Perceived Workload Using Separate (Filtering Facepiece Respirator and Face Shield) and Powered Air-Purifying Respirator and Integrated Lightweight Protective Air-Purifying Respirator: Protocol for an International Multisite Human Factors Randomized Crossover Feasibility Study.

BACKGROUND: The design of personal protective equipment (PPE) may affect well-being and clinical work. PPE as an integrated item may improve usability and increase adherence by healthcare professionals. Human factors design and safety may reduce occupational-acquired diseases. As an integrated PPE, a lightweight protective air-purifying respirator (L-PAPR) could be used during health procedures where healthcare professionals are exposed to airborne pathogens. The human factors affecting the implementation of alternative PPE such as L-PAPR have not been thoroughly studied. The population of interest is health care professionals, the intervention is the performance by PPE during tasks across the three PPE types 1.) N95 respirators and face shields, 2.)traditional powered air-purifying respirator(PAPR), and 3.) L-PAPR. The outcomes are user error, communications, safety, and end-user preferences. OBJECTIVE: This study will assess whether the L-PAPR improves health care professionals' comfort in terms of perceived workload and physical and psychological burden during direct patient care when compared with the traditional PAPR or N95 and face shield. This study also aims to evaluate human factors during the comparison of the use of L-PAPR with a combination of N95 respirators plus face shields or the traditional PAPRs. METHODS: This is an interventional randomized crossover quality improvement feasibility study consisting of a 3-site simulation phase with 10 participants per site and subsequent field testing in 2 sites with 30 participants at each site. The 3 types of respiratory PPE will be compared across medical tasks and while donning and doffing. We will evaluate the user's perceived workload, usability, usage errors, and heart rate. We will conduct semistructured interviews to identify barriers and enablers to implementation across each PPE type over a single continuous wear episode and observe interpersonal communications across conditions and PPE types. RESULTS: We expect the research may highlight communication challenges and differences in usability and convenience across PPE types along with error frequency during PPE use across PPE types, tasks, and time. CONCLUSIONS: The design of PPE may affect overall well-being and hinder or facilitate clinical work. Combining 2 pieces of PPE into a single integrated item may improve usability and reduce occupational-acquired diseases. The human factors affecting the implementation of an alternative PPE such as L-PAPR or PAPR have not been thoroughly studied. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): PRR1-10.2196/36549.

Body composition assessment after pediatric liver transplant.

BACKGROUND: Pediatric liver transplantation generally restores metabolic function; yet after transplantation, some children remain malnourished, have increased adiposity, and develop obesity. Measurement of body composition in the assessment of nutrition status could reduce adverse consequences in children. METHODS: Anthropometric measurements, multiple-frequency bioelectrical impedance analysis, air displacement plethysmography, and ultrasound measurements were conducted on children recruited from the liver transplant program at the University of Minnesota Masonic Children's Hospital. A cross-sectional study was conducted to describe the quality of weight gain in post-liver transplant children between the ages of 2 and 17 years using multiple assessment tools (air displacement plethysmography, multiple-frequency bioelectrical impedance analysis, and ultrasound) and to determine whether multiple-frequency bioelectrical impedance analysis and ultrasound accurately describe body composition and quality of weight gain. RESULTS: Mean percent body fat by air displacement plethysmography and multiple-frequency bioelectrical impedance analysis was 18.4% (±3.3) and 19.0% (±3.9), respectively (P > .99). There were insufficient data to examine the relationship between summed muscle and adipose thickness measures by ultrasound and percent body fat determined by air displacement plethysmography or multiple-frequency bioelectrical impedance analysis. CONCLUSION: Percent body fat, fat mass, and fat-free mass measures determined by air displacement plethysmography and multiple-frequency bioelectrical impedance analysis were not statistically different, which suggests the stand-on device used in this study could be a useful body composition assessment tool for the pediatric population.

Understanding Health Care Access Disparities Among Human Trafficking Survivors: Profiles of Health Care Experiences, Access, and Engagement.

