nils-herrmann/clean_scirepeval huggingface dataset:
Implementation salvage experiences from the Melbourne diabetes prevention study

Many public health interventions based on apparently sound evidence from randomised controlled trials encounter difficulties when being scaled up within health systems. Even under the best of circumstances, implementation is exceedingly difficult. In this paper we will describe the implementation salvage experiences from the Melbourne Diabetes Prevention Study, which is a randomised controlled trial of the effectiveness and cost-effectiveness nested in the state-wide Life! Taking Action on Diabetes program in Victoria, Australia.



The Melbourne Diabetes Prevention Study sits within an evolving larger scale implementation project, the Life! program. Changes that occurred during the roll-out of that program had a direct impact on the process of conducting this trial. The issues and methods of recovery the study team encountered were conceptualised using an implementation salvage strategies framework. The specific issues the study team came across included continuity of the state funding for Life! program and structural changes to the Life! program which consisted of adjustments to eligibility criteria, referral processes, structure and content, as well as alternative program delivery for different population groups. Staff turnover, recruitment problems, setting and venue concerns, availability of potential participants and participant characteristics were also identified as evaluation roadblocks. Each issue and corresponding salvage strategy is presented.



The experiences of conducting such a novel trial as the preliminary Melbourne Diabetes Prevention Study have been invaluable. The lessons learnt and knowledge gained will inform the future execution of this trial in the coming years. We anticipate that these results will also be beneficial to other researchers conducting similar trials in the public health field. We recommend that researchers openly share their experiences, barriers and challenges when conducting randomised controlled trials and implementation research. We encourage them to describe the factors that may have inhibited or enhanced the desired outcomes so that the academic community can learn and expand the research foundation of implementation salvage.
Phase III development of the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire module for women undergoing breast reconstruction.

Comprehensive outcome assessments after breast reconstruction (BRR) require surgery-specific patient-reported outcome measures. The aims of this study were to assess the relevance, acceptability and redundancy of questions/items (phase III pretesting) of a new BRR questionnaire evaluating patients' health-related quality of life before and after BRR. Phase III occurred in collaboration with the European Organization for Research and Treatment of Cancer (EORTC) following earlier development phases that identified 31 items.



The EORTC BRR subgroup applied decision-making rules to each question according to eight EORTC criteria. A total of 197 patients (from the UK, Austria, Belgium, Italy and Sweden) were recruited. Forty-seven patients completed pre- and post-BRR questionnaires prospectively, and 150 reported post-BRR questionnaires only retrospectively. Qualitative debriefing interviews were undertaken in 189 patients. Preliminary psychometric analyses were performed.



Thirty-one items fulfilled 'relevance', with none producing 'difficulties'. Ten items were not a priority for 10 per cent of respondents. Of these, two questions concerning muscle twitching in the affected breast and problem with donor-site swelling were deleted. Three redundant items were deleted: weakness in arm, which correlated significantly to the Quality of Life Questionnaire (QLQ) BR23 breast questionnaire, and shape and colour of the affected nipple. Descriptive statistics reduced the module to 26 items conceptualized into three provisional scales (disease treatment/surgery-related symptoms, sexuality and cosmetic outcome) within the newly completed questionnaire, EORTC QLQ-BRR26.



The QLQ-BRR26 is available for psychometric validation in a large-field international sample. The intended use for QLQ-BRR26 is alongside EORTC QLQ-C30 and QLQ-BR23, in women treated by mastectomy for breast cancer and undergoing all types of BRR.
Memantine induces reversible neurologic impairment in patients with MS.

Cognitive dysfunction is very common in multiple sclerosis (MS) and it severely impairs patients' quality of life. Thus, we explored whether memantine might improve cognitive performance in patients with MS.



