nils-herrmann/clean_scirepeval huggingface dataset:
Efficacy of antimicrobial-impregnated external ventricular drain catheters: a prospective, randomized, controlled trial.

Catheter-related infection of the cerebrospinal fluid (CSF) pathways is a potentially life-threatening complication of external ventricular drainage. A major source of infection is bacterial contamination along the external ventricular drain (EVD) catheter track. The authors examined the efficacy of EVD catheters impregnated with minocycline and rifampin in preventing these catheter-related infections.



The authors conducted a prospective, randomized clinical trial at six academic medical centers. All hospitalized patients 18 years or older who required placement of an EVD catheter were eligible for inclusion in the study. Patients were randomly assigned to undergo placement of an EVD with a catheter impregnated with minocycline and rifampin or a standard untreated catheter (control group). To assess primary outcome, CSF samples were collected using a sterile technique at the time of catheter insertion, at least every 72 hours while the catheter remained in place, and at the time of catheter removal. At the time of removal, CSF cultures were obtained from the tip and tunneled segments of each catheter by performing semiquantitative roll-plate and quantitative sonication techniques. Of the 306 patients enrolled in the study, data from 288 were included in the final analysis. Eighteen patients were excluded from analysis: 14 because the ventricular catheter was in place less than 24 hours, and four because CSF cultures obtained at the time of catheter insertion were positive for infection. Of these 288 patients, 139 were assigned to the control group and 149 to the treatment group. The two groups were well matched with respect to all clinical characteristics, including patient sex and mean age, indication for catheter placement, and length of time the catheter remained in place. The antibiotic-impregnated catheters were one half as likely to become colonized as the control catheters (17.9 compared with 36.7%, respectively, p < 0.0012). Positive CSF cultures were seven times less frequent in patients with antibiotic-impregnated catheters compared with those in the control group (1.3 compared with 9.4%, respectively, p = 0.002).



The use of EVD catheters impregnated with minocycline and rifampin can significantly reduce the risk of catheter-related infections.
Examining the challenges of family recruitment to behavioral intervention trials: factors associated with participation and enrollment in a multi-state colonoscopy intervention trial

Colonoscopy is one of the most effective methods of cancer prevention and detection, particularly for individuals with familial risk. Recruitment of family members to behavioral intervention trials remains uniquely challenging, owing to the intensive process required to identify and contact them. Recruiting at-risk family members involves contacting the original cancer cases and asking them to provide information about their at-risk relatives, who must then be contacted for study enrollment. Though this recruitment strategy is common in family trials, few studies have compared influences of patient and relative participation to nonparticipation. Furthermore, although use of cancer registries to identify initial cases has increased, to our knowledge no study has examined the relationship between registries and family recruitment outcomes.



This study assessed predictors of case participation and relative enrollment in a recruitment process that utilized state cancer registries. Participation characteristics were analyzed with separate multivariable logistic regressions in three stages: (1) cancer registry-contacted colorectal cancer (CRC) cases who agreed to study contact; (2) study-contacted CRC cases who provided at-risk relative information; and (3) at-risk relatives contacted for intervention participation.



Cancer registry source was predictive of participation for both CRC cases and relatives, though relative associations (odds ratios) varied across registries. Cases were less likely to participate if they were Hispanic or nonwhite, and were more likely to participate if they were female or younger than 50 at cancer diagnosis. At-risk relatives were more likely to participate if they were from Utah, if another family member was also participating in the study, or if they had previously had a colonoscopy. The number of eligible cases who had to be contacted to enroll one eligible relative varied widely by registry, from 7 to 81.



Family recruitment utilizing cancer registry-identified cancer cases is feasible, but highly dependent on both the strategies and protocols of those who are recruiting and on participant characteristics such as sex, race, or geography. Devising comprehensive recruitment protocols that specifically target those less likely to enroll may help future research meet recruitment goals.
Doppler resistive index to reflect regulation of renal vascular tone during sepsis and acute kidney injury

Renal resistive index (RI), determined by Doppler ultrasonography, directly reveals and quantifies modifications in renal vascular resistance. The aim of this study was to evaluate if mean arterial pressure (MAP) is determinant of renal RI in septic, critically ill patients suffering or not from acute kidney injury (AKI).



