nils-herrmann/clean_scirepeval huggingface dataset:
Association of low tumor RNA integrity with response to chemotherapy in breast cancer patients

The CAN-NCIC-MA22 phase I/II clinical trial evaluated women with locally advanced or inflammatory breast cancer treated with epirubicin and docetaxel at 2 or 3 weekly intervals in sequential cohorts. The relationship between various biomarkers and treatment response was assessed. Breast biopsy cores were obtained from 50 patients pre-, mid-, and post-treatment. Immunohistochemical staining was performed to determine baseline levels of estrogen receptor (ER), progesterone receptor (PR), Her2/Neu protein (HER2), and topoisomerase II (Topo 2), expressed as percent positive stain. Tumor RNA integrity (RIN) and tumor cellularity were measured pre-, mid- and post-treatment by capillary electrophoresis and light microscopy after hematoxylin/eosin staining, respectively. Associations between 1) maximum RIN and 2) tumor cellularity at the three time points with baseline levels of ER, PR, Her2, and topo II were assessed using Spearman and Pearson correlation coefficients. Associations between RIN and tumor cellularity with chemotherapy dose level or pathologic response were assessed using one-way ANOVA. In this study, we observed that low mid-treatment maximum RIN (but not tumor cellularity) was associated with high chemotherapy drug dose level (P = 0.05) and eventual pathologic complete response (pCR) (P = 0.01). Post-treatment, low maximum RIN was found to be associated with low tumor cellularity (P = 0.004), and low tumor cellularity with pCR (P = 0.01). Post-treatment tumor cellularity was lowest in patients with tumors having high baseline PR levels (P = 0.05). The association of mid-treatment RIN with drug dose level and with pCR suggests that tumor RIN may represent an important new biomarker for measuring response to chemotherapy in breast cancer patients.
Occupational formalin asthma.

Hypersensitivity to formalin used to sterilise artificial kidney machines was shown by inhalation provocation tests to be responsible for attacks of wheezing accompanied by productive cough in two members of the nursing staff of a haemodialysis unit. Three further members of the staff of 28 who were continually exposed to this substance occupationally had developed similar recurrent but less frequent episodes since joining the unit. Two underwent inhalation provocation tests with formalin which did not reproduce these symptoms. Single episodes of these symptoms had been noted by three additional staff members so that altogether eight (29%) had experienced attacks described as bronchitic since becoming exposed to formalin. We suggest that, while exposure to formalin did not seem to be directly responsible in all cases, it might have increased susceptibility to other provoking agents or induced a hyper-reactive responsiveness of the airways. The responses observed in the two nurses after inhalation provocation tests with fromalin were predominantly of airways obstruction. Wheezing began between two and three hours after exposure, and peak expiratory flow rates fell maximally by approximately 50%. Reactions persisted for 10 hours to 10 days depending on the exposure dose. A productive cough was a prominent feature. The sputum appeared to be mucopurulent, but culture produced a scanty growth of Haemophilus influenzae only, together with upper respiratory tract commensals. The cellular content was not homogeneous, neutrophil leucocytes and eosinophil leucocoytes variably dominating. Variable responses of neutrophil and eosinophil leucocytes were also seen in the peripheral blood.
Analysis of outcome in retrieved dropout patients in a rivastigmine vs placebo, 26-week, Alzheimer disease trial.

Treatment with cholinesterase inhibitors improves cognition in patients with Alzheimer disease (AD). In studies designed with a washout period at the end of the study, after treatment with a cholinesterase inhibitor is discontinued, the cognitive benefits of therapy are no longer apparent following washout. The rivastigmine trials discussed in this article were not designed with a posttreatment washout period at the end of the study. Therefore, to evaluate the effect of discontinuing treatment, we analyzed the retrieved dropout (RDO) population.



To evaluate the change in cognition (at week 26 vs baseline) observed in patients from 3 large clinical trials of AD who prematurely discontinued treatment with placebo or rivastigmine.



Eligible patients with AD (Mini-Mental State Examination [MMSE] score, 10-26, inclusive) were enrolled in 1 of three 26-week, double-blind, placebo-controlled studies (Novartis US Pivotal [dose-range] Trial, US fixed-dose study, and a Global Pivotal [dose-range] Trial) that compared rivastigmine therapy with placebo. Patients who discontinued study participation (for any reason) (considered to be the RDO population) were encouraged to return for their scheduled week 26 efficacy evaluations. Effects on cognition were assessed using the Alzheimer's Disease Assessment Scale-Cognitive subscale (ADAS-Cog).



