nils-herrmann/clean_scirepeval huggingface dataset:
Inhaled corticosteroid therapy reduces the early morning peak in cortisol and aldosterone.

1. As mineralocorticoid and adrenocorticoid activity are both under the diurnal control of adrenocorticotropic hormone secretion, we aimed to evaluate whether the normal circadian rhythm of cortisol and aldosterone secretion was suppressed by inhaled corticosteroid therapy.2.Ten normotensive patients with mild-moderate asthma, mean age 24.0 (S.D. 9.8) years and mean arterial pressure 90.7 (9.8) mmHg, were studied in a double-blind, randomized crossover design comparing placebo with fluticasone propionate, 1000 microgram administered twice daily at 08:00 h and 20:00 h. After 5 days of repeated dosing at steady state, measurements were made of plasma cortisol and aldosterone at midnight and 08:00 h.3. With placebo there was a significant (P<0.05) difference between cortisol values at 08:00 h (588.6+/-83.8 nmol/l) and midnight (109.6+/-35.0 nmol/l), whereas after treatment with fluticasone propionate there was no significant difference between levels at 08:00 h (143.3+/-57.4 nmol/l) and midnight (64.3+/-22.3 nmol/l). For cortisol at 08:00 h there was also a significant (P<0.05) difference between placebo and fluticasone propionate. The same pattern was observed for aldosterone. Plasma aldosterone levels at 08:00 h after treatment with placebo (129.6+/-30.9 nmol/l) were significantly different (P<0. 05) to those seen at midnight (40.4+/-6.2 nmol/l). After treatment with fluticasone propionate, there was no significant difference between levels at midnight (55.4+/-11.7 nmol/l) and 08:00 h (64. 8+/-12.7 nmol/l).4. These results show that inhaled corticosteroid therapy abolishes the circadian rhythm of aldosterone and cortisol secretion. This may have possible implications for patients taking inhaled corticosteroids in terms of the beneficial cardiac effects of suppressing early morning aldosterone.
Effects of thirty and sixty minutes of moderate-intensity aerobic exercise on postprandial lipemia and inflammation in overweight men: a randomized cross-over study

The transient rise in blood lipids following a high-fat meal (HFM), known as postprandial lipemia, is linked to systemic inflammation and cardiovascular disease, but can be blunted by exercise. However, minimal research has investigated the effects of realistic exercise bouts on postprandial lipemia and inflammation in at-risk individuals. The purpose of this study was to assess the effects of moderate-intensity aerobic exercise lasting 30 or 60 min performed the evening before a HFM, on postprandial lipemia and inflammation in overweight, insufficiently active men.



In this randomized-crossover study, twelve participants remained sedentary (CON), or performed a brisk walk on a treadmill at 60 % VO2peak for either 30 min (EX-30) or 60 min (EX-60), after which they consumed a small snack (270 kcal) to partially replace exercise energy expenditure. Following a 12-h overnight fast, participants consumed a standard HFM (1 g fat/kg; 1 g CHO/kg; 1117.8 ± 117.0 kcal). Blood draws were performed at baseline (pre-HFM) and 1, 2, 4, 6, and 8 h post-HFM to assess glucose, insulin, lipids, and systemic inflammation.



There were no significant differences (p > 0.05) in fasting triglycerides between EX-60 (118.7 ± 68.3 mg/dL), CON (134.8 ± 66.2 mg/dL) or EX-30 (135.5 ± 85.4 mg/dL). There were no differences in peak, time-to-peak, total or incremental area-under-the-curve between trials for triglyceride response (p > 0.05). There was no significant main effect of time (p > 0.05) in IL-1ra, IL-4, IL-5, IL-6, IL-10 or TNF-α from baseline to 8 h post-HFM in any trial.



