Use of sentinel lymph node biopsy in elderly patients with breast cancer - 10-year experience from a Swiss university hospital.

BACKGROUND: The Choosing Wisely initiative recommended the omission of routine sentinel lymph node biopsy (SLNB) in patients ≥ 70 years of age, with clinically node-negative, early stage, hormone receptor (HR) positive and human epidermal growth factor receptor 2 (Her2) negative breast cancer in August 2016. Here, we assess the adherence to this recommendation in a Swiss university hospital. METHODS: We conducted a retrospective single center cohort study from a prospectively maintained database. Patients ≥ 18 years of age with node-negative breast cancer were treated between 05/2011 and 03/2022. The primary outcome was the percentage of patients in the Choosing Wisely target group who underwent SLNB before and after the initiative went live. Statistical significance was tested using chi-squared test for categorical and Wilcoxon rank-sum tests for continuous variables. RESULTS: In total, 586 patients met the inclusion criteria with a median follow-up of 2.7 years. Of these, 163 were ≥ 70 years of age and 79 were eligible for treatment according to the Choosing Wisely recommendations. There was a trend toward a higher rate of SLNB (92.7% vs. 75.0%, p = 0.07) after the Choosing Wisely recommendations were published. In patients ≥ 70 years with invasive disease, fewer received adjuvant radiotherapy after omission of SLNB (6.2% vs. 64.0%, p < 0.001), without differences concerning adjuvant systemic therapy. Both short-term and long-term complication rates after SLNB were low, without differences between elderly patients and those < 70 years. CONCLUSIONS: Choosing Wisely recommendations did not result in a decreased use of SLNB in the elderly at a Swiss university hospital.

Maintenance Therapy with Aromatase Inhibitor in epithelial Ovarian Cancer (MATAO): study protocol of a randomized double-blinded placebo-controlled multi-center phase III Trial.

BACKGROUND: A high percentage of epithelial ovarian cancers (EOC) express the estrogen receptor (ER), which is an ideal target for endocrine therapy. Letrozole is a proven, potent aromatase inhibitor, extensively tested and used in the treatment of ER positive breast cancer. In addition, it seems a potent drug for patients with heavily pre-treated OC as demonstrated in several distinctive settings. However, it has never been evaluated prospectively in a maintenance setting for ovarian cancer after standard of care. The here proposed trial aims to define a population of EOC patients, who would benefit from the effectiveness of the generic agent letrozole, with little expected toxicity and thus beneficial impact on overall quality of life (QoL). METHODS: In this international multicenter randomized, placebo-controlled phase III trial at clinical centers in Switzerland, Germany and Austria, we plan to include 540 patients with primary, newly diagnosed FIGO Stage II to IV and histologically confirmed low- or high-grade serous or endometrioid epithelial ovarian/fallopian tube/peritoneal cancer. Patients are randomized in a 1:1 ratio into two groups: receiving blinded study treatment (letrozole or placebo tablets). When assuming a HR of 0.7, a median PFS of 18 months in the control arm and a median PFS of 25.7 months in the treatment arm, a two-sided alpha level of 5%, 3.5 years recruitment and 1.5 years observation time, we expect 330 events to have occurred within these 5 years in the total cohort yielding a power of 90%. Follow-up data for the whole cohort will be collected for up to 10 years and for the low-grade cancer for up to 12 years. DISCUSSION: The here proposed randomized phase III trial aims to identify patients with EOC in the maintenance setting, who benefit from the effectiveness of the letrozole, by proving its efficacy whilst maintaining a high standard of QoL due to the limited toxicity expected in comparison to the current alternative drugs on the market for this treatment phase. TRIAL REGISTRATION: This trial is registered at clinicaltrials.gov under the identifier NCT04111978 . Registered 02 October 2019.

A model for early failure prediction of blood pressure measurement devices in a stepped validation approach.

