nils-herrmann/clean_scirepeval huggingface dataset:
Inhibition of phenobarbitone N-glucosidation by valproate.

Plasma phenobarbitone concentrations and daily urinary excretion of phenobarbitone and its metabolites p-hydroxyphenobarbitone (conjugated and unconjugated), and [S]-phenobarbitone-N-glucoside were measured under steady-state conditions in two groups of epileptic patients, (i) taking phenobarbitone with or without other drugs, but not valproate (n = 12), and (ii) taking phenobarbitone with other drugs including valproate (n = 8). Mean steady-state plasma phenobarbitone concentrations were 5.9 mg l-1 higher, relative to drug dose, in the patients taking valproate than in those not taking valproate. Urinary excretion of [S]-phenobarbitone-N-glucoside was significantly lower in the group taking valproate (1.9 +/- s.d. 2.0% of phenobarbitone dose vs 16.2 +/- s.d. 9.9%). Urinary excretion of phenobarbitone (23.7 +/- s.d. 9.8% vs 48.2 +/- s.d. 13.6%) and unconjugated p-hydroxyphenobarbitone (5.7 +/- s.d. 3.9% vs 16.0 +/- s.d. 9.1%) was higher in those taking valproate, while conjugated p-hydroxyphenobarbitone excretion was similar in both groups (8.3 +/- s.d. 4.9% vs 6.5 +/- s.d. 2.9%). Valproate appeared to inhibit both the direct N-glucosidation of phenobarbitone and the O-glucuronidation of p-hydroxyphenobarbitone.
Petasites hybridus root (butterbur) is an effective preventive treatment for migraine.

To evaluate the clinical efficacy of a standardized special root extract from the plant Petasites hybridus as a preventive therapy for migraine.



This is a three-arm, parallel-group, randomized trial comparing Petasites extract 75 mg bid, Petasites extract 50 mg bid, or placebo bid in 245 patients with migraine. Eligible patients met International Headache Society criteria for migraine, were ages 18 to 65, and had at least two to six attacks per month over the preceding 3 months. The main outcome measure was the decrease in migraine attack frequency per month calculated as percentage change from baseline over a 4-month treatment period.



Over 4 months of treatment, in the per-protocol analysis, migraine attack frequency was reduced by 48% for Petasites extract 75 mg bid (p = 0.0012 vs placebo), 36% for Petasites extract 50 mg bid (p = 0.127 vs placebo), and 26% for the placebo group. The proportion of patients with a > or =50% reduction in attack frequency after 4 months was 68% for patients in the Petasites extract 75-mg arm and 49% for the placebo arm (p < 0.05). Results were also significant in favor of Petasites 75 mg at 1, 2, and 3 months based on this endpoint. The most frequently reported adverse reactions considered possibly related to treatment were mild gastrointestinal events, predominantly burping.



Petasites extract 75 mg bid is more effective than placebo and is well tolerated as a preventive therapy for migraine. Petasites 50 mg PO bid was not significantly more effective than placebo on the primary study endpoints.
Diversion of methadone and buprenorphine from opioid substitution treatment: patients who regularly sell or share their medication.

Diversion-the practice of patients selling or sharing their medication-is a much debated problem of opioid substitution treatment. Regular diversion by patients was studied at 11 opioid substitution treatment programs in the south of Sweden. Using quantitative and qualitative data, it was investigated whether those patients differ from other patients, their motives for and means of diversion, and who the recipients are. Regular diverters are a small, yet heterogeneous group. Continued illicit drug use, however, stands out as a common risk factor. Pecuniary need and a desire to help friends are other important motives. The client base mainly consists of people from the regular diverters' own drug milieus.
Effect of Perineal Self-Acupressure on Constipation: A Randomized Controlled Trial

