nils-herrmann/clean_scirepeval huggingface dataset:
Evaluation of point-of-care PRO assessment in clinic settings: integration, parallel-forms reliability, and patient acceptability of electronic QOL measures during clinic visits

Assessment of patient-reported outcomes (PROs), such as health-related quality of life, has become an important component of healthcare that measures the impact of disease and medical treatment on patient health. Collecting PROs during point-of-care assessments and integrating them into the clinical setting, however, remains challenging. The objective of this pilot study was to evaluate the reliability, usability, and acceptability of point-of-care electronic PRO assessments implemented in a prostate cancer clinic. Fifty subjects completed paper–pencil and computerized formats of the Expanded Prostate Cancer Index Composite (EPIC), a validated, condition-specific QOL instrument, at separate times before treatment. Parallel-forms reliability was evaluated by comparing mean scores, variations in response distribution, and correlations between administration formats. Correlation coefficients of at least 0.70 were used for reliability testing. Differences between administration forms, indicating potential bias, were compared using the signed-rank test. A 6-item acceptability scale was also used to evaluate patient acceptability and satisfaction with the electronic format. Mean scores and standard deviations were similar between the paper–pencil and electronic forms across all EPIC instrument domains, and no assessment bias was found. Each EPIC domain demonstrated a high reliability between administration formats (correlation coefficients: 0.70–0.98). The majority (>90 %) of respondents found that the computerized QOL format was user friendly and simple to use. Point-of-care computerized QOL assessments were reliable and acceptable to patients in this study, supporting the feasibility of PRO integration at the point-of-care in clinical settings.
Outcomes of Cardiac Resynchronization Therapy With or Without Defibrillation in Patients With Nonischemic Cardiomyopathy.

Recent studies have cast doubt on the benefit of cardiac resynchronization therapy (CRT) with defibrillation (CRT-D) versus pacing (CRT-P) for patients with nonischemic cardiomyopathy (NICM). Left ventricular myocardial scar portends poor clinical outcomes.



The aim of this study was to determine whether CRT-D is superior to CRT-P in patients with NICM either with (+) or without (-) left ventricular midwall fibrosis (MWF), detected by cardiac magnetic resonance.



Clinical events were quantified in patients with NICM who were +MWF (n = 68) or -MWF (n = 184) who underwent cardiac magnetic resonance prior to CRT device implantation.



In the total study population, +MWF emerged as an independent predictor of total mortality (adjusted hazard ratio [aHR]: 2.31; 95% confidence interval [CI]: 1.45 to 3.68), total mortality or heart failure hospitalization (aHR: 2.02; 95% CI: 1.32 to 3.09), total mortality or hospitalization for major adverse cardiac events (aHR: 2.02; 95% CI: 1.32 to 3.07), death from pump failure (aHR: 1.95; 95% CI: 1.11 to 3.41), and sudden cardiac death (aHR: 3.75; 95% CI: 1.26 to 11.2) over a maximum follow-up period of 14 years (median 3.8 years [interquartile range: 2.0 to 6.1 years] for +MWF and 4.6 years [interquartile range: 2.4 to 8.3 years] for -MWF). In separate analyses of +MWF and -MWF, total mortality (aHR: 0.23; 95% CI: 0.07 to 0.75), total mortality or heart failure hospitalization (aHR: 0.32; 95% CI: 0.12 to 0.82), and total mortality or hospitalization for major adverse cardiac events (aHR: 0.30; 95% CI: 0.12 to 0.78) were lower after CRT-D than after CRT-P in +MWF but not in -MWF.



In patients with NICM, CRT-D was superior to CRT-P in +MWF but not -MWF. These findings have implications for the choice of device therapy in patients with NICM.
Standards of resuscitation during inter-hospital transportation: the effects of structured team briefing or guideline review - A randomised, controlled simulation study of two micro-interventions

Junior physicians are sometimes sent in ambulances with critically ill patients who require urgent transfer to another hospital. Unfamiliar surroundings and personnel, time pressure, and lack of experience may imply a risk of insufficient treatment during transportation as this can cause the physician to loose the expected overview of the situation. While health care professionals are expected to follow complex algorithms when resuscitating, stress can compromise both solo-performance and teamwork.



