nils-herrmann/clean_scirepeval huggingface dataset:
Long-term effects of peginterferon alfa-2a therapy in Japanese patients with chronic hepatitis B virus infection

There is no information on the long-term effects of peginterferon (PEG-IFN) alfa-2a therapy for chronic hepatitis B (CHB) in Japan. This double-blind, randomized trial investigated the efficacy of PEG-IFN therapy. We analyzed 22 Japanese patients with CHB (hepatitis B e antigen [HBeAg]-positive: 17, HBeAg-negative: 5) treated with PEG-IFN alfa-2a and followed-up posttreatment for 5 years. Responders represented patients who showed persistent normalization of alanine transferase (ALT) levels, HBeAg clearance, and low hepatitis B virus (HBV) DNA levels (HBeAg-positive patient; <5 log copies/mL, HBeAg-negative patient; <4.3 log copies/mL) at end of treatment, and at 1, 2, 3, 4 and 5 years posttreatment. In addition, baseline HBeAg-positive patients who showed sustained normalization of ALT level, HBeAg clearance, and low HBV DNA level for more than 6 months until at 1, 2, 3, 4, and 5 years after completion of PEG-IFN were also classified as “triple responders” and the proportion of triple responders relative to all patients was termed the “triple response rate”. The response rates among HBeAg-positive patients were 13 %, 25 %, 14 %, 21 % and 21 % at end of treatment, and at 1, 2, 3, 4, and 5 years, respectively. The response rate tended to be higher in patients treated for 48 than 24 weeks. The respective response rates among HBeAg-negative patients were 0 %, 20 %, 20 %, 20 % and 25 %. During the treatment period, hepatitis B surface antigen (HBsAg) clearance at 3.5 years was noted in one patient, who was 37-year-old, male, had genotype C and received PEG-IFN alfa-2a at 90 μg for 48 weeks. At 5 years after completion of PEG-IFN, the triple response rate in HBeAg-positive patients and combined response rate in HBeAg-negative patients were 21 % (3/14) and 25 % (1/4), respectively. The triple response was seen in three patients who had all been treated with PEG-IFN for 48 weeks.
Differential effects of cocaine and cocaine alcohol on neurocognitive performance.

To investigate the dose-related effects of cocaine with or without alcohol use on the CNS by measuring performance on neurobehavioral tests.



Chronic use of cocaine is associated with persistent decrements in cognitive function that are most pronounced in heavy users. Specific neurobehavioral deficits in areas such as executive function and impulsivity would make it difficult for the cocaine abuser to discontinue using drugs. Because alcohol is often used in conjunction with cocaine, the CNS effects of alcohol when taken with cocaine deserve further investigation.



The authors evaluated the dose-related effects of cocaine and alcohol use on performance in a variety of neuropsychological tests after 1 to 3 days of abstinence and again after 4 weeks of abstinence. Fifty-six chronic cocaine abusers who had used cocaine during the past 24 to 48 hours volunteered to perform a battery of neuropsychological tests on two separate occasions during a period of enforced abstinence. In addition to using cocaine, most of the volunteers consumed alcohol. Approximately half of the participants consumed more than 10 alcohol-containing drinks per week.



After controlling for the effects of age, sex, and intelligence on performance, the authors found dose-related associations between neurobehavioral performance and cocaine dose and alcohol dose. When the influences of cocaine and alcohol on neurobehavioral performance were taken separately, cocaine and alcohol each selectively affected performance on different neurobehavioral tests after 1 to 3 days of abstinence, with these effects persisting after 4 weeks of abstinence.



The concomitant use of cocaine and alcohol may have additive negative effects on the brain as compared to the use of only one of these two substances.
Effectiveness of pharmacist intervention for asthma control improvement.

Education on optimal medication use is an essential strategy to improve asthma control. The current authors investigated whether pharmacist interventions, focused on appropriate use of asthma medication and tailor-made to the patient's current asthma control, would improve asthma control in adult patients. A 6-month randomised, controlled, parallel-group trial was conducted in 66 community pharmacies in Belgium. Patients were randomly assigned to receive usual pharmacist care (n = 94) or a pre-defined pharmacist intervention (n = 107). This intervention mainly focused on improving inhalation technique and medication adherence. Primary outcome was the level of asthma control, as assessed by the Asthma Control Test (ACT). Mean ACT scores did not change from baseline for both study groups. However, a pre-defined subgroup analysis of patients having insufficiently controlled asthma at baseline showed that the intervention had significantly increased the ACT score after 6 months compared with usual care. The intervention also reduced, for the complete study group, reliever medication use and the frequency of night-time awakenings due to asthma. Inhalation technique and adherence to controller medication were significantly better in the intervention group. In conclusion, pragmatic community pharmacy-based programmes can significantly improve therapeutic outcomes in adult asthma patients.
Lack of e Y cacy of low dose oral interferon alfa in symptomatic HIV-1 infection : a randomised , double blind , placebo controlled trial

