nils-herrmann/clean_scirepeval huggingface dataset:
Phase I–II study of docetaxel and ifosfamide combination in patients with anthracycline pretreated advanced breast cancer

Given the established individual activity of docetaxel and ifosfamide in anthracycline pretreated advanced breast cancer, the present phase I–II study aimed to define the maximum tolerated dose (MTD), the dose-limiting toxicities (DLTs), and activity of the docetaxel–ifosfamide combination in this setting. Cohorts of three to six patients with histologically confirmed metastatic breast cancer after prior anthracycline-based chemotherapy were treated at successive dose levels (DLs) with escalated doses of docetaxel 70–100 mg m−2 over 1 h on day 1 followed by ifosfamide 5–6 g m−2 divided over days 1 and 2 (2.5–3.0 g m−2 day−1 over 1 h), and recycled every 21 days. G-CSF was added once dose-limiting neutropenia was encountered at a certain DL and planned to be incorporated prophylactically in subsequent higher DLs. In total, 56 patients with a median age of 54.5 (range, 32–72) years and performance status (WHO) of 1 (range, 0–2) were treated at five DLs as follows: 21 in phase I DLs (DL1: 3, DL2: 6, DL3: 3, DL4: 6, and DL5: 3) and the remaining 35 were treated at DL4 (total of 41 patients at DL4), which was defined as the level for phase II testing. All patients were assessable for toxicity and 53 for response. Dose-limiting toxicity (with the addition of G-CSF after DL2) was reached at DL5 with two out of three initial patients developing febrile neutropenia (FN). Clinical response rates, on an intention-to-treat basis, in phase II were: 53.6% (95% CI, 38.3–68.9%); three complete remissions, 19 partial remissions, seven stable disease, and 12 progressive disease. The median response duration was 7 months (3–24 months), median time to progression 6.5 month (0.1–26 month), and median overall survival 13 months (0.1–33 months). Grade 3/4 toxicities included time to progression neutropenia in 78% of patients–with 63% developing grade 4 neutropenia (⩽7 days) and in 12% of these FN, while no grade 3/4 thrombocytopenia was observed. Other toxicities included peripheral neuropathy grade 2 only in 12%, grade 1/2 reversible CNS toxicity in 17%, no renal toxicity, grade 2 myalgias in 10%, grade 3 diarrhoea in 10%, skin/nail toxicity in 17%, and grade 2 fluid retention in 2% of patients. One patient in the study treated at phase II died as a result of acute liver failure after the first cycle. In conclusion, the present phase I–II study determined the feasibility of the docetaxel–ifosfamide combination, defined the MTD and demonstrated the encouraging activity of the regimen in phase II, thus warranting further randomised phase III comparisons to single-agent docetaxel or combinations of the latter with other active agents.
Bioengineering and phytomedicines among FY00 congressional priorities

Treatment of HIV-1-infected individuals with a combination of anti-retroviral agents results in sustained suppression of HIV-1 replication, as evidenced by a reduction in plasma viral RNA to levels below the limit of detection of available assays. However, even in patients whose plasma viral RNA levels have been suppressed to below detectable levels for up to 30 months, replication-competent virus can routinely be recovered from patient peripheral blood mononuclear cells and from semen. A reservoir of latently infected cells established early in infection may be involved in the maintenance of viral persistence despite highly active anti-retroviral therapy. However, whether virus replication persists in such patients is unknown. HIV-1 cDNA episomes are labile products of virus infection and indicative of recent infection events. Using episome-specific PCR, we demonstrate here ongoing virus replication in a large percentage of infected individuals on highly active anti-retroviral therapy, despite sustained undetectable levels of plasma viral RNA. The presence of a reservoir of 'covert' virus replication in patients on highly active anti-retroviral therapy has important implications for the clinical management of HIV-1-infected individuals and for the development of virus eradication strategies.
The incidence of hypoglycaemia in children with type 1 diabetes and treated asthma.

