Early and long-term outcomes following cardiac surgery for patients with heterotaxy syndrome.

Objective: Heterotaxy syndrome is a complex multisystem abnormality historically associated with high morbidity and mortality. We sought to evaluate the early and long-term outcomes after cardiac surgery in heterotaxy syndrome. Methods: This is a single-center retrospective review of patients with heterotaxy syndrome undergoing single-ventricle palliation or primary or staged biventricular repair from 1998 to 2018. Patients were stratified by single ventricle versus biventricular physiology, and the severity of atrioventricular valve regurgitation. Demographics, anatomic characteristics, and early and late outcomes, including the length of stay, mortality, and surgical or catheter reinterventions, were analyzed. Results: Among 250 patients, 150 (60%) underwent biventricular repair. In-hospital mortality was 7.6% (n = 19). Median follow-up was 5.2 (range, 0-16) years. Among survivors to discharge, mortality was 19% (n = 44) and reintervention was 52% (n = 120). Patients with moderate/severe atrioventricular valve regurgitation were older (32 vs 16 months, P = .02), were more likely to experience adverse events during their index surgical admission (72% vs 46%, P < .001), and had longer in-hospital length of stay (20 vs 12 days, P = .009). Among patients with moderate to severe atrioventricular valve regurgitation, single-ventricle palliation is associated with a greater risk of unplanned reintervention compared with patients undergoing biventricular repair (hazard ratio, 2.13; CI, 1.10-4.12; P = .025). Conclusions: There was no significant difference in early or late outcomes in single-ventricle versus biventricular repair strategies in heterotaxy. In the subgroup of patients with moderate/severe atrioventricular valve regurgitation, patients who underwent single-ventricle palliation were 2.5 times more likely to need a late reintervention compared with those undergoing biventricular repair.

An active-learning laboratory focused on critical care topics.

BACKGROUND AND PURPOSE: To describe an active-learning laboratory on critical care topics including advanced cardiac life support (ACLS), rapid sequence intubation (RSI), and toxicology and its effect on students' knowledge, skills, and confidence. EDUCATIONAL ACTIVITY AND SETTING: Third year pharmacy students (n = 88) participated in a critical care focused laboratory with four stations focused on ACLS review, ABBOJECTⓇ syringe assembly, ACLS simulations, RSI cases, and toxicology. Prior to the critical care focused skills laboratory, students completed an optional assessment composed of six confidence and eight knowledge questions. After the laboratory, students completed the same confidence and knowledge assessment. Descriptive statistics assessed pre/post-assessment responses. Paired pre/post-assessment Likert data were analyzed using the Wilcoxon signed-rank test and paired pre/post-test multiple choice responses were analyzed using the McNemar test. FINDINGS: Of the 88 students in the cohort, 76 students completed both the pre/post-assessments (response rate: 86.4%). Students demonstrated a significant increase in their overall knowledge and confidence scores on the post-assessment. All students successfully assembled an ABBOJECTⓇ syringe. The majority of respondents rated the critical care laboratory as excellent or good with regards to how enjoyable and effective the activity was to help understand critical care topics. SUMMARY: A hands-on, active-learning laboratory devoted to teaching and reinforcing common critical care concepts allowed students to gain knowledge and confidence regarding ACLS, RSI, and toxicology.

Work-Family Conflict and Wellbeing in US Pharmacy Faculty with Children.

OBJECTIVE: Objectives of this study included characterization of the current landscape of work-family conflict (WFC), family-work conflict (FWC), wellbeing, and childcare-related factors in United States (US) pharmacy faculty members with children, as well as relationship determination between faculty characteristics and WFC, FWC, and wellbeing indices. METHODS: A survey was developed and administered to US pharmacy faculty members with children in February 2022. Questions included demographic and childcare-related factors and the validated Netemeyer WFC and FWC scales, and World Health Organization (WHO-5) Wellbeing Index. Data were summarized using descriptive statistics, one-way analysis of variance and t tests, and multiple linear regression analysis. RESULTS: The survey was completed by 368 faculty members with children. Respondents were primarily married females who identify as White or European American, with>90% having children less than 18 years of age. Respondents scored an average of 24.1 ± 7.2 points on the WFC scale, 19.5 ± 7.5 points on the FWC scale, and 56.8 ± 17.5 on the WHO-5 Wellbeing Index. Having dependent children resulted in statistically significantly higher WFC and FWC and lower wellbeing scores. Linear regression models for WFC, FWC, and wellbeing explained 20%, 8%, and 9% of the variability in scores, respectively. CONCLUSION: This study identified the presence of WFC, FWC, and decreased wellbeing in pharmacy faculty members with children. Future research is needed to further qualify contributors to the indices and place findings into a larger context.

