nils-herrmann/clean_scirepeval huggingface dataset:
Additive effects of glucagon-like peptide 1 and pioglitazone in patients with type 2 diabetes.

To evaluate the effect of combination therapy with pioglitazone and glucagon-like peptide (GLP)-1 in patients with type 2 diabetes.



Eight patients with type 2 diabetes (BMI 32.7 +/- 1.3 kg/m(2) and fasting plasma glucose 13.5 +/- 1.2 mmol/l) underwent four different treatment regimens in random order: saline therapy, monotherapy with continuous subcutaneous infusion of GLP-1 (4.8 pmol x kg(-1) x min(-1)), monotherapy with pioglitazone (30-mg tablet of Actos), and combination therapy with GLP-1 and pioglitazone. The observation period was 48 h. End points were plasma levels of glucose, insulin, glucagon, free fatty acids (FFAs), and sensation of appetite.



Fasting plasma glucose decreased from 13.5 +/- 1.2 mmol/l (saline) to 11.7 +/- 1.2 (GLP-1) and 11.5 +/- 1.2 (pioglitazone) and further decreased to 9.9 +/- 1.0 (combination) (P < 0.001). Eight-hour mean plasma glucose levels were reduced from 13.7 +/- 1.1 mmol/l (saline) to 10.6 +/- 1.0 (GLP-1) and 12.0 +/- 1.2 (pioglitazone) and were further reduced to 9.5 +/- 0.8 (combination) (P < 0.0001). Insulin levels increased during monotherapy with GLP-1 compared with monotherapy with pioglitazone (P < 0.01). Glucagon levels were reduced in GLP-1 and combination therapy compared with saline and monotherapy with pioglitazone (P < 0.01). FFAs during breakfast (area under the curve, 0-3 h) were reduced in combination therapy compared with saline (P = 0.03). Sensation of appetite was reduced during monotherapy with GLP-1 and combination therapy (P < 0.05).



GLP-1 and pioglitazone show an additive glucose-lowering effect. A combination of the two agents may, therefore, be a valuable therapeutic approach for the treatment of type 2 diabetes.
A randomized controlled trial of soap opera videos streamed to smartphones to reduce risk of sexually transmitted human immunodeficiency virus (HIV) in young urban African American women.

Love, Sex, and Choices (LSC) is a soap opera video series created to reduce HIV sex risk in women.



LSC was compared to text messages in a randomized trial in 238 high-risk mostly Black young urban women. 117 received 12-weekly LSC videos, 121 received 12-weekly HIV prevention messages on smartphones. Changes in unprotected sex with high risk partners were compared by mixed models.



Unprotected sex with high risk men significantly declined over 6 months post-intervention for both arms, from 21-22 acts to 5-6 (p < 0.001). This reduction was 18 % greater in the video over the text arm, though this difference was not statistically significant. However, the LSC was highly popular and viewers wanted the series to continue.



This is the first study to report streaming soap opera video episodes to reduce HIV risk on smartphones. LSC holds promise as an Internet intervention that could be scaled-up and combined with HIV testing.
Regulation of peripheral vascular tone in patients with heart failure: contribution of angiotensin II.

To determine directly the contribution of angiotensin II to basal and sympathetically stimulated peripheral arteriolar tone in patients with heart failure.



Parallel group comparison.



Nine patients with New York Heart Association grade II-IV chronic heart failure, and age and sex matched controls.



Forearm plethysmography, lower body negative pressure, local intra-arterial administration of losartan, angiotensin II, and noradrenaline, and estimation of plasma hormone concentrations.



Forearm blood flow responses, plasma hormone concentrations.



Baseline blood pressure, heart rate, and forearm blood flow did not differ between patients and controls. In comparison with the non-infused forearm, losartan did not affect basal forearm blood flow (95% confidence interval -5.5% to +7.3%) or sympathetically stimulated vasoconstriction in controls. However, the mean (SEM) blood flow in patients increased by 13(5)% and 26(7)% in response to 30 and 90 micrograms/min of losartan respectively (p < 0.001). Lower body negative pressure caused a reduction in forearm blood flow of 20(5)% in controls (p = 0.008) and 13(5)% (p = 0.08) in patients (p = 0.007, controls v patients). Blood flow at 90 micrograms/min of losartan correlated with plasma angiotensin II concentration (r = 0.77; p = 0.03). Responses to angiotensin II and noradrenaline did not differ between patients and controls.