Interferon alfa (IFN-á) exhibits dose related in vitro activity against human immunodeficiency virus (HIV), with complete inhibition of HIV replication at IFN-á concentrations > 256 IU/ml. In mid-1990, Kenyan investigators reported that oral administration of an extremely low dose (150 IU/day) of natural human (nHu) IFN-á resulted in complete alleviation of AIDS related complex and AIDS symptoms and resolution of opportunistic infections without additional treatment. Moreover, loss of HIV antibody seropositivity was reported in approximately 10% of treated patients. Subsequent small studies failed to substantiate these spectacular claims, but controversy on the eYcacy of this treatment persisted.  We studied 559 adult Ugandan patients with WHO stage 2–4 HIV infection and a Karnofsky performance score of more than 50, who had not received any drugs with antiretroviral activity in the previous 3 months. The patients were randomly assigned in a double blind fashion either to 150 IU oral nHuIFN-á/day or placebo. The duration of treatment was extended from 28 weeks to 60 weeks 9 months after enrolment had started. At that time 112 subjects had already received 28 weeks of treatment and been discontinued from the study.  Both study groups were comparable with respect to all baseline characteristics studied, except that the nHuIFN-á group had slightly lower absolute CD4+ lymphocyte counts (median 60.7 × 10/l) than the placebo group (median 85.3 × 10/l) (p=0.033). Therefore, all analyses were adjusted for CD4+ lymphocyte counts at entry. In both treatment groups there was relentless progression of HIV disease. Subjects treated with nHuIFN-á and placebo had similar mortality, disease progression rates, decline of CD4+ lymphocyte counts and Karnofsky performance scores, and prevalence of symptoms. No patient reverted to HIV-l seronegative antibody status. Serious adverse events were not seen. Quality control of the study medication documented that the active drug indeed contained IFN-á activity.  The current large, randomised, double blind, placebo controlled study did not show any benefit from oral treatment with 150 IU nHuIFN-á/day in a population of African patients with symptomatic HIV infection.
High prevalence of brown adipose tissue in adult humans.

Positron emission tomography (PET)-computed tomography (CT) has identified metabolically active supraclavicular fat in adult humans based on uptake of labeled glucose and confirmed to be brown adipose tissue (BAT) histologically. However, PET-CT has estimated a prevalence of BAT as low as 5% in adult humans, casting doubt on its significance. The true prevalence of BAT is unknown because of the suboptimal sensitivity of standard PET-CT.



The objective of the study was to determine whether BAT is present in PET-negative supraclavicular fat.



This was a prospective cohort study.



The study was conducted at a tertiary referral hospital.



Seventeen patients who underwent preoperative PET-CT for staging of head and neck malignancy participated in the study.


MAIN OUTCOME
The main outcome was signature BAT gene transcripts and protein in biopsies of supraclavicular fat with sc fat as negative control.



PET-CT was positive in three and negative in 14 patients. PET-positive fat harbored multilobulated lipid droplets and stained strongly for uncoupling protein 1 (UCP1). These features are absent in sc fat. By contrast, PET-negative fat contained a predominance of cells with unilobulated lipid droplets, with scattered cells containing multilobulated lipid droplets and variable UCP1 staining. Molecular analyses of fat biopsies showed lower but clear expression of UCP1, NDUFS3 (NADH dehydrogenase (ubiquinone) iron-sulfur protein 3), β₃-adrenoceptor, and PRDM16 (PR domain containing 16) transcripts.



BAT is present in supraclavicular fat, regardless of PET status. BAT is highly prevalent in adult humans, and its abundance determines PET status.
Cabergoline effect on blood sugar in type 2 diabetic patients with oral agent failure.

Ergot-derived dopamine D2 receptor agonists are the usual treatment of hyperprolactinemia and Parkinson's disease and recently bromocriptine has been approved for the treatment of type 2 diabetes. The aim of this study was the evaluation of short-term effect of cabergoline in poorly controlled diabetic patients with oral agent failure who refused insulin therapy.