To investigate whether treatment of coexisting asthma has any effect on the incidence of hypoglycaemia and on glycaemic control in children with type 1 diabetes.



An observational study of children attending the paediatric diabetes clinics of five hospitals in the North Trent Region. Information on the frequency of hypoglycaemia in the preceding three months, treatment for asthma, and the individual's latest HbA1c, was recorded when they attended for review.



Data were collected on 226 children, of whom 27 (12%) had treated asthma. Only 11/27 children with asthma were taking their prescribed inhaled steroids. All used beta agonists at least once a week. There was a reduction of 20% in the incidence of hypoglycaemia in the diabetic children with treated asthma. Of the children with diabetes and treated asthma, 52% reported an episode of hypoglycaemia in the previous three months compared to 72% of those with only diabetes. There was no difference in the proportion of children experiencing nocturnal or severe hypoglycaemia. Although not significant, those with asthma and diabetes also had better overall control (HbA1c 8.8%) compared to those with diabetes alone (HbA1c 9.3%).



Diabetic children with treated asthma have significantly fewer episodes of hypoglycaemia and better glycaemic control compared to children with diabetes alone. This observation needs further investigation but raises an interesting question. Do the drugs used to treat asthma, in particular beta agonists, have the therapeutic potential to reduce hypoglycaemia and facilitate an improvement in glycaemic control?
Preventing acute decrease in renal function induced by coronary angiography (PRECORD): a prospective randomized trial.

Infusion of saline attenuates the decrease in renal function induced by radiographic contrast agents among patients with chronic renal insufficiency.



The Preventing Renal alteration in Coronary Disease (PRECORD) trial was a randomized trial to assess the effect on renal function of saline infusion during and after coronary angiography in 201 patients without severe chronic renal insufficiency (serum creatinine<140micromol/L).



All patients received standard oral hydration: 2000mL of tap water within the 24 hours after coronary angiography. Patients were randomized before the procedure to intravenous hydration (1000mL of 0.9% saline infusion) or no additional hydration. The infusion was started in the catheterization laboratory and continued for 24 hours. The primary endpoint was the change in calculated creatinine clearance between baseline and 24 hours after coronary angiography. The same ionic low osmolar radiographic contrast agent (ioxaglate) was used in all patients.



Both groups had similar baseline characteristics, including age, serum creatinine, volume of contrast and proportion of patients undergoing ad hoc coronary angioplasty. The overall decrease in serum creatinine clearance 24 hours after the procedure was -3.44 (0.68)mL/min. The change in serum creatinine clearance 24 hours after the procedure was -2.81 (1.07)mL/min in the infusion group vs -4.09 (0.91)mL/min in the control group (p=0.38).



Renal function is altered only slightly 24 hours after coronary angiography with standard oral hydration alone and is not affected by saline infusion started at the beginning of coronary angiography, even in patients with mild-to-moderate renal dysfunction.
International subarachnoid aneurysm trial – ISAT Part II: Study protocol for a randomized controlled trial

The International Subarachnoid Aneurysm Trial (ISAT) demonstrated improved one-year clinical outcomes for patients with ruptured intracranial aneurysms treated with endovascular coiling compared to surgical clipping. Patients included in ISAT were mostly good grade subarachnoid hemorrhage (SAH) patients with small anterior circulation aneurysms. The purported superiority of coiling is commonly extrapolated to patients not studied in the original trial or to those treated using new devices not available at the time. Conversely, many patients are treated by clipping despite ISAT, because they are thought either to be better candidates for surgery, or to offer more durable protection from aneurysm recurrences. These practices have never been formally validated. Thus, for many ruptured aneurysm patients the question of which treatment modality leads to a superior clinical outcome remains unclear.  ISAT II is a pragmatic, multicenter, randomized trial comparing clinical outcomes for non-ISAT patients with subarachnoid hemorrhage allocated to coiling or clipping. Inclusion criteria are broad. The primary end-point is the incidence of poor clinical outcome (defined as mRS >2) at one year, just as in ISAT. Secondary end-points include measures of treatment safety for a number of pre-specified subgroups, with efficacy end-points including the presence of a major recurrence at one year; 1,896 patients (862 each arm plus 10% losses) are required to demonstrate a significant difference between coiling and clipping, hypothesizing 23% and 30% poor clinical outcome rates, for coiling and clipping, respectively. The trial should involve at least 50 international centers, and will take approximately 12 years to complete. Analysis will be by intention-to-treat.
Neuroendocrine models of social anxiety disorder