The efficacy of perineal self-acupressure in treating constipation is uncertain. We aimed to evaluate whether perineal self-acupressure would improve patient reports of quality of life and bowel function at 4 weeks after training. A randomized, parallel group trial was conducted. The study took place at the UCLA Department of Medicine. One hundred adult patients who met Rome III criteria for functional constipation participated. The control group received information about standard constipation treatment options, while the treatment group received training in perineal self-acupressure plus standard treatment options. Primary outcome was the Patient Assessment of Constipation Quality of Life (PAC-QOL). Secondary outcomes included patient assessments of bowel function (as measured by a modified Bowel Function Index (BFI)), and health and well-being (as measured by the SF-12v2). The mean PAC-QOL was improved by 0.76 in the treatment group and by 0.17 in the control group (treatment-effect difference, 0.59 [95 % CI, 0.37 to 0.81]; p < 0.01). The mean modified BFI was improved by 18.1 in the treatment group and by 4.2 in the control group (treatment-effect difference, 13.8 [95 % CI, 5.1 to 22.5]; p < 0.01). The mean SF-12v2 Physical Component Score was improved by 2.69 in the treatment group and reduced by 0.36 in the control group (treatment-effect difference, 3.05, [95 % CI, 0.85 to 5.25]; p < 0.01); and the mean SF-12v2 Mental Component Score was improved by 3.12 in the treatment group and improved by 0.30 in the control group (treatment-effect difference, 2.82, [95 % CI, −0.10 to 5.74]; p < 0.07). The trial was not blinded. Among patients with constipation, perineal self-acupressure improves self-reported assessments of quality of life, bowel function, and health and well-being relative to providing standard constipation treatment options alone.
Maximum tolerated dose in a phase I trial on adaptive dose painting by numbers for head and neck cancer.

To determine the maximum tolerated dose (MTD) in a phase I trial on adaptive dose-painting-by-numbers (DPBN) for non-metastatic head and neck cancer.



Adaptive intensity-modulated radiotherapy was based on voxel intensity of pre-treatment and per-treatment [(18)F]fluoro-2-deoxy-d-glucose positron emission tomography ((18)F-FDG-PET) scans. Dose was escalated to a median total dose of 80.9 Gy in the high-dose clinical target volume (dose level I) and 85.9 Gy in the gross tumor volume (dose level II). The MTD would be reached, if ≥ 33% of patients developed any grade ≥ 4 toxicity (DLT) up to 3 months follow-up.



Between February 2007 and August 2009, seven patients at dose level I and 14 at dose level II were treated. All patients completed treatment without interruption. At a median follow-up for surviving patients of 38 (dose level I) and 22 months (dose level II) there was no grade ≥ 4 toxicity during treatment and follow-up but six cases of mucosal ulcers at latency of 4-10 months, of which five (36%) were observed at dose level II. Mucosal ulcers healed spontaneously in four patients.



Considering late mucosal ulcers as DLT, the MTD of a median dose of 80.9 Gy has been reached in our trial.
Cardiovascular Risk Factors in Parents of Food-Allergic Children

Previous studies suggest that chronic stress may induce immune system malfunction and a broad range of adverse health outcomes; however, the underlying pathways for this relationship are unclear. Our study aimed to elucidate this question by examining the relationship between parental cardiovascular risk factors including systolic blood pressure (SBP), diastolic blood pressure (DBP), body mass index (BMI), and waist-to-hip ratio (WHR) and maternal psychological stress score (MPSS) relative to the severity of the child's food allergy (FA) and number of affected children. SBP, DBP, BMI, and WHR were measured and calculated at the time of recruitment by trained nurses. MPSS was obtained based on self-report questionnaires covering lifestyle adjustments, perceived chronic stress, and quality of life. General linear models examined whether caregiver chronic stress was associated with FA. For mothers with children under age 5 years, SBP, DBP and number of affected children had strong and graded relationships with severity of the child's FA. MPSS was also significantly and positively associated with child FA severity (P < 0.001). However, no relationships were found between FA severity, BMI, or WHR for either parent. This was also the case for paternal SBP, DBP, and number of affected children of any age. There is a strong and graded link between cardiovascular risk and perceived stress in mothers of food-allergic children under age 5. Findings may have important implications for family-centered care of FA, may generalize to caregivers of children with chronic conditions, and extend the literature on allostatic load.
Does the organisational model of dementia case management make a difference in satisfaction with case management and caregiver burden? An evaluation study.