This study was performed in 17 overweight women and men with type 2 diabetes with persistent hyperglycemia in spite of treatment with maximum dose of sulfonylurea, metformin and pioglitazone. 10 patients (group I) randomized to be treated with cabergoline 0.5 mg weekly for 3 months and 7 patients (group II) with placebo. Fasting and postprandial plasma glucose concentration and HbAlc measured in beginning and end of the study.



FBS decreased from 210.70 +/- 21.29 to 144.90 +/- 26.56 mg/dl in cabergoline group whereas it decreased in placebo group insignificantly. Postprandial blood glucose decreased from 264.2 +/- 28 mg/dl to 203.6 +/- 34.34 mg/dl in cabergoline group whereas it increased in placebo group insignificantly. HbA1c decreased in cabergoline group from 8.48 +/- 0.44 to 7.7 +/- 0.11 whereas in control group it increased insignificantly from 8.7 +/- 0.33 to 8.8 +/- 0.16.



Cabergoline improves glycemic control in type 2 diabetic patients with oral agent failure. It reduces both fasting and postprandial plasma glucose levels and causes 0.45-1.11 reduction in HbA1c.
Children's Cancer Group trials in childhood acute lymphoblastic leukemia: 1983–1995

Since 1968, the Children's Cancer Group (CCG) has treated more than 16 000 children with acute lymphoblastic leukemia (ALL). Herein, we report improvements obtained in CCG trials during two successive series of studies (1983–1988 and 1989–1995). Overall, 10-year EFS was 62% ± 10% for the 1983–1988 series and 72% ± 1% for the 1988–1995 series (P < 0.0001). Five-year cumulative rates of isolated CNS relapses were 5.9% and 4.4%. Therapy based on the Berlin–Frankfurt–Münster 76/79 study improved outcomes for intermediate and higher risk patients in the first series. For intermediate risk patients, delayed intensification (DI) was most crucial for improved outcome and cranial irradiation was safely replaced with maintenance intrathecal methotrexate, providing patients received intensified systemic therapy. In the second series, randomized trials showed better outcome with one vs no DI phase for lower risk patients, with two vs one DI phase for intermediate risk patients, and with the CCG ‘augmented regimen’ for higher risk patients with a slow day 7 marrow response. Cranial irradiation was safely replaced with additional intrathecal methotrexate for higher risk patients with a rapid day 7 marrow response. In a subsequent study, substitution of dexamethasone in place of prednisone in induction and maintenance improved outcome for standard risk patients. All patients received dexamethasone in DI. These successful treatment strategies form the basis for our current ALL trials.
Safety and immunogenicity of the tau vaccine AADvac1 in patients with Alzheimer's disease: a randomised, double-blind, placebo-controlled, phase 1 trial

Neurofibrillary pathology composed of tau protein is a main correlate of cognitive impairment in patients with Alzheimer's disease. Immunotherapy targeting pathological tau proteins is therefore a promising strategy for disease-modifying treatment of Alzheimer's disease. We have developed an active vaccine, AADvac1, against pathological tau proteins and assessed it in a phase 1 trial.



We did a first-in-man, phase 1, 12 week, randomised, double-blind, placebo-controlled study of AADvac1 with a 12 week open-label extension in patients aged 50-85 years with mild-to-moderate Alzheimer's disease at four centres in Austria. We randomly assigned patients with a computer-generated sequence in a 4:1 ratio overall to receive AADvac1 or placebo. They received three subcutaneous doses of AADvac1 or placebo from masked vaccine kits at monthly intervals, and then entered the open-label phase, in which all patients were allocated to AADvac1 treatment and received another three doses at monthly intervals. Patients, carers, and all involved with the trial were masked to treatment allocation. The primary endpoint was all-cause treatment-emergent adverse events, with separate analyses for injection site reactions and other adverse events. We include all patients who received at least one dose of AADvac1 in the safety assessment. Patients who had a positive IgG titre against the tau peptide component of AADvac1 at least once during the study were classified as responders. The first-in-man study is registered with EU Clinical Trials Register, number EudraCT 2012-003916-29, and ClinicalTrials.gov, number NCT01850238; the follow-up study, which is ongoing, is registered with EU Clinical Trials Register, number EudraCT 2013-004499-36, and ClinicalTrials.gov, number NCT02031198.