Blood pressure monitoring (BPM) devices have to be validated according to strict international validation protocols. Each protocol requests a specific number of participants to be included. All protocols use vast amounts of resources, as three people have to be present for every measurement, making trials costly, especially when the manufacturer has no intention to execute a validation study, reflected in the low share of validated in the commercially available BPM devices. The aim of our study was to develop criteria, which could detect low accuracy devices that could not pass a validation protocol early in the course of the validation process. The 2010 European Society of Hypertension International Protocol (ESH-IP) and the Universal Standard for Validation of BPM devices (AAMI/ESH/ISO) were scrutinized for criteria which can be used for preclusion of passing. Based on this, we developed a fail model. We found that a BPM device cannot pass the ESH-IP protocol, if there are ≥27, 13, or 4 single measurements differing more than 5, 10, or 15 mmHg, respectively, from the reference. For the AAMI/ESH/ISO protocol, we developed a model, which calculates best-case standard deviations (SDs) to detect SDs which would prevent the passing of the protocol before its completion, making a stepwise validation process possible. In conclusion, we found that our model is able to predict failure of low-accuracy BPM devices early during a validation protocol if used in a stepwise-approach. This can be useful to keep costs of validation studies low and to enable investigator-initiated trials.

Cardiac autonomic function and cognitive performance in patients with atrial fibrillation.

BACKGROUND: Atrial fibrillation (AF) is associated with loss of cognition and dementia. Cardiac autonomic dysfunction has been linked to cognitive decline. We aimed to investigate if reduced cardiac autonomic function (CAF) is associated with cognitive impairment in AF patients. METHODS: Patients with paroxysmal, persistent and permanent AF were enrolled from a multicenter cohort study if they had AF ("AF group") or sinus rhythm ("SR group") on a baseline 5 min ECG recording. Parameters quantifying CAF (heart rate variability triangular index (HRVI), mean heart rate (MHR), RMSSD, SDNN, total power and power in the VLF, LF, HF ranges) were calculated. We used the Montreal Cognitive Assessment (MoCA) to assess global cognitive function. RESULTS: 1685 AF patients with a mean age of 73 ± 8 years, 29% females, were included. MoCA score was 24.5 ± 3.2 in the AF group (N = 710 patients) and 25.4 ± 3.2 in the SR group (N = 975 patients). After adjusting for multiple confounders, lower HRVI was associated with lower MoCA scores, both in the SR group [ß = 0.049; 95% confidence interval (CI) 0.016-0.081; p = 0.003] and in the AF group (ß = 0.068; 95% CI 0.020-0.116; p = 0.006). In the AF group, higher MHR was associated with a poorer performance in the MoCA (ß = - 0.008; 95% CI - 0.014 to - 0.002; p = 0.014). We found no convincing evidence of association for other CAF parameters with cognition. CONCLUSION: Our data suggest that impaired CAF is associated with worse cognitive performance in patients with AF. Among standard HRV parameters, HRVI might be the most promising ECG index. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02105844.

The influence of sample size on preferences from experience.

People often learn from experience about the distribution of outcomes of risky options. Typically, people draw small samples, when they can actively sample information from risky gambles to make decisions. We examine how the size of the sample that people experience in decision from experience affects their preferences between risky options. In two studies (N = 40 each), we manipulated the size of samples that people could experience from risky gambles and measured subjective selling prices and the confidence in selling price judgements after sampling. The results show that, on average, sample size influenced neither the selling prices nor confidence. However, cognitive modelling of individual-level learning showed that around half of the participants could be classified as Bayesian learners, whereas the other half adhered to a frequentist learning strategy and that if learning was cognitively simpler more participants adhered to the latter. The observed selling prices of Bayesian learners changed with sample size as predicted by Bayesian principles, whereas sample size affected the judgements of frequentist learners much less. These results illustrate the variability in how people learn from sampled information and provide an explanation for why sample size often does not affect judgements.

Consensus-based guidance for conducting and reporting multi-analyst studies.

