High-Sensitivity Cardiac Troponin Algorithms and the Value of Likelihood Ratios.

High-sensitivity cardiac troponin (hs-cTn) is now the recommended biomarker for diagnosis of non-ST-elevation myocardial infarction, but proper interpretation varies based on the assay being used. Nearly uniformly, suggested interpretations of assay-specific hs-cTn results are based on predictive values, which are not applicable to most patients. Through application of a published hs-cTn algorithm to several patient scenarios, we will demonstrate that likelihood ratios are superior to predictive values for patient-centered test interpretation and decision-making. Furthermore, we will provide a blueprint for how to use existing published data presented with predictive values to calculate likelihood ratios. Changing the output of diagnostic accuracy studies and diagnostic algorithms from predictive values to likelihood ratios can improve patient care.

Dynamic and reversible shape response of red blood cells in synthetic liquid crystals.

Mammalian cells are soft, and correct functioning requires that cells undergo dynamic shape changes in vivo. Although a range of diseases are associated with stiffening of red blood cells (RBCs; e.g., sickle cell anemia or malaria), the mechanical properties and thus shape responses of cells to complex viscoelastic environments are poorly understood. We use vapor pressure measurements to identify aqueous liquid crystals (LCs) that are in osmotic equilibrium with RBCs and explore mechanical coupling between RBCs and LCs. When transferred from an isotropic aqueous phase into a LC, RBCs exhibit complex yet reversible shape transformations, from initially biconcave disks to elongated and folded geometries with noncircular cross-sections. Importantly, whereas the shapes of RBCs are similar in isotropic fluids, when strained by LC, a large variance in shape response is measured, thus unmasking cell-to-cell variation in mechanical properties. Numerical modeling of LC and cell mechanics reveals that RBC shape responses occur at constant cell membrane area but with membrane shear moduli that vary between cells from 2 to 16 × 10-6 N/m. Temperature-dependent LC elasticity permits continuous tuning of RBC strains, and chemical cross-linking of RBCs, a model for diseased cells, leads to striking changes in shape responses of the RBCs. Overall, these results provide insight into the coupling of strain between soft mammalian cells and synthetic LCs, and hint at new methods for rapidly characterizing mechanical properties of single mammalian cells in a population and thus cell-to-cell variance.

The Virtual Hospitalist: a Critical Innovation During the COVID-19 Crisis.

A virtual hospitalist program expanded our ability to confront the challenges of the COVID-19 crisis at the epicenter of the pandemic in New York City. In concert with on-site hospitalists and redeployed physicians, virtual hospitalists aimed to expand capacity while maintaining high-quality care and communication. The program addressed multiple challenges created by our first COVID-19 surge: high patient census and acuity; limitations of and due to personal protective equipment; increased communication needs due to visitor restrictions and the uncertain nature of the novel disease, and limitations to in-person work for some physicians. The program created a mechanism to train and support new hospitalists and provide and expand palliative care services. We describe how our virtual hospitalist program operated during our COVID-19 surge in April and May 2020 and reflect on potential roles of virtual hospitalists after the COVID-19 crisis passes.

Geometric localization of thermal fluctuations in red blood cells.

The thermal fluctuations of membranes and nanoscale shells affect their mechanical characteristics. Whereas these fluctuations are well understood for flat membranes, curved shells show anomalous behavior due to the geometric coupling between in-plane elasticity and out-of-plane bending. Using conventional shallow shell theory in combination with equilibrium statistical physics we theoretically demonstrate that thermalized shells containing regions of negative Gaussian curvature naturally develop anomalously large fluctuations. Moreover, the existence of special curves, "singular lines," leads to a breakdown of linear membrane theory. As a result, these geometric curves effectively partition the cell into regions whose fluctuations are only weakly coupled. We validate these predictions using high-resolution microscopy of human red blood cells (RBCs) as a case study. Our observations show geometry-dependent localization of thermal fluctuations consistent with our theoretical modeling, demonstrating the efficacy in combining shell theory with equilibrium statistical physics for describing the thermalized morphology of cellular membranes.

The Critical Need for a Population Health Approach: Addressing the Nation's Behavioral Health During the COVID-19 Pandemic and Beyond.