The results for the Novartis US Pivotal Trials and for the 3 studies combined (Novartis studies B352, B351, and B303) are reported. In the US pivotal trial, RDO patients in the 6- to 12-mg/d group had been not receiving the drug (to be called "off drug") for 102 (57.7) days (mean [SD]) compared with 68 (51.7) days in the RDO placebo group. In these RDO analyses, a statistically significantly greater worsening on the ADAS-Cog mean change score was observed in the placebo group (n = 17) compared with the rivastigmine 6- to 12-mg/d group (n = 33) at week 26 (MMSE score, -8.2 vs -3.0; P =.009). In the pooled studies, the mean (SD) number of days off treatment was 95 (52.0) days for the rivastigmine 6- to 12-mg/d group and 66 (52.7) days for the placebo group. The RDO analysis also showed a statistically significantly greater decline in cognitive function as measured by the ADAS-Cog mean change score in the placebo group (n = 38) compared with the rivastigmine 6- to 12-mg/d group (n = 88) at week 26 (MMSE score, -5.69 vs -2.5; P =.004). A significantly greater proportion of patients in the placebo group exhibited at least a 4-point and 7-point worsening in ADAS-Cog scores at week 26 compared with the rivastigmine 6- to 12-mg/d group in both the Novartis US Pivotal Trials (P =.007, P =.009) and the pooled studies (P =.002, P =.017).



After discontinuation of therapy, rivastigmine-treated patients exhibited less deterioration in cognitive function compared with placebo-treated patients. The less severe worsening of cognition after withdrawal of treatment in patients previously treated with rivastigmine suggests an effect on disease progression.
The Canadian STOP-PAIN project: the burden of chronic pain-does sex really matter?

The Canadian STOP-PAIN Project assessed the human and economic burden of chronic pain (CP) in individuals on waitlists of Canadian multidisciplinary pain treatment facilities. This article focuses on sex differences. Objectives were to (1) determine the pain characteristics and related biopsychosocial factors that best differentiated women and men with CP; and (2) examine whether public and private costs associated with CP differed according to sex.



Sample consisted of 441 women and 287 men who were evaluated using self-administered questionnaires and a structured interview protocol. A subsample (233 women and 137 men) recorded all pain-related expenditures in a comprehensive diary over 3 months.



Results revealed that the burden of illness associated with CP was comparable in both sexes for average and worst pain intensity, pain impact on daily living, quality of life, and psychological well-being. The same was true for pain-related costs. The results of a hierarchical logistic regression analysis, in which sex was treated as the dependent variable, showed that factors that differentiated men and women were: work status, certain circumstances surrounding pain onset, present pain intensity, intake of particular types of pain medication, use of certain pain management strategies, pain beliefs, and utilization of particular health care resources.



This study suggests that women and men who are referred to multidisciplinary pain treatment facilities do not differ significantly in terms of their pain-related experience. However, the aspects that differ may warrant further clinical attention when assessing and managing pain.
Cefuroxime and cefuroxime axetil versus amoxicillin plus clavulanic acid in the treatment of lower respiratory tract infections

In a large multinational study, the clinical and bacteriological efficacy of intravenous cefuroxime 750 mg t.i.d. followed by oral cefuroxime axetil 500 mg b.i.d. was compared to that of amoxicillin plus clavulanic acid (CA) administered as 1.2 g intravenously t.i.d. followed by 625 mg orally t.i.d. in the treatment of lower respiratory tract infections in hospitalised patients. A total of 512 patients were entered (256 in each treatment group). All were suffering from pneumonia or acute exacerbations of chronic bronchitis or bronchiectasis and required initial parenteral antibiotic therapy. Parenteral therapy lasted 48 to 72 h and was followed by five days of oral therapy. The clinical responses in the two treatment groups were very similar: 223 of 256 (87.1 %) patients were cured or improved with cefuroxime/cefuroxime axetil compared to 220 of 256 (85.9 %) with amoxicillin/CA. Positive pre-treatment sputum samples were obtained from 44 % of the patients. Clearance rates obtained were again similar: 72.8 % with cefuroxime/cefuroxime axetil and 70 % with amoxicillin/CA. Ten percent of the isolates were beta-lactamase producers, similar numbers of which were cleared in both groups. Both regimens were generally well tolerated, with only 5 % of patients treated with the cefuroxime regimen and 4.3 % of patients treated with amoxicillin/CA experiencing drug-related adverse events. Cefuroxime/cefuroxime axetil “follow-on” therapy produces clinical and bacteriological efficacy equivalent to that of amoxicillin/CA, with the advantage of twice daily oral administration.
Repeatability of a Rasch Model of the AQ20 over Five Assessments