Economic Considerations and Cost-Saving Strategies for Sterile Compounding Education.

OBJECTIVE: To determine economic considerations associated with the facilitation of sterile compounding education for students in schools and colleges of pharmacy across the United States. METHODS: An online survey was sent to members of the American Association of Colleges of Pharmacy Pharmaceutics Section and Laboratory Instructor's Special Interest Group. Quantitative and qualitative data were collected on general information about the institution, student cohorts, compounding courses, types of compounds prepared, equipment, budgets, personnel, and cost-saving measures. Descriptive statistics were calculated using SPSS. Open-ended responses were used by respondents if the primary question could not adequately capture their institution-specific information. These answers were added to the study findings. RESULTS: Of 555 surveys sent, 40 were completed. Reported annual sterile compounding budgets ranged from $500 to $95,500. Twenty-two percent of respondents reported collecting a lab fee from students to offset associated costs. Seventy percent of respondents specified cost-saving measures, including the use of expired drugs, reusing supplies or personal protective equipment, price comparisons, simulated drugs, and donations. CONCLUSION: Findings from this study may assist pharmacy administrators and faculty in evaluating the costs associated with sterile compounding education and determining ways to reduce costs while maintaining the intent and quality of these courses.

Economic Considerations and Cost-Saving Strategies for Nonsterile Compounding Education.

OBJECTIVE: To determine the economic considerations, including cost-saving strategies, associated with nonsterile compounding education for students in schools and colleges of pharmacy across the United States. METHODS: An electronic survey was sent to the American Association of Colleges of Pharmacy Pharmaceutics Section and Laboratory Instructor's Special Interest Group members. Quantitative and qualitative data were collected about the institution, student cohorts, compounding courses, equipment, budgets, personnel, and cost-saving measures. Descriptive statistics were calculated using SPSS. Open-ended responses were used by respondents if the primary question could not adequately capture their institution-specific information. These answers were added to the study findings. RESULTS: Of 555 surveys sent, 46 were completed. Reported annual compounding budgets ranged from $3000 to $96,000. Reported annual equipment maintenance costs ranged from $400 to $18,000. Fifty percent of respondents reported students shared equipment, and 29.6% collected a lab fee from students to offset costs. Approximately half of respondents reported the use of cost-saving measures, including contract pricing, purchasing supplies in bulk, price comparisons, use of simulated drugs, re-use of personal protective equipment, and procurement of donations. Fifty percent of respondents employed laboratory assistants to support nonsterile compounding sessions, with paid positions ranging from $200 to $1000 per semester. CONCLUSION: Findings from this study may assist pharmacy administrators and course directors in evaluating the costs associated with nonsterile compounding education across the Academy and, more importantly, determining ways to reduce such costs while maintaining the intent and quality of these courses.

Assessing the effects of sunlight and water on asphalt binder and pavement leachability related to the environment.

Extensive global research conducted over 30 years explores asphalt leachability and stormwater runoff. Asphalt's widespread usage in construction materials underscores the importance of understanding its environmental consequences. This study aims to assess the influence of sunlight exposure on water quality, particularly regarding the release of hazardous organic compounds such as polycyclic aromatic compounds. We investigated the effect of concurrent versus sequential exposure to water and sunlight, and dark versus light trials utilizing thin films of asphalt binder as well as old and freshly prepared pavement cores for analysis. Initial laboratory experiments reveal significant water-soluble species when thin asphalt films are exposed to solar simulation while underwater. However, simulating environmental conditions found in roadways by exposing the asphalt binder to solar simulation followed by water immersion leads to a substantial decrease in compound formation. Leachate water from 17-year-old asphalt and 15-year-old concrete pavements exhibits complex compound compositions associated with atmospheric and/or vehicular deposition, posing challenges in deconvoluting their origins. Light and dark trials conducted on freshly prepared asphalt pavement under environmental conditions of sunlight and rain demonstrate minimal runoff variation, with semi-volatile organic compound levels resembling the background. Future investigations will focus on applying insights gained from this study to analyze larger sample sets, with an emphasis on inherent hazardous compound variations.