Any large dataset can be analyzed in a number of ways, and it is possible that the use of different analysis strategies will lead to different results and conclusions. One way to assess whether the results obtained depend on the analysis strategy chosen is to employ multiple analysts and leave each of them free to follow their own approach. Here, we present consensus-based guidance for conducting and reporting such multi-analyst studies, and we discuss how broader adoption of the multi-analyst approach has the potential to strengthen the robustness of results and conclusions obtained from analyses of datasets in basic and applied research.

Contact-Free Monitoring of Pulse Rate For Triage of Patients Presenting to the Emergency Department.

BACKGROUND: The evaluation of a patient's pulse rate (PR) plays a key role in emergency triage and is commonly measured in a contact-dependent way. OBJECTIVE: Our aims were to evaluate a camera-based prototype application (CBPA) measuring PR in an emergency department (ED) as an alternative to the current contact-dependent method of pulse oximetry and to determine the correlation between CBPA and pulse oximetry in measuring PR. METHODS: We simultaneously measured PR with CBPA and pulse oximetry as a reference method on a large group of ED walk-in patients. We then estimated correlation and agreement between the two methods, as well as the corresponding 95% confidence intervals. RESULTS: In a convenience sample of 446 patients, the correlation between CBPA and pulse oximetry in measuring PR was 0.939 (95% confidence interval [CI] 0.927-0.949) and the intraclass correlation was 0.939 (95% CI 0.927-0.949). CONCLUSIONS: Our study found that CBPA seems to be a viable alternative to the current method of measuring PR at triage. ClinicalTrials.gov identifier: NCT03393585.

Assessment of patient mobility improves the risk stratification of triage with the Emergency Severity Index: a prospective cohort study.

BACKGROUND AND IMPORTANCE: Formal triage may assign a low acuity to patients at high risk of deterioration and mortality. A patient's mobility can be easily assessed at triage. OBJECTIVE: To investigate if a simple assessment of mobility at triage can improve the Emergency Severity Index's (ESI) prediction of adverse outcomes. DESIGN, SETTING AND PARTICIPANTS: Prospective observational study of all patients attending the emergency department (ED) of a single academic hospital in Switzerland over a period of 3 weeks. OUTCOME MEASURES AND ANALYSIS: Triage clinicians classified participants as having normal or impaired mobility at triage. Impaired mobility was defined as the lack of a stable independent gait, regardless of its cause or duration (e.g. any patient who needed help to walk). The primary outcome was 30-day mortality. We performed a survival analysis stratified by mobility and ESI level. We compared the performance of regression models including the ESI alone or in combination with mobility as predictors of mortality using the Bayesian information criterion (BIC). MAIN RESULTS: 2523 patients were included in the study and 880 (34.9%) had impaired mobility. Patients with impaired mobility had a lower median 30-day survival in ESI levels 1-3. Survival of patients with normal mobility was similar regardless of their ESI level. CONCLUSION: The assessment of mobility at triage improves the ESI algorithm's risk stratification.

A factor score reflecting cognitive functioning in patients from the Swiss Atrial Fibrillation Cohort Study (Swiss-AF).