This study was done between June 9, 2013, and March 26, 2015. 30 patients were randomly assigned in the double-blind phase: 24 patients to the AADvac1 group and six to the placebo group. A total of 30 patients received AADvac1. Two patients withdrew because of serious adverse events. The most common adverse events were injection site reactions after administration (reported in 16 [53%] vaccinated patients [92 individual events]). No cases of meningoencephalitis or vasogenic oedema occurred after administration. One patient with pre-existing microhaemorrhages had newly occurring microhaemorrhages. Of 30 patients given AADvac1, 29 developed an IgG immune response. A geometric mean IgG antibody titre of 1:31415 was achieved. Baseline values of CD3+ CD4+ lymphocytes correlated with achieved antibody titres.



AADvac1 had a favourable safety profile and excellent immunogenicity in this first-in-man study. Further trials are needed to corroborate the safety assessment and to establish proof of clinical efficacy of AADvac1.
Influenza vaccination of pregnant women and protection of their infants.

There are limited data on the efficacy of vaccination against confirmed influenza in pregnant women with and those without human immunodeficiency virus (HIV) infection and protection of their infants.



We conducted two double-blind, randomized, placebo-controlled trials of trivalent inactivated influenza vaccine (IIV3) in South Africa during 2011 in pregnant women infected with HIV and during 2011 and 2012 in pregnant women who were not infected. The immunogenicity, safety, and efficacy of IIV3 in pregnant women and their infants were evaluated until 24 weeks after birth. Immune responses were measured with a hemagglutination inhibition (HAI) assay, and influenza was diagnosed by means of reverse-transcriptase-polymerase-chain-reaction (RT-PCR) assays of respiratory samples.



The study cohorts included 2116 pregnant women who were not infected with HIV and 194 pregnant women who were infected with HIV. At 1 month after vaccination, seroconversion rates and the proportion of participants with HAI titers of 1:40 or more were higher among IIV3 recipients than among placebo recipients in both cohorts. Newborns of IIV3 recipients also had higher HAI titers than newborns of placebo recipients. The attack rate for RT-PCR-confirmed influenza among both HIV-uninfected placebo recipients and their infants was 3.6%. The attack rates among HIV-uninfected IIV3 recipients and their infants were 1.8% and 1.9%, respectively, and the respective vaccine-efficacy rates were 50.4% (95% confidence interval [CI], 14.5 to 71.2) and 48.8% (95% CI, 11.6 to 70.4). Among HIV-infected women, the attack rate for placebo recipients was 17.0% and the rate for IIV3 recipients was 7.0%; the vaccine-efficacy rate for these IIV3 recipients was 57.7% (95% CI, 0.2 to 82.1).



Influenza vaccine was immunogenic in HIV-uninfected and HIV-infected pregnant women and provided partial protection against confirmed influenza in both groups of women and in infants who were not exposed to HIV. (Funded by the Bill and Melinda Gates Foundation and others; ClinicalTrials.gov numbers, NCT01306669 and NCT01306682.).
Effect of yoga on arrhythmia burden, anxiety, depression, and quality of life in paroxysmal atrial fibrillation: the YOGA My Heart Study.

The purpose of this study was to examine the impact of yoga on atrial fibrillation (AF) burden, quality of life (QoL), depression, and anxiety scores.



Yoga is known to have significant benefit on cardiovascular health. The effect of yoga in reducing AF burden is unknown.



This single-center, pre-post study enrolled patients with symptomatic paroxysmal AF with an initial 3-month noninterventional observation period followed by twice-weekly 60-min yoga training for next 3 months. AF episodes during the control and study periods as well as SF-36, Zung self-rated anxiety, and Zung self-rated depression scores at baseline, before, and after the study phase were assessed.



Yoga training reduced symptomatic AF episodes (3.8 ± 3 vs. 2.1 ± 2.6, p < 0.001), symptomatic non-AF episodes (2.9 ± 3.4 vs. 1.4 ± 2.0; p < 0.001), asymptomatic AF episodes (0.12 ± 0.44 vs. 0.04 ± 0.20; p < 0.001), and depression and anxiety (p < 0.001), and improved the QoL parameters of physical functioning, general health, vitality, social functioning, and mental health domains on SF-36 (p = 0.017, p < 0.001, p < 0.001, p = 0.019, and p < 0.001, respectively). There was significant decrease in heart rate, and systolic and diastolic blood pressure before and after yoga (p < 0.001).