In the Netherlands, various organisational models of dementia case management exist. In this study the following four models are distinguished, based on differences in the availability of the service and in the case management function: Model 1: the case management service is available from first dementia symptoms + is always a separate specialist function; Model 2: the case management service is only available after a formal dementia diagnosis + is always a separate specialist function; Model 3: the case management service is available from first dementia symptoms + is often a combined function; Model 4: the case management service is only available after a formal dementia diagnosis + is often a combined function. The objectives of this study are to give insight into whether satisfaction with dementia case management and the development of caregiver burden depend on the organisational model.



A survey was carried out in regional dementia care networks in the Netherlands among 554 informal carers for people with dementia at the start of case management (response of 85 %), and one year later. Descriptive statistics and multilevel models were used to analyse the data.



The satisfaction with the case manager was high in general (an average of 8.0 within a possible range of 1 to 10), although the caregiver burden did not decrease in the first year after starting with case management. No differences were found between the four organisational models regarding the development of caregiver burden. However, statistically significant differences (p < 0.05) were found regarding satisfaction: informal carers in the organisational model where case management is only available after formal diagnosis of dementia and is often a combined function had on average the lowest satisfaction scores. Nevertheless, the satisfaction of informal carers within all organisational models was high (ranging from 7.51 to 8.40 within a range of 1 to 10).



Organisational features of case management seem to make little or no difference to the development in caregiver burden and the satisfaction of informal carers. Future research is needed to explore whether the individual characteristics of the case managers themselves are associated with case management outcomes.
Assessing the effectiveness of enhanced psychological care for patients with depressive symptoms attending cardiac rehabilitation compared with treatment as usual (CADENCE): study protocol for a pilot cluster randomised controlled trial

Around 17% of people eligible for UK cardiac rehabilitation programmes following an acute coronary syndrome report moderate or severe depressive symptoms. While maximising psychological health is a core goal of cardiac rehabilitation, psychological care can be fragmented and patchy. This study tests the feasibility and acceptability of embedding enhanced psychological care, composed of two management strategies of proven effectiveness in other settings (nurse-led mental health care coordination and behavioural activation), within the cardiac rehabilitation care pathway.



This study tests the uncertainties associated with a large-scale evaluation by conducting an external pilot trial with a nested qualitative study. We aim to recruit and randomise eight comprehensive cardiac rehabilitation teams (clusters) to intervention (embedding enhanced psychological care into routine cardiac rehabilitation programmes) or control (routine cardiac rehabilitation programmes alone) arms. Up to 64 patients (eight per team) identified with depressive symptoms upon initial assessment by the cardiac rehabilitation team will be recruited, and study measures will be administered at baseline (before starting rehabilitation) and at 5 months and 8 months post baseline. Outcomes include depressive symptoms, cardiac mortality and morbidity, anxiety, health-related quality of life and service resource use. Trial data on cardiac team and patient recruitment, and the retention and flow of patients through treatment will be used to assess intervention feasibility and acceptability. Qualitative interviews will be undertaken to explore trial participants' and cardiac rehabilitation nurses' views and experiences of the trial methods and intervention, and to identify reasons why patients declined to take part in the trial. Outcome data will inform a sample size calculation for a definitive trial.



The pilot trial and qualitative study will inform the design of a fully powered cluster randomised controlled trial to evaluate the effectiveness and cost-effectiveness of the provision of enhanced psychological care within cardiac rehabilitation programmes.
ABCC3 Genetic Variants are Associated with Postoperative Morphine-induced Respiratory Depression and Morphine Pharmacokinetics in Children

