nils-herrmann/clean_scirepeval huggingface dataset:
Symptom Control Trials in Patients With Advanced Cancer: A Qualitative Study

Symptom control research in patients with advanced cancer is not common. This may be the result of a belief that this research is unethical, not practical, or that patients are not interested. However, the experiences of cancer patients who have actually taken part in symptom control research near the end of life have never been detailed.



The objective was to explore the experiences of patients with advanced cancer who had taken part in symptom control trials.



A prospective two-center study was undertaken using grounded theory methodology. Theoretical sampling was used to recruit patients from one of two double-blind, randomized, placebo-controlled trials studying novel analgesic agents for cancer-related pain. Participants completed one semistructured interview. Recruitment and interviewing continued until data saturation was achieved.



Twenty-one participants were recruited. Fifteen (71%) were male, with a mean age of 62 years. Key themes identified included reasons for trial participation, participants' interactions with the trial staff, and participants' responses to the effect the trial had on their pain. In general, participants regarded taking part in a clinical trial as a positive experience, and potentially improving overall well-being. Crucially, this was not related to whether there had been an improvement in symptoms.



The findings provide grounds for optimism that patients with advanced cancer may benefit from taking part in symptom control trials, supporting the paradigm that participation in symptom control research should be encouraged in this population.
Bacterial interference for prevention of urinary tract infection: a prospective, randomized, placebo-controlled, double-blind pilot trial.

This prospective, randomized, placebo-controlled, double-blind pilot trial examined the efficacy of bacterial interference in preventing urinary tract infection (UTI) in 27 patients with spinal cord injury. Patients whose bladders became colonized with Escherichia coli 83972 were half as likely (P=.01) than noncolonized patients to develop UTI during the subsequent year.
Using next-generation sequencing for high resolution multiplex analysis of copy number variation from nanogram quantities of DNA from formalin-fixed paraffin-embedded specimens

The use of next-generation sequencing technologies to produce genomic copy number data has recently been described. Most approaches, however, reply on optimal starting DNA, and are therefore unsuitable for the analysis of formalin-fixed paraffin-embedded (FFPE) samples, which largely precludes the analysis of many tumour series. We have sought to challenge the limits of this technique with regards to quality and quantity of starting material and the depth of sequencing required. We confirm that the technique can be used to interrogate DNA from cell lines, fresh frozen material and FFPE samples to assess copy number variation. We show that as little as 5 ng of DNA is needed to generate a copy number karyogram, and follow this up with data from a series of FFPE biopsies and surgical samples. We have used various levels of sample multiplexing to demonstrate the adjustable resolution of the methodology, depending on the number of samples and available resources. We also demonstrate reproducibility by use of replicate samples and comparison with microarray-based comparative genomic hybridization (aCGH) and digital PCR. This technique can be valuable in both the analysis of routine diagnostic samples and in examining large repositories of fixed archival material.
Can common-type atrial flutter be a sign of an arrhythmogenic substrate in paroxysmal atrial fibrillation? Clinical and ablative consequences in patients with coexistent paroxysmal atrial fibrillation/atrial flutter.

The coexistence of atrial fibrillation (AF) and atrial flutter (AFL) is well recognized. AF precedes the onset of AFL in almost all instances. We evaluated the effect of 2 ablation strategies in patients with paroxysmal AF (PAF) and AFL.



Ninety-eight patients with PAF/AFL were prospectively recruited to undergo pulmonary vein cryoisolation (PVI). Those with at least 1 episode of sustained common-type AFL were assigned to cavotricuspid isthmus cryoablation followed by a 6-week monitoring period and a subsequent PVI (n=36; group I). Patients with PAF only underwent PVI (n=62; group II). The study included 76 men with a mean age of 50+/-10 years. Most patients (76 [78%]) had no structural heart disease. When the 2 groups were compared, residual AF after a blanking period of 3 months after PVI occurred in 24 patients (67%) in group I versus 7 (11%) in group II (P<0.05).