Rasch analysis is now used widely to assess the measurement properties of health status questionnaires. This study tested the stability of the AQ20 – a dichotomous-response measure of health status in asthma, using parameters estimated by a Rasch model. One hundred forty-four asthma patients completed the AQ20 on five occasions over 3 months. At visit 1, two items showed significant misfit and were deleted. At each visit, the overall mean item–person and item–trait interaction statistics from the remaining 18 items (AQ18) were very similar. The repeatability of the item calibrations was excellent (intraclass correlation coefficient 0.95), despite the patients’ health having changed (repeated-measures ANOVA: FEV1 and AQ18 score p<0.0001). Tests of differential item functioning (DIF) over time showed that one item increased in severity. This item refers to ability to garden, and changes in response patterns could be related to seasonal changes over the study period. We conclude that this study has highlighted the usefulness of multiple repeat assessments which allow items to be tested for DIF over time. This is important as inclusion of ‘time-dependent’ items in a questionnaire may reduce the reliability of the instrument.
Controlled trial of slow-release aminophylline in childhood asthma: are short-term trials valid?

Slow-release aminophylline, although widely used for the prophylaxis of childhood asthma, has had only limited formal assessment. A four-month double-blind cross-over trial of slow-release aminophylline (14 mg/kg twice daily) was carried out in 24 children with perennial asthma. Satisfactory serum theophylline concentrations were obtained in 17 children, with few side effects. There was a significant improvement in mild daytime and night-time symptoms. The incidence of more severe symptoms was unaffected. Treatment did not improve the mean peak expiratory flow or reduce the incidence of use of bronchodilators. It is concluded that slow-release aminophylline has a place in the prophylaxis of perennial childhood asthma but is unsuitable for children who suffer from severe attacks. The cross-over trial design has severe limitations.
Knee flexion after total knee arthroplasty reduces blood loss

Extensive blood loss after total knee arthroplasty (TKA) may be a potential problem since it leads to anaemia, increased need for transfusion and prolonged hospitalization. Aim of this study was to investigate the effects of postoperative knee flexion after TKA on blood loss and the need for transfusion. One hundred consecutive patients undergoing primary TKA from 2012 to 2013 were randomizely divided into two groups. In one group, the knee was extended for the first 6 h after surgery, whereas in the other was flexed at 90° for the same time. Two doses of endovenous tranexamic acid were administered in all subjects. Patients were homogeneous for all the possible confounding factors. Calculated blood loss was 846 ± 197 (ml) in the flexion group and 1,242 ± 228 (ml) in the extension group (p < 0.05). Drop of haemoglobin levels at 24 h in the study group and the control group was 1.9 ± 0.8 (g/dl) and 3.0 ± 0.5 (g/dl), respectively (p < 0.01). Drop of haematocrit at 24 h was 4.5 ± 0.2 (%) in the flexion group and 6.7 ± 0.3 (%) in the extension group (p < 0.05). Blood transfusion was necessary in 5 patients in the control group and was not necessary in any patient of the study group. Average knee flexion at day 7 was 105° ± 4° in the flexion group and 98° ± 7° in the extension group. Knee flexion at 90° after TKA, associated with the intraoperative use of tranexamic, acid is an effective method to reduce blood loss and the need for blood transfusion. The routine use of the present protocol is effective in reducing social costs and length of hospitalization of TKA procedures. Prospective comparative study,
Iron supplementation in HIV-infected Malawian children with anemia: a double-blind, randomized, controlled trial.

It is unknown whether iron supplementation in human immunodeficiency virus (HIV)-infected children living in regions with high infection pressure is safe or beneficial. A 2-arm, double-blind, randomized, controlled trial was conducted to examine the effects of iron supplementation on hemoglobin, HIV disease progression, and morbidity.