The COVID-19 global pandemic highlights the necessity for a population health approach to identify and implement strategies across systems to improve behavioral health. Adopting a population health approach helps to address the needs of the total population, including at-risk subgroups, through multiple levels of intervention and to promote the public's behavioral health and psychological well-being.

Active matter invasion of a viscous fluid: Unstable sheets and a no-flow theorem.

We investigate the dynamics of a dilute suspension of hydrodynamically interacting motile or immotile stress-generating swimmers or particles as they invade a surrounding viscous fluid. Colonies of aligned pusher particles are shown to elongate in the direction of particle orientation and undergo a cascade of transverse concentration instabilities, governed at small times by an equation that also describes the Saffman-Taylor instability in a Hele-Shaw cell, or the Rayleigh-Taylor instability in a two-dimensional flow through a porous medium. Thin sheets of aligned pusher particles are always unstable, while sheets of aligned puller particles can either be stable (immotile particles), or unstable (motile particles) with a growth rate that is nonmonotonic in the force dipole strength. We also prove a surprising "no-flow theorem": a distribution initially isotropic in orientation loses isotropy immediately but in such a way that results in no fluid flow everywhere and for all time.

ROC Anatomy-Getting the Most Out of Your Diagnostic Test.

Clinical decision-making relies heavily on making a correct diagnosis. Clinicians have a responsibility to understand the full spectrum of the diagnostic information conveyed by a physical exam finding, laboratory test result, or imaging. Many laboratory tests, such as troponin and B-type natriuretic peptide (BNP), are continuous tests with many possible results. Yet, there is a tendency to dichotomize tests into positive and negative, and use sensitivity and specificity to describe the test characteristics. This approach can lead to waste of important diagnostic information and substandard clinical decision-making. The aim of this paper is to demonstrate the role of ROC curves in developing a more comprehensive understanding of diagnostic information portrayed by continuous tests to augment clinical decision-making.

Timely Use of Probiotics in Hospitalized Adults Prevents Clostridium difficile Infection: A Systematic Review With Meta-Regression Analysis.

BACKGROUND & AIMS: Systematic reviews have provided evidence for the efficacy of probiotics in preventing Clostridium difficile infection (CDI), but guidelines do not recommend probiotic use for prevention of CDI. We performed an updated systematic review to help guide clinical practice. METHODS: We searched MEDLINE, EMBASE, International Journal of Probiotics and Prebiotics, and The Cochrane Library databases for randomized controlled trials evaluating use of probiotics and CDI in hospitalized adults taking antibiotics. Two reviewers independently extracted data and assessed risk of bias and overall quality of the evidence. Primary and secondary outcomes were incidence of CDI and adverse events, respectively. Secondary analyses examined the effects of probiotic species, dose, timing, formulation, duration, and study quality. RESULTS: We analyzed data from 19 published studies, comprising 6261 subjects. The incidence of CDI in the probiotic cohort, 1.6% (54 of 3277), was lower than of controls, 3.9% (115 of 2984) (P < .001). The pooled relative risk of CDI in probiotic users was 0.42 (95% confidence interval, 0.30-0.57; I2 = 0.0%). Meta-regression analysis demonstrated that probiotics were significantly more effective if given closer to the first antibiotic dose, with a decrement in efficacy for every day of delay in starting probiotics (P = .04); probiotics given within 2 days of antibiotic initiation produced a greater reduction of risk for CDI (relative risk, 0.32; 95% confidence interval, 0.22-0.48; I2 = 0%) than later administration (relative risk, 0.70; 95% confidence interval, 0.40-1.23; I2 = 0%) (P = .02). There was no increased risk for adverse events among patients given probiotics. The overall quality of the evidence was high. CONCLUSIONS: In a systematic review with meta-regression analysis, we found evidence that administration of probiotics closer to the first dose of antibiotic reduces the risk of CDI by >50% in hospitalized adults. Future research should focus on optimal probiotic dose, species, and formulation. Systematic Review Registration: PROSPERO CRD42015016395.

Treating loss-to-follow-up as a missing data problem: a case study using a longitudinal cohort of HIV-infected patients in Haiti.