In patients with PAF and no documented common-type AFL, PVI alone prevented the occurrence of AF in 82%, whereas in patients with AFL/PAF, cavotricuspid isthmus cryoablation and PVI were used successfully to treat sustained common-type AFL but appeared to be insufficient to prevent recurrences of AF. In this population, AFL can be a sign that non-pulmonary vein triggers are the culprit behind AF or that sufficient electrical remodeling has already occurred in both atria, and thus a strategy that includes substrate modification may be required.
Actigraphy as a diagnostic aid for REM sleep behavior disorder in Parkinson’s disease

Rapid eye movement (REM) sleep behavior disorder (RBD) is a common parasomnia in Parkinson's disease (PD) patients. The current International Classification of Sleep Disorders (ICSD-II) requires a clinical interview combined with video polysomnography (video-PSG) to diagnose. The latter is time consuming and expensive and not always feasible in clinical practice. Here we studied the use of actigraphy as a diagnostic tool for RBD in PD patients.



We studied 45 consecutive PD patients (66.7% men) with and without complaints of RBD. All patients underwent one night of video-PSG and eight consecutive nights of actigraphy. Based on previous studies, the main outcome measure was the total number of bouts classified as "wake", compared between patients with (PD + RBD) and without RBD (PD- RBD).



23 (51.1%) patients had RBD according to the ICSD-II criteria. The total number of wake bouts was significantly higher in RBD patients (PD + RBD 73.2 ± 40.2 vs. PD-RBD 48.4 ± 23.3, p = .016). A cut off of 95 wake bouts per night resulted in a specificity of 95.5%, a sensitivity of 20.1% and a positive predictive value of 85.7%. Seven patients were suspected of RBD based on the interview alone, but not confirmed on PSG; six of whom scored below 95 wake bouts per night on actigraphy.



PD patients with RBD showed a significantly higher number of bouts scored as "wake" using actigraphy, compared to patients without RBD. In clinical practice, actigraphy has a high specificity, but low sensitivity in the diagnosis of RBD. The combination of actigraphy and previously reported RBD questionnaires may be a promising method to diagnose RBD in patients with PD.
Neurosurgical emergency transfers to academic centers in Cook County: a prospective multicenter study.

The absence of surgical subspecialty emergency care in the United States is a growing public health concern. Neurosurgery is a field lacking coverage in many areas of the country; however, this is generally thought to be of greater concern in rural areas. Because of decreasing numbers of neurosurgeons, medical malpractice, and liability concerns, neurosurgery coverage is becoming a public health crisis in urban areas. Our objective was to quantify neurosurgical emergency transfers to academic medical centers in Cook County, IL, including patient demographics, reasons for transfer, time lapse in transfer, and effects on patient condition.



Data on neurosurgery emergency transfers was gathered prospectively by all five of the academic neurosurgery departments in Cook County, IL, over a 2-month period. Patient demographics devoid of identifiers, diagnosis, transfer origin, time lapse of transfer, and patient condition at the time of transfer and at the receiving hospital were recorded.



Two-hundred thirty emergent neurosurgical transfers occurred during the study period. The most common diagnoses were parenchymal intracerebral hemorrhage (33%) and subarachnoid hemorrhage (28%). Sixty-six percent of neurosurgical transfers to academic medical facilities originated at hospitals without full-time neurosurgery coverage. The mean time to transfer for all patients was 5 hours 10 minutes (standard deviation, 3 h 42 min; range, 1-20 h 12 min). A decline in Glasgow Coma Scale score was seen in 29 patients. A shortage of neurosurgical intensive care unit beds occurred on 55% of the days in the study. Only 19% of the emergency cases were related to cranial trauma, and only 3% of transfers came from Level 1 trauma centers.



A combination of factors has led to decreases in availability of neurosurgical coverage in Cook County community hospital emergency departments. This has placed an increased burden on neurosurgical departments at academic centers, and, in some cases, delays led to a decline in patient condition. Eighty-one percent of the cases were not related to cranial trauma; thus, acute care trauma surgeons would be of little use. Coordinated efforts among local governments, medical centers, and emergency medical services to regionalize subspecialty services will be necessary to manage this problem.
Longitudinal study on Streptococcus pneumoniae, Haemophilus influenzae and Staphylococcus aureus nasopharyngeal colonization in HIV-infected and -uninfected infants vaccinated with pneumococcal conjugate vaccine.