This prospective observational study included 96 patients. AKI was defined according to RIFLE criteria and transient or persistent AKI according to renal recovery within 3 days.



Median renal RIs were 0.72 (0.68-0.75) in patients without AKI and 0.76 (0.72-0.80) in patients with AKI (P = 0.001). RIs were 0.75 (0.72-0.79) in transient AKI and 0.77 (0.70-0.80) in persistent AKI (P = 0.84). RI did not differ in patients given norepinephrine infusion and was not correlated with norepinephrine dose. RI was correlated with MAP (ρ = -0.47; P = 0.002), PaO2/FiO2 ratio (ρ = -0.33; P = 0.04) and age (ρ = 0.35; P = 0.015) only in patients without AKI.



A poor correlation between renal RI and MAP, age, or PaO2/FiO2 ratio was found in septic and critically ill patients without AKI compared to patients with AKI. These findings suggest that determinants of RI are multiple. Renal circulatory response to sepsis estimated by Doppler ultrasonography cannot reliably be predicted simply from changes in systemic hemodynamics. As many factors influence its value, the interest in a single RI measurement at ICU admission to determine optimal MAP remains uncertain.
Processes, barriers and facilitators to implementation of a participatory ergonomics program among eldercare workers.

This study aimed to investigate the processes of a participatory ergonomics program among 594 eldercare workers with emphasis on identified risk factors for low back pain and solutions, and reveal barriers and facilitators for implementation. Sixty-nine per cent of the identified risk factors were physical ergonomic, 24% were organisational and 7% were psychosocial risk factors. Most solutions were organisational (55%), followed by physical (43%) and psychosocial solutions (2%). Internal factors (e.g. team or management) constituted 47% of the barriers and 75% of the facilitators. External factors (e.g. time, financial resources, collaboration with resident or relatives) constituted 53% of the barriers and 25% of the facilitators. This study revealed the processes and implementation of a participatory ergonomics program among eldercare workers. The findings can be transferred to workers, workplaces, health and safety professionals, and researchers to improve future participatory ergonomics programs.
Repetitive transcranial magnetic stimulation for levodopa-induced dyskinesias in Parkinson's disease.

In a placebo-controlled, single-blinded, crossover study, we assessed the effect of "real" repetitive transcranial magnetic stimulation (rTMS) versus "sham" rTMS (placebo) on peak dose dyskinesias in patients with Parkinson's disease (PD). Ten patients with PD and prominent dyskinesias had rTMS (1,800 pulses; 1 Hz rate) delivered over the motor cortex for 4 consecutive days twice, once real stimuli and once sham stimulation were used; evaluations were done at the baseline and 1 day after the end of each of the treatment series. Direct comparison between sham and real rTMS effects showed no significant difference in clinician-assessed dyskinesia severity. However, comparison with the baseline showed small but significant reduction in dyskinesia severity following real rTMS but not placebo. The major effect was on dystonia subscore. Similarly, in patient diaries, although both treatments caused reduction in subjective dyskinesia scores during the days of intervention, the effect was sustained for 3 days after the intervention for the real rTMS only. Following rTMS, no side effects and no adverse effects on motor function and PD symptoms were noted. The results suggest the existence of residual beneficial clinical aftereffects of consecutive daily applications of low-frequency rTMS on dyskinesias in PD. The effects may be further exploited for potential therapeutic uses.
Ultrasonographic assessment of inflammatory activity in rheumatoid arthritis: comparison of extended versus reduced joint evaluation.

To investigate the validity of reduced joint counts for ultrasonographic (US) assessment of joint inflammatory activity in patients with rheumatoid arthritis (RA).