Losartan causes acute local peripheral arteriolar vasodilation in patients with heart failure but not in healthy control subjects. Endogenous angiotensin II directly contributes to basal peripheral arteriolar tone in patients with heart failure but does not augment sympathetically stimulated peripheral vascular tone.
Exquisite Sensitivity of TP53 Mutant and Basal Breast Cancers to a Dose-Dense Epirubicin−Cyclophosphamide Regimen

In breast cancers, only a minority of patients fully benefit from the different chemotherapy regimens currently in use. Identification of markers that could predict the response to a particular regimen would thus be critically important for patient care. In cell lines or animal models, tumor protein p53 (TP53) plays a critical role in modulating the response to genotoxic drugs. TP53 is activated in response to DNA damage and triggers either apoptosis or cell-cycle arrest, which have opposite effects on cell fate. Yet, studies linking TP53 status and chemotherapy response have so far failed to unambiguously establish this paradigm in patients. Breast cancers with a TP53 mutation were repeatedly shown to have a poor outcome, but whether this reflects poor response to treatment or greater intrinsic aggressiveness of the tumor is unknown.



In this study we analyzed 80 noninflammatory breast cancers treated by frontline (neoadjuvant) chemotherapy. Tumor diagnoses were performed on pretreatment biopsies, and the patients then received six cycles of a dose-dense regimen of 75 mg/m(2) epirubicin and 1,200 mg/m(2) cyclophosphamide, given every 14 days. After completion of chemotherapy, all patients underwent mastectomies, thus allowing for a reliable assessment of chemotherapy response. The pretreatment biopsy samples were used to determine the TP53 status through a highly efficient yeast functional assay and to perform RNA profiling. All 15 complete responses occurred among the 28 TP53-mutant tumors. Furthermore, among the TP53-mutant tumors, nine out of ten of the highly aggressive basal subtypes (defined by basal cytokeratin [KRT] immunohistochemical staining) experienced complete pathological responses, and only TP53 status and basal subtype were independent predictors of a complete response. Expression analysis identified many mutant TP53-associated genes, including CDC20, TTK, CDKN2A, and the stem cell gene PROM1, but failed to identify a transcriptional profile associated with complete responses among TP53 mutant tumors. In patients with unresponsive tumors, mutant TP53 status predicted significantly shorter overall survival. The 15 patients with responsive TP53-mutant tumors, however, had a favorable outcome, suggesting that this chemotherapy regimen can overcome the poor prognosis generally associated with mutant TP53 status.



This study demonstrates that, in noninflammatory breast cancers, TP53 status is a key predictive factor for response to this dose-dense epirubicin-cyclophosphamide regimen and further suggests that the basal subtype is exquisitely sensitive to this association. Given the well-established predictive value of complete responses for long-term survival and the poor prognosis of basal and TP53-mutant tumors treated with other regimens, this chemotherapy could be particularly suited for breast cancer patients with a mutant TP53, particularly those with basal features.
Implications of Infliximab Treatment Failure and Influence of Personalized Treatment on Patient-reported Health-related Quality of Life and Productivity Outcomes in Crohn's Disease.

This study assessed the effects of infliximab (IFX) treatment failure on patient-reported outcomes and explored the influence of using personalized treatment in this situation.



Sixty-nine Crohn's disease patients with IFX treatment failure were randomized to an intensified IFX regimen (n = 36) or personalized treatment defined by IFX and anti-IFX antibodies (n = 33). Health-related quality of life evaluated with the Short Inflammatory Bowel Disease Questionnaire (IBDQ) and productivity evaluated with the Work Productivity and Activity Impairment Questionnaire (WPAI:CD) were assessed at treatment failure and after 4, 8, 12 and 20 weeks.



