REACT: Rapid Evaluation Assessment of Clinical Reasoning Tool.

INTRODUCTION: Clinical reasoning encompasses the process of data collection, synthesis, and interpretation to generate a working diagnosis and make management decisions. Situated cognition theory suggests that knowledge is relative to contextual factors, and clinical reasoning in urgent situations is framed by pressure of consequential, time-sensitive decision-making for diagnosis and management. These unique aspects of urgent clinical care may limit the effectiveness of traditional tools to assess, teach, and remediate clinical reasoning. METHODS: Using two validated frameworks, a multidisciplinary group of clinicians trained to remediate clinical reasoning and with experience in urgent clinical care encounters designed the novel Rapid Evaluation Assessment of Clinical Reasoning Tool (REACT). REACT is a behaviorally anchored assessment tool scoring five domains used to provide formative feedback to learners evaluating patients during urgent clinical situations. A pilot study was performed to assess fourth-year medical students during simulated urgent clinical scenarios. Learners were scored using REACT by a separate, multidisciplinary group of clinician educators with no additional training in the clinical reasoning process. REACT scores were analyzed for internal consistency across raters and observations. RESULTS: Overall internal consistency for the 41 patient simulations as measured by Cronbach's alpha was 0.86. A weighted kappa statistic was used to assess the overall score inter-rater reliability. Moderate reliability was observed at 0.56. DISCUSSION: To our knowledge, REACT is the first tool designed specifically for formative assessment of a learner's clinical reasoning performance during simulated urgent clinical situations. With evidence of reliability and content validity, this tool guides feedback to learners during high-risk urgent clinical scenarios, with the goal of reducing diagnostic and management errors to limit patient harm.

Evaluating interventions to improve test, treat, and track (T3) malaria strategy among over-the-counter medicine sellers (OTCMS) in some rural communities of Fanteakwa North district, Ghana: study protocol for a cluster randomized controlled trial.

BACKGROUND: The World Health Organization initiated test, treat, and track (T3) malaria strategy to support malaria-endemic countries in their efforts to achieve universal coverage with diagnostic testing, antimalarial treatment, and strengthening surveillance systems. Unfortunately, T3 is not adopted by over-the-counter medicine sellers (OTCMS) where many patients with malaria-like symptoms first seek treatment. Sub-Saharan African countries are considering introducing and scaling up RDTs in these outlets to reduce malaria burden. In this context, this study is aimed at improving implementation of the T3 among OTCMS using a number of intervention tools that could be scaled-up easily at the national level. METHODS/DESIGN: The interventions will be evaluated using a two-arm, cluster randomized trial across 8 rural communities (4 clusters per arm), in two adjacent districts (Fanteakwa North and Fanteakwa South districts) of Ghana. A total of 8 OTCMS in the intervention arm and 5 OTCMS in the control arm in the selected communities will participate in the study. In the intervention arm only, subsidized malaria rapid diagnostic test (mRDT) kits will be introduced after the OTCMS have been trained on how to use the kit appropriately. Supervision, technical assistance, feedbacks, and collection of data will be provided on a regular basis at the participating medicine stores. The primary outcome is the proportion of children under 10 years with fever or suspected to have malaria visiting OTCMS and tested (using mRDT) before treatment. Secondary outcomes will include adherence to national malaria treatment guidelines and recommended mRDT retail price. Outcomes will be measured using mainly a household survey supplemented by mystery client survey and a surveillance register on malaria tests conducted by the OTCMS during patient consultations. Data collected will be double entered and verified using Microsoft Access 2010 (Microsoft Inc., Redmond, Washington) and analyzed using STATA version 11.0. DISCUSSION: The trial will provide evidence on the combined effectiveness of provider and community interventions in improving adherence to the T3 initiative among OTCMS in rural Ghana. ETHICAL CLEARANCE: NMIMR-IRB CPN 086/18-19 TRIAL REGISTRATION: ISRCTN registry ISRCTN77836926 . Registered on 4 November 2019.

Sports-related concussion (SRC) assessment in road cycling: a systematic review and call to action.