BACKGROUND: HIV programs are often assessed by the proportion of patients who are alive and retained in care; however some patients are categorized as lost to follow-up (LTF) and have unknown vital status. LTF is not an outcome but a mixed category of patients who have undocumented death, transfer and disengagement from care. Estimating vital status (dead versus alive) among this category is critical for survival analyses and program evaluation. METHODS: We used three methods to estimate survival in the cohort and to ascertain factors associated with death among the first cohort of HIV positive patients to receive antiretroviral therapy in Haiti: complete case (CC) (drops missing), Inverse Probability Weights (IPW) (uses tracking data) and Multiple Imputation with Chained Equations (MICE) (imputes missing data). Logistic regression was used to calculate odds ratios and 95% confidence intervals for adjusted models for death at 10 years. The logistic regression models controlled for sex, age, severe poverty (living on <$1 USD per day), Port-au-Prince residence and baseline clinical characteristics of weight, CD4, WHO stage and tuberculosis diagnosis. RESULTS: Age, severe poverty, baseline weight and WHO stage were statistically significant predictors of AIDS related mortality across all models. Gender was only statistically significant in the MICE model but had at least a 10% difference in odds ratios across all models. CONCLUSION: Each of these methods had different assumptions and differed in the number of observations included due to how missing values were addressed. We found MICE to be most robust in predicting survival status as it allowed us to impute missing data so that we had the maximum number of observations to perform regression analyses. MICE also provides a complementary alternative for estimating survival among patients with unassigned vital status. Additionally, the results were easier to interpret, less likely to be biased and provided an alternative to a problem that is often commented upon in the extant literature.

Geometrically controlled snapping transitions in shells with curved creases.

Curvature and mechanics are intimately connected for thin materials, and this coupling between geometry and physical properties is readily seen in folded structures from intestinal villi and pollen grains to wrinkled membranes and programmable metamaterials. While the well-known rules and mechanisms behind folding a flat surface have been used to create deployable structures and shape transformable materials, folding of curved shells is still not fundamentally understood. Shells naturally deform by simultaneously bending and stretching, and while this coupling gives them great stability for engineering applications, it makes folding a surface of arbitrary curvature a nontrivial task. Here we discuss the geometry of folding a creased shell, and demonstrate theoretically the conditions under which it may fold smoothly. When these conditions are violated we show, using experiments and simulations, that shells undergo rapid snapping motion to fold from one stable configuration to another. Although material asymmetry is a proven mechanism for creating this bifurcation of stability, for the case of a creased shell, the inherent geometry itself serves as a barrier to folding. We discuss here how two fundamental geometric concepts, creases and curvature, combine to allow rapid transitions from one stable state to another. Independent of material system and length scale, the design rule that we introduce here explains how to generate snapping transitions in arbitrary surfaces, thus facilitating the creation of programmable multistable materials with fast actuation capabilities.

Concordance Between Administrator and Clinician Ratings of Organizational Culture and Climate.

Organizational culture and climate are important determinants of behavioral health service delivery for youth. The Organizational Social Context measure is a well validated assessment of organizational culture and climate that has been developed and extensively used in public sector behavioral health service settings. The degree of concordance between administrators and clinicians in their reports of organizational culture and climate may have implications for research design, inferences, and organizational intervention. However, the extent to which administrators' and clinicians' reports demonstrate concordance is just beginning to garner attention in public behavioral health settings in the United States. We investigated the concordance between 73 administrators (i.e., supervisors, clinical directors, and executive directors) and 247 clinicians in 28 child-serving programs in a public behavioral health system. Findings suggest that administrators, compared to clinicians, reported more positive cultures and climates. Organizational size moderated this relationship such that administrators in small programs (<466 youth clients served annually) provided more congruent reports of culture and climate in contrast to administrators in large programs (≥466 youth clients served annually) who reported more positive cultures and climates than clinicians. We propose a research agenda that examines the effect of concordance between administrators and clinicians on organizational outcomes in public behavioral health service settings.

Assessing the Culture of Residency Using the C - Change Resident Survey: Validity Evidence in 34 U.S. Residency Programs.