Retention of students' knowledge of immunizations following a one-day or a five-week course.

INTRODUCTION: The American Pharmacists Association (APhA) Pharmacy-Based Immunization Delivery Certificate Program is commonly used by schools of pharmacy to train student pharmacists in immunizations. This study compared student pharmacists' knowledge retention of immunization content when the live seminar of the APhA Program was delivered as a one-day co-curricular activity or as a five-week required course. The impact of immunization experience on students' knowledge retention was a secondary objective. METHODS: A 45-question knowledge assessment about immunizations was administered to second and third-year student pharmacists eight months after completing either a five-week course (second-year students) or a one-day seminar (third-year students). Students were also asked about their experience providing patient education, screening, and administering immunizations. RESULTS: Knowledge assessment scores declined by an average of 26.3% from the initial to the eight-month assessment, and declines were similar for second and third-year students. However, students who reported immunizing over 50 patients had significantly higher knowledge retention than those who reported never immunizing. CONCLUSIONS: A live immunization training given over one day or five weeks did not impact the retention of immunization knowledge eight months later. However, students who immunized >50 patients had greater knowledge retention. These findings indicate the importance of including the application of immunization knowledge in pharmacy curricula to enhance long-term knowledge retention.

Introducing LGBTQIA+ Patient Care to Pharmacy Students Through Laboratory-Based Exercises.

Objective. To assess the impact of novel skills-based laboratory exercises on first-, second-, and third-year pharmacy students' confidence and knowledge regarding care for people identifying as lesbian, gay, bisexual, transgender, queer, intersex, asexual, and other (LGBTQIA+).Methods. An LGBTQIA+ lecture discussing pronouns, common terminology, health disparities, health screenings, and gender-affirming hormone therapy was presented to students. During laboratory sessions, students applied lecture topics via a learning level-specific activity. Students completed a pre- and post-activity survey assessing their knowledge, confidence, and activity experience.Results. Seventy-nine students (N=348) completed both the pre- and post-activity survey. Students' overall increase in knowledge scores was significant, with improvement in four out of six questions among each cohort. A significant increase was seen in students understanding of the role of the pharmacist, their confidence in caring for LGBTQIA+ patients, and their comfort with using appropriate terminology. Most students (92%) agreed or strongly agreed that learning about LGBTQIA+ patient care was a positive experience, while 74% agreed that additional education on LGBTQIA+ patients is needed within their pharmacy curriculum.Conclusion. After a brief skills-based laboratory course, students' knowledge and confidence in caring for LGBTQIA+ patients improved; however, students agreed that more exposure was necessary. Future studies will follow students as they progress through the curriculum to determine the impact of exposure to LGBTQIA+ content across all three didactic years.

A Case Report of Cangrelor Bridge Therapy for a Diagnostic Bronchoscopy With Biopsy.

Although premature discontinuation of dual antiplatelet therapy (DAPT) is associated with an increased risk of ischemic complications, patients may present with an urgent need for surgery that would require interruption of DAPT. Antiplatelet bridge therapy using cangrelor, an intravenous P2Y12 inhibitor, has been studied as a potential option to ensure continuation of DAPT perioperatively. However, limited evidence exists supporting the off-label use of cangrelor bridge therapy to noncardiac procedures. We describe the case of a 67-year-old class 3 obese female on DAPT (aspirin and ticagrelor) for recent drug-eluting stent placement who required a bronchoscopy with biopsy for suspected lung cancer. Cangrelor bridge therapy was utilized both preoperatively and postoperatively without ischemic or bleeding complications, and the patient was subsequently able to begin radiation therapy after a confirmed diagnosis of lung cancer.