BACKGROUND: Atrial fibrillation (AF), the most common sustained cardiac arrhythmia, is considered as risk factor for the development of mild cognitive impairment (MCI) and dementia. However, dynamics of cognitive functions are subtle, and neurocognitive assessments largely differ in detecting these changes. We aimed to develop and evaluate a score which represents the common aspects of the cognitive functions measured by validated tests (i.e., "general cognitive construct"), while reducing overlap between tests and be more sensitive to identify changes in overall cognitive functioning. METHODS: We developed the CoCo (cognitive construct) score to reflect the cognitive performance obtained by all items of four neurocognitive assessments (Montreal Cognitive Assessment (MoCA); Trail Making Test; Semantic Fluency, animals; Digital Symbol Substitution Test). The sample comprised 2,415 AF patients from the Swiss Atrial Fibrillation Cohort Study (Swiss-AF), 87% aged at least 65 years. Psychometric statistics were calculated for two cognitive measures based on (i) the full set of items from the neurocognitive test battery administered in the Swiss-AF study (i.e., CoCo item set) and (ii) the items from the widely used MoCA test. For the CoCo item set, a factor score was derived based on a principal component analysis, and its measurement properties were analyzed. RESULTS: Both the MoCA item set and the full neurocognitive test battery revealed good psychometric properties, especially the full battery. A one-factor model with good model fit and performance across time and groups was identified and used to generate the CoCo score, reflecting for each patient the common cognitive skill performance measured across the full neurocognitive test battery. The CoCo score showed larger effect sizes compared to the MoCA score in relation to relevant clinical variables. CONCLUSION: The derived factor score allows summarizing AF patients' cognitive performance as a single score. Using this score in the Swiss-AF project increases measurement sensitivity and decreases the number of statistical tests needed, which will be helpful in future studies addressing how AF affects the risk of developing cognitive impairment.

Effects of glucagon-like peptide-1 receptor agonists on fluid intake in healthy volunteers.

PURPOSE: Glucagon-like peptide-1 (GLP-1) receptor agonists (RA) reduce appetite and energy intake. Recent findings from animal studies suggest a role of GLP-1 in drinking and water homeostasis. We aimed to elucidate whether GLP-1 RA reduce fluid intake in healthy volunteers. METHODS: Double-blind, randomized, placebo-controlled, crossover study. 20 healthy volunteers received dulaglutide 1.5 mg and placebo (0,9% sodium chloride) subcutaneously once weekly for 3 weeks. At the end of each treatment period, participants attended an 8-h evaluation visit, during which they were requested to eat two standardized meals and to drink water ad libitum. The primary outcome was the total fluid intake (ml) during the evaluation visit. RESULTS: Mean [SD] age of participants (60% female) was 27 [9.2] years. All but four participants drank less on dulaglutide versus placebo treatment despite identical food intake. The median [IQR] difference of fluid intake on dulaglutide compared to placebo treatment was -100 ml [-400-0]. Median [IQR] total fluid intake was 1300 ml [888-1600] versus 1600 ml [1000-1720], on dulaglutide and placebo treatment, p = 0.06. Median [IQR] 24-h urine output was reduced in dulaglutide versus placebo-treated participants: 1250 ml [975-2080] versus 1680 ml [1400-2040], p = 0.04. Median serum sodium levels were 140 mmol/L on both visits and no difference in thirst perception was noted. CONCLUSIONS: GLP-1 RA such as dulaglutide seem to modulate fluid balance in humans. This leads us to speculate that GLP-1 RA may be an interesting therapeutic options for patients with excessive drinking behavior e.g., primary polydipsia.

Effect of age on outcome and revision in total ankle arthroplasty.

AIMS: To assess the effect of age on clinical outcome and revision rates in patients who underwent total ankle arthroplasty (TAA) for end-stage ankle osteoarthritis (OA). METHODS: A consecutive series of 811 ankles (789 patients) that underwent TAA between May 2003 and December 2013 were enrolled. The influence of age on clinical outcome, including the American Orthopaedic Foot and Ankle Society (AOFAS) hindfoot score, and pain according to the visual analogue scale (VAS) was assessed. In addition, the risk for revision surgery that includes soft tissue procedures, periarticular arthrodeses/osteotomies, ankle joint debridement, and/or inlay exchange (defined as minor revision), as well as the risk for revision surgery necessitating the exchange of any of the metallic components or removal of implant followed by ankle/hindfoot fusion (defined as major revision) was calculated. RESULTS: A significant improvement in the AOFAS hindfoot score and pain relief between the preoperative assessment and the last follow-up was evident. Age had a positive effect on pain relief. The risk for a minor or major revision was 28.7 % at the mean follow-up of 5.4 years and 11.0 % at a mean follow-up of 6.9 years respectively. The hazard of revision was not affected by age. CONCLUSION: The clinical outcome, as well as the probability for revision surgery following TAA, is comparable between younger and older patients. The overall revision rate of the Hintegra total ankle is comparable with other three component designs. TAA should no longer be reserved for low demand elderly patients, but should also be recognized as a viable option for active patients of younger age. Cite this article: Bone Joint J 2020;102-B(7):925-932.