BACKGROUND: Sports-related concussion (SRC) is a recognised risk in road cycling and can have serious health consequences. Recent high-profile cases of professional road cyclists continuing to participate in races despite suffering obvious SRC have highlighted the difficulties in assessing SRC within road cycling. PURPOSE: To undertake a systematic review of the literature on SRC assessment in road cycling. STUDY DESIGN: Systematic review. METHODS: Literature describing SRC assessment in road cycling was identified by searching MEDLINE, EMBASE, PsycINFO and Web of Science. Two reviewers independently screened titles and abstracts for eligibility and a qualitative analysis was undertaken of included studies. RESULTS: From 94 studies identified, two were included for review. Gordon et al describe the presentation of a single case of paediatric concussion following a cycling crash. They highlight the utility of SRC evaluation using the Sport Concussion Assessment Tool (SCAT) as well as the importance of a stepwise return-to-play protocol. Greve and Modabber discuss a number of traumatic brain injuries that occurred during the 2011 road cycling season and, as a minimum, call for riders to be withdrawn from competition following loss of consciousness or amnesia. Both studies are at high risk of bias and of low quality. CONCLUSION: Road cycling poses unique challenges for the assessment of SRC. This review illustrates the lack of published evidence to advise effective means of SRC assessment within road cycling. The Union Cycliste Internationale (UCI) regulations advise the use of SCAT-5 for concussion assessment but this tool is impractical, requiring modification for use in road cycling. We would like to call on the UCI to hold a consensus meeting to establish an evidence-based SRC assessment protocol and return-to-riding protocol for road cycling.

In vitro and schematic model eye assessment of glare or positive dysphotopsia-type photic phenomena: Comparison of a new material IOL to other monofocal IOLs.

PURPOSE: To compare the glare-type photic phenomena for a new intraocular lens (IOL) to other monofocal IOLs, and to investigate how IOL design features might affect these phenomena. SETTING: Alcon Laboratories, Inc., Fort Worth, Texas; John A Moran Eye Center, University of Utah, Salt Lake City, USA. DESIGN: Schematic model eye evaluation and in vitro study. METHODS: Five monofocal IOL models (Clareon CNA0T0, Tecnis ZCB00, enVista MX60, Eternity W-60, and Vivinex XY1) were used to evaluate glare or positive dysphotopsia-type phenomena. Optical simulations of incoming light were generated using nonsequential ray-tracing software based on a collimated light source for various off-axis angles of illumination. The simulation analyses were verified using a laboratory in vitro bench-top glare measurement system. RESULTS: The Clareon and Vivinex IOLs produced focused off-axis images with negligible peripheral glare characteristics. The Tecnis and enVista IOLs produced dispersed images with additional glare characteristics at 45 degrees of off-axis illumination and higher. The Eternity IOL showed the highest edge-reflected glare characteristic, likely because of its straight optic edge geometry. The laboratory bench images and glare intensity profiles were consistent with the simulation data. CONCLUSIONS: In vitro and nonsequential ray-tracing evaluations showed that straight optic edges and peripheral nonimaging optic geometry might contribute to positive dysphotopsia. The IOL designs with optic edge curvature and full functional optics demonstrated the lowest level of glare-type photic phenomena. Only clinical studies can confirm whether the differences observed between the IOLs in vitro are clinically significant.

Sociocultural determinants of US women's ethical views on various fertility treatments.

Ethical concerns over treatments for infertility can discourage patients from pursuing fertility healthcare. This study aims to evaluate the sociocultural factors that influence the ethical views of reproductive-aged women regarding various fertility treatments. A publicly available cross-sectional survey of 4792 nationally representative US women aged 25-52 years was analysed to identify the frequency of ethical concerns over such interventions. Concerns were most common for treatments that increase the chance of twins (54%), followed by third-party reproductive strategies (48-51%), IVF (30%) and partner insemination (14%). Regression analysis revealed distinct sociocultural determinants for each of the treatment approaches. While being black was associated with a higher level of concern for several distinct fertility treatments, Hispanic ethnicity was only associated with increased ethical concern about donor eggs. Additionally, religious attendance predicts increased odds of ethical concern for IVF and all third-party approaches, while Catholic or Christian religious affiliations also predict ethical concern over partner insemination. These findings show that ethical concerns over fertility treatments are not generally 'all-or-nothing', but rather are often specific to the treatment approach. This knowledge may help explain differences in help-seeking behaviours and improve the physician-patient relationship.