Streptococcus pneumoniae, Haemophilus influenzae and Staphylococcus aureus are all potentially pathogenic, which frequently colonize the nasopharynx (NP) prior to causing disease. We studied bacterial NP-colonization in 321 HIV-infected and 243 HIV-uninfected children vaccinated with 7-valent pneumococcal conjugate vaccine (PCV7) at 6, 10 and 14 weeks of age.



HIV-uninfected infants included those born to HIV-uninfected (HUU) and HIV-infected women (HEU); HIV-infected children with CD4+ lymphocyte ≥25% were randomized to initiate antiretroviral therapy immediately (ART-Immed) or when clinically indicated (ART-Def). Nasopharyngeal swabs for bacterial culture were taken prior to each PCV7 dose (Visits 1-3) and at 20, 39, 47 and 67 weeks of age (Visits 4-7). Swabs were cultured by standard methods and pneumococcal serotyping done by the Quellung method.



Colonization patterns for pneumococcus, H. influenzae and S. aureus did not differ between HUU and HEU children; and were also generally similar between ART-Def and ART-Immed children. Prevalence of PCV7-serotype colonization was similar between HIV-infected and HIV-uninfected children, however, overall pneumococcal and specifically non-vaccine serotype colonization tended to be lower in HIV-infected children. HIV-infected children also had a 44% lower prevalence of S. aureus colonization at Visit-1 (p=0.010); and H. influenzae colonization was also lower among HIV-infected than HIV-uninfected children at Visit-2, Visit-3, Visit-6 and Visit-7.



Vaccine-serotype colonization is similar in PCV-immunized HIV-infected and HIV-uninfected children. We, however, identified a lower prevalence of overall-pneumococcal and H. influenzae colonization in HIV-infected children post-PCV vaccination, the clinical-relevance of which warrants further study.
The Discriminative validity of "nociceptive," "peripheral neuropathic," and "central sensitization" as mechanisms-based classifications of musculoskeletal pain.

Empirical evidence of discriminative validity is required to justify the use of mechanisms-based classifications of musculoskeletal pain in clinical practice. The purpose of this study was to evaluate the discriminative validity of mechanisms-based classifications of pain by identifying discriminatory clusters of clinical criteria predictive of "nociceptive," "peripheral neuropathic," and "central sensitization" pain in patients with low back (± leg) pain disorders.



This study was a cross-sectional, between-patients design using the extreme-groups method. Four hundred sixty-four patients with low back (± leg) pain were assessed using a standardized assessment protocol. After each assessment, patients' pain was assigned a mechanisms-based classification. Clinicians then completed a clinical criteria checklist indicating the presence/absence of various clinical criteria.



Multivariate analyses using binary logistic regression with Bayesian model averaging identified a discriminative cluster of 7, 3, and 4 symptoms and signs predictive of a dominance of "nociceptive," "peripheral neuropathic," and "central sensitization" pain, respectively. Each cluster was found to have high levels of classification accuracy (sensitivity, specificity, positive/negative predictive values, positive/negative likelihood ratios).



By identifying a discriminatory cluster of symptoms and signs predictive of "nociceptive," "peripheral neuropathic," and "central" pain, this study provides some preliminary discriminative validity evidence for mechanisms-based classifications of musculoskeletal pain. Classification system validation requires the accumulation of validity evidence before their use in clinical practice can be recommended. Further studies are required to evaluate the construct and criterion validity of mechanisms-based classifications of musculoskeletal pain.
An Immunochip-based interaction study of contrasting interaction effects with smoking in ACPA-positive versus ACPA-negative rheumatoid arthritis.

To investigate the gene-environment interaction between smoking and single nucleotide polymorphisms (SNPs), using Immunochip material, on the risk of developing either of two serologically defined subsets of RA.