Respiratory depression (RD) is a serious side effect of morphine and detrimental to effective analgesia. We reported that variants of the ATP binding cassette gene ABCC3 (facilitates hepatic morphine metabolite efflux) affect morphine metabolite clearance. In this study of 316 children undergoing tonsillectomy, we found significant association between ABCC3 variants and RD leading to prolonged postoperative care unit stay (prolonged RD). Allele A at rs4148412 and allele G at rs729923 caused a 2.36 (95% CI=1.28–4.37, P=0.0061) and 3.7 (95% CI 1.47–9.09, P=0.0050) times increase in odds of prolonged RD, respectively. These clinical associations were supported by increased formation clearance of morphine glucuronides in children with rs4148412 AA and rs4973665 CC genotypes in this cohort, as well as an independent spine surgical cohort of 67 adolescents. This is the first study to report association of ABCC3 variants with opioid-related RD, and morphine metabolite formation (in two independent surgical cohorts).
Dose and schedule study of panitumumab monotherapy in patients with advanced solid malignancies.

This phase 1 study evaluated the safety, pharmacokinetics, and activity of panitumumab, a fully human, IgG2 monoclonal antibody that targets the epidermal growth factor receptor in patients with previously treated epidermal growth factor receptor-expressing advanced solid tumors.



Sequential cohorts were enrolled to receive four i.v. infusions of panitumumab monotherapy at various doses and schedules. Safety was continuously monitored. Serum samples for pharmacokinetic, immunogenicity, and chemistry assessments were drawn at preset intervals. Tumor response was assessed at week 8.



Ninety-six patients received panitumumab. Median (range) age was 61 years (32-79 years), and 72 (75%) patients were male. Tumor types were 41% colorectal cancer, 22% prostate, 16% renal, 15% non-small cell lung, 3% pancreatic, 3% esophageal/gastroesophageal, and 1% anal. The overall incidence of grade 3 or 4 adverse events was 32% and 7%, respectively. The incidence of skin-related toxicities was dose dependent. No maximum tolerated dose was reached. No human anti-panitumumab antibodies were detected. No investigator-determined panitumumab infusion-related reactions were reported. Serum panitumumab concentrations were similar in the 2.5 mg/kg weekly, 6.0 mg/kg every 2 weeks, and 9.0 mg/kg every 3 weeks dose cohorts. Five of 39 patients (13%) with colorectal cancer had a confirmed partial response, and 9 of 39 patients (23%) with colorectal cancer had stable disease.



Panitumumab was well tolerated with comparable exposure and safety profiles for the weekly, every 2 weeks, and every 3 weeks administration schedules. Rash and dry skin occurred more frequently in the dose cohorts receiving > or =2.5 mg/kg weekly dose. Panitumumab has single-agent antitumor activity, most notably in patients with advanced colorectal cancer.
Levels of cerebrospinal fluid neurofilament light protein in healthy elderly vary as a function of TOMM40 variants

Neurofilament light (NFL) proteins in cerebrospinal fluid (CSF) are a marker of neuronal damage, especially subcortical axonal injury and white matter disease. Subjects with Alzheimer's disease (AD) have shown elevated levels of CSF NFL as compared to controls. However, the presence of the APOE ε4 allele, an established risk factor for AD, was not found to associate with higher CSF NFL concentrations. We examined whether TOMM40 variants, which have been reported to influence age of onset of AD and are in linkage disequilibrium with APOE, have an effect on CSF NFL levels, in 47 healthy, cognitively intact individuals with or without APOE ε4. Our results show that the presence of APOE ε4 alone does not affect CSF NFL levels significantly; however APOE and TOMM40 appear to interact. Subjects with APOE ε4 have higher CSF NFL levels than non-ε4 carriers, only when they do not carry a short poly-T variant of TOMM40, which is associated with later age of onset of AD, and may act as protective against the dose effect of ε4.
A phase II study of Campath-1H in children with relapsed or refractory acute lymphoblastic leukemia: a Children's Oncology Group report.

Despite the increasing cure rates for children with acute lymphoblastic leukemia (ALL), patients who relapse continue to have poor prognosis. The Children's Oncology Group (COG) conducted a limited institution Phase II trial of Campath-1H, a monoclonal antibody that targets CD52 on leukemic cells, in children with relapsed or refractory ALL.



