nils-herrmann/clean_scirepeval huggingface dataset:
Phase II study of sorafenib in patients with relapsed or refractory lymphoma.

The safety and activity of the multikinase inhibitor sorafenib were investigated in patients with relapsed or refractory lymphoproliferative disorders who received sorafenib (400 mg) twice daily until disease progression or appearance of significant clinical toxicity. The primary endpoint was overall response rate (ORR). Biomarkers of sorafenib activity were analysed at baseline and during treatment. Thirty patients (median age, 61 years; range, 18-74) received a median of 4 months of therapy. Grade 3-4 toxicities included hand/foot skin reactions (20%), infections (12%), neutropenia (20%) and thrombocytopenia (14%). Two patients achieved complete remission (CR), and two achieved partial remission (PR) for an ORR of 13%. Stable disease (SD) and progressive disease (PD) was observed in 15 (50%) and 11 patients (37%), respectively. The median overall survival (OS) for all patients was 16 months. For patients who achieved CR, PR and SD, the median time to progression and OS was 5 and 24 months, respectively. Compared with patients with PD, responsive patients had significantly higher baseline levels of extracellular signal-regulated kinase phosphorylation and autophagy and presented a significant reduction of these parameters after 1 month of therapy. Sorafenib was well tolerated and had a clinical activity that warrants development of combination regimens.
Alterations in HbA1c following minimal or enhanced non-surgical, non-antibiotic treatment of gingivitis or mild periodontitis in type 2 diabetic patients: a pilot trial.

The purpose of this pilot study was to determine and compare the effects of two protocols aimed at reducing periodontal inflammation, upon the metabolic control of the diabetic condition in subjects with elevated baseline glycosylated hemoglobin (HbA1c).



Forty-two non-smoking type 2 diabetes subjects with mildly elevated HbA1c (>7 but < 9%) and severely elevated (>9%) were randomized to one of two non-surgical periodontal therapy protocols. Patients in the "minimal therapy" (MT) group received scaling, root planning, and oral hygiene instructions on two occasions six months apart. Participants randomized to the "frequent therapy" (FT) protocol received scaling, root planing, and oral hygiene instructions at two-month intervals and were provided a 0.12% chlorhexidine rinse for home use twice daily. Neither systemic nor local antibiotics were provided to either group. Subjects were asked to report any changes in diabetic medications, nutrition, and physical activity. Data analyses (ANOVA, t-test, Mann-Whitney) grouped subjects according to baseline HbA1c (>7 and < 9%, or > 9%), treatment protocol (minimal or frequent), and +/- medication change.



In both MT and FT groups the clinical attachment level (CAL) remained unchanged but the other measures [gingival index (GI) and pocket dept (PD)] of periodontal health improved. Mean reductions in plaque showed improvement but calculus was worse in the FT group, likely due to the use of chlorhexidine. At six months, the largest reduction of HbA1c was 3.7; experienced by a subject receiving FT but no changes in diabetic medication. Among the MT and no medication change subjects, the maximum reduction was 1.6. Overall mean reduction in HbA1c of 27 subjects with baseline HbA1c >9.0 and no medication change was 0.6 with no statistical difference between the MT and FT groups. Among the medication-change subjects with baseline HbA1c >9.0, mean reduction of 1.38 was seen with FT compared to 1.10 with MT.



Overall, modest improvements in HbA1c were detected with a trend towards FT being better than MT. Although this pilot trial was under-powered to detect small between-group differences, the magnitude of our findings (0.6 mean improvement in HbA1c) matches closely findings from the only meta-analysis conducted on this topic to date. Larger scale studies must be undertaken on diabetic patients with periodontal problems.