Human trafficking is associated with a profound burden of physical and psychological trauma. Survivors of trafficking interact with the health care system during and after their experiences of trafficking. Socioeconomic isolation, stigma, shame, guilt, fear of judgment, fear of retribution by traffickers, fear of law enforcement authorities, and other factors known to inhibit disclosure can exert a formative influence on survivors' health care experiences, health care access, and health services engagement. Using a mixed qualitative-quantitative social science research method, known as by-person factor analysis (or Q-methodology), the current analysis systematically examines the scope of trafficking survivors' health care experiences and perceptions of medical care, health care access behaviors, and degree of engagement with health services. Among 33 survivors of human trafficking surveyed, 21 met inclusion criteria for this analysis. Three distinct profiles of survivor health care experiences and health services engagement-Avoidant, Distrustful, and Constrained-are identified from the aggregate of survivors' perceptions of medical care. Although there are salient differences across the three survivor profiles, a feeling of disenfranchisement is a common thread and directly related to health care access behaviors and health services engagement. Understanding that the feeling of disenfranchisement functions as a filter through which trafficking survivors perceive and experience medical care can help health care professionals take appropriate countermeasures. Implications for improving health care access and engagement include the implementation of trauma-responsive, culturally sensitive, and survivor-centered care practices.

Pre-operative Sarcopenia Predicts Low Islet Cell Yield Following Total Pancreatectomy with Islet Autotransplantation for Chronic Pancreatitis.

BACKGROUND AND AIM: Sarcopenia defined as degenerative loss of skeletal muscle mass associated with aging, represents an objective parameter to measure frailty and to estimate patient's physiologic reserves. It is a robust predictor of post-operative complications in transplantation and major oncologic surgeries. There is no data regarding the prevalence of sarcopenia in chronic pancreatitis or its impact on the outcome of patients undergoing TPIAT for CP. We sought to estimate the prevalence of sarcopenia, its impact on post-operative morbidity and prediction of islet yield and metabolic outcomes in patients undergoing TPIAT. METHODS: Adult patients undergoing TPIAT between 2008 and 2018 were identified from our prospectively maintained database and were included if they had CT within 6 months before TPIAT. Skeletal muscle index (SMI) was evaluated by pre-operative CT at the level of L3 vertebra. Sarcopenia was defined as SMI < 52.4 in males and < 38.5 in females. Post-operative morbidity occurring within 90 days after TPIAT was graded as per the validated Clavien-Dindo score. Major post-surgical morbidity was defined as Clavien-Dindo score of IIIa or more. The yield of islets was quantified as islet equivalents (IEQ) and IEQ/kg recipient body weight was calculated. RESULTS: One hundred and thirty-eight patients underwent TPIAT, with 46 (one-third) being classified as having pre-operative sarcopenia based on CT. No significant differences were observed in the incidence of any major surgical complications, length of hospital stay (median (range in days) 111-8 vs. 122-9; p = 0.6) and 30-day readmission rate (7 (15.2%) vs, 2 (2.2%); p = 0.5) between sarcopenic and non-sarcopenic patients. More patients with sarcopenia needed to be discharged to residential rehabilitation facility compared with non-sarcopenic patients (7 (15.2%) vs. 2 (2.2%), p = 0.007). Sarcopenia (OR 7.4 (95% CI 1.32-41.24); p = 0.023) and presence of calcification (OR 5.5 (95% CI 0.94-32.19); p = 0.05) were independent predictors of low islet yield (< 2500 IEQ/kg) on multivariate analysis. CONCLUSION: Sarcopenia is frequent in CP patients undergoing TPIAT, but not readily recognized by standard anthropometric measurement. Sarcopenia was associated with increased chance of discharge to a residential rehabilitation facility and with a poor islet yield during TPIAT. It is therefore critical to optimize nutrition prior to TPIAT surgery in CP patients.

Update on body composition tools in clinical settings: computed tomography, ultrasound, and bioimpedance applications for assessment and monitoring.

Patients with acute/critical illness are particularly vulnerable to muscle loss and fluid shifts, which adversely impact clinical outcomes. Assessment of these parameters in hospital settings is often subjective and imprecise, which creates discrepancies in identification and difficulty in assessing longitudinal changes. Body composition (BC) technologies provide objective information about muscle and fluid status that can enhance clinical assessment, and BC variables could be biomarkers for prognosis and targets to monitor intervention. There is growing interest in computed tomography (CT), ultrasound (US), and bioimpedance techniques as bedside assessment tools in clinical populations, and specific muscle measures, whole-body BC estimates, and select BC variables show promise as biomarkers of muscle health, nutrition risk, and fluid status. This brief review highlights work within the past 5 years on the use of BC variables generated from CT, US, and bioimpedance in clinical populations with an emphasis on those with acute/critical illness and a brief discussion of implementation challenges in these populations. Consensus on measurement protocols will facilitate identification of BC targets that best reflect prognosis and outcomes and will ultimately allow clinicians to identify individuals who would benefit most from targeted nutrition and physical therapy interventions and reliably monitor their response to treatment.