Interaction between smoking and 133,648 genetic markers from the Immunochip was examined for two RA subsets, defined by the presence or absence of ACPA. A total of 1590 ACPA-positive and 891 ACPA-negative cases were compared with 1856 controls in the Swedish Epidemiological Investigation of RA (EIRA) case-control study. Logistic regression models were used to determine the presence of interaction. The proportion attributable to interaction was calculated for each smoking-SNP pair. Replication was carried out in an independent dataset from northern Sweden. To further validate and extend the results, interaction analysis was also performed using genome-wide association studies data on EIRA individuals.



In ACPA-positive RA, 102 SNPs interacted significantly with smoking, after Bonferroni correction. All 102 SNPs were located in the HLA region, mainly within the HLA class II region, 51 of which were replicated. No additional loci outside chromosome 6 were identified in the genome-wide association studies validation. After adjusting for HLA-DRB1 shared epitope, 15 smoking-SNP pairs remained significant for ACPA-positive RA, with 8 of these replicated (loci: BTNL2, HLA-DRA, HLA-DRB5, HLA-DQA1, HLA-DOB and TAP2). For ACPA-negative RA, no smoking-SNP pairs passed the threshold for significance.



Our study presents extended gene variation patterns involved in gene-smoking interaction in ACPA-positive, but not ACPA-negative, RA. Notably, variants in HLA-DRB1 and those in additional genes within the MHC class II region, but not in any other gene regions, showed interaction with smoking.
Hemodynamic Consequences of Malignant Ascites in Epithelial Ovarian Cancer Surgery∗

Malignant ascites (MA) is most commonly observed in patients scheduled for epithelial ovarian cancer (EOC) surgery and is supposed as a major risk factor promoting perioperative hemodynamic deterioration. We aimed to assess the hemodynamic consequences of MA on systemic circulation in patients undergoing cytoreductive EOC surgery.This study is a predefined post-hoc analysis of a randomized controlled pilot trial comparing intravenous solutions within a goal-directed algorithm to optimize hemodynamic therapy in patients undergoing cytoreductive EOC surgery. Ascites was used to stratify the EOC patients prior to randomization in the main study. We analyzed 2 groups according to the amount of ascites (NLAS: none or low ascites [<500 mL] vs HAS: high ascites group [>500 mL]). Differences in hemodynamic variables with respect to time were analyzed using nonparametric analysis for longitudinal data and multivariate generalized estimating equation adjusting the analysis for the randomized study groups of the main study.A total of 31 patients in the NLAS and 16 patients in the HAS group were analyzed. Although cardiac output was not different between groups suggesting a similar circulatory blood flow, the HAS group revealed higher heart rates and lower stroke volumes during surgery. There were no differences in pressure-based hemodynamic variables. In the HAS group, fluid demands, reflected by the time to reindication of a fluid challenge after preload optimization, increased steadily, whereas stroke volume could not be maintained at baseline resulting in hemodynamic instability after 1.5 h of surgery. In contrast, in the NLAS group fluid demands were stable and stroke volume could be maintained during surgery. Clinically relevant associations of the type of fluid replacement with hemodynamic consequences were particularly observed in the HAS group, in which transfusion of fresh frozen plasma (FFP) was associated to an improved circulatory flow and reduced vasopressor and fluid demands, whereas the administration of artificial infusion solutions was related to opposite effects.Malignant ascites >500 mL implies increased fluid demands and substantial alterations in circulatory blood flow during cancer surgery. Fresh frozen plasma transfusion promotes recovering hemodynamic stability in patients with malignant ascites >500 mL, in whom artificial infusion solutions could not prevent from hemodynamic deterioration.
Comprehensive assessment of genetic variation of catechol-O-methyltransferase and breast cancer risk.