To examine whether inter-hospital resuscitation improved with a structured team briefing between physician and ambulance crew in preparation for transfer vs. review of resuscitation guidelines. The effect parameters were physician team leadership (requesting help, delegating tasks), time to resuscitation key elements (chest compressions, defibrillation, ventilations, medication, or a combination of these termed "the first meaningful action"), and hands-off ratio.



46 physicians graduated within 5 years.



A simulation intervention study with a control group and two interventions (structured team briefing or review of guidelines).  Cardiac arrest during simulated inter-hospital transfer.



Forty-six candidates participated: 16 (control), 13 (review), and 17 (team briefing). Reviewing guidelines delayed requesting help to 162 seconds, compared to 21 seconds in control and team briefing groups (p = 0.021). Help was not requested in 15% of cases; never requesting help was associated with an increased hands-off ratio, from 39% if the driver's assistance was requested to 54% if not (p < 0.01). No statistically significant differences were found between groups regarding time to first chest compression, defibrillation, ventilation, drug administration, or the combined "time to first meaningful action".



Neither review nor team briefing improved the time to resuscitation key elements. Review led to an eight-fold increase in the delay to requesting help. The association between never requesting help and an increased hands-off ratio underpins the importance of prioritising available resources. Other medical and non-medical domains have benefited from the use of guidelines reviews and structured team briefings. Reviewing guidelines may compromise the ability to focus on aspects such as team leading and delegating tasks and warrants the need for further studies focusing on how to avoid this cognitive impairment.
Population pharmacokinetics of lamotrigine in Chinese children with epilepsy

To establish a population pharmacokinetics (PPK) model for lamotrigine (LTG) in Chinese children with epilepsy in order to formulate an individualized dosage guideline.LTG steady-state plasma concentration data from therapeutic drug monitoring (TDM) were collected retrospectively from 284 patients, with a total of 404 plasma drug concentrations. LTG concentrations were determined using a HPLC method. The patients were divided into 2 groups: PPK model group (n=116) and PPK valid group (n=168). A PPK model of LTG was established with NONMEM based on the data from PPK model group according to a one-compartment model with first order absorption and elimination. To validate the basic and final model, the plasma drug concentrations of the patients in PPK model group and PPK valid group were predicted by the two models.The final regression model for LTG was as follows: CL (L/h)=1.01*(TBW/27.87)0.635*e−0.753*VPA*e0.868*CBZ*e0.633*PB, Vd (L)= 16.7*(TBW/27.87). The final PPK model was demonstrated to be stable and effective in the prediction of serum LTG concentrations by an internal and external approach validation.A PPK model of LTG in Chinese children with epilepsy was successfully established with NONMEM. LTG concentrations can be predicted accurately by this model. The model may be very useful for establishing initial LTG dosage guidelines.
Validation of STA-Liatest D-Di assay for exclusion of pulmonary embolism according to the latest Clinical and Laboratory Standard Institute/Food and Drug Administration guideline. Results of a multicenter management study

: Combined clinical pretest probability (PTP) and D-dimer testing have great diagnostic value for pulmonary embolism exclusion. To harmonize performance levels of D-dimer assays available on the market, the Clinical and Laboratory Standard Institute (CLSI) has published a guideline, endorsed by the US Food and Drug Administration (FDA). Such guideline specifies the ideal D-dimer assay characteristic and target population. This study was conducted following the CLSI guideline to upgrade the assay-intended use and obtain FDA clearance of STA-Liatest D-Di assay for pulmonary embolism exclusion in patient with low/moderate PTP. This was an international, multicenter, prospective nonrandomized, noninterventional clinical outcome management study conducted in a standard of care setting. D-dimer assay was performed in consecutive, ambulatory outpatients suspected of pulmonary embolism, with low/moderate PTP, and without medical conditions or in clinical settings known to alter default D-dimer values regardless of the presence of thrombosis using a threshold of 0.5 μg/ml (fibrinogen equivalent units) for venous thromboembolism exclusion. Results were used to determine test performance. Of 1141 patients who underwent D-dimer testing, 1060 had valid results and completed study as planned. STA-Liatest D-Di assay performance has exceeded the CLSI/FDA guidance requirements, with a sensitivity of 97.6% (95% confidence interval: 91.7-99.7%) and a negative predictive value of 99.7% (95% confidence interval: 99.0-100%). STA-Liatest D-Di assay has an excellent performance when used in combination with a PTP score in relevant patients and has the potential to minimize the economic healthcare burden avoiding unnecessary and expensive imaging tests.
Efficacy of dosing and re-dosing of two oral fixed combinations of indomethacin, prochlorperazine and caffeine compared with oral sumatriptan in the acute treatment of multiple migraine attacks: a double-blind, double-dummy, randomised, parallel group, multicentre study

