nils-herrmann/clean_scirepeval huggingface dataset:
Multicentre surveillance study on feasibility, safety and efficacy of antifungal combination therapy for proven or probable invasive fungal diseases in haematological patients: the SEIFEM real-life combo study.

This multicentre observational study evaluated the feasibility, efficacy and toxicity of antifungal combination therapy (combo) as treatment of proven or probable invasive fungal diseases (IFDs) in patients with haematological malignancies. Between January 2005 and January 2010, 84 cases of IFDs (39 proven and 45 probable) treated with combo were collected in 20 Hematological Italian Centres, in patients who underwent chemotherapy or allogeneic haematopoietic stem cell transplantation for haematological diseases. Median age of patients was 34 years (range 1-73) and 37% had less than 18 years. Acute leukaemia was the most common underlying haematological disease (68/84; 81%). The phase of treatment was as follows: first induction in 21/84 (25%), consolidation phase in 18/84 (21%) and reinduction/salvage in 45/84 (54%). The main site of infection was lung with or without other sites. The principal fungal pathogens were as follows: Aspergillus sp. 68 cases (81%), Candida sp. six cases (8%), Zygomycetes four cases (5%) and Fusarium sp. four cases (5%). The most used combo was caspofungin+voriconazole 35/84 (42%), caspofungin + liposomal amphotericin B (L-AmB) 20/84 (24%) and L-AmB+voriconazole 15/84 (18%). The median duration of combo was 19 days (range 3-180). The overall response rate (ORR) was 73% (61/84 responders) without significant differences between the combo regimens. The most important factor that significantly influenced the response was granulocyte (PMN) recovery (P 0.009). Only one patient discontinued therapy (voriconazole-related neurotoxicity) and 22% experienced mild and reversible adverse events (hypokalaemia, ALT/AST increase and creatinine increase). The IFDs-attributable mortality was 17%. This study indicates that combo was both well tolerated and effective in haematological patients. The most used combo regimens were caspofungin + voriconazole (ORR 80%) and caspofungin + L-AmB (ORR 70%). The ORR was 73% and the mortality IFD related was 17%. PMN recovery during combo predicts a favourable outcome.
Biological explanations of generalized anxiety disorder: effects on beliefs about prognosis and responsibility.

Biological explanations of psychopathology can reduce the extent to which people with mental disorders are blamed for their symptoms but can also yield prognostic pessimism--the belief that psychiatric conditions are relatively immutable. However, few studies have examined whether these effects occur among persons who actually have psychiatric symptoms. This study sought to address this question.



Adults living in the United States (N=351) were recruited online in January and February 2012 and assessed for symptoms of generalized anxiety disorder. The participants were randomly assigned to two groups: a biological condition, in which participants (N=176) were provided a description of generalized anxiety disorder and a biological explanation of the etiology of the disorder, and a control condition, in which participants (N=175) were provided the same description without any explanation of etiology. Dependent measures of treatability, duration of symptoms, and responsibility for symptoms were used to gauge beliefs regarding the prognosis and personal responsibility of a typical person with generalized anxiety disorder.



Among participants with and without symptoms of generalized anxiety disorder, the biological condition was associated with decreased ascriptions of personal responsibility for anxiety (p=.02) and expectations of increased duration of symptoms of generalized anxiety disorder (p=.01).



This finding has important social and clinical implications, especially because biological conceptualizations of psychopathology are increasingly prevalent. By causing prognostic pessimism about generalized anxiety disorder, including among those with symptoms of the disorder, biological explanations could negatively affect treatment seeking and outcomes. Efforts to dispel the link between biological explanations and prognostic pessimism are needed.
Effect of health education on knowledge and oral hygiene practices of persons living with HIV in Nairobi, Kenya.

To assess the effect of oral health education on knowledge and oral health seeking behaviour of persons living with HIV/AIDS (PLWHA).