Systematic Review and Meta-analysis of Methodological Quality in In Vivo Animal Studies of Subarachnoid Hemorrhage.

As a result of increased awareness of wide-spread methodological bias and obvious translational roadblocks in subarachnoid hemorrhage (SAH) research, various checklists and guidelines were developed over the past decades. This systematic review assesses the overall methodological quality of preclinical SAH research. An electronic search for preclinical studies on SAH revealed 3415 potential articles. Of these, 765 original research papers conducted in vivo in mice, rats, rabbits, cats, dogs, pigs, goats, and non-human primates with a focus on brain damage related to delayed cerebral vasospasm and early brain injury met the inclusion criteria. We found methodological shortcomings still to prevail in preclinical SAH research. In addition, basic animal characteristics were typically well described but important technical parameters of SAH induction were often underreported. None of the species, models, or techniques used in preclinical SAH research was methodologically superior to the others. Methodological quality of preclinical SAH research was independent of the number of citations or impact factor of a publication. Consequently, we suggest the SAH research community should consider strategies to improve preclinical research quality in their field, such as public platforms to (pre)register preclinical experiments, consequent support of open science policies, stricter editorial (and reviewer) control of (pre)existing guidelines, and increased efforts in education and training of good laboratory practice for the next generation of researchers.

Double responding: A new constraint for models of speeded decision making.

Evidence accumulation models (EAMs) have become the dominant models of speeded decision making, which are able to decompose choices and response times into cognitive parameters that drive the decision process. Several models within the EAM framework contain fundamentally different ideas of how the decision making process operates, though previous assessments have found that these models display a high level of mimicry, which has hindered the ability of researchers to contrast these different theoretical viewpoints. Our study introduces a neglected phenomenon that we term "double responding", which can help to further constrain these models. We show that double responding produces several interesting benchmarks, and that the predictions of different EAMs can be distinguished in standard experiment paradigms when they are constrained to account for the choice response time distributions and double responding behaviour in unison. Our findings suggest that lateral inhibition (e.g., the leaky-competing accumulator) provides models with a universal ability to make accurate predictions for these data. Furthermore, only models containing feed-forward inhibition (e.g., the diffusion model) performed poorly under both of our proposed extensions of the standard EAM framework to double responding, suggesting a general inability of feed-forward inhibition to accurately predict these data. We believe that our study provides an important step forward in further constraining models of speeded decision making, though additional research on double responding is required before broad conclusions are made about which models provide the best explanation of the underlying decision-making process.

Impact of the rotational position of the hindfoot on measurements assessing the integrity of the distal tibio-fibular syndesmosis.