In this double-blind, double-dummy, randomised, parallel group, multicentre study, the efficacy of dosing and re-dosing of a fixed combination of indomethacin, prochlorperazine and caffeine (Indoprocaf) was compared with encapsulated sumatriptan in the acute treatment of two migraine attacks. Additionally, in the group taking Indoprocaf, two different oral formulations were tested: effervescent tablets and encapsulated coated tablets.



Of 297 patients randomised (150 assigned to Indoprocaf and 147 to sumatriptan), 281 were included in the intention-to-treat efficacy analysis. The initial dosing of Indoprocaf and sumatriptan was similarly effective with pain-free rates higher than 30% (95% CI of odds-ratio: 0.57-1.28) and headache relief rates of about 60% (95% CI of odds-ratio: 0.82-1.84) with both the drugs. The efficacy of re-dosing of Indoprocaf as rescue medication was more effective than that of sumatriptan with pain-free values of 47% vs. 27% in the total attacks with a statistically significant difference in the first migraine attack in favour of Indoprocaf. The efficacy of re-dosing to treat a recurrence/relapse was very high without differences between the drugs (pain-free: 60% with Indoprocaf and 50% with sumatriptan in the total attacks). Indoprocaf and sumatriptan were well-tolerated.



The study demonstrated that the efficacy of the initial dosing of Indoprocaf was not higher than that of sumatriptan, but that the strategy to use the lowest effective dose as soon as the headache occurred, followed by a second dose if the headache has not relieved or to treat a relapse, was very effective, especially with Indoprocaf.
Physical Activity and Mortality in Patients With Stable Coronary Heart Disease.

Recommendations for physical activity in patients with stable coronary heart disease (CHD) are based on modest evidence.



The authors analyzed the association between self-reported exercise and mortality in patients with stable CHD.



A total of 15,486 patients from 39 countries with stable CHD who participated in the STABILITY (Stabilization of Atherosclerotic Plaque by Initiation of Darapladib Therapy) study completed questions at baseline on hours spent each week taking mild, moderate, and vigorous exercise. Associations between the volume of habitual exercise in metabolic equivalents of task hours/week and adverse outcomes during a median follow-up of 3.7 years were evaluated.



A graded decrease in mortality occurred with increased habitual exercise that was steeper at lower compared with higher exercise levels. Doubling exercise volume was associated with lower all-cause mortality (unadjusted hazard ratio [HR]: 0.82; 95% confidence interval [CI]: 0.79 to 0.85; adjusting for covariates, HR: 0.90; 95% CI: 0.87 to 0.93). These associations were similar for cardiovascular mortality (unadjusted HR: 0.83; 95% CI: 0.80 to 0.87; adjusted HR: 0.92; 95% CI: 0.88 to 0.96), but myocardial infarction and stroke were not associated with exercise volume after adjusting for covariates. The association between decrease in mortality and greater physical activity was stronger in the subgroup of patients at higher risk estimated by the ABC-CHD (Age, Biomarkers, Clinical-Coronary Heart Disease) risk score (p for interaction = 0.0007).