Diagnosing clinical malnutrition: Perspectives from the past and implications for the future.

This review, intended for both researchers and clinicians, provides a history of the definition of clinical malnutrition. Despite global efforts, we remain without one clear, objective, internationally accepted definition; clarity in this regard will ultimately improve our evaluation and monitoring of nutritional status to achieve optimal patient outcomes. In this review we explore the development of the term malnutrition and its diagnosis and application in the setting of acute and chronic disease. We begin in the second century A.D. with the work of the Greek physician Galen who is credited as the first to apply the term marasmus to characterize three categories of malnutrition, which are surprisingly similar to components of current international definitions. We then highlight significant developments over the next 2000 years culminating in our current application of the clinical diagnosis of malnutrition. A perspective on historical practices may inform current efforts toward a global definition and diagnosis of malnutrition.

Evaluation of the safety and biodistribution of M032, an attenuated herpes simplex virus type 1 expressing hIL-12, after intracerebral administration to aotus nonhuman primates.

Herpes simplex virus type 1 (HSV-1) mutants lacking the γ(1)34.5 neurovirulence loci are promising agents for treating malignant glioma. Arming oncolytic HSV-1 to express immunostimulatory genes may potentiate therapeutic efficacy. We have previously demonstrated improved preclinical efficacy, biodistribution, and safety of M002, a γ(1)34.5-deleted HSV-1 engineered to express murine IL-12. Herein, we describe the safety and biodistribution of M032, a γ(1)34.5-deleted HSV-1 virus that expresses human IL-12 after intracerebral administration to nonhuman primates, Aotus nancymae. Cohorts were administered vehicle, 10(6), or 10(8) pfu of M032 on day 1 and subjected to detailed clinical observations performed serially over a 92-day trial. Animals were sacrificed on days 3, 31, and 91 for detailed histopathologic assessments of all organs and to isolate and quantify virus in all organs. With the possible exception of one animal euthanized on day 16, neither adverse clinical signs nor sex- or dose-related differences were attributed to M032. Elevated white blood cell and neutrophil counts were observed in virus-injected groups on day 3, but no other significant changes were noted in clinical chemistry or coagulation parameters. Minimal to mild inflammation and fibrosis detected, primarily in meningeal tissues, in M032-injected animals on days 3 and 31 had mostly resolved by day 91. The highest viral DNA levels were detected at the injection site and motor cortex on day 3 but decreased in central nervous system tissues over time. These data demonstrate the requisite safety of intracerebral M032 administration for consideration as a therapeutic for treating malignant brain tumors.

Preclinical evaluation of a genetically engineered herpes simplex virus expressing interleukin-12.

Herpes simplex virus 1 (HSV-1) mutants that lack the γ(1)34.5 gene are unable to replicate in the central nervous system but maintain replication competence in dividing cell populations, such as those found in brain tumors. We have previously demonstrated that a γ(1)34.5-deleted HSV-1 expressing murine interleukin-12 (IL-12; M002) prolonged survival of immunocompetent mice in intracranial models of brain tumors. We hypothesized that M002 would be suitable for use in clinical trials for patients with malignant glioma. To test this hypothesis, we (i) compared the efficacy of M002 to three other HSV-1 mutants, R3659, R8306, and G207, in murine models of brain tumors, (ii) examined the safety and biodistribution of M002 in the HSV-1-sensitive primate Aotus nancymae following intracerebral inoculation, and (iii) determined whether murine IL-12 produced by M002 was capable of activating primate lymphocytes. Results are summarized as follows: (i) M002 demonstrated superior antitumor activity in two different murine brain tumor models compared to three other genetically engineered HSV-1 mutants; (ii) no significant clinical or magnetic resonance imaging evidence of toxicity was observed following direct inoculation of M002 into the right frontal lobes of A. nancymae; (iii) there was no histopathologic evidence of disease in A. nancymae 1 month or 5.5 years following direct inoculation; and (iv) murine IL-12 produced by M002 activates A. nancymae lymphocytes in vitro. We conclude that the safety and preclinical efficacy of M002 warrants the advancement of a Δγ(1)34.5 virus expressing IL-12 to phase I clinical trials for patients with recurrent malignant glioma.