BACKGROUND: Approximately 20% of patients with ankle fractures demonstrate evidence of syndesmotic injuries. As intra-operative measurements have high specifity but low sensitivity for identifying injuries to the distal tibio-fibular syndesmosis, numerous measurements have been developed to assess pre-operative syndesmosis integrity. Several factors affecting measurements on conventional radiographs and computed tomography (CT) images have been identified. The influence of the rotational position of the hindfoot during imaging, however, remains unclear. METHODS: Twenty (20) healthy volunteers (mean age 49, standard deviation [SD] 7.5, range 40-66 years) underwent a weightbearing cone beam CT scan. From this dataset, digitally reconstructed radiographs (DRRs) and axial CT images of the hindfoot were reconstructed. For each image, an antero-posterior view (defined as a plane perpendicular to the longitudinal axis of the second metatarsal) was reconstructed. Then, internal and external rotation of the hindfoot was simulated in 10° increments (maximum rotation of 30°). The tibio-fibular clear space (TFCS), tibio-fibular overlap (TFO), and medial clear space (MCS) were measured on each reconstructed DRR and axial CT image. RESULTS: Internal rotation of the hindfoot substantially impacted inter-observer agreement for TFCS measurements on DRRs. Intra- und inter-observer agreement of measurements (MCS, TFCS, TFO) on axial CT images was minimally affected by hindfoot rotation. Hindfoot rotation highly impacted on absolute values of each measurement. As little as 10° of internal or external rotation significantly (P<0.05) impacted MCS and TFO measurements (DRRs and axial CT images). External rotation increased, while internal rotation decreased, MCS and TFO measurements. TFCS measurements performed on DRRs did not significantly differ for 10° (P=0.0931) and 20° (P=0.486) of external rotation or for 10° of internal (P=0.33) rotation. DISCUSSION: The rotational position of the hindfoot during imaging has a major impact on MCS, TFCS, and TFO measurements when using DRRs and axial CT images. To avoid misinterpretation of measurements, the position of the hindfoot during imaging must be standardized. CONCLUSIONS: DRRs and axial CT images require reliable reconstructions to allow accurate assessment of the TFCS, TFO, and MCS.

The Quality of Response Time Data Inference: A Blinded, Collaborative Assessment of the Validity of Cognitive Models.

Most data analyses rely on models. To complement statistical models, psychologists have developed cognitive models, which translate observed variables into psychologically interesting constructs. Response time models, in particular, assume that response time and accuracy are the observed expression of latent variables including 1) ease of processing, 2) response caution, 3) response bias, and 4) non-decision time. Inferences about these psychological factors, hinge upon the validity of the models' parameters. Here, we use a blinded, collaborative approach to assess the validity of such model-based inferences. Seventeen teams of researchers analyzed the same 14 data sets. In each of these two-condition data sets, we manipulated properties of participants' behavior in a two-alternative forced choice task. The contributing teams were blind to the manipulations, and had to infer what aspect of behavior was changed using their method of choice. The contributors chose to employ a variety of models, estimation methods, and inference procedures. Our results show that, although conclusions were similar across different methods, these "modeler's degrees of freedom" did affect their inferences. Interestingly, many of the simpler approaches yielded as robust and accurate inferences as the more complex methods. We recommend that, in general, cognitive models become a typical analysis tool for response time data. In particular, we argue that the simpler models and procedures are sufficient for standard experimental designs. We finish by outlining situations in which more complicated models and methods may be necessary, and discuss potential pitfalls when interpreting the output from response time models.

Effects of Glucagon-Like Peptide-1 Receptor Agonists on Hypothalamic-Pituitary-Adrenal Axis in Healthy Volunteers.

Context: Recent findings from animal and human studies indicate that glucagon-like peptide-1 (GLP-1) receptor agonists (RAs) modulate stress response by activating the hypothalamic-pituitary-adrenal (HPA) axis, which may have relevant clinical implications. Objective: To investigate the influence of GLP-1 RA treatment on HPA axis activity compared with placebo in healthy volunteers. Design: Double-blind, randomized, crossover study. Setting: University Hospital Basel, Switzerland. Participants: Twenty healthy volunteers. Intervention: Dulaglutide (Trulicity®) 1.5 mg and placebo (0.9% sodium chloride) were given subcutaneously once weekly for 3 weeks. Main Outcome Measures: Twenty-four-hour urinary free cortisol, circadian rhythm of serum and salivary cortisol, cortisol after 1 mg dexamethasone suppression test, and cortisol levels before and after stimulation with ACTH. Results: Urinary free cortisol levels were similar under dulaglutide [median (interquartile range) 240 nmol/L (164, 324)] vs placebo [188 nmol/L (133, 338), P = 0.131]. The circadian rhythm of serum and salivary cortisol were comparable in both groups as were cortisol levels after dexamethasone [dulaglutide 28 nmol/L (22, 47.5) vs placebo 26.5 nmol/L (15.8, 45.5), P = 0.4]. Serum cortisol levels in dulaglutide and placebo treated participants were 522 nmol (388, 710) and 530 nmol/L (394, 747), before (P = 0.6), and 658 nmol/L (604, 810) and 636 nmol/L (512, 910) after ACTH stimulation (P = 0.87). Conclusion: Our results suggest that there is no activation of the HPA axis by long-term GLP-1 RA exposure, particularly dulaglutide, at the medically approved dosage of 1.5 mg once weekly.