Ninety-four patients with RA were included. C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR) levels were recorded for each patient. The presence of tenderness, swelling and a subjective swelling score from 0 to 3 were assessed by two rheumatologists who reached consensus in 60 joints examined in each patient. All patients underwent an US examination by a third blinded rheumatologist, using power Doppler (PD). US joint effusion, synovitis and PD signal were graded from 0 to 3 in the 60 joints. A 60-joint count and index for effusion, synovitis and PD signal were recorded. A 6-, 10-, 16-, 18-, and two 12-joint counts and indices for US parameters that included the most frequently US involved joints were calculated for each patient.



A 12-joint assessment for effusion, synovitis and PD signal, including bilateral wrist, second and third MCP, second and third PIP of hands and knee joints highly correlated with corresponding 60-joint US counts and indices. This reduced-joint US evaluation showed a similar correlation with clinical and laboratory parameters of disease activity to corresponding 60-joint assessment.



We propose that a 12-joint evaluation may be a useful tool for US assessment of overall joint inflammatory activity in RA.
The PEX study – Exercise therapy for patellofemoral pain syndrome: design of a randomized clinical trial in general practice and sports medicine [ISRCTN83938749]

Patellofemoral complaints are frequently seen in younger and active patients. Clinical strategy is usually based on decreasing provoking activities as sports and demanding knee activities during work and leisure and reassuring the patient on the presumed good outcome. Exercise therapy is also often prescribed although evidence on effectiveness is lacking. The objective of this article is to present the design of a randomized clinical trial that examines the outcome of exercise therapy supervised by a physical therapist versus a clinically accepted "wait and see" approach (information and advice about the complaints only). The research will address to both effectiveness and cost effectiveness of supervised exercise therapy in patients with patellofemoral pain syndrome (PFPS).



136 patients (adolescents and young adults) with patellofemoral pain syndrome are recruited in general practices and sport medicine centers. They will be randomly allocated receiving either 3 months of exercise therapy (or usual care. The primary outcome measures are pain, knee function and perception of recovery after 3 months and 12 months of follow up and will be measured by self reporting. Measurements will take place at baseline, 6 weeks, and 3 monthly until 1 year after inclusion in the study. Secondary outcome measurements include an economic evaluation.A cost-utility analysis will be performed that expresses health improvements in Quality Adjusted Life Years (QALYs) and incorporates direct medical costs and productivity costs



This study has been designed after reviewing the literature on exercise therapy for patellofemoral pain syndrome. It was concluded that to merit the effect of exercise therapy a trial based on correct methodological concept needed to be executed. The PEX study is a randomized clinical trial where exercise therapy is compared to usual care. This trial started in April 2005 and will finish in June 2007. The first results will be available around December 2007.
Comparison of CO 2 in air versus carbogen for the measurement of cerebrovascular reactivity with magnetic resonance imaging

Measurement of cerebrovascular reactivity (CVR) can give valuable information about existing pathology and the risk of adverse events, such as stroke. A common method of obtaining regional CVR values is by measuring the blood flow response to carbon dioxide (CO2)-enriched air using arterial spin labeling (ASL) or blood oxygen level-dependent (BOLD) imaging. Recently, several studies have used carbogen gas (containing only CO2 and oxygen) as an alternative stimulus. A direct comparison was performed between CVR values acquired by ASL and BOLD imaging using stimuli of (1) 5% CO2 in air and (2) 5% CO2 in oxygen (carbogen-5). Although BOLD and ASL CVR values are shown to be correlated for CO2 in air (mean response 0.11±0.03% BOLD, 4.46±1.80% ASL, n1⁄4 16 hemispheres), this correlation disappears during a carbogen stimulus (0.36±0.06% BOLD, 4.97±1.30% ASL). It is concluded that BOLD imaging should generally not be used in conjunction with a carbogen stimulus when measuring CVR, and that care must be taken when interpreting CVR as measured by ASL, as values obtained from different stimuli (CO2 in air versus carbogen) are not directly comparable.
Learning and confirming with preclinical studies: modeling and simulation in the discovery of GDC-0917, an inhibitor of apoptosis proteins antagonist.