In patients with paroxysmal AF, yoga improves symptoms, arrhythmia burden, heart rate, blood pressure, anxiety and depression scores, and several domains of QoL.
Comparison of the effectiveness of six and two acupuncture point regimens in osteoarthritis of the knee: a randomised trial.

Although substantial data have supported the effectiveness of acupuncture for treating knee osteoarthritis (OA), the number of points used has varied. The objective of this study was to compare the effectiveness of six and two acupuncture points in the treatment of knee OA.



A randomised trial of knee OA patients was conducted. Patients were randomly allocated into two groups of 35. The "six point group" received treatment at six acupuncture points, ST35, EX-LE4 (Neixiyan), ST36, SP9, SP10 and ST34, while the "two point group" received treatment at just the first pair of points, ST35 and EX-LE4. Both groups received twice weekly electroacupuncture on 10 occasions. Electrical stimulation was carried out at low-frequency of 3 Hz to all points, with the intensity as high as tolerable. Both groups were allowed to take a 200 mg celecoxib capsule per day for intolerable pain. Patients were assessed at baseline, week 5, week 9 and week 13, using a  of the Western Ontario and McMaster Osteoarthritis Index (WOMAC). Global assessment of change after 10 treatments was also recorded.



Acupuncture at both six and two acupuncture points was associated with significant improvement. Mean total WOMAC score at weeks 5 and 13 of patients in both groups showed no significant difference statistically (p = 0.75 and p = 0.51). Moreover, the number of celecoxib capsules taken, global assessment of global change and body weight change of both groups also showed no statistical difference.



This evidence suggests that electroacupuncture to two local points may be sufficient to treat knee OA, but in view of some limitations to this study further research is necessary before this can be stated conclusively.
Feasibility of 7 Tesla breast magnetic resonance imaging determination of intrinsic sensitivity and high-resolution magnetic resonance imaging, diffusion-weighted imaging, and (1)H-magnetic resonance spectroscopy of breast cancer patients receiving neoadjuvant therapy.

To evaluate the feasibility of 7T breast magnetic resonance imaging (MRI) by determining the intrinsic sensitivity gain compared with 3T in healthy volunteers and to explore clinical application of 7T MRI in breast cancer patients receiving neoadjuvant chemotherapy (NAC).



In 5 volunteers, the signal-to-noise ratio (SNR) was determined on proton density MRI at 3T using a conventional 4-channel bilateral breast coil and at 7T using a dedicated 2-channel unilateral breast coil, both obtained at identical scan parameters. Subsequently, consecutive breast cancer patients on NAC were included. The 7T breast MRI protocol consisted of diffusion-weighted imaging, 3D high-resolution (450 μm isotropic) T1-weighted fat-suppressed gradient-echo sequences and quantified single voxel (1)H-magnetic resonance spectroscopy. Morphology was scored according to the MRI Breast Imaging-Reporting and Data System (BI-RADS)-lexicon, and the images were compared with 3T and histopathologic findings. Image quality was evaluated using a 5-point scale.



A 5.7-fold higher SNR was measured at 7T than at 3T, which reflects the advantages of a higher field strength and the use of optimized radiofrequency coils. Three breast cancer patients were included and received a total of 13 7T MRI examinations. The image quality of the high-resolution examinations was at least satisfactory, and good to excellent in 9 of the 13 examinations performed. More anatomic detail was depicted at 7T than at 3T. In 1 case, a fat plane between the muscle and tumor was visible at 7T, but not at the clinically performed 3T examination, suggesting that there was no muscle invasion, which was confirmed by pathology. Changes in tumor apparent diffusion coefficient values could be monitored in 2 patients and were found to increase during NAC, consistent with published results from studies at lower field strengths. Apparent diffusion coefficient values increased respectively from 0.33 × 10(-3) mm(2)/s to 1.78 × 10(-3) mm(2)/s after NAC and from 1.20 × 10(-3) mm(2)/s to 1.44 × 10(-3) mm(2)/s during NAC. Choline concentrations as low as 0.77 mMol/kg(water) could be detected. In 1 patient, choline levels showed an overall decrease from 4.2 mMol/kw(water) to 2.6 mMol/kg(water) after NAC and the tumor size decreased correspondingly from 3.9 × 4.1 × 5.6 cm(3) to 2.0 × 2.7 × 2.4 cm(3). All 7T MRI findings were consistent with pathology analysis.



Dedicated 7T breast MRI is technically feasible, can provide more SNR than at 3T, and has diagnostic potential.