Because catechol-O-methyltransferase (COMT) catalyzes the addition of methyl groups to stabilize catechol estrogens that may induce DNA damage, genetic variants could influence breast cancer risk. To comprehensively characterize genetic variation in this gene, we selected haplotype-tagging single nucleotide polymorphisms (htSNP) in COMT. A total of 11 htSNPs (including COMT Val(158)Met) were selected based on the resequencing and dense genotyping approach of the Breast and Prostate Cancer Cohort Consortium. htSNPs were genotyped in a population-based, case-control study in Poland (1,995 cases and 2,296 controls). Individual SNPs were not significantly associated with risk. Haplotypes were estimated using the expectation-maximization algorithm. Overall differences in the haplotype distribution between cases and controls were assessed using a global score test. The TGAG haplotype (frequent in 4.3% of controls), in a linkage disequilibrium (LD) block that included the 3' untranslated region (UTR) of COMT, was associated with breast cancer risk (odds ratio, 1.29; 95% confidence interval, 1.06-1.58) compared with the most common haplotype TGAA; however, the global test for haplotype associations was not significant (P = 0.09). Haplotypes in another LD block, which included COMT Val(158)Met, were not associated with breast cancer risk (global P = 0.76). Haplotype-breast cancer risk associations were not significantly modified by hormonally related risk factors, family history of breast cancer, or tumor characteristics. In summary, our data does not support a substantial overall association between COMT haplotypes and breast cancer. The suggestion of increased risk associated with a haplotype in the 3' UTR of COMT needs to be confirmed in independent study populations.
Impact of aortic stiffness attenuation on survival of patients in end-stage renal failure.

Aortic pulse wave velocity (PWV) is a predictor of mortality in patients with end-stage renal failure (ESRF). The PWV is partly dependent on blood pressure (BP), and a decrease in BP can attenuate the stiffness. Whether the changes in PWV in response to decreases in BP can predict mortality in ESRF patients has never been investigated.



One hundred fifty ESRF patients (aged 52+/-16 years) were monitored for 51+/-38 months. From entry until the end of follow-up, the changes of PWV in response to decreased BP were measured ultrasonographically. BP was controlled by adjustment of "dry weight" and, when necessary, with ACE inhibitors, calcium antagonists, and/or beta-blockers, in combination if necessary. Fifty-nine deaths occurred, including 40 cardiovascular and 19 noncardiovascular events. Cox analyses demonstrated that independent of BP changes, the predictors of all-cause and cardiovascular mortality were as follows: absence of PWV decrease in response to BP decrease, increased left ventricular mass, age, and preexisting cardiovascular disease. Survival was positively associated with ACE inhibitor use. After adjustment for all confounding factors, the risk ratio for the absence of PWV decrease was 2.59 (95% CI 1.51 to 4.43) for all-cause mortality and 2.35 (95% CI 1.23 to 4.41) for cardiovascular mortality. The risk ratio for ACE inhibitor use was 0.19 (95% CI 0.14 to 0.43) for all-cause mortality and 0.18 (95% CI 0.06 to 0.55) for cardiovascular mortality.



These results indicate that in ESRF patients, the insensitivity of PWV to decreased BP is an independent predictor of mortality and that use of ACE inhibitors has a favorable effect on survival that is independent of BP changes.
A phase I study of BI 811283, an Aurora B kinase inhibitor, in patients with advanced solid tumors

This phase I study investigated the maximum tolerated dose (MTD), safety, pharmacokinetics, pharmacodynamics, and antitumor activity of the Aurora B kinase inhibitor BI 811283 in patients with advanced solid tumors. BI 811283 was administered via 24-h infusion on Days 1 and 15 of a 4-week cycle (schedule A) or Day 1 of a 3-week cycle (schedule B) in a modified 3 + 3 dose-escalation design. Pharmacodynamic assessments included immunohistochemistry for phosphorylated histone H3 (pHH3) on skin biopsies to determine Aurora B kinase inhibition and plasma concentrations of caspase-cleaved CK-18 (apoptosis marker). A total of 121 patients were treated. The MTDs of BI 811283 were 125 mg (schedule A) and 230 mg (schedule B). Dose-limiting toxicities were primarily hematological (febrile neutropenia and grade 4 neutropenia); the most common drug-related adverse effects included neutropenia, fatigue, leukopenia, nausea, alopecia, diarrhea, and decreased appetite. A trend toward a decrease in pHH3 was observed, with increasing BI 811283 doses, indicating target engagement; there was no consistent trend regarding caspase-cleaved CK-18 levels. No objective response was observed although 19 patients in each schedule achieved clinical benefit (stable disease). BI 811283 demonstrated a generally manageable safety profile and disease stabilization in some patients. EudraCT No: 2007-000191-17,