Social anxiety disorder (SAD) is a highly prevalent and disabling disorder with key behavioral traits of social fearfulness, social avoidance, and submissiveness. Here we argue that hormonal systems play a key role in mediating social anxiety, and so may be important in SAD. Hormonal alterations, often established early in development through the interaction between biological and psychological factors (eg, genetic predisposition x early trauma), predispose to socially fearful, avoidant, and submissive behavior. However, whereas gene variants and histories of trauma persist, hormonal systems can be remodeled over the course of life. Hormones play a key role during the periods of all sensitive developmental windows (ie, prenatal, neonatal, puberty, aging), and are capable of opening up new developmental windows in adulthood. Indeed, the developmental plasticity of our social brain, and thus of social behavior in adulthood, critically depends on steroid hormones such as testosterone and peptide hormones such as oxytocin. These steroid and peptide hormones in interaction with social experiences may have potential for reprogramming the socially anxious brain. Certainly, single administrations of oxytocin and testosterone in humans reduce socially fearful, avoidant, and submissive behavior. Such work may ultimately lead to new approaches to the treatment of SAD.
A randomized controlled dismantling trial of post-workshop consultation strategies to increase effectiveness and fidelity to an evidence-based psychotherapy for Posttraumatic stress disorder

Posttraumatic Stress Disorder (PTSD) is a serious mental health condition with substantial costs to individuals and society. Among military veterans, the lifetime prevalence of PTSD has been estimated to be as high as 20%. Numerous research studies have demonstrated that short-term cognitive-behavioral psychotherapies, such as Cognitive Processing Therapy (CPT), lead to substantial and sustained improvements in PTSD symptoms. Despite known benefits, only a minority of clinicians provide these therapies. Transferring this research knowledge into clinical settings remains one of the largest hurdles to improving the health of veterans with PTSD. Attending a workshop alone is insufficient to promote adequate knowledge transfer and sustained skill; however, relatively little research has been conducted to identify effective post-training support strategies.



The current study investigates whether clinicians receiving post-workshop support (six-month duration) will deliver CPT with greater fidelity (i.e., psychotherapy adherence and competence) and have improved patient outcomes compared with clinicians receiving no formal post-workshop support. The study conditions are: technology-enhanced group tele-consultation; standard group tele-consultation; and fidelity assessment with no consultation. The primary outcome is independent assessment (via audio-recordings) of the clinicians' adherence and competence in delivering CPT. The secondary outcome is observed changes in patient symptoms during and following treatment as a function of clinician fidelity. Post-consultation interviews with clinicians will help identify facilitators and barriers to psychotherapy skill acquisition. The study results will inform how best to implement and transfer evidence-based psychotherapy (e.g., CPT) to clinical settings to attain comparable outcomes to those observed in research settings.