In patients with stable CHD, more physical activity was associated with lower mortality. The largest benefits occurred between sedentary patient groups and between those with the highest mortality risk.
Hyperinvasive approach to out-of hospital cardiac arrest using mechanical chest compression device, prehospital intraarrest cooling, extracorporeal life support and early invasive assessment compared to standard of care. A randomized parallel groups comparative study proposal. “Prague OHCA study”

Out of hospital cardiac arrest (OHCA) has a poor outcome. Recent non-randomized studies of ECLS (extracorporeal life support) in OHCA suggested further prospective multicenter studies to define population that would benefit from ECLS. We aim to perform a prospective randomized study comparing prehospital intraarrest hypothermia combined with mechanical chest compression device, intrahospital ECLS and early invasive investigation and treatment in all patients with OHCA of presumed cardiac origin compared to a standard of care. This paper describes methodology and design of the proposed trial. Patients with witnessed OHCA without ROSC (return of spontaneous circulation) after a minimum of 5 minutes of ACLS (advanced cardiac life support) by emergency medical service (EMS) team and after performance of all initial procedures (defibrillation, airway management, intravenous access establishment) will be randomized to standard vs. hyperinvasive arm. In hyperinvasive arm, mechanical compression device together with intranasal evaporative cooling will be instituted and patients will be transferred directly to cardiac center under ongoing CPR (cardiopulmonary resuscitation). After admission, ECLS inclusion/exclusion criteria will be evaluated and if achieved, veno-arterial ECLS will be started. Invasive investigation and standard post resuscitation care will follow. Patients in standard arm will be managed on scene. When ROSC achieved, they will be transferred to cardiac center and further treated as per recent guidelines. 6 months survival with good neurological outcome (Cerebral Performance Category 1–2). Secondary outcomes will include 30 day neurological and cardiac recovery. Authors introduce and offer a protocol of a proposed randomized study comparing a combined “hyperinvasive approach” to a standard of care in refractory OHCA. The protocol is opened for sharing by other cardiac centers with available ECLS and cathlab teams trained to admit patients with refractory cardiac arrest under ongoing CPR. A prove of concept study will be started soon. The aim of the authors is to establish a net of centers for a multicenter trial initiation in future. The protocol has been approved by an Institutional Review Board, will be supported by a research grant from Internal Grant Agency of the Ministry of Health, Czech Republic NT 13225-4/2012 and has been registered under ClinicalTrials.gov identifier: NCT01511666.
Parental experience at the end-of-life in children with cancer: ‘preservation’ and ‘letting go’ in relation to loss

For children with incurable cancer death usually is anticipated and preceded by a phase of palliative care. Despite recognition that parents have difficulty adapting to a palliative perspective there is little insight into this process. This study explored, from a parental perspective, the process parents go through when cure is no longer a possibility. A multicenter study using qualitative research was undertaken during the EoL phase. One-time and repeated open interviews were conducted with 44 parents of 23 children with incurable cancer. Feelings of loss play a prominent role during the EoL phase. Dealing with loss is a process of stepwise relinquishing that becomes manifest in an internal struggle between preservation and letting go. Preservation means that parents try to maintain the child’s status quo. Letting go means parents give up their resistance to loss in service of their child’s well-being. Although the relative measure of each changes over time, parents have great difficulty making the transition because it implies a change in source of control. A timely completion of this transition positively influences the child’s well-being as well as the evaluation of enacted parenthood. For parents the essence of the palliative process is not to accept death but to deal with the loss of their child. Although the need to avoid loss and gain control by means of preservation is fully understandable, the study indicated that parents who made the transition to letting go had an increased receptiveness of their child’s real situation and needs.
Relationships of capsule endoscopy Lewis score with clinical disease activity indices, C-reactive protein, and small bowel transit time in pediatric and adult patients with small bowel Crohn's disease