Cost-effectiveness of preimplantation genetic screening for women older than 37 undergoing in vitro fertilization.

PURPOSE: Adding preimplantation genetic screening to in vitro fertilization has been shown to increase live birth rate in women older than 37. However, preimplantation genetic screening is an expensive procedure. Information on the cost-effectiveness of preimplantation genetic screening can help inform clinical decision making. METHODS: We constructed a decision analytic model for a hypothetical fresh, autologous in vitro fertilization cycle (with versus without preimplantation genetic screening) for women older than age 37 who had a successful oocyte retrieval and development of at least one blastocyst. The model incorporated probability and cost estimates of relevant clinical events based on data from published literature. Sensitivity analyses were performed to examine the impact of changes in model input parameters. RESULTS: In base-case analysis, IVF-PGS offered a 4.2 percentage point increase in live birth rate for an additional cost of $4509, yielding an incremental cost-effectiveness ratio (ICER) of $105,489 per additional live birth. This ICER was below the expected cost of $145,063 for achieving one live birth with IVF (assuming an average LBR of 13.4% and $19,415 per cycle for this patient population). Sensitivity analysis suggested that ICER improved substantially with decreases in PGS cost and increases in PGS effectiveness. Monte Carlo simulation showed PGS to be cost-effective in 93.9% of iterations at an acceptability cutoff of $145,063. CONCLUSIONS: Considering the expected cost of achieving one live birth with IVF, PGS is a cost-effective strategy for women older than 37 undergoing IVF. Additional research on patients' willingness-to-pay per live birth would further inform our understanding regarding the cost-effectiveness of PGS.

Precision reproductive medicine: multigene panel testing for infertility risk assessment.

The concept of precision medicine relies on a thorough understanding of the consequences of unique features of individual patients, such as environmental exposures and genetic profiles. A key component of implementing individualized care in this paradigm will be improved assessment of genetic risk. Compared with single gene tests, multigene panel testing-which has recently become commercially available for female infertility-offers the possibility of a more comprehensive and efficient risk evaluation. However, as the use of multigene panel testing for breast cancer risk has shown, this approach must be used judiciously to ensure its usefulness in a clinical setting. Key challenges which have been encountered in oncology include the interpretation of gene variants of questionable clinical effect and a lack of evidence to guide management after variants are identified. In this review, the core concepts of multigene panel testing for risk assessment are discussed, with careful attention to both its shortcomings as well as its potential for benefit in reproductive medicine.

Liver biomarker and in vitro assessment confirm the hepatic origin of aminotransferase elevations lacking histopathological correlate in beagle dogs treated with GABAA receptor antagonist NP260.

NP260 was designed as a first-in-class selective antagonist of α4-subtype GABAA receptors that had promising efficacy in animal models of pain, epilepsy, psychosis, and anxiety. However, development of NP260 was complicated following a 28-day safety study in dogs in which pronounced elevations of serum aminotransferase levels were observed, although there was no accompanying histopathological indication of hepatocellular injury. To further investigate the liver effects of NP260, we assayed stored serum samples from the 28-day dog study for liver specific miRNA (miR-122) as well as enzymatic biomarkers glutamate dehydrogenase and sorbitol dehydrogenase, which indicate liver necrosis. Cytotoxicity assessments were conducted in hepatocytes derived from dog, rat, and human liver samples to address the species specificity of the liver response to NP260. All biomarkers, except ALT, returned toward baseline by Day 29 despite continued drug treatment, suggesting adaptation to the initial injury. In vitro analysis of the toxicity potential of NP260 to primary hepatocytes indicated a relative sensitivity of dog>human>rat, which may explain, in part, why the liver effects were not evident in the rodent safety studies. Taken together, the data indicate that a diagnostic biomarker approach, coupled with sensitive in vitro screening strategies, may facilitate interpretation of toxicity potential when an adaptive event masks the underlying toxicity.