Quasi-experimental study design conducted among 195 Persons living with HIV/AIDS attending two Comprehensive Care Centres (CCC) at the Kenyatta National Hospital (intervention group) and Mbagathi district hospital (non-intervention group) in Nairobi Kenya. The participants were selected using systematic random sampling method and data collected using a questionnaire. Data was collected at baseline, at three months (review 1) and at six months (review 2).



There was a significant change in oral health knowledge for KNH participants. However, no significant change in oral knowledge was recorded for MDH participants. The proportion of participants who brushed their teeth at least twice a day increased significantly from 52% to 88% for KNH. The proportion of those who had brushed the previous evening increased from 47% to 83.2%. There was no significant change in the proportion brushing at least twice a day among the non-intervention group. There was a significant association between change in knowledge and change to brushing at least twice a day among the intervention group.



Oral health education led to improved oral health knowledge and oral hygiene practices among PLWHA.
Effects of fluticasone plus salmeterol versus twice the dose of fluticasone in asthmatic patients

Objective. Current guidelines advocate adding a long acting β2-agonist (LABA) to an inhaled corticosteroid as an alternative to increasing the dose of the latter. Since it is unclear how this translates into effects on surrogate inflammatory markers, we evaluated the anti-inflammatory activity of fluticasone plus salmeterol in combination versus twice the dose of fluticasone alone.  Fifteen mild-to-moderate asthmatics (mean FEV1 80% predicted) uncontrolled on inhaled corticosteroids (mean dose 470 μg) were randomised in a single-blind crossover fashion to receive 2 weeks each of fluticasone 250 µg plus salmeterol 50 µg in combination (FP+SM), 1 puff b.i.d., and fluticasone 500 µg (FP), 1 puff b.i.d. Prior to each randomised treatment, there was a 2-week run-in and washout period during which patients used their usual inhaled corticosteroid therapy. Measurements were made before and after randomised treatment periods. The primary outcome was airway hyper-responsiveness to adenosine monophosphate (AMP PC20), while secondary endpoints were exhaled tidal nitric oxide (NO), forced expiratory volume in 1 second (FEV1) and forced mid-expiratory flow (FEF25–75).  For AMP PC20, FP alone but not FP+SM conferred a significant (P<0.05) improvement amounting to 3.27 (95% CI 1.46–7.32) and 1.44 (95% CI 0.64–3.23) geometric mean fold shifts, respectively, from baseline, while the difference between treatments was significantly (P<0.05) greater with FP alone: a 2.26-fold (95% CI 1.01–5.07) difference. Both FP alone and FP+SM conferred significant (P<0.05) falls in NO from baseline: 2.33 (95% CI 1.71–3.19) and 1.49 (95% CI 1.09–2.03) geometric mean fold changes, respectively, while between treatments the reduction was significantly (P<0.05) greater with FP alone: a 1.57-fold (95% CI 1.15–2.14) difference. Neither treatment significantly improved FEV1 or FEF25–75.  Double the dose of FP alone relative to FP+SM conferred superior effects on surrogate inflammatory markers but not on lung function. Long-term studies are required to evaluate whether these improvements on surrogate inflammatory markers translate into commensurate reductions in airway remodelling and exacerbations.
Effectiveness and safety of an induction therapy with epoetin alfa in anemic cancer patients receiving concomitant chemotherapy.

Epoetin alfa, administered at standard dosages of 10,000-20,000 IU three times weekly or 40,000-60,000 IU once weekly, has been shown to significantly increase hemoglobin (Hb) levels, decrease transfusion requirements, and improve quality-of-life parameters in patients undergoing chemotherapy. This open-label, nonrandomized, historically controlled study was conducted to evaluate the efficacy and safety of an induction dose of epoetin alfa in patients with moderate or severe anemia who were receiving chemotherapy.



