nils-herrmann/clean_scirepeval huggingface dataset:
Randomized, controlled pharmacokinetic and pharmacodynamic evaluation of albinterferon in patients with chronic hepatitis B infection.

Albinterferon is a fusion of albumin and interferon-α2b developed to improve the pharmacokinetics, convenience, and potential efficacy of interferon-α for the treatment of chronic hepatitis infections.



This open-label, randomized, active-controlled, multicenter study investigated the safety and efficacy of albinterferon in patients with chronic hepatitis B virus (HBV) infection who were e-antigen (HBeAg) positive. One hundred and forty-one patients received one of four albinterferon doses/regimens or pegylated-interferon-α2a. Primary efficacy outcomes were changes in serum HBeAg and antibody, HBV-DNA, and alanine aminotransferase. Principal safety outcomes were changes in laboratory values, pulmonary function, and adverse events.



The study was prematurely terminated as phase III trials in hepatitis C infection indicated noninferior efficacy but inferior safety compared with pegylated-interferon-α2a. Here, all treatment groups had a significant reduction in HBV-DNA from baseline. Reductions in HBV-DNA were not significantly different, except the 1200 μg every 4 weeks albinterferon dose which was inferior compared with pegylated-interferon-α2a. The serum alanine aminotransferase levels decreased in all arms. The per-patient incidence of adverse events was not significantly different for albinterferon (96.4-100%) and pegylated-interferon-α2a (93.1%). Total adverse events, however, were higher for albinterferon and correlated to dose. Decreased lung function was found in all arms (∼93% of patients), and was more common in some albinterferon groups.



Albinterferon doses with similar anti-HBV efficacy to pegylated-interferon-α2a had higher rates of certain adverse events, particularly changes in lung diffusion capacity (http://www.clinicaltrials.gov number NCT00964665).
New onset vasomotor symptoms but not musculoskeletal symptoms associate with clinical outcomes on extended adjuvant letrozole - Analyses from NCIC CTG MA.17.

New onset symptoms on adjuvant aromatase inhibitors for hormone receptor positive early breast cancer may associate with clinical outcomes. We performed this exploratory analysis of the association of new onset musculoskeletal (MSK) and vasomotor (VM) symptoms with clinical outcomes in the NCIC CTG MA.17 trial 5 years of extended adjuvant endocrine therapy with letrozole after tamoxifen.



Symptoms were collected at baseline, 1, 6, and every 12 months on study. Multivariate Cox Models adjusting for age, nodal status, duration of tamoxifen and prior chemotherapy were used to compare disease-free survival (DFS), distant disease-free survival (DDFS), and overall survival (OS) based on data collected before, and after, the unblinding between women with VM or MSK symptoms and those without.



Data post-unblinding showed new VM symptoms on extended letrozole significantly improved DFS and DDFS when occurring 1 month (DFS HR 0.52, 95% CI, 0.28-0.96; p = 0.04; DDFS HR 0.49, 95% CI, 0.24-0.99; p = 0.046) and 6 months (DFS HR 0.43, 95% CI, 0.24-0.78; p = 0.006; DDFS HR 0.44, 95% CI, 0.22-0.85; p = 0.02) after treatment initiation. Those with new VM symptoms at 12 months also had a significantly better DFS (HR 0.47, 95% CI 0.26, 0.84; P = 0.01) and a trend in improved DDFS. Only a trend to improved OS was found for those with VM symptoms 6 month after treatment. No significant improvement was found for those with new MSK symptoms at any time point or for any endpoint.



New onset VM symptoms with extended letrozole may be useful in predicting treatment benefit.
More rigorous protocol adherence to intensive structured management improves blood pressure control in primary care: results from the Valsartan Intensified Primary carE Reduction of Blood Pressure study

To examine protocol adherence to structured intensive management in the Valsartan Intensified Primary carE Reduction of Blood Pressure (VIPER-BP) study involving 119 primary care clinics and 1562 randomized participants.



Prospective criteria for assessing adherence to treatment prescription, uptitration, and visit attendance at 6, 10, 14, and 18 weeks postrandomization were applied to 1038 intervention participants. Protocol adherence scores of 1-5 (least to most adherent) were compared to blood pressure (BP) control during 26 weeks of follow-up.