Median IBDQ score at manifestation of IFX treatment failure was 40 and improved markedly in responders by 11 at weeks 4 and 8 (p < 0.001) and by 13 at weeks 12 and 20 (p < 0.001). Non-responders improved modestly at weeks 12 and 20 (increase of median 4, p < 0.05). Overall activity impairment was high at IFX failure (median 70%) and decreased substantially in responders (40-50%, p < 0.001) and to a lesser extent in non-responders (15-40%, p < 0.05). In employed patients (55%), absenteeism was negligible during the entire study period. However, median presenteeism was 40% at manifestation of IFX failure and decreased only among responders across time (decrease 10-30%, p < 0.05). Although anti-tumour necrosis factor (TNF) therapy was discontinued in most patients handled by personalized treatment, IBDQ and WPAI:CD scores were similar in these patients compared with patients routinely dose-intensified on IFX.



Regaining low disease activity after IFX failure is necessary for minimizing patient impairment and indirect disease-related costs. A personalized treatment strategy does not have a negative influence on patient-reported outcomes.
Leukotriene D 4-induced hypoxaemia in asthma is mediated by the cys-leukotriene 1 receptor

Bronchoprovocation with cysteinyl-leukotrienes (LTs) induces airflow obstruction and gas exchange abnormalities, namely ventilation-perfusion ratio (V9A/Q9) imbalance. However, it is unknown which of the two different receptors for cysteinyl-LTs mediate these V9A/Q9
Slow bolus injection of ribose in the identification of thallium-201 redistribution following combined adenosine/dynamic exercise stress.

A simple stress/redistribution thallium-201 myocardial perfusion imaging protocol may underestimate the degree of thallium redistribution in a defect identified on the stress images. We sought to investigate whether a slow-bolus injection of D-ribose improves the identification of thallium redistribution following combined adenosine/dynamic exercise stress.



Fifteen patients (10 males, five female, median age 63 years, range 50-75) were enrolled in the study. All underwent two successive adenosine plus exercise myocardial perfusion scintigraphy protocols 7-14 days apart. Adenosine was infused at 140 micrograms.kg-1.min-1 coupled with 25 W ergometer pedalling for 6 min with 74 Mbq of thallium-201 being injected at 4 min. Immediately following the stress image acquisition, patients received the one of either 60 mg.kg-1 of D-ribose or normal saline, injected over 5 min. Redistribution images were acquired after 4 h. The identical stress procedure was conducted in the crossover arm of the study, and patients received the alternative test article. SPECT images were visually analysed and scored in a nine segment model by two blinded observers. In addition, circumferential profile analysis was conducted.



By visual interpretation 25 segments displayed redistribution of the ribose, but not in the saline study, 14 reversible segments were seen on the saline study alone and 18 were seen on both studies (P = ns). In six patients ribose identified a greater number of redistributing segments and in a further six patients saline identified more reversible segments. Comparison of mean values of defect extent severity and percentage reversibility scores generated from the circumferential profile analysis showed no significant difference between the two arms of the study.



A 5 min bolus injection of D-ribose following combined adenosine/dynamic exercise stress confers little benefit on the identification of redistribution of thallium-201. These results differ from those of previous studies which showed that a 30 min infusion of D-ribose following treadmill exercise significantly enhanced thallium redistribution. The duration of the ribose infusion is likely to be an important factor influencing the effect brought to bear on the redistribution of the tracer, and should be run over 30 min, or longer.
Sensitivity of Axillary Specimen X-ray to Predict Nodal Count and Positivity

The number of examined axillary lymph nodes (ALN) has been proposed as an indicator of prognosis along with quality and adequacy in breast cancer surgery. The purpose of this study was to examine the utility of imaging axillary specimens with x-ray (lymphogram) to determine the number of lymph nodes. We sought to determine the sensitivity and specificity of a lymphogram in identifying nodal positivity. Patients who underwent sentinel lymph node (SLN) and axillary lymph node dissections (ALND) were prospectively accrued to this double-blinded, single-institution trial from December 2009 to January 2011. A single physician interpreted all lymphograms for the number of ALNs and positivity determined by size, spiculations, irregularities, and calcifications. Twenty female (age 50.8 ± 14.3 years) patients were accrued to the study. The lymphogram located more lymph nodes compared with pathology in 11 of 16 cases (68.8%). In these 11 cases, lymphogram identified 170 nodes and the pathologist located 132 (77.6%). Of the 16 ALND specimens, 6 were from patients naive to chemotherapy and averaged 13.8 ± 6.6 nodes; 10 were from neoadjuvant chemotherapy patients and had an average number of 14.9 ± 7.4 nodes. In neoadjuvant chemotherapy patients, sensitivity of the lymphogram to detect nodal positivity was 91.7% and specificity was 33.3%. This study demonstrated that lymphogram accurately identifies nodal count. This can be used for documentation of an adequate ALND for reimbursement. Furthermore, there may be potential value of lymphogram in intraoperative determination of nodal positivity.
A clinical evaluation of setup errors for a prostate immobilization system