Nineteen patients with solid tumors and Hb levels < 9.0 g/dl were enrolled. The patients received single s.c. injections of epoetin alfa, 40,000 IU, on study days 1, 4, 7, 10, and 13, and were then observed for the following 30 days. Nineteen other cancer patients who had matching characteristics and had received epoetin alfa, 10,000 IU, three times weekly for the 45-day study period, served as historical controls. The primary efficacy variable was change in Hb level from baseline to days 15 (approximately week 2) and 45 (approximately week 6.5). Secondary efficacy variables included the percent response (Hb increase > or = 1 g/dl) and percent major response (Hb increase > or = 2 g/dl) at days 15 and 45, the durations of response and major response after day 45, the proportion of patients transfused within the 45 study days, the changes in Eastern Cooperative Oncology Group performance status score at days 15 and 45, and the ability to maintain the planned chemotherapy dose (dose intensity) over the 45-day study.



Mean increases in Hb level in the epoetin alfa 40,000 IU group were significantly greater than those in the historical control group both at day 15 and at day 45. The increase in Hb level in the control group approximated increases reported with standard 3-times-weekly epoetin alfa at day 15 but was somewhat lower than the increases typically seen by day 45, presumably due to the fact that, in the present study, the epoetin alfa dose was not doubled in initial nonresponders, as is commonly done with standard epoetin alfa treatment. The rates of major response for epoetin alfa 40,000 IU patients (37% at day 15 and 84% at day 45) were higher than those for control patients (16% and 21%, respectively). Also, the transfusion rate was lower and performance status scores were better in the epoetin alfa 40,000 IU patients than in the control patients. In all, 74% of epoetin alfa 40,000 IU patients versus 47% of control patients received 100% of the planned chemotherapy dose. Epoetin alfa was well tolerated in both treatment groups.



Results of this study suggest that epoetin alfa at a dose of 40,000 IU administered five times over 2 weeks may confer even higher response rates than those seen with standard dosing regimens. These encouraging results support further study of the proposed induction dose of epoetin alfa in a larger, randomized, prospectively controlled trial.
Combined BRAF and MEK inhibition versus BRAF inhibition alone in melanoma.

Combined BRAF and MEK inhibition, as compared with BRAF inhibition alone, delays the emergence of resistance and reduces toxic effects in patients who have melanoma with BRAF V600E or V600K mutations.



In this phase 3 trial, we randomly assigned 423 previously untreated patients who had unresectable stage IIIC or stage IV melanoma with a BRAF V600E or V600K mutation to receive a combination of dabrafenib (150 mg orally twice daily) and trametinib (2 mg orally once daily) or dabrafenib and placebo. The primary end point was progression-free survival. Secondary end points included overall survival, response rate, response duration, and safety. A preplanned interim overall survival analysis was conducted.



The median progression-free survival was 9.3 months in the dabrafenib-trametinib group and 8.8 months in the dabrafenib-only group (hazard ratio for progression or death in the dabrafenib-trametinib group, 0.75; 95% confidence interval [CI], 0.57 to 0.99; P=0.03). The overall response rate was 67% in the dabrafenib-trametinib group and 51% in the dabrafenib-only group (P=0.002). At 6 months, the interim overall survival rate was 93% with dabrafenib-trametinib and 85% with dabrafenib alone (hazard ratio for death, 0.63; 95% CI, 0.42 to 0.94; P=0.02). However, a specified efficacy-stopping boundary (two-sided P=0.00028) was not crossed. Rates of adverse events were similar in the two groups, although more dose modifications occurred in the dabrafenib-trametinib group. The rate of cutaneous squamous-cell carcinoma was lower in the dabrafenib-trametinib group than in the dabrafenib-only group (2% vs. 9%), whereas pyrexia occurred in more patients (51% vs. 28%) and was more often severe (grade 3, 6% vs. 2%) in the dabrafenib-trametinib group.