Mean age was 59.3 ± 12.0 years, 963 (62%) were men, and 1045 (67%) had longstanding hypertension. Clinic attendance dropped from 91 (week 6) to 83% (week 26) and pharmacological instructions were followed for 93% (baseline) to 61% at week 14 (uptitration failures commonly representing protocol deviations). Overall, 26-week BP levels and BP target attainment ranged from 132 ± 14/79 ± 9 and 51% to 141 ± 15/83 ± 11  mmHg and 19% in those participants subject to the highest (n = 270, 26%) versus least (n = 148, 14%) per protocol adherence, respectively; adjusted relative risk (RR) 1.22 per unit protocol adherence score, 95% confidence interval (CI) 1.15-1.31; for achieving BP target (P < 0.001). Participants with a per protocol score of 4 or 5 (512/1038, 49.3%) were 1.54-fold (95% CI 1.31-1.81; P < 0.001) more likely to achieve their individual BP target compared with usual care. Clinics equipped with a practice nurse significantly influenced protocol adherence (adjusted RR 1.20, 95% CI 1.06-1.37; P = 0.004) and individual BP control (RR 1.21, 95% CI 1.04-1.41; P = 0.015).



There is considerable potential for structured care management to improve BP control in primary care, especially when optimally applied.
Long-term effects of the family bereavement program on multiple indicators of grief in parentally bereaved children and adolescents.

This article reports on results from a randomized experimental trial of the effects of the Family Bereavement Program (FBP) on multiple measures of grief experienced by parentally bereaved children and adolescents over a 6-year period.



Participants were 244 youths (ages 8-16, mean age = 11.4 years) from 156 families that had experienced the death of a parent. The sample consisted of 53% boys and 47% girls; ethnicity was 67% non-Hispanic White and 33% ethnic minority. Families were randomly assigned to the FBP (N = 135) or a literature control condition (N = 109). Two grief measures, the Texas Revised Inventory of Grief and the Intrusive Grief Thoughts Scale (IGTS) were administered at 4 times over 6 years: pretest, posttest, and 11-month and 6-year follow-ups. A 3rd measure, an adaptation of the Inventory of Traumatic Grief (ITG) was administered only at the 6-year follow-up.



Compared with the control group, the FBP group showed a greater reduction in their level of problematic grief (IGTS) at posttest and 6-year follow-up and in the percentage at clinical levels of problematic grief at the posttest. The FBP also reduced scores on a dimension of the ITG,  those who experienced lower levels of grief at program entry, older youths, and boys.



These are the first findings from a randomized trial with long-term follow-up of the effects of a program to reduce problematic levels of grief of parentally bereaved youths.
Development and pilot testing of a new psychosocial intervention for older Latinos with chronic psychosis.

Latinos constitute the largest minority in the United States, and there is an increasing number of Latino patients with schizophrenia and other psychoses living into old age. However, few specific behavioral interventions have been developed aimed at improving the functioning of this group. We evaluated a psychosocial intervention designed to improve the everyday living skills of middle-aged and older outpatients with very chronic psychotic disorders. Three psychiatric clinics, specializing in care of Latinos, were randomly assigned to (1) a 24-session intervention entitled Programa de Entrenamiento para el Desarrollo de Aptitudes para Latinos (PEDAL) group therapy (n = 21) targeting areas identified in our previous work as being problematic for this population (e.g., using public transportation) or (2) a time-equivalent friendly support group (SG; n = 8). Compared to the patients randomized to SG, PEDAL-treated patients' performance on everyday living skills improved significantly postintervention and was still significantly better at a 6-month maintenance follow-up period and at a 12-month no-treatment follow-up period. There was no significant change in psychopathology. Limitations of this pilot study are discussed. Results suggest that participation in this skills training program, designed specifically for older Latino patients with long-standing psychotic disorders, has the potential to significantly increase the patients' independence and improve functional skills.
Benefits associated with achieving optimal risk factor levels for the primary prevention of cardiovascular disease in older men.

Most incident cardiovascular disease (CVD) occurs after patients reach the age of 65. The additive benefits of aggressive risk factor management with advancing age are not well established.



To evaluate the relationship between control of four modifiable risk factors (smoking, non-high density lipoprotein cholesterol, blood pressure, and aspirin use) and risk of CVD in a primary prevention population of older men.