We conducted a pilot trial with memantine (30 mg/day) in patients with MS with cognitive impairment. The trial was designed as a 1-year, randomized, double-blind, crossover study comparing memantine against a placebo in 60 patients with MS and cognitive impairment. Cognitive impairment was defined as the performance 1.5 standard deviations below the normative data in at least two tests of two cognitive domains in the Brief Repeatable Battery-Neuropsychology. The primary endpoint was improvement of verbal memory and the secondary endpoints were safety and improvements in the other cognitive domains, disability and quality of life. 
Although 19 patients had been included, the trial was halted after nine patients reported a worsening of their neurologic symptoms that deteriorated their quality of life. Seven of the nine patients in the memantine arm had blurred vision, fatigue, severe headache, increased muscle weakness, walking difficulties, or unstable gait. Only two patients in the placebo group reported neurologic symptoms and in both cases they were related with changes in their disease-modifying therapy. The adverse events only occurred on reaching the maximum dose (30 mg/day). After stopping medication, the patients reverted to their baseline disability within a few days.



Memantine at a dose of 30 mg/day may induce transient worsening of neurologic symptoms of multiple sclerosis.
Factors associated with anxiety and depressive symptoms in colorectal cancer survivors.

Up to 37% of colorectal cancer (CRC) survivors report depressive and anxiety symptoms. The identification of risk factors for depressive or anxiety symptoms might help focus supportive care resources on those patients most in need. The present study aims to explore which factors are associated with heightened anxiety or depression symptom severity.



In this cross-sectional study, individuals diagnosed with CRC 3.5 to 6 years ago completed questionnaires on sociodemographic information, medical comorbidities, anxiety symptoms (Beck Anxiety Inventory), and depressive symptoms (Inventory of Depressive Symptomatology). The general linear model analysis of covariance was used to identify factors associated with heightened anxiety or depressive symptom severity.



The sample included 91 CRC survivors, 40.7% women, mean age 69.1 years. A minority of CRC survivors had moderate (3.4%) or severe (2.3%) anxiety symptoms, and moderate (7.7%) or severe (0%) depressive symptoms. Shorter time since diagnosis and higher number of comorbid diseases were associated with higher anxiety symptom severity. Female sex and higher number of comorbid diseases were associated with higher depressive symptom severity.



From this explorative study, it follows that survivors with multiple comorbid diseases, shorter time since diagnosis, and female survivors might be at risk for higher anxiety and/or depressive symptom severity. Survivors with these characteristics might need extra monitoring.
Phase I clinical and pharmacokinetic study of combination chemotherapy with topotecan and ifosfamide in patients with progressive or relapsed solid tumors.

Topotecan and ifosfamide are effective in the treatment of various solid tumors. Up to the time of this study, the two drugs have been combined just once (Smith et al. 1998). Due to its hematotoxicity, topotecan has been used predominantly within monochemotherapy protocols. However, the combination of topotecan and alkylating agents is supra-additive in many preclinical models. This phase-I trial was primarily performed to evaluate the maximum tolerable dose (MTD) and dose-limiting toxicity (DLT) of a combination chemotherapy with topotecan and ifosfamide using a 5-day schedule. A secondary goal was to estimate the response rate in a group of heavily pretreated patients with advanced solid tumors. The pharmacokinetics of topotecan were preliminarily determined in some of the patients. A total of 12 patients (three female/nine male), median age 49 years (range 19–69), 11 with prior chemotherapy, received a total of 24 courses of chemotherapy at three dose-levels of topotecan. Ifosfamide was administered by intravenous infusion over 3 h immediately followed by a 30-min infusion of topotecan. Mesna (3×300 mg·m2·day) was given routinely during chemotherapy as a uroprotector. G-CSF (filgrastim) was permitted only in cases of febrile neutropenia (FN). The major toxicity was non-hematologic; severe liver and renal toxicity were observed in three out of 11 patients. Two treatment-related deaths occurred. No clinical remissions occured in 11 evaluable patients. The pharmacokinetics of topotecan were relatively similar in our patients and supported findings in recent literature. The MTD of this combination was defined at dose-level 2 (1.0 mg/m2 of topotecan and 750 mg/m2 of ifosfamide). Further trials should not exceed this dose. The pharmacological causes for the pronounced toxicity have to be clarified.
Reliability of the Brazilian Portuguese version of the
fatigue severity scale and its correlation with pulmonary function, dyspnea, and
functional capacity in patients with COPD*


To describe the intra-rater and inter-rater reliability of the Brazilian Portuguese version of the fatigue severity scale (FSS) in patients with COPD and to identify the presence of its association with parameters of pulmonary function, dyspnea, and functional capacity.