Preventive periodontal regimens for diabetic patients should be sufficiently intense and sustained to eliminate periodontal inflammation and should be closely coordinated with the patient's overall clinical diabetic management.
Chemotherapy Does Not Influence Intestinal Amino Acid Uptake in Children

Chemotherapy will frequently induce intestinal damage (mucositis). Enteral nutrition is then often withheld for fear of impaired intestinal absorption as shown in animal models. There is no clinical evidence, however, that absorption is indeed compromised during chemotherapy-induced mucositis. The aim of this study was to evaluate systemic availability of dietary amino acids (leucine) during chemotherapy-induced mucositis. We studied eight childhood cancer patients (age 1.5–16 y) on 2 d, i.e. the day before chemotherapy and 3–5 d after. Chemotherapy-induced oral mucositis and diarrhea were scored on a World Health Organization toxicity scale. Stable isotope tracers were used to measure first-pass splanchnic leucine uptake and whole-body leucine kinetics. Patients showed increased mucositis and/or diarrhea toxicity scores (p < 0.0001) after chemotherapy. Systemic availability of enterally administered leucine was not significantly affected by chemotherapy (before 60%, after 90%, p = 0.46). Interestingly, five patients already showed a negative leucine balance before chemotherapy. In conclusion, most children receiving chemotherapy are already catabolic before start of a new cycle of chemotherapy. Amino acid transport as measured by leucine uptake in the intestine is not affected by chemotherapy-induced mucositis.
Initiating an online asthma management program in urban emergency departments: the recruitment experience.

The emergency department could represent a means of identifying patients with asthma who could benefit from asthma interventions.



To assess the initiation of a Web-based tailored asthma intervention in the emergency department of 2 urban tertiary care hospitals.



In addition to awareness strategies for emergency department staff (eg, attending nursing huddles, division meetings, etc), recruitment experiences are described for 2 strategies: (1) recruitment during an emergency department visit for acute asthma and (2) recruitment from patient listings (mail or telephone). Patient enrollment was defined as baseline completion, randomization, and completion of the first of 4 online sessions.



Of 499 eligible patients 13 to 19 years old visiting the emergency department for asthma during the study period, 313 (63%) were contacted in the emergency department (n = 65) or by mail or telephone (n = 350). Of these, 121 (38.6%) were randomized. Mean age of the study sample was 15.4 years and 88.4% were African American. Refusal rates for emergency department recruitment and mail or telephone were 18.5% (12 of 65) and 16.6% (58 of 350), respectively. On average, emergency department enrollment took 44 to 67 minutes, including downtime. When surveyed, emergency department providers were more positive about awareness activities and emergency department recruitment than were research staff.



Emergency department recruitment was feasible but labor intensive. Refusal rates were similar for the 2 strategies. Targeting patients with acute asthma in the emergency department is one way of connecting with youth at risk of future acute events.
Efficacy and tolerability of trandolapril in mild to moderate hypertension--a double blind comparative clinical trial with enalapril in Indian population.

Several large scale clinical trials have demonstrated that angiotensin converting enzyme inhibitors offer cardiovascular and renal protection independent of their effects on systolic BP. Trandolapril is a new angiotensin converting enzyme inhibitor approved for the treatment of hypertension. The potential advantages of this drug are long duration of action and better tolerability. The objective of the study was to compare the efficacy and tolerability of trandolapril with that of enalapril in mild to moderate hypertension in Indian population. In this double blind, multicentric, parallel comparative clinical study, 120 patients with mild to moderate hypertension were randomly assigned to receive trandolapril 2 mg or enalapril 5 mg once daily for 8 weeks. The attainment of sitting diastolic blood pressure <90 mmHg at the end of 8th week was considered as primary outcome measure and attainment of diastolic blood pressure <90 mmHg or reduction of at least 10 mmHg diastolic blood pressure compared to baseline at any visit was considered as secondary outcome measures. 98.4% patients treated with trandolapril and 92.6% patients treated with enalapril fulfilled the primary outcome measure. 54, 72 and 62% patients on trandolapril and 52, 61 & 64% patients on enalapril fulfilled secondary outcome measure at the end of 2nd, 4th and 8th week respectively. Also trandolapril was better tolerated than enalapril with no significant abnormality in lab parameters.
Nortriptyline and cognitive-behavioral therapy in the treatment of cigarette smoking.

A history of major depressive disorder (MDD) predicts failure to quit smoking. We determined the effect of nortriptyline hydrochloride and cognitive-behavioral therapy on smoking treatment outcome in smokers with a history of MDD. The study also addressed the effects of diagnosis and treatment condition on dysphoria after quitting smoking and the effects of dysphoria on abstinence.