U.S. male physicians from the Physicians' Health Study (n = 4182; an epidemiologic follow-up of a randomized trial of aspirin and beta-carotene) who in 1997 were ≥ 65 years, free of CVD and diabetes, and had a blood sample on file were studied. Cox proportional hazard models were adjusted for age and competing causes of death. The first of any CVD event, defined as cardiovascular death, nonfatal myocardial infarction, angina, coronary revascularization, nonfatal stroke, transient ischemic attack, carotid artery surgery, and other peripheral vascular disease surgery, was measured.



Mean follow-up was 9.3 years, mean age was 73 years, and 96% were nonsmokers. Compared with when 4 of 4 risk factors were controlled (6.0% of participants), control of 0 of 4 risk factors almost quadrupled the risk of CVD (0.4% of participants; event rate 41.2%; hazard ratio [HR] 3.83, 95% confidence interval [95% CI] 1.72-8.55); control of 1 of 4 risk factors more than doubled the risk (14.2% of participants; HR 2.53, 95% CI 1.80-3.57); control of 2 of 4 risk factors almost doubled the risk (43.8% of participants; HR 1.94, 95% CI 1.41-2.69), and those with control of 3 of 4 risk factors also were at increased risk (35.6% of participants; HR 1.80, 95% CI 1.30-2.50). Control of each additional risk factor was associated with greater cardiovascular protection (P for trend P = .002). Depending on the number of risk factors controlled, the number-needed to control to prevent one CVD event ranged from 5 to 22.



Control of 4 treatable risk factors (nonsmoking, control of non-high density lipoprotein cholesterol and blood pressure, and aspirin use) was associated with substantial protection against incident cardiovascular events in older men even after adjustment for competing causes of mortality.
Manipulating epileptiform bursting in the rat hippocampus using chaos control and adaptive techniques

Epilepsy is a relatively common disease, afflicting 1%-2% of the population, yet many epileptic patients are not sufficiently helped by current pharmacological therapies. Recent reports have suggested that chaos control techniques may be useful for electrically manipulating epileptiform bursting behavior in vitro and could possibly lead to an alternative method for preventing seizures. We implemented chaos control of spontaneous bursting in the rat hippocampal slice using robust control techniques: stable manifold placement (SMP) and an adaptive tracking (AT) algorithm designed to overcome nonstationarity. We examined the effect of several factors, including control radius size and synaptic plasticity, on control efficacy. AT improved control efficacy over basic SMP control, but relatively frequent stimulation was still necessary and very tight control was only achieved for brief stretches. A novel technique was developed for validating period-1 orbit detection in noisy systems by forcing the system directly onto the period-1 orbit. This forcing analysis suggested that period-1 orbits were indeed present but that control would be difficult because of high noise levels and nonstationarity. Noise might actually be lower in vivo, where regulatory inputs to the hippocampus are still intact. Thus, it may still be feasible to use chaos control algorithms for preventing epileptic seizures.
Addiction severity assessment tool: development of a self-report measure for clients in substance abuse treatment.

This article describes the development and reliability and validity testing of the Addiction Severity Assessment Tool (ASAT), a brief, 27-item multidimensional self-report measure of problem severity in daily functioning, relational functioning, dysphoric states, dependence severity, recovery skill/self-efficacy, and existential factors for adult substance abuse clients. Items generated for an Alpha version were conceptually and empirically evaluated. A Beta version underwent further empirical evaluation and item selection. Cross validation of the final version examined internal consistency, test-retest reliability, factor structure, and convergent/discriminant and known groups validity. Sensitivity to change was evaluated in a 3-month outcome study. Clients were recruited from inpatient, outpatient and residential substance abuse treatment centers, and a sample of 238 nonpatients were also recruited from community groups. The Beta version was tested with 201 clients, and cross validation involved 242 clients. Well-known standardized, self-report and interview-based comparison measures were used to test convergent/discriminant validity of the ASAT. Reliability coefficients for the six ASAT domains were acceptable. Reasonable convergent/discriminant and known groups, construct validity were demonstrated, along with sensitivity to change of the domain scale scores. The ASAT appears to comprise a useful new tool for assessing clinical outcomes of adult clients in substance abuse treatment.
Effect of Transcranial Direct-Current Stimulation Combined with Treadmill Training on Balance and Functional Performance in Children with Cerebral Palsy: A Double-Blind Randomized Controlled Trial

Cerebral palsy refers to permanent, mutable motor development disorders stemming from a primary brain lesion, causing secondary musculoskeletal problems and limitations in activities of daily living. The aim of the present study was to determine the effects of gait training combined with transcranial direct-current stimulation over the primary motor cortex on balance and functional performance in children with cerebral palsy.



