dose continuous 5-fluorouracil (5-FU) is able to overcome resistance to 5-FU bolus application in gastric carcinoma, a phase II study was performed to evaluate the activity and toxicity of weekly high-dose 5-FU and leucovorin plus biweekly alternating doxorubicin and cisplatin as the first-line treatment in patients with advanced gastric carcinoma. Between October 1995 and September 1997, 24 consecutive patients with locally advanced (n = 4) or metastatic (n = 20) gastric carcinomas were treated with a combination of 500 mg/m2 leucovorin as a 2-h infusion, followed by 2.0 g/m2 5-FU as a 24-h continuous infusion once weekly for 6 weeks, plus 20 mg/m2 doxorubicin as a bolus application and 50 mg/m2 cisplatin as a 1-h infusion, week 1, 3 and 5 (FLAP regimen). Response, toxicity and survival data were evaluated. A total of 20 patients were evaluable for response and 24 for toxicity. Objective responses were observed in 11 patients (55%) with no complete remission. Four patients (20%) showed stabilization and 5 patients (25%) experienced progressive disease. The median time to disease progression was 8 months and the overall duration of survival was 14 months. Myelosuppression was significant. In 2 patients, grade 4 WHO thrombocytopenia and leukopenia/anaemia respectively were registered, but there were no treatment-related deaths. We conclude that the weekly alternating FLAP regimen is effective in advanced gastric carcinoma with tolerable toxicity. However, significant myelotoxicity and frequent hospitalization suggest that FLAP should not be preferred to other regimens used in metastatic disease. Currently we intend to establish this regimen in the neoadjuvant setting in patients with primary unresectable localized gastric carcinomas.
Microwave ablation of hepatic tumors using dual-loop probes: Results of a phase I clinical trial

Hepatic tumors are a common cause of death worldwide. However, few patients are candidates for resection at the time of presentation. Microwave ablation is a viable alternative available for these patients. To date, only straight antennas are used for microwave ablation. Recently, a prototype loop-shaped microwave antenna was developed that, in animal studies, more effectively kills tumors. For this study, the dualprobe lesions were created by placing the probes in both tumors and normal livers. Lesions were created with 60 watts applied power for 5–7 minutes. The livers were sectioned and stained for viability. The average ablation volume was 63.9 ±8.7 cm3. Microwave ablation with the loop probes results in complete tumor kill at the ablation/tumor interface, and adjacent to surrounding blood vessels. In addition, vessels within the ablation/tumor interface failed to show viable cells. The shape of the lesions was not distorted by proximity to blood vessels. The advantages of this configuration over conventional straight probes include the ability to encircle a tumor, deliver large amounts of precisely targeted microwave energy to the tumor, and spare normal liver outside the loop.
Effects of delayed psychosocial interventions versus early psychosocial interventions for women with early stage breast cancer.

The importance of psychosocial counselling after a diagnosis of cancer has been acknowledged and many intervention studies have been carried out, with the aim to find out which types of intervention are most effective in enhancing quality of life in cancer patients. A factor which could be part of effective counselling could be the time of offering psychosocial counselling. The aim of this study was to research the effect of time of enrolment in a psychosocial group intervention on psychosocial adjustment.



In the present study, 67 women with early stage breast cancer were randomised in a psychosocial group intervention program starting within 4 months after surgery or in the same intervention program starting at least 3 months later.



The main conclusion of this study is that women who started with their intervention early were less distressed at 6 months follow-up than women who were in the delayed condition. Medical and demographic variables were predictive for some psychosocial adjustment indicators, but were not associated with time of enrolment. Regardless of time of enrolment, women improved in distress, body image and recreational activities, but showed a decrease in social interaction.



Though results are limited, based on these results we suggest that psychosocial counselling should be offered as soon after diagnosis or surgery for breast cancer.



Women diagnosed with primary breast cancer should be able to start with psychological counselling soon after being diagnosed, to prevent them from becoming distressed at long term.
Vitamin D status and coronary flow reserve measured by positron emission tomography: a co-twin control study.

Vitamin D insufficiency is associated with increased cardiovascular events in the general population. Additionally, low serum 25-hydroxyvitamin D [25(OH)D] is associated with endothelial dysfunction and arterial stiffness. However, little is known about the association between serum 25(OH)D level and myocardial blood flow.



Our objective was to examine the association between serum 25(OH)D levels and coronary flow reserve (CFR) measured by (13)N-positron emission tomography in asymptomatic middle-aged male twins.



The Emory Twin Study is a cross-sectional study of soldiers from the Vietnam Era Registry.



The study was conducted at the General Clinical Research Center, Emory University, Atlanta, GA.



A total of 368 middle-aged male twins were enrolled for the study. Serum 25(OH)D levels were measured in all subjects and classified as vitamin D insufficiency [25(OH)D <30 ng/ml] or sufficiency [25(OH)D ≥30 ng/ml]. Positron emission tomography with [(13)N]ammonia was used to evaluate myocardial blood flow at rest and after adenosine stress. CFR was measured as the ratio of maximum to rest myocardial blood flow.



Primary outcome was CFR measurement.



Mean overall serum 25(OH)D concentration was 37.0 ± 21.4 ng/ml; 167 twins (45%) were vitamin D insufficient. CFR was significantly lower in subjects with vitamin D insufficiency compared with subjects with vitamin D sufficiency (2.41 vs. 2.64; P = 0.007), even after adjustment for traditional cardiovascular risk factors, serum PTH, calcium, and phosphorus levels, and season. An abnormal CFR (CFR <2) was more prevalent in subjects with vitamin D insufficiency than with vitamin D sufficiency (31 vs. 20%; P = 0.03). In addition, in vitamin D status-discordant twin pairs, CFR was significantly lower in the vitamin D-insufficient twin than in the vitamin D-sufficient co-twin (2.35 vs. 2.58; P = 0.037).



Vitamin D insufficiency is associated with lower CFR in men. This association may help explain some of the increased cardiovascular risk reported in individuals with vitamin D insufficiency.
Factors related to psychosocial adjustment in children with end-stage renal failure

Psychological functioning and adjustment to dialysis were assessed in the families of 60 children and adolescents undergoing chronic dialysis. Sociodemographic factors, treatment variables, health status and satisfaction with health care provision were also measured. Correlation analyses identified a number of important factors associated with poor adjustment to dialysis and/or anxiety and depression in children and parents. Particularly at risk are parents in lower socioeconomic status households, parents with large families, parents with limited support and parents of young children. Children were more at risk where there was greater functional impairment caused by illness.