Usability of a patient education and motivation tool using heuristic evaluation.

BACKGROUND: Computer-mediated educational applications can provide a self-paced, interactive environment to deliver educational content to individuals about their health condition. These programs have been used to deliver health-related information about a variety of topics, including breast cancer screening, asthma management, and injury prevention. We have designed the Patient Education and Motivation Tool (PEMT), an interactive computer-based educational program based on behavioral, cognitive, and humanistic learning theories. The tool is designed to educate users and has three key components: screening, learning, and evaluation. OBJECTIVE: The objective of this tutorial is to illustrate a heuristic evaluation using a computer-based patient education program (PEMT) as a case study. The aims were to improve the usability of PEMT through heuristic evaluation of the interface; to report the results of these usability evaluations; to make changes based on the findings of the usability experts; and to describe the benefits and limitations of applying usability evaluations to PEMT. METHODS: PEMT was evaluated by three usability experts using Nielsen's usability heuristics while reviewing the interface to produce a list of heuristic violations with severity ratings. The violations were sorted by heuristic and ordered from most to least severe within each heuristic. RESULTS: A total of 127 violations were identified with a median severity of 3 (range 0 to 4 with 0 = no problem to 4 = catastrophic problem). Results showed 13 violations for visibility (median severity = 2), 38 violations for match between system and real world (median severity = 2), 6 violations for user control and freedom (median severity = 3), 34 violations for consistency and standards (median severity = 2), 11 violations for error severity (median severity = 3), 1 violation for recognition and control (median severity = 3), 7 violations for flexibility and efficiency (median severity = 2), 9 violations for aesthetic and minimalist design (median severity = 2), 4 violations for help users recognize, diagnose, and recover from errors (median severity = 3), and 4 violations for help and documentation (median severity = 4). CONCLUSION: We describe the heuristic evaluation method employed to assess the usability of PEMT, a method which uncovers heuristic violations in the interface design in a quick and efficient manner. Bringing together usability experts and health professionals to evaluate a computer-mediated patient education program can help to identify problems in a timely manner. This makes this method particularly well suited to the iterative design process when developing other computer-mediated health education programs. Heuristic evaluations provided a means to assess the user interface of PEMT.

Serial passage through human glioma xenografts selects for a Deltagamma134.5 herpes simplex virus type 1 mutant that exhibits decreased neurotoxicity and prolongs survival of mice with experimental brain tumors.

Previous studies have described in vitro serial passage of a Deltagamma(1)34.5 herpes simplex virus type 1 (HSV-1) strain in SK-N-SH neuroblastoma cells and selection of mutants that have acquired the ability to infect and replicate in this previously nonpermissive cell line. Here we describe the selection of a mutant HSV-1 strain by in vivo serial passage, which prolongs survival in two separate experimental murine brain tumor models. Two conditionally replication-competent Deltagamma(1)34.5 viruses, M002, which expresses murine interleukin-12, and its parent virus, R3659, were serially passaged within human malignant glioma D54-MG cell lines in vitro or flank tumor xenografts in vivo. The major findings are (i) viruses passaged in vivo demonstrate decreased neurovirulence, whereas those passaged in vitro demonstrate a partial recovery of the neurovirulence associated with HSV-1; and (ii) vvD54-M002, the virus selected after in vivo serial passage of M002 in D54-MG tumors, improves survival in two independent murine brain tumor models compared to the parent (unpassaged) M002. Additionally, in vitro-passaged, but not in vivo-passaged, M002 displayed changes in the protein synthesis profile in previously nonpermissive cell lines, as well as early U(S)11 transcription. Thus, a mutant HSV-1 strain expressing a foreign gene can be selected for enhanced antitumor efficacy via in vivo serial passage within flank D54-MG tumor xenografts. The enhanced antitumor efficacy of vvD54-M002 is not due to restoration of protein synthesis or early U(S)11 expression. This finding emphasizes the contribution of the in vivo tumor environment for selecting novel oncolytic HSV specifically adapted for tumor cell destruction in vivo.