The application of modeling and simulation techniques is increasingly common in the preclinical stages of the drug development process. GDC-0917 [(S)-1-((S)-2-cyclohexyl-2-((S)-2-(methylamino)propanamido)acetyl)-N-(2-(oxazol-2-yl)-4-phenylthiazol-5-yl)pyrrolidine-2-carboxamide] is a potent second-generation antagonist of inhibitor of apoptosis (IAP) proteins that is being developed for the treatment of various cancers. GDC-0917 has low to moderate clearance in the mouse (12.0 ml/min/kg), rat (27.0 ml/min/kg), and dog (15.3 ml/min/kg), and high clearance in the monkey (67.6 ml/min/kg). Accordingly, oral bioavailability was lowest in monkeys compared with other species. Based on our experience with a prototype molecule with similar structure, in vitro-in vivo extrapolation was used to predict a moderate clearance (11.5 ml/min/kg) in humans. The predicted human volume of distribution was estimated using simple allometry at 6.69 l/kg. Translational pharmacokinetic-pharmacodynamic (PK-PD) analysis using results from MDA-MB-231-X1.1 breast cancer xenograft studies and predicted human pharmacokinetics suggests that ED50 and ED90 targets can be achieved in humans using acceptable doses (72 mg and 660 mg, respectively) and under an acceptable time frame. The relationship between GDC-0917 concentrations and pharmacodynamic response (cIAP1 degradation) was characterized using an in vitro peripheral blood mononuclear cell immunoassay. Simulations of human GDC-0917 plasma concentration-time profile and cIAP1 degradation at the 5-mg starting dose in the phase 1 clinical trial agreed well with observations. This work shows the importance of leveraging information from prototype molecules and illustrates how modeling and simulation can be used to add value to preclinical studies in the early stages of the drug development process.
Relation of interatrial block to new-onset atrial fibrillation in patients with Chagas cardiomyopathy and implantable cardioverter-defibrillators.

Chagas cardiomyopathy is an endemic disease in Latin America. A significant proportion of patients develop atrial fibrillation (AF), which may result in stroke and increased morbidity or mortality. Interatrial block (IAB) has been associated with the development of AF in different clinical scenarios. The aim of our study was to determine whether IAB can predict new-onset AF in patients with Chagas cardiomyopathy and implantable cardioverter-defibrillators (ICDs). We conducted a retrospective study of patients with Chagas cardiomyopathy and ICDs from 14 centers in Latin America. Demographics, clinical, and device follow-up were collected. Surface electrocardiograms were scanned at 300 dpi and maximized ×8. Semiautomatic calipers were used to determine P-wave onset and offset. Partial IAB was defined as a P wave of >120 ms and advanced IAB as a P wave of >120 ms with biphasic morphology (±) in inferior leads. AF events and ICD therapies were reviewed during follow-up by 2 independent investigators. A total of 80 patients were analyzed. Mean age was 54.6 ± 10.4 years, and 52 (65%) were male. Mean left ventricular ejection fraction was 40 ± 12%. IAB was detected in 15 patients (18.8%), with 8 (10.0%) partial and 7 (8.8%) advanced. During a follow-up of 33 ± 20 months, 11 patients (13.8%) presented with new AF. IAB (partial + advanced) was strongly associated with new AF (p <0.0001) and inappropriate therapy by the ICD (p = 0.014). In conclusion, IAB (partial + advanced) predicted new-onset AF in patients with Chagas cardiomyopathy and ICDs.
Inhibition of airway hyperreactivity by oxybutynin chloride in subjects with cervical spinal cord injury