A double-blind randomized controlled study was carried out with 24 children aged five to 12 years with cerebral palsy randomly allocated to two intervention groups (blocks of six and stratified based on GMFCS level (levels I-II or level III).The experimental group (12 children) was submitted to treadmill training and anodal stimulation of the primary motor cortex. The control group (12 children) was submitted to treadmill training and placebo transcranial direct-current stimulation. Training was performed in five weekly sessions for 2 weeks. Evaluations consisted of stabilometric analysis as well as the administration of the Pediatric Balance Scale and Pediatric Evaluation of Disability Inventory one week before the intervention, one week after the completion of the intervention and one month after the completion of the intervention. All patients and two examiners were blinded to the allocation of the children to the different groups.



The experimental group exhibited better results in comparison to the control group with regard to anteroposterior sway (eyes open and closed; p<0.05), mediolateral sway (eyes closed; p<0.05) and the Pediatric Balance Scale both one week and one month after the completion of the protocol.



Gait training on a treadmill combined with anodal stimulation of the primary motor cortex led to improvements in static balance and functional performance in children with cerebral palsy.
Efficacy and Safety of Lisdexamfetamine Dimesylate in Children with Attention-Deficit/Hyperactivity Disorder and Recent Methylphenidate Use

Lisdexamfetamine dimesylate (LDX) is a long-acting prodrug stimulant for the treatment of attention-deficit/hyperactivity disorder (ADHD). Post hoc subgroup analyses were performed from two studies in children with ADHD to compare the efficacy of LDX in participants who had received prior methylphenidate (MPH) treatment with that of the overall study populations.



Study 1 (7-week; open-label design) and study 2 (randomized, double-blind, placebo-controlled, crossover, laboratory school design) enrolled children aged 6-12 years with ADHD and baseline ADHD Rating Scale IV (ADHD-RS-IV) total score ≥28. Both studies excluded children whose prestudy ADHD treatment provided effective control of ADHD symptoms with an acceptable safety profile. Post hoc efficacy analyses were performed in children who had received MPH within 6 months of study enrollment. Efficacy measures included the following scales: ADHD-RS-IV, Clinical Global Impressions-Improvement (CGI-I), Expression and Emotion Scale for Children (EESC), Behavior Rating Inventory of Executive Function (BRIEF), Swanson, Kotkin, Agler, M-Flynn, and Pelham (SKAMP), and Permanent Product Measure of Performance (PERMP).



In studies 1 and 2, 83/318 (26%) and 67/129 (52%) participants, respectively, had received MPH within 6 months and were not adequately controlled on current medication with acceptable tolerability; most of these participants had received long-acting MPH. In prior MPH participants, efficacy assessments demonstrated improvements from baseline (study 1) and versus placebo (study 2) that were comparable with those seen in the respective overall study population. Safety profiles were consistent with long-acting stimulant use.



In two studies, children who had received prior MPH treatment improved during treatment with LDX and experienced similar improvements in their symptoms as the overall study populations. For children with ADHD who were previously treated with MPH, LDX may, therefore, be an efficacious treatment option.
Post-traumatic stress disorder in the context of terrorism and other civil conflict in Northern Ireland: randomised controlled trial.

To evaluate the effectiveness of cognitive therapy for post-traumatic stress disorder related to terrorism and other civil conflict in Northern Ireland.



Randomised controlled trial.



Community treatment centre, Northern Ireland.



58 consecutive patients with chronic post-traumatic stress disorder (median 5.2 years, range 3 months to 32 years) mostly resulting from multiple traumas linked to terrorism and other civil conflict.



Immediate cognitive therapy compared with a waiting list control condition for 12 weeks followed by treatment. Treatment comprised a mean of 5.9 sessions during 12 weeks and 2.0 sessions thereafter.