How environmental regularities affect people's information search in probability judgments from experience.

In everyday life, people encounter smaller rewards with higher probability than larger rewards. Do people expect this reward-probability regularity to hold in experimental settings? To answer this question, we tested whether people's behavior in probability judgment tasks is affected by the correlation between reward size and reward probabilities. In Study 1, we asked people to judge reward probabilities under uncertainty. In line with the ecological reward-probability correlation, people assumed that larger rewards were less likely than smaller rewards. In Study 2, we tested the prediction that people's information search and integration depend on the representativeness of the environment. Participants performed an experience-based probability judgment task in which they sampled outcomes from unknown gambles until they felt confident to estimate the probabilities of the gambles' outcomes. We manipulated the reward-probability relationship of the gambles in 3 experimental groups. Rewards and reward probabilities were negatively correlated, positively correlated, or not correlated at all. A negative correlation mimics the ecological reward-probability relationship often present in real life. We analyzed people's search effort and whether they integrated sample-based uncertainty into their judgments. We found that people sampled fewer outcomes in the ecologically representative condition than in the other 2 conditions. However, people did not integrate sample-based uncertainty in their judgments: In all conditions people treated the observed outcomes as representative of the underlying outcome distribution. People's prior beliefs about regularities in environments provides a potential explanation of why people often rely on small sample sizes when making judgments and decisions from experience. (PsycINFO Database Record (c) 2019 APA, all rights reserved).

Systematic Review of In Vivo Animal Models of Subarachnoid Hemorrhage: Species, Standard Parameters, and Outcomes.

In preclinical models, modification of experimental parameters associated with techniques of inducing subarachnoid hemorrhage (SAH) can greatly affect outcomes. To analyze how parameter choice affects the relevance and comparability of findings, we systematically reviewed 765 experimental studies of in vivo animal SAH models (2000-2014). During the last decade, we found marked increases in publications using smaller species and models for simulating acute events after SAH. Overall, the fewer types of species and models used did not correlate with an increased standardization in the experimental characteristics and procedures. However, by species, commonly applied, reliable parameters for each experimental SAH technique were identified in mouse, rat, rabbit, and dog models. Our findings can serve as a starting point for discussion toward a more uniform performance of SAH experiments, development of preclinical SAH common data elements, and establishment of standardized protocols for multicenter preclinical trials.

The Creativity-Verification Cycle in Psychological Science: New Methods to Combat Old Idols.

Over the years, researchers in psychological science have documented and investigated a host of powerful cognitive fallacies, including hindsight bias and confirmation bias. Researchers themselves may not be immune to these fallacies and may unwittingly adjust their statistical analysis to produce an outcome that is more pleasant or better in line with prior expectations. To shield researchers from the impact of cognitive fallacies, several methodologists are now advocating preregistration-that is, the creation of a detailed analysis plan before data collection or data analysis. One may argue, however, that preregistration is out of touch with academic reality, hampering creativity and impeding scientific progress. We provide a historical overview to show that the interplay between creativity and verification has shaped theories of scientific inquiry throughout the centuries; in the currently dominant theory, creativity and verification operate in succession and enhance one another's effectiveness. From this perspective, the use of preregistration to safeguard the verification stage will help rather than hinder the generation of fruitful new ideas.