This was an observational cross-sectional study involving 50 patients with COPD, who completed the FSS in interviews with two researchers in two visits. The FSS scores were correlated with those of the Medical Research Council (MRC) scale, as well as with FEV1, FVC, and six-minute walk distance (6MWD).



The mean age of the patients was 69.4 ± 8.23 years, whereas the mean FEV1 was 46.5 ± 20.4% of the predicted value. The scale was reliable, with an intraclass correlation coefficient of 0.90 (95% CI, 0.81-0.94; p < 0.01). The FSS scores showed significant correlations with those of MRC scale (r = 0.70; p < 0.01), as well as with 6MWD (r = -0.77; p < 0.01), FEV1 (r = -0.38; p < 0.01), FVC (r = -0.35; p < 0.01), and stage of the disease in accordance with the Global Initiative for Chronic Obstructive Lung Disease criteria (r = 0.37; p < 0.01).



The Brazilian Portuguese version of the FSS proved reliable for use in COPD patients in Brazil and showed significant correlations with sensation of dyspnea, functional capacity, pulmonary function, and stage of the disease.
Impact of chest tube clearance on postoperative morbidity after thoracotomy: results of a prospective, randomised trial.

In many centres of thoracic surgery, milking of chest tubes is performed to prevent them from blocking. The usefulness of chest tube clearance is discussed controversially. Therefore, we investigated the impact of postoperative chest tube milking on postoperative outcome in a prospective, randomised trial.



Within a period of 11 months, 145 patients undergoing pulmonary resection through thoracotomy were included in the study. Two chest tubes each (silicone drainage, Redax, Mirandola, Italy) were placed in all patients (ventral tube 21Ch and dorsal tube 24Ch). Milking was applied to both chest tubes for 1 min every 2h within the first 48 h postoperatively and continuous suction of -20 cm H(2)O was maintained for 48 h. Duration of chest tube drainage, quantity and quality of effusion or air leakage, co-morbidity, length of hospital stay and 30-day postoperative morbidity and mortality were analysed. Furthermore, outcome was measured by assessment of chest radiographs at the time of discharge from hospital.



Randomisation resulted in milking of chest tubes of 73 patients and in observation of chest tubes without any manipulation in 72 patients. Twenty-one patients had to be excluded from further analysis due to violation from the study protocol (n=9), necessity of replacement of a chest tubes (n=9) and re-operation for bleeding (n=3). The 30-day mortality rate was 1.4% in each group and the 30-day morbidity was 49.3% in the milking group and 52.8% in the observation group. Milking of chest tubes was not associated with a lower postoperative mortality or morbidity (p=0.99 and p=0.67, respectively; chi-square test). We observed a significant increase of postoperative pleural effusion drainage in the milking group 48 h after surgery (p=0.004; unpaired t-test). No correlation was seen between milking of chest tubes and the duration of chest tube drainage, quality of effusion, air leakage or length of hospitalisation.



We showed for the first time that postoperative chest tube milking is associated with a significant increase of pleural fluid drainage. Postoperative morbidity and mortality was not improved and therefore chest tube milking cannot be recommended as a routine postoperative procedure.
The impact of anti-inflammatory cytokines provoked by CD163 positive macrophages on ventricular functional recovery after myocardial infarction