Relationships between the capsule endoscopy Lewis score (LS) and clinical disease activity indices and C-reactive protein (CRP) are controversial in adult patients with Crohn's disease (CD). Also, data on pediatric patients are relatively less. However, correlation between LS and small bowel transit time (SBTT) remains investigational. The aim of the present study was to explore the correlations between LS and clinical disease activity indices, CRP, SBTT in pediatric, and adult patients with small bowel CD.Retrospective, single-center study on consecutive inpatients with established small bowel CD was conducted. The clinical disease activity index was determined using the abbreviated Pediatric Crohn's Disease Activity Index (aPCDAI) in patients aged <18 years and the Harvey-Bradshaw Simple Index (HBI) in adults. Spearman's rank correlation coefficient was used to assess the correlations of LS with aPCDAI, HBI, CRP, and SBTT, respectively.150 patients were enrolled (30 children and adolescents). In pediatric patients, correlations between LS and aPCDAI, CRP were moderate (r1 = 0.413; r2 = 0.379; P1 = .023; P2 = .044). There was no correlation between LS and SBTT (r = -0.029; P = .88). In adults, weak correlations were found between LS and HBI, SBTT (r1 = 0.213; r2 = 0.237; P1 = .019; P2 = .009). Correlation between LS and CRP was moderate (r = 0.326; P < .001). Strong correlations were found between CRP and HBI, aPCDAI (r1 = 0.522; r2 = 0.650; P < .001). The follow-up patients were all in clinical remission after treatment within 4 months, whereas only a minority reached mucosal healing. HBI, aPCDAI, CRP, and LS in all patients were reduced after treatment, whereas difference in CRP in pediatric patients and difference in LS in adults between baseline and follow-up were not found to be statistically significant. Also, the average SBTT at baseline was not found to be different from that at follow-up in all patients.The role of capsule endoscopy should be emphasized both in pediatric and adult patients with small bowel CD. Furthermore, the small bowel transit time may not be affected by the grade of small intestinal inflammation.
Extended-release quetiapine fumarate (quetiapine XR) monotherapy and quetiapine XR or lithium as add-on to antidepressants in patients with treatment-resistant major depressive disorder.

Patients with treatment-resistant major depressive disorder (MDD) remain a common clinical challenge.



This 6-week, randomised, open-label, rater-blinded trial evaluated once-daily extended-release quetiapine fumarate (quetiapine XR; 300 mg/day) as add-on to ongoing antidepressant and quetiapine XR monotherapy (300 mg/day) compared with add-on lithium (0.6-1.2 mmol/L) in patients with treatment-resistant MDD.  change in Montgomery Åsberg Depression Rating Scale (MADRS) total score from randomisation to week 6 with a pre-specified non-inferiority limit of 3 points on the MADRS.



At week 6, both add-on quetiapine XR (n=231) and quetiapine XR monotherapy (n=228) were non-inferior to add-on lithium (n=229); least squares means (LSM) differences (97.5% CI) in MADRS total score changes were -2.32 (-4.6, -0.05) and -0.97 (-3.24, 1.31), respectively. LSM MADRS total score change was numerically greater at day 4 for both quetiapine XR groups (add-on and monotherapy; p<0.01) compared with add-on lithium. At week 6, the differences between groups for the secondary endpoints of MADRS response (≥ 50% reduction in total score), MADRS remission (total score ≤ 10, add-on quetiapine XR only) and Clinical Global Impressions ('much'/'very much' improved) were numerically similar. Overall tolerability was consistent with the known profiles of both treatments.



Limitations included the open-label study design (although MADRS and laboratory measurements were performed by treatment-blinded raters) and relatively short study duration with no assessments in the continuation phase.



Add-on quetiapine XR (300 mg/day) and quetiapine XR monotherapy (300 mg/day) are non-inferior to add-on lithium in the management of patients with treatment-resistant MDD.
Optimizing nucleic acid sequences for a molecular data recorder

We recently reported the design for a DNA nano-device that can record and store molecular signals. Here we present an evolutionary algorithm tailored to optimising nucleic acid sequences that predictively fold into our desired target structures. In our approach, a DNA device is first specified abstractly: the topology of the individual strands and their desired foldings into multi-strand complexes are described at the domain-level. Initially, this design is decomposed into a set of pairwise strand interactions. Then, we optimize candidate domains, such that the resulting sequences fold with high accuracy into desired target structures both (a) individually and (b) jointly, but also (c) to show high affinity for binding desired partners and simultaneously low affinity to bind with any undesired partner. As optimization heuristic we use a genetic algorithm that employs a linear combination of the above scores. Our algorithm was able to generate DNA sequences that satisfy all given criteria. Even though we cannot establish the theoretically achievable optima (as this would require exhaustive search), our solutions score 90% of an upper bound that ignores conflicting objectives. We envision that this approach can be generalized towards a broad class of toehold-mediated strand displacement systems.