Gold Nanoparticle Labels and Heterogeneous Immunoassays: The Case for the Inverted Substrate.

This paper examines how the difference in the spatial orientation of the capture substrate influences the analytical sensitivity and limits of detection for immunoassays that use gold nanoparticle labels (AuNPs) and rely on diffusion in quiet solution in the antigen capture and labeling steps. Ideally, the accumulation of both reactants should follow a dependence governed by the rate in which diffusion delivers reactants to the capture surface. In other words, the accumulation of reactants should increase with the square root of the incubation time, i.e., t1/2. The work herein shows, however, that this expectation is only obeyed when the capture substrate is oriented to direct the gravity-induced sedimentation of the AuNP labels away from the substrate. Using an assay for human IgG, the results show that circumventing the sedimentation of the gold nanoparticle labels by substrate inversion enables the dependence of the labeling step on diffusion, reduces nonspecific label adsorption, and improves the estimated detection limit by ∼30×. High-density maps of the signal across the two types of substrates also demonstrate that inversion in the labeling step results in a more uniform distribution of AuNP labels across the surface, which translates to a greater measurement reproducibility. These results, which are supported by model simulations via the Mason-Weaver sedimentation-diffusion equation, and their potential implications when using other nanoparticle labels and related materials in diagnostic tests and other applications, are briefly discussed.

Importance of specimen pretreatment for the low-level detection of mycobacterial lipoarabinomannan in human serum.

Patient care and prevention of disease outbreaks rely heavily on the performance of diagnostic tests. These tests are typically carried out in serum, urine, and other complex sample matrices, but are often plagued by a number of matrix effects such as nonspecific adsorption and complexation with circulating proteins. This paper demonstrates the importance of sample pretreatment to overcome matrix effects, enabling the low-level detection of a disease marker for tuberculosis (TB). The impact of pretreatment is illustrated by detecting a cell wall component unique to mycobacteria, lipoarabinomannan (LAM). LAM is a major virulence factor in the infectious pathology of Mycobacterium tuberculosis (Mtb) and has been successfully detected in the body fluids of TB-infected individuals; however, its clinical sensitivity - identifying patients with active infection - remains problematic. This and the companion paper show that the detection of LAM in an immunoassay is plagued by its complexation with proteins and other components in serum. Herein, we present the procedures and results from an investigation of several different pretreatment schemes designed to disrupt complexation and thereby improve detection. These sample pretreatment studies, aimed at determining the optimal conditions for complex disruption, were carried out by using a LAM simulant derived from the nonpathogenic M. smegmatis, a mycobacterium often used as a model for Mtb. We have found that a perchloric acid-based pretreatment step improves the ability to detect this simulant by ∼1500× with respect to that in untreated serum. This paper describes the approach to pretreatment, how pretreatment improves the detection of the LAM simulant in human serum, and the results from a preliminary investigation to identify possible contributors to complexation by fractionating serum according to molecular weight. The companion paper applies this pretreatment approach to assays of TB patient samples.

Detection of the tuberculosis antigenic marker mannose-capped lipoarabinomannan in pretreated serum by surface-enhanced Raman scattering.

The ability to detect tuberculosis (TB) continues to be a global health care priority. This paper describes the development and preliminary assessment of the clinical accuracy of a heterogeneous immunoassay that integrates a serum pretreatment process with readout by surface-enhanced Raman scattering (SERS) for the low-level detection of mannose-capped lipoarabinomannan (ManLAM). ManLAM is a major virulence factor in the infectious pathology of Mycobacterium tuberculosis (Mtb) that has been found in the serum and other body fluids of infected patients. The effectiveness of ManLAM as a TB diagnostic marker, however, remains unproven for reasons not yet well understood. As reported herein, we have found that (1) ManLAM complexes with proteins and possibly other components in serum; (2) these complexes have a strongly detrimental impact on the ability to detect ManLAM using an immunoassay; (3) a simple pretreatment step can disrupt this complexation; and (4) disruption by pretreatment improves detection by 250×. We also describe the results from a preliminary assessment on the utility of serum pretreatment by running immunoassays on archived specimens from 24 TB-positive patients and 10 healthy controls. ManLAM was measurable in 21 of the 24 TB-positive specimens, but not in any of the 10 control specimens. These findings, albeit for a very small specimen set, translate to a clinical sensitivity of 87.5% and a clinical specificity of 100%. Together, these results both provide much needed evidence for the clinical utility of ManLAM as a TB marker, and demonstrate the potential utility of our overall approach to serve as a new strategy for the development of diagnostic tests for this disease.