Findings will deepen our understanding of how much and what type of support is needed following a workshop to help clinicians become proficient in delivering a new protocol. Several influences on clinician learning and patient outcomes will be discussed. An evidence-based model of clinical consultation will be developed, with the ultimate goal of informing policy and influencing best practice in clinical consultation.
Patients' perspective on the comprehensive preventive health evaluation in veterans with spinal cord injury

Survey research methods.To assess patient satisfaction with the annual comprehensive preventative health evaluation (CPHE) and to determine if the patient's needs were being met.Department of Veterans Affairs National Survey, United States.A total of 853 subjects with spinal cord injuries participated in a mailed survey regarding the annual CPHE. Subjects were asked about satisfaction with the examination, preferences on how the examination is conducted and whether their needs were being met with the examination.In all, 76% of the subjects that responded to the survey had completed a CPHE within the previous year. Subjects cited getting their medication and supplies refilled and talking to the doctor as the top two reasons for completing the evaluation. Subjects indicated that they would most like to discuss their muscle strength and weakness, bladder care, chronic pain, digestion and bowel care issues, and equipment problems during their evaluation. The majority of subjects (81%) indicated that they were satisfied with the CPHE. Subjects that were satisfied with the CPHE were also more satisfied with other aspects of care as well.The majority of respondents had completed a CPHE within the previous year. Most respondents cite health issues related to the spinal cord injury as areas they would most like to discuss during the evaluation. The majority of subjects were satisfied with the conduct of the CPHE.
Effectiveness of a nurse-based outreach program for identifying and treating psychiatric illness in the elderly.

Elderly persons with psychiatric disorders are less likely than younger adults to be diagnosed as having a mental disorder and receive needed mental health treatment. Lack of access to care is 1 possible cause of this disparity.



To determine whether a nurse-based mobile outreach program to seriously mentally ill elderly persons is more effective than usual care in diminishing levels of depression, psychiatric symptoms, and undesirable moves (eg, nursing home placement, eviction, board and care placement).



Prospective randomized trial conducted between March 1993 and April 1996 to assess the effectiveness of the Psychogeriatric Assessment and Treatment in City Housing (PATCH) program.



Six urban public housing sites for elderly persons in Baltimore, Md.



A total of 945 (83%) of 1195 residents in the 6 sites underwent screening for psychiatric illness. Among those screened, 342 screened positive and 603 screened negative. All screen-positive subjects aged 60 years and older (n=310) and a 10% random sample of screen-negative subjects aged 60 years and older (n=61) were selected for a structured psychiatric interview. Eleven subjects moved or died; 245 (82%) of those who screened positive and 53 (88%) of those who screened negative were evaluated to determine who had a psychiatric disorder. Data were weighted to estimate the prevalence of psychiatric disorders at the 6 sites.



Among the 6 sites, residents in 3 buildings were randomized to receive the PATCH model intervention, which included educating building staff to be case finders, performing assessment in residents' apartments, and providing care when indicated; and residents in the remaining 3 buildings were randomized to receive usual care (comparison group).



Number of undesirable moves and scores on the Montgomery-Asberg Depression Rating Scale (MADRS), a measure of depressive symptoms, and the Brief Psychiatric Rating Scale (BPRS), a measure of psychiatric symptoms and behavioral disorder, in intervention vs comparison sites.



Based on weighted data, at 26 months of follow-up, psychiatric cases at the intervention sites had significantly lower (F(1)=31.18; P<.001) MADRS scores (9.1 vs 15.2) and significantly lower (F(1)=17.35; P<.001) BPRS scores (27.4 vs 33.9) than those at the nontreatment comparison sites. There was no significant difference between the groups in undesirable moves (relative risk, 0.97; 95% confidence interval, 0. 44-2.17).



These results indicate that the PATCH intervention was more effective than usual care in reducing psychiatric symptoms in persons with psychiatric disorders and those with elevated levels of psychiatric symptoms. JAMA. 2000;283:2802-2809
[Fish oil as joint lubricant?].