This was a 2 (nortriptyline vs placebo) x 2 (cognitive-behavioral therapy vs control) x 2 (history of MDD vs no history) randomized trial. The participants were 199 cigarette smokers. The outcome measures were biologically verified abstinence from cigarettes at weeks 12, 24, 38, and 64. Mood, withdrawal, and depression were measured at 3, 5, and 8 days after the smoking quit date.



Nortriptyline produced higher abstinence rates than placebo, independent of depression history. Cognitive-behavioral therapy was more effective for participants with a history of depression. Nortriptyline alleviated a negative affect occurring after smoking cessation. Increases in the level of negative affect from baseline to 3 days after the smoking quit date predicted abstinence at later assessments for MDD history-negative smokers. There was also a sex-by-depression history interaction; MDD history-positive women were less likely to be abstinent than MDD history-negative women, but depression history did not predict abstinence for men.



Nortriptyline is a promising adjunct for smoking cessation. Smokers with a history of depression are aided by more intensive psychosocial treatments. Mood and diagnosis interact to predict relapse. Increases in negative affect after quitting smoking are attenuated by nortriptyline.
The antioxidant status response to low-fat and walnut paste-enriched meat differs in volunteers at high cardiovascular Risk carrying different PON-1 polymorphisms.

Cardiovascular risk largely depends on diet, antioxidant status, and gene polymorphisms. Low-fat meat (CM) and walnut-enriched meat (WM) products may exert potential beneficial health effects with respect to conventional meat products.



To compare the effects of consuming WM vs CM on reduced and oxidized glutathione, lipoperoxides, α- and γ-tocopherol levels, and paraoxonase (PON-1), catalase (CAT), and superoxide dismutase (SOD) activities in 22 volunteers (mean age 54.8 years and body mass index 29.6 kg/m(2)) at high cardiovascular risk carrying different PON-1 192/55 polymorphisms.



The study was a 5-week nonblinded, randomized, crossover, controlled trial.



In general term, WM vs CM improved the volunteers' antioxidant status, with several result modifications occurring after the WM period. CM consumption increased oxidized glutathione and decreased PON-1 activity (at least p < 0.05). When WM vs CM effects were compared, SOD, CAT, and PON-1 enzyme activities increased (at least p < 0.05) in PON-1 192QQ carriers. γ-tocopherol levels and SOD and PON-1 activities increased in PON-1 192QR+RR carriers besides the significant decrease of lipoperoxide levels. In PON-1 55LM+MM carriers, the intervention increased significantly all the investigated enzyme activities and glutathione levels, whereas PON-1 55LL carriers increased their PON-1 activities.



WM consumption should be preferred to CM. The intake of WM vs CM increased PON-1 but the effect upon other antioxidant enzymes and substrates varied depending on the individual's PON-1 polymorphism. PON-1 192QR+RR carriers appear the targets for WM consumption as they increased enzyme activities and γ-tocopherol levels and decreased lipoperoxides.
Health-related quality of life and psychological distress during neoadjuvant endocrine therapy with letrozole to determine endocrine responsiveness in postmenopausal breast cancer

Trials of adjuvant endocrine therapy for breast cancer have shown that aromatase inhibitors have little impact on global health-related quality of life (HRQoL), but have significant effects on patient-reported endocrine symptoms (ESs). There are few studies of HRQoL and psychological distress during preoperative endocrine therapy performed to determine endocrine responsiveness. The NEOS trial is a multicenter, phase 3 randomized controlled trial in postmenopausal women with hormone receptor-positive breast cancer. The primary aim of the trial was to evaluate the need for adjuvant chemotherapy in patients with clinical T1c-T2N0M0, hormone receptor-positive tumors who responded to neoadjuvant letrozole (LET) administered for 24–28 weeks before surgery. The primary endpoint was disease-free survival and the secondary endpoints included adverse events, HRQoL, and cost-effectiveness. In a HRQoL sub-study, subjects were assessed at baseline and 4 and 16 weeks after starting neoadjuvant LET, using the functional assessment of cancer therapy-breast and its ES subscale, and the hospital anxiety and depression scale. HRQoL and psychosocial distress were analyzed in the uncontrolled phase during 24–28 weeks of neoadjuvant LET therapy in the NEOS trial. From May 16, 2008, to December 14, 2011, 503 patients were recruited into the HRQoL sub-study. The full analysis set included 497 patients with a mean age of 63-years old. The questionnaire response rates at enrollment and 4 and 16 weeks were 94.4, 90.7, and 89.1 %, respectively. There were no significant changes in the FACT-G or B-trial outcome index over time, but the social and family well-being score and the ES subscale deteriorated significantly, and the number of patients with clinically significant hot flush increased significantly. Anxiety, depression, and emotional well-being improved significantly after neoadjuvant LET. Neoadjuvant endocrine therapy with LET had no impact on global HRQoL, but did influence endocrine-related symptoms such as hot flush.
Simvastatin Therapy Reduces Prooxidant-Antioxidant Balance: Results of a Placebo-Controlled Cross-Over Trial