Advantages and limitations of nanoparticle labeling for early diagnosis of infection.

INTRODUCTION: Nanoparticle-based disease diagnostics harness a range of unique physical and chemical phenomena for the detection of biomarkers at exceedingly low levels. This capability potentially enables the diagnosis of disease earlier in its progression and improves the likelihood of positive treatment outcomes. This review highlights recent work in this area, and then projects the next steps needed to move this emerging capability beyond the research laboratory. AREAS COVERED: This review examines the advantages and limitations of in vitro health care diagnostic tests that utilize nanoparticles (e.g. noble metal, quantum dot, and magnetic). It includes a brief overview of their unique properties, syntheses, and applicable readout strategies. This is followed by a brief synopsis of the obstacles faced when attempting to translate nanoparticle-based diagnostics from the R&D laboratory to the clinic and other arenas (i.e. the difficulties common to in vitro diagnostics), and then by a much more in-depth examination of the need to control and characterize a range of nanoparticle properties (e.g. size, shape, surface composition, and stability) when making this transition. Expert commentary: The review wraps up with a short commentary and perspective for the next five years, focusing on possible guidelines for nanoparticle characterization.

Sampling Error: Impact on the Quantitative Analysis of Nanoparticle-Based Surface-Enhanced Raman Scattering Immunoassays.

This paper examines the impact of the sampling error caused by the small size of the focused laser spot when using surface-enhanced Raman scattering (SERS) as a quantitative readout tool to analyze a sandwich immunoassay. The assay consists of a thin-film gold substrate that is modified with a layer of capture monoclonal antibodies (mAbs) and extrinsic Raman labels (ERLs) that consist of gold nanoparticle cores (60 nm diameter) coated with a monolayer of a Raman reporter molecule and a layer of human IgG mAbs to tag the captured antigen. The contribution of sampling error to the measurement is delineated first by constructing and analyzing an antigenic random accumulation model; this is followed by an experimental study of the analysis of an assay substrate using two different laser spot sizes. Both sets of findings indicate that the analysis with a small laser spot can lead to a sampling error (i.e., undersampling) much like that found when the size of a measured soil sample fails to accurately match that of a larger, more representative sample. That is, the smaller the laser spot size, the larger probable deviation in the accuracy of the measurement and the greater the imprecision of the measurement. Possible implications of these results with respect to the general application of SERS for quantitative measurements are also briefly discussed.

Prospects for point-of-care pathogen diagnostics using surface-enhanced Raman scattering (SERS).

Surface-enhanced Raman scattering (SERS) has enabled the detection of pathogens and disease markers at extremely low levels. This review examines the potential impact of SERS in addressing unmet needs in pathogen diagnostics both in a traditional clinical setting and in the point of care (POC) arena. It begins by describing the strengths and weaknesses of today's diagnostics technologies in order to set a contextual stage for an overview which highlights a few of the many recent developments using SERS in biodefense, human and animal health, and monitoring food and water safety. These sections are followed by discussions of the challenges for the translation of these developments to POC settings, including the performance attributes and metrics for quantification of analytical and clinical figures of merit (e.g., limit of detection and clinical accuracy), and the pathways for large-scale test validation and the build-out of instrumentation and tests kits for POC deployment.

Confocal Raman microscopy for investigating synthesis and characterization of individual optically trapped vinyl-polymerized surfactant particles.