A prostate treatment immobilization system was evaluated with respect to setup errors and efficiency for a specific treatment setup. Prostate patients were treated in the prone position with a rectal catheter using the NOMOS intensity modulated radiotherapy system. Immobilization and setup consisted of a Vac-Loktrade mark bag (MED-TEC, Orange City, IO) fitted within a registration carrier box where patients were aligned to the bag using skin marks along the lower leg. Daily setup errors were analyzed using lateral portal films, registration plates mounted to the carrier box, and the pubic symphasis as a bony reference. Two studies were conducted to evaluate setup technique. In the first study, patient setup required 3-5 minutes for patient positioning and the corresponding superior/inferior errors were found to have a standard deviation of 3.5 mm. In the second study, the technique standards were reduced to allow for faster setup times and, consequently, larger errors; setup times were 1-2 minutes and the mean and standard deviation errors were approximately 2 and 5 mm, respectively.
Service use and cost of mental disorder in older adults with intellectual disability.

The cost of caring for people with intellectual disability currently makes up a large proportion of healthcare spending in western Europe, and may rise in line with the increasing numbers of people with intellectual disability now living to old age.



To report service use and costs of older people with intellectual disability and explore the influence of sociodemographic and illness-related determinants.



We collected data on receipt and costs of accommodation, health and personal care, physical as well as mental illness, dementia, sensory impairment and disability in a representative sample of adults with intellectual disability aged 60 years and older (n = 212).



The average weekly cost in GBP per older person was 790 pounds (41,080 pounds per year). Accommodation accounted for 74%. Overall costs were highest for those living in congregate settings. Gender, intellectual disability severity, hearing impairment, physical disorder and mental illness had significant independent relationships with costs. Mental illness was associated with an additional weekly cost of 202 pounds.



Older adults with intellectual disability comprise about 0.15-0.25% of the population of England but consume up to 5% of the total personal care budget. Interventions that meet needs and might prove to be cost-effective should be sought.
Bortezomib in combination with pegylated liposomal doxorubicin and thalidomide is an effective steroid independent salvage regimen for patients with relapsed or refractory multiple myeloma: results of a phase II clinical trial.

Novel agents have demonstrated enhanced efficacy when combined with other antimyeloma agents especially dexamethasone. The steroid doses employed in myeloma regimens are often poorly tolerated. Therefore, in a phase II clinical trial we investigated the efficacy of a steroid-free combination including bortezomib, pegylated liposomal doxorubicin and thalidomide (VDT regimen). Twenty-three patients with relapsed or refractory myeloma or other plasma cell cancers were treated with the VDT regimen. Patient had a median of five prior therapies and 65.2% were refractory to their last regimen. The overall response rates were 55.5% and 22%, respectively. The median progression free survival was 10.9 months (95% CI: 7.3-15.8) and the median overall survival was 15.7 months (95% CI: 9.1-not reached). Fatigue and sensory neuropathy were the most common side effects noted. We observe that VDT is an effective steroid-free regimen with ability to induce durable remission even in patients with refractory myeloma.
Stress management intervention for primary prevention of hypertension: detailed results from Phase I of Trials of Hypertension Prevention (TOHP-I).

Stress Management Intervention (SMI) was one of seven nonpharmacologic approaches evaluated in Phase I Trials of Hypertension Prevention (TOHP-I) for efficacy in lowering diastolic blood pressure (BP) in healthy men and women aged 30 to 54 years with diastolic BP 80-89 mm Hg.