To further investigate mechanisms of airway hyperreactivity among subjects with chronic cervical spinal cord injury (SCI), we assessed airway responsiveness to aerosolized methacholine and histamine in subjects receiving chronic oxybutynin chloride therapy, and compared the findings with those not receiving the agent.  Twenty-five male subjects with cervical SCI participated in this study; 12 were maintained on oral oxybutynin chloride and 13 served as age-matched controls. Six of the 12 subjects receiving oxybutynin were challenged with aerosolized methacholine, and six with histamine; seven of the 13 control subjects were challenged with aerosolized methacholine and the remaining six with histamine.  All 13 control subjects and all six oxybutynin/histamine subjects exhibited a significant bronchoconstrictor response (PC20<8 mg/ml), whereas mean PC20 values for the oxybutynin/methacholine group were ⩾25 mg/ml.  Our finding that the bronchoconstrictor effects of methacholine were blocked by oxybutynin chloride while those of histamine were not suggests that oxybutynin acts primarily through anticholinergic pathways rather than by causing generalized airway smooth muscle relaxation.
Trigger-Action-Circuits: Leveraging Generative Design to Enable Novices to Design and Build Circuitry

The dramatic decrease in price and increase in availability of hobbyist electronics has led to a wide array of embedded and interactive devices. While electronics have become more widespread, developing and prototyping the required circuitry for these devices is still difficult, requiring knowledge of electronics, components, and programming. In this paper, we present Trigger-Action-Circuits (TAC), an interactive system that leverages generative design to produce circuitry, firmware, and assembly instructions, based on high-level, behavioural descriptions. TAC is able to generate multiple candidate circuits from a behavioural description, giving the user a number of alternative circuits that may be best suited to their use case (e.g., based on cost, component availability or ease of assembly). The generated circuitry uses off-the-shelf, commodity electronics, not specialized hardware components, enabling scalability and extensibility. TAC supports a range of common components and behaviors that are frequently required for prototyping electronic circuits. A user study demonstrated that TAC helps users avoid problems encountered during circuit design and assembly, with users completing their circuits significantly faster than with traditional methods.
Prolonged episodes of hypoglycaemia in HNF4A-MODY mutation carriers with IGT. Evidence of persistent hyperinsulinism into early adulthood

HNF4A is an established cause of maturity onset diabetes of the young (MODY). Congenital hyperinsulinism can also be associated with mutations in the HNF4A gene. A dual phenotype is observed in HNF4A-MODY with hyperinsulinaemic hypoglycaemia in the neonatal period progressing to diabetes in adulthood. The nature and timing of the transition remain poorly defined. We performed an observational study to establish changes in glycaemia and insulin secretion over a 6-year period. We investigated glycaemic variability and hypoglycaemia in HNF4A-MODY using a continuous glucose monitoring system (CGMS). An OGTT with measurement of glucose, insulin and C-peptide was performed in HNF4A participants with diabetes mellitus (DM) (n = 14), HNF4A-IGT (n = 7) and age- and BMI-matched MODY negative family members (n = 10). Serial assessment was performed in the HNF4A-IGT cohort. In a subset of HNF4A-MODY mutation carriers (n = 10), CGMS was applied over a 72-h period. There was no deterioration in glycaemic control in the HNF4A-IGT cohort. The fasting glucose-to-insulin ratio was significantly lower in the HNF4A-IGT cohort when compared to the normal control group (0.13 vs. 0.24, p = 0.03). CGMS profiling demonstrated prolonged periods of hypoglycaemia in the HNF4A-IGT group when compared to the HNF4A-DM group (432 vs. 138 min p = 0.04). In a young adult HNF4A-IGT cohort, we demonstrate preserved glucose, insulin and C-peptide secretory responses to oral glucose. Utilising CGMS, prolonged periods of hypoglycaemia are evident despite a median age of 21 years. We propose a prolonged hyperinsulinaemic phase into adulthood is responsible for the notable hypoglycaemic episodes.
Intravenous prednisolone in chronic bronchial asthma.

A single injection of 40 mg prednisolone phosphate was given to 10 patients with chronic bronchial asthma. Changes in pulmonary function were followed over a 30-hour period. Statistically significant changes occurred in the tests employed one hour after the injection of prednisolone. The maximum change for the group as a whole was seen to occur after eight hours. This time course of response is very similar to that obtained in previous studies on similar groups of patients with oral prednisolone where the peak effect occurred nine hours after the drug had been given. Intravenous hydrocortisone produces a much earlier peak effect, at five hours, when it is administered to chronic asthmatic patients.