Mehr ist manchmal weniger: Das zeigt eine Studie, in der hochdosiertes Fischöl bei 202 Patienten mit Kniearthrose getestet wurde. Die Studientherapie, die die Patienten im Verhältnis 1 : 1 über zwei Jahre erhielten, bestand aus täglich 15 ml Fischöl in hoher (4,5 g Omega-3-Fettsäuren) bzw. in niedriger Dosierung (gemischt mit Sonnenblumenöl; 0,45 g Omega-3-Fettsäuren). Die niedrige Dosis wurde anstelle von Placebo verwendet. Beim primären Studienendpunkt Schmerz gemäß WOMACScore nach 3, 6, 12, 18 und 24 Monaten war nur zu den beiden letzten Terminen ein signikanter Unterschied zu erkennen, und zwar zugunsten der niedrig dosierten Supplementation. Diese schnitt zum letzten Zeitpunkt auch im WOMAC-Funktionsscore, einem sekundären Endpunkt, besser ab. Keine Veränderung und kein Unterschied zeigten sich dagegen nach zwei Jahren im Volumen der Knorpelplatten, dem zweiten primären Endpunkt.
Time-varying analysis of heart rate variability signals with a Kalman smoother algorithm.

A time-varying parametric spectrum estimation method for analysing non-stationary heart rate variability signals is presented. As a case study, the dynamics of heart rate variability during an orthostatic test is examined. In this method, the non-stationary signal is first modelled with a time-varying autoregressive model and the model parameters are estimated recursively with a Kalman smoother algorithm. The benefit of using the Kalman smoother is that the lag error present in a Kalman filter, as well as in all other adaptive filters, can be avoided. The spectrum estimates for each time instant are then obtained from the estimated model parameters. Statistics of the obtained spectrum estimates are derived using the error propagation principle. The obtained spectrum estimates can further be decomposed into separate components and, thus, the time variation of low- and high-frequency components of heart rate variability can be examined separately. By using the presented method, high resolution time-varying spectrum estimates with no lag error can be produced. Other benefits of the method are the straightforward procedure for evaluating the statistics of the spectrum estimates and the option of spectral decomposition.
Using randomized designs to evaluate client-centered programs to prevent adolescent pregnancy.

Interventions to prevent adolescent pregnancy (primarily curriculum-based programs) have not produced convincing evidence as to their success. Moreover, many evaluation approaches have been inadequate to assess program effectiveness. Therefore, rigorous evaluation of different kinds of interventions may help identify potentially effective strategies to prevent adolescent pregnancy.



An experimental design, in which clients were randomized to treatment and control groups, was used to evaluate the effects of a "client-centered" approach to reducing pregnancy among high-risk young people in seven communities in Washington State. Four projects served 1,042 youth (clients aged 9-13), and three served 690 teenagers (primarily clients aged 14-17). Projects offered a wide variety of services tailored to individual clients' needs, including counseling, mentoring and advocacy.



On average, clients in the treatment group at youth sites received 14 hours of service, and their teenage counterparts received 27 hours; controls received only 2-5 hours of service. At one youth site, clients were less likely to intend to have intercourse after the intervention than before; at another, they became less likely to intend to use substances. Clients at one teenage project reported reduced sexual behavior and improved contraceptive use after receiving services; teenagers at another site reported reduced sexual intentions and drug use, and a greater intention to use contraceptives. The programs showed no other effects on factors that place young people at risk of becoming pregnant, including their sexual values and educational aspirations, communication with their parents (measured at youth sites only), and sexual and contraceptive behavior (assessed for teenagers only).



High-risk clients likely need considerably more intervention time and more intensive services than programs normally provide. Rigorous evaluation designs allow continued assessment that can guide program modifications to maximize effects.
How Secure Are FPGAs in Cryptographic Applications? (Long Version) ?

The use of FPGAs for cryptographic applications is highly attractive for a variety of reasons but at the same time there are many open issues related to the general security of FPGAs. This contribution attempts to provide a state-of-the-art description of this topic. First, the advantages of reconfigurable hardware for cryptographic applications are discussed from a systems perspective. Second, potential security problems of FPGAs are described in detail, followed by a proposal of a some countermeasure. Third, a list of open research problems is provided. Even though there have been many contributions dealing with the algorithmic aspects of cryptographic schemes implemented on FPGAs, this contribution appears to be the first comprehensive treatment of system and