A combination of dabrafenib and trametinib, as compared with dabrafenib alone, improved the rate of progression-free survival in previously untreated patients who had metastatic melanoma with BRAF V600E or V600K mutations. (Funded by GlaxoSmithKline; Clinical Trials.gov number, NCT01584648.).
Factors impacting volumetric white matter changes following whole brain radiation therapy

Whole brain radiation therapy (WBRT) is one of the most effective modalities for treatment of brain metastases. With increasing cancer control there is growing concern regarding the long-term effects of treatment. These effects are seen as white matter change (WMC) on brain MRI. Severity of WMC is implicated in cognitive and functional decline in many patient groups. Our objective was to identify clinical factors associated with greater accumulation of WMC following WBRT. Through retrospective review of serial MRIs obtained from 30 patients surviving greater than 1 year after WBRT, treated at a single institution between 2002 and 2007, we calculated volumetric WMC over time using segmentation software. Changes related to tumor, secondary effects, surgery or radiosurgery were excluded. Factors that influenced the rate of WMC accumulation were identified through multivariate analysis. Following WBRT, patients accumulated WMC at an average rate of 0.07% of total brain volume per month. In multivariate analyses, greater rates of accumulation were independently associated with older age (β = 0.004, p < .0001), poor levels of glycemic control (β = 0.048, p < .0001) and hypertension diagnosis (β = 0.084, p < .0001). Long-term survivors of cancer allow assessment of late effects of treatment modalities. Radiation injury appears to be related to a steady rate of white matter damage over time, as indicated by progressive accumulation of WMC. Our results suggest that rate of WMC accumulation is enhanced by parameters such as hyperglycemia and hypertension. This has significant clinical impact by clearly identifying hyperglycemia, steroid-induced hyperglycemia, and other vascular risk factors as targets for intervention to decrease WMC in patients receiving WBRT.
Patients’ Perceptions of Health Related Quality of Life in Rheumatoid Arthritis and Chronic Low Back Pain

To determine how health related quality of life (HRQL) is perceived by patients with rheumatoid arthritis (RA) and chronic low back pain (CLBP) using a textual analysis approach.  Two-hundred and forty-eight outpatients (85% female), mean age 58±13 years (40% RA and 60% CLBP).Methods: Observational descriptive study. Sociodemographic and clinical variables were determined. A questionnaire was designed which included an open question “What does health related quality of life mean to you.” which patients answered in writing. Textual data analysis was performed using a previous described method based on multivariate descriptive statistical methods. The two groups were homogenous with respect to gender, educational level, disease duration, comorbid conditions and global functional status. Patients with RA and CLBP used clearly differentiated terms to describe HRQL (RA: to be able (capable), house; CLBP: life, health, quality). RA patients were specific and primarily concerned with functional status and CLBP patients with health and life. The most characteristic phrase used by RA patients was: “to be able to do housework” and for CLBP: “health is the most important thing for quality of life.” In the factorial representation, the two pathologies were markedly separated. A series of characteristic answers on HRQL may be identified in patients with RA and CLBP, showing that they have different perceptions about what HRQL is according to their pathology. The use of open questions in a group of homogenous patients with specific pathologies could result in more disease-specific responses. Textual statistical analysis of open questions may provide more information than standard methods, and may be considered as valid for the analysis of subjective issues such as quality of life.
Development and psychometric validation of a brief comprehensive health status assessment scale in older patients with hematological malignancies: The GAH Scale.

The purpose of this study was to develop a new brief, comprehensive geriatric assessment scale for older patients diagnosed with different hematological malignancies, the Geriatric Assessment in Hematology (GAH scale), and to determine its psychometric properties.



The 30-item GAH scale was designed through a multi-step process to cover 8 relevant dimensions. This is an observational study conducted in 363 patients aged≥65years, newly diagnosed with different hematological malignancies (myelodysplasic syndrome/acute myeloblastic leukemia, multiple myeloma, or chronic lymphocytic leukemia), and treatment-naïve. The scale psychometric validation process included the analyses of feasibility, floor and ceiling effect, validity and reliability criteria.