In summary, we found that in overweight, insufficiently active men, neither 30 nor 60 min of moderate-intensity exercise performed 12 h prior to a HFM attenuated postprandial lipemia or inflammation, which could potentially be explained by the partial caloric replacement of exercise energy expenditure.
Anti-collagenolytic mechanism of action of doxycycline treatment in rheumatoid arthritis

Tetracyclines exert, independently of their anti-microbial activity, anti-collagenolytic effects by inhibiting activities of human interstitial collagenases and by preventing the oxidative activation of latent pro-collagenases. We tested the clinical response to a 3-month doxycycline in concert with collagenase activity in 12 rheumatoid arthritis (RA) patients. Patients received 150 mg/day of doxycycline for 3 months. Clinical assessments at zero, six and 12 weeks comprised classification of the functional class, joint score index, Hb, CRP, ESR, health assessment questionnaire, visual analogue scale (VAS) of pain, pain disability index, comprehensible psychopathological rating scale (CPRS), SDS-PAGE laser densitometric collagenase activity measurements and Western blots. Significant reductions were seen in joint score index (P<0.01), pain VAS (P<0.05) and some CPRS parameters. Furthermore, collagenase activities measured from saliva by quantitative SDS-PAGE electrophoresis were significantly reduced during the 12-week intervention (P<0.01). Western blots demonstrated intact 75–80 kDa enzyme protein (classic neutrophil collagenase), but also a newly discovered mesenchymal, less glycosylated 40–55 kDa MMP-8 subtype of fibroblast/chondrocytic origin. These results indicate that the documented favourable clinical response may in part be due to in vivo inhibition of classic neutrophil and mesenchymal collagenase/MMP-8 activities produced by doxycycline. This anti-collagenolytic doxycycline effects is mediated through inhibition of the enzyme activity and not through degradation of the enzyme, which may have contributed to the reportedly reduced tissue destruction, as has been seen in clinical studies concerning RA as well as reactive arthritis.
The Cannabis Youth Treatment (CYT) Study: main findings from two randomized trials.

This article presents the main outcome findings from two inter-related randomized trials conducted at four sites to evaluate the effectiveness and cost-effectiveness of five short-term outpatient interventions for adolescents with cannabis use disorders. Trial 1 compared five sessions of Motivational Enhancement Therapy plus Cognitive Behavioral Therapy (MET/CBT) with a 12-session regimen of MET and CBT (MET/CBT12) and another that included family education and therapy components (Family Support Network [FSN]). Trial II compared the five-session MET/CBT with the Adolescent Community Reinforcement Approach (ACRA) and Multidimensional Family Therapy (MDFT). The 600 cannabis users were predominately white males, aged 15-16. All five CYT interventions demonstrated significant pre-post treatment during the 12 months after random assignment to a treatment intervention in the two main outcomes: days of abstinence and the percent of adolescents in recovery (no use or abuse/dependence problems and living in the community). Overall, the clinical outcomes were very similar across sites and conditions; however, after controlling for initial severity, the most cost-effective interventions were MET/CBT5 and MET/CBT12 in Trial 1 and ACRA and MET/CBT5 in Trial 2. It is possible that the similar results occurred because outcomes were driven more by general factors beyond the treatment approaches tested in this study; or because of shared, general helping factors across therapies that help these teens attend to and decrease their connection to cannabis and alcohol.
A phase I study of oral uracil/ftorafur (UFT) plus leucovorin and bis-acetato-ammine-dichloro-cyclohexylamine-platinum IV (JM-216) each given over 14 days every 28 days

To determine the feasibility, maximal tolerated doses, and response rates for a combined regimen of the platinum and 5-fluorouracil oral analogues bis-acetato-ammine-dichloro-cyclohexyl-amine platinum(IV) (JM-216) and uracil/ftorafur (UFT) coadministered as a 14 consecutive-day every 28-day schedule.  Of 20 patients enrolled in this investigation, 17 on the following dose escalation scheme were evaluable for toxicity and/or response: I UFT 300 mg/day, JM-216 5 mg/day (three patients), II UFT 300 mg/day, JM-216 10 mg/day (four patients), III UFT 300 mg/day, JM-216 20 mg/day (ten patients).  All 17 evaluable patients were evaluable for toxicity. At dose level III, dose-limiting nausea and emesis were observed in one patient despite maximal antiemetic support. Importantly, neurotoxicity and nephrotoxicity were not observed at the JM-216 dose levels examined in this study. This observation is consistent with results seen with single agent JM-216.  For JM-216 and UFT administered at 20 mg/day and 300 mg/day over 14 days, nausea and emesis were observed as the principal dose-limiting toxicities. These doses are considerably below the maximally tolerated doses of single agent JM-216 and UFT. Shorter administration schedules should be explored in an attempt to increase the dose intensity and minimize the toxicity of this combination oral regimen.
Psychometric properties of the Brazilian version of the Pain Catastrophizing Scale for acute low back pain.