BACKGROUND: A practical instrument is needed to reliably measure the clinical learning environment and professionalism for residents. OBJECTIVE: To develop and present evidence of validity of an instrument to assess the culture of residency programs and the clinical learning environment. DESIGN: During 2014-2015, we surveyed residents using the C - Change Resident Survey to assess residents' perceptions of the culture in their programs. PARTICIPANTS: Residents in all years of training in 34 programs in internal medicine, pediatrics, and general surgery in 14 geographically diverse public and private academic health systems. MAIN MEASURES: The C - Change Resident Survey assessed residents' perceptions of 13 dimensions of the culture: Vitality, Self-Efficacy, Institutional Support, Relationships/Inclusion, Values Alignment, Ethical/Moral Distress, Respect, Mentoring, Work-Life Integration, Gender Equity, Racial/Ethnic Minority Equity, and self-assessed Competencies. We measured the internal reliability of each of the 13 dimensions and evaluated response process, content validity, and construct-related evidence validity by assessing relationships predicted by our conceptual model and prior research. We also assessed whether the measurements were sensitive to differences in specialty and across institutions. KEY RESULTS: A total of 1708 residents completed the survey [internal medicine: n = 956, pediatrics: n = 411, general surgery: n = 311 (51% women; 16% underrepresented in medicine minority)], with a response rate of 70% (range across programs, 51-87%). Internal consistency of each dimension was high (Cronbach α: 0.73-0.90). The instrument was able to detect significant differences in the learning environment across programs and sites. Evidence of validity was supported by a good response process and the demonstration of several relationships predicted by our conceptual model. CONCLUSIONS: The C - Change Resident Survey assesses the clinical learning environment for residents, and we encourage further study of validity in different contexts. Results could be used to facilitate and monitor improvements in the clinical learning environment and resident well-being.

Wrinkling of milk skin is mediated by evaporation.

Wrinkling of thin films and membranes can occur due to various mechanisms such as growth and/or mismatch between the mechanical properties of the film and substrate. However, the physical origins of dynamic wrinkling in soft membranes are still not fully understood. Here we use milk skin as a tractable experimental system to investigate the physics of wrinkle formation in a thin, poroelastic film. Upon heating milk, a micron-thick hydrogel of denatured proteins and fat globules forms at the air-water interface. Over time, we observe an increase in the total length of wrinkles. By confocal imaging and profilometry, we determine that the composition and thickness of the milk skin appears to be homogeneous over the length scale of the wrinkles, excluding differences in milk skin composition as a major contributor to wrinkling. To explain the physical origins of wrinkle growth, we describe theory that considers the milk skin as a thin, poroelastic film where pressure is generated by the evaporative-driven flow of solvent across the film; this imparts in-plane stresses in the milk skin, which cause wrinkling. Viscous effects can explain the time-dependent growth of wrinkles. Our theoretical predictions of the effects of relative humidity on the total length of wrinkles over time are consistent with our experimental results. Our findings provide insight into the physics of the common phenomenon of milk skin wrinkling, and identify hydration gradients as another physical mechanism that can drive morphological instabilities in soft matter.

Effect of Post-Cesarean Delivery Oral Cephalexin and Metronidazole on Surgical Site Infection Among Obese Women: A Randomized Clinical Trial.