HIV-infected Malawian children aged 6-59 months with moderate anemia (hemoglobin level, 7.0-9.9 g/dL) were randomly assigned to receive 3 mg/kg/day of elemental iron and multivitamins (vitamins A, C, and D) or multivitamins alone for 3 months. Participants were followed for 6 months.



A total of 209 children were randomly assigned to treatment, and 196 (93.8%) completed 6 months of follow-up. Iron supplementation was associated with greater increases in hemoglobin concentrations (adjusted mean difference [aMD], 0.60; 95% confidence interval [CI], .06-1.13; P = .03) and reduced the risk of anemia persisting for up to 6 months follow-up (adjusted prevalence ratio, 0.59; 95% CI, .38-.92; P = .02). Children who received iron had a better CD4 percentage response at 3 months (aMD, 6.00; 95% CI, 1.84-10.16; P = .005) but an increased incidence of malaria at 6 months (incidence rate, 120.2 vs 71.7; adjusted incidence rate ratio [aIRR], 1.81 [95% CI, 1.04-3.16]; P = .04), especially during the first 3 months (incidence rate, 78.1 vs 36.0; aIRR, 2.68 [95% CI, 1.08-6.63]; P = .03).



Iron supplementation in anemic HIV-infected children has beneficial effects on hemoglobin, anemia, and immunity but increases the risk of malaria. Thus, iron supplementation in HIV-infected children living in malaria-endemic areas should only be provided in combination with adequate protection from malaria.
Repeated nebulisation of non-viral CFTR gene therapy in patients with cystic fibrosis: a randomised, double-blind, placebo-controlled, phase 2b trial

Lung delivery of plasmid DNA encoding the CFTR gene complexed with a cationic liposome is a potential treatment option for patients with cystic fibrosis. We aimed to assess the efficacy of non-viral CFTR gene therapy in patients with cystic fibrosis.



We did this randomised, double-blind, placebo-controlled, phase 2b trial in two cystic fibrosis centres with patients recruited from 18 sites in the UK. Patients (aged ≥12 years) with a forced expiratory volume in 1 s (FEV1) of 50-90% predicted and any combination of CFTR mutations, were randomly assigned, via a computer-based randomisation system, to receive 5 mL of either nebulised pGM169/GL67A gene-liposome complex or 0.9% saline (placebo) every 28 days (plus or minus 5 days) for 1 year. Randomisation was stratified by % predicted FEV1 (<70 vs ≥70%), age (<18 vs ≥18 years), inclusion in the mechanistic substudy, and dosing site (London or Edinburgh). Participants and investigators were masked to treatment allocation. The primary endpoint was the relative change in % predicted FEV1. The primary analysis was per protocol. 
Between June 12, 2012, and June 24, 2013, we randomly assigned 140 patients to receive placebo (n=62) or pGM169/GL67A (n=78), of whom 116 (83%) patients comprised the per-protocol population. We noted a significant, albeit modest, treatment effect in the pGM169/GL67A group versus placebo at 12 months' follow-up (3.7%, 95% CI 0.1-7.3; p=0.046). This outcome was associated with a stabilisation of lung function in the pGM169/GL67A group compared with a decline in the placebo group. We recorded no significant difference in treatment-attributable adverse events between groups.



Monthly application of the pGM169/GL67A gene therapy formulation was associated with a significant, albeit modest, benefit in FEV1 compared with placebo at 1 year, indicating a stabilisation of lung function in the treatment group. Further improvements in efficacy and consistency of response to the current formulation are needed before gene therapy is suitable for clinical care; however, our findings should also encourage the rapid introduction of more potent gene transfer vectors into early phase trials.
Phase-I dose finding and pharmacokinetic study of the novel hydrophilic camptothecin ST-1968 (namitecan) in patients with solid tumors