Measurement instruments of pain catastrophizing for middle-aged and elderly individuals are needed to understand its impact on low back pain. The goals were to cross-culturally adapt the Pain Catastrophizing Scale, assess the construct validity through Rasch analysis, and verify reliability and convergent validity of pain catastrophizing with psychosocial factors. 131 individuals aged 55 years and older with acute low back pain were interviewed . The intra-rater reliability was Kp = 0.80 and interrater Kp = 0.75. The Rasch analysis found adequate reliability coefficients (0.95 for items and 0.90 for individuals ). The separation index for the elderly was 2.95 and 4.59 items. Of the 13 items, one did not fit the model, which was justified in the sample evaluated. The pain catastrophizing correlated with most psychosocial factors. The instrument proved to be clinically useful. Subsequent studies should carry out the same analysis in different populations.
The SI! Program for Cardiovascular Health Promotion in Early Childhood: A Cluster-Randomized Trial.

The preschool years offer a unique window of opportunity to instill healthy life-style behaviors and promote cardiovascular health.



This study sought to evaluate the effect of a 3-year multidimensional school-based intervention to improve life-style-related behaviors.



We performed a cluster-randomized controlled intervention trial involving 24 public schools in Madrid, Spain, that were assigned to either the SI! Program intervention or the usual curriculum and followed for 3 years. The SI! Program aimed to instill and develop healthy behaviors in relation to diet, physical activity, and understanding how the human body and heart work. The primary outcome was change in the overall knowledge, attitudes, and habits (KAH) score (range 0 to 80). The intervention's effect on adiposity markers was also evaluated.



A total of 2,062 children from 3 to 5 years of age were randomized. After 3 years of follow-up, the overall KAH score was 4.9% higher in children in the intervention group compared with the control group (21.7 vs. 16.4; p < 0.001). A peak effect was observed at the second year (improvement 7.1% higher than in the control group; p < 0.001). Physical activity was the main driver of the change in KAH at all evaluation times. Children in the intervention group for 2 years and 1 year showed greater improvement than control subjects (5.9%; p < 0.001 and 2.9%; p = 0.002, respectively). After 3 years, the intervention group showed a higher probability than the control group of reducing the triceps skinfold z-score by at least 0.1 (hazard ratio: 1.40, 95% confidence interval: 1.04 to 1.89; p = 0.027).



The SI! Program is an effective strategy for instilling healthy habits among preschoolers, translating into a beneficial effect on adiposity, with maximal effect when started at the earliest age and maintained over 3 years. Wider adoption may have a meaningful effect on cardiovascular health promotion.
Phase I Study of Topotecan, Ifosfamide, and Etoposide (TIME) with autologous stem cell transplant in refractory cancer: pharmacokinetic and pharmacodynamic correlates.

To determine the maximum tolerated dose (MTD) of topotecan in combination with ifosfamide, mesna, and etoposide (TIME), followed by autologous hematopoietic cell transplant (HCT), in patients with chemotherapy-refractory malignancies.



Patients were treated with (in mg/m(2)/d) ifosfamide 3,333, mesna 3,333, and topotecan 3.3 to 28.3 during days -8 through -6 and etoposide 500 (days -5 through -3) followed by HCT on day 0. Once MTD was defined, we expanded this dosing cohort to include patients with high-risk lymphoma due to activity seen during dose escalation. Topotecan pharmacokinetic analyses were carried out, and topoisomerase I levels and activity were measured.



The topotecan MTD in this regimen was 64 mg/m(2) (21.3 mg/m(2)/d). Mucositis was dose limiting and correlated with topotecan dose level and area under the curve (AUC). Dose level was also correlated with length of hospitalization, number of days of parenteral nutrition, and neutrophil and platelet engraftment. Topotecan AUC was significantly correlated with time to platelet recovery. The baseline peripheral blood mononuclear cell topoisomerase I level was found to be a significant positive predictor for overall and progression-free survival. Topotecan AUC was positively correlated with dose level, with a trend toward decreasing clearance with increasing dose.