A total of 242 and 320 participants were randomized to SMI or an "assessment only" SMI Control, respectively, at four clinical centers. The SMI consisted of 37 contact hours in 21 group and two individual meetings over 18 months and included: training in four relaxation methods, techniques to reduce stress reactions, cognitive approaches, communication skills, time management, and anger management within a general problem-solving format. Standardized protocols detailed methods and timing for collecting BP, psychosocial measures, and urinary samples from both SMI and SMI Control participants.



In intention-to-treat analyses, although significant baseline to termination BP reductions were observed in both groups, net differences between the SMI and SMI Control groups' BP changes (mean (95% CI)) were not significant: -0.82 (-1.86, 0.22) for diastolic BP, and -0.47 (-1.96, 1.01) for systolic BP. Extensive adherence sub-group analyses found one effect: a significant 1.36 mm Hg (p = 0.01) reduction in diastolic BP relative to SMI Controls at the end of the trial for SMI participants who completed 61% or more of intervention sessions.



While the TOHP-I SMI was acceptable to participants as evident from high levels of session completion, the absence of demonstrated BP lowering efficacy in intention-to-treat analyses suggests that the TOHP-I SMI is an unlikely candidate for primary prevention of hypertension in a general population sample similar to study participants. The isolated finding of significant diastolic BP lowering in SMI participants with higher adherence provides very weak evidence of SMI BP lowering efficacy and may be a chance finding. Whether similar or other stress management interventions can produce significant BP lowering in populations selected for higher levels of BP, stress, or intervention adherence remains to be demonstrated.
Endovascular Revascularization and Supervised Exercise for Peripheral Artery Disease and Intermittent Claudication: A Randomized Clinical Trial.

Supervised exercise is recommended as a first-line treatment for intermittent claudication. Combination therapy of endovascular revascularization plus supervised exercise may be more promising but few data comparing the 2 therapies are available.



To assess the effectiveness of endovascular revascularization plus supervised exercise for intermittent claudication compared with supervised exercise only.



Randomized clinical trial of 212 patients allocated to either endovascular revascularization plus supervised exercise or supervised exercise only. Data were collected between May 17, 2010, and February 16, 2013, in the Netherlands at 10 sites. Patients were followed up for 12 months and the data were analyzed according to the intention-to-treat principle.



A combination of endovascular revascularization (selective stenting) plus supervised exercise (n = 106) or supervised exercise only (n = 106).



The primary end point was the difference in maximum treadmill walking distance at 12 months between the groups. Secondary end points included treadmill pain-free walking distance, vascular quality of life (VascuQol) score (1 [worst outcome] to 7 [best outcome]), and 36-item Short-Form Health Survey (SF-36) domain scores for physical functioning, physical role functioning, bodily pain, and general health perceptions (0 [severe limitation] to 100 [no limitation]).



Endovascular revascularization plus supervised exercise (combination therapy) was associated with significantly greater improvement in maximum walking distance (from 264 m to 1501 m for an improvement of 1237 m) compared with the supervised exercise only group (from 285 m to 1240 m for improvement of 955 m) (mean difference between groups, 282 m; 99% CI, 60-505 m) and in pain-free walking distance (from 117 m to 1237 m for an improvement of 1120 m vs from 135 m to 847 m for improvement of 712 m, respectively) (mean difference, 408 m; 99% CI, 195-622 m). Similarly, the combination therapy group demonstrated significantly greater improvement in the disease-specific VascuQol score (1.34 [99% CI, 1.04-1.64] in the combination therapy group vs 0.73 [99% CI, 0.43-1.03] in the exercise group; mean difference, 0.62 [99% CI, 0.20-1.03]) and in the score for the SF-36 physical functioning (22.4 [99% CI, 16.3-28.5] vs 12.6 [99% CI, 6.3-18.9], respectively; mean difference, 9.8 [99% CI, ). No significant differences were found for the SF-36 domains of physical role functioning, bodily pain, and general health perceptions.



Among patients with intermittent claudication after 1 year of follow-up, a combination therapy of endovascular revascularization followed by supervised exercise resulted in significantly greater improvement in walking distances and health-related quality-of-life scores compared with supervised exercise only.