Proposal for a "phase II" multicenter trial model for preclinical new antiepilepsy therapy development.

There is a pressing need to address the current major gaps in epilepsy treatment, in particular drug-resistant epilepsy, antiepileptogenic therapies, and comorbidities. A major concern in the development of new therapies is that current preclinical testing is not sufficiently predictive for clinical efficacy. Methodologic limitations of current preclinical paradigms may partly account for this discrepancy. Here we propose and discuss a strategy for implementing a "phase II" multicenter preclinical drug trial model based on clinical phase II/III studies designed to generate more rigorous preclinical data for efficacy. The goal is to improve the evidence resulting from preclinical studies for investigational new drugs that have shown strong promise in initial preclinical "phase I" studies. This should reduce the risk for expensive clinical studies in epilepsy and therefore increase the appeal for funders (industry and government) to invest in their clinical development.

Preimplantation genetic diagnosis: technical advances and expanding applications.

PURPOSE OF REVIEW: To review the foundations, recent technical advances, and increasing number of applications for in-vitro fertilization with preimplantation genetic diagnosis (PGD). RECENT FINDINGS: PGD is an important technique for reducing the burden of genetic disease. Studies have shown that the diagnostic accuracy and subsequent live-birth rate after PGD are impacted by the developmental stage at the time of biopsy, as well as the biopsy protocol used. Also essential for accurate diagnosis are refined mutation detection protocols which avoid the common problem of allele drop-out. As the technique has improved, there has been a concomitant increase in the popularity and breadth of application of PGD. A recently published 10-year dataset of worldwide PGD reveals the increasing frequency of its use and the growing number of indications for which PGD is offered. SUMMARY: Technical advances from biopsy to detection of mutations have led to improved diagnostic accuracy and an increased frequency and breadth of use for PGD.

Assessment of the diagnostic accuracy of circulating cardiac troponin I concentration to distinguish between cats with cardiac and non-cardiac causes of respiratory distress.

OBJECTIVE: To determine if serum cardiac troponin I (cTnI) concentrations can distinguish cardiac from non-cardiac causes of respiratory distress (RD) in cats. ANIMALS, MATERIALS AND METHODS: 53 cats. cTnI concentrations were measured in 30 cats with non-cardiac respiratory distress (RD-NC) and compared to 23 cats with RD due to congestive heart failure (RD+CHF). RESULTS: The RD+CHF group had higher median cTnI concentration (0.94 ng/ml interquartile range IQR 0.54-4.00, range < 0.20-90.14) than the RD-NC group (< 0.2 ng/ml IQR < 0.2-0.33, range < 0.20-41.1, p<0.001). The area under the curve (AUC) was 0.842 (95% CI 0.728-0.955) for the receiver operator curve (ROC) analysis of the accuracy of cTnI concentrations to discriminate RD+CHF from RD-NC cats. A cut-off of > or = 0.81 ng/ml discriminated RD+CHF from RD-NC cats with a sensitivity and specificity of 65.2% and 90.0% respectively. However considerable overlap in cTnI concentrations between the 2 groups was identified. CONCLUSIONS: Serum cTnI concentrations were different in RD+CHF compared to RD-NC cats. However the overlap in cTnI concentrations between the 2 groups reduced the clinical efficacy of the assay which therefore should not be used as a stand-alone test but in combination with other diagnostics such as echocardiography and radiography.

An assessment of response bias for the same-different task: implications for the single-interval task.

Two auditory amplitude discrimination experiments were conducted using the same-different experimental design. Observer bias was manipulated, in the first experiment, by varying payoff matrices and, in the second, by varying prior probabilities of signal presentation. Five levels of bias manipulation and four levels of difficulty were employed in each experiment. Each observer received all combinations of bias manipulation and difficulty, but with only one of these combinations within each block of trials. Nine indices of bias were assessed by simultaneously fitting isosensitivity and isobias functions to the data and by fitting isobias functions only. Although none of the indices tested provided an exceptionally good fit to the data, two indices stood out from the rest. These were c*sd and ci, indices with isobias contours similar in shape to those for the c index derived from the yes-no task.