Topotecan can be a useful drug in the high-dose setting given its activity in some malignancies when given in standard dose. Pharmacokinetic monitoring may be a valuable tool for optimizing the use of topotecan and to avoid toxicity seen with high-systemic exposures. Baseline topoisomerase I levels may have an important role in predicting topotecan efficacy.
Long-term follow-up of pulmonary function in chronic eosinophilic pneumonia

Long-term follow-up of pulmonary function in chronic eosinophilic pneumonia. J. Durieu, B. Wallaert, A-B. Tonnel and the Groupe d'Etude en Pathologie Interstitielle de la Société de Pathologie Thoracique du Nord. ERS Journals Ltd 1997.  The prognosis of chronic eosinophilic pneumonia (CEP) is usually good under corticosteroid therapy (CST). The main complications are relapses when treatment is tapered or discontinued. The aim of this retrospective, multicentre study was to evaluate the long-term consequences of CEP on pulmonary function tests. Nineteen patients (mean±SEM age 51±16 yrs) with CEP were studied. Lung function tests were performed at the time of diagnosis and at follow-up, and included flow-volume curve. The results of the first pulmonary function test were normal in six patients, restrictive in nine, and obstructive in four. Relapses (recurrence of initial signs) occurred in nine patients. The last evaluation (mean±SEM follow-up of 49±44 months, range 12–142 months) showed a complete recovery in 8 of the 19 patients. One patient developed bilateral apical fibrosis. The remaining 10 patients, exhibited obstructive pulmonary function without relapse of CEP at this time. Bronchoalveolar lavage (BAL) eosinophilia at the time of the initial evaluation tended to be higher (p=0.05) in these 10 patients than in those with normal pulmonary function findings at follow-up. This study demonstrates: firstly, that the development of an obstructive ventilatory defect is a common finding during the course of chronic eosinophilic pneumonia (CEP); secondly, that bronchial obstruction might appear despite the absence of clinical and radiological signs of relapse; and, thirdly, that a markedly increased bronchoalveolar lavage eosinophilia at the initial evaluation is associated with a higher risk of development of bronchial obstruction. These results suggest that pulmonary function tests should be included in the management of chronic eosinophilic pneumonia.
The effectiveness of a work style intervention and a lifestyle physical activity intervention on the recovery from neck and upper limb symptoms in computer workers

This study assessed the effectiveness of a single intervention targeting work style and a combined intervention targeting work style and physical activity on the recovery from neck and upper limb symptoms. Computer workers with frequent or long-term neck and upper limb symptoms were randomised into the work style group (WS, n=152), work style and physical activity group (WSPA, n=156), or usual care group (n=158). The WS and WSPA group attended six group meetings. All meetings focused on behavioural change with regard to body posture, workplace adjustment, breaks and coping with high work demands (WS and WSPA group) and physical activity (WSPA group). Pain, disability at work, days with symptoms and months without symptoms were measured at baseline and after 6 (T1) and 12 months (T2). Self-reported recovery was assessed at T1/T2. Both interventions were ineffective in improving recovery. The work style intervention but not the combined intervention was effective in reducing all pain measures. These effects were present in the neck/shoulder, not in the arm/wrist/hand. For the neck/shoulder, the work style intervention group also showed an increased recovery-rate. Total physical activity increased in all study groups but no differences between groups were observed. To conclude, a group-based work style intervention focused on behavioural change was effective in improving recovery from neck/shoulder symptoms and reducing pain on the long-term. The combined intervention was ineffective in increasing total physical activity. Therefore we cannot draw conclusions on the effect of increasing physical activity on the recovery from neck and upper limb symptoms.
Smartphone mobile application delivering personalized, real-time sun protection advice: a randomized clinical trial.

Mobile smartphones are rapidly emerging as an effective means of communicating with many Americans. Using mobile applications (apps), they can access remote databases, track time and location, and integrate user input to provide tailored health information.



A smartphone mobile app providing personalized, real-time sun protection advice was evaluated in a randomized clinical trial.



The trial was conducted in 2012 and had a randomized pretest-posttest controlled design with a 10-week follow-up. Data were collected from a nationwide population-based survey panel. A sample of 604 non-Hispanic and Hispanic adults from the Knowledge Panel 18 years or older who owned an Android smartphone were enrolled.



The mobile app provided advice on sun protection (ie, protection practices and risk of sunburn) and alerts (to apply or reapply sunscreen and get out of the sun), hourly UV Index, and vitamin D production based on the forecast UV Index, the phone's time and location, and user input.