This is a first-in-human, phase I, dose-escalation study to determine the maximum tolerated dose (MTD) of intravenous, flat-dosed ST-1968 (namitecan), a new hydrophilic camptothecan derivative.  Namitecan was administered intravenously over 2 h on day 1 and day 8 every 21 days (D1-D8-Q21D), starting at a flat dose of 2.5 mg, and increased according to a 3 + 3 cohort design. Due to frequent skipping of day 8 dosing for cytopenias, the study was expanded to test namitecan dosing on day 1 every 21 days (D1-Q21) at a starting dose of 17.5 mg. Major dose-limiting toxicity (DLT) was defined as grade (G) 4 neutropenia persisting >5 days, febrile neutropenia, G3 thrombocytopenia or G2 non-hematological toxicity.  Thirty-four patients were included into the D1-D8-Q21D group (2.5, 5, 10, 15, 17.5, 20 mg dosing cohorts), 29 patients into the D1-21D group (17.5, 20, 23, 27, 30 mg dosing cohorts). Neutropenia was the DLT in both groups, with 15 mg being defined as the recommended dose (RD) for the D1-D8-Q21D group, and 23 mg for the D1-Q21D group. Non-hematological toxicity was negligible. One patient with endometrial cancer in the D1-D8-Q21D group and one patient with cholangiocellular carcinoma in the D1-Q21D group experienced a partial remission. Namitecan exhibited fully dose-proportional pharmacokinetics.  This study demonstrates clinical safety, favourable pharmacokinetics and preliminary antitumor activity of the novel hydrophilic camptothecin analogue namitecan in patients with heavily pretreated solid malignancies, when given either on a 2 out of 3 weeks or 3-weekly regimen.
Neighborhood perceptions are associated with tobacco dependence among African American smokers.

The animal and human research literatures suggest that deprived environmental conditions may be associated with drug dependence, but the relation of neighborhood perceptions with a multidimensional measure of tobacco dependence has not been previously studied. The purpose of this study was to examine the associations between neighborhood perceptions (neighborhood problems and neighborhood vigilance) and tobacco dependence among smokers as measured by the Wisconsin Inventory of Smoking Dependence Motives-68 (WISDM).



Participants were 384 African American smokers (49% men, 80% < $30,000 annual household income) enrolled in a randomized clinical trial of a smoking cessation intervention. A series of regression models were conducted to examine the associations between neighborhood perceptions and tobacco dependence using a generalized estimating equation approach, which accounted for potential correlation in tobacco dependence between participants from the same neighborhood.



Results indicated that more self-reported neighborhood problems and greater neighborhood vigilance were significantly associated with tobacco dependence as measured by the WISDM total score in analyses adjusted for age, gender, income, education, employment status, and partner status (p ≤ .002). Neighborhood perceptions were related to both primary and secondary dependence motives (p ≤ .005).



Results suggest that the neighborhood context is associated with dependence on tobacco among African American smokers but longitudinal studies are needed to assess causation. Future research should also explore the mechanisms that account for the associations between neighborhood perceptions and tobacco dependence to better inform intervention development.
Final report of a phase II study of imatinib mesylate with hyper-CVAD for the front-line treatment of adult patients with Philadelphia chromosome-positive acute lymphoblastic leukemia.

We have previously reported on the efficacy and tolerability of hyper-CVAD regimen (cyclophosphamide, vincristine, Adriamycin, and dexamethasone) and imatinib followed by imatinib-based consolidation/maintenance therapy in 20 patients with newly diagnosed Philadelphia-positive acute lymphoblastic leukemia. Here, we present the 13-year follow up of our study. Fifty-four patients with newly diagnosed Philadelphia-positive acute lymphoblastic leukemia were enrolled: 39 (72%) with de novo disease, 6 (11%) whose disease was primary refractory after induction (without a tyrosine kinase inhibitor), and 9 (17%) in complete remission after one course of induction therapy (without tyrosine kinase inhibitor). Forty-two (93%) of the 45 patients treated for active disease achieved complete remission, one achieved complete remission with incomplete recovery of platelets, one achieved partial remission and one died during induction. Nineteen (35%) patients are alive and 18 are in complete remission. The 5-year overall survival rate for all patients was 43%. Significant negative predictors of overall survival were age over 60 years, p190 molecular transcript, and active disease at enrollment. Sixteen (30%) patients underwent allogeneic stem cell transplantation. Median overall survival was not significantly greater for patients who underwent transplant. Patients with residual molecular disease at three months had improved complete remission duration with transplant. The median time to hematologic recovery and severe toxicities with combination were not significantly different from those observed with conventional chemotherapy. Only one patient discontinued therapy due to toxicity. HyperCVAD chemotherapy and imatinib is an effective regimen for Philadelphia-positive acute lymphoblastic leukemia. Transplant may not be indicated in all patients with Philadelphia-positive acute lymphoblastic leukemia.