Present study aimed to investigate the impact of anti-inflammatory cytokines provoked by the hemoglobin scavenger receptor, CD163, on left ventricular (LV) functional recovery after successful reperfusion in patients with acute myocardial infarction (AMI). Intraplaque hemorrhage accelerates plaque destabilization. Extracellular hemoglobin is cleared by CD163, a macrophage scavenger receptor. This process provokes secretion of anti-inflammatory atheroprotective cytokine, interleukin (IL)-10. In 40 patients with the first AMI, coronary atherothrombotic debris was retrieved during percutaneous coronary intervention (PCI), stained with antibodies to CD163 and IL-10. LV function was determined by echocardiography before PCI and 6 months after PCI. %CD163 was defined as ratio of CD163 (+)-cells to whole cells. %IL-10 was expressed as the ratio of positively stained areas per total tissue. Patients were divided into two groups depending on the amount of CD163 (+)-cells: CD163 > 10 % (CD163high, n = 20) and CD163 ≤ 10 % (CD163low, n = 20). CD163high group had significantly higher %IL-10. Final thrombolysis in myocardial infarction (TIMI) flow grade was significantly lower in CD163high group. In subgroups with the final TIMI-3 flow (CD163high-Reflow, n = 15 and CD163low-Reflow, n = 20), the time to reperfusion, infarct size, LV dimensions and fractional shortening (%FS) before PCI were similar. Significant correlation was observed between %IL10 and changes in LV dimensions (diastole, r = −0.49, P = 0.01; systole, r = −0.65, P < 0.01) or %FS (r = 0.51, P < 0.01) at 6 months after PCI. Plaque with CD163(+)-macrophages could impair distal flow after primary PCI. However, CD163(+)-macrophages enhance the anti-inflammatory cytokine expression that aids in ventricular functional recovery if distal flow can be achieved by successful reperfusion.
A Bayesian Approach for Liver Analysis: Algorithm and Validation Study

We present a new method for the simultaneous, nearly automatic segmentation of liver contours, vessels, and metastatic lesions from abdominal CTA scans. The method repeatedly applies multi-resolution, multi-class smoothed Bayesian classification followed by morphological adjustment and active contours refinement. It uses multi-class and voxel neighborhood information to compute an accurate intensity distribution function for each class. The method requires only one or two user-defined voxel seeds, with no manual adjustment of internal parameters. A retrospective study on two validated clinical datasets totaling 56 CTAs was performed. We obtained correlations of 0.98 and 0.99 with a manual ground truth liver volume estimation for the first and second databases, and a total score of 67.87 for the second database. These results suggest that our method is accurate, efficient, and robust to seed selection compared to manually generated ground truth segmentation and to other semi-automatic segmentation methods.
Changes in JC Virus-Specific T Cell Responses during Natalizumab Treatment and in Natalizumab-Associated Progressive Multifocal Leukoencephalopathy

Progressive multifocal leukoencephalopathy (PML) induced by JC virus (JCV) is a risk for natalizumab-treated multiple sclerosis (MS) patients. Here we characterize the JCV-specific T cell responses in healthy donors and natalizumab-treated MS patients to reveal functional differences that may account for the development of natalizumab-associated PML. CD4 and CD8 T cell responses specific for all JCV proteins were readily identified in MS patients and healthy volunteers. The magnitude and quality of responses to JCV and cytomegalovirus (CMV) did not change from baseline through several months of natalizumab therapy. However, the frequency of T cells producing IL-10 upon mitogenic stimulation transiently increased after the first dose. In addition, MS patients with natalizumab-associated PML were distinguished from all other subjects in that they either had no detectable JCV-specific T cell response or had JCV-specific CD4 T cell responses uniquely dominated by IL-10 production. Additionally, IL-10 levels were higher in the CSF of individuals with recently diagnosed PML. Thus, natalizumab-treated MS patients with PML have absent or aberrant JCV-specific T cell responses compared with non-PML patients, and changes in T cell-mediated control of JCV replication may be a risk factor for developing PML. Our data suggest further approaches to improved monitoring, treatment and prevention of PML in natalizumab-treated patients.
Intravascular ultrasonic evidence by constant cross-sectional area of atherosclerotic plaques during coronary vasomotion in humans.

This study aims to visualize ultrasonically deformation of atherosclerotic plaques in human coronary arteries during vasoconstriction and vasodilatation.



Intravascular ultrasound detected occult atherosclerosis in angiographically normal coronary arteries of eight patients with chest pain at rest. During the acetylcholine provocative test, intravascular ultrasound monitored deformation of the atherosclerotic plaques. At the last step of the test, intracoronary injection of isosorbide dinitrate caused vasodilation. Under control, acetylcholine-treated, and isosorbide dinitrate-treated conditions, cross-sectional areas of sonolucent circle and vessel lumen were measured. Subtraction of the latter from the former gave the area of atherosclerotic plaque. In the process of vasoconstriction and vasodilation, the plaque area did not change significantly.