Small polymeric particles are increasingly employed as adsorbent materials, as molecular carriers, as delivery vehicles, and in preconcentration applications. The rational development of these materials requires in situ methods of analysis to characterize their synthesis, structure, and applications. Optical-trapping confocal Raman microscopy is a spectroscopic method capable of acquiring information at several stages of the development of such dispersed particulate materials. In the present study, an example material is developed and tested using confocal Raman microscopy for characterization at each stage of the process. Specifically, the method is used to investigate the synthesis, structure, and applications of individual polymeric surfactant particles produced by the vinyl polymerization of sodium 11-acrylamidoundecanoate (SAAU). The kinetics of polymerization can be monitored over time by measuring the loss of the acrylamide C=C functional groups using confocal Raman microscopy of particles optically trapped by the excitation laser, where, within the limits of detecting the vinyl functional group, the complete polymerization of the SAAU monomer was achieved. The polymerized SAAU particles are spherical, and they exhibit uniform access to water throughout their structure, as tested by the penetration of heavy water (D2O) and collection of spatially resolved Raman spectra from the interior of the particle. These porous particles contain hydrophobic domains that can be used to accumulate molecules for adsorption or carrier applications. This property was tested by using confocal Raman microscopy to measure the accumulation equilibria and kinetics of a model compound, dioxybenzone. The partitioning of this compound into the polymer surfactant could be determined on a quantitative basis using relative scattering cross sections of the SAAU monomer and the adsorbate. The study points out the utility of optical-trapping confocal Raman microscopy for investigating the synthesis, structure, and potential carrier applications of polymeric particle materials.

Contemporary Anticoagulation Reversal Focus on Direct Thrombin Inhibitors and Factor Xa Inhibitors.

Several oral direct thrombin inhibitors (DTIs) and factor Xa (FXa) inhibitors have recent Food and Drug Administration approval or are under investigation in late-stage clinical trials for the prevention and treatment of thromboembolic events. Rapid reversal of anticoagulation is typically recommended in patients with severe or life-threatening bleeding and in patients requiring surgery or invasive procedures. However, no antidote exists for DTIs or FXa inhibitors though replacement of coagulation factors using clotting factor concentrates is routinely considered in some clinical scenarios. Clotting factor concentrates available in the United States include prothrombin complex concentrate, activated prothrombin complex concentrate, and recombinant factor VII, activated. Coagulation tests to confirm adequate reversal of anticoagulation should be considered and commonly include activated partial thromboplastin time and thrombin time (TT) for DTIs, and chromogenic FXa assay and TT for FXa inhibitors. Monitoring of coagulation tests should continue for 1 to 2 days after achievement of hemostasis, since the duration of the clotting factor concentrate may be shorter than the oral anticoagulant, especially in patients with organ dysfunction. Utilization of decision-support tools and use of standardized reversal protocols are recommended to prevent errors in prescribing and dispensing for clotting factor concentrates.

Intravenous ketamine for treatment-resistant major depressive disorder.

OBJECTIVE: To evaluate the literature regarding the efficacy and safety of intravenous ketamine for treatment-resistant major depressive disorder (MDD). DATA SOURCES: A MEDLINE search (1966-September 2011) was performed using the terms treatment-resistant depression and ketamine. The search was restricted to articles published in English and reporting on use of ketamine in humans. STUDY SELECTION AND DATA EXTRACTION: All English-language articles identified from the data search were evaluated. Data were eligible for inclusion if they were primary literature and evaluated the efficacy of ketamine for depressive symptoms in treatment-resistant MDD. One case report, 3 case series, 3 open-label trials, and 1 randomized crossover trial were included. DATA SYNTHESIS: Several medications are available for treatment-resistant MDD; however, they are often limited by a slow onset of therapeutic effect and tolerability. It has been suggested that ketamine, a rapid-acting, N-methyl-D-aspartate glutamate receptor antagonist, may have antidepressant effects. Case reports, case series, and select trials evaluating ketamine use for depressive symptoms in treatment-resistant MDD have demonstrated a rapid effect for reductions of scores on a number of depression scales; however, its sustainability effect remains unknown. Several studies reported a large or moderate to large effect size for ketamine. Additionally, these studies showed that ketamine use in this patient population is associated with relatively well-tolerated adverse effects. CONCLUSIONS: Ketamine for treatment-resistant MDD requires further evaluation before it can be considered a viable treatment option.