Oxidative stress is thought to play an important role in atherogenesis. The statin group of cholesterol-lowering drugs have been shown to reduce cardiovascular events and possess antioxidant properties. We aimed to assess the effects of simvastatin on a novel measure of prooxidant–antioxidant balance (PAB) in dyslipidemic patients. The PAB assay can measure the prooxidant burden and the antioxidant capacity simultaneously in one assay, thereby giving a redox index. We treated 102 dyslipidemic individuals with simvastatin, or a placebo in a double-blind, cross-over, placebo-controlled trial. PAB values were measured before and after each treatment period. Seventy-seven subjects completed the study. We found that statin therapy was associated with a significant reduction in PAB values (P < 0.001). This effect appeared to be independent of the cholesterol-lowering effects of statins. We conclude that serum PAB values are decreased by simvastatin therapy. Regarding previous reports on the elevation of PAB in conditions associated with oxidative stress, the PAB assay, along with other markers of oxidative stress, may be applied to estimate the extent of oxidative stress in patients, assessment of the antioxidative efficacy of medication such as statins and perhaps also for the identification of those individuals who need antioxidant therapy.
Disposition of a new rate-controlled formulation of prazosin in the treatment of hypertension during pregnancy: transplacental passage of prazosin

Prazosin (PRZ) in conventional tablet form (P-CT) has the disadvantages of a relatively short terminal half-life, a slight solubility in water and the well-recognized adverse effect of symptomatic orthostatic hypotension. The pharmacokinetic study of a new rate-controlled formulation of prazosin (Praxosin-Gastrointestinal System: P-GS) was performed in 9 pregnant women during the third trimester of pregnancy. Patients had persistent elevation of blood pressure. The subjects gave their informed consent for oral administration of 1 daily dose of 5 mg P-GS at 8 a.m. A first analysis period on day 1 enabled definition of the initial pharmacokinetic behavior of the drug, while the aim of a second was to evaluate its fate at plateau. The clinical course of both mother and fetus was subsequently monitored.  The data show: (i) P-GS was well tolerated by all patients and there were no significant changes in fetal heart rate during the study. (ii) A significant decrease in diastolic blood pressure was observed after the 36th hour following the first dose of P-GS while a reduction in systolic blood pressure was observed on day 4. (iii) Anapproximated relative bioavailability (f′P-GS) of 36.5% was calculated. P-GS appears to have a lower bioavailability than P-CT in women of similar gestational age. (iv) Both Cmax and AUC0→∞ are significantly increased at plateau. Further, terminal half-life is increased with regard to the value determined with P-CT. No accumulation of PRZ was noted at steady-state. (v) P-GS is an example of an oral zero-order absorption product that offers one approach to control and improve the outcome of hypertensive therapy during pregnancy. This treatment could represent an alternative to methyldopa as a first treatment of pregnancy-associated hypertension. (vi) There is a slight transplacental passage of the drug (of the order of 10–20%). P-GS was well tolerated by all patients and there were no significant changes in fetal heart rate during the study. A significant decrease in diastolic blood pressure was observed after the 36th hour following the first dose of P-GS while a reduction in systolic blood pressure was observed on day 4. Anapproximated relative bioavailability (f′P-GS) of 36.5% was calculated. P-GS appears to have a lower bioavailability than P-CT in women of similar gestational age. Both Cmax and AUC0→∞ are significantly increased at plateau. Further, terminal half-life is increased with regard to the value determined with P-CT. No accumulation of PRZ was noted at steady-state. P-GS is an example of an oral zero-order absorption product that offers one approach to control and improve the outcome of hypertensive therapy during pregnancy. This treatment could represent an alternative to methyldopa as a first treatment of pregnancy-associated hypertension. There is a slight transplacental passage of the drug (of the order of 10–20%).
Lamotrigine in the acute treatment of bipolar depression: results of five double-blind, placebo-controlled clinical trials.