Mean time taken to complete the GAH scale was 11.9±4.7min that improved through a learning-curve effect. Almost 90% of patients completed all items, and no floor or ceiling effects were identified. Criterion validity was supported by reasonable correlations between the GAH scale dimensions and three contrast variables (global health visual analogue scale, ECOG and Karnofsky), except for comorbidities. Factor analysis (supported by the scree plot) revealed nine factors that explained almost 60% of the total variance. Moderate internal consistency reliability was found (Cronbach's α: 0.610), and test-retest was excellent (ICC coefficients, 0.695-0.928).



Our study suggests that the GAH scale is a valid, internally reliable and a consistent tool to assess health status in older patients with different hematological malignancies. Future large studies should confirm whether the GAH scale may be a tool to improve clinical decision-making in older patients with hematological malignancies.
Single-blinded, randomised preliminary study evaluating the effects of 2 Hz electroacupuncture for postoperative pain in patients with total knee arthroplasty

To explore the point-specific clinical effect of 2 Hz electroacupuncture (EA) in treating postoperative pain in patients undergoing total knee arthroplasty (TKA),  In a randomised, partially single-blinded preliminary study, 47patients with TKA were randomly divided into three groups: control group (CG, n=17) using only patient-controlled analgesia (PCA); EA group (EAG, n=16) with 2 Hz EA applied at ST36 (Zusanli) and GB34 (Yanglingquan) contralateral to the operated leg for 30 min on the first two postoperative days, also receiving PCA; and non-point group (NPG, n=14), with EA identical to the EAG except given 1 cm lateral to both ST36 and GB34. The Mann-Whitney test was used to show the difference between two groups and the Kruskal-Wallis test to show the difference between the three groups.



The time until patients first required PCA in the CG was 34.1±22.0 min, which was significantly shorter than the 92.0±82.7 min in the EAG (p<0.001) and 90.7±94.8 min in the NPG (p<0.001); there was no difference between the EAG and NPG groups (p>0.05). The total dosage of PCA solution given was 4.6±0.9 mL/kg body weight in the CG, 4.2±1.0 mL/kg in the EAG and 4.5±1.0 mL/kg in the NPG; there were no significant differences (p>0.05) among the three groups.



In this small preliminary study, EA retarded the first demand for PCA in comparison with no EA. No effect was seen on the total dosage of PCA required and no point-specific effect was seen.
Acute effects of salmeterol and fluticasone propionate alone and in combination on airway blood flow in patients with asthma.

The airway contains airway smooth muscle and airway vascular smooth muscle. The acute effects of inhaled long-acting β(2)-adrenergic agonists (LABAs) alone, or in combination with an inhaled glucocorticoid (ICS), on airway smooth muscle tone in asthma are known; however, to the best of our knowledge, their effect on airway vascular smooth muscle tone has not been investigated previously. The objective of this study was to investigate the immediate effects of a LABA and an ICS alone and in combination on airway blood flow (Qaw) as an index of airway vascular smooth muscle tone in patients with stable asthma.



Fourteen subjects with moderate asthma inhaled single doses of salmeterol (50 μg), fluticasone propionate (250 μg), salmeterol/fluticasone propionate (50/250 μg), or placebo; Qaw was measured before and serially for 240 min after drug administration.



Mean Qaw increased after salmeterol and salmeterol/fluticasone propionate, with peaks at 60 min of 34% and 40%, respectively, and returned to baseline by 240 min after inhalation. Fluticasone propionate alone caused a transient decrease in mean Qaw. The maximal changes in Qaw, which occurred at different times, were 60% for salmeterol, 67% for salmeterol/fluticasone propionate, and -19% for fluticasone propionate (P < .05 vs placebo for all).



The LABA salmeterol has an acute vasodilator action on the airway of subjects with stable asthma. The addition of fluticasone propionate, which by itself causes vasoconstriction, does not attenuate the salmeterol-induced vasodilation, suggesting that fluticasone propionate potentiates the vasodilator effect of salmeterol. The vasodilation could be of clinical benefit by promoting the vascular clearance of inflammatory mediators including spasmogens from the airway.