From October 2005 to December 2006, 13 eligible patients were enrolled on the COG phase II study of Campath-1H (ADVL0222). Campath-1H was initially administered as an intravenous infusion over 2 hr, five times per week for 1 week, then three times per week for three additional weeks. Patients with stable disease or better on day 29 could continue on to combination therapy with Campath-1H, methotrexate, and 6-mercaptopurine for two additional cycles.



One of 13 patients enrolled had a complete response to Campath-1H and 4 had stable disease. Dose limiting toxicity occurred in two out of nine fully evaluable patients (Grade IV pain and Grade III allergic reaction/hypersensitivity). No patients received combination therapy. Serum Campath-1H concentrations appeared to be somewhat lower in children with ALL compared with adult patients with chronic lymphocytic leukemia.



Although a single complete response was observed, activity of single agent Campath-1H appears limited. Our study does not support future single agent evaluation of Campath-1H in children with relapsed ALL.
Severe pneumonia mortality in elderly patients is associated with downregulation of Toll-like receptors 2 and 4 on monocytes.

Elderly patients with pneumonia have a high mortality rate. Since Toll-like receptor (TLR) signaling is involved in the inflammatory response, we conducted a prospective observational case-control study to assess the relationships of TLR2 and TLR4 mortality with elderly patients with pneumonia.



Clinical and laboratory data were collected from these elderly patients with pneumonia (patient group; n = 40) and healthy age-matched subjects (control 1; n = 20). TLR2 and TLR4 expression levels on blood monocytes were examined, and inflammatory cytokine tumor necrosis factor-α (TNF-α), interleukin-1 (IL-1) and interleukin-6 (IL-6) plasma concentrations were analyzed.



Increased TLR2 and TLR4 expression levels were detected in elderly patients with severe pneumonia compared with healthy subjects. Furthermore, we observed a positive correlation between TLR2 and TLR4 expression levels and IL-1 and IL-6 levels, and TLR2- and TLR4-positive cell percent expressions correlated with TNF-α levels. By day 28 of observation, the mortality rate of the patient group was 30%. Decreased TLR2 and TLR4 expression was observed in deceased patients compared with survivors. APACHE (Acute Physiology and Chronic Health Evaluation) II scores and CURB-65 scores (Confusion, blood Urea nitrogen, Respiratory rate and low Blood pressure scores) were lower in survivors.



These findings demonstrate a previously undocumented association between mortality in elderly patients with severe pneumonia and decreased TLR2 and TLR4 expression. Our results highlight that TLRs can be targeted in the development of improved immune modulation therapies for these patients.
Intranasal Dexmedetomidine as a Sedative Premedication for Patients Undergoing Suspension Laryngoscopy: A Randomized Double-Blind Study

Intranasal dexmedetomidine, a well-tolerated and convenient treatment option, has been shown to induce a favorable perioperative anxiolysis in children. We investigate intranasal dexmedetomidine as a sedative premedication for anesthesia recovery in an adult population.



A prospective randomized controlled trial; 81 adult patients scheduled for elective suspension laryngoscopy received intranasal dexmedetomidine (1 μg∙kg-1) or a placebo 45-60 min before anesthetic induction. Extubation time was used as the primary outcome measure. Secondary variables included the levels of sedation (Observer's Assessment of Alertness/Sedation scale, OAA/S) and anxiety (4-point anxiety score), anesthetic and analgesic requirements, hemodynamic fluctuations, and anesthesia recovery as well as side effects.



The levels of sedation and anxiety differed significantly between the two groups at anesthesia pre-induction (p < 0.001 and = 0.001, respectively). Repeated-measure general linear model determined no significant interaction effect between group and time on the targeted concentration of propofol (F = 1.635, p = 0.200), but a significant main effect of group existed (F = 6.880, p = 0.010). A moderate but significant decrease in the heart rate was recorded in the dexmedetomidine group at pre-induction. Episodes of tachycardia and hypertension after tracheal intubation and extubation were more frequent in the placebo group.



Intranasal dexmedetomidine as a sedative premedication induced a favorable perioperative anxiolysis without prolongation in anesthesia recovery; the hemodynamic effect was modest.