The efficacy of lamotrigine as maintenance treatment for bipolar disorder (BD), particularly for delaying depressive episodes, is well established, but its efficacy in the acute treatment of bipolar depression is less clear. This paper reports the results of five randomized, double-blind, placebo-controlled trials of lamotrigine monotherapy for the acute treatment of bipolar depression.



Adult subjects with bipolar I or II disorder experiencing a depressive episode were randomized to placebo or lamotrigine monotherapy (after titration, at a fixed dose of 50 mg or 200 mg daily in Study 1; a flexible dose of 100-400 mg daily in Study 2; or a fixed dose of 200 mg daily in Studies 3, 4 and 5) for 7-10 weeks.



Lamotrigine did not differ significantly from placebo on primary efficacy endpoints [17-item Hamilton Depression Rating Scale in Studies 1 and 2; Montgomery-Asberg Depression Rating Scale (MADRS) in Studies 3, 4 and 5]. In Study 1, lamotrigine significantly separated from placebo on some secondary measures of efficacy, including the MADRS, the Clinical Global Impressions-Severity (CGI-S) and the CGI-Improvement (CGI-I), but seldom differed on secondary efficacy endpoints for the other studies.



Lamotrigine monotherapy did not demonstrate efficacy in the acute treatment of bipolar depression in four out of five placebo-controlled clinical studies. Lamotrigine was well tolerated in the acute treatment of bipolar depression.
Restoration of depressed immune function in spinal cord injury patients receiving rehabilitation therapy

Both natural and adaptive immune responses were strikingly decreased 2 weeks after injury in 49 spinal cord injuries, 28 tetraplegie and 21 paraplegic patients compared to agematched controls. All values are expressed as means. NK cell function decreased to 21.0% 2 weeks after spinal cord injury compared to 48.6% in controls. At 2 weeks, plasma ACTH values increased to 17.0 pg/ml in patients compared to 11.2 pg/ml in controls and urine free Cortisol levels were elevated to 162.4 μg/24 h in patients compared to 53.6 ug/24 h in controls. T cell function decreased to 40.2% of normal (lymphocyte transformation) by 3 months post injury. T cell activation (IL-2R) was diminished, i.e., 183.4 ug/ml compared to 328.2 ug/ml in controls. With rehabilitation therapy, NK cell function increased to 41.6% by 7 months post injury. NK cell-mediated lysis diminished sharply between 7 and 9 months decreasing to 22.8% at 10 months and ultimately returning to the 2 week post injury level. Rehabilitation therapy contributed to the restoration of T cell function to 92.0% of normal by 6 months post injury where it remained for 6+ months. IL-2R values improved in parallel with lymphocyte transformation. Whereas NK cell-induced lysis remained depressed, i.e., 11.8% at 6 months and 11.4% at 12+ months in patients not receiving therapy, the restoration of NK cell function at 6 months to 40.6% in rehabilitated patients decreased to 23.0% with cessation of treatment. NK cell-mediated lysis values in cervical injury patients were significantly less than those in the thoracic injury group. FIM scores of the two paralleled their NK cell function. With rehabilitation therapy, NK cell-mediated lysis in the cervical group increased from 15.2% to 28.4%, whereas it improved in the thoracic group with therapy from 26.8% to 43.7%. With rehabilitation therapy, lymphocyte transformation in the cervical group increased from 37.3% to 85.6% and improved in the thoracic group from 48.4% to 88.9%. With rehabilitation therapy, FIM scores improved from 49.7 to 74.0 in the cervical group and from 79.8 to 97.3 in thoracic patients compared to 126 in controls of healthy age matched controls.