Percentage of days using sun protection and time spent outdoors (days and minutes) in the midday sun and number of sunburns in the past 3 months were collected.



Individuals in the treatment group reported more shade use (mean days staying in the shade, 41.0% vs 33.7%; P = .03) but less sunscreen use (mean days, 28.6% vs 34.5%; P = .048) than controls. There was no significant difference in number of sunburns in the past 3 months (mean, 0.60 in the treatment group vs 0.62 for controls; P = .87). Those who used the mobile app reported spending less time in the sun (mean days keeping time in the sun to a minimum, 60.4% for app users vs 49.3% for nonusers; P = .04) and using all protection behaviors combined more (mean days, 39.4% vs 33.8%; P = .04).



The mobile app improved some sun protection. Use of the mobile app was lower than expected but associated with increased sun protection. Providing personalized advice when and where people are in the sun may help reduce sun exposure.
Effect of Helicobacter pylori eradication on chronic gastritis during omeprazole therapy.

We have previously observed that profound acid suppressive therapy in Helicobacter pylori positive patients with gastro-oesophageal reflux disease is associated with increased corpus inflammation and accelerated development of atrophic gastritis.



To investigate if H pylori eradication at the start of acid suppressive therapy prevents the development of these histological changes.



In a prospective randomised case control study, patients with reflux oesophagitis were treated with omeprazole 40 mg once daily for 12 months. H pylori positive patients were randomised to additional double blind treatment with omeprazole 20 mg, amoxicillin 1000 mg and clarithromycin 500 mg twice daily or placebo for one week. Biopsy sampling for histology, scored according to the updated Sydney classification, and culture were performed at baseline, and at three and 12 months.



In the persistently H pylori positive group (n=24), active inflammation increased in the corpus and decreased in the antrum during therapy (p=0.032 and p=0.002, respectively). In contrast, in the H pylori positive group that became H pylori negative as a result of treatment (n=33), active and chronic inflammation in both the corpus and antrum decreased (p<or =0.0001). The decrease in active and chronic inflammation in the corpus differed significantly compared with the persistently H pylori positive group (both p=0.001). For atrophy scores, no significant differences were observed between H pylori eradicated and persistently H pylori positive patients within one year of follow up. No changes were observed in the H pylori negative control group (n=26).



H pylori eradication prevents the increase in corpus gastritis associated with profound acid suppressive therapy. Longer follow up is needed to determine if H pylori eradication prevents the development of atrophic gastritis.
Evaluation of platelet function in aspirin treated patients with CAD

Studies of platelet function in the acute coronary syndrome (ACS) have revealed both increased and unchanged platelet activation. To obtain a better understanding of platelet function in coronary artery disease in the setting of aspirin therapy, we performed platelet functional testing in patients with ACS and compared results to patients without CAD.  We measured platelet aggregation and activation in response to ADP and epinephrine in 80 age and gender matched hospitalized patients (40 with ACS, 40 with non-cardiac chest pain (NCCP)). All subjects received ASA (81–325 mg). Platelet aggregation was performed using standard light transmission in platelet-rich plasma and activation was measured via flow cytometric analyses. We also studied platelet function under high shear rates measured by the platelet function analyzer (PFA-100).  ASA effect was found to be present in all subjects by blunted platelet aggregation in response to arachidonic acid. Patients with ACS showed significantly higher levels of platelet aggregation to epinephrine compared to patients with NCCP (p = 0.001). Other measures of platelet function including ADP aggregation, Pselectin, activated glycoprotein IIb/IIIa expression, and PFA-100 were unchanged between the two groups.  We have found conflicting results of platelet functional testing in ACS. Specifically aspirin therapy in patients with ACS is effective in suppressing the platelet release response and is effective in the partial suppression of platelet aggregation; however, it appears that ACS patients have increased platelet aggregation to adrenergic stimuli when compared to age and gender matched controls without CAD despite the use of aspirin. In some studies, because ACS patients have an accentuated response to adrenergic stimuli this might be interpreted as aspirin resistance. Our study suggests that depending on the assay used to determine aspirin resistance, not all patients with this label are resistant to the biological effects of aspirin but they may have higher than normal baseline platelet sensitivity to adrenergic stimuli.