Importance: The rate of obesity among US women has been increasing, and obesity is associated with increased risk of surgical site infection (SSI) following cesarean delivery. The optimal perioperative antibiotic prophylactic regimen in this high-risk population undergoing cesarean delivery is unknown. Objective: To determine rates of SSI among obese women who receive prophylactic oral cephalexin and metronidazole vs placebo for 48 hours following cesarean delivery. Design, Setting, and Participants: Randomized, double-blind clinical trial comparing oral cephalexin and metronidazole vs placebo for 48 hours following cesarean delivery for the prevention of SSI in obese women (prepregnancy BMI ≥30) who had received standard intravenous preoperative cephalosporin prophylaxis. Randomization was stratified by intact vs rupture of membranes prior to delivery. The study was conducted at the University of Cincinnati Medical Center, Cincinnati, Ohio, an academic and urban setting, between October 2010 and December 2015, with final follow-up through February 2016. Interventions: Participants were randomly assigned to receive oral cephalexin, 500 mg, and metronidazole, 500 mg (n = 202 participants), vs identical-appearing placebo (n = 201 participants) every 8 hours for a total of 48 hours following cesarean delivery. Main Outcomes and Measures: The primary outcome was SSI, defined as any superficial incisional, deep incisional, or organ/space infections within 30 days after cesarean delivery. Results: Among 403 randomized participants who were included (mean age, 28 [SD, 6] years; mean BMI, 39.7 [SD, 7.8]), 382 (94.6%) completed the trial. The overall rate of SSI was 10.9% (95% CI, 7.9%-14.0%). Surgical site infection was diagnosed in 13 women (6.4%) in the cephalexin-metronidazole group vs 31 women (15.4%) in the placebo group (difference, 9.0% [95% CI, 2.9%-15.0%]; relative risk, 0.41 [95% CI, 0.22-0.77]; P = .01). There were no serious adverse events, including allergic reaction, reported in either the antibiotic group or the placebo group. Conclusions and Relevance: Among obese women undergoing cesarean delivery who received the standard preoperative cephalosporin prophylaxis, a postoperative 48-hour course of oral cephalexin and metronidazole, compared with placebo, reduced the rate of SSI within 30 days after delivery. For prevention of SSI among obese women after cesarean delivery, prophylactic oral cephalexin and metronidazole may be warranted. Trial Registration: clinicaltrials.gov Identifier: NCT01194115.

Assessing the Learning Environment for Medical Students: An Evaluation of a Novel Survey Instrument in Four Medical Schools.

OBJECTIVE: A practical, reliable, and valid instrument is needed to measure the impact of the learning environment on medical students' well-being and educational experience and to meet medical school accreditation requirements. METHODS: From 2012 to 2015, medical students were surveyed at the end of their first, second, and third year of studies at four medical schools. The survey assessed students' perceptions of the following nine dimensions of the school culture: vitality, self-efficacy, institutional support, relationships/inclusion, values alignment, ethical/moral distress, work-life integration, gender equity, and ethnic minority equity. The internal reliability of each of the nine dimensions was measured. Construct validity was evaluated by assessing relationships predicted by our conceptual model and prior research. Assessment was made of whether the measurements were sensitive to differences over time and across institutions. RESULTS: Six hundred and eighty-six students completed the survey (49 % women; 9 % underrepresented minorities), with a response rate of 89 % (range over the student cohorts 72-100 %). Internal consistency of each dimension was high (Cronbach's α 0.71-0.86). The instrument was able to detect significant differences in the learning environment across institutions and over time. Construct validity was supported by demonstrating several relationships predicted by our conceptual model. CONCLUSIONS: The C-Change Medical Student Survey is a practical, reliable, and valid instrument for assessing the learning environment of medical students. Because it is sensitive to changes over time and differences across institution, results could potentially be used to facilitate and monitor improvements in the learning environment of medical students.

A Non-randomized Comparison of Strategies for Consultation in a Community-Academic Training Program to Implement an Evidence-Based Psychotherapy.

Despite the central role of training and consultation in the implementation of evidence-based psychological interventions (EBPIs), comprehensive reviews of research on training have highlighted serious gaps in knowledge regarding best practices. Consultation after initial didactic training appears to be of critical importance, but there has been very little research to determine optimal consultation format or interventions. This observational study compared two consultation formats that included review of session audio and feedback in the context of a program to train clinicians (n = 85) in community mental health clinics to deliver cognitive therapy (CT). A "gold standard" condition in which clinicians received individual feedback after expert consultants reviewed full sessions was compared to a group consultation format in which short segments of session audio were reviewed by a group of clinicians and an expert consultant. After adjusting for potential baseline differences between individuals in the two consultation conditions, few differences were found in terms of successful completion of the consultation phase or in terms of competence in CT at the end of consultation or after a 2 year follow-up. However, analyses did not support hypotheses regarding non-inferiority of the group consultation condition. While both groups largely maintained competence, clinicians in the group consultation condition demonstrated increases in competence over the follow-up period, while a sub-group of those in the individual condition experienced decreases. These findings, if replicated, have important implications for EBP implementation programs, as they suggest that observation and feedback is feasible in community mental health setting, and that employing this method in a group format is an effective and efficient consultation strategy that may enhance the implementation and sustainability of evidence-based psychotherapies.