Primary outcome measures were patients' scores for post-traumatic stress disorder (post-traumatic stress diagnostic scale) and depression (Beck depression inventory). The secondary outcome measure was scores for occupational and social functioning (work related disability, social disability, and family related disability) on the Sheehan disability scale.



At 12 weeks after randomisation, immediate cognitive therapy was associated with significantly greater improvement than the waiting list control group in the symptoms of post-traumatic stress disorder (mean difference 9.6, 95% confidence interval 3.6 to 15.6), depression (mean difference 10.1, 4.8 to 15.3), and self reported occupational and social functioning (mean difference 1.3, 0.3 to 2.5). Effect sizes from before to after treatment were large: post-traumatic stress disorder 1.25, depression 1.05, and occupational and social functioning 1.17. No change was observed in the control group.



Cognitive therapy is an effective treatment for post-traumatic stress disorder related to terrorism and other civil conflict.
Borderline Hypertension Discovered During Screening: Effect of Twelve Months’ Treatment

The frequency of borderline hypertension (diastolic BP 95 to 109mm Hg) is described in 5,877 men and 1,125 women attending a screening clinic. Borderline hypertension is more frequent in each 5- year age group in men than women. The results of the initial 12 months treatment show a greater fall in mean systolic and diastolic pressures in those on active treatment in comparison with placebo. Over the same 12 months the sum of selected ECG precordial lead voltages shows a significant fall in those on active treatment as compared with those on placebo.
A modified regimen of pegylated liposomal doxorubicin, bortezomib and dexamethasone (DVD) is effective and well tolerated for previously untreated multiple myeloma patients.

The combination of pegylated liposomal doxorubicin (PLD), bortezomib and dexamethasone has shown efficacy in the treatment of multiple myeloma (MM) patients. Our earlier retrospective study suggested that modification of the doses, schedules and route of administration of these drugs appears to reduce toxicity without compromising anti-MM activity. As a result, we evaluated this modified drug combination in the frontline setting in a prospective multicentre phase II trial. Thirty-five previously untreated MM patients were enrolled. Dexamethasone IV 40 mg, bortezomib 1 mg/m(2) and PLD 5 mg/m(2) were administered on days 1, 4, 8 and 11 of a 4-week cycle. Patients were treated to their maximum response plus two additional cycles. The treatment regimen was discontinued after a maximum of eight cycles. Our modified schedule and dosing regimen achieved a high overall response rate of 86%, while showing a marked decrease in the incidence and severity of peripheral neuropathy, palmar-plantar erythrodysesthesia and myelosuppression compared to the standard dosing on a 3-week cycle using these drugs. This modified regimen of dexamethasone, bortezomib and PLD shows improved tolerability and safety while maintaining a high response rate when compared to standard treatment with these agents in the frontline setting.
Burden of gastroesophageal reflux disease in Shanghai, China.

Data on the impact of gastroesophageal reflux disease (GERD) on health-related quality of life (HRQL) in Asian countries are scarce.



This study evaluated the impact of GERD on HRQL in Shanghai, China.



One thousand two hundred adult inhabitants of Shanghai, selected using randomized cluster sampling.



Participants completed Mandarin versions of the Reflux Disease Questionnaire (RDQ), GERD impact scale, quality of life in reflux and dyspepsia (QOLRAD) questionnaire and short-form-36 (SF-36). GERD was defined as heartburn and/or regurgitation of any frequency during the 1-week recall period of the RDQ. A clinically meaningful impairment of HRQL was defined as a statistically significant decrease of >or=0.5 points in a QOLRAD dimension or >or=5 points in an SF-36 dimension.



Overall, 1034 subjects completed the survey (86.2% response rate); 919 responses were suitable for analysis. The prevalence of GERD was 6.2%. GERD was associated with meaningfully impaired HRQL in the QOLRAD dimensions of vitality, eating/drinking and emotional well-being, but not sleep or physical/social functioning, and in all SF-36 dimensions except social functioning. Respondents with GERD experienced eating and drinking problems (47%), sleep impairment (32%) and reduced work productivity (32%).



GERD has a clinically meaningful impact on HRQL in Shanghai, China.