The cross-sectional area of the atherosclerotic plaque appeared to be constant during vasomotion of human coronary arteries.
Pooled analysis of two randomized trials comparing titanium-nitride-oxide-coated stent versus drug-eluting stent in STEMI.

We performed a pooled analysis based on patient-level data from the TITAX-AMI and BASE-ACS trials to evaluate the outcome of titanium-nitride-oxide-coated bioactive stents vs drug-eluting stents in patients with ST-segment elevation myocardial infarction at 2-year follow-up.



The TITAX-AMI trial compared bioactive stents with paclitaxel-eluting stents in 425 patients with acute myocardial infarction. The BASE-ACS trial compared bioactive stents with everolimus-eluting stents in 827 patients with acute coronary syndrome. The primary endpoint for the pooled analysis was major adverse cardiac events: a composite of cardiac death, recurrent myocardial infarction, or ischemia-driven target lesion revascularization at 2-year follow-up.



The pooled analysis included 501 patients; 245 received bioactive stents, and 256 received drug-eluting stents. The pooled bioactive stent group was associated with a risk ratio of 0.85 for major adverse cardiac events (95% confidence interval, 0.53-1.35; P=.49) compared to the pooled drug-eluting stent group. Similarly, the pooled bioactive stent group was associated with a risk ratio of 0.71 for cardiac death (95% confidence interval, 0.26-1.95; P=.51), 0.44 for recurrent myocardial infarction (95% confidence interval, 0.20-0.97; P=.04), and 1.39 for ischemia-driven target lesion revascularization (95% confidence interval, 0.74-2.59; P=.30), compared to the pooled drug-eluting stent group. These results were confirmed by propensity-score adjusted analysis of the combined datasets.



In patients with ST-segment elevation myocardial infarction, bioactive stents were associated with lower rates of recurrent myocardial infarction compared to drug-eluting stents at 2-year follow-up; yet, the rates of cardiac death and ischemia-driven target lesion revascularization were similar.
Pharmacokinetic interactions between lersivirine and zidovudine, tenofovir disoproxil fumarate/emtricitabine and abacavir/lamivudine.

To investigate pharmacokinetic interactions associated with coadministration of lersivirine with zidovudine, tenofovir disoproxil fumarate (DF)/emtricitabine (Truvada(®)) or abacavir/lamivudine (Epzicom(®)/Kivexa(®)).



Three Phase I, open, crossover studies with two (studies 1 and 3) or three (study 2) treatment periods were conducted in healthy individuals. In study 1, individuals received zidovudine and placebo or zidovudine and lersivirine on days 1-14. In study 2, individuals received lersivirine and tenofovir DF/emtricitabine, lersivirine and placebo or tenofovir DF/emtricitabine and placebo on days 1-10. In study 3, individuals received abacavir/lamivudine only in period 1 (5 days) and abacavir/lamivudine and lersivirine in period 2 (10 days). Blood samples were taken on days 1-14 (study 1) or day of final dose (studies 2 and 3) and analysed using high performance liquid chromatography/dual mass spectrometry. Pharmacokinetic parameters were calculated by standard non-compartmental methods.



When coadministered with lersivirine, zidovudine exposure increased by 35%, and exposure of its metabolite zidovudine-glucuronide decreased by 19%. Following coadministration of lersivirine and tenofovir DF/emtricitabine, tenofovir exposure increased by 30%, and lersivirine exposure decreased by 12%. Coadministration of lersivirine and abacavir/lamivudine increased abacavir exposure by 27% and decreased lamivudine exposure by 8%. Adverse events were predominantly mild in these Phase I studies.



Coadministration of lersivirine with zidovudine, tenofovir DF/emtricitabine or abacavir/lamivudine influenced the systemic exposure of all nucleoside reverse transcriptase inhibitor agents investigated (except for lamivudine; emtricitabine pharmacokinetics were not assessed). Changes were not considered clinically meaningful for zidovudine and abacavir. The clinical relevance of the effect on tenofovir pharmacokinetics is currently unknown.